Eman Abdulfatah

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.

Endometrial cancer in morbidly obese women: do racial disparities affect surgical or survival outcomes?

OBJECTIVE Endometrial cancer mortality disproportionately affects black women and whether greater prevalence of obesity plays a role in this disparity is unknown. We examine the effect of race on post-surgical complications, length of stay, and mortality specifically in a morbidly obese population. METHODS Black and white women with endometrial cancer diagnosed from 1996 to 2012 were identified from the University Pathology Group database in Detroit, Michigan, and records were retrospectively reviewed to obtain clinicopathological, demographic, and surgical information. Analysis was limited to those with a body mass index of 40kg/m(2) or greater. Differences in the distribution of variables by race were assessed by chi-squared tests and t-tests. Kaplan-Meier and Cox regression analyses were performed to examine factors associated with mortality. RESULTS 97 white and 89 black morbidly obese women were included in this analysis. Black women were more likely to have type II tumors (33.7% versus 15.5% of white women, p-value=0.003). Hypertension was more prevalent in black women (76.4% versus 58.8%, p-value=0.009), and they had longer hospital stays after surgery despite similar rates of open vs minimally invasive procedures and lymph node dissection (mean days=5.4) compared to whites (mean days=3.5, p-value=0.036). Wound infection was the most common complication (16.5% in whites and 14.4% in blacks, p-value=0.888). Blacks were more likely to suffer other complications, but overall the proportions did not differ by race. In univariate analyses, black women had higher risk of endometrial cancer-related death (p-value=0.090). No racial differences were noted in adjusted survival analyses. CONCLUSION A more complete investigation, incorporating socio-demographic factors, is warranted to understand the effects of morbid obesity and race on endometrial cancer.

Vanishing Endometrial Cancer in Hysterectomy Specimens A Myth or a Fact

The incidence of endometrial cancers diagnosed on biopsy that have no residual cancer identified at hysterectomy is not well studied. The aim of our study was to determine the incidence and long-term follow-up of this “vanishing cancer” phenomenon. All slides from the initial biopsy/curettage and hysterectomy specimens were reviewed and the diagnosis confirmed by a gynecologic pathologist. The entire endometrium was serially sectioned and submitted for histologic examination. Clinical and pathologic variables were analyzed, including patient demographics, tumor histologic type and grade, stage, biopsy method, adjuvant therapy, surgical procedure, recurrence, and disease-specific survival. We identified 23 biopsy-proven cases of endometrial cancer with no residual disease on hysterectomy specimen. Of the 23 patients, 15 (65.2%) were diagnosed as endometrioid, 6 (26%) serous, 1 clear cell (4.3%), and 1 (4.3%) serous intraepithelial carcinoma. Seventeen underwent dilatation and curettage, and 6 had endometrial biopsy as the primary procedure. The median follow-up was 8.8 years (range, 1.2 to 17 y). Only 2 cases with serous carcinoma underwent adjuvant chemotherapy, and none received radiation therapy. Only 1 patient died of disease after 27 months and was diagnosed as FIGO grade II endometrioid carcinoma on dilatation and curettage. The inability to identify cancer in a hysterectomy specimen for biopsy-confirmed carcinoma does not indicate technical failure. Although there is no specific standard treatment for patients with “vanishing endometrial cancer,” the prognosis is excellent; however, close follow-up is suggested.

Role of Molecular Profiling in Diagnosis of Papillary Renal-cell Cancer Presenting as Cancer of Unknown Primary Site

Cancer of unknown primary site accounts for approximately 4% to 5% of all invasive cancer diagnoses. We present 2 cases of cancer of unknown primary site, both of which were successfully diagnosed as papillary renal-cell carcinoma by mRNA gene expression profiling. The use of molecular profiling should be contemplated on a case-by-case scenario. It should be strongly considered therapies are being targeted to tumor sites.

Histologic Transformation in NSCLC with PD-1 therapy

Histologic Transformation in NSCLC with PD-1 therapy Misako Nagasaka, MD, Rahul S. Pansare, MD, Eman Abdulfatah, MD, Hui Guan, MD, Paul Tranchida, MD, Shirish M. Gadgeel, MD* Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, Michigan Department of Infectious Disease, Wayne State University, Detroit, Michigan Department of Pathology, Wayne State University, Detroit, Michigan Department of Surgical Pathology, Detroit Medical Center/Karmanos Cancer Institute, Detroit, Michigan

Clear Cell Carcinoma of the Endometrium: Evaluation of Prognostic Parameters in a Multi-institutional Cohort of 165 Cases

Objectives Clear cell carcinoma (CCC) comprises a rare yet an aggressive subtype, accounting for less than 5% of all uterine carcinomas. Several clinicopathologic features have been predictive of poor prognosis; however, data remain controversial. The aim of this study was to evaluate the clinicopathologic features of a multi-institutional cohort of endometrial CCC in order to identify which, if any, have prognostic significance. Methods Retrospective review of endometrial CCC diagnosed between 1995 and 2012 at 3 institutions was conducted to evaluate clinicopathologic parameters: age, race, tumor size, stage, myometrial invasion (MI), lymphovascular invasion, lymph node and adnexal involvement, adjuvant therapy, and outcomes. Data were analyzed using Fisher exact, Cox regression, and Kaplan-Meier analyses. Results Patients’ ages ranged from 36 to 90 years (median, 67 years). The median tumor size was 3.6 cm. Inner-half MI was present in 44%, lymphovascular invasion in 34%, adnexal involvement in 16%, and lymph node metastasis in 30% of cases. Fifty-eight percent of the patients presented with early-stage disease. The 5-year overall survival (OS) was 58%. Shorter disease-free interval (DFI) was significantly associated with older age at diagnosis (>70 years), advanced-stage disease, adnexal involvement, and deep MI (P = 0.005, P = 0.001, P = 0.001, and P = 0.003, respectively). Patients who received adjuvant chemotherapy had a significantly worse DFI and 5-year OS (P = 0.001 and P = 0.001, respectively). A significantly shorter 5-year OS was noted with advanced stage (III–IV) and presence of adnexal involvement (P = 0.001 and P = 0.021, respectively). On Cox regression analysis, advanced-stage disease, older age, and adnexal involvement were significant independent predictors of worse DFI (P = 0.001, P = 0.005, and P = 0.019, respectively), whereas inner-half MI was a significant independent predictor of longer DFI (P = 0.004). Adjuvant radiotherapy alone was a significant independent predictor of better 5-year OS (P = 0.012). Conclusions In our series of endometrial CCC, older age at diagnosis, advanced stage, deep MI, and adnexal involvement were independent poor prognostic factors. Adjuvant radiotherapy had a significant positive impact on 5-year OS.

Abstract A16: Fibroadenomas on benign breast biopsy and subsequent breast cancer risk in an African American cohort

Introduction: The majority of the 1.6 million breast biopsies performed annually in the United States are benign; however, several breast cancer risk models consider a benign biopsy a factor that increases risk of subsequent breast cancer. Fibroadenomas (FA), benign tumors of epithelial and stromal tissue, occur frequently in premenopausal women and more frequently in African American (AA) women than European American (EA) women. A small increased risk of subsequent breast cancer due to FA has been reported in some studies of EA women. We sought to investigate whether the risk of this lesion differs for AA women. Methods: Benign breast biopsies from 3895 AA women diagnosed between 1997 and 2010 in metropolitan Detroit were reviewed for 12 benign features including FA, ductal ectasia, fibrosis, apocrine metaplasia, ductal hyperplasia, lobular hyperplasia, calcifications, cysts, intraductal papilloma, radial scar, sclerosing adenosis, and columnar alterations. These features were also used to categorize FA into simple and complex FA, where complex FA occurs when FA is accompanied by at least one of the following features: cysts, calcifications, apocrine metaplasia or intraductal papilloma. Women were followed for subsequent breast cancer using the Detroit Surveillance, Epidemiology, and End Results (SEER) cancer registry. Associations between FA and other benign lesions were examined using chi-square tests. Risk of breast cancer was estimated by relative risk ratios and 95% confidence intervals calculated using logistic regression. All models were adjusted for age at biopsy and additionally adjusted for presence of proliferative disease with or without atypia. Results: Of the 3895 AA women, 46.5% presented with FA on biopsy. FA occurred more frequently in biopsies of younger women (p-value Conclusions: FA are negatively associated with other benign breast disease features. Risk of breast cancer may be reduced in women with FA compared to women with other types of benign lesions. These findings have important implications for modeling breast cancer risk particularly among AA women for whom FAs are common. Citation Format: Asra N. Shaik, Julie J. Ruterbusch, Eman Abdulfatah, Marcel T. Ghanim, MHD Fayez Daaboul, Visakha Pardeshi, Rouba Ali-Fehmi, Daniel W. Visscher, Sudeshna Bandyopadhyay, Michele L. Cote. Fibroadenomas on benign breast biopsy and subsequent breast cancer risk in an African American cohort. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A16.

Abstract A15: Breast cancer subtype subsequent to a benign breast biopsy among African American women

Introduction: Most clinical models to estimate risk of invasive breast cancer include history of benign breast disease (BBD) as a covariate, as these women represent a higher risk group compared to the general population. A better understanding of the association between BBD and breast cancer is necessary to improve the utility of these risk models, particularly with respect to tumor subtype. This may be especially important for African American women who are more likely to present with aggressive cancers compared to white women. Here we present tumor subtypes from a higher risk cohort of African American women with a history of BBD. Methods: Benign breast biopsies from 3,865 African American women with BBD diagnosed from 1997-2010 were examined for 14 benign features, and followed for subsequent breast cancers in metropolitan Detroit, Michigan using medical records and data from the Detroit Surveillance, Epidemiology and End Results (SEER) program. Immunohistochemistry analysis was performed for the following 6 markers: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK 5/6) in order to categorize the subsequent breast cancers by subtype. Briefly, ER and PR were utilized to classify tumors as luminal or non-luminal, and then further classification was made based HER2. Luminal tumors were also classified by Ki-67 expression, and triple negative tumors (ER/PR/HER2 negative) were further classified based on expression of either CK5/6 or EGFR, resulting in 6 categories. Results: 210 women (5.4% of the total cohort) with a subsequent breast cancer were identified over a median follow-up time of 12.3 years (range: 0.6 - 18.0). Analysis of all 6 markers is complete for half of the tumors (104). The majority of the subsequent cancers were invasive (n=72, 69.2%). Most of the invasive tumors were luminal B, HER2- (37.5%), followed by luminal A (31.9%), triple negative (19.4%), non-luminal, HER2+ (6.9%) and luminal B, HER2+ (4.2%). Of the 14 triple negative cancers (19.4%), 8 were negative for CK5/6 and EGFR (5 negative phenotype, 57.1%) and 6 were core basal (42.9%). Among the 32 in situ tumors, the majority were luminal A (n=26, 81.3%), followed by luminal B, HER2- (n=5, 15.6%) and there was a single tumor classified as 5 negative. Compared to population-based SEER data from 5,268 African American women with invasive breast cancer and available data on 3 markers (ER, PR, and HER2) diagnosed in 2010, our cohort is similar with respect to tumor subtype. Conclusions: The women with a previous benign breast biopsy in our cohort who develop a subsequent breast cancer have subtypes that are similar to the general African American population in the United States. Thus, our BBD cohort represents the full spectrum of invasive breast cancers with respect to subtype, including triple negative tumors. Citation Format: Julie J. Ruterbusch, Michele L. Cote, Julie Boerner, Eman Abdulfatah, Baraa Alosh, Vishakha Pardeshi, MHD Fayez Daaboul, Woodlyne Roquiz, Rouba Ali-Fehmi, Sudeshna Bandyopadhyay. Breast cancer subtype subsequent to a benign breast biopsy among African American women. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A15.

Abstract A25: Benign breast disease and subsequent breast cancer risk: The Detroit cohort

Introduction: Atypical hyperplasia (also known as proliferative disease with atypia), while categorized as a benign finding, has been consistently associated with an increased risk of subsequent breast cancer that persists for decades after initial diagnosis. There are various other lesions that are classified as benign breast disease (BBD) that are routinely identified by pathologists that may also increase risk and be of use to inform breast cancer risk models. We sought to identify which BBD lesions were associated with increased risk of breast cancer in an African American (AA) cohort. Methods: Benign breast biopsies from 3,895 AA women diagnosed with BBD between 1997 and 2010 in metropolitan Detroit were reviewed for 12 benign features including columnar alterations, ductal ectasia, ductal hyperplasia, fibrosis, apocrine metaplasia, lobular hyperplasia, calcifications, cysts, intraductal papilloma, radial scar, sclerosing adenosis, and fibroadenomas. Women were followed for subsequent breast cancer using the Metropolitan Detroit Cancer Surveillance System, part of the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Associations between BBD features and subsequent breast cancer were examined using chi-square tests. Features that had a significant chi-square test result were also combined into scores describing the overall number of BBD features identified, termed busy breast score. Multivariable log-binomial regression with backward selection based on BIC criteria was performed to assess risk ratio and 95% confidence intervals of breast cancer on 12 candidate features. Multivariable log-binomial regression was performed for busy breast score as well. All regression models were adjusted for age at biopsy and overall impression for presence of proliferative disease with or without atypia using non-proliferative disease as the reference. Models were checked for multicollinearity using a variable inflation factor (VIF). Results: Of the 3,895 AA women in the BBD cohort, 210 developed a subsequent breast cancer. The median age at biopsy among those without a subsequent cancer (controls) was 47 years of age, while cases were 53 years of age (p-value Conclusions: Columnar alterations confer increased risk of breast cancer beyond the risks associated with atypical hyperplasia, as does the presence of multiple types of BBD lesions in a single biopsy. These estimates may help improve the current risk assessment models for African American women and highlight the need for additional research regarding the utility of closer surveillance and potentially chemoprevention for reduction of breast cancer in these women. Citation Format: Michele L. Cote, Wei Chen, Julie J. Ruterbusch, Eman Abdulfatah, Visakha Pardeshi, Asra N. Shaik, Marcel T. Ghanim, MHD Fayez Daaboul, Daniel W. Visscher, Sudeshna Bandyopadhyay, Rouba Ali-Fehmi. Benign breast disease and subsequent breast cancer risk: The Detroit cohort. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A25.

Abstract 1769: Presence of cysts in benign breast tissue and the risk of subsequent breast cancer in African American women

Introduction: Benign breast disease (BBD) is an established risk factor for developing breast cancer, and certain pathologic features in benign breast tissue are more strongly associated with breast cancer risk. Most of the studies evaluating BBD and breast cancer risk have been done in primarily white populations. Our previous work among African American (AA) women with BBD suggested the presence of cysts was associated with increased breast cancer risk. This finding may be unique to AA women as other studies among white populations have not replicated these findings. We sought to further explore the association between breast cysts and breast cancer risk in our expanded AA BBD cohort. Methods: Biopsies from AA women initially diagnosed with BBD from 1997 to 2009 were examined for 14 pathologic features, including the microscopic presence of cysts, and followed for subsequent breast cancer. The association between cysts and the other pathologic features were compared using chi-square tests, and the risk of developing breast cancer was estimated using logistic regression and summarized with odds ratios (OR) and 95% confidence intervals (95% CI). Results: A total of 3,360 AA women with BBD have been identified and their benign biopsies reviewed. 190 women have developed a subsequent breast cancer with a mean follow-up time of 11.5 years. Cysts were present on 1,366 (38%) of the biopsies, and were significantly associated with nearly all of the other benign features evaluated: apocrine metaplasia, ductal hyperplasia, calcifications, duct ectasia, fibrodenomas, fibrosis, intra-ductal papillomas, sclerosing adenosis, columnar alterations, mucocelle-like lesions, radial scars, and proliferation with and without atypia (all p Conclusion: Among AA women, cysts are highly correlated with other BBD features that increase subsequent breast cancer risk, but the risk associated with cysts does not appear to be independent of hyperplasia with atypia. Understanding the etiology of BBD and cyst development may provide insight into breast tumorigenesis, and the interplay between cysts and other BBD features warrant further investigation. Citation Format: Julie J. Ruterbusch, Michele L. Cote, Sudeshna Bandyopadhyay, Baraa Alosh, Eman Abdulfatah, Vishakha Pardeshi, Woodlyne Roquiz, Daniel Visscher, Rouba Ali-Fehmi. Presence of cysts in benign breast tissue and the risk of subsequent breast cancer in African American women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1769.