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. 2013 Dec;47(6):549-56.
doi: 10.4132/KoreanJPathol.2013.47.6.549. Epub 2013 Dec 24.

Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16(INK4a) Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma

Su Hyun Yoo  1 , Eun-Mi Son  2 , Chang Okh Sung  2 , Kyu-Rae Kim  2
Affiliations

Primary Squamous Cell Carcinoma of the Upper Genital Tract: Utility of p16(INK4a) Expression and HPV DNA Status in its Differential Diagnosis from Extended Cervical Squamous Cell Carcinoma

Su Hyun Yoo et al. Korean J Pathol. 2013 Dec.

Abstract

Background: Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site.

Methods: We compared histologic findings, p16(INK4a) expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract.

Results: All five SCCs of cervical origin showed strong expression of p16(INK4a), whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA.

Conclusions: Although a thorough histological examination is important, immunonegativity for p16(INK4a) and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract.

Keywords: Carcinoma, squamous cell; DNA probes, HPV; Genes, p16.

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Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
A primary squamous cell carcinoma arising in the endometrium and showing continuous upward mucosal extension and serosal involvement. Squamous lesions in the endometrium (A, solid arrow and B) and fallopian tubes (C, D) show bland cytomorphologic features mimicking squamous metaplasia, with obvious stromal invasion of the tubal wall (C, D), ovary, and uterine serosa (A, open arrow). Note that three samples are completely immunonegative for p16INK4a (E) and one had weak, focal staining (F), which can be interpreted as negative.
Fig. 2
Fig. 2
Squamous cell carcinoma in situ with glandular extension of the uterine cervix (A), showing upward extension to the endometrium (B), fallopian tube (C, D), and ovarian surface (E). Note the residual endometrial glandular epithelium (B, arrow) and ciliated tubal epithelium (D, arrow) over the tumor cells. All tumor cells of cervical origin show diffuse strong positivity for p16 (F).
Fig. 3
Fig. 3
Human papillomavirus (HPV) DNA chip analysis of 40 subtypes of HPV, including 21 high-risk and 19 low-risk subtypes, in the nine patients of this study (A). Three cervical squamous cell carcinomas are positive for HPV DNA type 16 (B).
See this image and copyright information in PMC

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