Atypical fibroxanthoma with pseudoangiomatous features: a histological and immunohistochemical mimic of cutaneous angiosarcoma

Abstract

Atypical fibroxanthoma and pleomorphic dermal sarcoma may be difficult to separate from cutaneous angiosarcoma. We aim to study the morphological spectrum of pseudoangiomatous features in these tumors and the value of staining for endothelial markers CD31, CD34, FLI1, and ERG. Eleven atypical fibroxanthomas and 3 pleomorphic dermal sarcomas were identified. All tumors arose on sun-damaged skin of elderly men. Atypical fibroxanthomas were nodular and confined to the dermis, whereas pleomorphic dermal sarcoma invaded into underlying fascia. All tumors were composed of pleomorphic epithelioid and spindle cells showing blood-filled spaces and intratumoral hemorrhage. Intracytoplasmic vacuoles (n = 4), hemosiderin deposition (n = 2), and keloidal stromal change (n = 1) were also noted. Immunohistochemically, CD31 was expressed in 43% of cases, FLI1 in 79% and smooth muscle actin in 50%. Staining for CD34, ERG, S100, HMB-45, desmin, p63 and cytokeratins was negative. Follow up (median, 43.1 months; range 1-100), available for 10 patients, showed no adverse outcome. Pseudoangiomatous features and aberrant expression of CD31 and FLI1 in atypical fibroxanthoma and pleomorphic dermal sarcoma may lead to an erroneous diagnosis of cutaneous angiosarcoma. Negativity for CD34 and ERG, in particular, is a reliable differentiating feature in this setting.

Introduction

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are distinctive and closely related cutaneous mesenchymal tumors affecting sun-damaged skin of the elderly [1], [2], [3]. Although their morphological spectrum and immunohistochemical expression profile is similar, use of the term AFX is restricted to tumors with nodular growth confined to the dermis. In contrast, PDS is characterized by the additional presence of invasion of deep subcutis, diffusely infiltrative growth, tumor necrosis, lymphovascular invasion, or perineural infiltration. When these strict diagnostic criteria are applied, the behavior of AFX is entirely benign, while PDS is best regarded as a low-grade malignant tumor with risk for local recurrence but only rare metastasis and disease related mortality [2], [4], [5]. Confident diagnosis is, however, challenging due to the lack of positive discriminatory morphological and immunohistochemical features. Tumor sampling, careful histological evaluation, broad use of immunohistochemical markers, and interpretation of the findings in the appropriate clinical context are necessary, in particular, to exclude melanoma, carcinoma, leiomyosarcoma, and angiosarcoma. Cutaneous angiosarcoma is a consideration of particular significance. It arises in the same clinical setting, but it is characterized by aggressive behavior with high recurrence, metastasis and mortality rates [6], [7]. Differentiation from AFX and PDS with pseudoangiomatous features showing florid intratumoral hemorrhage, blood-filled spaces, and hemosiderin deposition is a particular diagnostic challenge, further complicated by the recent demonstration of aberrant immunohistochemical expression of CD31 and FLI1, markers more typically associated with endothelial differentiation [2], [8], [9], [10], [11].

The aim of the present study was to further characterize the histological features of pseudoangiomatous AFX and PDS and study the value of immunohistochemistry for the endothelial cell markers CD31, CD34, FLI1, and ERG as a diagnostic aid in the differential diagnosis with cutaneous angiosarcoma.