Resident Program - Case of the Month

Discussion

Morphologically the glottis mass shows clearly identifiable squamous cell carcinoma component as well as pleomorphic sarcoma-like component. Immunohistochemical staining shows tumor cells are positive for AE1/AE3, vimentin, P40, focal positive for CK5/6, negative for P16 and S100. The histological features and immunohistochemistry profile are most consistent with sarcomatoid squamous cell carcinoma. Due to the aggressiveness of the patient’s disease process and subglottic and paraglottic extension, the patient received cocurrent chemoradiation therapy. 

Squamous cell carcinoma (SCC) is the most common type of malignant laryngeal tumor.  Sarcomatoid squamous cell carcinoma, also named Spindle cell carcinoma (SpCC) designates a rare variant of squamous cell carcinoma in which the spindle epithelial cell resembles a sarcoma on histological examination. Sometimes the sarcoma-like formation blends with SCC or represents the recurrence of what originally thought was an obvious SCC.

Sarcomatoid SCC of the glottis is an uncommon, highly aggressive variant of SCC and comprises of 1% of all laryngeal cancers. According to WHO definition, it is considered as a biphasic tumor, so the diagnosis requires histological demonstration of both spindle cell carcinoma with sarcomatous appearance and squamous cell carcinoma components. Immunohistochemical studies of epithelial and mesenchymal markers are often used to diagnose the tumor. It has been suggested sarcomatoid SCC is a monoclonal epithelial neoplasm, and the sarcomatous component are derived from squamous epithelium with divergent mesenchymal differentiation.

Differential diagnosis

Sarcoma: Sarcoma are usually deeply located with no surface epithelium connection while Sarcomatoid SCC usually starts on the surface epithelium. Features of clear-cut squamous differentiation are absent. Immunostains are helpful for distinction between sarcoma and SpCC. CK5/6, epithelial membrane antigen (EMA) and nuclear p63 are usually positive in Sarcomatoid SCC, while sarcomas are positive for mesenchymal markers depending on differentiation: Leiomyosarcoma (SMA, desmin); Angiosarcoma (CD31, FLI-1, CD34, ERG); Malignant fibrous histiocytoma (vimentin, CD10).

Spindle Cell Melanoma (SCM): A rare subtype of malignant melanoma composed of spindled neoplastic cells arranged in sheets and fascicles. SCM may occur anywhere on the body, including scarring and inflammation. SpSCC and SCM may show similar histopathological features, so a careful search for adjacent melanoma in situ is helpful. Immunohistochemical stains of S100, SOX10 are usually positive.

Pleomorphic Carcinoma (PC): A rare but advanced malignancy in the lung. In WHO 2015, PC is grouped with “sarcomatoid” carcinomas of lung. The malignant epithelial neoplasm composes of spindle and multinucleated giant cells in different proportions. It is also called carcinoma with giant cells.  It has been suggested PC may represent dedifferentiated neoplasm from conventional squamous or adenocarcinoma. Morphologically, in addition to spindle cell component, the presence of multinucleated giant cells is helpful for distinction, although PC and sarcomatoid SCC may share similar immunohistochemical profile.

References

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