International Journal of Gynecological Pathology最新文献

PTCH1::GLI1 Fusion Tumors of the Ovary: A Clinicopathologic Study of 3 Cases. 卵巢PTCH1::GLI1融合瘤3例临床病理分析

IF 1.6 4区医学

International Journal of Gynecological Pathology Pub Date : 2025-07-16 DOI: 10.1097/PGP.0000000000001110

Rania Bakkar, Michelle Afkhami, Bonnie Balzer, Horacio Maluf, Mihae Song, Robin Moore, Lois Ramondetta, Diana Bell, Anais Malpica

{"title":"PTCH1::GLI1 Fusion Tumors of the Ovary: A Clinicopathologic Study of 3 Cases.","authors":"Rania Bakkar, Michelle Afkhami, Bonnie Balzer, Horacio Maluf, Mihae Song, Robin Moore, Lois Ramondetta, Diana Bell, Anais Malpica","doi":"10.1097/PGP.0000000000001110","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001110","url":null,"abstract":"GLI1-altered tumors of the gynecologic tract are extremely rare. We report 3 cases of ovarian PTCH1::GLI1 fusion tumor in patients ranging from 54 to 58 yrs of age, who presented with unilateral FIGO stage I tumors. The tumors ranged from 12 to 20 cm and consisted of uniform epithelioid cells with eosinophilic/clear cytoplasm, arranged in nests and trabeculae surrounded by delicate vessels. Variable features included short spindle cells within a myxoid stroma, follicles, small glands/Call-Exner body-like structures, dilated vessels/blood lakes, focal pleomorphism, nuclear grooves, and necrosis. Mitoses ranged from 1 to 10/10 HPFs. Immunohistochemical marker results/number of tumors tested (including primary tumors and recurrences) were as follows: positive for SF-1 (6/6), CD56 (4/4), EMA (3/5), keratins (3/5), SMA (2/5), CD10 (3/4), S100 (3/4), caldesmon (2/3), D2-40 (2/2), Ber-EP4 (2/2), and MOC-31 (1/1), and negative for WT-1 (5/5), calretinin (5/5), inhibin (4/5), ER (4/5), and PR (5/5). Diagnoses initially rendered included adult granulosa cell tumor, unclassified sex cord-stromal tumor, low-grade Müllerian adenocarcinoma, and low-grade endometrioid stromal sarcoma. Surgery was the primary treatment for all. One patient had multiple recurrences at 7, 9, and 13 yrs, had additional surgery, received chemotherapy and radiotherapy, and was alive with no evidence of disease at 13.6 yrs. Another patient had omental recurrence at 5 yrs, received chemotherapy, immunotherapy, and tyrosine kinase inhibitor-targeted therapy, and was alive with disease at 7.9 yrs. The third patient was alive with no evidence of disease at 2 mos. Ovarian PTCH1::GLI1 fusion tumors represent a diagnostic challenge and may recur after several years. Their proper recognition may prompt the use of targeted therapy.","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Uterine Mesenchymal Neoplasm With BRD8::PHF1 Fusion: Low-grade Endometrial Stromal Sarcoma or Uterine Ossifying Fibromyxoid Tumor? 子宫间质肿瘤合并BRD8::PHF1融合：低级别子宫内膜间质肉瘤还是子宫骨化纤维黏液样肿瘤？

IF 1.6 4区医学

International Journal of Gynecological Pathology Pub Date : 2025-07-16 DOI: 10.1097/PGP.0000000000001108

Niall O'Neill, James Sampson, W Glenn McCluggage

引用次数: 0

Histotype and Grade Are of Prognostic Significance in the No Specific Molecular Prolife Molecular Subtype of Endometrial Carcinoma But Not in POLEmut, MMRd, or p53abn Endometrial Carcinomas: Results From a 2478 Case Series and a Systematic Review of the Literature. 组织型和分级在子宫内膜癌的无特异性分子增殖分子亚型中具有预后意义，但在POLEmut， MMRd或p53abn子宫内膜癌中没有：来自2478例病例系列和文献系统回顾的结果。

IF 1.6 4区医学

International Journal of Gynecological Pathology Pub Date : 2025-07-10 DOI: 10.1097/PGP.0000000000001120

Jutta Huvila, Aline Talhouk, Blake Gilks, Jessica N McAlpine, Amy Jamieson

{"title":"Histotype and Grade Are of Prognostic Significance in the No Specific Molecular Prolife Molecular Subtype of Endometrial Carcinoma But Not in POLEmut, MMRd, or p53abn Endometrial Carcinomas: Results From a 2478 Case Series and a Systematic Review of the Literature.","authors":"Jutta Huvila, Aline Talhouk, Blake Gilks, Jessica N McAlpine, Amy Jamieson","doi":"10.1097/PGP.0000000000001120","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001120","url":null,"abstract":"Histotype and grade of endometrial carcinoma (EC) have been cornerstones of risk assessment, as both are known to be associated with differences in prognosis. The aim of this study was to analyze the prognostic significance of grade and histotype (comparing low-grade endometrioid, high-grade endometrioid, serous, and all others) within each EC molecular subtype, with further stratification by stage. A cohort of 2478 patients with EC were identified from our center. Disease-specific survival was compared for tumors of each molecular subtype after stratification of patients into 1 of 4 groups (low-grade endometrioid, high-grade endometrioid, serous, other). In addition, a systematic review of the literature was undertaken to identify all previous studies where the prognostic significance of grade and histotype within molecular subtypes was reported. Grade and histotype were not of prognostic significance in POLEmut or p53abn EC across all stages and when just considering stage I ECs. MMRd low-grade ECs were associated with a better prognosis; however, they were also associated with lower stage disease, and within stage I tumors, grade and histotype were not of prognostic significance. Grade and histotype were of prognostic significance in NSMP ECs, in all stages and in the subset of stage I tumors (P<0.001 for both analyses). On a systematic review of the literature, we identified 7 studies; there was no prognostic significance of grade and histotype (comparing low-grade endometrioid, high-grade endometrioid and serous) in POLEmut, and p53abn EC, and no prognostic significance of grade and histotype independent of stage in MMRd. Histotype and grade are strongly associated with prognosis in NSMP EC, but not in other molecular subtypes.","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antibody-drug Conjugate Biomarker Expression in Gestational Trophoblastic Disease: Folate Receptor Alpha, Nectin-4, Trop-2, and Tissue Factor. 抗体-药物偶联生物标志物在妊娠滋养细胞疾病中的表达：叶酸受体α、连接素-4、Trop-2和组织因子。

IF 1.6 4区医学

International Journal of Gynecological Pathology Pub Date : 2025-07-10 DOI: 10.1097/PGP.0000000000001119

Lawrence Hsu Lin, Kathleen T Hasselblatt, Carlos Parra-Herran, Neil S Horowitz, Ross S Berkowitz, Bradley J Quade, Kevin M Elias

{"title":"Antibody-drug Conjugate Biomarker Expression in Gestational Trophoblastic Disease: Folate Receptor Alpha, Nectin-4, Trop-2, and Tissue Factor.","authors":"Lawrence Hsu Lin, Kathleen T Hasselblatt, Carlos Parra-Herran, Neil S Horowitz, Ross S Berkowitz, Bradley J Quade, Kevin M Elias","doi":"10.1097/PGP.0000000000001119","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001119","url":null,"abstract":"Antibody-drug conjugates (ADC) are emerging therapies with promising results in the treatment of solid tumors. In this study, we aimed to evaluate biomarker expression of ADCs, including folate receptor alpha (FOLR1), Nectin-4, trophoblast cell surface antigen 2 (Trop-2), and tissue factor (TF) in a diverse cohort of gestational trophoblastic disease. Immunohistochemistry for FOLR1, Nectin-4, Trop-2, and TF was evaluated in tissue microarray of 18 complete hydatidiform moles (CHM) and whole tissue sections of 62 gestational trophoblastic neoplasia (GTN) by 2 gynecologic pathologists. Western blotting for FOLR1, Nectin-4, and Trop-2 was performed in JEG-3 and JAR choriocarcinoma cell lines, 2 CHM and 3 GTN clinical samples. Results: The overall immunohistochemical positive rate in GTN was 11% for FOLR1, 59% for Nectin-4, 38% for Trop-2, and 26% for TF. Choriocarcinomas showed 27% positivity for FOLR1, 75% for Nectin-4, 40% for Trop-2, and 25% for TF. Epithelioid trophoblastic tumors (ETT) were positive for Nectin-4 in 58%, for Trop-2 in 79%, and for TF in 67% of cases. Placental site trophoblastic tumors were positive only for Nectin-4 (23% of cases). In CHM, only Nectin-4 revealed a higher degree of expression and limited staining for the other markers. Western blotting showed FOLR1 expression in CHM, JEG-3, and JAR; Nectin-4 in CHM and PSTT; and Trop-2 in CHM, JEG-3, and choriocarcinoma. Conclusion: A subset of GTN shows expression for FOLR1, Nectin-4, Trop-2, and TF, particularly choriocarcinoma and ETT. These results suggest that patients with GTN could potentially benefit from ADC treatment.","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HPV-negative Differentiated Intraepithelial Neoplasia in the Anogenital Region Including the Cervix. 包括子宫颈在内的肛门生殖器区hpv阴性分化上皮内瘤变。

IF 1.6 4区医学

International Journal of Gynecological Pathology Pub Date : 2025-07-10 DOI: 10.1097/PGP.0000000000001105

Sigrid Regauer, Olaf Reich

引用次数: 0

EML4::NTRK3 Rearranged Ovarian Neoplasm: Case Report and Literature Review. EML4::NTRK3重排卵巢肿瘤病例报告及文献复习。

IF 1.6 4区医学

International Journal of Gynecological Pathology Pub Date : 2025-07-07 DOI: 10.1097/PGP.0000000000001122

Steven H Smith, Emily Hinchcliff, Christopher Felicelli

引用次数: 0

Cellular Angiofibroma With Sarcomatous Transformation: Case Report With Molecular Characterization and Review of the Literature. 细胞血管纤维瘤伴肉瘤转化：1例分子表征及文献复习。

IF 1.6 4区医学

International Journal of Gynecological Pathology Pub Date : 2025-07-07 DOI: 10.1097/PGP.0000000000001123

Haley Corbin, Esther Elishaev, Ivy John, Catherine K Gestrich, John M Skaugen, Rohit Bhargava

{"title":"Cellular Angiofibroma With Sarcomatous Transformation: Case Report With Molecular Characterization and Review of the Literature.","authors":"Haley Corbin, Esther Elishaev, Ivy John, Catherine K Gestrich, John M Skaugen, Rohit Bhargava","doi":"10.1097/PGP.0000000000001123","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001123","url":null,"abstract":"Cellular angiofibroma is a benign mesenchymal neoplasm which usually occurs in the vulvovaginal or inguinoscrotal areas. Although benign, cellular angiofibroma may rarely undergo sarcomatous transformation. We report a case of vulvar cellular angiofibroma with sarcomatous transformation in a 62-yr-old woman and a literature review of previously reported cases. By immunohistochemistry, our case was positive for vimentin and ER, mostly negative for smooth muscle markers, and showed patchy reactivity for CD10, Pan-TRK, and Rb1. The bland component was negative for p16 with wild-type p53 expression, while the sarcomatous area showed strong, diffuse p16 staining with p53 overexpression. Targeted DNA and RNA next-generation sequencing of the bland area showed chromosome 9p/9q copy number loss, while the sarcomatous area showed TP53 (p.G154V) mutation (90% allele frequency) and copy number loss of chromosome 17p (including TP53). Whole transcriptome sequencing was negative for tumor-associated gene fusions. As the lesion was completely encapsulated and excised, and with limited published data indicating an uneventful clinical course, the decision was made to follow the patient with no further therapeutic intervention. Four months following excision, the patient has no signs or symptoms of local recurrence.","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leiomyosarcomas of the Visceral Adnexal and Uterine Ligaments and Adnexal Connective Tissue: Immunohistochemical, Molecular Genetic, and MDM2 Fluorescence In Situ Hybridization Analysis. 内脏附件和子宫韧带及附件结缔组织的子宫肌瘤：免疫组化、分子遗传和 MDM2 荧光原位杂交分析。

IF 1.6 4区医学

International Journal of Gynecological Pathology Pub Date : 2025-07-01 Epub Date: 2024-07-23 DOI: 10.1097/PGP.0000000000001064

Nooshin K Dashti, Amy A Swanson, Vatsal Patel, Deyin Xing, Michael Feely, Gary L Keeney, Sounak Gupta, J Kenneth Schoolmeester

引用次数: 0

TP53 Mutations and PD-L1 Amplification in Vulvar Adenocarcinoma of the Intestinal Type: Insights From Whole Exome Sequencing of 2 Cases. 肠型外阴腺癌TP53突变和PD-L1扩增：来自2例全外显子组测序的启示

IF 1.6 4区医学

International Journal of Gynecological Pathology Pub Date : 2025-07-01 Epub Date: 2025-01-09 DOI: 10.1097/PGP.0000000000001093

Erisa Fujii, Mayumi Kobayashi Kato, Hanako Ono, Maiko Yamaguchi, Daiki Higuchi, Takafumi Koyama, Masaaki Komatsu, Ryuji Hamamoto, Mitsuya Ishikawa, Tomoyasu Kato, Takashi Kohno, Kouya Shiraishi, Hiroshi Yoshida

{"title":"TP53 Mutations and PD-L1 Amplification in Vulvar Adenocarcinoma of the Intestinal Type: Insights From Whole Exome Sequencing of 2 Cases.","authors":"Erisa Fujii, Mayumi Kobayashi Kato, Hanako Ono, Maiko Yamaguchi, Daiki Higuchi, Takafumi Koyama, Masaaki Komatsu, Ryuji Hamamoto, Mitsuya Ishikawa, Tomoyasu Kato, Takashi Kohno, Kouya Shiraishi, Hiroshi Yoshida","doi":"10.1097/PGP.0000000000001093","DOIUrl":"10.1097/PGP.0000000000001093","url":null,"abstract":"Vulvar adenocarcinoma of the intestinal type (VAIt) is a rare subtype of primary vulvar carcinoma, with ∼30 cases documented in the English literature. This study presents 2 new cases of HPV-independent VAIt with lymph node metastasis and discusses their clinical presentation, histopathologic features, and whole exome sequencing (WES) analysis. Both cases exhibited histologic features consistent with VAIt, including tubular, papillary, and mucinous carcinoma components. Immunohistochemical analysis showed p16 patchy staining, CDX2, CK20, and SATB2 positivity, while being negative for ER, PAX8, and CK7. WES revealed pathogenic TP53 mutations in both cases, accompanied by distinct additional mutations ( GRIN2A and KDM6A in Case #1; CHD4 in Case #2). Common copy number alterations (CNAs) included TP53 loss of heterozygosity and CD274/PD-L1 amplification. However, other CNAs varied between the cases. Immunohistochemistry for p53 suggests the presence of both wild-type and mutant subclones, indicating that TP53 abnormalities may be acquired during tumor progression. Both tumors showed mutational signatures SBS1 and SBS5, associated with aging and DNA damage. Our findings deepen the understanding of the genetic events involved in the tumorigenesis of HPV-independent VAIt. Given the TP53 abnormalities and CD274/PD-L1 amplification, emerging p53-based therapies and immune checkpoint inhibitors may represent potential treatment targets. While these findings contribute to the understanding of VAIt tumorigenesis, further research is required to validate these observations in a larger cohort.","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"358-363"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of Immunohistochemical Analysis of p16 and p53 in Vulvar Carcinoma. 外阴癌中 p16 和 p53 免疫组化分析的作用

IF 1.6 4区医学

International Journal of Gynecological Pathology Pub Date : 2025-07-01 Epub Date: 2024-10-31 DOI: 10.1097/PGP.0000000000001077

Matthias Choschzick, Andre Gut, Ladina Hoesli, Cristina Stergiou

{"title":"Role of Immunohistochemical Analysis of p16 and p53 in Vulvar Carcinoma.","authors":"Matthias Choschzick, Andre Gut, Ladina Hoesli, Cristina Stergiou","doi":"10.1097/PGP.0000000000001077","DOIUrl":"10.1097/PGP.0000000000001077","url":null,"abstract":"Tumor human papillomavirus (HPV) status is an important prognostic factor in vulvar cancer as indicated in the latest WHO classification of female genital tract tumors. Immunohistochemical detection of p16 is well established as a surrogate biomarker for tumor HPV association, including squamous cell carcinomas of the vulva. HPV-independent vulvar carcinomas are heterogeneous with 2 subcategories according to the TP53 mutation status. Therefore, the simultaneous use of p53 and p16 immunohistochemistry is recommended for accurate subclassification of vulvar squamous cell carcinomas. However, the role of molecular analytical tools, in particular RNA ISH and TP53 sequencing, is not so clear. This study aimed to investigate the performance of p53 and p16 immunohistochemistry for the diagnosis of vulvar carcinomas in comparison to TP53 mutation analysis and HPV RNA ISH. We analyzed 48 vulvar carcinomas in a tissue microarray format. Sensitivity and specificity for both methods, p16 (100% and 96%) and p53 (95% and 90%) immunohistochemistry for detection of HPV association as well as for TP53 mutations was high. Combining p16 and p53 immunohistochemistry we correctly classified all carcinomas in our series according to current WHO criteria. The sensitivity of HPV RNA ISH for the detection of HPV association was lower compared to p16 immunohistochemistry. Rare HPV-associated cases with TP53 mutation and HPV-independent tumors with p16 overexpression are discussed. In summary, the combined use of p16 and p53 immunohistochemistry for subclassification of vulvar carcinomas is justified in daily practice. Molecular tests should be restricted to rare cases with ambiguous clinicopathologic or immunohistochemical features.","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"308-313"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0