Histologic and Immunohistochemical Characteristics of Neoplastic and Nonneoplastic Subgroups of Atypical Squamous Lesions of the Uterine Cervix

Department of Pathology, Olive View-UCLA Medical Center, Sylmar, CA 91342, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 06/2005; 123(5):699-706. DOI: 10.1309/FB900YXTF7D2HE99
Source: PubMed


Atypical squamous lesion (ASL), a histologic diagnosis of unclear significance in the uterine cervix, can be divided into neoplastic and nonneoplastic groups. We aimed to determine the morphologic characteristics of these 2 groups. Histologic and immunohistochemical features were evaluated on the original biopsy specimen from 37 ASL cases, and the results were compared between neoplastic (19 cases) and nonneoplastic (18 cases) groups, which were determined based on the follow-up histopathologic findings. Mitosis, vertical nuclear growth pattern, no perinuclear halo, indistinct cytoplasmic border, primitive cells in the upper third of the squamous layer, p16+ cells in the upper two thirds of the squamous layer, and Ki-67+ cells in the upper two thirds of the squamous layer were significant indicators for neoplastic ASLs. Of the 19 neoplastic ASLs, 16 (84%) had 5 or more of these 7 indicators. The majority (16/18 [89%]) of the nonneoplastic ASLs had 2 or fewer indicators. Determination of the histologic and immunohistochemical characteristics is useful for distinguishing neoplastic and nonneoplastic ASLs.

11 Reads
  • Source
    • "In cervical intraepithelial neoplasia, p16INK4a (CDKN2A, cyclin-dependent kinase inhibitor 2A) was shown to indicate malignancy and progression into carcinoma [8, 9]. p16INK4a restrains the progression of the cell cycle by inhibiting the activity of CDK (cyclin dependent kinase) 4, the latter targets pRb for phosphorylation and abolish pRb inhibition of E2F, driving cell cycle progression. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of our study was to identify the frequency of expression of p16INK4a (CDKN2A) and HPV (human papilloma virus) in different grades of conjunctival intraepithelial neoplasia (CIN). Twelve specimens including CIN I (2), II (3), III (5), and CIN with beginning invasion (2), as well as 15 control specimens, were stained with antibodies against p16INK4a and MIB1. The presence of HPV was examined by PCR. p16 as well as MIB1 were significantly elevated in CIN compared to control specimens (p<0.01) without correlation with the differentiation grade. Only two cases with CIN grade 3 contained HPV 16. As few control specimens also showed increased p16INK4a expression, p16INK4a seems not to be a very reliable marker for the exact determination of CIN. It could serve as an additional diagnostic tool besides the morphological characterization. Our study suggested that p16INK4a elevation is not associated with HPV infection.
    The Open Ophthalmology Journal 03/2008; 2(1):48-56. DOI:10.2174/1874364100802010048
  • [Show abstract] [Hide abstract]
    ABSTRACT: p16 is a cyclin-dependent kinase-4 inhibitor that is expressed in a limited range of normal tissues and tumors. In recent years, immunohistochemistry with p16 antibodies has been used as a diagnostic aid in various scenarios in gynecologic pathology. Diffuse (as opposed to focal) positivity with p16 in the cervix can be regarded as a surrogate marker of the presence of high-risk human papillomavirus (HPV). In cervical squamous lesions, p16 is positive in most high-grade cervical intraepithelial neoplasia (CIN) and in some cases of low-grade CIN, usually those associated with high-risk HPV. p16 may be useful to identify small focal high-grade CIN lesions, to distinguish some cases of CIN involving immature metaplastic squamous epithelium from immature metaplastic squamous epithelium not involved by CIN and to distinguish high-grade CIN from benign mimics. Most cervical carcinomas of squamous, glandular, and small cell type are p16-positive. In cervical glandular lesions, p16 is useful, as part of a panel, in the distinction between adenocarcinoma in situ (diffusely positive) and benign mimics, including tuboendometrial metaplasia and endometriosis, which are usually p16-negative or focally positive. p16 may be used, in combination with other markers, to distinguish between a cervical adenocarcinoma (diffuse positivity) and an endometrioid-type endometrial adenocarcinoma (negative or focally positive). Some uterine serous carcinomas are diffusely positive. In the vulva, p16 is positive in HPV-associated vulval intraepithelial neoplasia (VIN) but negative in VIN not associated with HPV. Similarly, HPV-associated invasive squamous carcinomas are p16-positive, whereas the more common non-HPV-associated neoplasms are largely negative or focally positive. In the uterus, p16 positivity is more common and widespread in leiomyosarcomas than leiomyomas, and this may be a useful aid to diagnosis, although problematic uterine smooth muscle neoplasms have not been extensively studied. Metastatic cervical adenocarcinomas in the ovary are usually diffusely p16-positive, and because these may closely mimic a primary ovarian endometrioid or mucinous adenocarcinoma, this may be a valuable diagnostic aid, although p16 expression in primary ovarian adenocarcinomas of these morphologic subtypes has not been widely investigated. Some ovarian serous carcinomas, similar to their uterine counterparts, are p16-positive.
    Advances in Anatomic Pathology 02/2006; 13(1):8-15. DOI:10.1097/01.pap.0000201828.92719.f3 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: p16INK4a has emerged as a valuable surrogate marker for high-risk human papillomavirus infection and shows increased immunoexpression with worsening grades of cervical intraepithelial neoplasia (CIN). Numerous studies have emerged in recent years supporting its role in the detection of high-grade dysplasia and have lead to the use of p16INK4a immunohistochemistry in many laboratories. However, only a few studies have examined the possible predictive or prognostic value of p16INK4a in CIN or cervical cancer. This review addresses some of the practical issues in the application of p16INK4a in everyday practice, with an emphasis on integrating the extensive data that have emerged in the literature on p16INK4a immunoreactivity in CIN. The potential role of p16INK4a immunohistochemistry in the prediction of CIN progression is also discussed.
    Advances in Anatomic Pathology 08/2006; 13(4):190-4. DOI:10.1097/00125480-200607000-00006 · 3.23 Impact Factor
Show more


11 Reads
Available from