Christine J. Ko and Tammie Ferringer

Angiomyofibroblastoma

Angiomyofibroblastoma is a benign genital stromal tumor composed of clustered epithelioid to spindled cells in a myxoid to hyaline vascular stroma. Cellularity is somewhat variable. Tumor cells generally stain with desmin but are negative with actin and CD34. The differential diagnosis includes cellular angiofibroma.

Atypical vascular lesion (AVL)

Atypical vascular lesion is generally located on the breast and appears several years after irradiation. Clinically, the lesions are initially small purple-pink to red-brown multifocal papules that are well circumscribed histopathologically. While initially described as benign (acquired progressive lymphangioma or benign lymphangiomatous papules of the skin), many authors now consider these lesions to be potential precursors of angiosarcoma. Thus, close clinical follow-up or sometimes complete excision has been recommended. Amplification of MYC and FLT4 expression suggests a diagnosis of angiosarcoma rather than AVL.

Microscopically, there is a spectrum of “more banal to more worrisome”. Banal lesions appear well-delimited in the superficial dermis, with non-atypical endothelial cells in a single layer lining vessel lumens with minimal luminal anastomosis. More worrisome lesions show deeper, infiltrative involvement of the dermis with anastomosing vessels. Features that are absent include significant cytologic atypia, papillated endothelial cells, and lakes of blood. Such findings would be suspicious for angiosarcoma.

Calcifying aponeurotic fibroma (juvenile aponeurotic fibroma)

These tumors have a propensity for recurrence and a predilection for the palms and soles of children.

Carcinosarcoma (biphasic)

Carcinosarcoma is composed of two different malignant cell types: epithelial and mesenchymal spindle cells. Examples of carcinosarcoma in the skin include tumors with foci of basal cell carcinoma or squamous cell carcinoma intimately associated with a malignant spindle cell population that is negative with keratin stains. This spindle cell population sometimes has some resemblance to the cells of atypical fibroxanthoma. The differential diagnosis includes other malignant epithelial and spindle cell tumors, with the key to carcinosarcoma being recognition of the close admixture of two different malignant cell types.

Collagenous fibroma (desmoplastic fibroblastoma)

These tumors most commonly involve the subcutis of adults in a variety of sites, including arms, legs, back, hands, and feet. Typically, they are well-demarcated but can focally infiltrate surrounding tissue and vessels are inconspicuous, differentiating desmoplastic fibroblastoma from the more cellular fibromatosis. Mitoses are not a component. S100, CD34, and desmin are negative. Clonal abnormalities involving 11q12 have been reported.

Cutaneous myoepithelioma

Myoepitheliomas are often considered in the spectrum with mixed tumor of the skin but lack ductal differentiation. Parachordomas belong to this spectrum but have more cytoplasmic vacuolations (physaliferous cells). Myoepithelioma has a propensity for the limbs of young adults. Expression of cytokeratin and/or EMA, as well as S100 is helpful in diagnosis. Calponin, SMA, and p63 may also be expressed. Malignant and benign tumors exist in this spectrum.

Extra-abdominal desmoid (extra-abdominal fibromatosis)

Extra-abdominal desmoids originate from the fascia and connective tissue surrounding muscles, especially in the shoulder/pelvic girdle/thighs. Adolescents and young adults are most commonly affected. Although less common in children, extra-abdominal desmoids can present on the head/neck in this age group. Tumors can be multicentric and large and erode into bone or other nearby structures. Histologic findings include slender, elongated, bland spindle cells that are separated by collagen in long fascicles. Tumor cells may infiltrate surrounding structures, especially striated muscle. Tumor cell differentiation is fibroblastic/myofibroblastic, as suggested by positive staining with smooth muscle actin and muscle-specific actin and, rarely, desmin. Tumor cells are also positive with beta-catenin. The main differential diagnosis includes fibrosarcoma and reactive fibroblastic/myofibroblastic proliferations.

Giant cell tumor of the soft tissue

These lesions, seen most on the limb of adults, are the soft tissue counterpart of giant cell tumor of bone. They are also known as giant cell tumor of low malignant potential. Mitoses can be common but are typical figures. The mononuclear and osteoclastic giant cells are CD68 positive.

Intravascular fasciitis