Pub Date : 2025-07-01Epub Date: 2024-07-23DOI: 10.1097/PGP.0000000000001064
Nooshin K Dashti, Amy A Swanson, Vatsal Patel, Deyin Xing, Michael Feely, Gary L Keeney, Sounak Gupta, J Kenneth Schoolmeester
{"title":"Leiomyosarcomas of the Visceral Adnexal and Uterine Ligaments and Adnexal Connective Tissue: Immunohistochemical, Molecular Genetic, and MDM2 Fluorescence In Situ Hybridization Analysis.","authors":"Nooshin K Dashti, Amy A Swanson, Vatsal Patel, Deyin Xing, Michael Feely, Gary L Keeney, Sounak Gupta, J Kenneth Schoolmeester","doi":"10.1097/PGP.0000000000001064","DOIUrl":"10.1097/PGP.0000000000001064","url":null,"abstract":"","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"355-357"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125672","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}
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.
{"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":"<p><p>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.</p>","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}
Pub Date : 2025-07-01Epub Date: 2024-10-31DOI: 10.1097/PGP.0000000000001077
Matthias Choschzick, Andre Gut, Ladina Hoesli, Cristina Stergiou
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.
{"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":"<p><p>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.</p>","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}
Pub Date : 2025-07-01Epub Date: 2025-01-20DOI: 10.1097/PGP.0000000000001096
Samah Saharti, Fadwa Altaf
Abstract: Endometrial carcinoma is a heterogeneous disease with distinct molecular subtypes that have varied prognosis and therapeutic implications. Since the development of molecular signatures of malignancy is prominent, we are trying to implement this development in our cases of previously diagnosed endometrial cancer. The aim was to determine the prevalence of specific molecular alterations and correlate the genetic profile with the pathologic features and clinical characteristics. We identified 100 cases of endometrial carcinoma, which were eventually classified using immunostains for mismatch repair (MMR) and p53 proteins, in addition to Sanger analysis for POLE gene (Ex, 9, 13, 14). Our findings showed a high prevalence of nonspecific molecular profile (NSMP) in 46 cases (46%), and MMR deficiency in 30 cases (30%). The worst prognosis was observed in the p53 mutant pattern expressed tumors. No statistical difference in pathologic characteristics was observed when the molecular classification was applied. Of note, mutual molecular grouping assignment appears to be present in 5 (5%) of cases of endometrial carcinoma. This is the first study conducted in Saudi Arabia that investigated the prevalence and implications of these molecular subtypes in endometrial carcinoma. The percentage of cases in our result is similar to what had been published globally.
{"title":"Molecular Classification of Endometrial Carcinoma: Insights From a Teaching Hospital.","authors":"Samah Saharti, Fadwa Altaf","doi":"10.1097/PGP.0000000000001096","DOIUrl":"10.1097/PGP.0000000000001096","url":null,"abstract":"<p><strong>Abstract: </strong>Endometrial carcinoma is a heterogeneous disease with distinct molecular subtypes that have varied prognosis and therapeutic implications. Since the development of molecular signatures of malignancy is prominent, we are trying to implement this development in our cases of previously diagnosed endometrial cancer. The aim was to determine the prevalence of specific molecular alterations and correlate the genetic profile with the pathologic features and clinical characteristics. We identified 100 cases of endometrial carcinoma, which were eventually classified using immunostains for mismatch repair (MMR) and p53 proteins, in addition to Sanger analysis for POLE gene (Ex, 9, 13, 14). Our findings showed a high prevalence of nonspecific molecular profile (NSMP) in 46 cases (46%), and MMR deficiency in 30 cases (30%). The worst prognosis was observed in the p53 mutant pattern expressed tumors. No statistical difference in pathologic characteristics was observed when the molecular classification was applied. Of note, mutual molecular grouping assignment appears to be present in 5 (5%) of cases of endometrial carcinoma. This is the first study conducted in Saudi Arabia that investigated the prevalence and implications of these molecular subtypes in endometrial carcinoma. The percentage of cases in our result is similar to what had been published globally.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"336-339"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468169","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}
The incidence of neurotrophic tyrosine kinase receptor ( NTRK ) fusion uterine sarcoma is extremely low, and reports have been mostly focused on cases localized to the cervix. So far, only 4 cases have been reported of the uterine corpus. In this study, we reported a case of NTRK fusion corpus sarcoma. This study aimed to expand the morphologic spectrum of this tumor, which showed adenosarcoma-like features not previously described. The tumor was confined to the uterine corpus, polypoid growth, comprised predominantly of a fascicular proliferation of spindle cells, entrapping benign endometrial glands, and exhibited a pseudo-biphasic growth pattern. The tumor showed coexpression of S-100, CD34, and pan-Trk by immunohistochemistry, DNA-sequencing identified TPR-NTRK1 gene fusion and AKT1(E17K) mutation. Four cases of NTRK fusion corpus sarcoma were reviewed. The clinicopathologic features, immunohistochemical phenotype, molecular testing, and prognosis of 5 cases including this one were summarized and analyzed. Most cases exhibited an infiltrative growth pattern and showed mild or moderate cytologic atypia. The potential for these tumors to be misclassified as uterine adenosarcoma or other uterine mesenchymal tumors. The diagnosis relies on pan-Trk, S-100, CD34 immunohistochemistry, and molecular testing. Surgical resection is the mainstay of treatment for most patients. Distinguishing these tumors from morphologic mimics is significant because patients with advanced-stage disease may be treated with TRK inhibitors.
{"title":"A Case of NTRK Fusion Corpus Sarcoma With Pseudobiphasic Growth Pattern and Literature Review.","authors":"Xiao-Ying Zhang, Han-Wen Jiang, Xiao-Bo Wen, Qian Yu, Ying Li, Hao Wang, Jing Han, Shi-Cong Yang","doi":"10.1097/PGP.0000000000001078","DOIUrl":"10.1097/PGP.0000000000001078","url":null,"abstract":"<p><p>The incidence of neurotrophic tyrosine kinase receptor ( NTRK ) fusion uterine sarcoma is extremely low, and reports have been mostly focused on cases localized to the cervix. So far, only 4 cases have been reported of the uterine corpus. In this study, we reported a case of NTRK fusion corpus sarcoma. This study aimed to expand the morphologic spectrum of this tumor, which showed adenosarcoma-like features not previously described. The tumor was confined to the uterine corpus, polypoid growth, comprised predominantly of a fascicular proliferation of spindle cells, entrapping benign endometrial glands, and exhibited a pseudo-biphasic growth pattern. The tumor showed coexpression of S-100, CD34, and pan-Trk by immunohistochemistry, DNA-sequencing identified TPR-NTRK1 gene fusion and AKT1(E17K) mutation. Four cases of NTRK fusion corpus sarcoma were reviewed. The clinicopathologic features, immunohistochemical phenotype, molecular testing, and prognosis of 5 cases including this one were summarized and analyzed. Most cases exhibited an infiltrative growth pattern and showed mild or moderate cytologic atypia. The potential for these tumors to be misclassified as uterine adenosarcoma or other uterine mesenchymal tumors. The diagnosis relies on pan-Trk, S-100, CD34 immunohistochemistry, and molecular testing. Surgical resection is the mainstay of treatment for most patients. Distinguishing these tumors from morphologic mimics is significant because patients with advanced-stage disease may be treated with TRK inhibitors.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"374-383"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01Epub Date: 2025-01-09DOI: 10.1097/PGP.0000000000001092
Ferheen Abbasi, Marisa R Nucci, Ben Doron, Rachel Ruskin, Jeremy Chien, Jaclyn C Watkins, Anthony N Karnezis
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare, typically benign uterine tumor occurring over a wide age range (mean 52.4 yr). UTROSCTs often harbor translocations between ESR1 and nuclear receptor coactivators NCOA1-NCOA3 . Here, we present a 21-yr-old woman with a 16 cm complex uterine mass on CT. Grossly, the tumor had an infiltrative appearance. Histologically, it consisted of mild to moderately atypical, spindled cells with ovoid nuclei, growing in fascicles and cords within fibrous to myxohyaline stroma, with tongue-like infiltration of the myometrium. Immunohistochemically, tumor cells were positive for AE1/AE3, ER, PR, vimentin, WT-1, and CD56, and negative for inhibin, calretinin, SMA, desmin, and CD10. Whole exome and whole transcriptome sequencing identified a pathogenic ESR1::CITED2 fusion. The tumor recurred twice (15 and 21 mo after initial surgery) in the abdomen and pelvis. Taken together, the findings suggest this tumor may represent a malignant UTROSCT variant with a novel translocation.
{"title":"Case Report: ESR1::CITED2 Fusion in a Malignant Uterine Tumor Resembling Ovarian Sex Cord Tumor.","authors":"Ferheen Abbasi, Marisa R Nucci, Ben Doron, Rachel Ruskin, Jeremy Chien, Jaclyn C Watkins, Anthony N Karnezis","doi":"10.1097/PGP.0000000000001092","DOIUrl":"10.1097/PGP.0000000000001092","url":null,"abstract":"<p><p>Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare, typically benign uterine tumor occurring over a wide age range (mean 52.4 yr). UTROSCTs often harbor translocations between ESR1 and nuclear receptor coactivators NCOA1-NCOA3 . Here, we present a 21-yr-old woman with a 16 cm complex uterine mass on CT. Grossly, the tumor had an infiltrative appearance. Histologically, it consisted of mild to moderately atypical, spindled cells with ovoid nuclei, growing in fascicles and cords within fibrous to myxohyaline stroma, with tongue-like infiltration of the myometrium. Immunohistochemically, tumor cells were positive for AE1/AE3, ER, PR, vimentin, WT-1, and CD56, and negative for inhibin, calretinin, SMA, desmin, and CD10. Whole exome and whole transcriptome sequencing identified a pathogenic ESR1::CITED2 fusion. The tumor recurred twice (15 and 21 mo after initial surgery) in the abdomen and pelvis. Taken together, the findings suggest this tumor may represent a malignant UTROSCT variant with a novel translocation.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"368-373"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046073","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}
Vulval leiomyosarcomas with variant features are rare with limited data available in the literature compared to their uterine counterparts. Gynecologic leiomyosarcoma with nuclear receptor 4A3 (NR4A3) gene fusion is a rare, recently described neoplasm that has been reported mostly in the uterus and rarely in the pelvis. Herein, we report the first case of this entity occurring as a primary vulva tumor in a 46-year-old patient. Histologic examination showed a multi-nodular tumor composed of monomorphic epithelioid, rhabdoid and spindled cells arranged in sheets, cords and microcysts within a richly vascularised, myxoid stroma. On immunohistochemistry, the tumor cells were positive for desmin, smooth muscle actin, h-caldesmon, as well as ER and WT1. Gene fusion analysis revealed the presence of a PGR::NR4A3 gene fusion involving exon 2 of PGR and exon 2 of NR4A3 . Local recurrence occurred one year after initial excision. Recognition of this rare subtype of gynecologic leiomyosarcoma in the vulva may help refine the classification of unusual vulvovaginal smooth muscle neoplasms.
{"title":"Gynecologic Leiomyosarcoma With Epithelioid Features and PGR::NR4A3 Gene Fusion: First Report in the Vulva.","authors":"Prerna Chadha, Justin Soon Boon Wong, Dimple Kandhari Ahluwalia, Jeffrey Jen Hui Low, Yingting Mok","doi":"10.1097/PGP.0000000000001089","DOIUrl":"10.1097/PGP.0000000000001089","url":null,"abstract":"<p><p>Vulval leiomyosarcomas with variant features are rare with limited data available in the literature compared to their uterine counterparts. Gynecologic leiomyosarcoma with nuclear receptor 4A3 (NR4A3) gene fusion is a rare, recently described neoplasm that has been reported mostly in the uterus and rarely in the pelvis. Herein, we report the first case of this entity occurring as a primary vulva tumor in a 46-year-old patient. Histologic examination showed a multi-nodular tumor composed of monomorphic epithelioid, rhabdoid and spindled cells arranged in sheets, cords and microcysts within a richly vascularised, myxoid stroma. On immunohistochemistry, the tumor cells were positive for desmin, smooth muscle actin, h-caldesmon, as well as ER and WT1. Gene fusion analysis revealed the presence of a PGR::NR4A3 gene fusion involving exon 2 of PGR and exon 2 of NR4A3 . Local recurrence occurred one year after initial excision. Recognition of this rare subtype of gynecologic leiomyosarcoma in the vulva may help refine the classification of unusual vulvovaginal smooth muscle neoplasms.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"364-367"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614883","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}
Pub Date : 2025-07-01Epub Date: 2025-04-29DOI: 10.1097/PGP.0000000000001109
Ting Zhao, Yin P Hung, Kyle M Devins, Robert H Young, Esther Oliva
Upper female genital tract vascular proliferations are rare and generally not well characterized. We evaluated types, differences in distribution, and associations of such lesions. Fifty-five vascular lesions were identified: 42 benign (ovary 24; uterine corpus 11; para-adnexal 4; fallopian tube 1; ovaries, fallopian tubes, and corpus 1; ovary and fallopian tube 1) and 13 angiosarcomas. Patients with benign vascular lesions had a mean age of 55 (range: 13-82) yr. Twenty-six lesions were incidental findings, and 11 were associated with clinical manifestations. They had a mean size of 2.0 (range: <1-13) cm, and often were grossly cystic and hemorrhagic. Uterine benign vascular lesions included 6 arteriovenous malformations, 3 venous hemangiomas/malformations, 2 cavernous hemangiomas, and 1 mixed venous-cavernous hemangioma. In the ovary, there were 10 anastomosing hemangiomas, 8 arteriovenous malformations, 6 venous (2 in mature cystic teratomas, 1 bilateral in a patient with Klippel-Trenaunay syndrome), and 2 cavernous hemangiomas. Anastomosing hemangiomas were frequently associated with peripheral stromal luteinization/hilar cell hyperplasia; intravascular growth, extramedullary hematopoiesis, and one with adipocytic metaplasia. Venous hemangiomas/malformations were noted at a younger age in the ovary when compared to the uterine corpus. Patients with angiosarcomas had a mean age of 32 (range: 12-58) yr and a mean tumor size of 9.7 (range: 1.5-23) cm. Eight presented with a pelvic mass. Most angiosarcomas were grossly hemorrhagic and/or necrotic. Eleven arose in the ovary, 4 of them were associated with mature cystic teratoma, 1 with adenosarcoma with sarcomatous overgrowth, and 1 was part of a malignant mesenchymoma. Five were predominantly spindled, 3 epithelioid, 2 spindled and epithelioid, and one pleomorphic. Both uterine angiosarcomas were epithelioid. Follow-up was available for 8 patients: 7 died of disease between 6 and 43 mo, and 1 was alive and well at 106 mo. Vascular lesions in the upper female genital tract are uncommon, morphologically heterogeneous, and more frequent and clinically evident in the adnexa. Anastomosing hemangioma is the most common benign vascular lesion in the ovary and may be misdiagnosed as a steroid cell tumor due to associated stromal luteinization/hilar cell hyperplasia. Arteriovenous malformation is the most common benign vascular lesion in the uterine corpus. Angiosarcomas may be associated with another neoplasm, more commonly mature cystic teratoma, and have a poor prognosis.
{"title":"The Spectrum of Vascular Lesions of the Upper Female Genital Tract: A Report of 55 Cases.","authors":"Ting Zhao, Yin P Hung, Kyle M Devins, Robert H Young, Esther Oliva","doi":"10.1097/PGP.0000000000001109","DOIUrl":"10.1097/PGP.0000000000001109","url":null,"abstract":"<p><p>Upper female genital tract vascular proliferations are rare and generally not well characterized. We evaluated types, differences in distribution, and associations of such lesions. Fifty-five vascular lesions were identified: 42 benign (ovary 24; uterine corpus 11; para-adnexal 4; fallopian tube 1; ovaries, fallopian tubes, and corpus 1; ovary and fallopian tube 1) and 13 angiosarcomas. Patients with benign vascular lesions had a mean age of 55 (range: 13-82) yr. Twenty-six lesions were incidental findings, and 11 were associated with clinical manifestations. They had a mean size of 2.0 (range: <1-13) cm, and often were grossly cystic and hemorrhagic. Uterine benign vascular lesions included 6 arteriovenous malformations, 3 venous hemangiomas/malformations, 2 cavernous hemangiomas, and 1 mixed venous-cavernous hemangioma. In the ovary, there were 10 anastomosing hemangiomas, 8 arteriovenous malformations, 6 venous (2 in mature cystic teratomas, 1 bilateral in a patient with Klippel-Trenaunay syndrome), and 2 cavernous hemangiomas. Anastomosing hemangiomas were frequently associated with peripheral stromal luteinization/hilar cell hyperplasia; intravascular growth, extramedullary hematopoiesis, and one with adipocytic metaplasia. Venous hemangiomas/malformations were noted at a younger age in the ovary when compared to the uterine corpus. Patients with angiosarcomas had a mean age of 32 (range: 12-58) yr and a mean tumor size of 9.7 (range: 1.5-23) cm. Eight presented with a pelvic mass. Most angiosarcomas were grossly hemorrhagic and/or necrotic. Eleven arose in the ovary, 4 of them were associated with mature cystic teratoma, 1 with adenosarcoma with sarcomatous overgrowth, and 1 was part of a malignant mesenchymoma. Five were predominantly spindled, 3 epithelioid, 2 spindled and epithelioid, and one pleomorphic. Both uterine angiosarcomas were epithelioid. Follow-up was available for 8 patients: 7 died of disease between 6 and 43 mo, and 1 was alive and well at 106 mo. Vascular lesions in the upper female genital tract are uncommon, morphologically heterogeneous, and more frequent and clinically evident in the adnexa. Anastomosing hemangioma is the most common benign vascular lesion in the ovary and may be misdiagnosed as a steroid cell tumor due to associated stromal luteinization/hilar cell hyperplasia. Arteriovenous malformation is the most common benign vascular lesion in the uterine corpus. Angiosarcomas may be associated with another neoplasm, more commonly mature cystic teratoma, and have a poor prognosis.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"291-307"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077986","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}
Pub Date : 2025-07-01Epub Date: 2024-07-30DOI: 10.1097/PGP.0000000000001059
Kristýna Němejcová, Adam Šafanda, Michaela Kendall Bártů, Nikola Hájková, Jana Drozenová, Pavel Fabian, Jan Laco, Radoslav Matěj, Gábor Méhes, Petr Škapa, Ivana Stružinská, Pavel Dundr
Using immunohistochemistry, we examined a large cohort of 135 ovarian tumors, made up of 96 low-grade serous carcinomas (LGSCs) and 39 serous borderline tumors (micropapillary variant, mSBT), with the aim of exploring their HER2 status (overexpression). We followed with comprehensive genomic analyses on this sample set from our previous study, which revealed HER2 mutation in 5% (4/75) of LGSC and 10% (3/29) of mSBT. No cases were evaluated as HER2-positive, but 6 LGSCs and 1 mSBT were scored as HER2 1+, and 2 LGSCs and 1 mSBT showed the so-called HER2 "ultra-low" phenotype. This could be of clinical value as a potential therapeutical target concerning emerging therapeutic treatments (antibody conjugates). However, the clinical significance of this expression still needs to be established.
{"title":"HER2 Status in Low-grade Serous Ovarian Tumors.","authors":"Kristýna Němejcová, Adam Šafanda, Michaela Kendall Bártů, Nikola Hájková, Jana Drozenová, Pavel Fabian, Jan Laco, Radoslav Matěj, Gábor Méhes, Petr Škapa, Ivana Stružinská, Pavel Dundr","doi":"10.1097/PGP.0000000000001059","DOIUrl":"10.1097/PGP.0000000000001059","url":null,"abstract":"<p><p>Using immunohistochemistry, we examined a large cohort of 135 ovarian tumors, made up of 96 low-grade serous carcinomas (LGSCs) and 39 serous borderline tumors (micropapillary variant, mSBT), with the aim of exploring their HER2 status (overexpression). We followed with comprehensive genomic analyses on this sample set from our previous study, which revealed HER2 mutation in 5% (4/75) of LGSC and 10% (3/29) of mSBT. No cases were evaluated as HER2-positive, but 6 LGSCs and 1 mSBT were scored as HER2 1+, and 2 LGSCs and 1 mSBT showed the so-called HER2 \"ultra-low\" phenotype. This could be of clinical value as a potential therapeutical target concerning emerging therapeutic treatments (antibody conjugates). However, the clinical significance of this expression still needs to be established.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"331-335"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125670","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}
Pub Date : 2025-07-01Epub Date: 2024-10-31DOI: 10.1097/PGP.0000000000001068
Rachelle P Mendoza, Madhurya Ramineni, Kristina Doytcheva, Elmer C Gabutan, Raavi Gupta, Cole Miller, Donghyuk Choi, Anusha Vemuri, Renee Briese, Lisa Brannon, Anum Shahid, Kristin Petras, Minhaz Ud Dean, Carrie Fitzpatrick, Jeremy Segal, Peng Wang, Ricardo R Lastra
HER2 amplification in cervical cancer has been associated with worse clinical prognosis and a potential favorable response to HER2 inhibitors. Immunohistochemistry for the HER2 receptor is a universally accepted surrogate test for HER2 amplification, but no standardized scoring system currently exists for cervical carcinomas. In this study, we investigated HER2 overexpression in cervical squamous cell carcinoma and correlated it with HER2 amplification using fluorescence in situ hybridization (FISH) and molecular methods. Seventy-two cases of human papillomavirus-associated cervical cancer were retrospectively reviewed, and at least 2 representative tumor sections were stained for HER2. HER2 scoring was performed using the 2018 American Society of Clinical Oncology/College of American Pathologist breast cancer criteria, and cases with equivocal (2+) to positive (3+) expression were analyzed for HER2 amplification using FISH and next-generation sequencing. The average patient age was 50 yrs (range: 27-85 yr), with most patients being African American (73.6%) and diagnosed at FIGO stage I (65.3%). Nineteen (26.4%) had equivocal HER2 expression and 4 (5.5%) showed positive expression. Three of the 4 cases with positive expression had enough tumors for FISH, and all 3 were amplified. Three cases with equivocal expression showed HER2 polysomy on FISH, and none showed HER2 amplification. Late clinical stage, high tumor grade, and regional lymph node metastasis were significantly correlated with HER2 overexpression and HER2 amplification. Next-generation sequencing of the 3 HER2-amplified tumors showed amplification of various genes, including CD274, JAK2, BIRC3, and ERBB2, and a PIK3CA missense mutation. In summary, HER2 immunohistochemistry is a reliable predictive marker of HER2 amplification in cervical cancer.
{"title":"Molecular and Clinicopathologic Characterization of HER2-overexpressed Squamous Cell Carcinoma of the Cervix.","authors":"Rachelle P Mendoza, Madhurya Ramineni, Kristina Doytcheva, Elmer C Gabutan, Raavi Gupta, Cole Miller, Donghyuk Choi, Anusha Vemuri, Renee Briese, Lisa Brannon, Anum Shahid, Kristin Petras, Minhaz Ud Dean, Carrie Fitzpatrick, Jeremy Segal, Peng Wang, Ricardo R Lastra","doi":"10.1097/PGP.0000000000001068","DOIUrl":"10.1097/PGP.0000000000001068","url":null,"abstract":"<p><p>HER2 amplification in cervical cancer has been associated with worse clinical prognosis and a potential favorable response to HER2 inhibitors. Immunohistochemistry for the HER2 receptor is a universally accepted surrogate test for HER2 amplification, but no standardized scoring system currently exists for cervical carcinomas. In this study, we investigated HER2 overexpression in cervical squamous cell carcinoma and correlated it with HER2 amplification using fluorescence in situ hybridization (FISH) and molecular methods. Seventy-two cases of human papillomavirus-associated cervical cancer were retrospectively reviewed, and at least 2 representative tumor sections were stained for HER2. HER2 scoring was performed using the 2018 American Society of Clinical Oncology/College of American Pathologist breast cancer criteria, and cases with equivocal (2+) to positive (3+) expression were analyzed for HER2 amplification using FISH and next-generation sequencing. The average patient age was 50 yrs (range: 27-85 yr), with most patients being African American (73.6%) and diagnosed at FIGO stage I (65.3%). Nineteen (26.4%) had equivocal HER2 expression and 4 (5.5%) showed positive expression. Three of the 4 cases with positive expression had enough tumors for FISH, and all 3 were amplified. Three cases with equivocal expression showed HER2 polysomy on FISH, and none showed HER2 amplification. Late clinical stage, high tumor grade, and regional lymph node metastasis were significantly correlated with HER2 overexpression and HER2 amplification. Next-generation sequencing of the 3 HER2-amplified tumors showed amplification of various genes, including CD274, JAK2, BIRC3, and ERBB2, and a PIK3CA missense mutation. In summary, HER2 immunohistochemistry is a reliable predictive marker of HER2 amplification in cervical cancer.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"323-330"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545353","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}