Does pTis Exist for HPV Driven Tonsillar Carcinoma?
Candice C Black, Christopher O Ogomo. Dartmouth Hitchcock Medical Center, Lebanon, NH; Dartmouth College, Hanover, NH
Background: Many tonsillar primary tumors (∼13%) present clinically as neck nodal metastases. Indolent tonsillar primaries may be found upon histologic examination. InHPV-driven tumors, positivity for HPV in the nodal met may serve to guide the surgeon to the tonsil. HPV-driven tonsillar carcinoma begins in the reticulated crypt epithelium, possibly through viral integration. P16 is a putative surrogate of HPV infected cells, although not synonymous with neoplasia. The crypt serves an immune function through the presentation of antigen via specialized squamous cells, “M” cells that endocytose antigens at their apical membrane and present them to B and T lymphocytes and other immune cells. The basement membrane is not complete in the reticulated crypt epithelium, which may enhance the immune function. The overlay of epithelial cells and immune cells makes this a difficult part of the tonsil to examine, and the distinction of carcinoma in-situ from invasion may be indistinguishable. We examined the reticulated crypt epithelium in normal and neoplastic tonsils to further investigate whether a carcinoma is ever really “contained” by basement membrane if arising in a tonsillar crypt, as in HPV-driven tonsillar tumors.
Design: Tonsils from 3 cases of cTXN1 were reviewed. IHC for p16, collagen IV and PAS stain were examined on one case. The tonsils showed small crypt centered carcinomas positive for HPV 16 by a two-tiered approach, using the Roche Linear Array HPV Genotyping Test® kit. Normal tonsil was also examined by transmission electron microscopy (EM).
Results: The small tumor s appeared to partially “line” the crypts and focally extend to the surface epithelium. P16 stained the tumor cells and showed a highly irregular epithelial-lymphoid interface characteristic of the specialized crypts. Lack of BM stain was greatest in the H&E areas of greatest irregularity. The EM confirmed an apparent basement membrane of the surface squamous epithelium with loss and disruptions in the continuity within the crypts, associated with many small blood vessels.
Conclusions: H&E examination of tonsillar crypt primary tumors, such as the HPV-driven family of tumors, does not allow the observer to make a distinction of in-situ carcinoma from invasive carcinoma because this distinction does not appear to exist. Even early onset neoplasia appears to be already invasive into the tonsillar stroma with metastatic potential. The stage of pTis, likely seldom used, may therefore need to be excluded from the future system of staging for tonsillar crypt tumors
Category: Head & Neck
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 138, Tuesday Afternoon