Primary cutaneous carcinosarcoma: case report with expanded immunohistochemical analysis

Abstract

An 83‐year‐old woman presented with a nodular, eroded tumor on the skin between the nose and the upper lip of 18 months’ duration. There were no palpable lymph nodes and no infiltrates on chest radiography. Complete surgical excision showed a tumor measuring 65 × 40 × 30 mm. On histopathologic examination, it was composed of typical basal cell carcinoma (BCC) nodules and large sheets of oval or short spindle cells (Fig. 1a), with vesicular nuclei, distinct nucleoli, moderate pleomorphism, and pronounced mitotic activity (more than 40 mitoses/10 high‐power fields). In parts abutting the upper lip, BCC nodules were found in the muscle layer, but the small salivary glands were uninvolved (Fig. 1b). Immunohistochemical analysis (Table 1) revealed a cytokeratin (CK)‐positive, Ber‐EP4‐positive, and vimentin‐negative BCC component (Fig. 2a), and a vimentin‐positive, CK‐negative sarcomatous component (Fig. 2b). In addition, mesenchymal tumor components were focally positive for smooth muscle actin (SMA). The BCC component showed irregular reaction with CK7, which stained some lobules and parts of individual nests (Fig. 2c). The final diagnosis was primary cutaneous carcinosarcoma. At the last visit, 3 months after operation, no signs of recurrence or metastatic spread were observed. Additional immunohistochemical analyses showed preserved membranous β‐catenin staining in the BCC component, without nuclear reaction in the mesenchymal component. The labeling index (LI) is expressed as the percentage of positive cells, and is calculated from the number of positive tumor cells divided by the total number of tumor cells counted (minimum 300 cells) in the areas with most pronounced immunopositivity. Counting was performed on images taken from microscopic high‐power fields with an Olympus DP70 digital camera (Olympus Corporation, Tokyo, Japan). The program analySYS (Soft Imaging System, Munster, Germany) was used, with the screen grid and the manual touch‐count method. The LI values of Ki‐67 and telomerase reverse transcriptase (hTERT) were higher in the sarcomatous component. hTERT displayed enhanced nucleolar localization and diffuse staining of mitotic cells. Histone deacetylase 1 (HDAC1) was expressed in a smaller percentage of cells than HDAC2, with a higher LI in the sarcomatous component. HDAC2 was the only marker analyzed that stained more cells in the BCC component (Fig. 2d).(a) Basal cell carcinoma (BCC) nodules and diffuse proliferation of sarcomatous cells. (b) Deep peripheral parts of the tumor show BCC nodules infiltrating into the muscle layer, but the small salivary glands are uninvolved. Hematoxylin and eosin; original magnification: (a) ×100; (b) ×40image Immunohistochemical staining in carcinosarcoma Antigen Source Epithelial (BCC) component Mesenchymal component CK (AE1/AE3) Dako* + – EA (Ber‐EP4) Dako + – CK7 Dako + (variable) – EMA Dako – – CEA Dako – – S‐100 Dako – – HMB‐45 Dako – – Vimentin Dako – + Factor VIII‐related Ag Dako – – CD34 Dako – – CD68 Dako – – CD99 Dako – – LCA Dako – – α‐SMA Dako – + (focal) Desmin Dako – – β‐Catenin Santa Cruz† + (membranous) – Ki‐67 (LI) Dako 10% 32% hTERT (LI) Novocastra‡ 22% 41% HDAC1 (LI) Santa Cruz 16% 40% HDAC2 (LI) Santa Cruz 76% 37% CEA, carcinoembryonic antigen; CK, cytokeratin; EA, epithelial antigen; EMA, epithelial membrane antigen; HDAC, histone deacetylase; hTERT, telomerase reverse transcriptase; LCA, leukocyte common antigen; LI, labeling index; SMA, smooth muscle actin. Glostrup, Denmark. Santa Cruz, CA, USA. Newcastle, UK. (a) Cytokeratin (CK) stain reveals epithelial (basal cell carcinoma, BCC) nodules, whereas the large sheet of sarcomatous cells (top left) is unstained. (b) Vimentin‐positive sarcomatous component and negative BCC nodules. (c) Variations of CK7 staining between BCC nodules and inside individual nodules. (d) Histone deacetylase 2 (HDAC2) expression is higher in the BCC component (right) than in the sarcomatous component. Streptavidin–biotin; original magnification: (a) ×12.5; (b, c) ×100; (d) ×400image