Interobserver Variability in the Diagnosis of Uterine High-Grade Endometrioid Carcinoma

Context.—Low interobserver diagnostic agreement exists among high-grade endometrial carcinomas. Objective.—To evaluate diagnostic variability in International Federation of Gynecology and Obstetrics (FIGO) grade 3 endometrioid adenocarcinoma (G3EC) in 2 different sign-out practices. Design.—Sixty-six G3EC cases were identified from pathology archives of Wayne State University (WSU, Detroit, Michigan) (general surgical pathology sign-out) and 65 from Memorial Sloan Kettering Cancer Center (MSK, New York, New York) (gynecologic pathology focused sign-out). Each case was reviewed together by 2 gynecologic pathologists, one from each institution, and classified into the G3EC group or a reclassified group. Clinicopathologic parameters were compared. Results.—Twenty-five WSU cases (38%) were reclassified as undifferentiated (n = 2), serous (n = 4), mixed endometrioid and serous carcinomas (n = 12), and FIGO grade 2 endometrioid adenocarcinomas with focal marked nuclear atypia (n = 7). Eleven MSK cases (17%) were reclassified as undifferentiated (n = 5), serous (n = 1), mixed endometrioid and serous carcinomas (n = 4), and mixed endometrioid and clear cell carcinomas (n = 1). Agreement rate between original and review diagnosis was 83% (54 of 65) at MSK and 62% (41 of 66) at WSU (P = .01) with an overall rate of 73% (95 of 131). There were more undifferentiated carcinomas at MSK than there were at WSU (45% [5 of 11] versus 8% [2 of 25]; P = .02). There were more grade 2 endometrioid adenocarcinomas with focal, marked nuclear atypia at WSU (28%; 7 of 25) than there were at MSK (0%) (P = .03). Mixed endometrioid and serous carcinoma was the most common misclassified subtype (44%; 16 of 36). Conclusion.—Moderate interobserver variability exists in the diagnosis of G3EC with a significantly greater diagnostic agreement rate in gynecologic pathology–focused sign-out than in general sign-out practice.

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Metachronous Skeletal Osteosarcoma in Patients Treated with Adjuvant and Neoadjuvant Chemotherapy for Nonmetastatic Osteosarcoma

Journal of Clinical Oncology ◽

10.1200/jco.2003.06.177 ◽

2003 ◽

Vol 21 (2) ◽

pp. 342-348 ◽

Cited By ~ 33

Author(s):

LeLe Aung ◽

Richard Gorlick ◽

John H. Healey ◽

Weiji Shi ◽

Howard T. Thaler ◽

...

Keyword(s):

New York ◽

Combined Modality Therapy ◽

Initial Therapy ◽

Cancer Center ◽

Small Subset ◽

High Grade ◽

Combined Modality ◽

Individualized Chemotherapy

Purpose: The prognosis for patients who develop metachronous skeletal osteosarcoma (OS) has been considered grave compared with that for patients with relapse limited to the lungs. We investigated the incidence and outcome of metachronous skeletal OS after initial treatment of the primary tumor. Patients and Methods: Twenty-three (median age 18.7 years) of 426 patients with nonmetastatic, high-grade primary OS treated at Memorial Sloan-Kettering Cancer Center (New York, NY) between February 1973 and May 2000 developed metachronous skeletal OS. Initial therapy included combination chemotherapy and surgery. Treatment of subsequent relapses consisted of chemotherapy or radiation alone or surgery with or without additional individualized chemotherapy. Results: The median time from the diagnosis of primary OS to the development of metachronous OS was 1.4 years (range, 0.2 to 11.3 years). Median survival was 1.5 years (95% confidence interval [CI], 0.8 to 6.9 years). Two- and 5-year postmetachronous overall survival was 43.5% (95% CI, 23.2% to 63.7%) and 33% (95% CI, 13% to 53%), respectively. At last follow-up (range, 0.1 to 12.8 years), five (30.4%) patients were alive with no evidence of disease (range, 1.7 to 12.8 years; median, 4.4 years). For 11 patients who developed metachronous OS 24 months or more from initial diagnosis, 5-year postmetachronous survival rate for patients receiving combined modality versus monotherapy was 83% (95% CI, 54% to 100%) and 40% (95% CI, 0% to 83%), respectively. Conclusion: In a small subset of patients who developed late metachronous OS, combined-modality therapy with surgery and aggressive chemotherapy may result in long-term postmetachronous survival. This implies that principles used in treatment of primary OS may be applied to patients with late metachronous skeletal OS.

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Changes in the Management and Prognosis of Ovarian Cancer Due to the New FIGO and WHO Classifications: A Case Series Observational Descriptive Study. Seven Years of Follow-up

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001331 ◽

2018 ◽

Vol 28 (8) ◽

pp. 1461-1470 ◽

Cited By ~ 1

Author(s):

Monica Gomes Ferreira ◽

Magdalena Sancho de Salas ◽

Rogelio González Sarmiento ◽

Maria José Doyague Sánchez

Keyword(s):

Ovarian Cancer ◽

Case Series ◽

Advanced Ovarian Cancer ◽

Figo Stage ◽

Descriptive Study ◽

World Health ◽

Serous Carcinoma ◽

High Grade ◽

Gynecology And Obstetrics ◽

Observational Descriptive Study

ObjectiveOvarian cancer is the deadliest of gynecologic cancers. In recent years, International Federation of Gynecology and Obstetrics (FIGO) and the World Health Organization (WHO) classifications were revised. We compared the major changes between the classifications and examined the effects on the therapy and prognosis of the ovarian, fallopian tubes, and peritoneum cancer in our series according to both classifications.Methods/MaterialsWe performed an observational descriptive study of 210 patients who were diagnosed with a malignant ovarian tumor from 2010 to 2016. The accepted FIGO and WHO classifications at each point in time were registered. We reclassified both data, obtaining both classifications for each patient. The changes in the therapeutic management and prognosis were examined.ResultsIn both FIGO classifications of our case series, most patients with ovarian cancer were in FIGO stage III. We found that 4.2% of the previous stage IIIC patients have changed to stage IIIA2 or stage IIIB, with better prognosis and survival rate. In the new WHO classification, the main change, in our case series, was the increase in the high-grade serous carcinoma percentage. According to the current recommendations, we observed 7.56% more patients in early ovarian cancer stages treated with platinum and taxane. In both early and advanced ovarian cancer group, high-grade serous carcinoma tumors were predominant.ConclusionsThe newly created WHO and FIGO classifications have improved the ability to predict the prognosis and consequently to change the therapeutic managements of patients with ovarian cancer.

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Undifferentiated Endometrial Carcinoma: A Diagnosis Frequently Overlooked

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2011-0461-rs ◽

2013 ◽

Vol 137 (3) ◽

pp. 438-442 ◽

Cited By ~ 19

Author(s):

Shaymaa Al-Loh ◽

Maysa Al-Hussaini

Keyword(s):

Endometrial Carcinoma ◽

Cancer Center ◽

Endometrioid Adenocarcinoma ◽

Diagnostic Challenge ◽

Gynecology And Obstetrics ◽

Proper Definition ◽

Grade 3 ◽

Md Anderson ◽

Endometrial Endometrioid Adenocarcinoma ◽

Uncommon Neoplasm

Undifferentiated endometrial carcinoma (UEC) is a relatively uncommon neoplasm with only few studies published thus far. It has always been a diagnostic challenge because of the lack of proper definition cited in most of the standard textbooks. Recently however, a few studies have highlighted the clinicopathologic features of UEC. The distinctive morphology of UEC was noted by the group from MD Anderson Cancer Center, which enabled them to establish the defining criteria. It appears to be more aggressive than endometrial endometrioid adenocarcinoma, FIGO (International Federation of Gynecology and Obstetrics) grade 3, its main differential diagnosis. Proper recognition of this entity is important owing to its aggressive behavior.

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Aberrant Diffuse Intense CD10 Expression In P16 Positive Undifferentiated Endometrial Carcinoma: A Diagnostic Dilemma

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.097 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S45-S46

Author(s):

R Derakhshandeh ◽

B Kallakury

Keyword(s):

Endometrial Carcinoma ◽

Hormone Receptors ◽

Undifferentiated Carcinoma ◽

Serous Carcinoma ◽

Proliferation Index ◽

Endometrioid Adenocarcinoma ◽

High Grade ◽

Stromal Sarcoma ◽

Cd10 Expression ◽

High Grade Carcinoma

Abstract Introduction/Objective High-grade endometrial neoplasms frequently pose a diagnostic challenge on purely histologic evaluation due to their ambiguous morphologic features. High grade endometrioid adenocarcinoma, serous carcinoma, undifferentiated carcinoma, and a minority of sarcoma cases can present with a solid growth pattern. Methods We present a 59-year-old patient who underwent a hysterectomy and bilateral salpingo-oophorectomy for a biopsy proven FIGO grade 2 endometrial carcinoma. Results Grossly, the entire endometrial cavity was involved by a hemorrhagic tumor. Microscopic examination showed the entire specimen to be replaced by predominantly non-cohesive diffuse sheets of mitotically active, pleomorphic cells without any glandular, papillary, serous or clear cell features.The differential diagnosis included undifferentiated carcinoma, serous carcinoma, carcinosarcoma, stromal sarcoma and other tumors including high- grade lymphoma. By immunohistochemistry, the tumor cells showed variable positivity for CK7, EMA, CK19, CK18, CK8, AE1/AE3, pan-keratin, CAM5.2, CD56, synaptophysin, p53, cyclinD1 and with a high Ki-67 proliferation index of 80%. The tumor was diffusely/intensely positive for CD10 and P16 while being negative for ER, PR, PAX8, HPV, mesenchymal and lymphoid markers. While diffuse/intense CD10 positivity and ER/PR negativity raised a concern for stromal sarcoma component, the above phenotype confirmed an aggressive/high grade carcinoma. Diffuse/intense p53 and p16 expression raised a consideration of serous carcinoma, but morphology and absence of PAX-8 failed to support this diagnosis. Undifferentiated carcinoma of the endometrium is a high-grade carcinoma which has been recognized as a distinct entity with diffuse p16 and p53 positivity in the absence of PAX-8 and hormone receptors. Positive vimentin, along with a negative HPV, confirmed the endometrial rather than cervical origin of this neoplasm. Conclusion By reporting this case, we draw attention to the previously unreported diffuse intense CD10 expression in undifferentiated carcinoma of endometrium to avoid misdiagnosis with considerations that include stromal sarcoma.

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HER-2 Is an Independent Prognostic Factor in Endometrial Cancer: Association With Outcome in a Large Cohort of Surgically Staged Patients

Journal of Clinical Oncology ◽

10.1200/jco.2005.03.4827 ◽

2006 ◽

Vol 24 (15) ◽

pp. 2376-2385 ◽

Cited By ~ 141

Author(s):

Carl Morrison ◽

Vanna Zanagnolo ◽

Nilsa Ramirez ◽

David E. Cohn ◽

Nicole Kelbick ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

Outcome Data ◽

Large Cohort ◽

Surgical Staging ◽

Serous Carcinoma ◽

Low Grade ◽

Endometrioid Adenocarcinoma ◽

High Grade ◽

Her 2

Purpose To evaluate HER-2 expression and amplification in a large cohort of endometrial cancer with complete surgical staging and outcome data. Patients and Methods A tissue microarray was constructed of 483 patients with endometrial cancer of diverse histologic type and stage and tested for HER-2 expression and amplification using current standards of practice. There was outcome data for 83% of all patients and 81% with complete surgical staging. Results Both expression and amplification of HER-2 was associated with high-grade (P = .0001) and high stage (P = .0001) endometrial cancer. The highest rate of HER-2 expression and amplification was seen in serous carcinoma (43% and 29%), while grade 1 endometrioid adenocarcinoma showed the lowest levels (3% and 1%). For all histologic types, the rate of HER-2 expression and amplification was remarkably different (P < .0001) for grade 3 cancers (31% and 15%) versus grade 2 (7% and 3%) and grade 1 cancers (3% and 1%), with similar results for endometrioid type (P < .0001). Both HER-2 expression and amplification correlated with disease-specific survival and progression-free survival in univariate analyses. By multivariate analysis HER-2 expression in the presence of amplification (P = .012) correlated with overall survival, but not expression in the absence of amplification. Overall survival was significantly shorter (P = .0001) in patients who overexpressed (median, 5.2 years) and/or showed amplification of HER-2 (median, 3.5 years) versus those that did not (median of all cases, 13 years). Conclusion Our results would suggest that HER-2 is an important oncogene in high grade and stage endometrial cancer, but plays only a minor role in the much more common low grade and stage tumors that encompass the majority of clinical practice.

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Survival Rates for International Federation of Gynecology and Obstetrics Stage III Ovarian Carcinoma by Cell Type: A Study of 262 Unselected Patients With Uniform Pathologic Review

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31823c6f80 ◽

2012 ◽

Vol 22 (3) ◽

pp. 367-371 ◽

Cited By ~ 29

Author(s):

Jeffrey D. Seidman ◽

Anna Yemelyanova ◽

Jonathan A. Cosin ◽

Anthony Smith ◽

Robert J. Kurman

Keyword(s):

Ovarian Cancer ◽

International Federation ◽

Stage Iii ◽

Serous Carcinoma ◽

Published Data ◽

Low Grade ◽

High Grade ◽

Cell Type ◽

Ovarian Carcinomas ◽

Gynecology And Obstetrics

ObjectivePublished data are conflicting on the influence of cell type on prognosis in ovarian cancer. The recent separation of low-grade serous carcinoma as a distinctive cell type of ovarian cancer with an indolent behavior, in retrospect, suggests that survival in studies that have not separated this group may be inaccurate.MethodsAn unselected series of 262 International Federation of Gynecology and Obstetrics stage III ovarian carcinomas was studied. Diagnostic classification of each tumor was made with particular attention to recent refinements in cell-type classification. Survival curves were constructed according to Kaplan-Meier and compared with the log-rank test.ResultsThe 5-year survival for 207 high-grade serous carcinomas was 40%, as compared with 71% for 18 patients with low-grade serous carcinoma (P = 0.0113). Low-grade serous carcinoma was significantly more likely to be optimally debulked (P = 0.0039) and significantly less likely to be substage IIIC (P < 0.0001). The survival for carcinosarcoma was significantly inferior to all serous carcinomas (P = 0.0322). The significance of this latter comparison was lost when carcinosarcomas were compared with only high-grade serous carcinoma (P > 0.05).ConclusionsLow-grade serous carcinoma has a significantly better prognosis than high-grade serous carcinoma and also differs with regard to substage distribution and proportion of patients optimally debulked. Because of its excellent prognosis, failure to separate low-grade serous carcinomas, notwithstanding its infrequent occurrence, can change the results of survival analyses that do not make this separation.

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