**4. Soft tissue tumors**

The most common soft tissue tumors needing IHC are:


a) b)

A malignant epithelial neoplasm demonstrating serous acinar cell differentiation with

PAS-positive, diastase-resistant zymogen granules. Acinic cells may stain positively for amylase, transferrin, lactoferrin, CEA, VIP, and others. About 10% show some positivity for

**Figure 14.** a) Serous acinar cells have abundant pale to basophilic, heavily granular cytoplasm (H&E). b) Trypsin is

**Figure 13.** a) Clear cell carcinoma b) Highlighted clear cells by S100

318 A Textbook of Advanced Oral and Maxillofacial Surgery Volume 2

cytoplasmic zymogen secretory granules (Figure 14).

**3.12. Acinic cell carcinoma**

*3.12.2. Immunohistochemical stains*

*3.12.1. Definition*

S100 protein. [38, 39]

detectable in acinar cells.


#### **4.1. Lobular capillary hemangioma**

#### *4.1.1. Definition*

Lobular capillary hemangioma previously commonly referred to as "pyogenic granuloma, " is a reactive soft tissue growth with a predilection for the oral cavity that is histologically characterized by a lobular arrangement (Figure15).

#### *4.1.2. Immunohistochemical stains*

Positive for endothelial markers including factor VIII–related antigen and CD31 of proliferat‐ ing small blood vessels. [17-19]

**Figure 15.** a) H&E capillary hemangioma b) CD31 highlights the endothelial cell C) Factor VIII noted in the endothelial cells.

#### **4.2. Fibrosarcoma**

### *4.2.1. Definition*

Malignant neoplasm with only fibroblastic/myofibroblastic differentiation (Figure 16).

#### *4.2.2. Immunohistochemical stains*

Vimentin, and rarely, focal actin positivity. [40, 41]

**Figure 16.** a) Hypercellular tumor, showing spindle cells. b) Vimentin is highly positive

#### **4.3. Angiosarcoma**

#### *4.3.1. Definition*

Uncommon, high-grade malignant vascular neoplasm, occasionally associated with radiation.

#### *4.3.2. Immunohistochemical stains*

Positive with CD34, CD31, factor VIII–RAg, vimentin, podoplanin. ERG shows nuclear positivity in nearly 100% of angiosarcomas. FLI1 expression is found in as many as 100% of angiosarcomas, but utility is limited by poor specificity for vascular lesions. CD31 expression is found in more than 90% of angiosarcomas (Figure 17).

VEGFR3 expression is found in approximately 50% of angiosarcomas, [42-50]

#### **4.4. Kaposis sarcoma**

#### *4.4.1. Definition*

Kaposi sarcoma is a malignant neoplasm of endothelial cells. Oral lesions are commonly multifocal. Early lesions: are flat, red, and asymptomatic. Older lesions: larger, darker, nodular, and ulcerated. KS is common in patients with AIDS.

c)

**Figure 17.** a) Richly vascularized tumor with open vascular channels and mitotic figures b) CD 31 is positive.

#### *4.4.2. Immunohistochemical stains*

**4.2. Fibrosarcoma**

**4.3. Angiosarcoma**

**4.4. Kaposis sarcoma**

*4.4.1. Definition*

*4.3.2. Immunohistochemical stains*

*4.3.1. Definition*

*4.2.2. Immunohistochemical stains*

Vimentin, and rarely, focal actin positivity. [40, 41]

320 A Textbook of Advanced Oral and Maxillofacial Surgery Volume 2

**Figure 16.** a) Hypercellular tumor, showing spindle cells. b) Vimentin is highly positive

is found in more than 90% of angiosarcomas (Figure 17).

and ulcerated. KS is common in patients with AIDS.

Uncommon, high-grade malignant vascular neoplasm, occasionally associated with radiation.

Positive with CD34, CD31, factor VIII–RAg, vimentin, podoplanin. ERG shows nuclear positivity in nearly 100% of angiosarcomas. FLI1 expression is found in as many as 100% of angiosarcomas, but utility is limited by poor specificity for vascular lesions. CD31 expression

Kaposi sarcoma is a malignant neoplasm of endothelial cells. Oral lesions are commonly multifocal. Early lesions: are flat, red, and asymptomatic. Older lesions: larger, darker, nodular,

VEGFR3 expression is found in approximately 50% of angiosarcomas, [42-50]

Malignant neoplasm with only fibroblastic/myofibroblastic differentiation (Figure 16).

*4.2.1. Definition*

Human herpes virus 8 has variable expression for endothelial markers (CD31, CD34)[17, 18, 19, 48, 51] (Figure 18).

**Figure 18.** a) Nodular aggregates of spindle cells forming slit-like spaces (H&E). b) CD34 is positive.

#### **4.5. Leiomyosarcoma**

#### *4.5.1. Definition*

Malignant tumor of smooth muscle

#### *4.5.2. Immunohistochemical stains*

Currently, IHC confirmation of smooth muscle differentiation in LMS is based on the dem‐ onstration of desmin, α–SMA, muscle actin (HHF-35), and h-Caldesmon PAS with diastase will highlight intracellular glycogen. Tumor cells will be strongly and diffusely reactive with vimentin and actins (smooth muscle, muscle-specific), while variably positive for desmin [49, 50, 51, 52, 53, 54] (Figure 19) [52-57].

**Figure 19.** a) Spindle cell population. b) Desmin reactivity.

#### **4.6. Synovial sarcoma**

#### *4.6.1. Definition*

Synovial sarcoma is a malignant soft tissue tumor that shows epithelial and mesenchymal differentiation and has distinct clinical, genetic, and morphologic features.

Although it was once thought that synovial sarcoma arose in association with synovium, it is now well known that this is not the case and that these tumors may arise at any anatomic location.

#### *4.6.2. Immunohistochemical stains*

Morphologically, synovial sarcoma takes three main forms: 1) biphasic, 2) monophasic, and 3) poorly differentiated. Biphasic synovial sarcoma (BSS) consists of a fascicular spindle cell component and an epithelial component that usually shows glandular differentiation, whereas monophasic synovial sarcoma (MSS) lacks the epithelial component. The glandular compo‐ nent of synovial sarcoma expresses cytokeratins, including AE1/AE3. EMA expression is typically observed in both BSS and MSS. however, unlike its biphasic counterpart, MSS tends to be focally and inconsistently reactive for cytokeratins.

In particular, MSS may show reactivity for simple keratins: CK7, CK8, CK18, and CK19. S-100 protein expression is found in approximately 30% of synovial sarcomas. CD99 is commonly observed in MSS, but expression of this marker is also shared by some other spindle cell neoplasms. Strong positivity for BCL2 protein has also been noted in the spindle cell compo‐ nent of synovial sarcoma. [55-58]. TLE1 is positive in synovial sarcoma (Figure 20).

**Figure 20.** a) Spindle or epithelioid cells show a predominantly nested growth pattern. b) TLE1 is positive

#### **4.7. Rhabdomyosarcoma**

#### *4.7.1. Definition*

**Figure 19.** a) Spindle cell population. b) Desmin reactivity.

322 A Textbook of Advanced Oral and Maxillofacial Surgery Volume 2

Synovial sarcoma is a malignant soft tissue tumor that shows epithelial and mesenchymal

Although it was once thought that synovial sarcoma arose in association with synovium, it is now well known that this is not the case and that these tumors may arise at any anatomic

Morphologically, synovial sarcoma takes three main forms: 1) biphasic, 2) monophasic, and 3) poorly differentiated. Biphasic synovial sarcoma (BSS) consists of a fascicular spindle cell component and an epithelial component that usually shows glandular differentiation, whereas monophasic synovial sarcoma (MSS) lacks the epithelial component. The glandular compo‐ nent of synovial sarcoma expresses cytokeratins, including AE1/AE3. EMA expression is typically observed in both BSS and MSS. however, unlike its biphasic counterpart, MSS tends

In particular, MSS may show reactivity for simple keratins: CK7, CK8, CK18, and CK19. S-100 protein expression is found in approximately 30% of synovial sarcomas. CD99 is commonly observed in MSS, but expression of this marker is also shared by some other spindle cell neoplasms. Strong positivity for BCL2 protein has also been noted in the spindle cell compo‐

nent of synovial sarcoma. [55-58]. TLE1 is positive in synovial sarcoma (Figure 20).

differentiation and has distinct clinical, genetic, and morphologic features.

**4.6. Synovial sarcoma**

*4.6.2. Immunohistochemical stains*

to be focally and inconsistently reactive for cytokeratins.

*4.6.1. Definition*

location.

A malignant neoplasm with skeletal muscle phenotype: Embryonal type (80%): Alveolar type (20%)

#### *4.7.2. Immunohistochemical stain*

MYOD1, SMA positive A variety of myoid markers are positive (desmin, myogenin, MyoD1, myoglobin, actins), but it is important to remember that AE1/AE3, CAM5. 2, and CD56, along with synaptophysin, may be focally positive in some cases. [59, 60, 61] (Figure 21)

**Figure 21.** a) Mesenchymal cells and rhabdomyoblasts b) Desmin

### **4.8. Granular cell tumor**

#### *4.8.1. Definition*

This is an uncommon tumor composed of poorly demarcated granular cells, thought to be Schwann-cell derived, that frequently arise below a mucosa, the latter often showing pseu‐ doepitheliomatous hyperplasia. Granular cell tumor tends to affect the oral cavity (tongue most commonly). Tumors are usually smooth surfaced, poorly demarcated, and are often polypoid, and measure from1 to 2 cm.

#### *4.8.2. Immunohistochemical stains*

The neoplastic cells yield a strong and diffuse nuclear and cytoplasmic S-100 protein reaction and are also positive for CD68, NSE, α-1–antitrypsin [17-19, 62] (Figure 22).

**Figure 22.** a) Polygonal granular cells H&E b) neoplastic ells with s-100
