Microglandular endocervical hyperplasia and tubal metaplasia: Pitfalls in the diagnosis of adenocarcinoma on cervical smears

Selvaggi, Suzanne M.; Haefner, Hope K.

doi:10.1002/(sici)1097-0339(199702)16:2<168::aid-dc15>3.0.co;2-k

Cited by 48 publications

(21 citation statements)

References 9 publications

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“…The body's normal response mechanisms, such as inflammation and response to irradiation, can also result in glandular atypia [46]. Other mimics include tunnel clusters [36], microglandular hyperplasia [37,45] and, commonly, TEM [12,37,46]. In this study, glands with TEM were analysed for their p16 INK4A expression.…”

Section: Discussionmentioning

confidence: 99%

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P16INK4A positivity in benign, premalignant and malignant cervical glandular lesions: a potential diagnostic problem

et al. 2004

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A wide array of immunohistochemical markers have been evaluated with respect to their specificity in staining dysplastic cervical cells in cervical biopsies and cervical cytological smears. However, there is still a significant demand for better biomarkers to identify neoplastic cervical glandular and squamous epithelial cells precisely. The CDKN2A gene, located on chromosome 9p21, encodes the tumour suppressor protein, p16INK4A, which decelerates the cell cycle by inactivating CDK4 and CDK6. The aim of this study was to compare and contrast the expression pattern of p16INK4A in benign and neoplastic glandular lesions and tubo-endometrioid metaplasia. All cases in each category displayed some p16INK4A expression. Adenocarcinoma and in situ cases showed a combination of intense nuclear and cytoplasmic staining. It was observed that all cases of tubo-endometrioid metaplasia showed occasional nuclear positivity and definite cytoplasmic staining. These findings may have important implications for the potential utility of p16INK4A as a biomarker for glandular dysplastic lesions. While p16INK4A has been demonstrated to be an excellent marker of cervical dysplasia in squamous neoplastic lesions of the cervix, it has potential pitfalls in cervical glandular lesions that may limit the utility of this biomarker in resolving the nature of suspicious glandular lesions, particularly in cytopathology.

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Section: Discussionmentioning

confidence: 99%

“…This lesion was originally diagnosed in women treated for cervical squamous intraepithelial neoplasia and may commonly be found in cone and hysterectomy specimens [5,13]. It is vital that TEM is correctly recognised, as it may often mimic cGIN or AIS of the uterine cervix [28,29,37].…”

Section: Introductionmentioning

confidence: 99%

P16INK4A positivity in benign, premalignant and malignant cervical glandular lesions: a potential diagnostic problem

et al. 2004

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“…In our laboratory, the AGUS rate was 0.11% during the study period, amounting to 92 patients over approximately 5.5 years. 6 -9 Benign lesions associated with AGUS include direct sampling of the lower uterine segment, 16,17 tubal metaplasia, 16,18,19 reactive endocervical cells, 20 cervical endometriosis, 21,22 endometrial metaplasia, 23 microglandular hyperplasia, 24,25 effects of radiation, 26 postcone-biopsy smear, [27][28][29] pregnancy-related changes, 30 and endosalpingiosis, as shown in one of our patients in this series. [3][4][5][6] Our lower AGUS rate may be explained by the fact that our patient population is not high risk.…”

Section: Discussionmentioning

confidence: 71%

Atypical glandular cells of undetermined significance

Soofer

Sidawy

2000

Cancer

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“…Tubal metaplasia and variants of microglandular hyperplasia may mimic AIS. 15,16 p16 Has been documented to be useful in identifying true glandular neoplasia. 17 AIS and CIN are frequently associated and both are HPV-related lesions.…”

Section: Christal and Valentementioning

confidence: 99%

The Utility of p16 Immunohistochemistry in the Diagnosis of Cervical Intraepithelial Neoplasia

Christal

Valente

2006

Pathology Case Reviews

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The morphologic diagnosis of squamous and glandular dysplasia in cervical biopsies may be complicated by a variety of inflammatory and hormonal conditions. Cellular changes associated with inflammation, pregnancy, and atrophy may mimic precancerous lesions. p16 Immunohistochemical staining has been shown to be one of a group of useful dysplasia markers in this setting. Five cases are presented to illustrate how p16 may be an aid in diagnosis. The advantages of p16 over other markers are also discussed. CASE REVIEWp16 has emerged as a useful biomarker for human papillomavirus (HPV) -related dysplastic and malignant lesions of the cervix. The p16 protein (also known as p16INK4A) is a cyclin-dependent kinase inhibitor that generally functions as a tumor suppressor and is inactivated in many cancers such as melanoma, glioma, leukemia, pancreatic carcinoma, and lung carcinoma. The protein has been found to be overexpressed in precancerous and malignant cervical lesions and is thought to be the result of inactivation of the retinoblastoma (Rb) protein by the E7 gene product of integrated HPV DNA. The Rb protein participates in a negative feedback loop with p16, whereby the inactivation of Rb leads to overexpression of p16. The expression of p16 has been extensively studied and it is widely accepted as a sensitive and specific marker of squamous and glandular dysplasia in the cervix. The use of p16 immunohistochemistry as a valuable adjunct in the diagnosis of difficult cervical biopsy specimens is illustrated in the following 5 cases. CASE REPORTS Case 1A 46-year-old patient was referred to colposcopy for an abnormal Papanicolaou (Pap) test and was found to have a cervical lesion confirmed on biopsy as cervical intraepithelial neoplasia (CIN) 3. A conization was performed and confirmed the presence of severe squamous dysplasia, CIN 3, involving the cervical epithelium from the 5 o'clock to the 6 o'clock position, with glandular involvement noted. Several deeper glands showed cellular and nuclear atypia characterized by nuclear stratification with nuclear hyperchromasia and mitotic activity. p16 Immunohistochemical staining of these glands showed a strong nuclear, as well as cytoplasmic, positivity, confirming their neoplastic nature and the diagnosis of high-grade endocervical gland dysplasia bordering on adenocarcinoma in situ (AIS) (Fig. 1). Case 2A 31-year-old had ASCUS (atypical squamous cells of undetermined significance) suggestive of LGSIL (low-grade intraepithelial lesion) on a Pap test and subsequently underwent cervical biopsy. The cervical biopsy specimen showed a rather intense infiltrate of acute and chronic inflammatory cells. The overlying epithelium appeared reactive, with enlarged nuclei displaying smooth nuclear contours and prominent nucleoli. There were areas of the epithelium, however, that appeared more disorganized with irregularly shaped and hyperchromatic nuclei, but still displaying prominent nucleoli. The differential diagnosis was between reactive changes and epithelial dysplasia. Immunohist...

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Microglandular endocervical hyperplasia and tubal metaplasia: Pitfalls in the diagnosis of adenocarcinoma on cervical smears

Cited by 48 publications

References 9 publications

P16INK4A positivity in benign, premalignant and malignant cervical glandular lesions: a potential diagnostic problem

P16INK4A positivity in benign, premalignant and malignant cervical glandular lesions: a potential diagnostic problem

Atypical glandular cells of undetermined significance

The Utility of p16 Immunohistochemistry in the Diagnosis of Cervical Intraepithelial Neoplasia

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