Histopathologic diagnosis of endometrial precancers: Updates and future directions

Chen, Hao; Strickland, Amanda; Castrillón, Diego H.

doi:10.1053/j.semdp.2021.12.001

Cited by 20 publications

(30 citation statements)

References 95 publications

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“…This is consistent with prior observations that Pax2 silencing can be an early or initiating event in endometrial carcinogenesis 16,17. Although definitive conclusions cannot be drawn, the absence of β-catenin aberrant cases in the ambiguous/difficult category is in agreement with prior observations that well-defined clusters of crowded glands (ie, clonal-type patterns) are often β-catenin positive and thus classifiable as AH/EIN even if minute 1. However, some DPE and NAH were β-catenin aberrant (Fig.…”

Section: Discussionsupporting

confidence: 91%

“…16,17 Although definitive conclusions cannot be drawn, the absence of β-catenin aberrant cases in the ambiguous/difficult category is in agreement with prior observations that well-defined clusters of crowded glands (ie, clonal-type patterns) are often β-catenin positive and thus classifiable as AH/EIN even if minute. 1 However, some DPE and NAH were β-catenin aberrant (Fig. 1B), arguing that CTNNB1 mutations can also be relatively early events in endometrial cancer progression.…”

Section: Discussionmentioning

confidence: 94%

“…[41][42][43][44] Thus, there must be "pre-AH/EIN" lesions that harbor neoplastic drivers, putting them at increased risk of progression relative to non-neoplastic endometria (mimics) with architectural disorder due to external factors such as higher circulating estrogen levels during perimenopause. 1 Also, classic studies argued that endometria can be histologically stratified into diagnostic categories with increasing risks of neoplasia, including cases that do not reach current diagnostic criteria for AH/ EIN. 45 Although distinction between DPE and NAH in clinical specimens is commonplace, there is a continuum between the 2 and the distinction is likely to be poorly reproducible.…”

Section: Discussionmentioning

confidence: 99%

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β-catenin, Pax2, and Pten Panel Identifies Precancers Among Histologically Subdiagnostic Endometrial Lesions

Aguilar¹,

Chen²,

Sahoo³

et al. 2023

American Journal of Surgical Pathology

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Despite refinements in histologic criteria for the diagnosis of endometrioid precancers, many challenging cases are encountered in daily practice, creating diagnostic uncertainty and suboptimal patient management. Recently, an immunohistochemical 3-marker panel consisting of β-catenin, Pax2, and Pten was identified as a useful diagnostic adjunct. However, previous studies focused either on cancers or diagnostically unambiguous precancers, leaving questions about the applicability and utility of the panel in endometria with architectural features near or below the threshold of accepted histologic criteria for endometrioid precancers. Here, in a retrospective study of 90 patients, we evaluated the performance of the 3-marker panel. Notably, the panel detected a subset of disordered proliferative endometria (8/44, 18%), nonatypical hyperplasias (19/40, 48%), and cases with ambiguous features (3/6, 50%) with aberrancy for ≥1 markers. Marker-aberrant cases were more likely to progress to endometrioid precancer or cancer (P=0.0002). Patterns of marker aberrancy in the index and progressor cases from individual patients provided evidence for origin in a common precursor, and next-generation sequencing of the progressor cases rationalized marker aberrancy for β-catenin and Pten. The results unequivocally demonstrate that some lesions that do not approach current histologic thresholds are bona fide neoplastic precursors with clinically-relevant driver events that can be detected by the 3-marker panel. The findings provide further validation for the diagnostic utility of the panel in clinical practice and its application in difficult or ambiguous cases.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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β-catenin, Pax2, and Pten Panel Identifies Precancers Among Histologically Subdiagnostic Endometrial Lesions

Aguilar¹,

Chen²,

Sahoo³

et al. 2023

American Journal of Surgical Pathology

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“…When tumor glands showed confluence, a diagnosis of EEC was rendered. Information regarding interpretation of β-catenin, PAX2 and PTEN was detailed and further reviewed in our recent publication 29,31. Briefly, when absence of staining was observed in ≥5% of lesional glands, PAX2 and PTEN were interpreted as lost.…”

Section: Methodsmentioning

confidence: 99%

Morules But Not Squamous Differentiation are a Reliable Indicator of CTNNB1 (β-catenin) Mutations in Endometrial Carcinoma and Precancers

Niu

Lucas

Molberg

et al. 2022

American Journal of Surgical Pathology

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Although collectively regarded as "squamous differentiation (SD)" in endometrial endometrioid carcinoma (EEC) and atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), morules (often referred to as "squamous morules") and true SD may represent two distinct phenomena. Here, we explored the distinction between morules versus SD and investigated the association of morules and SD with CTNNB1 mutations. A total of 270 cases of EEC and AH/EIN were studied, including EEC with (n = 36) or without (n = 36) morules and AH/ EIN with (n = 80) or without (n = 118) morules. Cases were analyzed by immunohistochemistry and selected cases (n = 20) by targeted next-generation sequencing panel. Near-perfect agreement was found between morules and glandular β-catenin nuclear staining in AH/EIN and EEC. A strong positive association was found between morules and glandular β-catenin nuclear staining (P < 0.0001, Φ = 0.59 in AH/EIN; P < 0.0001, Φ = 0.85 in EEC). There was no association between (1) morules and glandular PAX2 or PTEN aberrant expression or (2) SD and aberrant expression of β-catenin, PAX2 or PTEN (Φ = 0.09, β-catenin; Φ = 0.16, PAX2; Φ = 0.13, PTEN). CTNNB1 mutations were identified in all 20 selected morule-containing cases (100%). Next-generation sequencing was performed on 2 (preprogestin and postprogestin treatment) biopsies from 1 patient, revealing identical mutational profile in morules and glands. In conclusion, (1) SD and morules are distinct biological phenomena; (2) the presence of morules, but not SD, is a reliable indicator of CTNNB1 mutations in EEC and AH/EIN. Our findings demonstrate that SD and morules are distinct biological phenomena. Since morules but not SD are associated with β-catenin mutations, the distinction is clinically relevant and should be included in diagnostic reports.

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“…Ideally, the addition of pathologic or molecular characteristics of the pre-operative biopsy2 7 8 can further refine this approach and create an even more comprehensive algorithm. Moreover, in some centers (like the Mayo Clinic), an intra-operative frozen section of the uterus, obtained after mapping and identification of the SLN, can greatly contribute to the decision of whether to remove SLNs at the time of hysterectomy.…”

mentioning

confidence: 99%

Knowing when to hold and when to fold: sentinel lymph node biopsy in endometrial intraepithelial neoplasia

Mariani

Glaser

2022

Int J Gynecol Cancer

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Histopathologic diagnosis of endometrial precancers: Updates and future directions

Cited by 20 publications

References 95 publications

β-catenin, Pax2, and Pten Panel Identifies Precancers Among Histologically Subdiagnostic Endometrial Lesions

β-catenin, Pax2, and Pten Panel Identifies Precancers Among Histologically Subdiagnostic Endometrial Lesions

Morules But Not Squamous Differentiation are a Reliable Indicator of CTNNB1 (β-catenin) Mutations in Endometrial Carcinoma and Precancers

Knowing when to hold and when to fold: sentinel lymph node biopsy in endometrial intraepithelial neoplasia

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