**Pediatric Soft Tissue Tumors**

Ezequiel Trejo-Scorza1, Belinda Beatriz Márquez Álvarez2, Carlos José Trejo-Scorza3 and Simón Paz- Ivannov3 *1Department of Pediatric Surgery Maternity "Concepción Palacios" 2Department of Pathology of Maternity "Concepción Palacios" 3Universidad Central de Venezuela Venezuela* 

## **1. Introduction**

The literature on cancer, of the Children Hospital "JM de los Ríos", allowed us to distinguish two series of solid tumors in children. The first serie (1, 2, 3), from 1937 to 1976, with 581 cases of malignant solid tumors, 75 of which were sarcomas (Table N° 1) and a second serie (4, 5), from 1985 to 2001, with 1.796 cases of solid tumors, with 280 cases of soft tissue tumors (Table N° 2). In both series, soft tissue tumors ranked the third in frequency with the 12.90% and 15.96% of cases, respectively. We refer to these statistics, since they are the base of our discussion.


Pediatric Soft Tissue Tumors 105

Table 3. Soft tissue tumors. Distribution by age groups. Children's Hospital "J.M. de los

Soft tissue have been defined as nonepithelial extraskeletal tissue of the body, exclusive the reticuloendothelial system, glia and supporting tissue of various parenchymal organs (6); it is represented by voluntary muscle, fat, fibrous tissue and vessels serving these tissues. The soft tissue tumors are a heterogeneous group of tumors that derived from embryonic mesenchymal cells; they are histopathológically classified, according to adult tissue that resembles, and may be benign or malignant. Malignant soft tissue tumors are called sarcomas, and there are three main groups: - rhabdomyosarcoma, - non-rhabdomyosarcoma

Rhabdomyosarcoma is the most common malignant soft tissue tumor in childhood and adolescense; and represents 60% of cases in under 18 years of age. It is originate from embryonic mesenchymal cells, with potential to differentiate into skeletal muscle cells, and is characterized by a tendency to exhibit histologic and molecular features of skeletal myogenesis. These tumors may arise anywhere in the body, even in sites where skeletal muscle is not normally found (7), and at diagnosis, the more frequent location of the tumor

The incidence of rhabdomyosarcoma in childhood and adolescence is 60%, and is higher in the first decade of life with 82.73%. Approximately, 50 percent of the cases of rhabdomyosarcoma (48.80%) are diagnosed in children under 5 years old (1-4 years old) (5),

Age groups soft tissue tumors Rhabdomyosarcomas

Table 4. Relation rhabdomyosarcoma/soft tissue tumor. Distribution by age groups.

and, represent 75% of soft tissue tumors in this age group tumors. (Table No. 4).

Under 1 year of age 27 12 (44.44%) 1 to 4 years 109 82 (75.22%) 5 to 9 years 71 45 (63.38%) 10 to 15 years 69 27 (39.13%) 16 to 18 years 4 2 (50%) Total 280 168 (60%)

Age groups Porcentaje Under 1 year of age 27 (9.64%) 1 to 4 years 109 (38.92%) 5 to 9 years 71 (25.35%) 10 to 15 years 69 (24.64%) 16 to 18 years 4 (1.42%)

Ríos" 1985-2001 (5)

soft tissue sarcoma, and - Ewing's sarcoma.

was: head and neck, genitourinary and limbs (8).

Children's Hospital "J.M. de los Ríos" 1985-2001 (5)

**2. Rhadomyosarcoma (RMS)** 

**2.1 Definition e incidence** 

**2.2 Age distribution** 

**1.2 Definition** 


Table 1. Solid tumors in the Children´s Hospital "JM de los Ríos" 1937-1976 (1, 2, 3)


Table 2. Solid tumors in the Children´s Hospital "JM de los Ríos" 1985-2001

#### **1.1 Incidence**

Solid tumors are approximately the 70% of cases of cancer in the children, and the other 30% are leukemias. In the group of solid tumors, soft tissue tumors rank third in frequency with 15.59%, only surpassed by lymphomas 21.71% and central nervous system tumors 21.60% (5) Table N° 2.

Incidence of soft tissue tumors in children and adolescents is not uniform across all ages. It is greater in children younger than 10 years with 73.92% and, children less of 5 years old, account for nearly half (48.57%) the cases of soft tissue tumors (Table N° 3).

Teratomas 17 11 12 40 (6.88%) Carcinoma 8 10 2 20 (3.44%)

dysgerminoma 1 1 (0.17%)

Total 174 291 116 581

Lymphoma / Hodgkin 304/135 86/7 390/142 (21.71%) Central nervous system tumors 199 189 388 (21.60%)

/ Wilms' tumor. 115/98 80/71 195/169 (10.85%)

/Rhabdomyosarcomas 178/114 102/54 280/168 (15.59%)

Neuroblastoma 79 62 141 (7.85%) Bone tumors 58 67 125 (6.95%) Retinoblastoma 35 19 54 (3.00%) Germ cell tumors Germ 111 16 127 (7.07%) Carcinoma 31 15 46 (2.56%)

Liver tumors 25 18 43 (2.39%) Other tumors 12 -5 7 (0.38%) Total 1147 649 1796

Solid tumors are approximately the 70% of cases of cancer in the children, and the other 30% are leukemias. In the group of solid tumors, soft tissue tumors rank third in frequency with 15.59%, only surpassed by lymphomas 21.71% and central nervous system tumors 21.60%

Incidence of soft tissue tumors in children and adolescents is not uniform across all ages. It is greater in children younger than 10 years with 73.92% and, children less of 5 years old,

Table 2. Solid tumors in the Children´s Hospital "JM de los Ríos" 1985-2001

account for nearly half (48.57%) the cases of soft tissue tumors (Table N° 3).

1985-1995 (4) 1996-2001 1985-2001 (5)

Table 1. Solid tumors in the Children´s Hospital "JM de los Ríos" 1937-1976 (1, 2, 3)

Ovarian

Liver tumors Other tumors

Renal Tumors

Soft tissue tumors

Ovarian dysgerminoma

**1.1 Incidence** 

(5) Table N° 2.


Table 3. Soft tissue tumors. Distribution by age groups. Children's Hospital "J.M. de los Ríos" 1985-2001 (5)

## **1.2 Definition**

Soft tissue have been defined as nonepithelial extraskeletal tissue of the body, exclusive the reticuloendothelial system, glia and supporting tissue of various parenchymal organs (6); it is represented by voluntary muscle, fat, fibrous tissue and vessels serving these tissues. The soft tissue tumors are a heterogeneous group of tumors that derived from embryonic mesenchymal cells; they are histopathológically classified, according to adult tissue that resembles, and may be benign or malignant. Malignant soft tissue tumors are called sarcomas, and there are three main groups: - rhabdomyosarcoma, - non-rhabdomyosarcoma soft tissue sarcoma, and - Ewing's sarcoma.

## **2. Rhadomyosarcoma (RMS)**

## **2.1 Definition e incidence**

Rhabdomyosarcoma is the most common malignant soft tissue tumor in childhood and adolescense; and represents 60% of cases in under 18 years of age. It is originate from embryonic mesenchymal cells, with potential to differentiate into skeletal muscle cells, and is characterized by a tendency to exhibit histologic and molecular features of skeletal myogenesis. These tumors may arise anywhere in the body, even in sites where skeletal muscle is not normally found (7), and at diagnosis, the more frequent location of the tumor was: head and neck, genitourinary and limbs (8).

## **2.2 Age distribution**

The incidence of rhabdomyosarcoma in childhood and adolescence is 60%, and is higher in the first decade of life with 82.73%. Approximately, 50 percent of the cases of rhabdomyosarcoma (48.80%) are diagnosed in children under 5 years old (1-4 years old) (5), and, represent 75% of soft tissue tumors in this age group tumors. (Table No. 4).


Table 4. Relation rhabdomyosarcoma/soft tissue tumor. Distribution by age groups. Children's Hospital "J.M. de los Ríos" 1985-2001 (5)

Pediatric Soft Tissue Tumors 107




The histopathological types found in order of decreasing frequency, in Children's Hospital

Table 6. Rhabdomyosarcoma, Rhabdomyosarcoma histopathological types, Children's

The most common sites of primary tumor are: head and neck, including the orbit; genitourinary tract including the prostate, testis, vulva, cérvix and uterus; and extremities. (Table N° 7); and less frequent are: trunk, retroperitoneum, perianal and anal

The histologic variants embryonal and alveolar are the two more common.

in the classification of Imbach (9), so we add it)




Embryonal rhabdomyosarcoma 39 (66.10%)

subtype 6 (10.16%)

cell subtype 1 (1.69%) Alveolar rhabdomyosarcoma 11 (18.64%) Non typeable 2 (3.38%) Total 59 (100%)

histopathological types number of cases (%)

**2.5.2 Alveolar** 

**2.5.3 Pleomorphic** 


fibrotic septation (alveolar structure)


structured in rows and bundles.

"J.M. de los Ríos", are shown in Table N°6 (10):

Embryonal rhabdomyosarcoma botryoides

Embryonal rhabdomyosarcoma spindle

Hospital "J.M. de los Ríos" 1997-2005 (10)

**2.6 Location** 

(7, 9, 10, 12).

**2.5.4 Undifferentiated subtype** 

## **2.3 Histopathologic classification**

According to the histopathological and prognosis features, the rhadomyosarcomas are classified in the following varieties (8). Table N°5:


Table 5. International Prognostic Classification of Pediatric Rhabdomyosarcoma

The incidence of the different varieties of rhabdomyosarcoma, in descending order, is the following (9): Embryonic (64%), Alveolar (21%), undifferenciated (8%), botryoides (6%), pleomorphic (1%).

## **2.4 Etiology, pathogenesis and cytogenetics**

Most rhabdomyosarcomas occur sporadically without predisposing factors, and only one third of patients have recognizable genetic anomalies (7, 9). The cause of the rhabdomyosarcomas remains unknown; but now we know, that certain genetic alterations are associated with the development of this tumor. Alveolar RMS has a characteristic translocation between the long arm of chromosome 2 and the long arm of chromosome 13. This translocation has been cloned molecularly, and shown to involve the juxtaposition of the PAX3 gene, which thought to regulate transcription during early neuromuscular development (7). The embryonal rhabdomyosarcoma, has loss of heterozygosity (LOH) at the 11p15 locus (10).

The Li-Fraumeni syndrome, a well-defined family cancer, that includes rhabdomyosarcoma and other soft tissue sarcomas has been associated with germline mutations of the p53 gene. Rhabdomyosarcoma has been observed in association with Beckwith-Wiedemann syndrome, a fetal overgrowth syndrome associated with abnormalities on 11p15.

The history of cancer in the family is an important, reported in 45.76% of cases. (11).

#### **2.5 Histopathological varieties**

There are 4 types of rhabdomyosarcoma in children, clearly defined by Imbach (9), which we reproduce it textually.

#### **2.5.1 Embryonal**



## **2.5.2 Alveolar**

106 Soft Tissue Tumors

According to the histopathological and prognosis features, the rhadomyosarcomas are

The incidence of the different varieties of rhabdomyosarcoma, in descending order, is the following (9): Embryonic (64%), Alveolar (21%), undifferenciated (8%), botryoides (6%),

Most rhabdomyosarcomas occur sporadically without predisposing factors, and only one third of patients have recognizable genetic anomalies (7, 9). The cause of the rhabdomyosarcomas remains unknown; but now we know, that certain genetic alterations are associated with the development of this tumor. Alveolar RMS has a characteristic translocation between the long arm of chromosome 2 and the long arm of chromosome 13. This translocation has been cloned molecularly, and shown to involve the juxtaposition of the PAX3 gene, which thought to regulate transcription during early neuromuscular development (7). The embryonal rhabdomyosarcoma, has loss of heterozygosity (LOH) at

The Li-Fraumeni syndrome, a well-defined family cancer, that includes rhabdomyosarcoma and other soft tissue sarcomas has been associated with germline mutations of the p53 gene. Rhabdomyosarcoma has been observed in association with Beckwith-Wiedemann

There are 4 types of rhabdomyosarcoma in children, clearly defined by Imbach (9), which



syndrome, a fetal overgrowth syndrome associated with abnormalities on 11p15. The history of cancer in the family is an important, reported in 45.76% of cases. (11).


characteristic of skeletal muscle in about 30% of cases.

Poor prognosis

**2.3 Histopathologic classification** 

Alveolar rhabdomyosarcoma Undifferentiated sarcoma

pleomorphic (1%).

the 11p15 locus (10).

**2.5 Histopathological varieties** 

a dense subepithelial cell layer.

we reproduce it textually.

**2.5.1 Embryonal** 

classified in the following varieties (8). Table N°5:

Botryoid embryonal rhabdomyosarcoma

Rhabdomyosarcoma with diffuse anaplasia

**2.4 Etiology, pathogenesis and cytogenetics** 

**Histopathologic varieties Prognosis** 

Spindle cell rhabdomyosarcoma Superior prognosis Embryonal rhabdomyosarcoma Intermediate prognosis

Table 5. International Prognostic Classification of Pediatric Rhabdomyosarcoma


## **2.5.3 Pleomorphic**


## **2.5.4 Undifferentiated subtype**


The histopathological types found in order of decreasing frequency, in Children's Hospital "J.M. de los Ríos", are shown in Table N°6 (10):


Table 6. Rhabdomyosarcoma, Rhabdomyosarcoma histopathological types, Children's Hospital "J.M. de los Ríos" 1997-2005 (10)

The histologic variants embryonal and alveolar are the two more common.

#### **2.6 Location**

The most common sites of primary tumor are: head and neck, including the orbit; genitourinary tract including the prostate, testis, vulva, cérvix and uterus; and extremities. (Table N° 7); and less frequent are: trunk, retroperitoneum, perianal and anal (7, 9, 10, 12).

Pediatric Soft Tissue Tumors 109

To plan appropriate treatment, it is necessary to determine the degree of progression of the disease. The clinical classification grouping (15), classifies the extent of the disease into four

Regional nodes not involved—lymph node biopsy or dissection is required except for head

Notation: This includes both gross inspection and microscopic confirmation of complete resection. Any nodes that may be inadvertently taken with the specimen must be negative. If the latter should be involved microscopically, then the patient is placed in group IIB or

Surgeon believes that all the tumor has been removed, but the pathologist finds tumor at the margin of resection, and additional resection to achieve a clean margin is not feasible. No evidence of gross residual tumor; no evidence of regional node involvement; once radiotherapy and/or chemotherapy have been started, re-exploration and removal of the

B. Regional disease with involved nodes, completely resected with no microscopic

Notation: Complete resection with microscopic confirmation of no residual disease makes this different from group IIA and group IIC. Additionally, in contrast to group IIA, regional nodes (which are completely resected, however) are involved, but the most distal node is

C. Regional disease with involved nodes, grossly resected, but with evidence of microscopic residual and/or histologic involvement of the most distal regional node

Notation: The presence of microscopic residual disease makes this group different from

Notation: The above excludes regional nodes and adjacent organ infiltration, which places

group IIB, and nodal involvement makes this group different from group IIA.

Lung, liver, bones, bone marrow, brain, and distant muscle and nodes.

the patient in a more favorablegrouping (as noted above under group II).

**Group II: Total gross resection with evidence of regional spread, completely resected** 

**Group I: Localized disease, completely resected, no microscopic residual** 

A. Confined to muscle or organ of origin, completed resected B. Infiltrating beyond site of origin, completely resected

A. Grossly resected tumor with microscopic residual disease

area of microscopic residual does not change the patient's group.

(from the primary site) in the dissection

**Group III: Incomplete resection with gross residual disease** 

B. After gross or major resection of the primary (>50%) **Group IV: Distant metastatic disease present at onset** 

Rhabdomyosarcomas are located in the extremities present clinically as painless masses. As soon as the suspected tumor, this diagnosis should be confirmed through an MRI, and to establish the histopathological diagnosis of the lesion should be performed an open biopsy, or with needle. If frozen sections suggest that the lesion is malignant, tissue samples must be

**2.7.3 Extremities** 

groups.

and neck lesions

group IIC (see below).

residual

histologically negative.

A. After biopsy only

sent for chromosome analysis.

**2.8 Staging classification, treatment and prognosis** 

**IRS clinical grouping classification (stage)** 


Table 7. Rhabdomyosarcoma, Location of primary tumor, Children's Hospital "J.M. de los Ríos" 1997-2005 (10)

The age and location of the tumor are associated with histological varieties certain of rhabdomyosarcoma. Head and neck tumors are more common in children younger than eight years of age and when arising in the orbit are almost always of the embryonal variety, while extremity tumors are more common in adolescents and are typically of the alveolar subtype. The variant botryoides of bladder or vagina, occurs almost exclusively in infants (7).

#### **2.7 Clinical presentation**

The clinical manifestations of rhabdomyosarcoma depends on the age at diagnosis, location of primary tumor, and the presence or absence of metastasis.

#### **2.7.1 Head and neck**

The primary tumor is usually located in: orbit, head and neck superficial, and parameningeal. Clinical symptoms will depend on the location of the tumor and usually present with a painless, enlarging mass that can obstruct a sinus, grow into the nasal cavity, cause proptosis, or simulate chronic otitis media (12) and clinical symptoms include nasal discharge or obstruction of the airways, otorrhea, and rapid proptosis. The more deepseated tumors, signs and symptoms may result from compression of nerves, blocked vessels, or both; cranial nerve palsy or other neurological deficits indicates the extent of the tumor at the base of the skull or the central nervous system. (13). The parameningeal localization is the most frequent and a poorer prognosis; usually located in pterygoid infratemporal fossa, nasopharyngeal cavity, paranasal sinuses and middle ear and mastoid, and these four locations include the 91.52% of cases (14).

#### **2.7.2 Genitourinary tract**

The embryonal type is the commonest in this región, and arise in the bladder, prostate, vagina, uterus, vulva, paratesticular regions. Children with bladder rhadomyosarcoma are usually under 4 years of age, and may present with hematuria, urinary obstruction and rarely extrusion of tumor tissue. The bladder tumors usually grow intra-luminally, in the region of the trigone and have a polypoidal appearance on gross or endoscopic examination. Prostatic tumors can occur in relatively older children and usually present as large pelvic masses with or without urethral strangury and/ or constipation. Within the category of genitourinary rhabdomyosarcoma, tumors located in the vulva, vagina and paratesticular are a good prognosis; whereas those located in the bladder and prostate have the worst prognosis.

## **2.7.3 Extremities**

108 Soft Tissue Tumors

Table 7. Rhabdomyosarcoma, Location of primary tumor, Children's Hospital "J.M. de los

The age and location of the tumor are associated with histological varieties certain of rhabdomyosarcoma. Head and neck tumors are more common in children younger than eight years of age and when arising in the orbit are almost always of the embryonal variety, while extremity tumors are more common in adolescents and are typically of the alveolar subtype. The variant botryoides of bladder or vagina, occurs almost exclusively in infants

The clinical manifestations of rhabdomyosarcoma depends on the age at diagnosis, location

The primary tumor is usually located in: orbit, head and neck superficial, and parameningeal. Clinical symptoms will depend on the location of the tumor and usually present with a painless, enlarging mass that can obstruct a sinus, grow into the nasal cavity, cause proptosis, or simulate chronic otitis media (12) and clinical symptoms include nasal discharge or obstruction of the airways, otorrhea, and rapid proptosis. The more deepseated tumors, signs and symptoms may result from compression of nerves, blocked vessels, or both; cranial nerve palsy or other neurological deficits indicates the extent of the tumor at the base of the skull or the central nervous system. (13). The parameningeal localization is the most frequent and a poorer prognosis; usually located in pterygoid infratemporal fossa, nasopharyngeal cavity, paranasal sinuses and middle ear and mastoid,

The embryonal type is the commonest in this región, and arise in the bladder, prostate, vagina, uterus, vulva, paratesticular regions. Children with bladder rhadomyosarcoma are usually under 4 years of age, and may present with hematuria, urinary obstruction and rarely extrusion of tumor tissue. The bladder tumors usually grow intra-luminally, in the region of the trigone and have a polypoidal appearance on gross or endoscopic examination. Prostatic tumors can occur in relatively older children and usually present as large pelvic masses with or without urethral strangury and/ or constipation. Within the category of genitourinary rhabdomyosarcoma, tumors located in the vulva, vagina and paratesticular are a good prognosis; whereas those located in the bladder and prostate have the worst

Location number of cases (%)

Head and neck 20 (33.89%) Genitourinary 14 (23.72%) Extremities 13 (22.03%) Pelvic floor 7 (11.86%) Trunk 4 (6.77%) Perianal and anal 1 (1.69%)

of primary tumor, and the presence or absence of metastasis.

and these four locations include the 91.52% of cases (14).

Ríos" 1997-2005 (10)

**2.7 Clinical presentation** 

**2.7.1 Head and neck** 

**2.7.2 Genitourinary tract** 

prognosis.

(7).

Rhabdomyosarcomas are located in the extremities present clinically as painless masses.

As soon as the suspected tumor, this diagnosis should be confirmed through an MRI, and to establish the histopathological diagnosis of the lesion should be performed an open biopsy, or with needle. If frozen sections suggest that the lesion is malignant, tissue samples must be sent for chromosome analysis.

## **2.8 Staging classification, treatment and prognosis**

To plan appropriate treatment, it is necessary to determine the degree of progression of the disease. The clinical classification grouping (15), classifies the extent of the disease into four groups.

## **IRS clinical grouping classification (stage)**

## **Group I: Localized disease, completely resected, no microscopic residual**

Regional nodes not involved—lymph node biopsy or dissection is required except for head and neck lesions


Notation: This includes both gross inspection and microscopic confirmation of complete resection. Any nodes that may be inadvertently taken with the specimen must be negative. If the latter should be involved microscopically, then the patient is placed in group IIB or group IIC (see below).

#### **Group II: Total gross resection with evidence of regional spread, completely resected**

A. Grossly resected tumor with microscopic residual disease

Surgeon believes that all the tumor has been removed, but the pathologist finds tumor at the margin of resection, and additional resection to achieve a clean margin is not feasible. No evidence of gross residual tumor; no evidence of regional node involvement; once radiotherapy and/or chemotherapy have been started, re-exploration and removal of the area of microscopic residual does not change the patient's group.

B. Regional disease with involved nodes, completely resected with no microscopic residual

Notation: Complete resection with microscopic confirmation of no residual disease makes this different from group IIA and group IIC. Additionally, in contrast to group IIA, regional nodes (which are completely resected, however) are involved, but the most distal node is histologically negative.

C. Regional disease with involved nodes, grossly resected, but with evidence of microscopic residual and/or histologic involvement of the most distal regional node (from the primary site) in the dissection

Notation: The presence of microscopic residual disease makes this group different from group IIB, and nodal involvement makes this group different from group IIA.

#### **Group III: Incomplete resection with gross residual disease**


#### **Group IV: Distant metastatic disease present at onset**

Lung, liver, bones, bone marrow, brain, and distant muscle and nodes.

Notation: The above excludes regional nodes and adjacent organ infiltration, which places the patient in a more favorablegrouping (as noted above under group II).

Pediatric Soft Tissue Tumors 111

most resembles and represent 4.23% of solid tumors (5) and 27.14% of soft tissue tumors in

Fig. 1. Soft tissue tumors 280 cases, Children Hospital "JM de los Rios" 1985-2001.

There are differences in soft tissue sarcomas in children and adults in terms of histological types and frequency; differences which have therapeutic implications (20). In Children are more frequent the malignant tumors of the peripheral nerve sheath and fibrosarcoma (5), while adults are more frequent Kaposi's sarcoma, leiomyosarcoma and malignant fibrous

The distribution of the different varieties of norhabdomyosarcomas soft tissue tumors varies with age; myofibromas and fibrosarcoma are more common in infants, whereas the synovial sarcoma and malignant peripheral nerve sheath tumor is more common in older children and adolescents (12). It is necessary to highlight the characteristics of soft tissue tumors in the first year of life. Approximately 20% of soft tissue tumors that occur in children under 20 years are presented in the first year of age, and of these just over half presented in the first three months of life. 85% of soft tissue tumors present in the first year of life are classified as benign or borderline lesions and the remaining 15% are malignant. The benign and borderline lesions most common are: infantile hemangioendothelioma, lymphangiomas, myofibromas, fibrous histiocytoma, and congenital or infantile fibrosarcoma and represent 68.71% of this group, while embryonal rhabdomyosarcoma and primitive neuroectodermal tumor are the most common malignant lesions, and represent for

Soft tissue tumors are grouped for classification according to cell type that most resembles.

patients under 18 years Fig Nº 1

histiocytoma (20).

**3.2 Age distribution** 

62.96% of this group (21).

Table Nº 8.

**3.3 Histopathologic classification** 

The presence of positive cytology in the cerebrospinal fluid, pleural or abdominal fluids, as well as implants on pleural or peritoneal surfaces are regarded as indications for placing the patient in group IV.

The size of the primary tumor is a prognostic factor. Tumors less than or equal to 5 cm are classified in the subgroup a, and tumors larger than 5 cm are classified in subgroup b (16). However, this tumor size has a different meaning according to the body surface. A tumor of 5 cm in a children or an adolescent have not the same meaning a 5 cm tumor in a neonate or an infant, what is proposed, relating the size of the primary tumor with the patient's body surface (17).

Rhabdomyosarcoma is a systemic disease, with high probability of spread to lymph nodes, bone marrow, bone, soft tissue distance, and pleural or peritoneal spaces adjacent to the primary site; and have propensity to spread to the lung parenchyma. Therefore, the diagnostic study to determine the extent of the disease includes: obtaining a chest radiograph and lateral, computed tomography (CT) scan of the chest, bone marrow aspiration, biopsy, total body bone scan and cerebrospinal fluid samples from patients with orbital tumors parameningeal or other (eg, tumors of the nasopharynx, paranasal sinuses, pterygoid fossa / infratemporal, and the region middle-ear/mastoid). Patients with rhabdomyosarcomas are classified on the basis de their low, intermediate, or high risk for treatment failure (18). Treatment is then tailored to the appropriate risk level. It is standard practice to repeat imaging studies at 2- to 4-month intervals during and after therapy and to obtain blood samples and chemistries before each course of multiple-agent chemotherapy. (12).

At the present time, more than 70% of children and adolescents with rhabdomyosarcoma are cured with combined modality treatment (chemotherapy, radiation and surgery) (19), but the results will be different depending on the clinical group, histological type, anatomic location and age at presentation of disease, factors that determine the prognosis of the disease and levels of risk of treatment failure.


## **3. Nonrhabdomyosarcomas soft tissue tumors**

#### **3.1 Definition e incidence**

Nonrhabdomyosarcomas soft tissue tumors are a heterogeneous group of mesenchymal cell neoplasms, most of which are typified with the named for the mature tissue that the tumor

The presence of positive cytology in the cerebrospinal fluid, pleural or abdominal fluids, as well as implants on pleural or peritoneal surfaces are regarded as indications for placing the

The size of the primary tumor is a prognostic factor. Tumors less than or equal to 5 cm are classified in the subgroup a, and tumors larger than 5 cm are classified in subgroup b (16). However, this tumor size has a different meaning according to the body surface. A tumor of 5 cm in a children or an adolescent have not the same meaning a 5 cm tumor in a neonate or an infant, what is proposed, relating the size of the primary tumor with the patient's body

Rhabdomyosarcoma is a systemic disease, with high probability of spread to lymph nodes, bone marrow, bone, soft tissue distance, and pleural or peritoneal spaces adjacent to the primary site; and have propensity to spread to the lung parenchyma. Therefore, the diagnostic study to determine the extent of the disease includes: obtaining a chest radiograph and lateral, computed tomography (CT) scan of the chest, bone marrow aspiration, biopsy, total body bone scan and cerebrospinal fluid samples from patients with orbital tumors parameningeal or other (eg, tumors of the nasopharynx, paranasal sinuses, pterygoid fossa / infratemporal, and the region middle-ear/mastoid). Patients with rhabdomyosarcomas are classified on the basis de their low, intermediate, or high risk for treatment failure (18). Treatment is then tailored to the appropriate risk level. It is standard practice to repeat imaging studies at 2- to 4-month intervals during and after therapy and to obtain blood samples and chemistries before each

At the present time, more than 70% of children and adolescents with rhabdomyosarcoma are cured with combined modality treatment (chemotherapy, radiation and surgery) (19), but the results will be different depending on the clinical group, histological type, anatomic location and age at presentation of disease, factors that determine the prognosis of the

 The low-risk patients are those with rhabdomyosarcomas of the embryonal variety, in any anatomical location, which have been surgically resected (stages 1-3), or irresectables but in favorable anatomical sites. Favorable anatomic locations are considered nonparameningeal head and neck sites (oropharynx, scalp, parotid, neck, larynx, cheeks, eyelids, hypopharynx), and genitourinary system excluding the bladder and prostate. Their survival rate is over 90% when treated with vincristine and dactinomycin or

vincristine, dactinomycin and cyclophosphamide with or without radiotherapy. The intermédiate-risk patients are those with unresectable tumors of the embrional variety, in unfavorable locations, ó that are metastatic at the time of diagnosis in patients younger than 10 years old; and all those with non metastatic rhabdomyosarcomas of the alveolar variety. The survival of this group is about 50%- 75% and investigated the effectiveness of new drugs such as topotecan. Rhabdomyosarcomas of the alveolar variety, stages I-III, require complementary

The high-risk patients are those with metastatic at the time of diagnosis and the

Nonrhabdomyosarcomas soft tissue tumors are a heterogeneous group of mesenchymal cell neoplasms, most of which are typified with the named for the mature tissue that the tumor

patient in group IV.

course of multiple-agent chemotherapy. (12).

disease and levels of risk of treatment failure.

treatment with radiotherapy

**3.1 Definition e incidence** 

survival of this group is only 25%

**3. Nonrhabdomyosarcomas soft tissue tumors** 

surface (17).

most resembles and represent 4.23% of solid tumors (5) and 27.14% of soft tissue tumors in patients under 18 years Fig Nº 1

Fig. 1. Soft tissue tumors 280 cases, Children Hospital "JM de los Rios" 1985-2001.

There are differences in soft tissue sarcomas in children and adults in terms of histological types and frequency; differences which have therapeutic implications (20). In Children are more frequent the malignant tumors of the peripheral nerve sheath and fibrosarcoma (5), while adults are more frequent Kaposi's sarcoma, leiomyosarcoma and malignant fibrous histiocytoma (20).

## **3.2 Age distribution**

The distribution of the different varieties of norhabdomyosarcomas soft tissue tumors varies with age; myofibromas and fibrosarcoma are more common in infants, whereas the synovial sarcoma and malignant peripheral nerve sheath tumor is more common in older children and adolescents (12). It is necessary to highlight the characteristics of soft tissue tumors in the first year of life. Approximately 20% of soft tissue tumors that occur in children under 20 years are presented in the first year of age, and of these just over half presented in the first three months of life. 85% of soft tissue tumors present in the first year of life are classified as benign or borderline lesions and the remaining 15% are malignant. The benign and borderline lesions most common are: infantile hemangioendothelioma, lymphangiomas, myofibromas, fibrous histiocytoma, and congenital or infantile fibrosarcoma and represent 68.71% of this group, while embryonal rhabdomyosarcoma and primitive neuroectodermal tumor are the most common malignant lesions, and represent for 62.96% of this group (21).

#### **3.3 Histopathologic classification**

Soft tissue tumors are grouped for classification according to cell type that most resembles. Table Nº 8.

Pediatric Soft Tissue Tumors 113

Non rhabdomiosarcomas soft tissue tumors can be benign or malignant and malignant are called sarcomas. The histopathologic features determine the prognosis and treatment follow

The mitotic count is <5 mitotic figures per 10 high-power fields using a 340 objective

Any other sarcoma not in grade 1 with >15% necrosis and/or ‡5 mitotic figures per10

The proper classification of non rhabdomyosarcomas soft tissue tumors is not easy and raises diagnostic problems that require additional methods such as immunohistochemistry, genetic studies, and consultation by experts (30). Myofibromas are benign lesions with difficulty diagnostic because they may be mistaken for malign lesions with

The evalucación diagnosed, requires magnetic resonance imaging and computed

Treatment and prognosis depends on the extent of disease and histological type of injury, poor prognostic factors are: high histologic grade, intra-abdominal primary tumor, and microscopic residual disease after initial resection (32, 33). Radiation therapy is useful in tumors whose location does not allow excision and all tumors larger than 5 cm. or that could not be completely resected. Sarcomas in children are more sensitive to chemotherapy report answer 40 to 60% using multiple drugs, hence its use in all tumors larger than 5 cm, of axial

tomography to determine the extent of the disease and a plan for surgery (32).

location, with histological high grade, or with metastatic disease.

Table 9. The Pediatric Oncology Group Grading System for Nonrhabdomyosarcomatous

**3.7 Staging classification, treatment and prognosis** 

(28, 29) and hence the classification of degrees. Table Nº 9

Well-differentiated or infantile (≤4 years old) fibrosarcoma

Well-differentiated or infantile (≤4 years old) hemangiopericytoma Well-differentiated malignant peripheral nerve sheath tumor

Myxoid and well-differentiated liposarcoma

Angiomatoid malignant fibrous histiocytomab Deep-seated dermatofibrosarcoma protuberans

≤15% of the surface area shows necrosis

Pleomorphic or round-cell liposarcoma

high-power fields using a 340 objective

hemangiopericytoma-like findings (31).

Myxoid chondrosarcoma

Nuclear atypia is not marked The tumor is not markedly cellular

Mesenchymal chondrosarcoma Extraskeletal osteogenic sarcoma

Soft Tissue Sarcomas of Children

Malignant triton tumor Alveolar soft part sarcoma

Grade 1

Grade 2

Grade 3


aIntermediate categories between benign and malignant tumors are excluded for simplicity.

Table 8. Simplified Chart of the Major Types of Primary Soft Tissue Tumors Grouped According to the Cell Types that They Resemblea (22)

#### **3.4 Etiology, pathogenesis and cytogenetics**

The cause of the soft tissue sarcomas remains unknown, but in nonrhabdomyosarcomas soft tissue tumors have identified genetic alterations. In the fibrosarcoma, a characteristic translocation t (12; 15) (p13; q25) with an ETV6-NTRK3 gene fusion, and gains of chromosomes 8, 11, 17 and 20 (23). Synovial sarcoma has and a specific chromosomal translocation t(X;18)(p11;q11) (23).

#### **3.5 Location**

The anatomical location of primary tumor in descending order of frequency is: head and neck, trunk and extremities. However this varies depending on the histologic type of tumor. The most frequent primary tumor site was: in fibrosarcoma, the limbs in 66% (24); in myofibromas, head, neck, and trunk in 69% (25); in sinovial sarcoma, the limbs nears joints and tendons in the 77.96% (26).

#### **3.6 Clinical presentation**

The most common clinical presentation is a painless mass, although the involvement of adjacent structures can cause pain and other symptoms (27)

Fibroma, myxoma Fibrosarcoma, malignant

fibrous histiocytoma

Some malignant peripheral nerve sheath tumors

Gastrointestinal stromal tumors, a spectrum from benign to malignant

(True histiocytic lymphoma)

Extranodal lymphomas in

Histiocytic sarcoma

Ewing family tumors Synovial sarcoma Epithelioid sarcoma Alveolar soft part sarcoma

soft tissues

sarcoma

Cell Type Benign Tumor Malignant Tumor

Adipocyte Lipoma Liposarcoma Smooth muscle cell Leiomyoma Leiomyosarcoma Skeletal muscle cell Rhabdomyoma Rhabdomyosarcoma Endothelial cell Hemangioma Angiosarocoma, Kaposi

neurofibroma

hyperplasia

Cartilage cell Chondroma Chondrosarcoma

Rosai-Dorfman disease?

aIntermediate categories between benign and malignant tumors are excluded for simplicity. Table 8. Simplified Chart of the Major Types of Primary Soft Tissue Tumors Grouped

The cause of the soft tissue sarcomas remains unknown, but in nonrhabdomyosarcomas soft tissue tumors have identified genetic alterations. In the fibrosarcoma, a characteristic translocation t (12; 15) (p13; q25) with an ETV6-NTRK3 gene fusion, and gains of chromosomes 8, 11, 17 and 20 (23). Synovial sarcoma has and a specific chromosomal

The anatomical location of primary tumor in descending order of frequency is: head and neck, trunk and extremities. However this varies depending on the histologic type of tumor. The most frequent primary tumor site was: in fibrosarcoma, the limbs in 66% (24); in myofibromas, head, neck, and trunk in 69% (25); in sinovial sarcoma, the limbs nears joints

The most common clinical presentation is a painless mass, although the involvement of

Fibroblast, including myofibroblast

Interstitial cell of Cajal of

No known normal cell or benign counterparts

intestines

Schwann cell Schwannoma,

Histiocyte Juvenile xanthogranuloma

Lymphoid cells Benign lymphoid

According to the Cell Types that They Resemblea (22)

adjacent structures can cause pain and other symptoms (27)

**3.4 Etiology, pathogenesis and cytogenetics** 

translocation t(X;18)(p11;q11) (23).

and tendons in the 77.96% (26).

**3.6 Clinical presentation** 

**3.5 Location** 

## **3.7 Staging classification, treatment and prognosis**

Non rhabdomiosarcomas soft tissue tumors can be benign or malignant and malignant are called sarcomas. The histopathologic features determine the prognosis and treatment follow (28, 29) and hence the classification of degrees. Table Nº 9


Table 9. The Pediatric Oncology Group Grading System for Nonrhabdomyosarcomatous Soft Tissue Sarcomas of Children

The proper classification of non rhabdomyosarcomas soft tissue tumors is not easy and raises diagnostic problems that require additional methods such as immunohistochemistry, genetic studies, and consultation by experts (30). Myofibromas are benign lesions with difficulty diagnostic because they may be mistaken for malign lesions with hemangiopericytoma-like findings (31).

The evalucación diagnosed, requires magnetic resonance imaging and computed tomography to determine the extent of the disease and a plan for surgery (32).

Treatment and prognosis depends on the extent of disease and histological type of injury, poor prognostic factors are: high histologic grade, intra-abdominal primary tumor, and microscopic residual disease after initial resection (32, 33). Radiation therapy is useful in tumors whose location does not allow excision and all tumors larger than 5 cm. or that could not be completely resected. Sarcomas in children are more sensitive to chemotherapy report answer 40 to 60% using multiple drugs, hence its use in all tumors larger than 5 cm, of axial location, with histological high grade, or with metastatic disease.

Pediatric Soft Tissue Tumors 115

[17] Ferrari A, Miceli R, Meazza C, Zaffignani E, Gronchi A, Piva L, Collini P, Podda M,

[18] McCarville, M. Beth, Spunt, Sheri L., Pappo, Alberto S. Rhabdomyosarcoma in Pediatric

[19] Breitfeld P, Meyer WH. Rhabdomyosarcoma: New windows of opportunity. The

[20] Spunt SL, Pappo AS. Childhood Nonrhabdomyosarcoma Soft Tissue Sarcomas Are Not

[21] Coffin ChM, Dehner LP. Soft tissue tumors in first year of life: A report of 190 cases.

[22] Miettinen M. Overview of soft tissue tumors. In Miettinen M, Editor. Modern soft

[23] Cheryl M. Coffin, MD, Amy Lowichik, MD, PhD, and Holly Zhou, MD. Treatment

[24] Daniel Orbach D, et al. Infantile Fibrosarcoma: Management Based on the European

[28] Parham DM, Webber BL, Jenkins JJ, 3rd, Cantor AB, Maurer HM.

[29] Khoury JD, Coffin CM, Spunt SL, Anderson JR, Meyer WH, Parham DM. Grading of

[30] Arbiser ZK, Folpe AL, and Weiss SW, MD. Consultative (Expert) Second Opinions in

[31] Trejo-Scorza E, Viña-Ramírez MI, Oviedo-Ayala N, ernández-Faraco AA, Alvarado-

[32] Merchant MS, Mackall CL. Current approach to pediatric soft tissue sarcomas. The

Nonrhabdomyosarcomatous soft tissue sarcomas of childhood: formulation of a

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[25] Chung EB, Enzinger FM. Infantile myofibromatosis. Cancer 1981; 48:1807-1818. [26] McCarville MB; et al. Synovial Sarcoma in Pediatric Patients *AJR* 2002; 179:797-801 [27] Spunt SL, Skapen SX, Coffin Ch M. Pediatric nonrhabdomyosarcoma soft tissue

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[4] Pereira G A, Martínez Siso M, Machado AC, Moschella F, Casale E, Santos S, Mora E,

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[7] Wesler LH, Helman LJ. Pediatric Soft Tissue Sarcomas CA Cancer J Clin 1994; 44 (4): 211

[8] Prasad V, Sayed K, Ramji F, Parham DM. Rhabdomyomas and Rhabdomyosarcomas. In:

[9] Imbach P. Soft tissue sarcoma. In: Imbach P, KühneTh, Arceci R, editors. Pediatric

[10] Dagher R, Helman L. Rhabdomyosarcoma: An Overview. The Oncologist 1999; 4: 34-44. [11] Arcamone G, Gimenez C, Pereira A, et al. Rhabdomiosarcoma en niños. Rev Venez

[12] Beverly Raney R, Andrassy RJ, Blakely M, Fanning TV, Maor MH, and Stewart J. Soft-

[13] Agarwala S. Pediatric Rhabdomyosarcoma and NonRhabdomyosarcoma soft tissue

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MMT 89 and 95. Journal of Clinical Oncology 2009; 27(8): 1310-1315. [15] Maurer HM, Beltangady M, Gehan EA, Crist W, Hammond D, Hays D, et al. The Intergroup Rhabdomyosarcoma Study I: A final report. Cancer 1988; 61:209-20. [16] Crist WC, Anderson JR, Meza JL, Fryer Ch, Berverly Raney R, Ruymann FB, Breneman

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Nonmetastatic Cranial Parameningeal Rhabdomyosarcoma in Children Younger Than 3 Years Old: Results From International Society of Pediatric Oncology Studies

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**7** 

*Mexico* 

**Head and Neck Soft Tissue Sarcoma** 

Rogelio Gonzalez – Gonzalez, Ronell Bologna – Molina, Omar Tremillo – Maldonado, Ramon Gil Carreon – Burciaga

Soft tissue sarcomas are a group of heterogeneous tumors that have their origin primarily in the embryonic mesoderm; more than 50 histological subtypes and diverse clinical behaviors have been identified. Soft tissue sarcomas can range from relatively slow growth, causing little destructive growth, to being locally aggressive, regionally destructive and having a great potential for systemic metastases [Greene et al, 2002; Pelliteri et al, 2003]. The approximate incidence for this kind of neoplasia is 3-4.5/100,000 [Zahm et al, 1997], representing approximately 1% of all malignant adult neoplasias. Soft tissue sarcomas are rare in the head and neck and have an approximate frequency of 5-15% of all adult sarcomas and less than 1% of all head and neck neoplasias [Patel et al, 2001; Pandey et al, 2003; Colville et al, 2005]. The age at presentation is variable with a mean of 50 to 55 years (minimum is 3 months and the maximum is 89 years old) and the male/female ratio is approximately 2:1, which varies depending on the review series. The symptoms depend on location, but the most frequently reported symptoms are the following: headache, nasal obstruction, dysphagia, hoarseness and dyspnea. However, the majority of patients are asymptomatic [Farhood et al]. The most frequently reported involved sites include the following: the face, neck, scalp, nasopharynx, maxillary antrum, cranial base and parotid gland. However, frequencies at each site differ depending on the published series [Colville et al, 2005; Bentz et al, 2004; de Bree et al, 2006]. The histological varieties are diverse, but the most frequent are malignant fibrous histiocytoma (MFH) and fibrosarcoma [de Bree et al, 2006]. In Mexico, a total of 27 cases were reported by the National Institute of Cancerology (INCan) from 1982-1993, and the most frequent histological types were rhabdomyosarcoma and malignant peripheral nerve sheath tumors [Barrera et al, 1997]. The General Hospital of Mexico reported a total of 29 head and neck sarcomas cases 1993 to 1997, and the most frequent histological types were neurogenic sarcomas and leiomyosarcomas [Lazos et al, 1999]. The natural history of head and neck sarcomas is similar to that of sarcomas in other parts of the body; however, because of their location, they present a greater surgical difficulty, and residual disease is often left behind thus reducing the patient's life expectancy [Barrera et al, 1997]. Despite this variety of histologic subtypes, soft tissue sarcomas have some clinical and pathologic features in common. The current American Joint Committee on Cancer (AJCC) and International Union Against Cancer (UICC) staging

**1. Introduction** 

and Marcelo Gomez Palacio - Gastelúm

*Universidad Juarez del Estado de Durango* 

*Departamento de Investigacion, Escuela de Odontologia,* 

[33] Spunt SL et al. Prognostic Factors for Children and Adolescents With Surgically Resected Nonrhabdomyosarcoma Soft Tissue Sarcoma: An Analysis of 121 Patients Treated at St Jude Children's Research Hospital. Journal of Clinical Oncology 2002;20(15): 3225-3235

## **Head and Neck Soft Tissue Sarcoma**

Rogelio Gonzalez – Gonzalez, Ronell Bologna – Molina, Omar Tremillo – Maldonado, Ramon Gil Carreon – Burciaga and Marcelo Gomez Palacio - Gastelúm *Departamento de Investigacion, Escuela de Odontologia, Universidad Juarez del Estado de Durango Mexico* 

### **1. Introduction**

116 Soft Tissue Tumors

[33] Spunt SL et al. Prognostic Factors for Children and Adolescents With Surgically

2002;20(15): 3225-3235

Resected Nonrhabdomyosarcoma Soft Tissue Sarcoma: An Analysis of 121 Patients Treated at St Jude Children's Research Hospital. Journal of Clinical Oncology

> Soft tissue sarcomas are a group of heterogeneous tumors that have their origin primarily in the embryonic mesoderm; more than 50 histological subtypes and diverse clinical behaviors have been identified. Soft tissue sarcomas can range from relatively slow growth, causing little destructive growth, to being locally aggressive, regionally destructive and having a great potential for systemic metastases [Greene et al, 2002; Pelliteri et al, 2003]. The approximate incidence for this kind of neoplasia is 3-4.5/100,000 [Zahm et al, 1997], representing approximately 1% of all malignant adult neoplasias. Soft tissue sarcomas are rare in the head and neck and have an approximate frequency of 5-15% of all adult sarcomas and less than 1% of all head and neck neoplasias [Patel et al, 2001; Pandey et al, 2003; Colville et al, 2005]. The age at presentation is variable with a mean of 50 to 55 years (minimum is 3 months and the maximum is 89 years old) and the male/female ratio is approximately 2:1, which varies depending on the review series. The symptoms depend on location, but the most frequently reported symptoms are the following: headache, nasal obstruction, dysphagia, hoarseness and dyspnea. However, the majority of patients are asymptomatic [Farhood et al]. The most frequently reported involved sites include the following: the face, neck, scalp, nasopharynx, maxillary antrum, cranial base and parotid gland. However, frequencies at each site differ depending on the published series [Colville et al, 2005; Bentz et al, 2004; de Bree et al, 2006]. The histological varieties are diverse, but the most frequent are malignant fibrous histiocytoma (MFH) and fibrosarcoma [de Bree et al, 2006]. In Mexico, a total of 27 cases were reported by the National Institute of Cancerology (INCan) from 1982-1993, and the most frequent histological types were rhabdomyosarcoma and malignant peripheral nerve sheath tumors [Barrera et al, 1997]. The General Hospital of Mexico reported a total of 29 head and neck sarcomas cases 1993 to 1997, and the most frequent histological types were neurogenic sarcomas and leiomyosarcomas [Lazos et al, 1999]. The natural history of head and neck sarcomas is similar to that of sarcomas in other parts of the body; however, because of their location, they present a greater surgical difficulty, and residual disease is often left behind thus reducing the patient's life expectancy [Barrera et al, 1997]. Despite this variety of histologic subtypes, soft tissue sarcomas have some clinical and pathologic features in common. The current American Joint Committee on Cancer (AJCC) and International Union Against Cancer (UICC) staging

Head and Neck Soft Tissue Sarcoma 119

survival of all clinical types of angiosarcomas ranges between 15 and 30 months [Penel N et al, 2003, Favia G et al, 2002]. Angiosarcoma can occur in pre-existing benign or intermediate vascular lesions; there are several case reports of angiosarcomas arising spontaneously from hemangiomas or vascular malformations. The mechanism of malignant transformation in benign vascular tumors is unclear because there are few case reports [Hunt SJ et al, 2004]. A history of trauma may be an etiological factor in angiosarcomas, but most authors think that a traumatic event only alerts the patient to a lesion that already existed. Other factors that have been implicated include hormonal influences from anabolic steroids, synthetic estrogens or pregnancy, exposure to environmental toxins, such as thorium dioxide, vinyl chloride, thorotrast (used for angiography in the past), or insecticides. Immunohistochemical analysis is an important adjunctive diagnostic approach for angiosarcoma [Koch M et al, 2008]. The tumors are usually positive for factor VIII-related antigen, vimentin, CD31, CD34 and UEA-1. Among these factors, CD31 is positive in almost 80– 90% of angiosarcomas, with relatively good specificity and excellent sensitivity [Morgan MB et al, 2004]. The microscopic appearance of angiosarcoma varies from epithelioid to spindled areas, with the former being more common. Various prognostic factors have been reported, including older age, tumor size larger than 5 cm, high grade, positive margin and lymphedema field location [Skubitz KM et al, 2005]. A prospective clinical study with a larger sample size is needed to determine the prognostic factors in angiosarcoma patients. Early diagnosis is important for early treatment. A medical history should be obtained, and a thorough physical examination should be performed. Magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CT) are nonspecific for diagnosis, but they may be used to define the extent of the primary tumor and evaluate distant metastasis. The diagnosis of angiosarcoma can only be established by microscopic examination. The macroscopic and microscopic appearance of this tumor can lead to a misdiagnosis of pyogenic granuloma. The differential clinical diagnoses should include pyogenic granuloma, giant cell granuloma, Kaposi sarcoma, hemangioma, and malignant melanoma [Mullick SS et al, 1997]. Likewise, the differential microscopic diagnoses should include hemangioma, hemangiopericytoma, papillary endothelial hyperplasia, angiolymphoid hyperplasia with eosinophilia, Kaposi sarcoma, malignant melanoma, metastatic renal cell carcinoma, and pyogenic granuloma [Mullick SS et al, 1997]. Treatment of angiosarcomas is greatly complicated by the diffuse infiltration typical of these tumors. Various interventions have been attempted to stem the disease process. In a recent detailed treatment analysis, surgery in combination with radiation therapy affords the most favorable opportunity for angiosarcoma control [Mark RJ et al, 1996]. The prognosis for patients with angiosarcoma is generally considered to be rather poor, although tumor size (and hence stage), site, and the histopathologic grade may influence survival. Investigations indicate that one-half of patients die within 15 months of diagnosis, with only approximately 12% surviving 5 years or longer. However, those patients presenting with lesions less than 10 cm in diameter respond better to therapy

Recurrence after local treatment manifests primarily in local failure, yet distant metastasis is not insignificant in the post-treatment failure group [Mark RJ et al, 1996]. These factors, both for local and distant spread, are reflective of the highly aggressive nature of this illness and

[Mentzel T et al, 1998].

serve to explain the poor survival statistics.

criteria for soft tissue sarcomas are universal for almost all histologic subtypes and rely on the histologic grade, tumor size and depth and the presence of distant or nodal metastases. Therefore, the particular subtype seems to be of less importance [de Bree et al, 2006]. The main prognostic factor for soft tissue sarcomas is histological grade and tumor size. Staging is performed according to the AJCC, which has four clinical stages ranging from I to IV [Mendenhall et al, 2005]. Regarding the evolution of the disease, head and neck sarcomas frequently present metastases, most commonly lung metastases, and the initial management therefore includes a chest X-ray or a computed tomography scan. The absence of metastatic lesions excludes the possibility of a systemic disease [Mendenhall et al, 2005]. In children, head and neck sarcomas respond appropriately when treated with chemotherapy and radiation therapy. In adults, the main treatment modality is surgical, although multidisciplinary treatment is also important because these kinds of tumors frequently invade or are in close proximity to vital structures. As a result, surgical resection could be incomplete, making it necessary to locally control the disease by means of adjuvant therapies [Le QT et al, 1997].

The purpose of this chapter is a review of frequency, clinical features, histopathology, molecular biology, metastasis and treatment of soft tissue sarcomas of the head and neck.

#### **2. Angiosarcoma of head and neck**

Angiosarcoma is a malignant neoplasm that frequently occurs in the skin and subcutis or in a visceral location and very rarely affects the oral cavity [Loudon JA et al, 2000, Oliver AJ et al, 1991]. Clinically, angiosarcoma appears as a poorly demarcated nodular tumor that is red-blue to purplish in color [Toth BB, et al, 1981]. Angiosarcomas of the head and neck most commonly involve the scalp, and only 4–5% of them form in the pharynx, oral cavity or maxillary sinus [Loudon JA et al, 2000, Lanigan DT, et al 1989]. They may represent either primary or metastatic lesions. In a recent review of the literature, only 23 cases were reported to involve the head and neck, with the exception of the scalp, at an age of presentation ranging from 1 day to 68 years [Abdullah BH et al, 2000, Loudon JA et al, 2000]. Angiosarcomas predominantly affect elderly men and may be present in any region of the body, but they usually occur in the skin or superficial soft tissues (head and neck) in the post-radiotherapy area. The prognosis is poor because of frequent local recurrence and metastatic spread to the lymph nodes, bones (vertebrae) and lungs [Forton Glen EJ et al, 2005]. Primary angiosarcoma of the non-irradiated parotid gland is extremely rare. There are only a few articles in literature that discuss patients with angiosarcoma, but most of these angiosarcomas affected the irradiated region or originated in the skin and secondarily affected the parotid gland. All angiosarcomas tend to be aggressive, and they are often multicentered. These tumors have a high local recurrence rate and metastasize because of their intrinsic biological properties and because they are often misdiagnosed, which leads to a poor prognosis and high mortality rate. This malignant vascular tumor is clinically aggressive, difficult to treat, and has a reported five-year survival rate of less than 20%. Advanced stage at presentation and lack of extensive excision are associated with higher recurrence, distant metastasis rates, and worsened survival [Mahdhaoui A et al, 2004]. About 30% of oral metastases are the first sign of an undiscovered malignancy at a distant site. Angiosarcomas represent 1% of all soft tissue sarcomas. Their clinical outcomes are poor due to a rapid growth and high risk of metastatic extension. The median overall

criteria for soft tissue sarcomas are universal for almost all histologic subtypes and rely on the histologic grade, tumor size and depth and the presence of distant or nodal metastases. Therefore, the particular subtype seems to be of less importance [de Bree et al, 2006]. The main prognostic factor for soft tissue sarcomas is histological grade and tumor size. Staging is performed according to the AJCC, which has four clinical stages ranging from I to IV [Mendenhall et al, 2005]. Regarding the evolution of the disease, head and neck sarcomas frequently present metastases, most commonly lung metastases, and the initial management therefore includes a chest X-ray or a computed tomography scan. The absence of metastatic lesions excludes the possibility of a systemic disease [Mendenhall et al, 2005]. In children, head and neck sarcomas respond appropriately when treated with chemotherapy and radiation therapy. In adults, the main treatment modality is surgical, although multidisciplinary treatment is also important because these kinds of tumors frequently invade or are in close proximity to vital structures. As a result, surgical resection could be incomplete, making it necessary to locally control the disease by means of adjuvant

The purpose of this chapter is a review of frequency, clinical features, histopathology, molecular biology, metastasis and treatment of soft tissue sarcomas of the head and neck.

Angiosarcoma is a malignant neoplasm that frequently occurs in the skin and subcutis or in a visceral location and very rarely affects the oral cavity [Loudon JA et al, 2000, Oliver AJ et al, 1991]. Clinically, angiosarcoma appears as a poorly demarcated nodular tumor that is red-blue to purplish in color [Toth BB, et al, 1981]. Angiosarcomas of the head and neck most commonly involve the scalp, and only 4–5% of them form in the pharynx, oral cavity or maxillary sinus [Loudon JA et al, 2000, Lanigan DT, et al 1989]. They may represent either primary or metastatic lesions. In a recent review of the literature, only 23 cases were reported to involve the head and neck, with the exception of the scalp, at an age of presentation ranging from 1 day to 68 years [Abdullah BH et al, 2000, Loudon JA et al, 2000]. Angiosarcomas predominantly affect elderly men and may be present in any region of the body, but they usually occur in the skin or superficial soft tissues (head and neck) in the post-radiotherapy area. The prognosis is poor because of frequent local recurrence and metastatic spread to the lymph nodes, bones (vertebrae) and lungs [Forton Glen EJ et al, 2005]. Primary angiosarcoma of the non-irradiated parotid gland is extremely rare. There are only a few articles in literature that discuss patients with angiosarcoma, but most of these angiosarcomas affected the irradiated region or originated in the skin and secondarily affected the parotid gland. All angiosarcomas tend to be aggressive, and they are often multicentered. These tumors have a high local recurrence rate and metastasize because of their intrinsic biological properties and because they are often misdiagnosed, which leads to a poor prognosis and high mortality rate. This malignant vascular tumor is clinically aggressive, difficult to treat, and has a reported five-year survival rate of less than 20%. Advanced stage at presentation and lack of extensive excision are associated with higher recurrence, distant metastasis rates, and worsened survival [Mahdhaoui A et al, 2004]. About 30% of oral metastases are the first sign of an undiscovered malignancy at a distant site. Angiosarcomas represent 1% of all soft tissue sarcomas. Their clinical outcomes are poor due to a rapid growth and high risk of metastatic extension. The median overall

therapies [Le QT et al, 1997].

**2. Angiosarcoma of head and neck** 

survival of all clinical types of angiosarcomas ranges between 15 and 30 months [Penel N et al, 2003, Favia G et al, 2002]. Angiosarcoma can occur in pre-existing benign or intermediate vascular lesions; there are several case reports of angiosarcomas arising spontaneously from hemangiomas or vascular malformations. The mechanism of malignant transformation in benign vascular tumors is unclear because there are few case reports [Hunt SJ et al, 2004]. A history of trauma may be an etiological factor in angiosarcomas, but most authors think that a traumatic event only alerts the patient to a lesion that already existed. Other factors that have been implicated include hormonal influences from anabolic steroids, synthetic estrogens or pregnancy, exposure to environmental toxins, such as thorium dioxide, vinyl chloride, thorotrast (used for angiography in the past), or insecticides. Immunohistochemical analysis is an important adjunctive diagnostic approach for angiosarcoma [Koch M et al, 2008]. The tumors are usually positive for factor VIII-related antigen, vimentin, CD31, CD34 and UEA-1. Among these factors, CD31 is positive in almost 80– 90% of angiosarcomas, with relatively good specificity and excellent sensitivity [Morgan MB et al, 2004]. The microscopic appearance of angiosarcoma varies from epithelioid to spindled areas, with the former being more common. Various prognostic factors have been reported, including older age, tumor size larger than 5 cm, high grade, positive margin and lymphedema field location [Skubitz KM et al, 2005]. A prospective clinical study with a larger sample size is needed to determine the prognostic factors in angiosarcoma patients. Early diagnosis is important for early treatment. A medical history should be obtained, and a thorough physical examination should be performed. Magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CT) are nonspecific for diagnosis, but they may be used to define the extent of the primary tumor and evaluate distant metastasis. The diagnosis of angiosarcoma can only be established by microscopic examination. The macroscopic and microscopic appearance of this tumor can lead to a misdiagnosis of pyogenic granuloma. The differential clinical diagnoses should include pyogenic granuloma, giant cell granuloma, Kaposi sarcoma, hemangioma, and malignant melanoma [Mullick SS et al, 1997]. Likewise, the differential microscopic diagnoses should include hemangioma, hemangiopericytoma, papillary endothelial hyperplasia, angiolymphoid hyperplasia with eosinophilia, Kaposi sarcoma, malignant melanoma, metastatic renal cell carcinoma, and pyogenic granuloma [Mullick SS et al, 1997]. Treatment of angiosarcomas is greatly complicated by the diffuse infiltration typical of these tumors. Various interventions have been attempted to stem the disease process. In a recent detailed treatment analysis, surgery in combination with radiation therapy affords the most favorable opportunity for angiosarcoma control [Mark RJ et al, 1996]. The prognosis for patients with angiosarcoma is generally considered to be rather poor, although tumor size (and hence stage), site, and the histopathologic grade may influence survival. Investigations indicate that one-half of patients die within 15 months of diagnosis, with only approximately 12% surviving 5 years or longer. However, those patients presenting with lesions less than 10 cm in diameter respond better to therapy [Mentzel T et al, 1998].

Recurrence after local treatment manifests primarily in local failure, yet distant metastasis is not insignificant in the post-treatment failure group [Mark RJ et al, 1996]. These factors, both for local and distant spread, are reflective of the highly aggressive nature of this illness and serve to explain the poor survival statistics.

Head and Neck Soft Tissue Sarcoma 121

The histological appearance of fibrosarcoma does not allow a distinction between a tumor of the bone from one arising in soft tissue [Chen Y et al, 2007]. Histologically, the degree of differentiation is variable, from being comparable to a benign fibroma to a highly anaplastic tumor, thus presenting a diagnostic dilemma to histopathologists. Fibrosarcoma can be graded as either a low or high grade of malignancy. Low-grade fibrosarcoma shows spindle cells arranged in fascicles with low to moderate cellularity and a herringbone appearance. This type of fibrosarcoma has a mild degree of nuclear pleomorphism and rare mitosis, with a collagenous stroma. High-grade lesions show an intense nuclear pleomorphism, greater cellularity and atypical mitosis. The nuclei can be spindle shaped, oval or round. The histological appearance of high-grade fibrosarcoma may be similar to other tumors, such as malignant fibrous histiocytoma, liposarcoma or synovial sarcoma. The positive immunostaining for vimentin, together with negative staining for muscular

Sclerosing epithelioid fibrosarcoma was originally described in 1995 by Meis-Kindblom et al [Meis-Kindblom JM et al, 1995], as an uncommon low-grade variant of fibrosarcoma that is found mainly in the deep soft tissue of the extremities. It is characterized by distinctive epithelioid cytomorphology associated with extensive stromal hyalinization. Tumors with definitive intraosseous origin are uncommon, despite the fact that sclerosing epithelioid fibrosarcoma has a predilection for bone invasion [Antonescu CR et al, 2001]. Histologically, it is characterized by a multinodular proliferation of sheets, nests, or cords of uniform round to oval epithelioid cells with distinctive cell borders. The cytoplasm of the tumor cells is pale eosinophilic to clear, and the nuclei are rounded, although in some areas where the tumor cells are tightly packed together, nuclear angulation may be evident. These cells are embedded in a densely hyalinized stroma. Areas of myxoid degeneration, cystic change, foci of metaplastic bone, hyaline cartilage, and calcification are additional features that may be present [Eyden BP et al, 1998]. Immunohistochemically, the tumor cells of sclerosing epithelioid fibrosarcoma do not display definitive evidence of differentiation along a specific lineage. Most examples are immunoreactive with vimentin, but variable staining for EMA, S100, AE1/AE3, Bcl-2, CD34 and CD99 has been reported [Antonescu et al, 2001, Donner LR

Ameloblastic fibrosarcoma, first described by Heath in 1887, is an extremely rare malignant odontogenic tumor. It is composed of a benign odontogenic epithelium and a malignant ectomesenchymal component. It is regarded as the malignant counterpart of the ameloblastic fibroma. Ameloblastic fibrosarcoma normally presents as a painful swelling and intraosseous mass (2-6 cm), with occasional ulceration in the posterior regions of the mandible and/or maxilla. The posterior mandibular area is the most commonly affected site; the disease is more likely to occur in males than females (1.6:1). Ameloblastic fibrosarcoma occurs in a wide age range, from 3 to 83 years (mean age, 27.3 years). Only one case of peripheral presentation has been reported. The histopathology of ameloblastic fibrosarcoma is characterized by a consistent appearance in which a malignant ectomesenchymal component is mixed with a benign epithelial odontogenic component; the malignant ectomesechymal component consistently takes up more than 70% of the tumor

immunomarkers, helps to diagnose fibrosarcoma [Wadhwan V et al, 2010].

**3.1 Sclerosing epithelioid fibrosarcoma of head and neck** 

et al, 2000].

**3.2 Ameloblastic fibrosarcoma** 

Fig. 1. a) Angiosarcoma of the maxilla in an elderly woman, b) Epithelioid angiosarcoma of oral mucosal maxillar region, 40X, c) Inmunostain for factor VIII shows intense staining of most angiosarcoma cells, 40X.

## **3. Fibrosarcoma of head and neck**

Fibrosarcoma is defined as a malignant spindle cell tumor that shows a herringbone or interlacing fasicular pattern without the expression of other connective tissue cell markers [Sapp JP et al, 2004]. Fibrosarcoma can arise in soft tissues or within bones. Intraossesous fibrosarcomas may develop enosteally or possibly periosteally, affecting the bone by spreading from adjacent soft tissue. Fibrosarcomas can occur in any location, but the bone extremities are the main affected sites; occurrence in the maxilla is rare, with an incidence ranging from 0-6.1% of all primary fibrosarcomas of the bone. The mandible is the most common site for fibrosarcomas [Soares et al 2006, Pereira CM et al, 2005]. The clinical behavior of fibrosarcoma is characterized by a high local recurrence rate and a low incidence of locoregional lymph node and/or distant hematogenous metastases. However, hematogenus metastases may involve the lungs, mediastinum, abdominal cavity and bone [Conley J et al, 1967]. Local recurrence poses a serious and complex problem, particularly with occurrence of mediastinum infiltration, local destruction, airway compression, esophageal compression and extension. Radiation therapy is generally considered only in cases for which resection is impossible; chemotherapy is only used for palliative treatment. Prognosis is directly related to adequate, complete resection, which obviously requires early detection before the extensive involvement of soft tissue [Lukinmaa P et al, 1988].

Fig. 1. a) Angiosarcoma of the maxilla in an elderly woman, b) Epithelioid angiosarcoma of oral mucosal maxillar region, 40X, c) Inmunostain for factor VIII shows intense staining of

Fibrosarcoma is defined as a malignant spindle cell tumor that shows a herringbone or interlacing fasicular pattern without the expression of other connective tissue cell markers [Sapp JP et al, 2004]. Fibrosarcoma can arise in soft tissues or within bones. Intraossesous fibrosarcomas may develop enosteally or possibly periosteally, affecting the bone by spreading from adjacent soft tissue. Fibrosarcomas can occur in any location, but the bone extremities are the main affected sites; occurrence in the maxilla is rare, with an incidence ranging from 0-6.1% of all primary fibrosarcomas of the bone. The mandible is the most common site for fibrosarcomas [Soares et al 2006, Pereira CM et al, 2005]. The clinical behavior of fibrosarcoma is characterized by a high local recurrence rate and a low incidence of locoregional lymph node and/or distant hematogenous metastases. However, hematogenus metastases may involve the lungs, mediastinum, abdominal cavity and bone [Conley J et al, 1967]. Local recurrence poses a serious and complex problem, particularly with occurrence of mediastinum infiltration, local destruction, airway compression, esophageal compression and extension. Radiation therapy is generally considered only in cases for which resection is impossible; chemotherapy is only used for palliative treatment. Prognosis is directly related to adequate, complete resection, which obviously requires early detection before the extensive involvement of soft tissue

most angiosarcoma cells, 40X.

[Lukinmaa P et al, 1988].

**3. Fibrosarcoma of head and neck** 

The histological appearance of fibrosarcoma does not allow a distinction between a tumor of the bone from one arising in soft tissue [Chen Y et al, 2007]. Histologically, the degree of differentiation is variable, from being comparable to a benign fibroma to a highly anaplastic tumor, thus presenting a diagnostic dilemma to histopathologists. Fibrosarcoma can be graded as either a low or high grade of malignancy. Low-grade fibrosarcoma shows spindle cells arranged in fascicles with low to moderate cellularity and a herringbone appearance. This type of fibrosarcoma has a mild degree of nuclear pleomorphism and rare mitosis, with a collagenous stroma. High-grade lesions show an intense nuclear pleomorphism, greater

cellularity and atypical mitosis. The nuclei can be spindle shaped, oval or round. The histological appearance of high-grade fibrosarcoma may be similar to other tumors, such as malignant fibrous histiocytoma, liposarcoma or synovial sarcoma. The positive immunostaining for vimentin, together with negative staining for muscular immunomarkers, helps to diagnose fibrosarcoma [Wadhwan V et al, 2010].

#### **3.1 Sclerosing epithelioid fibrosarcoma of head and neck**

Sclerosing epithelioid fibrosarcoma was originally described in 1995 by Meis-Kindblom et al [Meis-Kindblom JM et al, 1995], as an uncommon low-grade variant of fibrosarcoma that is found mainly in the deep soft tissue of the extremities. It is characterized by distinctive epithelioid cytomorphology associated with extensive stromal hyalinization. Tumors with definitive intraosseous origin are uncommon, despite the fact that sclerosing epithelioid fibrosarcoma has a predilection for bone invasion [Antonescu CR et al, 2001]. Histologically, it is characterized by a multinodular proliferation of sheets, nests, or cords of uniform round to oval epithelioid cells with distinctive cell borders. The cytoplasm of the tumor cells is pale eosinophilic to clear, and the nuclei are rounded, although in some areas where the tumor cells are tightly packed together, nuclear angulation may be evident. These cells are embedded in a densely hyalinized stroma. Areas of myxoid degeneration, cystic change, foci of metaplastic bone, hyaline cartilage, and calcification are additional features that may be present [Eyden BP et al, 1998]. Immunohistochemically, the tumor cells of sclerosing epithelioid fibrosarcoma do not display definitive evidence of differentiation along a specific lineage. Most examples are immunoreactive with vimentin, but variable staining for EMA, S100, AE1/AE3, Bcl-2, CD34 and CD99 has been reported [Antonescu et al, 2001, Donner LR et al, 2000].

#### **3.2 Ameloblastic fibrosarcoma**

Ameloblastic fibrosarcoma, first described by Heath in 1887, is an extremely rare malignant odontogenic tumor. It is composed of a benign odontogenic epithelium and a malignant ectomesenchymal component. It is regarded as the malignant counterpart of the ameloblastic fibroma. Ameloblastic fibrosarcoma normally presents as a painful swelling and intraosseous mass (2-6 cm), with occasional ulceration in the posterior regions of the mandible and/or maxilla. The posterior mandibular area is the most commonly affected site; the disease is more likely to occur in males than females (1.6:1). Ameloblastic fibrosarcoma occurs in a wide age range, from 3 to 83 years (mean age, 27.3 years). Only one case of peripheral presentation has been reported. The histopathology of ameloblastic fibrosarcoma is characterized by a consistent appearance in which a malignant ectomesenchymal component is mixed with a benign epithelial odontogenic component; the malignant ectomesechymal component consistently takes up more than 70% of the tumor

Head and Neck Soft Tissue Sarcoma 123

adults (mean age, 45 years), with men affected more frequently than women. The sinonasal tract is the most common site of origin, followed by the soft tissue of the face and neck, the oral cavity, and the craniofacial region [Park SW et al, 2009]. The signs and symptoms of MFH of the maxilla include swelling of the cheek, facial pain, nasal obstruction and rhinorrhea. The rarer symptoms include infraorbital nerve paresthesia, visual disturbance, and ocular proptosis. In cases of MFH of the mandible, Kanazawa et al [Kanazawa H et al, 2003]. reported in their review that those lesions are usually first noticed due to swelling, paresthesia, and loosening of teeth. A history of antecedent trauma in about 20% of the cases suggests that some of these tumors may represent an initial proliferative response to the trauma [Senel FC et al, 2006]. Although radical tumor resection with adequate tumor-free margins is essential, from the anatomic point of view, it is often difficult to perform in the head and neck region [Kearney MM et al, 1980]. Park et al [Park SW et al, 2009]. reported in a review that CT and MRI features of MFH of the head and neck have also been nonspecific. On CT scans, MFH is usually seen as a large lobulated soft-tissue mass, which is isoattenuated to muscle. Sato et al [Sato T et al, 2001] . reported that lesions of the maxilla sometimes present radiographically as fairly well-demarcated bone margins, with uniform density or no necrotic areas, and with a clear separation from surrounding soft tissues in CT images, which lead to a misdiagnosis of low-grade malignant tumors or benign tumors. On the MRI, MFH is seen as a heterogeneous hyperintense pattern on T2-weighted images, with an isointensity that is almost the same as that of the muscles on T1-weighted images [Park SW et al, 2009]. Intraosseous MFH has a tendency to indicate a poor prognosis. However, in the maxillary area, it is difficult to differentiate intraosseous MFHs from extraosseous MFHs and to definitively determine the origin when these MFHs were large in size and had aggressive bone involvement [Yamaguchi S et al, 2004]. Also, survival rates of MFH of the maxilla are difficult to evaluate due to the small number of documented cases Chan YW et al, 2004]. With regard to sinonasal MFH, the five year disease-free survival rate and the five year overall survival rate are only 21.5% and 25.1%, respectively [Wang CP et al, 2009]. Anavi et al [Anavi Y et al, 1989]. reported in their review of mandibular MFH that the overall survival estimate at five years was 46% regardless of the type of treatment. Clinical stage, histological grade of malignancy, and local recurrences were the most important prognostic factors for MFH in the bone. Huvos et al [Huvos AG et al, 1985]. suggested that metastatic spread in patients with MFH primarily in the bone was not to the regional lymph nodes, but rather a hematogenous dissemination predominantly to the lungs. The reported frequency of nodal metastases for head and neck MFH varies between 0% and 15%. Prognosis differs according to the morphologic subtypes of MFH [Park SW et al, 2009], Derbel F et al [Derberl F et al, 2010], reported a case of MFH in the neck with metastases to liver. Metastases from MFH in liver are rare, representing 1% of reported metastasis of MFH [Derbel F et al, 2010]. Metastasis occurs in 42% of cases. Lung (82%) and lymph nodes (32%) metastases are most frequent [Derbel et al, 2010]. Factors that influence the rate of metastasis included depth, size and the inflammatory component of the tumour [Derbel F et al, 2010]. The myxoid type has a higher rate of local recurrence, with recurrence in approximately 50– 60% of patients and with an overall risk of subsequent metastases at 20–35% [Marotta D et, al, 2009, Mentzel T et al, 2002]. Histologically, the tumor contains both fibroblast-like and histiocyte-like cells in varying proportions, with spindle and round cells exhibiting a storiform arrangement. These tumors have been divided into four morphologic subtypes that depend on the predominant cellular components: storiform – pleomorphic (50–60%), myxoid (25%), giant cell (5–10%), and inflammatory (about 5%). The myxoid variant has

area compared with 30% by the odontogenic epithelium. Ameloblastic fibrosarcoma resembles a malignant connective tissue. The World Health Organization distinguishes odontogenic sarcomas devoid of dental hard tissue ameloblastic fibrosarcoma from those displaying focal evidence of dentinoid (ameloblastic fibrodentinosarcoma) or dentinoid plus enameloid (ameloblastic fibro-odontosarcoma) but acknowledges that the presence or absence of dental hard tissue in an odontogenic sarcoma is of no prognostic significance. This sacorma has an unknown etiology, with some cases representing malignant transformation of a preexistent ameloblastic fibrosarcoma. Although approximately twothirds of ameloblastic fibrosarcomas seemed to have arisen de novo, several authors have demonstrated that ameloblastic fibroma to be the precursor of ameloblastic fibrosarcoma, i.e., malignant transformation. This neoplasm has a higly localized behavior with low potential for distant metastasis. The treatment of choice is the radical extensive surgery, usually necessitating partial or total mandibulectomy. The prognosis of ameloblastic fibrosarcoma seems better than that for other fibrosarcomas of the orofacial region [Carlos R et al, 2005, Reichart PA et al, 2004]

## **4. Malignant fibrous histiocytoma of head and neck**

Malignant fibrous histiocytoma (MFH) was first described by Ozzelo et al, in 1963 [Pezzi CM et al, 1992] and by O'Brien and Stout in 1964 [Sabesan T et al, 2006]. It was widely accepted as a clinicopathological entity after the description of cases by Kempson and Kyriakos in 1972 [Barnes L et al, 1988]. The etiology is unknown, and the histiogenesis remains controversial. Several hypotheses have been suggested, including an origin from true histiocytes, fibroblasts, both fibroblasts and histiocytes, or from primitive mesenchymal cells. [Ogawa A et al, 2005].

Malignant fibrous histiocytoma is now recognized as one of the most common soft tissue sarcomas in adults. In addition to occurring in soft tissue, it can also occur as a primary intraosseous tumor in bones. It affects, in order of frequency, the lower extremity, the upper extremity, the retroperitonoum and abdominal cavity, and lastly, the head and neck, where it accounts for 1–3% of all cases [Gibbs JF et al, 2001]. Therefore, it is relatively uncommon in the head and neck region. Surgery is the most reliable treatment for MFH, but the five year survival rate for MFH in the head and neck is low compared with MFH in the extremities and trunk. In the head and neck, MFH has been observed in the nasal sinus, salivary gland, oral cavity, mandible, larynx, auricula and eyelid, and Barnes et al [Barnes L et al, 1988], reported that MFH onset occurs most commonly in the accessory nasal sinuses, followed by the salivary glands. In a study of 11 sarcomas of the parotid gland, histological classification showed that three of the lesions were MFH and two cases each of neurosarcoma, rhabdomyosarcoma, fibrosarcoma, and osteosarcoma. A single case of MFH in the buccal region was also reported [Ogawa A et al, 2005]. In the literature, in cases of MFH in the head and neck, the onset age ranged from 16 years old in a patient with MFH in the mandible to 85 years old in a patient with MFH in the eyelid, and the mean age of 12 patients with head and neck MFH was reported to be 55 years old [Khong JJ et al, 2005, Barnes L et al, 1988, Narvaez JA et al, 1996]. The occurrence of MFH in membranous bones is unusual. Involvement of the mandible accounts for only 3% of all MFH of the bone. MFH of the head and neck that extend into bony structures are associated with a much more aggressive clinical course than those that are restricted to soft tissues [Rinaldo A et al, 2004, Iguchi Y et al, 2002] The occurrence of MFH in the head and neck region was primarily in middle-aged

area compared with 30% by the odontogenic epithelium. Ameloblastic fibrosarcoma resembles a malignant connective tissue. The World Health Organization distinguishes odontogenic sarcomas devoid of dental hard tissue ameloblastic fibrosarcoma from those displaying focal evidence of dentinoid (ameloblastic fibrodentinosarcoma) or dentinoid plus enameloid (ameloblastic fibro-odontosarcoma) but acknowledges that the presence or absence of dental hard tissue in an odontogenic sarcoma is of no prognostic significance. This sacorma has an unknown etiology, with some cases representing malignant transformation of a preexistent ameloblastic fibrosarcoma. Although approximately twothirds of ameloblastic fibrosarcomas seemed to have arisen de novo, several authors have demonstrated that ameloblastic fibroma to be the precursor of ameloblastic fibrosarcoma, i.e., malignant transformation. This neoplasm has a higly localized behavior with low potential for distant metastasis. The treatment of choice is the radical extensive surgery, usually necessitating partial or total mandibulectomy. The prognosis of ameloblastic fibrosarcoma seems better than that for other fibrosarcomas of the orofacial region [Carlos R

Malignant fibrous histiocytoma (MFH) was first described by Ozzelo et al, in 1963 [Pezzi CM et al, 1992] and by O'Brien and Stout in 1964 [Sabesan T et al, 2006]. It was widely accepted as a clinicopathological entity after the description of cases by Kempson and Kyriakos in 1972 [Barnes L et al, 1988]. The etiology is unknown, and the histiogenesis remains controversial. Several hypotheses have been suggested, including an origin from true histiocytes, fibroblasts, both fibroblasts and histiocytes, or from primitive mesenchymal

Malignant fibrous histiocytoma is now recognized as one of the most common soft tissue sarcomas in adults. In addition to occurring in soft tissue, it can also occur as a primary intraosseous tumor in bones. It affects, in order of frequency, the lower extremity, the upper extremity, the retroperitonoum and abdominal cavity, and lastly, the head and neck, where it accounts for 1–3% of all cases [Gibbs JF et al, 2001]. Therefore, it is relatively uncommon in the head and neck region. Surgery is the most reliable treatment for MFH, but the five year survival rate for MFH in the head and neck is low compared with MFH in the extremities and trunk. In the head and neck, MFH has been observed in the nasal sinus, salivary gland, oral cavity, mandible, larynx, auricula and eyelid, and Barnes et al [Barnes L et al, 1988], reported that MFH onset occurs most commonly in the accessory nasal sinuses, followed by the salivary glands. In a study of 11 sarcomas of the parotid gland, histological classification showed that three of the lesions were MFH and two cases each of neurosarcoma, rhabdomyosarcoma, fibrosarcoma, and osteosarcoma. A single case of MFH in the buccal region was also reported [Ogawa A et al, 2005]. In the literature, in cases of MFH in the head and neck, the onset age ranged from 16 years old in a patient with MFH in the mandible to 85 years old in a patient with MFH in the eyelid, and the mean age of 12 patients with head and neck MFH was reported to be 55 years old [Khong JJ et al, 2005, Barnes L et al, 1988, Narvaez JA et al, 1996]. The occurrence of MFH in membranous bones is unusual. Involvement of the mandible accounts for only 3% of all MFH of the bone. MFH of the head and neck that extend into bony structures are associated with a much more aggressive clinical course than those that are restricted to soft tissues [Rinaldo A et al, 2004, Iguchi Y et al, 2002] The occurrence of MFH in the head and neck region was primarily in middle-aged

et al, 2005, Reichart PA et al, 2004]

cells. [Ogawa A et al, 2005].

**4. Malignant fibrous histiocytoma of head and neck** 

adults (mean age, 45 years), with men affected more frequently than women. The sinonasal tract is the most common site of origin, followed by the soft tissue of the face and neck, the oral cavity, and the craniofacial region [Park SW et al, 2009]. The signs and symptoms of MFH of the maxilla include swelling of the cheek, facial pain, nasal obstruction and rhinorrhea. The rarer symptoms include infraorbital nerve paresthesia, visual disturbance, and ocular proptosis. In cases of MFH of the mandible, Kanazawa et al [Kanazawa H et al, 2003]. reported in their review that those lesions are usually first noticed due to swelling, paresthesia, and loosening of teeth. A history of antecedent trauma in about 20% of the cases suggests that some of these tumors may represent an initial proliferative response to the trauma [Senel FC et al, 2006]. Although radical tumor resection with adequate tumor-free margins is essential, from the anatomic point of view, it is often difficult to perform in the head and neck region [Kearney MM et al, 1980]. Park et al [Park SW et al, 2009]. reported in a review that CT and MRI features of MFH of the head and neck have also been nonspecific. On CT scans, MFH is usually seen as a large lobulated soft-tissue mass, which is isoattenuated to muscle. Sato et al [Sato T et al, 2001] . reported that lesions of the maxilla sometimes present radiographically as fairly well-demarcated bone margins, with uniform density or no necrotic areas, and with a clear separation from surrounding soft tissues in CT images, which lead to a misdiagnosis of low-grade malignant tumors or benign tumors. On the MRI, MFH is seen as a heterogeneous hyperintense pattern on T2-weighted images, with an isointensity that is almost the same as that of the muscles on T1-weighted images [Park SW et al, 2009]. Intraosseous MFH has a tendency to indicate a poor prognosis. However, in the maxillary area, it is difficult to differentiate intraosseous MFHs from extraosseous MFHs and to definitively determine the origin when these MFHs were large in size and had aggressive bone involvement [Yamaguchi S et al, 2004]. Also, survival rates of MFH of the maxilla are difficult to evaluate due to the small number of documented cases Chan YW et al, 2004]. With regard to sinonasal MFH, the five year disease-free survival rate and the five year overall survival rate are only 21.5% and 25.1%, respectively [Wang CP et al, 2009]. Anavi et al [Anavi Y et al, 1989]. reported in their review of mandibular MFH that the overall survival estimate at five years was 46% regardless of the type of treatment. Clinical stage, histological grade of malignancy, and local recurrences were the most important prognostic factors for MFH in the bone. Huvos et al [Huvos AG et al, 1985]. suggested that metastatic spread in patients with MFH primarily in the bone was not to the regional lymph nodes, but rather a hematogenous dissemination predominantly to the lungs. The reported frequency of nodal metastases for head and neck MFH varies between 0% and 15%. Prognosis differs according to the morphologic subtypes of MFH [Park SW et al, 2009], Derbel F et al [Derberl F et al, 2010], reported a case of MFH in the neck with metastases to liver. Metastases from MFH in liver are rare, representing 1% of reported metastasis of MFH [Derbel F et al, 2010]. Metastasis occurs in 42% of cases. Lung (82%) and lymph nodes (32%) metastases are most frequent [Derbel et al, 2010]. Factors that influence the rate of metastasis included depth, size and the inflammatory component of the tumour [Derbel F et al, 2010]. The myxoid type has a higher rate of local recurrence, with recurrence in approximately 50– 60% of patients and with an overall risk of subsequent metastases at 20–35% [Marotta D et, al, 2009, Mentzel T et al, 2002]. Histologically, the tumor contains both fibroblast-like and histiocyte-like cells in varying proportions, with spindle and round cells exhibiting a storiform arrangement. These tumors have been divided into four morphologic subtypes that depend on the predominant cellular components: storiform – pleomorphic (50–60%), myxoid (25%), giant cell (5–10%), and inflammatory (about 5%). The myxoid variant has

Head and Neck Soft Tissue Sarcoma 125

excision has been achieved under frozen section control, and all margins were free of tumor. The prognosis depends on the size and site of the tumor and its malignant potential in terms of metastasis. The lungs are the most common site of metastasis. Post-radiation sarcomas have been reported to have poor prognosis [LinkTM et al, 1998]. One patient, however, has been reported to have long-term disease- free survival despite earlier exposure to radiation. Overall, the five year survival for mandibular malignant fibrous histioctyoma has been

Leiomyosarcoma is a malignant tumor derived from smooth muscle that accounts for 5–6% of all soft tissue sarcomas. Leiomyosarcoma usually occurs in the soft tissues of the extremities and trunk; only 3% of leiomyosarcomas are in the head and neck. In the head and neck region, most leiomyosarcomas occur in the nasal cavity and paranasal sinuses, mouth, and larynx [Marioni G et al, 2000]. The signs and symptoms of leiomyosarcoma involving the head and neck region depend on the site and the size of the tumor. Hoarseness, stridor, dyspnea and dysphagia are the most common complaints of the laryngeal and the parapharyngeal tumors. While the initial symptom in a patient with laryngeal leiomyosarcoma in one report was dysphonia, the main symptom in a second patient with parapharyngeal leiomyosarcoma was dysphagia due to the mechanic compression of the cervical esophagus. The scarcity of the smooth muscle in the head and neck region may be the probable reason for the rarity of leiomyosarcoma. Because blood vessels are the only structures in the larynx and parapharyngeal region with smooth muscles, leiomyosarcoma may develop from the smooth muscle in the tunica media of vessel walls. Aberrant mesenchymal differentiation and metastasis are the other possible modes of origin [Freije JE et al, 1992, Chen JM et al, 1991]. Leiomyosarcoma that originate in the head and neck region are very rare. Leiomyosarcoma of the hypopharynx has been reported only four times in the English medical literature. The rarity of a leiomyosarcoma in the hypopharynx can be attributed to the limited smooth muscle tissue in the hypopharynx. A possible candidate for the origin of leiomyosarcoma in the hypopharynx is the smooth muscle surrounding blood vessels. Among the four cases presented in these previous reports, two were located in the posterior wall of the hypopharynx, one in the pyriform sinus, and one in the postcricoid. The age at onset was 39–65 years (mean age, 55.4 years). The lack of any distinguishing clinical features and the rarity of these lesions often result in their being mistaken for the more common lesions affecting the oral cavity, and correct diagnosis is made only following definitive histological examination [Freedman AM et al, 1989, Cocks H et al, 1999]. The sites of the tumors in this series are similar to the regional variation within the oral cavity noted in the literature, with the maxilla being the most commonly involved site followed by the mandible, tongue, cheek and floor of mouth, in descending frequency. The cause of this apparent variation is unknown and different from benign leiomyomas, which occur more frequently in the lips, tongue, cheeks and palate. Almost 65% of reported tumors are in the maxilla or mandible, and they often involve the jaw bones [Dry SM et al, 2000, Kratochvil FJ et al 1982, Montgomery E et al, 2002]. In cases of head and neck leiomyosarcoma, the success of initial surgical management is an important prognostic factor because complete surgical excision is associated with low local recurrence and longer survival. Resection with microscopically tumor-free margins is of

reported to be 46%, irrespective of the treatment type [Anavi et al, 1989].

**5. Leiomyosarcoma of head and neck** 

been reported to have better prognosis when compared with the storiform-pleomorphic type [Park SW et al, 2009]. In the treatment of MFH of the region, adjuvant chemotherapy is considered for high-grade tumors because these tumors may present subclinical or microscopic metastases at the time of diagnosis [Pereira CM et al, 2005]. The effectiveness of surgery in combination with radiotherapy and/or chemotherapy has not been well established. Three-drug regimens with high-dose MTX, CDDP and DOX or four-drug regimens with high-dose IFO, high-dose MTX, CDDP, and DOX used in patients with osteosarcoma have been evaluated.

Fig. 2. a) Malignant fibrous histiocytoma of the dorsum tongue , b) Gross appearance of intramuscular malignant fibrous histiocytoma involving tongue, c) Malignant fibrous histiocytoma with fascicular pattern degree nuclear atypia and mitotic activity.

The regimen of neoadjuvant chemotherapy with three or four drugs has been tested in a randomized study of MFH in the bone [Hugate RR et al, 2008]. Few studies estimate the survival benefits of chemotherapy with IFO, CDDP and DOX for osteosarcoma [Zalupski MM et al, 2004]. Further research is needed to determine if adjuvant chemotherapy with the three-drug combination of IFO, CDDP and DOX would be effective for MFH of the jaws. Radiotherapy alone may be reserved for inoperable patients and patients with high surgical risk or those with regional or systemic metastases. Incomplete excision may lead to a high rate of recurrence. High rates local recurrence of MFH in the bone are due to the fact that this tumor infiltrates skeletal muscle fibers and fascial planes [Enjoji M et al, 1980]. Complete

been reported to have better prognosis when compared with the storiform-pleomorphic type [Park SW et al, 2009]. In the treatment of MFH of the region, adjuvant chemotherapy is considered for high-grade tumors because these tumors may present subclinical or microscopic metastases at the time of diagnosis [Pereira CM et al, 2005]. The effectiveness of surgery in combination with radiotherapy and/or chemotherapy has not been well established. Three-drug regimens with high-dose MTX, CDDP and DOX or four-drug regimens with high-dose IFO, high-dose MTX, CDDP, and DOX used in patients with

Fig. 2. a) Malignant fibrous histiocytoma of the dorsum tongue , b) Gross appearance of intramuscular malignant fibrous histiocytoma involving tongue, c) Malignant fibrous histiocytoma with fascicular pattern degree nuclear atypia and mitotic activity.

The regimen of neoadjuvant chemotherapy with three or four drugs has been tested in a randomized study of MFH in the bone [Hugate RR et al, 2008]. Few studies estimate the survival benefits of chemotherapy with IFO, CDDP and DOX for osteosarcoma [Zalupski MM et al, 2004]. Further research is needed to determine if adjuvant chemotherapy with the three-drug combination of IFO, CDDP and DOX would be effective for MFH of the jaws. Radiotherapy alone may be reserved for inoperable patients and patients with high surgical risk or those with regional or systemic metastases. Incomplete excision may lead to a high rate of recurrence. High rates local recurrence of MFH in the bone are due to the fact that this tumor infiltrates skeletal muscle fibers and fascial planes [Enjoji M et al, 1980]. Complete

osteosarcoma have been evaluated.

excision has been achieved under frozen section control, and all margins were free of tumor. The prognosis depends on the size and site of the tumor and its malignant potential in terms of metastasis. The lungs are the most common site of metastasis. Post-radiation sarcomas have been reported to have poor prognosis [LinkTM et al, 1998]. One patient, however, has been reported to have long-term disease- free survival despite earlier exposure to radiation. Overall, the five year survival for mandibular malignant fibrous histioctyoma has been reported to be 46%, irrespective of the treatment type [Anavi et al, 1989].

## **5. Leiomyosarcoma of head and neck**

Leiomyosarcoma is a malignant tumor derived from smooth muscle that accounts for 5–6% of all soft tissue sarcomas. Leiomyosarcoma usually occurs in the soft tissues of the extremities and trunk; only 3% of leiomyosarcomas are in the head and neck. In the head and neck region, most leiomyosarcomas occur in the nasal cavity and paranasal sinuses, mouth, and larynx [Marioni G et al, 2000]. The signs and symptoms of leiomyosarcoma involving the head and neck region depend on the site and the size of the tumor. Hoarseness, stridor, dyspnea and dysphagia are the most common complaints of the laryngeal and the parapharyngeal tumors. While the initial symptom in a patient with laryngeal leiomyosarcoma in one report was dysphonia, the main symptom in a second patient with parapharyngeal leiomyosarcoma was dysphagia due to the mechanic compression of the cervical esophagus. The scarcity of the smooth muscle in the head and neck region may be the probable reason for the rarity of leiomyosarcoma. Because blood vessels are the only structures in the larynx and parapharyngeal region with smooth muscles, leiomyosarcoma may develop from the smooth muscle in the tunica media of vessel walls. Aberrant mesenchymal differentiation and metastasis are the other possible modes of origin [Freije JE et al, 1992, Chen JM et al, 1991]. Leiomyosarcoma that originate in the head and neck region are very rare. Leiomyosarcoma of the hypopharynx has been reported only four times in the English medical literature. The rarity of a leiomyosarcoma in the hypopharynx can be attributed to the limited smooth muscle tissue in the hypopharynx. A possible candidate for the origin of leiomyosarcoma in the hypopharynx is the smooth muscle surrounding blood vessels. Among the four cases presented in these previous reports, two were located in the posterior wall of the hypopharynx, one in the pyriform sinus, and one in the postcricoid. The age at onset was 39–65 years (mean age, 55.4 years).

The lack of any distinguishing clinical features and the rarity of these lesions often result in their being mistaken for the more common lesions affecting the oral cavity, and correct diagnosis is made only following definitive histological examination [Freedman AM et al, 1989, Cocks H et al, 1999]. The sites of the tumors in this series are similar to the regional variation within the oral cavity noted in the literature, with the maxilla being the most commonly involved site followed by the mandible, tongue, cheek and floor of mouth, in descending frequency. The cause of this apparent variation is unknown and different from benign leiomyomas, which occur more frequently in the lips, tongue, cheeks and palate. Almost 65% of reported tumors are in the maxilla or mandible, and they often involve the jaw bones [Dry SM et al, 2000, Kratochvil FJ et al 1982, Montgomery E et al, 2002]. In cases of head and neck leiomyosarcoma, the success of initial surgical management is an important prognostic factor because complete surgical excision is associated with low local recurrence and longer survival. Resection with microscopically tumor-free margins is of

Head and Neck Soft Tissue Sarcoma 127

Liposarcoma is the second most common soft tissue sarcoma in adults. Its occurrence in the head and neck region is reported to be very rare. The majority of liposarcomas occur in middle-aged adults; however, very uncommon cases of liposarcoma can be generated in infancy and early childhood [Hicks J et al, 2001]. The occurrence of liposarcoma in the head and neck region is rare, comprising 5.6–9% of all cases [Enzinger FM et al, 2001]. Liposarcoma of the oral cavity is even less frequent, making up about 10% of all cases in the head and neck. In a 1995 literature review, Golledge et al [Golledge J et al, 1995]. found that liposarcoma of the head and neck was poorly addressed and that its incidence is rare, representing approximately 4-5% of liposarcomas (50 reported cases). Most cases originated in the neck (28%), followed by the head (scalp and face, 26%), larynx (20%), pharynx (18%),

Since the publication of that review, liposarcomas of the head and neck have gained more attention; however, most of the subsequent reports have addressed the primary liposarcomas of the head and neck. Fifteen cases of liposarcoma metastases to the head and neck region have been previously reported. The associated primary tumors from these reports occurred most fequently in the thigh and retroperitoneum and equally between men and women, showing no deviance from the normal trends found in liposarcoma. The average age of the patients was 53 years old. Most of the head and neck metastases were to the orbit, thyroid, and dura mater in 31%, 25%, and 19% of the cases, respectively. Other metastatic foci included the gingival mucosa, submandibular region, and scalp [McElderry et al, 2008]. Although head and neck liposarcomas are rare, specialists should be aware of the natural history, prognosis and treatment. As with liposarcomas elsewhere in the body, most cases present in adults, and there is a male predominance. Factors considered to be important in the etiology of liposarcomas include genetics, trauma and irradiation. Usually, the tumor appears firm, relatively fixed to adjacent tissues, encapsulated, and to be growing steadily but not rapidly. Patients do not usually have regional lymph node or distant metastasis at presentation [Feles RA et al, 1993, Freedman AM et al, 1989]. Radiological investigations are necessary in most cases to determine precise size, localization, limits, extensions of the tumor and its relations with neurovascular structures. It is also necessary for detecting distant metastases [Enzinger FM et al, 2001].. Liposarcoma originates from primitive mesenchymal cells rather than mature fat cells. Thus, liposarcoma seldom originates from normal fat tissue or lipoma. Furthermore, in contrast to lipoma, which ordinarily arises in the subcutaneous, submucous, or subserous tissue, liposarcoma rarely arises in such tissues, but rather in the perimuscular or perifascial structures of spindle cell liposarcoma. The next major type is the myxoid type, which is composed of three main tissue components: proliferating lipoblasts at varying stages of differentiation, a delicate plexiform capillary pattern, and a myxoid matrix containing abundant nonsulfated glycosaminoglycans. A subset of myxoid liposarcomas shows histological progression to hypercellular or round cell morphology, which is associated with poor prognosis [Christopher DM et al, 2002]. The most infrequent type is pleomorphic liposarcoma, which contains huge lipoblastic multinucleated cells by which it distinguishes itself from other pleomorphic sarcomas, such as malignant fibrohistiocytoma.The dedifferentiated type was added to these criteria recently and is composed of a well-differentiated area and a poorly differentiated area in parts of the same neoplasm, recurrent tumor or metastatic lesion. The prognosis of this tumor depends on the tumor subtype; well-differentiated and myxoid

**6. Liposarcoma of head and neck** 

and mouth (8%) [Golledge J et al, 1995].

paramount importance for long-term survival. Adjuvant radiation treatment or chemotherapy appears to be ineffective in achieving local control when there is residual tumor postoperatively [Dry SM et al, 2000]. However, gemcitabine has been one of the few agents that shows activity in these tumors, with an observed response rate of 20.5%. Hensley et al [Hensley ML et al, 2002], combined gemcitabine with docetaxel and reported a response rate of 53% in 34 patients, some of whom had failed doxorubicin therapy. The cause of leiomyosarcoma remains uncertain, although cases may be associated with trauma, oestrogenic stimulation, and ion involvement. Other publications suggest that the prognosis of oral leiomyosarcoma that affects the tongue is good if clear excision can be achieved. In the previous eight cases reported in which follow-up ranged from one to five years, there has been no evidence of recurrence [Bass B et al, 1986]. This suggests that primary leiomyosarcoma has a better prognosis if it arises within the tongue than elsewhere in the body. The recurrence rate for tumors that arise from and are limited to the dermis is reported to be between 14% and 42% [Farman AG et al, 1977]. Histopathologically displayed a prominent spindle cell component, with the cells arranged in intersecting fascicles, containing characteristic `cigar-shaped' nuclei. These features are typical for leiomyosarcoma. Nevertheless, similar findings may occur in a wide number of diferent neoplasms, such as fibrobrosarcoma, myofibrosarcoma, synovial sarcoma, solitary fibrous tumor, malignant peripheral nerve sheath tumors (MPNSTs), spindle cell rhabdomyosarcoma, spindle cell liposarcoma, spindle cell carcinoma and other spindle cell neoplasms [Izumi et al, 1995]. The arrangement of neoplastic fascicles in perpendicular, intersecting bundles, the peculiar `cigar-shaped' nuclear morphology, the occurrence of paranuclear vacuolization and intracytoplasmic PAS-positive granularity are indicative, but not exclusive, of leiomyosarcomatous diferentiation. In addition, the diagnosis of spindle cell carcinoma should always be ruled out when a spindle cell neoplasm occurs in a visceral location. In most instances, immunohistochemistry may provide useful clues to the diagnosis; muscle-specific markers for smooth muscle actin and vimentin are most frequently detectable, but myofibroblastic tumor cells, rhabdomyosarcoma and, inconstantly, spindle cell carcinomas may display a similar immunoprofile. Cytokeratin and EMA negativity, as in the case reported herein, rules out the diagnosis of spindle cell carcinoma as well as that of synovial sarcoma, the latter being vimentin and CD99 positive. Desmin immunoreactivity is not detectable in myofibroblasts, neither normal or neoplastic, but is encountered in other myogenic neoplasms, such as rhabdomyosarcoma [Muzio L et al, 2000]. Although numerous prognostic factors, including size, site, grade and TNM stage, have been identified for leiomyosarcoma arising in other sites, there are no reliable prognostic factors in the case of primary oral leiomyosarcoma. The TNM classification of soft-tissue tumors is not directly applicable to oral leiomyosarcoma, especially in terms of the T stage, and the histological grade of the tumor has rarely been reported in oral leiomyosarcoma. It is important to identify factors of prognostic significance in this patient group. The estimated five year survival for the whole group is 55%. Tumors that demonstrated bony involvement (maxilla/mandible) and metastasis were associated with poorer prognosis. Increasing age and male gender showed a trend toward worse prognosis, although this was not statistically significant. Interestingly, neither the increased size of the tumor nor recurrence was associated with poor survival, unlike tumors occurring at other sites [Miyajima K et al 2002, Weiss SW et al, 2001, Dry SM et al, 2000, Nikitakis NG et al,

2002].

paramount importance for long-term survival. Adjuvant radiation treatment or chemotherapy appears to be ineffective in achieving local control when there is residual tumor postoperatively [Dry SM et al, 2000]. However, gemcitabine has been one of the few agents that shows activity in these tumors, with an observed response rate of 20.5%. Hensley et al [Hensley ML et al, 2002], combined gemcitabine with docetaxel and reported a response rate of 53% in 34 patients, some of whom had failed doxorubicin therapy. The cause of leiomyosarcoma remains uncertain, although cases may be associated with trauma, oestrogenic stimulation, and ion involvement. Other publications suggest that the prognosis of oral leiomyosarcoma that affects the tongue is good if clear excision can be achieved. In the previous eight cases reported in which follow-up ranged from one to five years, there has been no evidence of recurrence [Bass B et al, 1986]. This suggests that primary leiomyosarcoma has a better prognosis if it arises within the tongue than elsewhere in the body. The recurrence rate for tumors that arise from and are limited to the dermis is reported to be between 14% and 42% [Farman AG et al, 1977]. Histopathologically displayed a prominent spindle cell component, with the cells arranged in intersecting fascicles, containing characteristic `cigar-shaped' nuclei. These features are typical for leiomyosarcoma. Nevertheless, similar findings may occur in a wide number of diferent neoplasms, such as fibrobrosarcoma, myofibrosarcoma, synovial sarcoma, solitary fibrous tumor, malignant peripheral nerve sheath tumors (MPNSTs), spindle cell rhabdomyosarcoma, spindle cell liposarcoma, spindle cell carcinoma and other spindle cell neoplasms [Izumi et al, 1995]. The arrangement of neoplastic fascicles in perpendicular, intersecting bundles, the peculiar `cigar-shaped' nuclear morphology, the occurrence of paranuclear vacuolization and intracytoplasmic PAS-positive granularity are indicative, but not exclusive, of leiomyosarcomatous diferentiation. In addition, the diagnosis of spindle cell carcinoma should always be ruled out when a spindle cell neoplasm occurs in a visceral location. In most instances, immunohistochemistry may provide useful clues to the diagnosis; muscle-specific markers for smooth muscle actin and vimentin are most frequently detectable, but myofibroblastic tumor cells, rhabdomyosarcoma and, inconstantly, spindle cell carcinomas may display a similar immunoprofile. Cytokeratin and EMA negativity, as in the case reported herein, rules out the diagnosis of spindle cell carcinoma as well as that of synovial sarcoma, the latter being vimentin and CD99 positive. Desmin immunoreactivity is not detectable in myofibroblasts, neither normal or neoplastic, but is encountered in other myogenic neoplasms, such as rhabdomyosarcoma [Muzio L et al, 2000]. Although numerous prognostic factors, including size, site, grade and TNM stage, have been identified for leiomyosarcoma arising in other sites, there are no reliable prognostic factors in the case of primary oral leiomyosarcoma. The TNM classification of soft-tissue tumors is not directly applicable to oral leiomyosarcoma, especially in terms of the T stage, and the histological grade of the tumor has rarely been reported in oral leiomyosarcoma. It is important to identify factors of prognostic significance in this patient group. The estimated five year survival for the whole group is 55%. Tumors that demonstrated bony involvement (maxilla/mandible) and metastasis were associated with poorer prognosis. Increasing age and male gender showed a trend toward worse prognosis, although this was not statistically significant. Interestingly, neither the increased size of the tumor nor recurrence was associated with poor survival, unlike tumors occurring at other sites [Miyajima K et al 2002, Weiss SW et al, 2001, Dry SM et al, 2000, Nikitakis NG et al,

2002].

#### **6. Liposarcoma of head and neck**

Liposarcoma is the second most common soft tissue sarcoma in adults. Its occurrence in the head and neck region is reported to be very rare. The majority of liposarcomas occur in middle-aged adults; however, very uncommon cases of liposarcoma can be generated in infancy and early childhood [Hicks J et al, 2001]. The occurrence of liposarcoma in the head and neck region is rare, comprising 5.6–9% of all cases [Enzinger FM et al, 2001]. Liposarcoma of the oral cavity is even less frequent, making up about 10% of all cases in the head and neck. In a 1995 literature review, Golledge et al [Golledge J et al, 1995]. found that liposarcoma of the head and neck was poorly addressed and that its incidence is rare, representing approximately 4-5% of liposarcomas (50 reported cases). Most cases originated in the neck (28%), followed by the head (scalp and face, 26%), larynx (20%), pharynx (18%), and mouth (8%) [Golledge J et al, 1995].

Since the publication of that review, liposarcomas of the head and neck have gained more attention; however, most of the subsequent reports have addressed the primary liposarcomas of the head and neck. Fifteen cases of liposarcoma metastases to the head and neck region have been previously reported. The associated primary tumors from these reports occurred most fequently in the thigh and retroperitoneum and equally between men and women, showing no deviance from the normal trends found in liposarcoma. The average age of the patients was 53 years old. Most of the head and neck metastases were to the orbit, thyroid, and dura mater in 31%, 25%, and 19% of the cases, respectively. Other metastatic foci included the gingival mucosa, submandibular region, and scalp [McElderry et al, 2008]. Although head and neck liposarcomas are rare, specialists should be aware of the natural history, prognosis and treatment. As with liposarcomas elsewhere in the body, most cases present in adults, and there is a male predominance. Factors considered to be important in the etiology of liposarcomas include genetics, trauma and irradiation. Usually, the tumor appears firm, relatively fixed to adjacent tissues, encapsulated, and to be growing steadily but not rapidly. Patients do not usually have regional lymph node or distant metastasis at presentation [Feles RA et al, 1993, Freedman AM et al, 1989]. Radiological investigations are necessary in most cases to determine precise size, localization, limits, extensions of the tumor and its relations with neurovascular structures. It is also necessary for detecting distant metastases [Enzinger FM et al, 2001].. Liposarcoma originates from primitive mesenchymal cells rather than mature fat cells. Thus, liposarcoma seldom originates from normal fat tissue or lipoma. Furthermore, in contrast to lipoma, which ordinarily arises in the subcutaneous, submucous, or subserous tissue, liposarcoma rarely arises in such tissues, but rather in the perimuscular or perifascial structures of spindle cell liposarcoma. The next major type is the myxoid type, which is composed of three main tissue components: proliferating lipoblasts at varying stages of differentiation, a delicate plexiform capillary pattern, and a myxoid matrix containing abundant nonsulfated glycosaminoglycans. A subset of myxoid liposarcomas shows histological progression to hypercellular or round cell morphology, which is associated with poor prognosis [Christopher DM et al, 2002]. The most infrequent type is pleomorphic liposarcoma, which contains huge lipoblastic multinucleated cells by which it distinguishes itself from other pleomorphic sarcomas, such as malignant fibrohistiocytoma.The dedifferentiated type was added to these criteria recently and is composed of a well-differentiated area and a poorly differentiated area in parts of the same neoplasm, recurrent tumor or metastatic lesion. The prognosis of this tumor depends on the tumor subtype; well-differentiated and myxoid

Head and Neck Soft Tissue Sarcoma 129

positivity for vimentin, MSA, and desmins confirm the diagnosis. Rhabdomyosarcoma is a malignant neoplasm consisting of undifferentiated mesodermal tissue that expresses myogenic differentiation. Histopathologic diagnosis is based on conventional light microscopy and confirmed by immunhistochemistry. Antibodies against desmin, musclespecific actin, and myoglobulin are most widely used for diagnostic purposes. The three major morphologic categories of rhabdomyosarcomas are embryonal, alveolar, and pleomophic. The embryonal subtype is the most common, accounting for 70–75% of all rhabdomyosarcomas, followed by the alveolar (20–25%) and pleomorphic differentiations (5%). While the embryonal and alveolar subtypes are most commonly seen in children – therefore termed juvenile - the pleomorphic subtype occurs almost exclusively in adults. Rhabdomyosarcomas are generally seen in children, usually consisting of the embryonal type, which represents the most frequent form of soft tissue sarcomas at this age. The pleomorphic subtype is one of the most malignant sarcomas. In a publication in 1998, Akyol [Akyol MU et al, 1998] reviewed the 13 documented cases of laryngeal pleomorphic rhabdomyosarcoma. Radiotherapy as the primary treatment has been reported with varying success, while adjunctive radiation therapy is given whenever a tumor is not completely surgically removed. Randomized trials on adult sarcoma in general found that

Fig. 3. a) Rhabdomyosarcoma of larynx showing a multinodular white and brown mass, b)

Pleomorphic Rabdomiosarcoma with large cells containing deeply eosinophilic

rhabdomyosarcoma

liposarcomas are considered to be low-grade malignancies, whereas the pleomorphic and round cell types are regarded to be high-grade. Golledge et al [Golledge J et al, 1995]. reported 5-year survival rates of 100% for well-differentiated, 73% for myxoid, 42% for pleomorphic, and 0% for round cell liposarcomas in 76 cases in the head and neck area. The best choice for treatment is complete surgical excision, where a wide or radical excision with sufficient margins is possible. McCulloch et al [McCulloch et al, 1992]. reported an 80% rate of local or distant recurrence in patients with incomplete surgical excision compared with a rate of only 17% when complete excision was accomplished.

Liposarcoma appears to have a clear capsule and is easy to separate, but it often infiltrates the surrounding structures microscopically, so occasionally, incomplete resection occurs. In contrast to its characteristic high recurrence, lymph node metastasis is quite rare, so neck lymph node dissection is considered unnecessary [Weing BM et al, 1995]. Cases of distant metastasis, which result from hematogenous metastasis, are occasionally reported, and the most common metastatic sites are the lung, intra-abdominal area, bone, skull and liver [Wong CK et al, 1997]. In the head and neck area, the majority of metastasized cases appear to be round cell or pleomorphic liposarcomas. Radiotherapy, particularly postoperative radiation, is considered useful and might delay or prevent local recurrence.

#### **7. Rhabdomyosarcoma of head and neck**

Rhabdomyosarcomas (RMS) account for 40% of all sarcomas found in the head and neck region, and they are a morphologically and clinically heterogeneous family of malignant soft tissue tumors of a myogenic lineage [Abali H et al, 2003]. Alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) represent the two main histologic patterns and must be differentiated from other small round cell tumors. RMS is the most common soft tissue sarcoma in the pediatric population, comprising approximately 5% of all childhood cancers and nearly 50% of soft tissue sarcomas arising in children 0 to 14 years of age [Ferlito A et al, 1999]. By contrast, RMS is remarkably uncommon in older adults, representing merely 2-5% of all malignant soft tissue tumors, with the majority being the pleomorphic subtype [Sivanandan R et al, 2004]. Head and neck tumors are divided into three major groups based on anatomic location and propensity for invasion of the central nervous system: orbital, parameningeal, and nonparameningeal. Parameningeal tumors carry the worst prognosis. Orbital RMS represents 75% of those tumors in the head and neck and is associated with the best prognosis. Oral rhabdomyosarcomas are classified within the non-orbital, nonparameningeal group of tumors, which present a better prognosis and tend not to invade the central nervous system. The five-year survival rate is approximately 85% for this RMS subtype. RMS is more aggressive in adults compared with children. Poor prognosis in adults is thought to be due to a combination of advanced tumor stage, unfavorable histology, a decreased tolerance to treatment and other unknown biological factors [Franca CM et al, 2006, Bras J et al 1987, Pavithran K et al, 1997]. Alveolar rhabdomyosarcoma is known to be rare in adults aged over 45 years and to be commonly located in the extremities; the clinical features of the case presented were exceptional. As a result of the lack of characteristic histopathologic features, the final diagnosis of alveolar rhabdomyosarcoma is difficult to establish. The histochemical findings suggested differentiation from other small anaplastic round cell tumors, such as undifferentiated carcinoma, neuroblastoma, neuroepithelioma, Ewing's sarcoma, and malignant lymphoma. The immunohistochemical character of the tumor cells increases the diagnostic accuracy;

liposarcomas are considered to be low-grade malignancies, whereas the pleomorphic and round cell types are regarded to be high-grade. Golledge et al [Golledge J et al, 1995]. reported 5-year survival rates of 100% for well-differentiated, 73% for myxoid, 42% for pleomorphic, and 0% for round cell liposarcomas in 76 cases in the head and neck area. The best choice for treatment is complete surgical excision, where a wide or radical excision with sufficient margins is possible. McCulloch et al [McCulloch et al, 1992]. reported an 80% rate of local or distant recurrence in patients with incomplete surgical excision compared with a

Liposarcoma appears to have a clear capsule and is easy to separate, but it often infiltrates the surrounding structures microscopically, so occasionally, incomplete resection occurs. In contrast to its characteristic high recurrence, lymph node metastasis is quite rare, so neck lymph node dissection is considered unnecessary [Weing BM et al, 1995]. Cases of distant metastasis, which result from hematogenous metastasis, are occasionally reported, and the most common metastatic sites are the lung, intra-abdominal area, bone, skull and liver [Wong CK et al, 1997]. In the head and neck area, the majority of metastasized cases appear to be round cell or pleomorphic liposarcomas. Radiotherapy, particularly postoperative

Rhabdomyosarcomas (RMS) account for 40% of all sarcomas found in the head and neck region, and they are a morphologically and clinically heterogeneous family of malignant soft tissue tumors of a myogenic lineage [Abali H et al, 2003]. Alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) represent the two main histologic patterns and must be differentiated from other small round cell tumors. RMS is the most common soft tissue sarcoma in the pediatric population, comprising approximately 5% of all childhood cancers and nearly 50% of soft tissue sarcomas arising in children 0 to 14 years of age [Ferlito A et al, 1999]. By contrast, RMS is remarkably uncommon in older adults, representing merely 2-5% of all malignant soft tissue tumors, with the majority being the pleomorphic subtype [Sivanandan R et al, 2004]. Head and neck tumors are divided into three major groups based on anatomic location and propensity for invasion of the central nervous system: orbital, parameningeal, and nonparameningeal. Parameningeal tumors carry the worst prognosis. Orbital RMS represents 75% of those tumors in the head and neck and is associated with the best prognosis. Oral rhabdomyosarcomas are classified within the non-orbital, nonparameningeal group of tumors, which present a better prognosis and tend not to invade the central nervous system. The five-year survival rate is approximately 85% for this RMS subtype. RMS is more aggressive in adults compared with children. Poor prognosis in adults is thought to be due to a combination of advanced tumor stage, unfavorable histology, a decreased tolerance to treatment and other unknown biological factors [Franca CM et al, 2006, Bras J et al 1987, Pavithran K et al, 1997]. Alveolar rhabdomyosarcoma is known to be rare in adults aged over 45 years and to be commonly located in the extremities; the clinical features of the case presented were exceptional. As a result of the lack of characteristic histopathologic features, the final diagnosis of alveolar rhabdomyosarcoma is difficult to establish. The histochemical findings suggested differentiation from other small anaplastic round cell tumors, such as undifferentiated carcinoma, neuroblastoma, neuroepithelioma, Ewing's sarcoma, and malignant lymphoma. The immunohistochemical character of the tumor cells increases the diagnostic accuracy;

rate of only 17% when complete excision was accomplished.

**7. Rhabdomyosarcoma of head and neck** 

radiation, is considered useful and might delay or prevent local recurrence.

positivity for vimentin, MSA, and desmins confirm the diagnosis. Rhabdomyosarcoma is a malignant neoplasm consisting of undifferentiated mesodermal tissue that expresses myogenic differentiation. Histopathologic diagnosis is based on conventional light microscopy and confirmed by immunhistochemistry. Antibodies against desmin, musclespecific actin, and myoglobulin are most widely used for diagnostic purposes. The three major morphologic categories of rhabdomyosarcomas are embryonal, alveolar, and pleomophic. The embryonal subtype is the most common, accounting for 70–75% of all rhabdomyosarcomas, followed by the alveolar (20–25%) and pleomorphic differentiations (5%). While the embryonal and alveolar subtypes are most commonly seen in children – therefore termed juvenile - the pleomorphic subtype occurs almost exclusively in adults. Rhabdomyosarcomas are generally seen in children, usually consisting of the embryonal type, which represents the most frequent form of soft tissue sarcomas at this age. The pleomorphic subtype is one of the most malignant sarcomas. In a publication in 1998, Akyol [Akyol MU et al, 1998] reviewed the 13 documented cases of laryngeal pleomorphic rhabdomyosarcoma. Radiotherapy as the primary treatment has been reported with varying success, while adjunctive radiation therapy is given whenever a tumor is not completely surgically removed. Randomized trials on adult sarcoma in general found that

Fig. 3. a) Rhabdomyosarcoma of larynx showing a multinodular white and brown mass, b) Pleomorphic Rabdomiosarcoma with large cells containing deeply eosinophilic rhabdomyosarcoma

Head and Neck Soft Tissue Sarcoma 131

tumors, and malignant fibrous histiocytoma. A panel of antibodies in an immunohistochemistry assay must be assessed together with other observations. Several investigations showed that the epithelial component of biphasic synovial sarcomas stains for cytokeratin in almost 90% of cases and that EMA is also frequently expressed. The spindle cells in some, but not all, tumors express cytokeratin or EMA focally and less intensely than epithelial cells. In monophasic synovial sarcoma, the expression of these epithelial markers is less evident, necessitating the examination of many sections from different sites. Reactivity for vimentin is observed in epithelial elements in about 15-30% of biphasic tumors; in spindle cells, it is observed in about 80-90% of both biphasic synovial sarcomas and monophasic synovial sarcomas and a wide variety of epithelial neoplasms express vimentin, making its reactivity less significant in the diagnosis of synovial sarcoma. The S-100 protein may be detectable in 30% of these tumors, causing confusion with malignant peripheral nerve-sheath tumors. In addition, bcl-2 protein was reported in 75-100% of Sinovial sarcomas, typically in a strong and diffuse fashion, especially in spindle cells [Fletcher et al, 2002, Kempson et al, 2001]. CD99 can be detected in 60% to 70% of cases. Nevertheless, these findings are of little diagnostic value because bcl-2 and CD99 are also expressed in a variety of distinct neoplasms. Chromosomal studies showed a balanced reciprocal translocation t (X;18)(p11.2;q11.2) in more than 90% of all synovial sarcoma subtypes in all anatomic sites, including the oral cavity. The translocation results in the fusion of SYT or SSXT from chromosome 18 to either SSX1, SSX2, or SSX4 genes from the X-

chromosome [Almeida – Lawall M et al., 2009, Kempson RL et al, 2001].

**9. Malignant Peripheral Nerve Sheath Tumors of head and neck** 

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare neoplasms with an estimated incidence of 0.1 per 100,000 per year in the general population. They account for approximately 5-10% of all soft tissue sarcomas and have a strong association with neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's neurofibromatosis [Hajdu SI, 1993]. MPNSTs have been defined as any malignant tumor that arises from or differentiates toward cells of the peripheral nerve sheath, with the exception of tumors that originate from the epineurium or the peripheral nerve vasculature [Wong WW et al, 1998]. Various misleading synonyms, including the terms neurofibrosarcoma, neurogenic sarcoma, malignant neurilemmoma and malignant schwannoma, have previously all been applied to this neoplasm and are merely a reflection of the controversial clinicopathologic classification of this rare tumor [Wanebo JE, 1993]. MPNSTs of the head and neck, in particular, represent exceptional neoplasms; MPNSTs are one of the most aggressive malignant tumors and have the highest local recurrence rate of any sarcoma, and they have a marked propensity for dissemination and metastatic spread [Stark AM. 2001]. Despite multimodal therapy, including radical surgical resection and adjuvant radiochemotherapy, the prognosis of MPNSTs is said to remain dismal, particularly in the head and neck. However, prognostic factors and treatment modalities have not been consistently identified [Anghileri M et al, 2006]. Up to 30-50% of all MPNSTs are found in association with NF-1, with a reported incidence of MPNSTs in this subgroup ranging from 2-29% [al - Otieschan AA et al, 1998] MPNSTs can affect all age groups but usually present in adult life between 20 and 50 years of age, with no established predilection for sex or race. However, the mean age of patients with NF-1-associated MPNSTs is approximately a decade younger [Nagayama I et al, 1993]. The most common sites of involvement are the extremities, trunk, chest, and

the addition of radiation resulted in significant improvement in local control over surgery alone. However, rhabdomyosarcomas in adults are not as radiosensitive as those in children [Haerr RW et al, 1987, Little DJ et al, 2002].

## **8. Synovial sarcoma of head and neck**

Synovial sarcoma is a malignant soft tissue neoplasm that occurs most frequently in the extremities of young adults, near large joints [Enzinger FM et al, 2001]. The most common site is around the knee. As opposed to most other soft tissue sarcomas, these lesions are occasionally painful [Devita TJ et al, 2001]. Synovial sarcoma is more common in males than in females, although there is no evidence of a race difference. This sarcoma represents 5.6- 10% of all soft tissue sarcomas. The tumor usually occurs in close association with tendon sheaths, bursae, and joint capsules, primarily in the paraarticular regions of the extremities. The origin of synovial sarcoma remains unknown, but the neoplasm is thought to arise from primitive undifferentiated pluripotential mesenchymal cells unrelated to synovial tissue [Grayson et al, 1998]. Although 85% of synovial sarcomas arise in the extremities, sites in the head and neck, trunk, abdomen, pelvis, mediastinum and lung are rarely involved. Approximately 3.7% of patients of all ages with synovial sarcoma have it in the head and neck [Ferrari A et al,2004]. Jernstrom [Jernstrom P et al, 1994] was the first to report the occurrence of synovial sarcoma in the head and neck region in 1954, and since then, more than 100 cases have been reported. The parapharyngeal region is the most frequently affected site, and few cases have been documented to arise within the orofacial region [Almeida – Lawall M et al, 2009]. The most important and accurate prognostic factors in synovial sarcoma are the extent of tumor resection and the presence of metastatic disease, the most common sites of which are the lung and regional lymph node [Rangheard AS et al, 2001]. The other prognostic factors associated with synovial sarcoma are conflicting. Previously reported favorable prognostic factors include age below 20-25 years, tumor size smaller than 5 cm, distal extremity location, and biphasic histological type. However, some studies have shown that age, location of the tumor, and histology type are not significantly associated with prognosis. In many instances, synovial sarcomas are so poorly differentiated that they do not show any specific features sufficient to suggest their true origin, and hence, they may be confused with other poorly differentiated sarcomas [Limon J et al, Turc – Carel et al, 1986].

The following factors have potential prognostic value: age at diagnosis, sex, tumor site, size, histology, mitotic count, necrosis, histological grade, stage, surgical margin status, and fusion type. The presence of poorly differentiated areas was the strongest prognostic factor associated with local recurrence, metastases, and tumor-related death [de Silva MV et al, Guillou J et al, 2004]. Three histologic subtypes originating from the presence of 2 cell types exist along a continuous spectrum: biphasic, monophasic (predominantly fibrous or rare epithelial), and poorly differentiated. Monophasic epithelial synovial cell sarcoma and gland-predominant biphasic synovial cell sarcoma are similar to adenocarcinoma, leading to potential misidentification as adenocarcinoma [Weinreb et al, 2008]. The poorly differentiated type poses a diagnostic challenge and has structures that resemble those of high-grade small round cell tumors: high cellularity, frequent mitosis, and necrosis. The common diagnosis of synovial cell sarcoma is the biphasic pattern or monophasic fibrous type but can also be easily confused with spindle cell carcinoma, myofibromatosis, leiomyosarcoma, primitive neuroectodermal tumors, malignant peripheral nerve sheath

the addition of radiation resulted in significant improvement in local control over surgery alone. However, rhabdomyosarcomas in adults are not as radiosensitive as those in children

Synovial sarcoma is a malignant soft tissue neoplasm that occurs most frequently in the extremities of young adults, near large joints [Enzinger FM et al, 2001]. The most common site is around the knee. As opposed to most other soft tissue sarcomas, these lesions are occasionally painful [Devita TJ et al, 2001]. Synovial sarcoma is more common in males than in females, although there is no evidence of a race difference. This sarcoma represents 5.6- 10% of all soft tissue sarcomas. The tumor usually occurs in close association with tendon sheaths, bursae, and joint capsules, primarily in the paraarticular regions of the extremities. The origin of synovial sarcoma remains unknown, but the neoplasm is thought to arise from primitive undifferentiated pluripotential mesenchymal cells unrelated to synovial tissue [Grayson et al, 1998]. Although 85% of synovial sarcomas arise in the extremities, sites in the head and neck, trunk, abdomen, pelvis, mediastinum and lung are rarely involved. Approximately 3.7% of patients of all ages with synovial sarcoma have it in the head and neck [Ferrari A et al,2004]. Jernstrom [Jernstrom P et al, 1994] was the first to report the occurrence of synovial sarcoma in the head and neck region in 1954, and since then, more than 100 cases have been reported. The parapharyngeal region is the most frequently affected site, and few cases have been documented to arise within the orofacial region [Almeida – Lawall M et al, 2009]. The most important and accurate prognostic factors in synovial sarcoma are the extent of tumor resection and the presence of metastatic disease, the most common sites of which are the lung and regional lymph node [Rangheard AS et al, 2001]. The other prognostic factors associated with synovial sarcoma are conflicting. Previously reported favorable prognostic factors include age below 20-25 years, tumor size smaller than 5 cm, distal extremity location, and biphasic histological type. However, some studies have shown that age, location of the tumor, and histology type are not significantly associated with prognosis. In many instances, synovial sarcomas are so poorly differentiated that they do not show any specific features sufficient to suggest their true origin, and hence, they may be confused with other poorly differentiated sarcomas [Limon J et al, Turc – Carel

The following factors have potential prognostic value: age at diagnosis, sex, tumor site, size, histology, mitotic count, necrosis, histological grade, stage, surgical margin status, and fusion type. The presence of poorly differentiated areas was the strongest prognostic factor associated with local recurrence, metastases, and tumor-related death [de Silva MV et al, Guillou J et al, 2004]. Three histologic subtypes originating from the presence of 2 cell types exist along a continuous spectrum: biphasic, monophasic (predominantly fibrous or rare epithelial), and poorly differentiated. Monophasic epithelial synovial cell sarcoma and gland-predominant biphasic synovial cell sarcoma are similar to adenocarcinoma, leading to potential misidentification as adenocarcinoma [Weinreb et al, 2008]. The poorly differentiated type poses a diagnostic challenge and has structures that resemble those of high-grade small round cell tumors: high cellularity, frequent mitosis, and necrosis. The common diagnosis of synovial cell sarcoma is the biphasic pattern or monophasic fibrous type but can also be easily confused with spindle cell carcinoma, myofibromatosis, leiomyosarcoma, primitive neuroectodermal tumors, malignant peripheral nerve sheath

[Haerr RW et al, 1987, Little DJ et al, 2002].

et al, 1986].

**8. Synovial sarcoma of head and neck** 

tumors, and malignant fibrous histiocytoma. A panel of antibodies in an immunohistochemistry assay must be assessed together with other observations. Several investigations showed that the epithelial component of biphasic synovial sarcomas stains for cytokeratin in almost 90% of cases and that EMA is also frequently expressed. The spindle cells in some, but not all, tumors express cytokeratin or EMA focally and less intensely than epithelial cells. In monophasic synovial sarcoma, the expression of these epithelial markers is less evident, necessitating the examination of many sections from different sites. Reactivity for vimentin is observed in epithelial elements in about 15-30% of biphasic tumors; in spindle cells, it is observed in about 80-90% of both biphasic synovial sarcomas and monophasic synovial sarcomas and a wide variety of epithelial neoplasms express vimentin, making its reactivity less significant in the diagnosis of synovial sarcoma. The S-100 protein may be detectable in 30% of these tumors, causing confusion with malignant peripheral nerve-sheath tumors. In addition, bcl-2 protein was reported in 75-100% of Sinovial sarcomas, typically in a strong and diffuse fashion, especially in spindle cells [Fletcher et al, 2002, Kempson et al, 2001]. CD99 can be detected in 60% to 70% of cases. Nevertheless, these findings are of little diagnostic value because bcl-2 and CD99 are also expressed in a variety of distinct neoplasms. Chromosomal studies showed a balanced reciprocal translocation t (X;18)(p11.2;q11.2) in more than 90% of all synovial sarcoma subtypes in all anatomic sites, including the oral cavity. The translocation results in the fusion of SYT or SSXT from chromosome 18 to either SSX1, SSX2, or SSX4 genes from the Xchromosome [Almeida – Lawall M et al., 2009, Kempson RL et al, 2001].

## **9. Malignant Peripheral Nerve Sheath Tumors of head and neck**

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare neoplasms with an estimated incidence of 0.1 per 100,000 per year in the general population. They account for approximately 5-10% of all soft tissue sarcomas and have a strong association with neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's neurofibromatosis [Hajdu SI, 1993]. MPNSTs have been defined as any malignant tumor that arises from or differentiates toward cells of the peripheral nerve sheath, with the exception of tumors that originate from the epineurium or the peripheral nerve vasculature [Wong WW et al, 1998]. Various misleading synonyms, including the terms neurofibrosarcoma, neurogenic sarcoma, malignant neurilemmoma and malignant schwannoma, have previously all been applied to this neoplasm and are merely a reflection of the controversial clinicopathologic classification of this rare tumor [Wanebo JE, 1993]. MPNSTs of the head and neck, in particular, represent exceptional neoplasms; MPNSTs are one of the most aggressive malignant tumors and have the highest local recurrence rate of any sarcoma, and they have a marked propensity for dissemination and metastatic spread [Stark AM. 2001]. Despite multimodal therapy, including radical surgical resection and adjuvant radiochemotherapy, the prognosis of MPNSTs is said to remain dismal, particularly in the head and neck. However, prognostic factors and treatment modalities have not been consistently identified [Anghileri M et al, 2006]. Up to 30-50% of all MPNSTs are found in association with NF-1, with a reported incidence of MPNSTs in this subgroup ranging from 2-29% [al - Otieschan AA et al, 1998] MPNSTs can affect all age groups but usually present in adult life between 20 and 50 years of age, with no established predilection for sex or race. However, the mean age of patients with NF-1-associated MPNSTs is approximately a decade younger [Nagayama I et al, 1993]. The most common sites of involvement are the extremities, trunk, chest, and

Head and Neck Soft Tissue Sarcoma 133

Y; the literature also revealed another gene, PTPN11, which encodes the non-receptor protein tyrosine phosphatase SHP-2. This gene was mapped to the chromosome 5 region on 12q24.1, the same region involved in the second translocation of our patient. Noonan syndrome is an autosomal dominant disorder characterized by dysmorphic body features, heart disease, mental retardation, and bleeding diatheses. Interestingly, a child with Noonan syndrome and malignant schwannoma of the left forearm has been reported. These findings initially raised our suspicion, and we have further tested the possibility that the patient carried concealed characteristics of Noonan syndrome [Rao UN et al, 1996, Tartaglia M et al,

MTT was first described by Masson in 1932. It is a rare subtype of MPNSTs in which the malignant schwannoma has rhabdomyoblastic differentiation, a so-called mosaic tumor with both a muscular and a neurogene component. One third of these tumors arise in the head and neck region, and at least one third of these are associated with neurofibromatosis type 1. In sporadic cases, the mean age at debut is 38 years, while cases associated with neurofibromatosis are, on average, 12 years younger [Kim ST et al, 2001, Barnes L. 2004]. The MTT is named after the Triton salamander, which is capable of regenerating limbs consisting of both muscle and nerve tissue after the cut end of the sciatic nerve is implanted into the soft tissue of its back. The MTT pathogenesis is not known. One hypothesis is that malignant schwan cells differentiate into rhabdomyoblasts. Another hypothesis is that both cell lines arise from less differentiated neural crest cells with both ectodermal and mesodermal potential. Although MTT can occur as a sporadic tumor, approximately half to two thirds of cases occur in association with neurofibromatosis type 1 (NF1), usually affecting individuals in their third or fourth decade of life. MTT is generally considered a high-grade malignant neoplasm with a poor outcome [Yakulis et al, 1996]. Previous studies [Daimaru Y et al, 1984, Victoria L et al, 1999], reviewed the treatment and outcome of 27 MTTs arising in the head and neck and commented that there may be a subset of MTTs that occurr in this region as low-grade malignancies with favorable long-term prognosis. The primary involvement of the oral cavity is extremely rare. MTTs occur predominantly in the trunk, head and neck, and lower extremities [Enzinger FM, 2001]. Among all reported cases, approximately one third appear to arise in the head and neck region. In a recent detailed review of the literature, Victoria et al [Victoria L et al, 1999] summarized the anatomic distribution of head and neck cases. The data showed that 12 of the 27 cases described were

Taken together with a recent report describing MTT of the maxilla, it can be concluded that intraoral presentation of MTT is rare. The hallmark of this tumor is the presence of rhabdomyoblasts scattered throughout the stroma indistinguishably from ordinary MPNST. The number of rhabdomyoblasts varies greatly from tumor to tumor and even from area to area in the same tumor. Chromosome analysis of MTTs showed a complex hyperdiploid karyotype with multiple unbalanced translocations, large markers, and ring formations. Although some of the markers were highly variable, other markers were reasonably stable and were seen in the majority of the abnormal metaphases. Haddadin et al [Haddadin et al, 2003], compared the chromosomal breakpoints in MTT, MPNST, and rhabdomyosarcoma to identify common regions of involvement. These included 7p22, 7q36, 11p15, 12p13, 13p11.2,

2001, Noonan JA et al, 1968, Kaplan et al, 1968].

**9.1 Malignant Triton Tumor (MTT) of head and neck** 

found to arise in the structures of the neck or upper thorax.

17q11.2, and 19q13.1.

retroperitoneum. While benign peripheral nerve sheath tumors, such as benign schwannoma and neurofibroma, have a propensity for the head and neck, fewer than 10% of MPNSTs affect this anatomic region. The majority of MPNSTs arise either de novo or from pre-existing neurofibromas, with an estimated incidence of malignant transformation ranging 3-30%. Only very rare examples of MPNSTs arise in the schwannoma, ganglioneuroma or phaeochromocytoma, and they arise from all cranial nerves except the optic and olfactory nerves, which have no nerve sheath [Shingh B et al, 2001]. CT and MRI scans delineate the extent of the disease and the involvement of vital structures and allow staging. MPNSTs infiltrate local tissues extensively and spread preferentially, as with other sarcomas, via the bloodstream to the liver, lungs and bone rather than the lymphatic system.

 Regional lymph node involvement occurs in less than 1% of deep-seated disease [Ducatman BS et al, 2006] and is even rarer in the superficial form, but no studies have described the statistics. Punjabi described an MPNST in the left parotid that metastased to the contralateral parotid and auditory canal with intra-cranial extension, but it is unclear whether the right parotid was the site of the metastasis or was secondarily invaded. Histological diagnosis has become more stringent because of similarities with other spindle cell malignancies, e.g., leiomyosarcomas, malignant fibrous histiocytomas and neurotropic malignant melanoma. In the past, it was necessary to demonstrate the origin from a nerve; however, cutaneous nerves are generally too small to be grossly identified, and hence, electron microscopy and immunochemistry are used to show ultrastructural evidence of Schwann cell differentiation with the absence of premelanosomes and absence of epidermal melanocyte proliferation. There are no specific immunohistological markers, and therefore, to make a diagnosis, a panel of antibodies and immunoreactivity with at least two of the following antibodies is required: S100, Leu7, myelin basic protein, glial fibrillary acid protein and PGP 9.5. [Wick MR et al, 1990]. Surgery is the main treatment for MPNSTs, which require radical resection and additional frozen sectioning of the proximal nerve to ensure clear margins, although reviews do not suggest a margin of excision. Because lymph node involvement is very unusual, elective neck dissection is not recommended. Adjuvant high-dose radiotherapy is used, particularly after incomplete resection or where radical excision is impossible, and chemotherapy remains controversial. The superficial form of the disease after primary surgery has a local recurrence rate of 78%, metastatic spread rate of 22% and a 4-year survival rate of 66%. Unfortunately, Dabski's series was small, and only half the lesions were located in the head and neck region [Dabski C et al, 1990]. The fiveyear survival of all patients with MPNSTs of the head and neck ranges from 15 to 34%, with 50% of the cases developing local recurrences and 33% metastases, particularly to the lung [Punjabi et al, 1996, Hujala K et al, 1993]. MPNSTs have been described in English in the literature, and most of these cases presented with a complex karyotype with triploid or tetraploid clones. The most frequent structural aberrations found in MPNST involve chromosomes 7, 9, 13, and 17, whereas the most frequent numerical chromosomal abnormalities include trisomy 7 and 2 and monosomy X and 17. Breakpoints at 12q24, as a part of a complex karyotype, were previously described in six cases of MPNSTs and in two cases of Xq22. Breakpoints at 2q35 or 4q31 have not been described for MPNSTs. Moreover, of the previously described cases of MPNSTs, only eight displayed a diploid karyotype, and six displayed a simple karyotype with unbalanced chromosomal aberrations 47,XY, 7/45,X,

retroperitoneum. While benign peripheral nerve sheath tumors, such as benign schwannoma and neurofibroma, have a propensity for the head and neck, fewer than 10% of MPNSTs affect this anatomic region. The majority of MPNSTs arise either de novo or from pre-existing neurofibromas, with an estimated incidence of malignant transformation ranging 3-30%. Only very rare examples of MPNSTs arise in the schwannoma, ganglioneuroma or phaeochromocytoma, and they arise from all cranial nerves except the optic and olfactory nerves, which have no nerve sheath [Shingh B et al, 2001]. CT and MRI scans delineate the extent of the disease and the involvement of vital structures and allow staging. MPNSTs infiltrate local tissues extensively and spread preferentially, as with other sarcomas, via the bloodstream to the liver, lungs and bone

 Regional lymph node involvement occurs in less than 1% of deep-seated disease [Ducatman BS et al, 2006] and is even rarer in the superficial form, but no studies have described the statistics. Punjabi described an MPNST in the left parotid that metastased to the contralateral parotid and auditory canal with intra-cranial extension, but it is unclear whether the right parotid was the site of the metastasis or was secondarily invaded. Histological diagnosis has become more stringent because of similarities with other spindle cell malignancies, e.g., leiomyosarcomas, malignant fibrous histiocytomas and neurotropic malignant melanoma. In the past, it was necessary to demonstrate the origin from a nerve; however, cutaneous nerves are generally too small to be grossly identified, and hence, electron microscopy and immunochemistry are used to show ultrastructural evidence of Schwann cell differentiation with the absence of premelanosomes and absence of epidermal melanocyte proliferation. There are no specific immunohistological markers, and therefore, to make a diagnosis, a panel of antibodies and immunoreactivity with at least two of the following antibodies is required: S100, Leu7, myelin basic protein, glial fibrillary acid protein and PGP 9.5. [Wick MR et al, 1990]. Surgery is the main treatment for MPNSTs, which require radical resection and additional frozen sectioning of the proximal nerve to ensure clear margins, although reviews do not suggest a margin of excision. Because lymph node involvement is very unusual, elective neck dissection is not recommended. Adjuvant high-dose radiotherapy is used, particularly after incomplete resection or where radical excision is impossible, and chemotherapy remains controversial. The superficial form of the disease after primary surgery has a local recurrence rate of 78%, metastatic spread rate of 22% and a 4-year survival rate of 66%. Unfortunately, Dabski's series was small, and only half the lesions were located in the head and neck region [Dabski C et al, 1990]. The fiveyear survival of all patients with MPNSTs of the head and neck ranges from 15 to 34%, with 50% of the cases developing local recurrences and 33% metastases, particularly to the lung [Punjabi et al, 1996, Hujala K et al, 1993]. MPNSTs have been described in English in the literature, and most of these cases presented with a complex karyotype with triploid or tetraploid clones. The most frequent structural aberrations found in MPNST involve chromosomes 7, 9, 13, and 17, whereas the most frequent numerical chromosomal abnormalities include trisomy 7 and 2 and monosomy X and 17. Breakpoints at 12q24, as a part of a complex karyotype, were previously described in six cases of MPNSTs and in two cases of Xq22. Breakpoints at 2q35 or 4q31 have not been described for MPNSTs. Moreover, of the previously described cases of MPNSTs, only eight displayed a diploid karyotype, and six displayed a simple karyotype with unbalanced chromosomal aberrations 47,XY, 7/45,X,

rather than the lymphatic system.

Y; the literature also revealed another gene, PTPN11, which encodes the non-receptor protein tyrosine phosphatase SHP-2. This gene was mapped to the chromosome 5 region on 12q24.1, the same region involved in the second translocation of our patient. Noonan syndrome is an autosomal dominant disorder characterized by dysmorphic body features, heart disease, mental retardation, and bleeding diatheses. Interestingly, a child with Noonan syndrome and malignant schwannoma of the left forearm has been reported. These findings initially raised our suspicion, and we have further tested the possibility that the patient carried concealed characteristics of Noonan syndrome [Rao UN et al, 1996, Tartaglia M et al, 2001, Noonan JA et al, 1968, Kaplan et al, 1968].

#### **9.1 Malignant Triton Tumor (MTT) of head and neck**

MTT was first described by Masson in 1932. It is a rare subtype of MPNSTs in which the malignant schwannoma has rhabdomyoblastic differentiation, a so-called mosaic tumor with both a muscular and a neurogene component. One third of these tumors arise in the head and neck region, and at least one third of these are associated with neurofibromatosis type 1. In sporadic cases, the mean age at debut is 38 years, while cases associated with neurofibromatosis are, on average, 12 years younger [Kim ST et al, 2001, Barnes L. 2004]. The MTT is named after the Triton salamander, which is capable of regenerating limbs consisting of both muscle and nerve tissue after the cut end of the sciatic nerve is implanted into the soft tissue of its back. The MTT pathogenesis is not known. One hypothesis is that malignant schwan cells differentiate into rhabdomyoblasts. Another hypothesis is that both cell lines arise from less differentiated neural crest cells with both ectodermal and mesodermal potential. Although MTT can occur as a sporadic tumor, approximately half to two thirds of cases occur in association with neurofibromatosis type 1 (NF1), usually affecting individuals in their third or fourth decade of life. MTT is generally considered a high-grade malignant neoplasm with a poor outcome [Yakulis et al, 1996]. Previous studies [Daimaru Y et al, 1984, Victoria L et al, 1999], reviewed the treatment and outcome of 27 MTTs arising in the head and neck and commented that there may be a subset of MTTs that occurr in this region as low-grade malignancies with favorable long-term prognosis. The primary involvement of the oral cavity is extremely rare. MTTs occur predominantly in the trunk, head and neck, and lower extremities [Enzinger FM, 2001]. Among all reported cases, approximately one third appear to arise in the head and neck region. In a recent detailed review of the literature, Victoria et al [Victoria L et al, 1999] summarized the anatomic distribution of head and neck cases. The data showed that 12 of the 27 cases described were found to arise in the structures of the neck or upper thorax.

Taken together with a recent report describing MTT of the maxilla, it can be concluded that intraoral presentation of MTT is rare. The hallmark of this tumor is the presence of rhabdomyoblasts scattered throughout the stroma indistinguishably from ordinary MPNST. The number of rhabdomyoblasts varies greatly from tumor to tumor and even from area to area in the same tumor. Chromosome analysis of MTTs showed a complex hyperdiploid karyotype with multiple unbalanced translocations, large markers, and ring formations. Although some of the markers were highly variable, other markers were reasonably stable and were seen in the majority of the abnormal metaphases. Haddadin et al [Haddadin et al, 2003], compared the chromosomal breakpoints in MTT, MPNST, and rhabdomyosarcoma to identify common regions of involvement. These included 7p22, 7q36, 11p15, 12p13, 13p11.2, 17q11.2, and 19q13.1.

Head and Neck Soft Tissue Sarcoma 135

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Fig. 4. a) Malignant Triton Tumor high-grade located in the neck with extensive areas of necrosis and hemorrhage, b) Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation 40X, c) Rounded or enlongated rhabdomyoblasts throughout the tumor, 40X.

## **10. Conclusions**

Head and neck soft tissue sarcomas are rare and represent 1-5% of all corporal neoplasias. The cause of the majority of sarcomas is yet unknown; however, it is thought that a number of environmental and genetic factors are closely linked to the development of these types of neoplasias. The survival range depends on the histological grade and the clinical stage. At five years, survival is approximately 60–70%, and with local control, it becomes 60–80%. The survival range depends on the histological grade and the clinical stage. Approximately 10–30% of patients presented with distant metastases within the first two years. In general, young patients with low-grade, small and superficial sarcomas have a better prognosis than high-grade sarcomas. Patients with sarcomas greater than 5 cm in clinical stage III or IV with positive surgical margins, can die from progression and metastases. To determine how a neoplasm is likely to behave, with or without treatment, it is necessary to know certain facts about the disease. The management of soft tissue sarcomas of the head and neck is particularly challenging and depends upon some prognostic factors. The assessment of prognostic factors, which correlate baseline clinical and experimental covariables to outcomes, is one of the major objectives of clinical research.

## **11. References**

134 Soft Tissue Tumors

Fig. 4. a) Malignant Triton Tumor high-grade located in the neck with extensive areas of

Head and neck soft tissue sarcomas are rare and represent 1-5% of all corporal neoplasias. The cause of the majority of sarcomas is yet unknown; however, it is thought that a number of environmental and genetic factors are closely linked to the development of these types of neoplasias. The survival range depends on the histological grade and the clinical stage. At five years, survival is approximately 60–70%, and with local control, it becomes 60–80%. The survival range depends on the histological grade and the clinical stage. Approximately 10–30% of patients presented with distant metastases within the first two years. In general, young patients with low-grade, small and superficial sarcomas have a better prognosis than high-grade sarcomas. Patients with sarcomas greater than 5 cm in clinical stage III or IV with positive surgical margins, can die from progression and metastases. To determine how a neoplasm is likely to behave, with or without treatment, it is necessary to know certain facts about the disease. The management of soft tissue sarcomas of the head and neck is particularly challenging and depends upon some prognostic factors. The assessment of prognostic factors, which correlate baseline clinical

necrosis and hemorrhage, b) Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation 40X, c) Rounded or enlongated rhabdomyoblasts

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**8** 

**Dermatofibrosarcoma Protuberans –** 

Titus Osita Chukwuanukwu and Stanley Anyanwu

Dermatofibrosarcoma protuberans (DFSP) is best described as a fibroblastic neoplasm. It is a low to moderate grade type of soft tissue sarcoma (STS) arising from cells of mesenchymal origin in the dermal layer of the skin1-4. This entity was first described in 1924 by Darier and Ferrand5. Though DFSP is a low grade malignancy, fibrosarcomatous variant can be very aggressive especially when provoked by inadequate excision. It is a rare type of skin cancer that can grow deeply into the skin to invade the fat, muscle, and bone. DFSP is a locally aggressive tumour and rarely metastasizes. This gives it a higher survival rate when

In developing countries however, late presentation to hospitals are very common. Patients here seek help first from unqualified persons and only come to the specialists late into their

DFSP comprises 0.01% of all malignant tumours and 2 – 6% of all soft tissue sarcomas1,2,3. STS constitute overall less than 1% of human adult solid malignant tumour7 but can be life threatening and sometimes difficult to diagnose and very challenging to treat. It has no sex predilection nor specified age incidence but is commoner between the ages of 20 and 50 years6-8. It is stated to be commoner in blacks with an estimated incidence of 0.8 to 5

The exact cause of Soft Tissue Sarcomas and Dermatofibrosarcoma Protuberans is not well known. Predisposing factors include genetic mutation of the P 53 gene, exposure to ionising radiations, post burn and other scars and exposure to certain carcinogens have been documented. Of particular note is its recurrent nature especially following inadequate

**1. Introduction** 

adequately excised1-7.

**2. Epidemiology** 

**3. Aetiology** 

illness. This has led to poor outcomes in many cases.

per/million persons per year in America6,8.

**Special Challenges of** 

**Constrained Countries** 

*Nnamdi Azikiwe University* 

*Teaching Hospital* 

*Nigeria* 

**Management in Resources** 

