Endometrial Adenocarcinomas With Significant Mucinous Differentiation

Jackson, Cynthia L.; Hang, Steven; Hansen, Katrine; He, Mai; Sung, C. James; Quddus, M. Ruhul; Xiong, Michelle; Wang, Yihong; Patel, Nimesh R.; Lawrence, W. Dwayne; Xiong, Jinjun

doi:10.1097/igc.0000000000001168

Cited by 8 publications

(8 citation statements)

References 31 publications

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“…Future studies would benefit by defining strict morphologic criteria for the presence of MD, including identification of mucinous cytoplasm, intracytoplasmic mucin vacuoles, and endocervical versus intestinal-type mucinous metaplasia, as well as avoidance of interpreting extracellular mucin as definitive evidence of MD. Even so, many CNL EAs with KRAS mutations displayed MD, which supports previous observations of KRAS mutations in EAs with MD 18,19. KRAS mutations are commonly associated with a variety of tumors of the female genital tract, including mucinous tumors of the ovary 20, mesonephric-like adenocarcinomas of the endometrium 21,22, and atypical mucinous proliferations of the uterus 18.…”

Section: Discussionsupporting

confidence: 84%

Endometrial Adenocarcinomas With No Specific Molecular Profile: Morphologic Features and Molecular Alterations of “Copy-number Low” Tumors

Meljen

Mittenzwei

Wong

et al. 2021

International Journal of Gynecological Pathology

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The study evaluated morphologic patterns, mutational profiles, and β-catenin immunohistochemistry (IHC) in copy-number low (CNL) endometrial adenocarcinomas (EAs). CNL EAs (n = 19) with next-generation or whole genome sequencing results and available tissue for IHC were identified from our institutional database. Clinical data and histologic slides were reviewed. IHC for β-catenin was performed and correlated with mutation status. Images of digital slides of CNL EAs from The Cancer Genome Atlas (TCGA) database (n = 90) were blindly reviewed by 4 pathologists, and morphology was correlated with mutation status. Categorical variables were analyzed using the Fisher exact test, and agreement was assessed using Fleiss κ. CTNNB1 mutations were present in 63% (12/19) of CNL EAs. β-catenin nuclear localization was present in 83% of CTNNB1-mutated tumors (10/12) and in 0% (0/7) of CTNNB1-wildtype tumors (sensitivity 0.83, specificity 1.00). Squamous differentiation (SD) was present in 47% (9/19) and was more often observed in CTNNB1-mutated tumors (P = 0.02). Mucinous differentiation (MD) was associated with KRAS mutations (Po0.01). Digital image review of TCGA CNL EAs revealed that pathologist agreement on SD was strong (κ = 0.82), whereas agreement on MD was weak (κ = 0.48). Pathologists identified SD in 22% (20/90), which was significantly associated with

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Section: Discussionsupporting

confidence: 84%

Endometrial Adenocarcinomas With No Specific Molecular Profile: Morphologic Features and Molecular Alterations of “Copy-number Low” Tumors

Meljen

Mittenzwei

Wong

et al. 2021

International Journal of Gynecological Pathology

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“…Interestingly, both these tumors also bore KRAS mutations: 1 (case 4) was a serous carcinoma bearing both TP53 and KRAS mutations and the other (case 7) was a grade 1 endometrioid tumor with prominent mucinous differentiation. KRAS mutations are found in ~20% of ECs3,15–17 and have been previously described in a variety of tumor histotypes, including endometrioid tumors with extensive mucinous differentiation 20,21. It may be that KRAS mutations can drive diffuse TTF-1 expression not only in the context of mesonephric-like differentiation, but also in other histotypes bearing this molecular signature.…”

Section: Discussionmentioning

confidence: 99%

“…KRAS mutations are found in ~20% of ECs 3,15-17 and have been previously described in a variety of tumor histotypes, including endometrioid tumors with extensive mucinous differentiation. 20,21 It may be that KRAS mutations can drive diffuse TTF-1 expression not only in the context of mesonephric-like differentiation, but also in other histotypes bearing this molecular signature. Notably, however, at < 3% in this series TTF-1 expression is far less common than the reported rates of KRAS mutations in ECs, therefore the presence of a KRAS mutation does not appear to be sufficient to produce this immunophenotype.…”

Section: Figure 1 This Tumor (Case 1) Was Originally Classified As a ...mentioning

confidence: 99%

Mesonephric-like Endometrial Carcinoma

Mills

Jenkins²,

Howitt³

et al. 2022

American Journal of Surgical Pathology

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Mesonephric-like endometrial carcinoma is a rare but frequently misclassified and aggressive malignancy. KRAS mutations, limited estrogen receptor (ER) expression, and TTF-1, GATA3, and luminal CD10 expression are described in these tumors, but an immunohistochemistry-based screening approach has not been studied. We assessed 300 endometrial carcinomas/carcinosarcomas to ascertain the specificity of TTF-1/GATA3/luminal CD10 expression with or without ER staining for this diagnosis. Next-generation sequencing and morphologic review were performed on screen-positive cases. In all, 3% (9/300) were TTF-1+; 2 coexpressed GATA3. No cases expressed luminal CD10 or GATA3 in isolation. Two TTF-1+/ER− cases, one of which was also GATA3+, were reclassified as mesonephric-like based on morphology and molecular results (KRAS mutations without mismatch repair deficiency, TP53 mutations, or PTEN mutations): these represented 0.7% of all cases (2/300). The reclassified cases were originally diagnosed as grade 1 and 2 endometrioid carcinoma, and the latter had pulmonary metastases and pelvic recurrences. Six TTF-1+ cases retained their original serous (3) and endometrioid (3) diagnoses; 1 was reclassified as dedifferentiated. All had negative or low ER. KRAS mutations were identified in 4 TTF-1+ non–mesonephric-like cases, including 1 serous and 1 grade 3 endometrioid with p53 abnormalities, 1 mismatch repair–deficient endometrioid with a complex molecular profile, and 1 endometrioid with mucinous differentiation. These findings suggest that TTF-1 and ER are good first-line screens for mesonephric-like carcinoma, but caution that a TTF-1+/ER− immunoprofile is not specific, even in the setting of KRAS mutations. A final diagnosis of mesonephric-like carcinoma requires integration of morphologic and immunohistochemical features, with molecular support when relevant.

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“…Nonetheless, they do provide some insight, especially in mucinous epithelial neoplasms, a histotype with which they appear to be particularly associated. 86,[89][90][91] As was previously noted, most studies have found no KRAS mutations in MM, whereas 55% to 67% of AMGP have been reported to display such mutations. 20,22,31,32,37 Eighty percent to 89% of mucinous carcinomas have been shown to display a KRAS mutation, 20,86,90 as compared with ∼58% of endometrioid carcinomas with mucinous differentiation, 20,90,91 and 8% to 25% of concurrently tested pure endometrioid carcinomas.…”

Section: The Kras Proto-oncogene In Endometrial Mucinous Proliferationsmentioning

confidence: 72%

Mucinous Proliferations of the Uterine Corpus: Comprehensive Appraisal of an Evolving Spectrum of Neoplasms

Fadare¹

2022

Advances in Anatomic Pathology

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A variety of endometrial lesions may contain mucinous cells. Herein, the author reviews the literature on the classification and clinicopathologic significance of uterine corpus proliferations with a significant mucinous component, assesses the 2020 World Health Organization classification of such lesions, and presents a diagnostic framework. The key epithelial mucinous lesions include mucinous metaplasia, atypical mucinous glandular proliferation and mucinous carcinoma. Each of these categories are classifiable into "usual" and gastrointestinal subtypes, the latter being indicative of intestinal (presence of goblet cells) and/or gastric-type (abundant, pale eosinophilic or clear cytoplasm and well-defined cell borders) morphology. It has been proposed that at least focal expression of gastrointestinal immunohistochemical markers be required for all gastrointestinal type lesions, and for gastrointestinal type atypical mucinous glandular proliferation and carcinoma, minimality or absence of estrogen receptor expression, and the absence of an endometrioid component. Mucinous carcinomas of the usual type, in which > 50% of the tumor is comprised of a mucinous component, are the most common. Morphologic subtypes include mucinous carcinoma with microglandular features and mucinous carcinoma with signet rings (signet ring carcinoma). Endometrioid carcinomas with a less than a 50% mucinous component are classified as endometrioid carcinoma with mucinous differentiation. Several studies have directly compared endometrioid and mucinous carcinomas, the latter presumably of the usual type, with respect to patient outcomes after treatment. All have found no difference in overall and disease free survival between these groups. However, three major studies have found mucinous carcinomas to be associated with a higher risk of lymph node metastases. Nineteen cases of mucinous carcinoma of the gastrointestinal type have been reported, and the limited data on their follow-up after primary treatment suggests that this subtype is more clinically aggressive and should accordingly be classified separately from mucinous carcinomas of the usual type. The morphologic spectrum of mucinous carcinoma of the gastrointestinal type is unclear and continues to evolve. Mucinous change, which may sometimes be extensive, may also be associated with papillary proliferation of the endometrium, adenomyoma of the endocervical type, atypical, and typical adenomyomas. In a curettage or biopsy, intestinal type mucinous epithelium may be indicative of any of the gastrointestinal lesions mentioned above, but may also represent samplings of uterine teratomas, yolk sac tumors, genital and extragenital adenocarcinomas with intestinal differentiation, or lowgrade appendiceal mucinous neoplasms that secondarily involve the endometrium.

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Endometrial Adenocarcinomas With Significant Mucinous Differentiation

Cited by 8 publications

References 31 publications

Endometrial Adenocarcinomas With No Specific Molecular Profile: Morphologic Features and Molecular Alterations of “Copy-number Low” Tumors

Endometrial Adenocarcinomas With No Specific Molecular Profile: Morphologic Features and Molecular Alterations of “Copy-number Low” Tumors

Mesonephric-like Endometrial Carcinoma

Mucinous Proliferations of the Uterine Corpus: Comprehensive Appraisal of an Evolving Spectrum of Neoplasms

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