Squamous Cell Carcinoma With Clear Cells: How Often is There Evidence of Tricholemmal Differentiation?

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Clear-cell carcinoma of the skin was described by Kuo in 1980 as a cutaneous tumor composed of clear cells that lacked cytoplasmic glycogen or evidence of tricholemmal keratinization. Tricholemmal carcinoma (TC) is conventionally considered to be a neoplasm derived from adnexal keratinocytes with glycogenated clear cells and evidence of outer root sheath or tricholemmal differentiation. The existence of TC has been questioned as it has been argued that without clear immunohistochemical evidence of outer root sheath differentiation, TC cannot be distinguished from clear-cell carcinoma of the skin. Our laboratory has not routinely stained the cases that appear to be carcinomas with clear keratinocytes to determine if glycogen is present and has not made the diagnosis of TC. We sought to test whether the presence of glycogen, light microscopic features said to be typical of TC, or immunohistochemical findings would delineate a group of “true” TC among the cases that we have been recording as squamous cell carcinomas with clear cells (SCC-C). 40 cases of SCC-C were evaluated for 7 histologic and histochemical criteria (a lobular arrangement, peripheral palisading, tricholemmal keratinization, folliculocentricity, evidence of a preexisting tricholemmoma, the presence of intracytoplasmic glycogen, and a thickened basement membrane) said to characterize TC. Selected cases were then stained for immunohistochemical markers (CD34, CK17, and NGFR/p75) that have been used as evidence for tricholemmal differentiation in some studies. Of the 40 cases, 38 (95%) SCC-C showed intracytoplasmic glycogen (periodic Schiff positivity abolished by diastase) and 55% of cases showed foci of tricholemmal keratinization. Overall, the carcinomas showed a spectrum of the above aggregated criteria ranging from 0 to 5. None possessed all the criteria expected in an ideal TC. In addition, the majority of the selected SCC-C in this study were negative (85%) for antigens typically found in the outer root sheath epithelium of the hair follicle. The glycogen-free clear-cell carcinoma described by Kuo seems uncommon in our patient population. Rare cases of SCC-C met the majority of Headington's criteria for TC or showed immunohistochemical evidence of tricholemmal differentiation. Thus, we also conclude that well-differentiated TC is rare and its description in the literature may overstate the case that it is a well-characterized cutaneous neoplasm.

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