**Dermatofibrosarcoma Protuberans – Special Challenges of Management in Resources Constrained Countries**

Titus Osita Chukwuanukwu and Stanley Anyanwu *Nnamdi Azikiwe University Teaching Hospital Nigeria* 

## **1. Introduction**

142 Soft Tissue Tumors

Turc-Carel C, Pietrzak E, Kakati S, Kinniburgh AJ, Sandberg AA.(1987)The human int-1

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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 adequately excised1-7.

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

## **2. Epidemiology**

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 per/million persons per year in America6,8.

## **3. Aetiology**

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

Dermatofibrosarcoma Protuberans –

manage residual tumours and metastasis.

recommended for proper treatment of DFSP.

scars is subjected to full investigations and expert care.

reconstructing full thickness abdominal /chest wall defects3,31,14.

generally.

**7. Treatment** 

**8. Follow up** 

**9. Prognosis** 

Special Challenges of Management in Resources Constrained Countries 145

capable of delineating tissues planes thereby detecting extent of invasion of surrounding tissues including muscles and fat. This diagnostic tool is usually not available in developing countries. CT scan and contrast enhanced studies aid the diagnosis. X Rays of the affected parts and chest for metastasis to the lungs are also indicated in many cases. Biopsy of all suspicious tissues is recommended and for all lesions more than 5cm in diameter, an incision biopsy should precede definitive resection for adequate planning to avoid the danger of inadequate excision. Other investigations are done to determine the extent of local spread, distant metastasis and effects of the tumour on the patient

Surgery is the main stay of treatment. Wide local excision with histologically negative margins is the cornerstone of treatment3,6. For tumour less than 5cm in diameter a 3cm margin is recommended and for lesions greater than 5cm and recurrent lesions resection margin should be 5cm. The underlying tissue is also excised beyond the normal plane. The margins are examined to ensure they are tumour-free. Adjuvant radiotherapy increases tumour clearance and decreases rate of recurrence. Resection of tumours close to neurovascular bundle, bone and other vital structures may not obey these rules and adjuvant radiotherapy and chemotherapy will then be absolutely indicated. It is usually difficult to identify the margin of the tumour macroscopically as the finger like projections into muscle, fascia, fat resemble normal tissue. Fibrosis from previous surgeries may also make adequate excision difficult. Radiotherapy and chemotherapy may be used preoperatively to downsize the tumour and make it more resectable or post-operatively to

Mohs micrographic surgery is presently employed (where available) and hold great promise for complete tumour excision7. Very large defects may be created after tumour excision which requires the services of a plastic reconstructive surgeon. When the limb is involved, limb sparing surgeries are first attempted where feasible otherwise amputation may be resorted to. Reconstructive procedures include local rotation and advancement flaps, regional flaps, pedicle and free tissue transfers. Prosthetic mesh has been used for

A multidisciplinary approach by healthcare team with experience in management of STS is

Follow up of the patient is for life. Tumours have been known to recur many years after adequate excision. Any suspicious lesion around the area of an initial excision including the

Prognosis depends on both tumour and patient factors as well as availability of investigative and support services. Size is an important prognostic variable and so affects the quality of

excision either in margin or depth. High rate recurrence is noted in developing countries like Nigeria3.

## **4. Pathology**

DFSP are skin cancers that arise from the dermal fibroblasts. Recent evidences by immunohistochemical tests however suggest that they may arise from the dendritic cells in the skin

It grows in a finger like manner into the surrounding tissues leading to uneven penetration. This is a major cause of recurrence as some malignant cells may have projected far beyond the macroscopic margin at the time of initial resection.

DFSP is highly cellular and comprises spindle cells arranged in a radial fashion most characteristic at the periphery of the tumor. It displays immunoreactivity to CD34. Haematogenous spread to the lungs is the commonest route of metastasis, regional lymph nodes are rarely involved7.

The variants of DFSP include the Bednar tumour, myxiod DFSP, atrophic type and the fibrosarcomatous variant which is very aggressive.

There is no staging system yet developed specific for DFSP but it is currently staged in accordance with the American Musculoskeletal Tumour society staging system taking into account tumour grade and compartmentalization6.

## **5. Clinical presentation**

The usual pattern is an initial painless slow growing tumour. It may remain indolent for many years and sometimes grow to a very large size (more than 5cm in diameter over a few years). It may ulcerate but more commonly the patient intervenes one way or the other. Inadequate excision lead to recurrence of larger tumour and sometimes very slow healing ulcer. In the developing countries, they usually present with very large often fungating recurrent tumours. Other symptoms then depend on local effects and its site of location.

Metastasis is a late event and is commonest to the lung1,2,6,7,10. Later to liver, lymph nodes, peritoneum (for abdominal wall tumours) and nearby structures. Progression depends on the histological variant, grade, stage, size, how deeply seated the tumour is and presence or absence of other tumours and patients genetic predisposition. The immune status may also play a role as a rare recurrence of the fibrosarcomatous variant has been reported to occur in pregnancy11.

Rate of recurrence depends on the adequacy of resection margin and other management modalities employed. A DFSP has been reported to occur at the surgical scar of an earlier excised tumour after many years12.

Pain is as a result of pressure. When infected, there may be fever, anorexia and Weight loss. Overall, patient presents with large tumours without much constitutional symptoms/sign.

## **6. Investigations**

Biopsy of all suspicious lesions is mandatory. Histological and immunochemistry studies are done. The investigative tool of choice is the magnetic resonance imaging (MRI). This is capable of delineating tissues planes thereby detecting extent of invasion of surrounding tissues including muscles and fat. This diagnostic tool is usually not available in developing countries. CT scan and contrast enhanced studies aid the diagnosis. X Rays of the affected parts and chest for metastasis to the lungs are also indicated in many cases. Biopsy of all suspicious tissues is recommended and for all lesions more than 5cm in diameter, an incision biopsy should precede definitive resection for adequate planning to avoid the danger of inadequate excision. Other investigations are done to determine the extent of local spread, distant metastasis and effects of the tumour on the patient generally.

## **7. Treatment**

144 Soft Tissue Tumors

excision either in margin or depth. High rate recurrence is noted in developing countries

DFSP are skin cancers that arise from the dermal fibroblasts. Recent evidences by immunohistochemical tests however suggest that they may arise from the dendritic cells in

It grows in a finger like manner into the surrounding tissues leading to uneven penetration. This is a major cause of recurrence as some malignant cells may have projected far beyond

DFSP is highly cellular and comprises spindle cells arranged in a radial fashion most characteristic at the periphery of the tumor. It displays immunoreactivity to CD34. Haematogenous spread to the lungs is the commonest route of metastasis, regional lymph

The variants of DFSP include the Bednar tumour, myxiod DFSP, atrophic type and the

There is no staging system yet developed specific for DFSP but it is currently staged in accordance with the American Musculoskeletal Tumour society staging system taking into

The usual pattern is an initial painless slow growing tumour. It may remain indolent for many years and sometimes grow to a very large size (more than 5cm in diameter over a few years). It may ulcerate but more commonly the patient intervenes one way or the other. Inadequate excision lead to recurrence of larger tumour and sometimes very slow healing ulcer. In the developing countries, they usually present with very large often fungating recurrent tumours. Other symptoms then depend on local effects and its site of location. Metastasis is a late event and is commonest to the lung1,2,6,7,10. Later to liver, lymph nodes, peritoneum (for abdominal wall tumours) and nearby structures. Progression depends on the histological variant, grade, stage, size, how deeply seated the tumour is and presence or absence of other tumours and patients genetic predisposition. The immune status may also play a role as a rare recurrence of the fibrosarcomatous variant has been reported to occur in

Rate of recurrence depends on the adequacy of resection margin and other management modalities employed. A DFSP has been reported to occur at the surgical scar of an earlier

Pain is as a result of pressure. When infected, there may be fever, anorexia and Weight loss. Overall, patient presents with large tumours without much constitutional

Biopsy of all suspicious lesions is mandatory. Histological and immunochemistry studies are done. The investigative tool of choice is the magnetic resonance imaging (MRI). This is

the macroscopic margin at the time of initial resection.

fibrosarcomatous variant which is very aggressive.

account tumour grade and compartmentalization6.

like Nigeria3.

**4. Pathology** 

nodes are rarely involved7.

**5. Clinical presentation** 

excised tumour after many years12.

pregnancy11.

symptoms/sign.

**6. Investigations** 

the skin

Surgery is the main stay of treatment. Wide local excision with histologically negative margins is the cornerstone of treatment3,6. For tumour less than 5cm in diameter a 3cm margin is recommended and for lesions greater than 5cm and recurrent lesions resection margin should be 5cm. The underlying tissue is also excised beyond the normal plane. The margins are examined to ensure they are tumour-free. Adjuvant radiotherapy increases tumour clearance and decreases rate of recurrence. Resection of tumours close to neurovascular bundle, bone and other vital structures may not obey these rules and adjuvant radiotherapy and chemotherapy will then be absolutely indicated. It is usually difficult to identify the margin of the tumour macroscopically as the finger like projections into muscle, fascia, fat resemble normal tissue. Fibrosis from previous surgeries may also make adequate excision difficult. Radiotherapy and chemotherapy may be used preoperatively to downsize the tumour and make it more resectable or post-operatively to manage residual tumours and metastasis.

Mohs micrographic surgery is presently employed (where available) and hold great promise for complete tumour excision7. Very large defects may be created after tumour excision which requires the services of a plastic reconstructive surgeon. When the limb is involved, limb sparing surgeries are first attempted where feasible otherwise amputation may be resorted to. Reconstructive procedures include local rotation and advancement flaps, regional flaps, pedicle and free tissue transfers. Prosthetic mesh has been used for reconstructing full thickness abdominal /chest wall defects3,31,14.

A multidisciplinary approach by healthcare team with experience in management of STS is recommended for proper treatment of DFSP.

## **8. Follow up**

Follow up of the patient is for life. Tumours have been known to recur many years after adequate excision. Any suspicious lesion around the area of an initial excision including the scars is subjected to full investigations and expert care.

## **9. Prognosis**

Prognosis depends on both tumour and patient factors as well as availability of investigative and support services. Size is an important prognostic variable and so affects the quality of

Dermatofibrosarcoma Protuberans –

**10. References** 

Lyon 2006.

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Surg; 2010; 3(3): 167-169.

1995. 180 (2).146-149.

peau. Ann Dermatol Syphiliga 1924; 5:545-562.

study of fifty-six cases. Am J Surg 1966;111:634-644.

Special Challenges of Management in Resources Constrained Countries 147

In developed countries, the prognosis has improved remarkably but in the developing world however, prognosis remain poor due to a variety of factors. These include poverty, ignorance, late presentation with very large often fungating and metastatic lesions, low

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[2] Fletcher C.D.M., Rydholm A., Singer S., Sundaram M., Coindre J.M: In Fletcher C.D.M.,

[3] Chukwuanukwu T.O.G., Anyanwu S.N.C. Giant Fibrosarcoma Protuberans of

[4] Adigun I.A., Rahman G.A. A review of soft tissue sarcoma: Nig. J. Med. 16 (2); 94-

[5] Darier J, Ferrand M: Dermatofibromes progressifs et recidivants ou fibrosarcomes de la

[6] Kenny R.J, Cheney R., Stull M. A., Kraybill W. Soft Tissue Sarcomas; Current Management and Future Directions. Surg Clin N. AM 89 (2009) 235-247. [7] Burkhardt BR, Soule EH, Winkelmann RK, Ivans JC: Dermatofibrosarcoma protuberans:

[8] Derek D, Vincent C, Lori I, Timothy M.J., Vernon K.S., Low recurrence rate after Surgery

[9] Stojanovic A, Hoos A, Karpoff HM, Leung DH, Antonescu CR, Brennan MF, Lewis JJ.

[10] Canale ST. Campbell's operative Orthopaedics. 10th ed. Philadelphia P.A: Mosby;

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[12] Kshirsugar A.Y., Kanetkar S.R., Nikam Y.P., Vasisth G.O: Recurrent

[13] Kao CC, Rand RP, Stridde BC, Marchioro TL. Techniques in the composite

for Dermetofibrosarcoma protuberans. A multidisciplinary approach from a single

Soft tissue tumours of the Abdominal wall; Analysis of disease patterns and

doumatofibnrosarcoma protuberance on the scalp during pregnancy. Dermatol

dermatofibrosarcoma proliberans over auterior abdominal wall. J. Cutan Aesthet

reconstruction of extensive thoracoabdominal tumour resections. J. AM Coll. Surg.

Classification of tumours. Pathology and Genetics of Skin Tumour. IARC Press:

Unni K.K., Mertens F. (Eds): World Health Organisation classification of Tumours. Pathology and Genetics of Tumours of soft Tissue and Bone. IARC Press Lyon

Abdominal Wall Management Problems in Resources – Constrained Country. Nig.

Fig. 1. Recurrence in pregnancy after 3rd excision, now very aggressive and fatal.resection.

In developed countries, the prognosis has improved remarkably but in the developing world however, prognosis remain poor due to a variety of factors. These include poverty, ignorance, late presentation with very large often fungating and metastatic lesions, low infrastructure and low availability of expertise.

## **10. References**

146 Soft Tissue Tumors

Fig. 1. Recurrence in pregnancy after 3rd excision, now very aggressive and fatal.resection.


**9** 

**Clinical and Molecular Biology** 

N.J. Andersen1, R.E. Froman1, B.E. Kitchell2 and N.S. Duesbery1

*1Laboratory of Cancer and Developmental Cell Biology, Van Andel Research Institute* 

*2College of Veterinary Medicine, Michigan State University East Lansing, Michigan,* 

*'Skepticism is a healthy response to diagnosis of any tumor as angiosarcoma.* ' (Lane, 1952)

comparative framework to focus further discussion and scientific enquiry.

disease may be classified as environmental, familial, and iatrogenic.

Angiosarcoma (AS) is an aggressive malignancy of vascular tissue or vessel forming cells (Requena & Sangueza 1998). AS is rare in humans, making up 1-2 % of soft-tissue sarcomas (Young et al. 2010) and having an estimated incidence of 0.2/100,000 persons per year. Although AS can present anywhere in the body, in humans they typically arise in the skin or superficial soft tissues. It is most frequently noted on the face and scalp of elderly men where their persistent growth causes ulceration and infection, as well as on breasts, and extremities (Brennan et al. 2001; Fayette et al. 2007; Glazebrook et al. 2008). Less frequently AS arises in liver, heart, and spleen (Young et al. 2010). The literature is replete with retrospective analyses and case studies on AS but the rarity of patients diagnosed with this disease makes it difficult to perform more than a superficial investigation on the biology and clinical behavior of AS. However, the occurrence of AS is not restricted to humans and there are several alternative animal models with the potential to inform human studies. We have written this review to collect, compare, and contrast diverse reports on the biology and treatment of AS in humans and alternative animal models. Our objective is to establish a

While there is general agreement angiosarcomas arise from endothelial cells, its causes are uncertain. There appears to be no single cause of AS in humans; rather, a variety of factors have been reported to contribute to risk of disease. Broadly speaking the causes of this

Chronic exposure to any of several environmental risk factors has been linked with AS. Each of these directly or indirectly induce genetic mutations and alter gene expression. Vinyl chloride was first identified as an AS inducing compound when it was noticed that industrial plastic and synthetic rubber manufacturers as well as beauty salon personnel had

**1. Introduction** 

**2. Types of AS** 

**2.1 Environmental AS** 

**of Angiosarcoma** 

*Grand Rapids,* 

*USA* 

[14] Servant JM., Arnault E., Revol M., Damino A. Reconstruction of large thoracoabdominal defects using two-stage free tissue transfers and prosthetic materials. J Plast Reconstr. Aesthet. Surg. 2006; 59(4): 360-365.
