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Book: Gynecologic Pathology

Ali-Fehmi, Rouba / Stolnicu, Simona

(Encyclopedia of Pathology)

2023

Author's details	Simona Stolnicu studied medicine and graduated from the University of Medicine and Pharmacy of Iasi, Romania, in 1991. She became Assistant Professor in 1993, completed pathology residency training, and received her PhD in Medicine at the University of Medicine, Pharmacy, Sciences and Technology of Targu Mures (UMFST), Romania. She completed her training in gynecologic and breast pathology as a fellow/ observer at University of Granada, Spain; University of Trieste, Italy; MD Anderson Cancer Center, Houston, USA; and Memorial Sloan Kettering Cancer Center, New York, USA. Since 1997, she is a consultant pathologist at the Department of Pathology, UMFST, Romania, specialized in the diagnosis of gynecologic and breast diseases. She is also a Professor of Pathology at the same university, teaching students, residents, and PhD students for three decades. She was an invited Lecturer and Course Director of continuing education courses on gynecologic and breast pathology offered by national
Series title	Encyclopedia of Pathology
Keywords	Female genital tract ; Tumors ; Immunophenotype ; Lesions ; microscopic features ; macroscopic featrues ; gynecologic pathology ; female genital tract ; tumors ; immunophenotype ; lesions
Language	English
Size	680 p.
Edition	1
Publisher	Springer International Publishing
Document type	Book
Note	PDA Manuell_24
Format	183 x 260 x 40
ISBN	9783030973773 ; 3030973778
Database	PDA

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Article ; Online: Human epidermal growth factor receptor-2 (HER2) expression in FIGO3 high-grade endometrial endometrioid carcinoma: Clinicopathologic characteristics and future directions.

Abada, Evi / Kim, Seongho / Jang, Hyejeong / Kheil, Mira / Singh, Kamaljeet / Bandyopadhyay, Sudeshna / Ali-Fehmi, Rouba / Quddus, M Ruhul

Gynecologic oncology

2024 Volume 185, Page(s) 25–32

Abstract: Objectives: To study the expression of HER2 in high-grade FIGO3 endometrial endometroid carcinoma (EEC) and to correlate our findings with the clinicopathologic characteristics of this tumor.: Methods: HER2 expression by immunohistochemistry (IHC) ... ...

Abstract	Objectives: To study the expression of HER2 in high-grade FIGO3 endometrial endometroid carcinoma (EEC) and to correlate our findings with the clinicopathologic characteristics of this tumor. Methods: HER2 expression by immunohistochemistry (IHC) was performed on 10% formalin-fixed paraffin embedded tissue on cases diagnosed as FIGO3 EEC. HER2 expression was interpreted as negative (0), low (1+ and 2+) or positive (3+) using similar criteria as in the breast. HER2 amplification by Fluorescence in situ hybridization (FISH) was performed on cases interpreted as 2+ and 3+ by IHC. Results: One hundred and forty-three FIGO3 EEC were identified. Of these, 70 (49%) cases were HER2 negative (IHC 0), and 73 (51%) cases expressed/amplified HER2 by IHC and/or FISH. Of the 73 cases expressing or amplifying HER2, 59 cases were IHC 1+, 12 cases were IHC 2+, and 2 cases were IHC 3+. FISH testing was performed in 12 cases. Only one of the two HER2 IHC 3+ cases showed HER2 gene amplification by FISH and the other 11 cases were not amplified. The 5-year overall survival (OS) rate for HER2 IHC 1+ cases was 92.20% (95% CI: 83.97-100.00), and the 5-year OS rate for HER2 IHC 2+/3+ cases was 89.50% (95% CI: 56.41-100.00). Conclusion: Our findings indicate that about one half of FIGO3 EEC variably expresses HER2 and with the emerging concept of "HER2 low", anti-HER2 agents may be explored as potential therapeutic options in these patients, for possible survival benefits.
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2024.01.048
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Article ; Online: Comparing mutation frequencies for homologous recombination genes in uterine serous and high-grade serous ovarian carcinomas: A case for homologous recombination deficiency testing in uterine serous carcinoma.

Wallbillich, John J / Morris, Robert T / Ali-Fehmi, Rouba

Gynecologic oncology

2020 Volume 159, Issue 2, Page(s) 381–386

Abstract: Objective: To compare the frequencies of somatic homologous recombination (HR) gene mutations identified in next-generation sequencing (NGS) genomic profiling of uterine serous carcinomas (USCs) and high-grade serous ovarian carcinomas (HGSOCs).: ... ...

Abstract	Objective: To compare the frequencies of somatic homologous recombination (HR) gene mutations identified in next-generation sequencing (NGS) genomic profiling of uterine serous carcinomas (USCs) and high-grade serous ovarian carcinomas (HGSOCs). Methods: Data for this analysis was obtained from AACR Project GENIE, a multi-institutional dataset of clinical-grade NGS genomic profiling results for many cancer sites and histologic subtypes, through cBioPortal. Patient/specimen groups used for analysis were USC and HGSOC. 14 HR genes were queried for each group with respect to mutation frequency. For each HR gene, the difference in mutation frequency between the two groups was evaluated using Fisher's exact test. The threshold for statistical significance was p-value < .05. Results: In the USC group, there were 457 samples from 451 patients. In the HGSOC group, there were 1537 samples from 1515 patients. The most frequently mutated HR gene for USC was BRCA2 (4.84%) and for HGSOC was BRCA1 (9.07%). Mutation frequency was significantly different between USC and HGSOC for BRCA 1 (p < .001) and BRCA2 (p = .0379). For the 12 non-BRCA HR genes, mutation frequency was not significantly different between USC and HGSOC. The rate of patients with at least one HR gene mutation in their profiled tumor was 16.85% for USC and 25.21% of HGSOC. Most USC patients with a somatic HR mutation had only one HR gene mutated. Conclusions: Somatic HR gene mutations were commonly identified in NGS genomic profiling of USC. Mutation frequencies for non-BRCA HR genes were not significantly different between USC and HGSOC. These data add to the growing rationale for HR deficiency tumor testing and targeting (e.g., with PARP inhibitors) in future clinical trial development for women with USC.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; BRCA1 Protein ; BRCA2 Protein ; Cystadenocarcinoma, Serous/genetics ; Female ; Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Homologous Recombination ; Humans ; Middle Aged ; Mutation Rate ; Ovarian Neoplasms/genetics ; Uterine Neoplasms/genetics
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human
Language	English
Publishing date	2020-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2020.08.012
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Article: A clinicopathologic and immunohistochemical study of primary and secondary breast angiosarcoma.

Abada, Evi / Jang, Hyejeong / Kim, Seongho / Ali-Fehmi, Rouba / Bandyopadhyay, Sudeshna

Journal of pathology and translational medicine

2022 Volume 56, Issue 6, Page(s) 342–353

Abstract: Background: We aimed to study the clinicopathologic and immunohistochemical (IHC) (CD117, c-Myc, and p53) characteristics, and overall survival of primary and secondary breast angiosarcoma (BAS).: Methods: This was a retrospective study of BAS cases ... ...

Abstract	Background: We aimed to study the clinicopathologic and immunohistochemical (IHC) (CD117, c-Myc, and p53) characteristics, and overall survival of primary and secondary breast angiosarcoma (BAS). Methods: This was a retrospective study of BAS cases diagnosed between 1997 and 2020 at our institution. Hematoxylin and eosin-stained slides were reviewed for tumor morphology, margin status, and lymph node metastasis. CD117, p53, D2-40, CD31, and c-Myc IHC stains were performed on 11 viable tissue blocks. Additional clinical information was obtained from the electronic medical records. Results: Seventeen patients with BAS were identified. Of these, five (29%) were primary and 12 (71%) were secondary BAS, respectively. The median age at diagnosis for primary BAS was 36 years. The median age at diagnosis for secondary BAS was 67 years. The median time to secondary BAS development following radiotherapy was 6.5 years (range, 2 to 12 years). There was no significant difference between primary and secondary BAS in several histopathologic parameters examined, including histologic grade, necrosis, mitotic count, lymph node metastasis, and positive tumor margins. There was also no difference in CD117, p53, D2-40, CD31, and c-Myc expression by IHC between primary and secondary BAS. During a median followup of 21 months, primary BAS had two (40%) reported deaths and secondary BAS had three (25%) reported deaths. However, this difference in survival between both groups was not statistically significant (hazard ratio, 0.51; 95% confidence interval, 0.09 to 3.28; p = .450). Conclusions: BAS is a rare and aggressive disease. No histologic, IHC (CD117, c-Myc, and p53), or survival differences were identified between primary and secondary BAS in this study.
Language	English
Publishing date	2022-10-27
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	3022395-7
ISSN	2383-7845 ; 2383-7837
ISSN (online)	2383-7845
ISSN	2383-7837
DOI	10.4132/jptm.2022.08.31
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Article: Correlation between steroid receptor expression and response to progestational therapy in patients with atypical endometrial hyperplasia or cancer.

Zaiem, Fadi / Bedi, Mannat / Kheil, Mira / Abujamea, Asem / Jain, Deepti / Rosen, Dovid / Alkaram, Waed / Kim, Seongo / Ali-Fehmi, Rouba / Gogoi, Radhika

Gynecologic oncology reports

2024 Volume 53, Page(s) 101402

Abstract: Background: Conservative management of atypical endometrial hyperplasia (AEH) or endometrial cancer (EMCA) often relies on the treatment of synthetic progestins, which show varied success and response rates. We evaluate the correlation between steroid ... ...

Abstract	Background: Conservative management of atypical endometrial hyperplasia (AEH) or endometrial cancer (EMCA) often relies on the treatment of synthetic progestins, which show varied success and response rates. We evaluate the correlation between steroid receptor expression and response to progestin therapy in patients with AEH and EMCA. Methods: Retrospective cohort study collected data for patients with AEH or EMCA who had an endometrial sample after receiving conservative therapy utilizing either Megestrol acetate or Levonorgestrel Intrauterine device (IUD). Immunohistochemistry (IHC) was performed on pre- and post- treatment biopsy samples to assess androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) expression. IHC scores (1-12) were calculated based on staining intensity and percentage of positive cells. Results and analysis: We identified 15 patients with AEH and EMCA between 2015 and 2023 with the majority of African American ethnicity (53 %). Fourteen patients (93 %) received Megestrol acetate, and 1 patient received Levonorgestrel IUD alone. Three patients ultimately underwent hysterectomy. Seven (46.6 %) endometrial samples had strong positivity for AR, PR and ER expression on pre-treatment biopsies, and only 3 (20 %) of them maintained strong positivity for the 3 receptors in the post-treatment. Patients who successfully responded to the treatment demonstrated a significantly greater decrease in IHC scores after the treatment compared to those who did not respond (p = 0.009). Conclusion: Steroid receptor expression could be used as a possible biomarker for response to progestin therapy in patients undergoing conservative management for AEH and EMCA.
Language	English
Publishing date	2024-04-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2818505-5
ISSN	2352-5789
ISSN	2352-5789
DOI	10.1016/j.gore.2024.101402
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Article ; Online: Breast Carcinoma: Updates in Molecular Profiling 2018.

Bandyopadhyay, Sudeshna / Bluth, Martin H / Ali-Fehmi, Rouba

Clinics in laboratory medicine

2018 Volume 38, Issue 2, Page(s) 401–420

Abstract: The most significant contribution of molecular subtyping of breast carcinomas has been the identification of estrogen-positive and estrogen-negative tumor subtypes. Knowledge of genetic alterations in these tumors will help clinicians identify novel ... ...

Abstract	The most significant contribution of molecular subtyping of breast carcinomas has been the identification of estrogen-positive and estrogen-negative tumor subtypes. Knowledge of genetic alterations in these tumors will help clinicians identify novel therapeutic targets. Understanding the progression pathways involved in the transition of in situ carcinoma to invasive carcinoma might lead to efficient risk stratification in these patients. The Cancer Genome Analysis Network has collected genomic and epigenomic data to provide comprehensive information regarding carcinogenesis and pathway interactions. Such information improves understanding of the disease process and also provides more accurate information toward identifying targetable mutations for treatment.
MeSH term(s)	Breast Neoplasms/classification ; Breast Neoplasms/diagnosis ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Female ; Humans ; Molecular Diagnostic Techniques
Language	English
Publishing date	2018-04-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604580-7
ISSN	1557-9832 ; 0272-2712
ISSN (online)	1557-9832
ISSN	0272-2712
DOI	10.1016/j.cll.2018.02.006
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Article: Atypical glandular cells (AGC): Cytology of glandular lesions of the uterine cervix.

Khan, Mir Yousufuddin Ali / Bandyopadhyay, Sudeshna / Alrajjal, Ahmed / Choudhury, Moumita Saha Roy / Ali-Fehmi, Rouba / Shidham, Vinod B

CytoJournal

2022 Volume 19, Page(s) 31

Abstract: The Pap smear is a well-known screening tool for squamous lesions of the uterine cervix. However, its screening role in glandular lesions is less effective. The incidence of squamous cell carcinoma of the cervix has dramatically decreased with the advent ...

Abstract	The Pap smear is a well-known screening tool for squamous lesions of the uterine cervix. However, its screening role in glandular lesions is less effective. The incidence of squamous cell carcinoma of the cervix has dramatically decreased with the advent of Pap smear and recent understanding related to HPV carcinogenesis of cervical cancers including the advent of HPV vaccines. However, in recent years, the incidence of glandular abnormalities, diagnosed on Pap smears, has increased with greater sensitivity and precision. The incidence of atypical glandular cells (AGC) is approximately 0.18-0.74% of all cervical smears with a reported prevalence of 2.5% among all Pap smears. A high degree of suspicion, good clinical history, and the presence of diagnostic cytomorphological findings are essential for the proper interpretation of glandular cell abnormalities. A methodical approach to evaluate Pap smear greatly helps interpretation and avoids the diagnostic pitfalls. The Bethesda System for reporting cervical cytology has categorized glandular cell abnormalities into various categories as follows: Endocervical adenocarcinoma in situ (AIS)Atypical glandular cells (AGCs) Endocervical cells: a1 NOS or specify in comments; a2 Favor neoplasticEndometrial cells: NOS or specify in comments Adenocarcinoma (AdCa) EndocervicalEndometrialExtrauterineNOS Subtle differences in quantitative and qualitative cytologic features are essential for distinguishing one category from another. In this chapter, we highlight an organized approach for the interpretation of glandular abnormalities in Pap smear for our readers. This is an overview of the Bethesda categories, the reason for classification, and differential diagnosis with key characteristic features. An approach to the methodical evaluation of hyperchromatic crowded groups is discussed with key cytomorphologic differences. An algorithmic approach is suggested to facilitate the interpretation of various AGC categories.
Language	English
Publishing date	2022-04-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2158838-7
ISSN	1742-6413 ; 0974-5963
ISSN (online)	1742-6413
ISSN	0974-5963
DOI	10.25259/CMAS_03_11_2021
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Article ; Online: Clinicopathologic Characteristics and Outcome Descriptors of Metaplastic Breast Carcinoma.

Abada, Evi / Daaboul, Fayez / Ebare, Kingsley / Jang, Hyejeong / Fehmi, Ziad / Kim, Seongho / Ali-Fehmi, Rouba / Bandyopadhyay, Sudeshna

Archives of pathology & laboratory medicine

2022 Volume 146, Issue 3, Page(s) 341–350

Abstract: Context.—: Metaplastic breast carcinoma is an aggressive form of breast cancer that accounts for 0.5% to 3% of all breast cancers.: Objective.—: To study the clinicopathologic characteristics and outcomes of this rare disease.: Design.—: ... ...

Abstract	Context.—: Metaplastic breast carcinoma is an aggressive form of breast cancer that accounts for 0.5% to 3% of all breast cancers. Objective.—: To study the clinicopathologic characteristics and outcomes of this rare disease. Design.—: Retrospective study of patients with a diagnosis of metaplastic breast carcinoma between 2000 and 2019. Hematoxylin-eosin-stained slides were reviewed and additional clinical data were obtained from electronic medical records. Univariable and multivariable Cox proportional hazard regression analyses were used to determine associations between overall survival and several clinicopathologic variables. Results.—: Of the 125 patients with metaplastic breast carcinoma identified, only patients with high-grade disease (N = 115) were included in the data analysis. A total of 38 participants (33%) were white, 66 (57%) were African American, and 11 (10%) belonged to other ethnicities. The median age at diagnosis was 57 years. The median tumor size was 3 cm. Heterologous histology was seen in 30% of cases. Multivariable analyses showed that patients with a larger tumor size had worse overall survival (hazard ratio [HR], 1.25; 95% CI, 1.10-1.44; P < .001). Distant metastatic disease was also associated with worse overall survival on multivariable analysis (HR, 10.27; 95% CI, 2.03-55.54; P = .005). In addition to treatment with either partial or complete mastectomies, 84 patients (73%) received chemotherapy. Multivariable analyses showed that chemotherapy had no effect on overall survival (HR, 0.53; 95% CI, 0.09-6.05; P = .55). Conclusions.—: A larger tumor size and distant metastatic disease are associated with worse overall survival in patients with metaplastic breast carcinoma. Additional studies are needed to further characterize our findings.
MeSH term(s)	Breast Neoplasms/pathology ; Female ; Humans ; Prognosis ; Proportional Hazards Models ; Retrospective Studies
Language	English
Publishing date	2022-01-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2020-0830-OA
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Article ; Online: Accuracy and Reproducibility of Frozen Section Diagnosis in Ovarian Tumors.

Zaiem, Feras / Deirawan, Hany / Kherallah, Raghad / Fehmi, Omar / Jang, Hyejeong / Kim, Seongho / Bandyopadhyay, Sudeshna / Ali-Fehmi, Rouba

Archives of pathology & laboratory medicine

2021 Volume 146, Issue 5, Page(s) 626–631

Abstract: Context.—: Intraoperative consultation-frozen section diagnosis (FSD)-determines tumor pathology and guides the optimal surgical management of ovarian neoplasms intraoperatively.: Objective.—: To evaluate the diagnostic accuracy of the FSD and ... ...

Abstract	Context.—: Intraoperative consultation-frozen section diagnosis (FSD)-determines tumor pathology and guides the optimal surgical management of ovarian neoplasms intraoperatively. Objective.—: To evaluate the diagnostic accuracy of the FSD and analyze the discrepancy between the FSD and final diagnosis. Design.—: This is a retrospective study of 618 ovarian neoplasm FSDs from 2009 to 2018 at a tertiary health care center. The discrepant cases were reviewed and reevaluated by gynecologic and general surgical pathologists. The outcomes of interest were performing unnecessary procedure, returning for a second surgery, and 30-day postoperative mortality. Results.—: The sensitivity and the positive predictive value of the FSD were lower in borderline tumors than in benign and malignant epithelial ovarian tumors. Major and minor discrepancies were identified in 5.3% (33 of 618) and 12.3% of (76 of 618) cases, respectively. A root cause analysis of the major discrepant cases showed that sampling error accounted for 43% (14 of 33). The discrepancy distributions of gynecologic and general surgical pathologists were statistically similar in the overall cohort (P = .65). The overall κ for diagnostic agreement among gynecologic pathologists, general surgical pathologists, and final diagnosis was 0.18 (0.10-0.26, P < .001), implying only a slight overall agreement. Of the major discrepant cases, only 3 had a clinical implication. One overdiagnosed patient underwent an unecessary procedure, and 2 underdiagnosed patients were recommended to return for a second surgery. No patient had 30-day postoperative mortality. Conclusions.—: Frozen section diagnosis remains a definitive diagnostic tool in ovarian neoplasms and plays a crucial role in guiding intraoperative surgical management.
MeSH term(s)	Female ; Frozen Sections/methods ; Humans ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/surgery ; Predictive Value of Tests ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity
Language	English
Publishing date	2021-08-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2020-0686-OA
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Article ; Online: Breast carcinoma: molecular profiling and updates.

Bandyopadhyay, Sudeshna / Ali-Fehmi, Rouba

Clinics in laboratory medicine

2013 Volume 33, Issue 4, Page(s) 891–909

Abstract: The most significant contribution of molecular subtyping of breast carcinomas has been the identification of estrogen-positive and estrogen-negative tumor subtypes, which are 2 distinct entities with differing prognoses and requiring different therapy. ... ...

Abstract	The most significant contribution of molecular subtyping of breast carcinomas has been the identification of estrogen-positive and estrogen-negative tumor subtypes, which are 2 distinct entities with differing prognoses and requiring different therapy. Molecular and genetic analyses can provide prognostic information; however, a thorough histopathologic evaluation with an evaluation of predictive biomarkers will provide similar information. Knowledge of genetic alterations in these tumors will help identify novel therapeutic targets, which might have an impact on prognosis. Understanding the progression pathways involved in the transition of in situ carcinoma to invasive carcinoma might lead to efficient risk stratification in these patients.
MeSH term(s)	Breast Neoplasms ; Female ; Humans ; Molecular Diagnostic Techniques
Language	English
Publishing date	2013-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604580-7
ISSN	1557-9832 ; 0272-2712
ISSN (online)	1557-9832
ISSN	0272-2712
DOI	10.1016/j.cll.2013.08.009
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