Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder—p63, MOC-31, and TTF-1

Abstract

Sarcomatoid carcinomas are rare malignancies which represent poorly differentiated epithelial tumors that may be difficult to recognize as such. While some cases may have obvious epithelial areas, the sarcomatoid areas are poorly distinguishable from true sarcoma at the light microscopic level and, by immunohistochemistry, often show only limited staining for traditional epithelial markers such as cytokeratin or epithelial membrane antigen. This can be particularly problematic for diagnosis on small biopsy specimens. We sought to assess the diagnostic utility of several immunohistochemical markers of epithelial differentiation including p63, MOC-31, and thyroid transcription factor-1 on sarcomatoid carcinomas of the head and neck (19 cases; 'spindle cell carcinomas'), lung (19 cases), and urinary bladder (11 cases). These results were compared to immunohistochemistry for the traditional epithelial markers pan-cytokeratin and epithelial membrane antigen. Staining for p63 showed the greatest diagnostic utility, positive in 63, 50, and 36% of head and neck, lung, and urinary bladder sarcomatoid carcinomas, respectively. p63 stains were positive in many cases where immunohistochemistry was negative for both pan-cytokeratin and epithelial membrane antigen. All three alternative markers were quite specific for epithelial differentiation, each staining less than 10% of the control group of 73 various primary and metastatic sarcomas, melanomas, and benign spindle cell lesions. In conclusion, immunostaining beyond traditional pan-cytokeratin and epithelial membrane antigen may have diagnostic utility in this context.

Spindle Cell Lesions—Neoplastic or Non-Neoplastic?

“…The exophytic masses are usually smooth, dark brown, and lobulated with extensive mucosal ulceration. As previously mentioned, most SpCC are biphasic tumors with areas of conventional squamous cell carcinoma admixed with areas of spindled and/or pleomorphic tumor [1,5,7]. In the Thompson et al study of laryngeal SpCC from the Armed Forces Institute of Pathology, they performed extensive H&E leveling of cases sent to them in consultation looking keenly for a conventional squamous component.…”

“…The larynx, particularly the glottis, is the most common primary site followed by the oral cavity, specifically the tongue, floor of mouth, and gingivae. Less common sites are the hypopharynx, oropharynx, sinuses, and nasal cavity [4,6,7]. A significant minority of patients have a history of previous radiation to the originating site.…”

“…SpCC has the same demographics as conventional squamous cell carcinoma, occurring primarily in the fifth and sixth decades, being strongly associated with smoking and drinking, and showing a strong male preponderance [1,2,[4][5][6][7]. The larynx, particularly the glottis, is the most common primary site followed by the oral cavity, specifically the tongue, floor of mouth, and gingivae.…”

“…Most SpCC are biphasic tumors. In other words, they are composed of both a conventional squamous cell carcinoma and a spindle cell or pleomorphic component [1,7,8]. However, as many as one-third are monophasic spindled or pleomorphic tumors making the diagnosis of carcinoma more difficult.…”

“…Many different theories to explain the morphology were put forward in the past, including divergent differentiation of carcinoma cells, so-called ''collision'' tumors where there are two separate neoplastic clones combined in the same lesion, and the concept that squamous carcinoma ''drives'' the proliferation of a pseudosarcomatous stromal response. Over time, numerous studies analyzing the morphologic [2], immunohistochemical [1,3,[5][6][7][8], ultrastructural [8], and molecular [9] features of SpCC have shown epithelial characteristics in the spindle cell population as well as marked genetic similarity between the spindled and squamous portions of biphasic tumors, clearly indicating that the spindle cell component represents divergent differentiation by what is a true carcinoma. Most SpCC are biphasic tumors.…”