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Presented by Justin A. Bishop, M.D. and prepared by Robert E LeBlanc, M.D.
Case 1: 45 year old man presented with a tonsillar mass and widespread metastatic disease.
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1. Question
Week 540: Case 1
45 year old man presented with a tonsillar mass and widespread metastatic disease.images/JABONE1.jpg
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images/JABONE4.jpgCorrect
Answer: HPV-related small cell carcinoma
Histology: The tumor consists of a proliferation of hyperchromatic cells with numerous mitotic figures and foci of tumor necrosis. The cells have minimal cytoplasm, and the tumor nuclei exhibit molding. Immunostains show that the tumor is positive for cytokeratin and the neuroendocrine markers synaptophysin and chromogranin. CK5/6 and p63 (not shown) were negative. HPV studies showed that the tumor was positive for p16 by immunohistochemistry and high risk human papillomavirus by in situ hybridization.
Discussion: Human papillomavirus (HPV)-related cancers represent an increasingly large subset of head and neck cancers, particularly those arising in the oropharynx. While HPV-related head and neck cancer typically demonstrates a non-keratinizing squamous histologic appearance, widespread HPV testing has uncovered rare histologic variants, including the basaloid, papillary, and adenosquamous subtypes. For the most part, the HPV-related carcinoma variants behave in a manner similar to conventional HPV-related cancer, with an excellent prognosis and response to therapy. However, the small cell variant seems to be an exception, as it behaves in an aggressive fashion, similar to small cell carcinoma of other sites. As a result, recognizing the presence of a small cell carcinoma (which may coexist with squamous cell carcinoma) is important. Histologically, compared to conentional HPV-related squamous cell carcinoma, HPV-related small cell carcinoma has less cytoplasm, more hyperchromatic nuclei without prominent nucleoli, and exhibits nuclear molding. If in doubt, immunohistochemistry is helpful: HPV related small cell carcinoma is consistently positive for at least one neuroendocrine marker (i.e., synaptophysin, chromogranin, CD56), is sometimes positive for TTF-1, and is consistently negative for the squamous marker CK5/6. (It should be noted that small cell carcinoma of the head and neck may be positive for the squamous marker p63, but the staining is usually focal and weak)
Reference(s):
– Bishop JA and Westra WH. Human papillomavirus related small cell carcinoma of the oropharynx. AJSP. 2011;35(11):1679-84.Incorrect
Answer: HPV-related small cell carcinoma
Histology: The tumor consists of a proliferation of hyperchromatic cells with numerous mitotic figures and foci of tumor necrosis. The cells have minimal cytoplasm, and the tumor nuclei exhibit molding. Immunostains show that the tumor is positive for cytokeratin and the neuroendocrine markers synaptophysin and chromogranin. CK5/6 and p63 (not shown) were negative. HPV studies showed that the tumor was positive for p16 by immunohistochemistry and high risk human papillomavirus by in situ hybridization.
Discussion: Human papillomavirus (HPV)-related cancers represent an increasingly large subset of head and neck cancers, particularly those arising in the oropharynx. While HPV-related head and neck cancer typically demonstrates a non-keratinizing squamous histologic appearance, widespread HPV testing has uncovered rare histologic variants, including the basaloid, papillary, and adenosquamous subtypes. For the most part, the HPV-related carcinoma variants behave in a manner similar to conventional HPV-related cancer, with an excellent prognosis and response to therapy. However, the small cell variant seems to be an exception, as it behaves in an aggressive fashion, similar to small cell carcinoma of other sites. As a result, recognizing the presence of a small cell carcinoma (which may coexist with squamous cell carcinoma) is important. Histologically, compared to conentional HPV-related squamous cell carcinoma, HPV-related small cell carcinoma has less cytoplasm, more hyperchromatic nuclei without prominent nucleoli, and exhibits nuclear molding. If in doubt, immunohistochemistry is helpful: HPV related small cell carcinoma is consistently positive for at least one neuroendocrine marker (i.e., synaptophysin, chromogranin, CD56), is sometimes positive for TTF-1, and is consistently negative for the squamous marker CK5/6. (It should be noted that small cell carcinoma of the head and neck may be positive for the squamous marker p63, but the staining is usually focal and weak)
Reference(s):
– Bishop JA and Westra WH. Human papillomavirus related small cell carcinoma of the oropharynx. AJSP. 2011;35(11):1679-84.
