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}
Nuclear laminar or inner nuclear membrane proteins, including lamin A, B1, and B2 and emerin, are involved in maintaining nuclear morphology. However, their expression patterns vary among tumors and remain incompletely understood. Endometrioid carcinoma (EC) exhibits mild nuclear atypia, although the underlying reasons have not been thoroughly explored. In this study, we quantitatively analyzed emerin and lamin A, B1, and B2 expression levels in normal endometrium (NE), precancerous lesions, and EC using computer-assisted image analysis to assess the proteins' roles in nuclear morphologic change during tumorigenesis. From NE to EC, nuclear size remained unchanged, and lamin A and emerin were consistently expressed at low levels, whereas lamin B1 and B2 expression gradually decreased. Given the association between lamin A and emerin as well as their roles in nuclear morphology, these results indicate that their consistent low expression may underlie the preservation of nuclear size and shape in EC relative to NE. Conversely, lamin B1 and B2 are implicated in tumor progression rather than nuclear morphology maintenance. As lamin A and emerin are expressed in many organs and tumors, the consistently low expression of these proteins from NE to EC highlights a notable feature of the endometrium and endometrial carcinogenesis.
核片层或核内膜蛋白,包括片层 A、B1 和 B2 以及应急蛋白,参与维持核形态。然而,它们在不同肿瘤中的表达模式各不相同,至今仍不完全清楚。子宫内膜样癌(EC)表现出轻度核不典型性,但其根本原因尚未得到深入探讨。在这项研究中,我们利用计算机辅助图像分析技术定量分析了正常子宫内膜(NE)、癌前病变和EC中emerin和层粘连蛋白A、B1和B2的表达水平,以评估这些蛋白在肿瘤发生过程中核形态变化中的作用。从NE到EC,核大小保持不变,层粘连蛋白A和emerin持续低水平表达,而层粘连蛋白B1和B2的表达则逐渐下降。鉴于片层A和胚乳素之间的联系以及它们在核形态中的作用,这些结果表明,它们持续低水平表达可能是相对于NE而言,EC中核大小和形状得以保留的原因。相反,片层蛋白 B1 和 B2 与肿瘤进展而非核形态维持有关。由于层粘连蛋白 A 和emerin 在许多器官和肿瘤中都有表达,因此这些蛋白从 NE 到 EC 的持续低表达突显了子宫内膜和子宫内膜癌变的一个显著特点。
{"title":"Lamin A and Emerin Protein Expression Remains Consistently Low and Nuclear Size is Unchanged in Normal Endometrium, Precancerous Lesions, and Endometrioid Carcinoma.","authors":"Yoshimi Nishijima, Naoki Inoue, Akira Iwase, Hayato Ikota, Sayaka Kobayashi, Hideaki Yokoo, Masanao Saio","doi":"10.1097/PGP.0000000000001080","DOIUrl":"10.1097/PGP.0000000000001080","url":null,"abstract":"<p><p>Nuclear laminar or inner nuclear membrane proteins, including lamin A, B1, and B2 and emerin, are involved in maintaining nuclear morphology. However, their expression patterns vary among tumors and remain incompletely understood. Endometrioid carcinoma (EC) exhibits mild nuclear atypia, although the underlying reasons have not been thoroughly explored. In this study, we quantitatively analyzed emerin and lamin A, B1, and B2 expression levels in normal endometrium (NE), precancerous lesions, and EC using computer-assisted image analysis to assess the proteins' roles in nuclear morphologic change during tumorigenesis. From NE to EC, nuclear size remained unchanged, and lamin A and emerin were consistently expressed at low levels, whereas lamin B1 and B2 expression gradually decreased. Given the association between lamin A and emerin as well as their roles in nuclear morphology, these results indicate that their consistent low expression may underlie the preservation of nuclear size and shape in EC relative to NE. Conversely, lamin B1 and B2 are implicated in tumor progression rather than nuclear morphology maintenance. As lamin A and emerin are expressed in many organs and tumors, the consistently low expression of these proteins from NE to EC highlights a notable feature of the endometrium and endometrial carcinogenesis.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"340-348"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545352","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: 2024-10-30DOI: 10.1097/PGP.0000000000001071
Constance V Chen, Megan S Orlando, Mary Kathryn Abel, Jessica Opoku-Anane, Joseph T Rabban
Definitive diagnosis of endometriosis is established by histologic confirmation in tissue from surgically visualized lesions; however, the diagnostic sensitivity of this approach varies widely. We hypothesized that incomplete tissue block sampling may contribute to false-negative diagnosis, particularly if the focus of endometriosis in the tissue section is scant. This study defined the diagnostic value of deeper level tissue sections in cases in which none of the specimen parts contained endometriosis on the initial tissue sections, using the World Health Organization essential criteria for diagnosis of endometriosis (presence of endometrial glands and endometrial stroma). Among 135 patients who underwent surgery for suspected endometriosis by a single surgeon at an academic institution from 2015 to 2019, the initial tissue sections resulted in a diagnosis of endometriosis in 73.3% (99/135), at an average diagnostic yield of 5.9 slides per diagnosis of endometriosis. An additional 9 patients were diagnosed with endometriosis by deeper level tissue sections, increasing the diagnostic rate to 80% (108/135). This 6.7% gain in the diagnostic rate came at an increase in resource utilization, with an overall overage diagnostic yield of 9.8 slides per diagnosis of endometriosis. Overall, 8.3% of patients had a false-negative diagnosis on the initial tissue sections. When extrapolated to a population level, the number of patients potentially affected by this source of false-negative diagnosis and the implications for patients merit consideration of the use of deeper level sections if none of the initial sections of any of the specimens contains endometriosis.
{"title":"Diagnostic Utility of Deeper Level Tissue Sections of Negative Peritoneal Biopsies for Clinically Suspected Endometriosis.","authors":"Constance V Chen, Megan S Orlando, Mary Kathryn Abel, Jessica Opoku-Anane, Joseph T Rabban","doi":"10.1097/PGP.0000000000001071","DOIUrl":"10.1097/PGP.0000000000001071","url":null,"abstract":"<p><p>Definitive diagnosis of endometriosis is established by histologic confirmation in tissue from surgically visualized lesions; however, the diagnostic sensitivity of this approach varies widely. We hypothesized that incomplete tissue block sampling may contribute to false-negative diagnosis, particularly if the focus of endometriosis in the tissue section is scant. This study defined the diagnostic value of deeper level tissue sections in cases in which none of the specimen parts contained endometriosis on the initial tissue sections, using the World Health Organization essential criteria for diagnosis of endometriosis (presence of endometrial glands and endometrial stroma). Among 135 patients who underwent surgery for suspected endometriosis by a single surgeon at an academic institution from 2015 to 2019, the initial tissue sections resulted in a diagnosis of endometriosis in 73.3% (99/135), at an average diagnostic yield of 5.9 slides per diagnosis of endometriosis. An additional 9 patients were diagnosed with endometriosis by deeper level tissue sections, increasing the diagnostic rate to 80% (108/135). This 6.7% gain in the diagnostic rate came at an increase in resource utilization, with an overall overage diagnostic yield of 9.8 slides per diagnosis of endometriosis. Overall, 8.3% of patients had a false-negative diagnosis on the initial tissue sections. When extrapolated to a population level, the number of patients potentially affected by this source of false-negative diagnosis and the implications for patients merit consideration of the use of deeper level sections if none of the initial sections of any of the specimens contains endometriosis.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"349-354"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545350","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: 2025-03-12DOI: 10.1097/PGP.0000000000001041
Anna S Erem, Krisztina Hanley, Gulisa Turashvili
Cellular angiofibromas (CAFs) are benign mesenchymal neoplasms of the vulva and lower genitourinary tract. Although most cases are benign with excellent prognosis, data on CAFs with cytologic atypia (aCAF) and sarcomatous transformation (tCAF) is limited. We identified 13 vulvar CAFs comprising 4 aCAFs and 9 tCAFs. The median age at presentation was 49 yr (40-84). All tumors involved the subcutis with a median size of 4.75 cm (0.8-11.7). Vascular and stromal hyalinization was present in all cases. Fascicular growth pattern and chronic perivascular inflammation were seen in 10 cases, followed by wispy collagen in 11 and stromal inflammation in 12. Common features were fat entrapment (n=8), stromal edema (n=7), and hemangiopericytoma-like vessels (n=5), while myxoid change, necrosis (n=3 each), hemorrhage, collagen bundles (n=2 each), solitary fibrous tumor-like appearance, and large hyalinized vessels (n=1 each) were rare. The atypia ranged from isolated atypical cells to foci of multinucleated cells, with brisk mitoses in 1 case. The sarcomatous transformation involved 10% to 80% of total tumor volume and comprised features of well-differentiated liposarcoma, pleomorphic liposarcoma, leiomyosarcoma, and spindle and epithelioid cell sarcoma. Diffuse p16 expression was present in 2 tCAFs. Of 10 patients with available follow-up (median: 103.3 mo, 13.3-156.6), 2 (20%) recurred at 41 mo and 66 mo and remained disease-free at 157 and 99 mo post reexcision, respectively. The study provides a detailed clinicopathologic characterization of rare variants of CAF, aCAFs, and tCAFs, and reports rare recurrences, most likely due to incomplete surgical excision.
{"title":"Vulvar Cellular Angiofibroma With Cytologic Atypia and Sarcomatous Transformation: A Clinicopathologic Analysis.","authors":"Anna S Erem, Krisztina Hanley, Gulisa Turashvili","doi":"10.1097/PGP.0000000000001041","DOIUrl":"10.1097/PGP.0000000000001041","url":null,"abstract":"<p><p>Cellular angiofibromas (CAFs) are benign mesenchymal neoplasms of the vulva and lower genitourinary tract. Although most cases are benign with excellent prognosis, data on CAFs with cytologic atypia (aCAF) and sarcomatous transformation (tCAF) is limited. We identified 13 vulvar CAFs comprising 4 aCAFs and 9 tCAFs. The median age at presentation was 49 yr (40-84). All tumors involved the subcutis with a median size of 4.75 cm (0.8-11.7). Vascular and stromal hyalinization was present in all cases. Fascicular growth pattern and chronic perivascular inflammation were seen in 10 cases, followed by wispy collagen in 11 and stromal inflammation in 12. Common features were fat entrapment (n=8), stromal edema (n=7), and hemangiopericytoma-like vessels (n=5), while myxoid change, necrosis (n=3 each), hemorrhage, collagen bundles (n=2 each), solitary fibrous tumor-like appearance, and large hyalinized vessels (n=1 each) were rare. The atypia ranged from isolated atypical cells to foci of multinucleated cells, with brisk mitoses in 1 case. The sarcomatous transformation involved 10% to 80% of total tumor volume and comprised features of well-differentiated liposarcoma, pleomorphic liposarcoma, leiomyosarcoma, and spindle and epithelioid cell sarcoma. Diffuse p16 expression was present in 2 tCAFs. Of 10 patients with available follow-up (median: 103.3 mo, 13.3-156.6), 2 (20%) recurred at 41 mo and 66 mo and remained disease-free at 157 and 99 mo post reexcision, respectively. The study provides a detailed clinicopathologic characterization of rare variants of CAF, aCAFs, and tCAFs, and reports rare recurrences, most likely due to incomplete surgical excision.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"314-322"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614892","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 : 2025-05-09DOI: 10.1097/PGP.0000000000001117
Elaina Daniels, David B Chapel, Douglas A Rottmann, Stephanie L Skala, Jean H Siedel, Tao Huang
Mesonephric-like adenocarcinoma (MLA) of the uterus is a rare, aggressive malignancy of presumed Müllerian origin that was recently included in the 2020 World Health Organization (WHO) Classification of Female Genital Tumours. MLA is challenging to diagnose given its rarity and morphologic heterogeneity. The recently published first case report of MLA that underwent dedifferentiation via TP53 mutation expands the morphologic spectrum of dedifferentiated carcinoma. In here, we describe a second case of an endometrial MLA with dedifferentiation from a 41-yr-old woman who presented with bilateral ovarian masses, peritoneal carcinomatosis, and hypercalcemia. A diagnosis of small cell carcinoma of the ovary, hypercalcemic type, was initially rendered at an outside institution from an omental biopsy, which only showed the undifferentiated component. The subsequent endometrial curettings performed at our institution showed both the MLA and undifferentiated components, each of which demonstrated distinct immunophenotype with the immunoreactivity to epithelial markers, GATA3 and TTF1 limited to the MLA component and the aberrant nuclear expression of beta catenin, global loss of expression of SMARCA4 and loss of expression of SMARCA2 limited to the undifferentiated component. Molecular studies on the undifferentiated component from the omental biopsy identified not only a mutation in KRAS, gene mutation commonly seen in MLA, but also mutations in SMARCA4 and CTNNB1. In summary, we describe a second case of dedifferentiated MLA with dedifferentiation driven by various genetic alterations, including SMARCA4 and CTNNB1 gene mutations, novel gene alterations that have never been described in dedifferentiated MLA.
{"title":"A Case Report of Uterine Dedifferentiated Mesonephric-Like Adenocarcinoma With Comprehensive Molecular Profiling.","authors":"Elaina Daniels, David B Chapel, Douglas A Rottmann, Stephanie L Skala, Jean H Siedel, Tao Huang","doi":"10.1097/PGP.0000000000001117","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001117","url":null,"abstract":"<p><p>Mesonephric-like adenocarcinoma (MLA) of the uterus is a rare, aggressive malignancy of presumed Müllerian origin that was recently included in the 2020 World Health Organization (WHO) Classification of Female Genital Tumours. MLA is challenging to diagnose given its rarity and morphologic heterogeneity. The recently published first case report of MLA that underwent dedifferentiation via TP53 mutation expands the morphologic spectrum of dedifferentiated carcinoma. In here, we describe a second case of an endometrial MLA with dedifferentiation from a 41-yr-old woman who presented with bilateral ovarian masses, peritoneal carcinomatosis, and hypercalcemia. A diagnosis of small cell carcinoma of the ovary, hypercalcemic type, was initially rendered at an outside institution from an omental biopsy, which only showed the undifferentiated component. The subsequent endometrial curettings performed at our institution showed both the MLA and undifferentiated components, each of which demonstrated distinct immunophenotype with the immunoreactivity to epithelial markers, GATA3 and TTF1 limited to the MLA component and the aberrant nuclear expression of beta catenin, global loss of expression of SMARCA4 and loss of expression of SMARCA2 limited to the undifferentiated component. Molecular studies on the undifferentiated component from the omental biopsy identified not only a mutation in KRAS, gene mutation commonly seen in MLA, but also mutations in SMARCA4 and CTNNB1. In summary, we describe a second case of dedifferentiated MLA with dedifferentiation driven by various genetic alterations, including SMARCA4 and CTNNB1 gene mutations, novel gene alterations that have never been described in dedifferentiated MLA.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077973","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 : 2025-05-01Epub Date: 2024-10-31DOI: 10.1097/PGP.0000000000001076
Natthawadee Laokulrath, Yin P Hung, Jaclyn C Watkins, Esther Oliva, Kyle M Devins
SOX17 has recently emerged as a novel immunohistochemical marker for cancers of endometrial and ovarian origin with improved specificity compared with the widely used Mullerian marker PAX8. However, evaluation of SOX17 in benign and malignant peritoneal mesothelial proliferations remains limited, and these may mimic gynecologic carcinomas, particularly on small biopsies. We evaluated SOX17 and PAX8 expression in 20 benign mesothelial lesions (5 adenomatoid tumors, 5 well-differentiated papillary mesothelial tumors, and 10 peritoneal inclusion cysts) and 16 epithelioid peritoneal mesotheliomas. The 17 female and 3 male patients with benign mesothelial lesions ranged from 20 to 80 yr (median: 56.5 yr), while the 9 females and 7 males with mesothelioma ranged from 47 to 85 yr (median: 57.5 yr). SOX17 was positive in 5 (25%) benign lesions (2 adenomatoid tumors, 3 peritoneal inclusion cysts) and 2 (13%) mesotheliomas, while PAX8 stained 8 (40%) benign lesions (1 adenomatoid tumor, 1 well-differentiated papillary mesothelial tumor, 6 peritoneal inclusion cysts), and 2 (13%) mesotheliomas. Results for the 2 stains showed incomplete concordance, with agreement in 15 (75%) benign proliferations and 14 (88%) mesotheliomas. Our findings suggest that SOX17 positivity alone is insufficient to confirm a diagnosis of gynecologic carcinoma over a mesothelial proliferation and pathologists should exercise caution when these entities are diagnostic considerations.
{"title":"SOX17 Expression in Mesotheliomas and Benign Mesothelial Proliferations: Implications for Differential Diagnosis With Gynecologic Carcinomas.","authors":"Natthawadee Laokulrath, Yin P Hung, Jaclyn C Watkins, Esther Oliva, Kyle M Devins","doi":"10.1097/PGP.0000000000001076","DOIUrl":"10.1097/PGP.0000000000001076","url":null,"abstract":"<p><p>SOX17 has recently emerged as a novel immunohistochemical marker for cancers of endometrial and ovarian origin with improved specificity compared with the widely used Mullerian marker PAX8. However, evaluation of SOX17 in benign and malignant peritoneal mesothelial proliferations remains limited, and these may mimic gynecologic carcinomas, particularly on small biopsies. We evaluated SOX17 and PAX8 expression in 20 benign mesothelial lesions (5 adenomatoid tumors, 5 well-differentiated papillary mesothelial tumors, and 10 peritoneal inclusion cysts) and 16 epithelioid peritoneal mesotheliomas. The 17 female and 3 male patients with benign mesothelial lesions ranged from 20 to 80 yr (median: 56.5 yr), while the 9 females and 7 males with mesothelioma ranged from 47 to 85 yr (median: 57.5 yr). SOX17 was positive in 5 (25%) benign lesions (2 adenomatoid tumors, 3 peritoneal inclusion cysts) and 2 (13%) mesotheliomas, while PAX8 stained 8 (40%) benign lesions (1 adenomatoid tumor, 1 well-differentiated papillary mesothelial tumor, 6 peritoneal inclusion cysts), and 2 (13%) mesotheliomas. Results for the 2 stains showed incomplete concordance, with agreement in 15 (75%) benign proliferations and 14 (88%) mesotheliomas. Our findings suggest that SOX17 positivity alone is insufficient to confirm a diagnosis of gynecologic carcinoma over a mesothelial proliferation and pathologists should exercise caution when these entities are diagnostic considerations.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"217-221"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545355","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 : 2025-05-01Epub Date: 2024-08-12DOI: 10.1097/PGP.0000000000001065
Anne K Bartels, Oluwole Fadare
The International Society of the Study of Vulvovaginal Diseases (ISSVD) recently defined nonsclerotic lichen sclerosus (NSLS) as a scenario wherein the clinical findings are consistent with lichen sclerosus (LS), but no microscopic evidence of dermal sclerosis is found and recognized 4 histologic subcategories. Herein, we present an institutional experience with NSLS, with an emphasis on frequency, application of the ISSVD categories in routine practice, and clinicopathologic correlation. The authors reviewed clinical and pathologic findings for consecutive vulvar biopsies in which LS was a clinical and/or pathologic consideration. Cases were classified as classical/sclerotic LS (CLS), NSLS (per ISSVD criteria), and "unclassified," the latter of which were cases not classifiable as NSLS or CLS, despite a clinical impression or LS or LS being a significant clinical consideration (ie, "clinical LS"). In clinical LS cases, CLS and NSLS were diagnosed histologically in 61% (182/298) and 15% (44/298), respectively, whereas the remainder were histologically unclassified. The latter group was microscopically heterogeneous, devoid of a consistent pathologic profile, and generally showed absence, focality, minimality, ambiguity, or infrequency of features that would have allowed their categorization into one of the NSLS categories. Among the 4 categories for the categorizable NSLS cases, the "lichenoid dermatitis" pattern (61.4%) was the commonest, followed by dermal fibrosis with acanthosis (22.7%), dermal fibrosis without acanthosis (9.1%), and hypertrophic lichenoid dermatitis (6.8%). The clinical response rates to topical therapies for the NSLS and unclassified groups were 71% and 62%, respectively ( P =0.4). Our findings highlight the significance of clinicopathologic correlation in the diagnosis of NSLS. In the setting of clinical LS, some histologic evidence to support that impression is found in most cases when the ISSVD system for diagnosis and classification of biopsies is applied. However, a subset of clinical LS cases are not pathologically classifiable as either CLS or any of the NSLS categories; these display nonspecific histologic features and require future study.
国际外阴疾病研究学会(ISSVD)最近将非硬化性苔藓硬化症(NSLS)定义为临床表现与苔藓硬化症(LS)一致,但显微镜下未发现真皮硬化的证据,并确认了 4 个组织学亚类。在此,我们介绍了一家机构在 NSLS 方面的经验,重点是频率、ISSVD 分类在常规实践中的应用以及临床病理相关性。作者回顾了以 LS 为临床和/或病理考虑因素的连续外阴活检的临床和病理结果。病例被分为经典/硬化性LS(CLS)、NSLS(根据ISSVD标准)和 "未分类",后者是指尽管临床印象或LS或LS是一个重要的临床考虑因素(即 "临床LS"),但无法归类为NSLS或CLS的病例。在临床LS病例中,经组织学诊断为CLS和NSLS的分别占61%(182/298)和15%(44/298),而其余病例则未经组织学分类。后者在显微镜下表现为异质性,没有一致的病理特征,通常表现为缺乏、病灶性、微小性、模糊性或不常见特征,而这些特征本可将其归入 NSLS 的某个类别。在可归类的 NSLS 病例的 4 个类别中,"苔癣样皮炎 "模式(61.4%)最常见,其次是伴有棘皮症的真皮纤维化(22.7%)、不伴有棘皮症的真皮纤维化(9.1%)和肥厚性苔癣样皮炎(6.8%)。NSLS组和未分级组对局部疗法的临床反应率分别为71%和62%(P=0.4)。我们的研究结果凸显了临床病理相关性在诊断 NSLS 中的重要性。在临床 LS 的情况下,应用 ISSVD 系统对活检组织进行诊断和分类时,大多数病例都能找到一些组织学证据来支持这种印象。然而,有一部分临床 LS 病例在病理上无法归类为 CLS 或任何 NSLS 类别;这些病例显示出非特异性组织学特征,需要在未来进行研究。
{"title":"Nonsclerotic Lichen Sclerosus of Vulva: A Clinicopathologic Analysis.","authors":"Anne K Bartels, Oluwole Fadare","doi":"10.1097/PGP.0000000000001065","DOIUrl":"10.1097/PGP.0000000000001065","url":null,"abstract":"<p><p>The International Society of the Study of Vulvovaginal Diseases (ISSVD) recently defined nonsclerotic lichen sclerosus (NSLS) as a scenario wherein the clinical findings are consistent with lichen sclerosus (LS), but no microscopic evidence of dermal sclerosis is found and recognized 4 histologic subcategories. Herein, we present an institutional experience with NSLS, with an emphasis on frequency, application of the ISSVD categories in routine practice, and clinicopathologic correlation. The authors reviewed clinical and pathologic findings for consecutive vulvar biopsies in which LS was a clinical and/or pathologic consideration. Cases were classified as classical/sclerotic LS (CLS), NSLS (per ISSVD criteria), and \"unclassified,\" the latter of which were cases not classifiable as NSLS or CLS, despite a clinical impression or LS or LS being a significant clinical consideration (ie, \"clinical LS\"). In clinical LS cases, CLS and NSLS were diagnosed histologically in 61% (182/298) and 15% (44/298), respectively, whereas the remainder were histologically unclassified. The latter group was microscopically heterogeneous, devoid of a consistent pathologic profile, and generally showed absence, focality, minimality, ambiguity, or infrequency of features that would have allowed their categorization into one of the NSLS categories. Among the 4 categories for the categorizable NSLS cases, the \"lichenoid dermatitis\" pattern (61.4%) was the commonest, followed by dermal fibrosis with acanthosis (22.7%), dermal fibrosis without acanthosis (9.1%), and hypertrophic lichenoid dermatitis (6.8%). The clinical response rates to topical therapies for the NSLS and unclassified groups were 71% and 62%, respectively ( P =0.4). Our findings highlight the significance of clinicopathologic correlation in the diagnosis of NSLS. In the setting of clinical LS, some histologic evidence to support that impression is found in most cases when the ISSVD system for diagnosis and classification of biopsies is applied. However, a subset of clinical LS cases are not pathologically classifiable as either CLS or any of the NSLS categories; these display nonspecific histologic features and require future study.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"210-216"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035818","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 : 2025-05-01Epub Date: 2024-12-27DOI: 10.1097/PGP.0000000000001086
Namra Ajmal, Olivia Nicolais, Mark S Shahin, Lucy Ma
{"title":"Pilomatrix-like High-grade Endometrioid Carcinoma of the Uterine Corpus With Excellent Response to Immune Checkpoint Inhibitor Therapy.","authors":"Namra Ajmal, Olivia Nicolais, Mark S Shahin, Lucy Ma","doi":"10.1097/PGP.0000000000001086","DOIUrl":"10.1097/PGP.0000000000001086","url":null,"abstract":"","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"255-257"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894308","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}