Case of Week Home
7 April 2011 – Case of the Week #202
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Thanks to Dr. Jamie Shutter, University of South Florida, for contributing this case. To contribute a Case of the Week, follow the guidelines on our Case of the Week page.
(1) Thanks to Michael Constantinescu, M.D., Overton Brooks VA Medical Center, Louisiana, for writing a new section for the Thyroid Gland chapter on Bethesda Guidelines for Cytology. Thanks to Dr. Larry Bernstein, Triplex Consulting, Connecticut, for writing Cardiac topics for the Clinical Chemistry chapter.
(2) Recent articles posted on our Management Page include: 1993 Medicaid Reform Comes to Florida, by Mick Raich, Vachette Pathology, click here, Déjà vu all Over Again, by Mick Raich, Vachette Pathology, click here and Stories That Will Curl Your Hair… Or Close To It!, by Michelle Miller, Vachette Pathology, click here.
(3) Per the suggestion of Dr. Thomas Dudley, we are now soliciting your "best practices" related to pathology. We will post them on a new Best Practices page, organized in a logical way, with a link from our website. We anticipate that this feature will be widely read. Email your pathology best practices to NatPernick@hotmail.com .
Case of the Week #202
A 30 year old woman had a pap smear diagnosis of HSIL, followed by a cervical biopsy, which is shown below with Ki-67 and p16 staining.
Ki-67 (left) and p16 (right) staining
What is your diagnosis?
Adenocarcinoma in situ (AIS) of the endocervix
The biopsy shows the typical appearance of adenocarcinoma in situ of the endocervix. Low power shows malignant, darkened glands composed of hyperchromatic, enlarged, crowded nuclei with coarse chromatin, small single or multiple nucleoli, and frequent mitotic figures. In this case, the surface epithelium is uninvolved, but the malignant glands are superficial to a large benign gland.
In pap smears, adenocarcinoma in situ has a higher false negative rate than HSIL and squamous cell carcinoma (Arch Pathol Lab Med 2004;128:153). As a result, the use of p16 may be helpful in difficult cases.
p16 (p16INK4A) is an inhibitor of cyclin-dependent kinases, and p16 overexpression has been observed in cervical intraepithelial lesions and invasive carcinomas associated with high-risk HPV types (Am J Surg Pathol 2004;28:160). p16 distinguishes uterine cervical adenocarcinomas (p16+) from benign lesions (p16 negative, Am J Surg Pathol 2003;27:187), and from endometrioid adenocarcinomas of the uterine corpus (p16 negative, Virchows Arch 2006;448:597). p16 immunostains and HPV DNA analysis are also helpful in determining if endometrial tumors originate in endometrium (HPV and p16 negative) or from the endocervix (HPV and p16 positive, Am J Surg Pathol 2009;33:914). In this case, Ki-67 staining shows the high proliferative index of the lesion, and the basal layer of squamous epithelium serves as a positive internal control.
The differential diagnosis of endocervical adenocarcinoma in situ includes:
- tubal or tuboendometrial hyperplasia: involves only a single gland or portion of a gland, no significant nuclear atypia
- nonspecific glandular atypia or dysplasia: less atypia, typically p16 negative
- invasive adenocarcinoma: infiltrating glands with more atypia, budding and other architectural alterations, desmoplasia, extension of glands beyond normal glandular depth
- metastatic adenocarcinoma from ovary (serous or clear cell) or other sites (Am J Surg Pathol 2010;34:735)
Treatment consists of loop electrosurgical excision procedure (LEEP), laser therapy, conization or cryotherapy. Follow up is recommended.
Additional references: Cervix chapter of PathologyOutlines.com.
Nat Pernick, M.D., President
and Liz Parker, B.A., Associate Medical Editor
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Bingham Farms, Michigan (USA) 48025
Alternate email: NatPernick@gmail.com