Immunohistochemical Distinction of Cutaneous Spindle Cell Carcinoma

Abstract

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.

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis

“…QPCR analysis, which displays increased sensitivity for detecting low expression levels of isoforms, dem onstrated infrequent expression of TP63 isoforms in primary human melanocyte cultures but significantly elevated expres sion in >70% of established melanoma cell lines. In contrast with previous immunohistochemistry studies, which showed little or no expression of p63 protein (Brinck et al, 2002;Di Como et al, 2002;ReisFilho et al, 2003b;Dotto and Glusac, 2006;Bourne et al, 2008;Morgan et al, 2008;Sakiz et al, 2009;Kanner et al, 2010), our data provide the first evi dence of marked upregulation of both p63 mRNA and pro tein in melanoma cell lines.…”

“…Expression of TAp63 and Np63 in uveal melanoma was dem onstrated in 12/18 (66.7%) and 1/18 (5.6%) cell lines, respec tively (Kilic et al, 2008). Other studies have suggested a lack of p63 expression in melanoma in situ or invasive disease Dotto and Glusac, 2006;Bourne et al, 2008;Morgan et al, 2008;Sakiz et al, 2009;Glusac, 2011).…”

A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma

“…37 Whether CD68 can become important in terms of classification remains to be determined. Currently, the reason for the ectopic CD68 expression remains unclear 20,38,39 and we interpret this histiocytic feature of desmoplastic melanoma as part of the Abbreviations: c þ n, cytoplasmic and nuclear staining were combined; N, number of cases. P-value derived from Fisher's exact test.…”

Desmoplastic spindle cell squamous cell carcinoma of skin

“…The present tumor is carcinoma. Atypical fibroxanthoma and desmoplastic melanoma was excluded because the present tumor expressed various CKs and did not express HMB45, Melan-A, SOX10, MITF; [3][4][5][6][7][8][9][10] the specificity of S100 protein is low, [3][4][5][6][7][8][9][10] the possibility of desmoplastic melanoma is quite unlikely. Because the present tumor expressed CKs, it is carcinoma.…”

“…[4][5][6][7][8][9][10] These two variants of skin SCC lack keratinization and intercellular bridge, thus causing diagnostic problems. [1][2][3][4][5][6][7][8][9][10] The author herein reports a case of desmoplastic SCC composed predominantly of spindle cells.…”