Pleomorphic Dermal Neoplasms

Abstract

Pleomorphic neoplasms are typically associated with high-grade malignant behavior, but this does not readily apply to primary cutaneous tumors. Despite morphologic features suggestive of malignancy, atypical fibroxanthoma, the classic example of a pleomorphic dermal neoplasm, is characterized by indolent clinical behavior. Atypical fibroxanthoma is a distinctive clinicopathologic disease affecting sun-damaged skin of elderly males. Histologically, it is often ulcerated and dermal based with pushing growth, characterized by a sheet-like and fascicular growth of pleomorphic epithelioid, spindled, and multinucleated tumor cells with brisk and atypical mitotic activity. However, no positive discriminatory histologic or immunohistochemical features exist. Its diagnosis is one exclusion with a wide differential diagnosis, mainly including other mesenchymal, melanocytic, and epithelial neoplasms. Particular considerations are pleomorphic dermal sarcoma, invasive melanoma, squamous cell carcinoma, metaplastic carcinoma, poorly differentiated cutaneous angiosarcoma, cutaneous leiomyosarcoma, myxofibrosarcoma, variants of fibrous histiocytoma (FH), pleomorphic fibroma, and non-neural granular cell tumor. The behavior of these tumors is varied and ranges from outright malignant to entirely benign, requiring confident diagnosis to reliably predict behavior and guide treatment. Although challenging, because of significant clinical and pathologic overlap, it is usually possible to establish a definitive diagnosis when attention is paid to the often subtle differentiating features. This requires careful tumor sampling, recognition of the subtle distinguishing morphologic features, judicious use and analysis of immunohistochemistry, and interpretation of the findings in the appropriate clinical setting.

S-100 Negative Granular Cell Tumor (So-called Primitive Polypoid Non-neural Granular Cell Tumor) of the Oral Cavity

“…The lesional cells would be NKI/C3 positive (CD63, melanoma associated antigen). However, the cells would also show strong reactivity to S-100 protein and other key melanoma markers such as HMB45 and Melan A [21]. The atypical fibroxanthoma (AFX) may show granular cell change (Granular cell AFX).…”

“…Tumor cells are consistently negative to S-100 protein and express reactivity to CD68. Multinucleate cells may be reactive to Melan A. Spindle cells express SMA reactivity and occasional reactivity to EMA [21].…”

Cutaneous Pleomorphic Rhabdomyosarcoma Occurring on Sun-Damaged Skin

“…Cutaneous angiosarcoma has a propensity to occur on the scalp or face of elderly men, and when poorly differentiated, can show appearances of an undifferentiated malignant epithelioid or spindle cell tumor. 13 Cutaneous angiosarcoma, however, is positive for vascular markers such as CD31 and CD34 and does not show skeletal muscle differentiation. 13 Cutaneous leiomyosarcoma usually has a fascicular spindle cell appearance, is positive for smooth muscle actin in addition to desmin, and is negative for myogenin and myoD1.…”

“…13 Cutaneous angiosarcoma, however, is positive for vascular markers such as CD31 and CD34 and does not show skeletal muscle differentiation. 13 Cutaneous leiomyosarcoma usually has a fascicular spindle cell appearance, is positive for smooth muscle actin in addition to desmin, and is negative for myogenin and myoD1. 1,2,13,14 Other tumors that can show rhabdoid morphology are the malignant rhabdoid tumor (MRT) of soft tissue and proximal type epithelioid sarcoma.…”

Atypical Fibroxanthoma

“…Also, SCC frequently invades subcutaneous tissue and shows presence of lymphovascular and perineural invasion. 16 Positive immunoreactivity for pankeratin (AE1/AE3), epithelial membrane antigen, or high-molecular-weight keratins (34bE12, cytokeratin 5/6) are often useful markers for SCC. 17 More recently, p40 antibody was proven to be more specific than p63 in differentiating SCC from AFX.…”