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High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations.
Int J Gynecol Pathol. 2019 Jan; 38 Suppl 1:S40-S63.IJ

Abstract

This review of challenging diagnostic issues concerning high-grade endometrial carcinomas is derived from the authors' review of the literature followed by discussions at the Endometrial Cancer Workshop sponsored by the International Society of Gynecological Pathologists in 2016. Recommendations presented are evidence-based, insofar as this is possible, given that the levels of evidence are weak or moderate due to small sample sizes and nonuniform diagnostic criteria used in many studies. High-grade endometrioid carcinomas include FIGO grade 3 endometrioid carcinomas, serous carcinomas, clear cell carcinomas, undifferentiated carcinomas, and carcinosarcomas. FIGO grade 3 endometrioid carcinoma is diagnosed when an endometrioid carcinoma exhibits >50% solid architecture (excluding squamous areas), or when an architecturally FIGO grade 2 endometrioid carcinoma exhibits marked cytologic atypia, provided that a glandular variant of serous carcinoma has been excluded. The most useful immunohistochemical studies to make the distinction between these 2 histotypes are p53, p16, DNA mismatch repair proteins, PTEN, and ARID1A. Endometrial clear cell carcinomas must display prototypical architectural and cytologic features for diagnosis. Immunohistochemical stains, including, Napsin A and p504s can be used as ancillary diagnostic tools; p53 expression is aberrant in a minority of clear cell carcinomas. Of note, clear cells are found in all types of high-grade endometrial carcinomas, leading to a tendency to overdiagnose clear cell carcinoma. Undifferentiated carcinoma (which when associated with a component of low-grade endometrioid carcinoma is termed "dedifferentiated carcinoma") is composed of sheets of monotonous, typically dyscohesive cells, which can have a rhabdoid appearance; they often exhibit limited expression of cytokeratins and epithelial membrane antigen, are usually negative for PAX8 and hormone receptors, lack membranous e-cadherin and commonly demonstrate loss of expression of DNA mismatch repair proteins and SWI-SNF chromatin remodeling proteins. Carcinosarcomas must show unequivocal morphologic evidence of malignant epithelial and mesenchymal differentiation.

Authors+Show Affiliations

Department of Pathology, Memorial Sloan Kettering Cancer Center (R.M., R.A.S.) New York University Medical Center and School of Medicine, Tisch Hospital (K.M.), New York Department of Pathology, University Hospital, Stony Brook School of Medicine, Stony Brook (C.T.), New York Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway (B.D.) Department of Pathology, University of California San Diego, San Diego (O.F.) Department of Pathology, Cedars-Sinai Medical Center, Los Angeles (J.K.L.R.), California Department of Pathology, Karolinska Institutet, Stockholm, Sweden (J.A.C.) Department of Pathology, Brigham and Women's Hospital, Harvard Medical School (C.P.C.) Department of Pathology, Massachussetts General Hospital, Harvard Medical School (E.O.), Boston, Massachussetts Department of Pathology, University of British Columbia, Vancouver (C.B.G., J.A.I.) Department of Laboratory Medicine, Pathology and Medical Genetics, Royal Jubilee Hospital, Victoria (J.A.I.), BC, Canada Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (A.M.) Department of Pathology, Hospital University Arnau de Vilanova; and Department of Pathology, Hospital University de Bellvitge, IRBLLEIDA, IDIBELL, University of Lleida, CIBERONC, Barcelona, Spain (X.M.-G.) Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK (W.G.M.) Department of Pathology and Obstetrics and Gynecology, Yale School of Medicine and Yale School of Publich Health, New Haven, Connecticut (V.P.) Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland (P.N.S.) Department of Pathology, KEMH and School for Women's and Infants' Health, University of Western Australia, Perth, WA, Australia (C.J.R.S.).No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

30550483

Citation

Murali, Rajmohan, et al. "High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations." International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists, vol. 38 Suppl 1, 2019, pp. S40-S63.
Murali R, Davidson B, Fadare O, et al. High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations. Int J Gynecol Pathol. 2019;38 Suppl 1:S40-S63.
Murali, R., Davidson, B., Fadare, O., Carlson, J. A., Crum, C. P., Gilks, C. B., Irving, J. A., Malpica, A., Matias-Guiu, X., McCluggage, W. G., Mittal, K., Oliva, E., Parkash, V., Rutgers, J. K. L., Staats, P. N., Stewart, C. J. R., Tornos, C., & Soslow, R. A. (2019). High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations. International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists, 38 Suppl 1, S40-S63. https://doi.org/10.1097/PGP.0000000000000491
Murali R, et al. High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations. Int J Gynecol Pathol. 2019;38 Suppl 1:S40-S63. PubMed PMID: 30550483.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations. AU - Murali,Rajmohan, AU - Davidson,Ben, AU - Fadare,Oluwole, AU - Carlson,Joseph A, AU - Crum,Christopher P, AU - Gilks,C Blake, AU - Irving,Julie A, AU - Malpica,Anais, AU - Matias-Guiu,Xavier, AU - McCluggage,W Glenn, AU - Mittal,Khush, AU - Oliva,Esther, AU - Parkash,Vinita, AU - Rutgers,Joanne K L, AU - Staats,Paul N, AU - Stewart,Colin J R, AU - Tornos,Carmen, AU - Soslow,Robert A, PY - 2018/12/15/entrez PY - 2018/12/15/pubmed PY - 2019/4/10/medline SP - S40 EP - S63 JF - International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists JO - Int. J. Gynecol. Pathol. VL - 38 Suppl 1 N2 - This review of challenging diagnostic issues concerning high-grade endometrial carcinomas is derived from the authors' review of the literature followed by discussions at the Endometrial Cancer Workshop sponsored by the International Society of Gynecological Pathologists in 2016. Recommendations presented are evidence-based, insofar as this is possible, given that the levels of evidence are weak or moderate due to small sample sizes and nonuniform diagnostic criteria used in many studies. High-grade endometrioid carcinomas include FIGO grade 3 endometrioid carcinomas, serous carcinomas, clear cell carcinomas, undifferentiated carcinomas, and carcinosarcomas. FIGO grade 3 endometrioid carcinoma is diagnosed when an endometrioid carcinoma exhibits >50% solid architecture (excluding squamous areas), or when an architecturally FIGO grade 2 endometrioid carcinoma exhibits marked cytologic atypia, provided that a glandular variant of serous carcinoma has been excluded. The most useful immunohistochemical studies to make the distinction between these 2 histotypes are p53, p16, DNA mismatch repair proteins, PTEN, and ARID1A. Endometrial clear cell carcinomas must display prototypical architectural and cytologic features for diagnosis. Immunohistochemical stains, including, Napsin A and p504s can be used as ancillary diagnostic tools; p53 expression is aberrant in a minority of clear cell carcinomas. Of note, clear cells are found in all types of high-grade endometrial carcinomas, leading to a tendency to overdiagnose clear cell carcinoma. Undifferentiated carcinoma (which when associated with a component of low-grade endometrioid carcinoma is termed "dedifferentiated carcinoma") is composed of sheets of monotonous, typically dyscohesive cells, which can have a rhabdoid appearance; they often exhibit limited expression of cytokeratins and epithelial membrane antigen, are usually negative for PAX8 and hormone receptors, lack membranous e-cadherin and commonly demonstrate loss of expression of DNA mismatch repair proteins and SWI-SNF chromatin remodeling proteins. Carcinosarcomas must show unequivocal morphologic evidence of malignant epithelial and mesenchymal differentiation. SN - 1538-7151 UR - https://www.unboundmedicine.com/medline/citation/30550483/High_grade_Endometrial_Carcinomas:_Morphologic_and_Immunohistochemical_Features_Diagnostic_Challenges_and_Recommendations_ L2 - http://dx.doi.org/10.1097/PGP.0000000000000491 DB - PRIME DP - Unbound Medicine ER -