Ciliated/tubal-type in-situ and invasive endocervical adenocarcinoma: Report of three cases with limited follow-up and review of the literature.

In situ (AIS) and invasive endocervical adenocarcinoma have two broad categories, HPV-associated (HPV) and HPV-independent groups. (1) These entities show various types of cell morphology. Tubal and tubo-endometrioid type metaplasia of the cervix is a benign finding (Suh and Silverberg, 1990). Tubal metaplasia is also encountered in benign and malignant endometrial lesions. During cervical biopsy interpretations, differentiating the site of origin of the tissue is often tricky. We intend to document three cases of the sparsely reported hrHPV-associated ciliated/tubal-type endocervical AIS and invasive adenocarcinoma and bring it to the attention of readers how to avoid any misinterpretation during routine sign-out. Only three of fifty-three cases of hrHPV-associated AIS and invasive adenocarcinoma were of ciliated/tubal type in our department over a 5-year time. The presence of tubal-type epithelium should not automatically trigger the assumption of endometrial origin of the lesion. These cases are red herrings as tubal/ciliated type dysplasia, and carcinoma is rare and have potential to escape accurate diagnosis.

Somatic mutation analysis of Mesonephric-Like adenocarcinoma and associated putative precursor Lesions: Insight into pathogenesis and potential molecular treatment targets.

Aims: Mesonephric-like adenocarcinoma (MLA) is a recently described histologic tumor subtype of the Müllerian tract. MLA can arise in association with Müllerian lesions that share common mutations. We report three MLAs and hypothesize that concurrent endometriosis and cystadenofibroma with focal borderline changes might also carry common mutations. Methods and results: We searched "mesonephric" in our database from 2015 to mid-2021 to retrieve MLA cases. Somatic mutation analysis was performed on tumors and on associated benign proliferative lesions. All MLAs (2 ovarian and 1 uterine) harbored KRAS G12D or G12 V mutations. A PIK3CA alteration (H1047Q) was detected in one MLA and in the associated cystadenofibroma with focal borderline changes. The molecular profile of MLA-associated Müllerian lesions (endometriosis and seromucinous cystadenofibroma with focal borderline changes) was similar to concurrent adenocarcinoma. However, tumor contamination could not be excluded in the endometriotic lesion. Patients presented at various stages, with no evidence of post-operative recurrence after 15 months (FIGO IC) and 33 months (FIGO IIA2). One patient (FIGO IIIA1) died of disease 32 months after surgery. Conclusions: KRAS mutations commonly characterize MLA. At least some MLA-associated Müllerian lesions show MLA-like genetic profiles, suggesting a precursor role. As far as we are aware, we describe for the first time in MLA the potentially actionable H1047Q variant of PIK3CA.

Localized amyloidosis in usual-type vulvar intraepithelial neoplasia: High-risk HPV association and potential clinical significance. A series of 45 cases.

Localized cutaneous amyloidosis was reported recently in association with vulvar squamous intraepithelial neoplasia (VIN). High-risk human papillomavirus (hrHPV) type 16 is the most commonly reported subtype found in usual-type VIN. However, it is unknown whether any hrHPV subtype(s) is/are prevalent in simultaneous squamous intraepithelial lesions and localized amyloidosis in the same individual - the subject matter of this report. To observe the potential clinical significance, study cases were followed and compared to usual-type VINs without amyloid deposition. Of 45 patients of usual-type VINs associated with amyloidosis, 33 had detectable hrHPV, and 12 were negative. HPV 16 alone or in combination with HPV 31 accounted for 72%, HPV 51 alone accounted for 2% of the cases, and 26% were negative for hrHPV. Lack of demonstrable hrHPV in a significant proportion of cases (26%) raises the possibility of a novel or presently undetected hrHPV subtype. Five of the total 22 (23%) patients with amyloid had either Squamous cell carcinoma or high-grade VIN on follow-up. In contrast, 14 of 18 (78%) patients exhibiting lesions without amyloid had disease on follow-up. These findings may indicate that amyloid deposition may represent a feature of regression or a potential favorable prognostic indicator.

Type of Architecture, Presence of Punctate Necrosis, and Extent of Involvement in Atypical Ductal Hyperplasia Can Predict the Diagnosis of Breast Carcinoma on Excision: A Clinicopathologic Study of 143 Cases.

The literature shows a wide range in the frequencies of finding breast carcinoma in the excised specimens following a biopsy diagnosis of atypical ductal hyperplasia (ADH), likely due to a poor diagnostic reproducibility among different pathologists as well as an inherent heterogeneity in ADH. We evaluated whether histologic subtyping of ADH would help predict the risk of breast carcinoma. Our study consisted of 143 cases of ADH diagnosed by core needle biopsy and followed by excision. Of these, 54 cases (37.8%) showed carcinoma in the excised specimens (47 cases of ductal carcinoma in situ alone, 3 cases of invasive ductal carcinoma alone, and 4 cases of mixed invasive ductal carcinoma and ductal carcinoma in situ). We arbitrarily divided ADH into two subtypes: type A was considered when one or more ducts were completely replaced by low-grade ductal carcinoma in situ type cells but the lesion was <2 mm and type B was considered when one or more ducts were partially involved by low-grade ductal carcinoma in situ type cells regardless of lesion size. Type A was associated with a significantly higher frequency of breast carcinoma (63.6%) than type B (30.0%). ADH containing punctate necrosis showed a higher association of carcinoma (66.7%) compared to those without necrosis (35.1%). Within type B ADH, involvement of 3 or more foci had a higher frequency of carcinoma (50.0%) than involvement of fewer foci (26.6%). These histologic features of ADH may prove useful in predicting the likelihood of breast carcinoma and provide helpful information for patient's management.

Expression of cyclin D1 in normal, metaplastic, hyperplastic endometrium and endometrioid carcinoma suggests a role in endometrial carcinogenesis.

CONTEXT: Endometrioid carcinoma is often preceded by characteristic histopathologic lesions known as endometrial hyperplasia. Estrogen appears to be involved in the development of endometrioid carcinoma. Other mechanisms of endometrial carcinogenesis include mutations in p53 and PTEN tumor suppressor genes and overexpression of cyclin D1. However, the pattern of cyclin D1 expression is not well defined in normal, hyperplastic, neoplastic, and metaplastic endometrium. DESIGN: Cyclin D1 immunohistochemical analysis was used to evaluate 108 fixed, paraffin-embedded endometrial biopsy specimens and uterine resections obtained from 108 patients. Specimens included proliferative and secretory endometria, simple and complex hyperplastic lesions, and endometrioid adenocarcinoma. Normal and metaplastic surface epithelia were also evaluated independently of glandular morphologic features. RESULTS: Cyclin D1 was significantly overexpressed in glands with complex hyperplasia and endometrioid adenocarcinoma compared with proliferative or secretory endometrium and simple hyperplasia. Significant overexpression was also noted in papillary, syncytial, and squamous metaplasias compared with normal surface epithelium or epithelium with tubal metaplasia. CONCLUSION: Overexpression of cyclin D1 increases from normal endometrium to hyperplasia and carcinoma, suggesting that it may play a role in endometrial carcinogenesis. Overexpression of cyclin D1 in endometrial glands was independent from overexpression of cyclin D1 in surface metaplastic epithelium.