PAX2 and Cyclin D1 Expression in the Distinction Between Cervical Microglandular Hyperplasia and Endometrial Microglandular-like Carcinoma

Abstract

Microglandular hyperplasia (MGH) is a common endocervical alteration that in most cases presents no diagnostic difficulty. However, MGH rarely shows atypical features that may mimic endocervical neoplasia, while conversely endometrial carcinomas can show deceptively bland MGH-like appearances. It has been suggested that immunohistochemical analysis is useful in this context, but relatively few studies have specifically investigated microglandular pattern lesions and the results have been conflicting. In this study, we have examined a series of MGH (n=24), atypical MGH (n=2), and endometrial microglandular-like carcinomas (EMC, n=8), with a panel of antibodies including PAX2, cyclin D1, p16, vimentin, and Ki67. Loss of PAX2 staining was identified only in EMC but had relatively poor sensitivity for a malignant diagnosis (3/8 cases). Seven EMCs showed p16 expression and staining was diffuse (≥50% cells) in 6 cases, whereas all conventional MGH lesions were negative. However, 1 case of atypical MGH was also p16-positive. Cyclin D1, vimentin, and Ki67 did not reliably distinguish the benign and malignant microglandular lesions because of considerable overlap in staining patterns. In summary, none of the antibodies examined proved completely sensitive and specific, but a p16-positive/PAX2-negative phenotype favored a diagnosis of EMC. Pathologists should be aware that EMC, like some other types of endometrial carcinoma, are commonly p16-positive to avoid misinterpretation as a primary endocervical neoplasm. In practice, correlation of the histologic, immunohistologic, and clinical findings is necessary for accurate interpretation of microgandular-pattern lesions, particularly in small biopsy samples.

How to approach the many faces of endometrioid carcinoma

“…28 The role of immunohistochemistry in distinguishing this tumor from cervical microglandular hyperplasia is limited due to the potential overlap in commonly used markers (ie, CEA, p63, p16, vimentin, and Ki-67). [29][30][31][32][33] PAX2 may be helpful if negative, as it would support the diagnosis of ECa. CD10 strongly positive and lack of p63 expression would also favor an ECa.…”

Recent Developments in Surgical Pathology of the Uterine Corpus

“…7,8 A subset of mucinous carcinomas, designated microglandular-like carcinoma due to its morphologic similarity to microglandular hyperplasia of the endocervical glands, is acknowledged by the WHO 2014 ( Figure 3). 9 Neuroendocrine tumors are now classified as low-grade neuroendocrine tumors (corresponding to carcinoids in previous classifications) and high-grade neuroendocrine carcinomas, encompassing small and large cell neuroendocrine carcinomas. 6 Undifferentiated and dedifferentiated carcinomas tend to occur in younger women, often show MSI, and have an association with LS.…”

Florid Endocervical Microglandular Hyperplasia in Association with Tamoxifen Treatment

“…The data thus suggest that tamoxifen is a contributory factor in microglandular hyperplasia in this older age group, and that we may see more cases of endocervical hyperplasia with adenocarcinoma in the future. Diagnosing microglandular hyperplasia of the endocervix is often difficult especially when a differential diagnosis with adenocarcinoma is necessary [15] although recent immunohistochemical approaches are showing some promise [14].…”

“…Although these growths may show architectural or cytological abnormalities, they differ from malignant tumours, and can easily be misinterpreted as pre-malignant or malignant neoplasms of the endocervix [9][10][11]. Microglandular hyperplasia is found most commonly in younger women (between the ages of 25-37) and is often an incidental microscopic finding [12,13], is just like adenocarcinoma of the endometrium, associated with endogenous hormones, and induced by pregnancy hormones, gynecological therapeutic treatments or through oral contraceptive therapy [6,7,14]. Although there are reports of endocervical microglandular hyperplasia in post-menopausal women without a history of hormone replacement, these are far rarer [8].…”