Nicotinamide N‐methyltransferase is related to MELF pattern invasion in endometrioid carcinoma

AbstractPrimary ovarian neuroendocrine neoplasms (Ov-NENs) are infrequent and mainly represented by well-differentiated forms (neuroendocrine tumors — NETs — or carcinoids). Poorly differentiated neuroendocrine carcinomas (Ov-NECs) are exceedingly rare and only few cases have been reported in the literature. A subset of Ov-NECs are admixed with non-neuroendocrine carcinomas, as it occurs in other female genital organs, as well (mostly endometrium and uterine cervix), and may be assimilated to mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs) described in digestive and extra-digestive sites. Here, we present a case of large cell Ov-NEC admixed with an endometrioid carcinoma of the ovary, arising in the context of ovarian endometriosis, associated with a uterine endometrial atypical hyperplasia (EAH). We performed targeted next-generation sequencing analysis, along with a comprehensive immunohistochemical study and FISH analysis for TP53 locus, separately on the four morphologically distinct lesions (Ov-NEC, endometrioid carcinoma, endometriosis, and EAH). The results of our study identified molecular alterations of cancer-related genes (PIK3CA, CTNNB1, TP53, RB1, ARID1A, and p16), which were present with an increasing gradient from preneoplastic lesions to malignant proliferations, both neuroendocrine and non-neuroendocrine components. In conclusion, our findings underscored that the two neoplastic components of this Ov-MiNEN share a substantially identical molecular profile and they progress from a preexisting ovarian endometriotic lesion, in a patient with a coexisting preneoplastic proliferation of the endometrium, genotypically and phenotypically related to the ovarian neoplasm. Moreover, this study supports the inclusion of MiNEN in the spectrum ovarian and, possibly, of all gynecological NENs, among which they are currently not classified.

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Clinical pathological characteristics and survival of high‐grade endometrioid carcinoma

Journal of Obstetrics and Gynaecology Research ◽

10.1111/jog.14839 ◽

2021 ◽

Author(s):

Shuang Liang ◽

Ying Zhang

Keyword(s):

High Grade ◽

Endometrioid Carcinoma ◽

Pathological Characteristics

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Diagnostic Pitfalls Related to Morular Metaplasia in Endometrioid Carcinoma: An Underestimated Issue

Pathobiology ◽

10.1159/000515491 ◽

2021 ◽

pp. 1-6

Author(s):

Antonio Travaglino ◽

Antonio Raffone ◽

Annarita Gencarelli ◽

Serena Saracinelli ◽

Fulvio Zullo ◽

...

Keyword(s):

Patient Management ◽

Hormone Receptors ◽

Immunohistochemical Analysis ◽

Endometrioid Carcinoma ◽

Rectosigmoid Colon ◽

Solid Carcinoma ◽

Colorectal Origin ◽

A Minor ◽

Diagnostic Pitfalls

Here, we present a case that highlights the crucial pitfalls related to the presence of morular metaplasia (MM) in endometrioid carcinoma, which are insufficiently recognized in the routine pathology practice. A 45-year-old woman underwent hysterectomy with rectosigmoidectomy due to a 11-cm mass involving uterus, right ovary, and rectosigmoid colon. Histologically, the lesion appeared as a predominantly solid carcinoma with a minor glandular component. Results of the first immunohistochemical analysis suggested a colorectal origin (PAX8-, CK7-, WT1-, hormone receptors-, and CDX2+ in the absence of mucinous features). Subsequent immunohistochemistry (nuclear β-catenin+, CD10+, and low ki67 in the solid areas) supported a diagnosis of endometrioid carcinoma with diffuse MM. This case remarks that morphological and immunohistochemical features of MM may conceal the glandular architecture and the typical immunophenotype of endometrioid carcinomas. Acknowledging the diagnostic issues related to MM appears crucial to avoid misdiagnosis and inappropriate patient management.

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Molecular evidence for a clonal relationship between synchronous uterine endometrioid carcinoma and ovarian clear cell carcinoma: a new example of “precursor escape”?

Journal of Molecular Medicine ◽

10.1007/s00109-021-02064-4 ◽

2021 ◽

Author(s):

Cindy Hsuan Weng ◽

Ren-Chin Wu ◽

Shu-Jen Chen ◽

Hua-Chien Chen ◽

Kien Thiam Tan ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Molecular Evidence ◽

Endometrioid Carcinoma ◽

Ovarian Clear Cell Carcinoma ◽

Clonal Relationship

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Mixed large and small cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium with high microsatellite instability: A case report and literature review

SAGE Open Medical Case Reports ◽

10.1177/2050313x21999200 ◽

2021 ◽

Vol 9 ◽

pp. 2050313X2199920

Author(s):

Kotaro Inoue ◽

Kentaro Kai ◽

Shimpei Sato ◽

Haruto Nishida ◽

Koji Hirakawa ◽

...

Keyword(s):

Microsatellite Instability ◽

Neuroendocrine Carcinoma ◽

Immune Checkpoint Blockade ◽

Japanese Woman ◽

Endometrial Biopsy ◽

Small Cell ◽

Endometrioid Carcinoma ◽

Small Cell Neuroendocrine Carcinoma ◽

Mutation Burden ◽

Solid Part

A 65-year-old, gravida 3, para 2 Japanese woman was referred to our hospital for symptomatic thickening of the endometrial lining. Endocervical and endometrial cytology revealed an adenocarcinoma. The endometrial biopsy specimen was mixed, with a glandular part diagnosed as endometrioid carcinoma and a solid part diagnosed as high-grade mixed large and small cell neuroendocrine carcinoma (L/SCNEC). She underwent extra-fascial hysterectomy with bilateral salpingo-oophorectomy, complete pelvic and para-aortic lymphadenectomy, and omentectomy (FIGO IIIB, pT3b pN0 M0). She currently has no deleterious germline mutation, but high tumor mutation burden and high microsatellite instability (MSI) were identified. She underwent six cycles of platinum-based frontline chemotherapy and achieved complete remission. Immune checkpoint blockade therapy is a promising second-line therapy for MSI-high solid tumors. However, the MSI or mismatch repair (MMR) status of endometrial L/SCNEC remains unclear in the literature. Universal screening for MSI/MMR status is needed, particularly for a rare and aggressive disease.

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