Endometrial carcinomas with ambiguous features
Section snippets
Background
Several studies performed in the past 5 years have shed some light on the perplexing heterogeneity of endometrial carcinomas and provided insights into the development of valid diagnostic criteria. Two recent studies7, 8 have formally addressed interobserver diagnostic agreement in particular subsets of endometrial carcinoma and described the performance of a single immunohistochemical stain to enhance diagnostic objectivity and, in one instance,7 to provide prognostic information. Although it
Morphologically ambiguous endometrial carcinomas for which biological and clinical data exist
Another study from our group,15 in addition to others,8 examined carcinomas with hyperplastic or low-grade endometrioid architecture and diffusely high nuclear grade. One particular study included cases that had been originally (and mistakenly) diagnosed as complex atypical hyperplasia or FIGO grades 1-2 endometrioid carcinoma. Immunohistochemistry directed at p53, PTEN, and PR distinguished tumors whose clinical course more closely resembled serous carcinoma (overexpressed p53, retained PTEN,
Morphologically ambiguous endometrial carcinomas for which biologically relevant data exist
Tumors resembling CCC, but with columnar or highly pleomorphic cells, tumors resembling serous carcinoma, but with clear cells, and epithelial tumors thought to be “mixed” are examples of interrelated problems about which we have relatively little knowledge. The first two studies discussed below provide insights into the extent to which endometrioid and CCCs and serous carcinomas, can resemble each other, and how immunohistochemistry and molecular typing can distinguish between biologically
Morphologically ambiguous endometrial carcinomas for which little, if any, diagnostically relevant data exist
Despite the fact that tumors in this category are largely biphasic in appearance, there are several biphasic endometrial tumors for which a good deal of relevant data exist: MMMTs with separable, high-grade epithelial and mesenchymal components18; low-grade spindle cell carcinomas, some of which have nonrhabdomyomatous heterologous elements34; combined differentiated and undifferentiated carcinomas (dedifferentiated carcinomas)20; low-grade Müllerian adenosarcomas; and atypical polypoid
Lynch syndrome
Lynch syndrome (LS) is an autosomal dominant, inherited cancer susceptibility syndrome featuring high rate of colorectal, endometrial, ovarian, gastric, urinary, and biliary cancers, among others. A mutation in one, or rarely more, of the DNA MMR genes, hMSH6, hMSH2, hMLH1, hPMS2,37 characterizes the syndrome, with hMSH6 mutations being most common in endometrial cancers. The lifetime cumulative risk of developing an endometrial cancer for an LS patient ranges from 27% to 71%, depending on
Which tumors are morphologically ambiguous
The first part of this discussion centers on which combinations of morphologic features lead to clinically relevant diagnosis in the preponderance of cases. Serous carcinomas can be diagnosed with confidence, provided the tumor shows at least focal papillary and micropapillary architecture and diffusely high grade nuclear features (Figure 6). MMMT can be diagnosed when separable, high-grade epithelial, and pleomorphic spindle cell sarcomatous elements are present (Figure 7). Endometrioid
Acknowledgments
This review is based on an idea suggested by Dr. Karuna Garg. She contributed significantly to the development of the concept of “histologically ambiguous endometrial carcinoma.”
References (52)
Two pathogenetic types of endometrial carcinoma
Gynecol Oncol
(1983)- et al.
Identification of prognostically relevant and reproducible subsets of endometrial adenocarcinoma based on clustering analysis of immunostaining data
Mod Pathol
(2007) - et al.
Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma
Hum Pathol
(2008) - et al.
p53 overexpression in morphologically ambiguous endometrial carcinomas correlates with adverse clinical outcomes
Mod Pathol
(2010) - et al.
Histologic and immunohistochemical decision-making in endometrial adenocarcinoma
Mod Pathol
(2008) - et al.
P53 overexpression predicts endometrial carcinoma recurrence better than HER-2/neu overexpression
Eur J Obstet Gynecol Reprod Biol
(2001) - et al.
p53 mutations and overexpression affect prognosis of ovarian endometrioid cancer but not clear cell cancer
Gynecol Oncol
(2003) - et al.
Expression profiling of 22 genes involved in the PI3K-AKT pathway identifies two subgroups of high-grade endometrial carcinomas with different molecular alterations
Mod Pathol
(2010) - et al.
Concomitant PI3K-AKT and p53 alterations in endometrial carcinomas are associated with poor prognosis
Mod Pathol
(2009) - et al.
Immunohistochemical analysis of PTEN in endometrial carcinoma: a tissue microarray study with a comparison of four commercial antibodies in correlation with molecular abnormalities
Mod Pathol
(2005)
Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms
Mod Pathol
Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen, and progesterone receptor expression
Hum Pathol
Endometrial intraepithelial carcinoma: a distinctive lesion specifically associated with tumors displaying serous differentiation
Hum Pathol
Molecular characterization of uterine clear cell carcinoma
Mod Pathol
Tumor type and substage predict survival in stage I and II ovarian carcinoma: insights and implications
Gynecol Oncol
ZEB1 expression in type I vs type II endometrial cancers: a marker of aggressive disease
Mod Pathol
Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis
Gastroenterology
Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer
Gastroenterology
Immunohistochemical detection of hepatocyte nuclear factor 1beta in ovarian and endometrial clear-cell adenocarcinomas and nonneoplastic endometrium
Hum Pathol
Diagnosis of ovarian carcinoma cell type is highly reproducible: a transcanadian study
Am J Surg Pathol
Ovarian carcinoma subtypes are different diseases: implications for biomarker studies
PLoS Med
A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary
Am J Surg Pathol
p53 overexpression as a prognostic indicator in endometrial carcinoma
Eur J Gynaecol Oncol
Prognostic factors in surgical stage I endometrial carcinoma
Acta Oncol
Serous endometrial cancers that mimic endometrioid adenocarcinomas: a clinicopathologic and immunohistochemical study of a group of problematic cases
Am J Surg Pathol
High-grade endometrial carcinoma: serous and grade 3 endometrioid carcinomas have different immunophenotypes and outcomes
Int J Gynecol Pathol
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Distinct histological and clinical features associated with pure uterine serous carcinoma: A single institution experience
2023, Annals of Diagnostic PathologyHigh-grade endometrial carcinomas: Morphologic spectrum and molecular classification
2022, Seminars in Diagnostic PathologyClinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India
2020, Annals of Diagnostic PathologyCitation Excerpt :Uncommonly, clear cell component was observed in two tumors; focal neuroendocrine differentiation in another two and spindly cells in another single tumor. Earlier, Soslow [23] and Carcangiu, et al. [25], in two different studies reported an increased frequency of non-endometrioid types, including clear cell carcinoma and high grade EMACs in cases of Lynch syndrome-related ECs. In another study, abnormal staining for MMR proteins was observed in 7/12 cases (58%) of undifferentiated endometrial carcinoma [26].
Immunohistochemistry and Molecular Diagnostics in the Differential Diagnosis of Female Genital Tract Pathology
2020, Gynecologic Pathology, Second EditionHigh-Grade Endometrial Carcinomas: Classification with Molecular Insights
2019, Surgical Pathology ClinicsA potpourri of pathogenetic pathways in endometrial carcinoma with a focus on Lynch Syndrome
2019, Annals of Diagnostic PathologyCitation Excerpt :The spread of these neoplasms is usually limited to the uterus [14]. Such tumors have a reasonably good clinical outcome and the majority of patients are often cured following a hysterectomy [2,13,14]. The Type II tumors, or non-Endometrioid Endometrial Carcinomas (non-EEC) include serous and clear cell carcinomas and carcinosarcomas which have a relatively worse outcome than Type I neoplasms [2,13,14,16] This group of tumors is estrogen independent and has a proclivity to arise in older females who are usually not obese. [2,17]