Role of CD10, Wide-Spectrum Keratin, p63, and Podoplanin in the Distinction of Epithelioid and Spindle Cell Tumors of the Skin

Abstract

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.

Study of Epithelial to Mesenchymal Transition in Atypical Fibroxanthoma and Undifferentiated Pleomorphic Sarcoma to Discern an Epithelial Origin

“…28,29 However, some degree of D2-40 expression can be found in 56% of nonmetastasizing cSCC. 28 Although some authors have previously reported a weak D2-40 expression in a low percentage of AFXs, 23,30 we found D2-40 to be completely negative in our series, while lymph vessels could be delineated.…”

“…9,22 Both neoplasms appear on sun-exposed areas of old patients, and some patients develop both types of lesions in a close area over a short period. Although usually negative, the expression of cytokeratins can be positive in AFX, 23,24 and the p40 isoform of p63 has been claimed to be a better marker to distinguish both entities. 25 To explain the aberrant cytokeratin staining in AFX, the possible phagocytosis of cytokeratinexpressing epithelial cells has been postulated.…”

Immunohistochemistry in Dermatopathology

“…That can be further complicated by occasional expression of D2-40, FLI1, and CD31 in AFX. 68,77,91,92 CD34 and ERG may be useful to differentiate those entities.…”

“…However, p63 is not entirely specific and shows focal labeling in rare cases of AFX and leiomyosarcoma. [67][68][69] As part of an IHC panel, p63 can be helpful in the differential diagnosis of spindle cell neoplasms (Table 3). 67 …”

“…Reactivity in AFX has ranged from 100% to 78%. 68,69,[76][77][78][79] Focal expression of myogenic markers (calponin, SMA, HHF35), indicative of myofibroblastic differentiation, can be seen in up to one-third of AFXs. 62,80 Therefore, use of SMA or calponin alone may be insufficient to diagnosis leiomyosarcoma, and a panel should include another muscle marker, such as desmin or h-caldesmon.…”