HMB-45 (gp103) and MART-1 expression within giant cells in an atypical fibroxanthoma: a case report

BACKGROUND: Atypical fibroxanthoma (AFX) is a cutaneous tumor that primarily occurs in the sun-damaged skin of the head and neck of adults. It is often a rapidly growing, solitary lesion that may clinically resemble squamous cell carcinoma, malignant melanoma, or lobular hemangioma. The histologic differential diagnosis primarily includes spindle cell squamous carcinoma and spindle cell melanoma, and immunohistochemical studies are often needed to establish the diagnosis. CASE REPORT: We report an unusual case of an AFX with aberrant HMB-45 and MART-1 (melanoma antigen recognized by T cells-1) immunohistochemical expression. Clinical information was obtained. Histologic examination and immunohistochemical studies were performed. RESULTS: A 54-year-old woman presented with a 1.5 cm posterior scalp lesion, which was excised. Microscopic examination revealed a dermal tumor composed of pleomorphic and spindled cells with numerous giant cells. The tumor cells expressed CD68 but did not express either keratin or S-100. In addition, there was focal gp100 (with HMB-45) and MART-1 expression limited to the large, multinucleated cells with vacuolated cytoplasm. A diagnosis of AFX was subsequently made. CONCLUSIONS: This is the first reported case of an AFX with HMB-45 and MART-1 reactivity.     

The histopathologic spectrum of regression in atypical fibroxanthoma

Background: Atypical fibroxanthoma (AFX) with prominent fibrosis, sclerosis and hyalinization, and near‐total tumor regression is rare. Methods: Eight cases of AFX presenting with fibrosis were reviewed as to their tumor architecture, the degree and pattern of fibrosis and the associated inflammatory cell infiltrate. Results: Seven of eight cases had an exophytic architecture, with ulceration in one case. The degree of fibrosis ranged from 10% to 90%. Early fibrosis (2/8 cases) occurred as thickened sclerotic collagen bundles, either dispersed between the neoplastic cells or as septa imparting a multilobular appearance. Advanced fibrosis (6/8 cases) was associated with lamellar sclerosis, keloidal features, hyalinization and with near‐total tumor replacement. Prominent fibrosis rimming the periphery was present in all tumors. An associated lymphoid cell infiltrate with plasma cells and occasionally eosinophils was observed. Conclusions: Fibrosis with prominent sclerosis and hyalinization replacing the tumor is rare in AFX. Advanced fibrosis, in the absence of a history of prior trauma or surgery, may indicate spontaneous regression. These cases emphasize the importance of recognizing this subset of AFX in order to avoid misinterpretation, particularly in cases with few residual atypical cells. Stefanato CM, Robson A and Calonje JE. The histopathologic spectrum of regression in atypical fibroxanthoma.     

The role of CD10 in distinguishing atypical fibroxanthoma from sarcomatoid (spindle cell) squamous cell carcinoma

Background: The role of CD10 needs clarification in a broader immunohistochemical battery for distinguishing atypical fibroxanthoma (AFX) from spindle cell squamous cell carcinoma (sSCC). Methods: We retrospectively reviewed 23 cutaneous spindle cell tumors previously classified as AFX (n = 11) or as sSCC (n = 12). Each tumor was stained with CD10, S‐100, p63 and two or more cytokeratin stains. Defining AFX as a diagnosis of exclusion based on multiple negative cytokeratin stains and negative p63 staining, we reclassified four squamous cell carcinomas (SCCs) as AFX. CD10 staining was reviewed and graded in all tumors. Results: Fifteen tumors were classified as AFX. Strongly positive CD10 staining was observed in all 15 AFXs, as well as four (50%) of the eight SCCs. Expression of p63 was seen in six sSCCs (75%). Conclusions: CD10 is consistently expressed by AFX. However, CD10 is also often strongly expressed by sSCC. Positive staining with p63 favors a diagnosis of sSCC. An immunohistochemical battery useful for distinguishing AFX from sSCC may include CD10, p63 and two cytokeratin markers. However, CD10 alone should not be relied upon in the distinction of these entities. Wieland CN, Dyck R, Weenig RH, Comfere NI. The role of CD10 in distinguishing atypical fibroxanthoma from sarcomatoid (spindle cell) squamous cell carcinoma.     

Atypical fibroxanthoma with dermal amyloid deposit

Atypical fibroxanthoma (AFX) has been associated with several secondary changes, such as keloidal areas, myxoid or chondroid changes, osteoclast-like giant cells, sclerosis, fibrosis, pigmentation, hyalinization, or hemorrhagic areas. We report a case of an AFX 4 cm in diameter on the forehead of a 77-year-old male patient. There were dermal amyloid deposits intermingled with the tumor fascicles on the periphery of the lesion. A moderate inflammatory chronic lymphoplasmacytic infiltrate was found in the periphery of the tumor. The amyloid deposits were positive with Congo red staining (but negative after permanganate-treatment). The deposit was also immunostained with antibodies against CKs (AE1/AE3 and CK5/6). It did not stain with anti-amyloid A, or with antibodies against either kappa light or lambda light chains. Therefore the amyloid deposit was keratinic in nature.     

Keloidal atypical fibroxanthoma: a case series

Background:  Keloidal atypical fibroxanthoma (AFX) is a rare variant of AFX with thick bands of hyalinized collagen. The identification of keloidal collagen associated with fibrohistiocytic cells may erroneously lead to the diagnosis of keloidal dermatofibroma. Although AFX is a pleomorphic cutaneous tumor typically associated with a good prognosis, occasional reports of metastatic AFX highlight the importance of accurate identification.
Methods:  A total of nine cases of an unusual variant of AFX with keloidal tumoral sclerosis were collected and examined. The cases were stained with antibodies directed against S100, cytokeratin, CD68 and CD31.
Results:  Histopathological examination revealed pleomorphic cells trapped within hyalinized keloidal collagen bands. In several cases, the keloidal collagen also formed ring-shaped structures surrounding CD31-positive vascular structures. Pleomorphic cells were negative for S100 protein and keratin, but consistently labeled with antibodies directed against CD68.
Conclusions:  The diagnosis of keloidal AFX requires the exclusion of other malignant and benign lesions with keloidal or sclerotic collagen. Awareness of the rare variant of keloidal AFX may avoid a diagnostic pitfall leading to an erroneous diagnosis, particularly in small biopsies. The finding of sclerotic collagen preferentially deposited around vessels is an interesting and poorly understood phenomenon.     

Diagnostic value of CD163 in cutaneous spindle cell lesions

Background:  The histologic diagnosis of atypical fibroxanthoma (AFX) can sometimes be challenging. No specific marker exists to confirm the diagnosis other than excluding other entities. CD163 has been shown to have great specificity for tumors of monocyte/histiocyte lineage. In this study, we evaluated the diagnostic utility of CD163 in diagnosing AFX and in identifying skin lesions with histiocytic/dendritic derivation.
Methods:  A total of 157 cases, including 14 AFXs, 5 spindle cell squamous cell carcinomas (SCCs), and 7 spindle cell/desmoplastic melanomas, along with other cutaneous spindle cell and histiocytic/fibrohistiocytic lesions, were stained with CD163.
Results:  CD163 was expressed in 11 of 14 (79%) AFXs, with moderate to strong intensity. No staining was observed in cases of spindle cell SCC (0/5) and dermatofibrosarcoma protuberans (0/10). Rare spindle cell/desmoplastic melanomas (2/7) and cutaneous leiomyosarcomas (1/5) demonstrated positive staining. CD163 reactivity was seen in 24 of 29 of benign fibrous histiocytomas (BFHs), including 8 of 8 celular fibrous histiocytomas and 6 of 9 epithelioid cell histiocytomas. The majority of cutaneous histiocytic lesions, including juvenile xanthogranuloma, Langerhans cell histiocytosis and Rosai–Dorfman disease, were positive for CD163.
Conclusion:  CD163 is a useful adjunct in distinguishing AFX from other malignant cutaneous spindle cell tumors and offers improved specificity in identifying cutaneous histiocytic/dendritic lesions.     

p63 is a useful marker for cutaneous spindle cell squamous cell carcinoma

BACKGROUND: Cutaneous spindle cell squamous cell carcinoma (SCSCC) is a rare variant of SCC. This lesion is sometimes difficult to diagnose based purely on morphologic features. p63 is a member of the p53 gene family that can be identified in epithelial malignancies. METHODS: Thirteen cases of spindle SCC were stained with p63, CK34betaE12, MNF116, vimentin, and S100. Control cases included desmoplastic melanoma (eight cases), atypical fibroxanthoma (AFX) (10 cases), dermatofibrosarcoma protuberans (eight cases), and cutaneous leiomyosarcoma (LMS) (four cases). RESULTS: p63 was expressed diffusely in the nuclei of 100% (13/13) of SCSCCs. Of controls, p63 showed focal labeling of two LMS and two AFX. MNF116 and CK34betaE12 were positive in 13/13 SCSCCs. Of controls, one LMS was focally positive for MNF116. All SCSCCs and all control cases were positive for vimentin. CONCLUSIONS: In the given differential diagnosis, p63 appears relatively specific to SCSCC and adds a useful nuclear marker to the available repertoire. The findings also suggest that cytokeratins MNF116 and CK34betaE12 may be more useful than standard cytokeratins in labeling SCSCC.     

Atypical fibroxanthoma presenting in a patient with stage III mycosis fungoides

The association of atypical fibroxanthoma (AFX) and mycosis fungoides (MF) has never been reported. We report a 77-year-old female who was referred for Mohs micrographic surgery (MMS) of an AFX on the right hand. At the time of presentation, this patient had stage III MF, with erythroderma and palpable lymph nodes. Our patient's AFX measured 1.5x2.8 cm. The tumor was removed by MMS with clear margins. The pathologic specimen revealed a relatively well-circumscribed neoplasm in the upper dermis composed of atypical spindle cells with pleomorphism, hyperchromatic nuclei, and brisk mitotic activity. Immunohistochemical stains were focally positive for CD68, and negative for S-100, Melan-A, desmin, smooth muscle actin and neurofilament. Perilesional skin revealed epidermal hyperplasia, parakeratosis, and multiple epidermotropic lymphocytes with enlarged and hyperchromatic nuclei. One year after the initial MMS, our patient developed another tumor on the right hand, which measured 4x6 mm. This neoplasm underwent a fusiform excision with clear margins. Histological examination revealed evidence of MF and an AFX. To our knowledge, this is the first report of an AFX arising in a patient with MF.     

Myxoid atypical fibroxanthoma: a previously undescribed variant

Background: Atypical fibroxanthomas (AFX) are dermal-based cutaneous tumors typically found in sun-damaged skin of the elderly. Histologic variants include spindle cell, clear cell, osteoid, osteoclastic, chondroid, pigmented, and granular cell. To date, myxoid change in AFX, has not been described.
Methods: Four cases were retrieved from the consultation and surgical pathology files of Knoxville Dermatopathology Laboratory, Knoxville, Tennessee during a 4-year period. The clinical and histologic findings were reviewed and Alcian blue/periodic acid-Schiff (PAS) stain and panel of immunohistochemical stains was obtained.
Results: All 4 lesions occurred as solitary lesions in elderly males on the head and neck (2 cases) and upper extremity (2 cases). Histologically all tumors demonstrated a well-circumscribed, cellular lesion centered in the dermis and composed of a mix of atypical pleomorphic and spindle cells in a prominent myxomatous background. A junctional component was absent and the tumors did not arise from the epidermis or adnexal structures. Subcutaneous involvement was absent in all cases. Tumor cells were negative for melanocytic and epithelial markers. Positive staining was noted with CD10 (3/4 cases) and vimentin (4/4 cases).
Conclusion: Myxoid change in AFX is rare and previously undescribed in the English literature. Myxoid change may be a prominent finding in benign and malignant cutaneous tumors and awareness of this variant of AFX will avoid misdiagnosis.     

CD10, p63 and CD99 expression in the differential diagnosis of atypical fibroxanthoma,spindle cell squamous cell carcinoma and desmoplastic melanoma

Background: Atypical fibroxanthoma (AFX) is a pleomorphic spindle cell lesion of the skin; it is considered in the differential diagnosis with spindle cell malignant melanoma (MM) and sarcomatoid carcinoma/spindle cell squamous cell carcinoma (SCC). An optimum approach has yet to fully emerge with respect to the immunohistochemical discrimination of these lesions. Methods: Departmental archives from 1978 onwards were searched for clinicopathologically confirmed cases of AFX, MM and SCC. Immunostains for CD10, CD99 and p63 were performed in each case. Scored staining results were analyzed using Fisher's Exact Test. Results: Twenty‐seven of 31 cases of AFX were positive for CD10, as compared with 3 of 22 SCCs and 0 of 20 MMs. CD10 positivity was preferentially associated with the diagnosis of AFX (p < 0.001). p63 reactivity was observed in 15/22 cases of SCCs, 5/31 AFXs and 1/20 MMs. CD99 reactivity was observed in 3/31 cases of AFX, 2/22 SCCs and 3/20 MMs. Conclusion: CD10 positivity is relatively specific in this context for the diagnosis of AFX. Its utility is enhanced when only strong, diffuse membranocytoplasmic staining is considered as a positive result. In contrast to prior reports, p63 was not found to be highly sensitive for SCC. Similarly, CD99 showed no preferential staining of any single diagnostic group of lesions. Kanner WA, Brill LB, Patterson JW, Wick MR. CD10, p63 and CD99 expression in the differential diagnosis of atypical fibroxanthoma, spindle cell squamous cell carcinoma and desmoplastic melanoma.     

Cutaneous lipomatous neurofibroma: characterization and frequency

BACKGROUND: There are numerous variants of cutaneous neurofibroma reflecting its manner of growth and histologic composition. Lipomatous neurofibroma is the latest described variant with only eight cases reported. METHODS: A systematic study based on 320 consecutive specimens diagnosed of cutaneous neurofibroma was carried out. Conventional microscopy, immunohistochemistry, and statistical methods were used to determine the presence of fat cells, their amount, distribution, and frequency. RESULTS: Intratumoral fat was observed in 22 (6.9%) neurofibromas. All these were dermal neurofibromas. Intraneoplastic fat was divided into two groups: focal and diffuse (regularly interspersed). Eighteen tumors (5.6%) presented adipocytes focally intermingled with the spindle cells. There were four (1.3%) neurofibromas showing spindle cell proliferation with regularly scattered adipocytes. Lipomatous neurofibroma was more frequent located on head and neck than non-lipomatous neurofibroma ( p = 0.04). Neurofibromas without mature adipocytes were more frequently immunoreactive for CD34 compared with tumors showing intratumoral fat ( p = 0.02). CONCLUSIONS: We suggest that both metaplasia and aberrant adipose differentiation from multipotential cells may result in lipomatous neurofibroma. Focal presence of adipose cells may be attributable to metaplasia as the pathogenic mechanism. The fatty tissue being intrinsic to the tumor structure in its diffuse form, the lesion represents a distinctive tumor of the peripheral nerve sheath.     

Diagnostic utility of low-affinity nerve growth factor receptor (P 75) immunostaining in atypical fibroxanthoma

Background: Atypical fibroxanthoma (AFX) is a locally destructive, dermal‐based, fibrohistiocytic, mesenchymal tumor. Immunohistochemistry helps to differentiate AFX from squamous cell carcinoma and spindle cell melanoma. Immunomarkers against p75 yield positive stains in spindled cell melanomas and negative stains in AFX, suggesting that these may be useful in differentiating these two entities. However, a recent study concluded that p75 is not a specific marker of neuroectodermal tumors; furthermore, p75 staining in AFX has only been evaluated in a few cases. Methods: We stained 20 AFXs for p75 and various other markers. Results: Reactivity was noted for vimentin (20 of 20 cases), CD10 (17/20), CD68 (14/20), CD99 (13/20), D2‐40 (10/20) and p75 (1/20). Conclusions: We confirmed that CD99 and CD10 are frequently expressed in AFX (65 and 85%, respectively) and that CD31 rarely stains positive (5%). The 50% positivity rate of D2‐40, in contrast with published evidence for its absence in melanoma, suggests that D2‐40 may be useful for distinguishing AFX from melanoma. Furthermore, because only one sample was positive for p75, we confirm that p75 is useful in differentiating AFX from spindle cell melanoma. We advocate adding p75 and D2‐40 to assist in differentiating AFX from melanoma. Bull C, Mirzabeigi M, Laskin W, Dubina M, Traczyc T, Guitart J, Gerami P. Diagnostic utility of low‐affinity nerve growth factor receptor (P 75) immunostaining in atypical fibroxanthoma.     

Utility of p63 in the differential diagnosis of atypical fibroxanthoma and spindle cell squamous cell carcinoma

Atypical fibroxanthoma (AFX), spindle cell squamous cell carcinoma (SCSCC) and spindle cell melanoma are the primary entities in the differential diagnosis of a cytologically atypical spindle cell tumor arising on sun-damaged skin. AFX is generally regarded as a diagnosis of exclusion in this context: in the absence of S100 or keratin reactivity, a diagnosis of AFX is favored. However, keratin reactivity may be focal or even absent in SCSCC, and although numerous positive markers of AFX have been proposed, none has shown sufficient sensitivity and specificity for routine diagnostic use. We evaluated 20 AFX and 10 SCSCC with a panel of cytokeratins and p63 to assess the utility of the latter antibody in this differential diagnosis. All 10 SCSCC showed strong expression of p63, whereas all 20 AFX were p63 negative. Two additional cases (excluded from the study) were negative for keratins and S100 on initial shave biopsies, resulting in a favored diagnosis of AFX, but p63 stains performed retrospectively were positive. However, review of the excision specimens in both cases revealed deep subcutaneous extension, excluding AFX. p63 reactivity argues against the diagnosis of AFX and is therefore a useful addition to the standard immunohistochemical panel for cutaneous spindle cell neoplasms.     

Ultrastructure of Spindle Cell Squamous Carcinoma

A 63-year-old white male presented with a nine-month history of a nontender ulcerated lesion on his ear. Light microscopy demonstrated a moderately well circumscribed lesion in the dermis which abutted upon epidermis. There was no evidence of continuity between the tumor and overlying epithelium. The tumor was very cellular with an admixture of cells - spindle, polyhedral and bizarre giant cells. Mitotic figures were abundant and frequently abnormal. We interpreted this lesion to have the clinical and pathologic features of an atypical fibroxanthoma (AFX). Ultrastructure, however, showed abundant tonofilaments and desmosomes indicative of an epithelial origin and therefore most consistent with a spindle cell squamous carcinoma (SCSC). It is urged that, when possible, electron microscopy be performed on problematic cases diagnosed either as an AFX or spindle cell squamous carcinoma since it is the most valid basis on which a correct diagnosis can be made.     

人类原始抗原（CD34）在毛发上皮瘤和基底细胞癌中的表达

毛发上皮瘤是一种向毛囊分化的良性肿瘤，常与基底细胞癌混淆。应用人类原始抗原（ＣＤ３４）检测７例毛发上皮瘤和１２例基底细胞瘤中表达，结果：在正常皮肤血 皮细胞、血管周围和真皮内梭形细胞、毛囊、小汗腺周围梭形细胞阳性。毛发上皮瘤瘤团周围梭形细胞阳性，而基底细胞癌外周间质阴性，说明ＣＤ３４染色有助于临别这两种肿瘤。     

Atypical fibroxanthoma with lymphomatoid reaction

Background: Atypical fibroxanthoma (AFX) represents an uncommon skin tumor typically occurring on sun‐damaged skin of the elderly. Histopathologic variants include spindled, clear cell, osteoid, osteoclastic, chondroid, pigmented, granular cell and myxoid lesions. To date, an atypical lymphoid infiltrate, including CD30‐positive large cells mimicking lymphomatoid papulosis, has not been described in association with AFX. Methods: The clinical and histopathological characteristics of two AFX cases inciting an atypical lymphoid infiltrate, along with immunohistochemical profiles and T‐cell receptor gamma (TCRγ) gene rearrangement results, were reviewed. Results: Lesions in both cases occurred as solitary nodules in elderly patients. Microscopically, both lesions showed a cellular proliferation composed of pleomorphic spindle cells, associated with a prominent intralesional atypical lymphoid infiltrate. The spindle cells expressed CD10 but lacked the expression of S‐100, cytokeratins and muscle markers, thereby confirming the diagnosis of AFX. CD30 highlighted a significant subset of large mononuclear cells in the lymphoid infiltrate of one case. TCRγ gene rearrangement analyses were negative for both cases. Conclusion: An atypical lymphoid infiltrate, including the one resembling lymphomatoid papulosis, associated with AFX has not been previously described. It is important to recognize the reactive nature of the infiltrate to avoid a misdiagnosis of lymphoma. Zheng R, Ma L, Bichakjian CK, Lowe L, Fullen DR. Atypical fibroxanthoma with lymphomatoid reaction.     

CD117 immunoreactivity in atypical fibroxanthoma

Atypical fibroxanthoma (AFX) is a spindle cell neoplasm of the skin seen typically on sun-damaged skin of the elderly. Though described as a benign entity, local recurrence and distant metastasis have been reported. This study aims to investigate the potential pathogenic role of CD117, the c-kit receptor in AFX. CD117 was detected in 15 of the 16 cases (94%). The percentage of positive cells for CD117 expression among all tumors was approximately 30%. CD117 proved to be a very sensitive marker of AFX. This antibody may be a useful diagnostic adjunct in AFX.     

A case of sarcomatoid carcinoma of the skin

We describe the histological and immunocytochemical findings of an exophytic cutaneous tumour with mixed features of atypical fibroxanthoma (AFX) and basal cell carcinoma (BCC). A 73-year-old woman presented with a rapidly growing tumour measuring 35 mm in diameter and 10 mm in height on the left forearm. The tumour was excised and histology revealed a biphasic tumour with a pleomorphic spindle cell component and an associated tumour composed of discrete islands of atypical basaloid cells with peripheral palisading consistent with BCC. The two tumours merged into each other at one point. The spindle cell tumour showed a positive immunocytochemical reaction to fibrohistiocytic marker of KP-1 (CD68) and a negative immunocytochemical reaction to AE1/AE3, CAM5.2, S-100 and HMB-45, features consistent with AFX. Immunocytochemistry of the basaloid tumour showed a positive reaction to epithelial markers AE1/AE3 and CAM5.2, and a negative reaction to S-100, HMB-45 and KP-1 (CD68). To date, 15 cases of primary cutaneous carcinosarcoma have been reported in the literature. It has been postulated that these tumours may originate from undifferentiated progenitor cells capable of producing multiple cell lines.     

Atypisches Fibroxanthom – eine nicht‐„histiozytäre” Neoplasie.

Summary: On account of the controversial histogenesis of atypical fibroxanthoma (AFX) we examined 9 typical cases of this tumor histologically and by immunohistochemistry. Histology revealed eroded, ill‐defined dermal lesions with a pleomorph‐storiform growth pattern, predominantly composed of pleomorphic cells with numerous, in part atypical mitoses and variably accompanied by monomorphous cells among them also spindle cell areas. Three of our specimens contained osteoclast‐like giant cells. Immunohistologically, lesions consistently expressed vimentin, focally in histological monomorphous spindle areas alpha smooth muscle actin and reacted focally with KP1 and stronger with Ki‐M1p also in histologically bland areas without atypia and mitoses, but were generally negative for keratin, desmin and S‐100 protein. The average Ki‐M1p positivity accounted for 10 – 20 % of cells, in single cases focally up to 60 %. In order to investigate the nature of this cell population, sections were co‐labeled with the proliferation marker MIB1. MIB1 positivity accounted for up to 40 % of cells, yet only very occasional ones exhibited double staining with Ki‐M1p. Osteoclast‐like giant cells reacted with macrophage markers KP1 and Ki‐M1p, but not with MIB1. Thus, a macrophage differentiation of AFX appears to be excluded and the in part strong reactivity pattern for Ki‐M1p should best be regarded as an inflammatory background reaction against a neoplastic tissue destruction.     

Macrophage-rich epithelioid angiosarcoma mimicking malignant melanoma

BACKGROUND: Cutaneous epithelioid angiosarcoma is a type of cutaneous angiosarcoma and usually arise both on the head or neck of the elderly. CASE REPORT: An 86-year-old male with an epithelioid angiosarcoma of the scalp that mimicked malignant melanoma. RESULTS: A large irregular dark grey-blue plaque with an adjacent speckled tan nodule was suggestive of a primary cutaneous malignant melanoma with adjacent in-transit metastasis. Both had a well-circumscribed growth pattern and were composed of numerous large epithelioid cells with scattered severe atypia and mitoses. The tumor was positive for S-100 protein and vimentin and negative for low- and high-molecular weight cytokeratins. However, at high power, the epithelioid cells with severe atypia were negative for S-100 protein, and abundant large epithelioid macrophages were responsible for the S-100 protein positivity. The malignant tumor cells were negative for HMB-45, positive for CD31 and Factor VIII-related antigen, and focally positive for CD34. A focus of infiltrative, classical angiosarcoma with irregular vascular channels lined with plump, anaplastic endothelial cells was then found deep to the epithelioid tumor. CONCLUSIONS: Macrophage-rich epithelioid angiosarcoma demonstrates abundant S-100 protein-positive epithelioid macrophages. This subset of epithelioid angiosarcoma may mimic malignant melanoma and may present as a pitfall in diagnosis.