Histologic Variants of Squamous Cell Carcinoma of the Skin

Margaret H. Rinker, MD; Neil A. Fenske, MD; Leigh Ann Scalf, MD, and L. Frank Glass, MD, Division of Dermatology and Cutaneous Surgery, Department of Internal Medicine at the University of South Florida, Tampa, Fla.

Cancer Control. 2001;8(4) 

In This Article

Clear Cell Squamous Cell Carcinoma

Clear cell carcinoma is also referred to as hydropic SCC. It was first described by Kuo[32] in 1980 as a variant of SCC with extensive hydropic change. The hydropicde generation of neoplastic cells and the accumulation of intracellular fluid, not the accumulation of glycogen, lipid, or mucin, results in its clear cell appearance. Clear cell carcinoma occurs most commonly in elderly white men with a history of excessive sun exposure. All cases have occurred in the head and neck region, with the mandible being the most common site. Clinically, it appears as a nodule or mass that may occasionally be ulcerated. Of the six cases reported, four were noted to have rapid growth.

Kuo[32] further classified the six cases of clear cell carcinoma into three major histologic types: keratinizing(type I), nonkeratinizing(type II), and pleomorphic (type III). Type I is characterized by sheets or islands of tumor cells in a fibrotic stroma, with a sparse lymphocytic infiltrate. The tumor cells appear clear, with peripherally displaced nuclei, and may be indistinguishable from adipose cells. Some cells may also appear to have a"bubbled" cytoplasm, resembling sebaceous cells. Distinguishing features include foci of keratinization and keratin pearls. Type II is characterized by parallel or anastomosing cords of tumor cells in a compressed fibrotic stroma with a dense, inflammatory infiltrate composed of plasma cells and lymphocytes.Central necrosis may be evident within tumor cords. The tumor cells appear to have central nuclei with finely reticulated clear cytoplasm. Unlike type I, this variant does not demonstrate evidence of keratinization. Type III demonstrates marked pleomorphism with extensive vascular and perineural invasion. Foci of squamous differentiation and microcysts with acantholytic tumor cells may be seen. In all three types, none has evidence of either glycogen or mucin in tumor cells.[32]

This clear cell variant of SCC may be easily mistaken histologically for a sebaceous neoplasm. Distinguishing features, however,include evidence of squamous differentiation and a negative fat stain using Oil Red O. It may also appear similar to other clear cell tumors,including clear cell acanthoma,clear cell hidradenoma, clear cell hidradenocarcinoma, tricholemmoma,metastatic renal cell carcinoma,pilar tumor, balloon cell nevus, and balloon cell melanoma. Clear cell acanthoma, clear cell hidradenoma,clear cell hidradenocarcinoma, tricholemmoma,and metastatic renal cell carcinoma have a high content of cytoplasmic glycogen, which is not seen in the clear cell variant of SCC. Pilar tumors with clear cell change demonstrate marginated nuclei simulating the lower hair sheath cells and have glassy keratinization surrounded by a vitreous membrane-like stroma. Balloon cell nevus and melanoma usually demonstrate nests of melanocytes and pigment production.

It is difficult to determine the prognosis of clear cell SCC based on the few cases that have been reported in the literature. Of the six patients reported, one died of metastatic disease, one died postoperatively,and one was noted to have recurrence after 3 months.

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