CD10‐positive myxofibrosarcomas: a pitfall in the differential diagnosis of atypical fibroxanthoma

CD10 is now commonly used to differentiate atypical fibroxanthoma (AFX) from melanoma, spindle cell and dedifferentiated variants of squamous cell carcinoma and leiomyosarcoma. However, we have encountered CD10‐positive tumors that mimicked AFX but proved to be myxofibrosarcomas. The purpose of this study was to evaluate CD10 expression in a wide range of mesenchymal neoplasms that may involve the skin using tissue microarrays. Our results indicate that in addition to AFX, CD10 expression is common in myxofibrosarcomas, undifferentiated pleomorphic sarcomas, dermatofibromas and dermatofibrosarcoma protuberans. Myxofibrosarcomas commonly present in the skin and may be difficult to distinguish from AFX on small biopsies and CD10 positivity may confound the diagnostic difficulty. Clarke LE, Frauenhoffer E, Fox E, Neves R, Bruggeman RD, Helm KF. CD10‐positive myxofibrosarcomas: a pitfall in the differential diagnosis of atypical fibroxanthoma.     

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.     

Clear cell atypical fibroxanthoma: a case report and review of the literature

Atypical fibroxanthoma (AFX) is a group of cutaneous tumors characterized by a population of fusiform, epithelioid and pleomorphic cells. Clinically, AFX is commonly found on the head and neck of older adults as a solitary ulcerated nodule. Clear cell atypical fibroxanthoma is a very rare variant of AFX, with only 13 cases reported to date. The differential diagnoses often include dermal neoplasms composed of clear cells, such as squamous cell carcinoma, basal cell carcinoma, metastatic renal cell carcinoma and balloon cell malignant melanoma. These diagnoses can be ruled out by the typical immunohistochemical profile of clear cell AFX, which is negative for specific epithelial and melanocytic markers. Herein, we describe a rare and unusual case of clear cell AFX arising on the ear of a relatively young adult patient. Histologically, the dermis was completely replaced by an atypical population of vacuolated cells with numerous atypical mitoses. Immunohistochemical stains were negative forpancytokeratin, CK5/6, CK7, and p63 S100 and Melan‐A stains. CD10 and CD68 stains were positive, making the findings consistent with the diagnosis of clear cell 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.     

Immunohistochemical staining of CD10 in atypical fibroxanthomas

BACKGROUND: The histologic diagnosis of atypical fibroxanthoma (AFX) may be difficult at times with a differential diagnosis including spindle cell/desmoplastic melanoma and a poorly differentiated squamous cell carcinoma (SCC). While there are immunohistochemical stains that may be used to support a diagnosis of either melanoma or carcinoma, the diagnosis of AFX tends to be one of exclusion. METHODS: A total of 35 cases including 16 AFXs, 10 poorly differentiated SCCs and nine spindle cell/desmoplastic melanomas were stained with the antibody against CD10. RESULTS: There was strong (3+) diffuse expression of CD10 in 15/16 (94%) AFXs, weak (1+) to moderate (2+) patchy expression of CD10 in 5/10 (50%) SCCs and weak (1+) expression of CD10 in 3/9 (33%) spindle cell/desmoplastic melanomas. CONCLUSION: CD10 expression is helpful in distinguishing between AFXs, carcinomas and melanomas and will be useful in a panel of antibodies when distinguishing between these entities.     

Immunohistochemical distinction of cutaneous spindle cell carcinoma

Cutaneous spindle cell squamous carcinoma is an uncommon variant of squamous cell carcinoma in which keratinocytes infiltrate the dermis as single cells with elongated nuclei rather than as cohesive nests or islands, and signs of keratinization of conventional squamous cell carcinoma are insubstantial or nonexistent. Spindle cell carcinoma must be distinguished from spindle cell/desmoplastic melanoma, cutaneous leiomyosarcoma, atypical fibroxanthoma (AFX), and scar. In instances when there is no definitive evidence of squamous differentiation, immunohistochemical studies may confer diagnostic discrimination. Twenty-four cases consisting of 12 spindle cell squamous cell carcinomas, 3 AFXs, 3 leiomyosarcomas, 3 desmoplastic melanomas, and 3 scars were evaluated with a battery of immunohistochemical stains, with the specificity and sensitivity of each marker calculated. The immunohistochemical battery consisted of S-100, desmin, CD68, and smooth muscle actin and cytokeratins P KER (keratins predominantly of molecular weight 56 and 69 kd) and low-molecular weight keratin (CAM 5.2), AE1/AE3, p63, and 34 beta E12 (CK903). Spindle cell squamous carcinomas were negative for S-100, CD68, smooth muscle actin, and desmin with the exception of 2 cases with weak staining for smooth muscle actin. 34 beta E12 provided positive results for each spindle cell squamous carcinoma. The other cytokeratin stains were less sensitive for spindle cell squamous carcinoma than 34 beta E12. The final immunohistochemical results were as follows: 34 beta E12 (12/12, 100%), p63 (10/12, 80%), AE1/AE3 (8/12, 67%), low-molecular weight keratin (7/12, 58%), and P KER (4/12, 33%). The 3 AFXs were positive for CD68 and negative for all other stains, whereas the 3 leiomyosarcomas stained positively for desmin and smooth muscle actin and negatively for all other stains. The 3 melanomas stained positively for S-100 and negatively for all other immunohistochemistry. The scars were negative for all stains. In conclusion, our study of 34 beta E12 proved most promising in distinguishing spindle cell squamous carcinoma from the histologic mimickers, AFX, spindle cell melanoma, scar, and leiomyosarcoma.     

Diagnosis: atypical fibroxanthoma or not? Evaluating spindle cell malignancies on sun damaged skin: a practical approach

Poorly differentiated spindle cell malignancies on sun damaged skin frequently pose a diagnostic challenge for dermatopathologists. The vast majority of these neoplasms ultimately are diagnosed as either atypical fibroxanthoma (AFX), spindle cell squamous cell carcinoma (SCSCC), or spindle cell melanoma (SCM), and rarely leiomyosarcoma or angiosarcoma. Light microscopic clues may suggest one of these neoplasms, but subtle and overlapping characteristics often render precise diagnosis impossible based on morphological features alone. Immunohistochemistry therefore is necessary to firmly and accurately diagnose the majority of spindle cell malignancies on sun damaged skin. We summarize typical clinical and histological findings associated with this group of malignancies and offer a practical immunohistochemical approach to use in their diagnosis.     

Dermatoscopic features of cutaneous atypical fibroxanthoma: three cases

Atypical fibroxanthoma (AFX) is an uncommon, low‐grade, malignant, spindle‐cell tumour of fibrohistiocytic histogenesis, which can mimic other malignant skin tumours, such as basal and squamous cell carcinoma (CC), melanoma, and Merkel cell carcinoma (MCC). Three cases of AFX were examined by dermatoscopy, which revealed white areas and an atypical polymorphous vascular pattern characterized by the concurrence of different structures: linear, dotted, hairpin, arborescent and highly tortuous vessels, irregularly distributed over the surface. Seborrhoeic elements and photoageing may be accompanying features depending on the anatomical location of the AFX. AFX may be added to the list of slightly pigmented, reddish, malignant cutaneous tumours, such as SCC, MCC, amelanotic/hypomelanotic melanoma and eccrine porocarcinoma, which display prominent and chaotic dermatoscopic neoangiogenetic features in more advanced stages of proliferation.     

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.     

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.     

Spindle cell neoplasms coexpressing cytokeratin and vimentin (metaplastic squamous cell carcinoma)

Spindle cell squamous carcinoma (SCSC) and atypical fibroxanthoma (AFX) are both spindle cell neoplasms (SCN) that usually arise in areas of solar or ionizing radiation of elderly patients. Both lesions have a similar biologic behavior. In addition, the morphologic and ultrastructural similarities found in AFX and the spindle cell component of SCSC, have led some investigators to conclude that these tumors have a similar cell of origin. We studied 15 SCNs with no evidence of epithelial origin and no morphologic epithelial component, that showed immunohistochemical and ultrastructural evidence that would support metaplastic changes of a squamous cell carcinoma to a neoplasm with mesenchymal characteristics.     

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.     

Role of CD10, wide-spectrum keratin, p63, and podoplanin in the distinction of epithelioid and spindle cell tumors of the skin: an immunohistochemical study of 81 cases

Cutaneous epithelioid and spindle cell neoplasms occasionally pose a significant diagnostic challenge on purely histologic grounds. Given the substantial clinicopathologic overlap between these lesions, especially in small biopsies, the use of immunohistochemical studies are essential. We evaluated the utility of a battery of immunohistochemical markers, including podoplanin (D2-40), CD10, p63, and wide-spectrum cytokeratin, for distinguishing cutaneous epithelioid and spindle cell tumors. A total of 81 cases, including 42 atypical fibroxanthoma (AFX), 13 spindle cell melanoma, 10 sarcomatoid carcinoma, 9 leiomyosarcoma (LMS), and 7 leiomyoma, formed the basis of our study. Immunohistochemical results were as follows-AFX: CD10 (35 of 42), p63 (1 of 42), CK (1 of 42), and podoplanin (19 of 42); spindle cell melanoma: CD10 (7 of 13), p63 (0 of 13), CK (0 of 13), and podoplanin (2 of 13); sarcomatoid carcinoma: CD10 (5 of 10), p63 (7 of 10), CK (4 of 10), and podoplanin (7 of 10); LMS: CD10 (4 of 9), p63 (0 of 9), CK (2 of 9), and podoplanin (1 of 9); and leiomyoma: CD10 (0 of 7), p63 (0 of 7), CK (0 of 7), and podoplanin (1 of 7). Our findings showed that the combination of certain immunohistochemical markers may be a useful adjunct in the evaluation of epithelioid and spindle cell tumors of the skin. In this study, we found that a combination of wide-spectrum cytokeratin and p63 are most helpful in the distinction of sarcomatoid carcinomas from other tumors; however, there remains a substantial minority of cases of sarcomatoid carcinoma that will consistently demonstrate negative staining for these markers. We also found that CD10 and podoplanin (D2-40) have limited diagnostic utility in epithelioid and spindle cell tumors of the skin; however, a strong and diffuse pattern of staining will favor the diagnosis of AFX. Caution should also be observed in the diagnosis of spindle cell malignant melanoma because some cases may express CD10, p63, and podoplanin while being nonreactive to S100 protein. Awareness of the limitations of the use of these stains and familiarity with their staining patterns in spindle and epithelioid cell tumors of the skin are extremely important because the prognostic and therapeutic implications for such neoplasms may be quite different.     

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.     

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.     

Cutaneous papillary squamous cell carcinoma. A report of two cases

Several histologic patterns of squamous cell carcinomas (SCC) have been described, including classical, adenoid, verrucous, and clear cell. We report 2 cases of an unusual purely exophytic papillary growth pattern. Both tumors occurred on sun-exposed skin of elderly patients and exhibited rapid growth. The tumors were red-tan and fungating, raising the clinical differential diagnoses of pyogenic granuloma, SCC, metastatic carcinoma or amelanotic melanoma. Histologically there was a prominent papillary growth pattern with several layers of notably atypical squamous epithelium overlying a fibro-vascular core in both cases. Mitoses were frequent. The tumors lacked deep invasion, although focal invasion of the stalk was present. These tumors were histologically distinct from verrucous carcinoma, verrucous Bowen's disease, and previously described adnexal carcinomas. The lack of deep invasion and the absence of local recurrence or metastatic disease after 18 months follow-up suggest that this histologic variant is a low-grade malignancy, although study of more cases and longer follow-up will be necessary to accurately assess the biology of this papillary variant of SCC. We believe that this growth pattern has not yet been described and a pure papillary form must be included as one of the histological subtypes of cutaneous SCC.     

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.     

Aberrant Melan-A expression in atypical fibroxanthoma and undifferentiated pleomorphic sarcoma of the skin

Background: Atypical fibroxanthoma (AFX) is a distinctive clinicopathologic entity presenting on sun‐damaged skin of the elderly. Its behavior is benign if strict diagnostic criteria are applied. Tumors showing invasion of deeper structures or perineural/lymphovascular invasion are best regarded as undifferentiated pleomorphic sarcoma of the skin. The diagnosis requires immunohistochemical studies to exclude melanoma, squamous cell carcinoma, angiosarcoma and leiomyosarcoma. Methods: Two AFX and one undifferentiated pleomorphic sarcoma showing aberrant expression of Melan‐A were identified. Clinical data were obtained and histopathological features, immunohistochemical profile and electron microscopy were assessed. Results: All tumors arose on sun‐damaged skin of elderly males. Two AFX showed pushing growth into superficial subcutis only. The undifferentiated pleomorphic sarcoma was characterized by infiltrative growth into galea as well as perineural invasion. Multifocal expression of Melan‐A and MART‐1 was largely limited to tumor giant cells in the absence of S100 or HMB‐45 labeling. No melanosomes or premelanosomes were identified by electron microscopy. Conclusions: Aberrant expression of Melan‐A and MART‐1 in AFX and undifferentiated pleomorphic sarcoma of the skin represents an important diagnostic pitfall with potential for misdiagnosis as melanoma. Melan‐A expression limited to tumor giant cells, in the absence of S‐100 positivity, is a helpful diagnostic feature. Thum C, Hollowood K, Birch J, Goodlad JR, Brenn T. Aberrant Melan‐A expression in atypical fibroxanthoma and undifferentiated pleomorphic sarcoma of the skin.     

Atypical fibroxanthoma/malignant fibrous histiocytoma

ABSTRACT: Atypical fibroxanthoma (AFX) is an unusual spindle cell tumor occurring on actinically damaged skin of the head and neck. Clinically, it is often confused with basal cell carcinoma, squamous cell carcinoma, or even melanoma. Although initially thought to be a diagnosis of exclusion histologically, newer immunostains have helped in the identification of AFX. Mohs micrographic surgery has been utilized for the treatment due to its tissue sparing ability along with lower recurrence rate.     

Immunoreactivity of CD99 in invasive malignant melanoma

BACKGROUND: CD99, also known as p30/32, is a glycoprotein product of the MIC2 gene. It was originally utilized in immunohistochemistry as a unique marker for Ewing sarcoma, other primitive neuroectodermal tumors, and subsequently in other tumors. Its expression in malignant melanoma (MM) has not been well documented, with just two isolated cases of MM recently reported. Recent studies have documented CD99 expression in a significant percentage of atypical fibroxanthomas (AFX), posing potential diagnostic problems in differentiating these two entities. As mistaking MM for AFX based on immunohistochemical staining pattern has significant consequences, we sought to determine the percentage of invasive MM in our archives that have this staining pattern. METHODS: Seventy-eight cases of invasive melanoma were retrieved from our files. Each case was stained with mouse anti-human CD99 and evaluated for membranous expression. RESULTS: Our evaluation revealed that 47 of 78 MM cases (60%) stain positive for CD99. CONCLUSION: This study is the first to demonstrate, in a large series, the prevalence of CD99 expression in primary cutaneous melanoma. Additionally, this introduces in the histologic differential diagnosis of CD99 expressing dermal spindle cell lesions.