International Journal of Gynecological Pathology最新文献

{"title":"Acantholytic Dyskeratoses of the Vulva: Clinicopathologic Characterization of 16 Cases and Review of the Literature.","authors":"Maxwell D Wang, Scott C Bresler, May P Chan, Rajiv M Patel, David B Chapel","doi":"10.1097/PGP.0000000000001066","DOIUrl":"10.1097/PGP.0000000000001066","url":null,"abstract":"<p><p>The vulva and perineum are rarely involved by acantholytic dyskeratoses, including Hailey-Hailey disease, Darier disease, papular acantholytic dyskeratosis of the genitocrural area, acantholytic dyskeratotic acanthoma, and warty dyskeratoma. These entities show broad histomorphologic overlap, generally requiring clinical correlation for definitive classification. This institutional series aims to better characterize vulvar acantholytic dyskeratoses and provide a practical literature review and diagnostic aid for gynecologic pathologists. Our institutional archives contained 16 vulvar acantholytic dyskeratoses diagnosed between 1990 and 2023. Affected patients were 36 to 79 (mean, 58) years old and presented with one or more asymptomatic (n = 9) or pruritic (n = 6) lesions involving the vulva (predominantly the labia majora), with additional perineal involvement in 2. Four patients have known Hailey-Hailey disease. Eleven cases comprised singular, raised, erythematous, or skin-colored papules, measuring 0.2 to 0.6 (mean, 0.3) cm. Two patients had oligofocal (both with known Hailey-Hailey disease) vulvar lesions, and 2 had multifocal vulvar lesions (one with known Hailey-Hailey disease). Histologically, all showed acantholysis and dyskeratoses (abundant in 8, focal in 8, with corps ronds generally more conspicuous than corps grains). Additional features included suprabasal clefting (n = 14), dermal papillomatosis (n = 12), and acanthosis (n = 8). Adnexal involvement was rare (n = 1). No histologic features reliably distinguished sporadic versus syndromic acantholytic dyskeratoses. Sporadic lesions were cured by local excision. Patients with Hailey-Hailey disease were variably responsive to corticosteroids. Neither our series nor the literature indicate a significant correlation between sporadic or syndromic acantholytic dyskeratosis and squamous cell carcinoma. Important differential diagnoses include pemphigus vulgaris and pemphigus vegetans, for which direct immunofluorescence may be performed, when indicated.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"112-119"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035815","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}

{"title":"Malignant Brenner Tumor of the Ovary: A Critical Reappraisal.","authors":"Gulisa Turashvili, Krisztina Hanley","doi":"10.1097/PGP.0000000000001060","DOIUrl":"10.1097/PGP.0000000000001060","url":null,"abstract":"<p><p>Malignant Brenner tumors (MBTs) are rare epithelial tumors of the ovary, most likely arising from benign and borderline Brenner tumors. MBTs may be misdiagnosed as other primary carcinomas or nonepithelial tumors of the ovary as well as metastatic carcinomas. Accurate diagnosis usually requires clinical-radiologic correlation, extensive sampling, and immunohistochemical studies. Treatment is not standardized and may include surgery with or without chemotherapy. More than half of MBTs are diagnosed at stage I, with 47.7% and at least 20% recurrence and mortality rates, respectively. Awareness of key diagnostic features and pitfalls is essential to differentiate MBT from its mimics and ensure optimal clinical management. This comprehensive review includes classification, etiopathogenesis, historical overview, epidemiology, clinical features, treatment, prognosis, gross pathology, key morphologic features, ancillary testing, and differential diagnostic considerations for ovarian MBTs.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"182-192"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948614","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}

{"title":"Folate Receptor Alpha Expression and the Tumor Immune Microenvironment in Patients with Cervical Cancer.","authors":"Shu Yazaki, Yohei Chiba, Yuki Kojima, Hiroshi Yoshida, Shigemasa Takamizawa, Rui Kitadai, Ayumi Saito, Shousuke Kita, Kasumi Yamamoto, Hitomi Sumiyoshi-Okuma, Tadaaki Nishikawa, Kazuki Sudo, Tatsunori Shimoi, Emi Noguchi, Masaya Uno, Mitsuya Ishikawa, Tomoyasu Kato, Yasuhiro Fujiwara, Kan Yonemori","doi":"10.1097/PGP.0000000000001051","DOIUrl":"10.1097/PGP.0000000000001051","url":null,"abstract":"<p><p>Folate receptor α (FRα) is a cell-surface protein and an attractive target for cancer treatment. We investigated the association between FRα expression and the tumor immune microenvironment in patients with cervical cancer. We examined whole tumor sections of 123 patients with cervical cancer: 67 and 56 sections of squamous cell carcinoma (SCC) and non-SCC, respectively. FRα expression was assessed using immunohistochemical staining with the anti-FRα monoclonal antibody clone 26B3. Programmed death-ligand 1 (PD-L1) expression was assessed using a combined positive score (CPS). The intratumoral CD3 and CD8 cell densities were calculated as the average number of positive cells in five independent areas. FRα-positivity was identified in 72.4% of the patients, and it differed by histology (SCC vs. non-SCC; 55.2% vs. 92.9%, P <0.001). PD-L1 status was positive (CPS ≥1) in 75.6% and was more commonly expressed in patients with SCC (SCC vs. non-SCC; 83.5% vs. 66.1%, P =0.02). FRα expression had a weak correlation with PD-L1 expression ( r =-0.22, P <0.001) and CD8-positive cells ( r =-0.19, P =0.03). FRα-positivity was more frequently observed in the PD-L1 CPS <10 group than in the PD-L1 CPS ≥10 group (81% vs. 64%, P =0.03). FRα-high was significantly associated with poor prognosis, especially in the PD-L1 CPS ≥10 groups (hazard ratio: 4.10, 95% confidence interval: 1.39-12.06, P =0.01). In conclusion, FRα expression was higher in patients with cervical cancer and PD-L1 CPS <10 than in those with CPS ≥10. Targeting FRα expression may be a potential therapeutic strategy for cervical cancer patients with low or negative PD-L1 expression.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"104-111"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446116","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}

{"title":"Synchronous Endometrial and Ovarian Endometrioid Carcinoma With MUTYH Germline Mutation: A Case Report With Genetic Analysis.","authors":"Xiaoya Zhao, Zixiu Song, Yan Liu, Xianjing Zheng, Wei Zheng, Congrong Liu","doi":"10.1097/PGP.0000000000001048","DOIUrl":"10.1097/PGP.0000000000001048","url":null,"abstract":"<p><p>Synchronous endometrial and ovarian endometrioid carcinoma, which simultaneously involves the endometrium and ovary, is a relatively rare entity among gynecological cancers. Precise diagnosis and risk stratification are crucial for disease management. We present a unique case of a 40-year-old woman diagnosed with synchronous endometrial and ovarian endometrioid carcinoma carrying a monoallelic pathogenic MUTYH germline variant. Despite the histological morphology of the right ovarian tumor exhibiting some differences compared to the uterine tumor, we identified three identical somatic mutations shared between the uterine tumor and right ovarian tumor, along with four additional mutations exclusive to the uterine tumor, through the utilization of massively parallel sequencing of a 196-gene panel. These findings enabled us to elucidate the clonal relatedness and potential clonal evolution of the tumor across the two anatomical sites. Furthermore, in accordance with the 2023 FIGO staging system, the patient was diagnosed with Stage IIIB2 uterine cancer, and consequently, adjuvant radiation and chemotherapy were administered after surgery. She is being followed periodically and is normal 15 months after surgery. To the best of our knowledge, this study presents the first case of a patient with synchronous endometrial and ovarian endometrioid carcinoma harboring a monoallelic pathogenic MUTYH germline variant.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"155-159"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446136","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}

{"title":"Comparison of PD-L1, VISTA, LAG-3, and GAL-3 Expressions and Their Relationships to Mismatch Repair Protein and p53 Expression in 529 Cases of Endometrial Carcinoma.","authors":"Dilara Irem Arslan-Kahraman, Betul Ogut, Mehmet Arda Inan, Ferah Kazanci, Mehmet Anil Onan, Mehmet Erdem, Ozlem Erdem","doi":"10.1097/PGP.0000000000001049","DOIUrl":"10.1097/PGP.0000000000001049","url":null,"abstract":"<p><p>The aim of this study is to evaluate the expressions of programmed death-ligand 1 (PD-L1), V-domain Ig suppressor of T-cell activation (VISTA), lymphocyte activation gene-3 (LAG-3), and galectin-3 (GAL-3), in mismatch repair-deficient (MMRd)/MMR-proficient and abnormal p53 expressing endometrial carcinomas and their relationship with clinical-histopathological features. Patients who underwent surgery for endometrial carcinoma between January 2008 and December 2018 were included in the study. Immunohistochemical analysis of MLH1, PMS2, MSH2, MSH6, p53, PD-L1, VISTA, LAG-3, and GAL-3 was performed on the tissue samples of microarray. A total of 529 patients were included. MMRd and p53-mutant tumors accounted for 31.5% and 11.5% of cases, respectively. PD-L1 and LAG-3 expressions in the MMRd and p53-mutant groups were higher than in the MMR-proficient group ( P < 0.001). GAL-3 expression in the MMR-proficient group was statistically higher than in the MMRd and p53-mutant groups ( P < 0.001). Mean age, grade, International Federation of Gynecology and Obstetrics stage, lymphovascular invasion, and lymph node metastasis were significantly higher in the p53-mutant group ( P < 0.001). In the group with PD-L1 expression, nonendometrioid histologic type, tumor grade, and lymphovascular invasion were significantly higher ( P < 0.001). Tumor grade, lymphovascular invasion, lymph node metastasis, and microcystic, elongated and fragmented pattern of invasion were significantly higher in the group with high VISTA expression ( P < 0.05). Tumor grade was significantly higher in the group with LAG-3 expression ( P < 0.001). Immunohistochemically determined subgroups and PD-L1, VISTA, LAG-3, and GAL-3 expression levels may be useful indicators of molecular features, and clinical outcomes also may have important implications for the development of targeted therapies in endometrial carcinoma.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"130-143"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446115","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}

{"title":"Targetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations.","authors":"Padmini A Manrai, Austin McHenry, Tong Sun, Alessandro D Santin, Elena Ratner, Douglas I Lin, Julia A Elvin, Pei Hui, Natalia Buza","doi":"10.1097/PGP.0000000000001050","DOIUrl":"10.1097/PGP.0000000000001050","url":null,"abstract":"<p><p>Targeted anti-HER2 therapy has been recently added to the standard treatment recommendations in endometrial serous carcinoma. Current eligibility requires testing for HER2 overexpression and/or gene amplification by immunohistochemistry and by fluorescence in situ hybridization. However, clinical trials have also demonstrated the efficacy of anti-HER2 drugs against activating ERBB2/HER2 mutations in a variety of solid tumor types, and fam-trastuzumab deruxtecan is now approved by the US Food and Drug Administration for HER2 -mutant non-small cell lung cancer. This study aimed at evaluating the detailed clinical, histomorphological, immunohistochemical, and molecular characteristics of gynecologic malignancies with ERBB2/HER2 mutations. We identified 16 tumors with 19 ERBB2/HER2 mutations in our departmental archives: 11 endometrial primaries, 2 endocervical adenocarcinomas, 1 ovarian mucinous adenocarcinoma, 1 tubo-ovarian undifferentiated carcinoma, and 1 high-grade endometrioid adenocarcinoma of Mullerian origin. ERBB2/HER2 mutations most often involved the tyrosine kinase domain (52.6%), and the most frequent specific mutation was R678Q (31.6%), involving the juxtamembrane domain. More than half (54.5%) of endometrial carcinomas and half of all tumors were MMR-deficient, resulting from MSH6 loss in all but 2 tumors. None of the tumors (0%) were POLE- mutated, while 18.8% were TP53 -mutated. HER2 IHC was negative (score 0 or 1+) in 12 tumors (67%) and equivocal (score 2+) in 4 tumors (33%), whereas none of the tumors were scored as HER2 3+. Score 2+ was associated with R678Q, L755S, I767M mutations, and ERBB2/HER2 rearrangement with a breakpoint in exon 23. Concurrent ERBB2/HER2 amplification was identified in 2 endometrial carcinomas, with HER2/CEP17 ratios of 3.1 and 3.5. We also queried the cBioportal database, which revealed 70 ERBB2/HER2 -mutant gynecologic tumors with a total of 77 ERBB2/HER2 mutations, most often involving the active site of the tyrosine kinase domain (n=36; 46.8%), and the most common specific mutation was S310F (n=20; 26%), located in the extracellular domain. Our results provide important details regarding the clinicopathological and molecular associations of potentially actionable ERBB2/HER2 mutations in endometrial carcinoma and other gynecological cancer types and contribute to addressing clinical treatment needs and improving pathology testing recommendations in the future.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"144-154"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446137","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}

{"title":"Whole-exome Sequence Analysis of Gastric-type Adenocarcinoma of the Uterine Cervix and Adjacent Lobular Endocervical Glandular Hyperplasia in the Same Case.","authors":"Tsutomu Miyamoto, Koichi Ida, Yasuhiro Tanaka, Shiho Asaka, Tanri Shiozawa","doi":"10.1097/PGP.0000000000001052","DOIUrl":"10.1097/PGP.0000000000001052","url":null,"abstract":"<p><p>Lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion of gastric-type adenocarcinoma of the uterine cervix (GAS). However, the genetic mechanisms underlying its carcinogenesis remain unclear. To elucidate the oncogenic process from LEGH to GAS, we compared gene mutations in early-stage GAS and adjacent LEGH in the same case. Fresh-frozen tissue sections were obtained from a patient with Stage IB3 GAS and adjacent LEGH who had undergone hysterectomy. Using laser microdissection, we harvested the LEGH and GAS portions separately from these sections and extracted the genomic DNA. Somatic variant analysis using whole-exome sequencing used DNA from the normal myometrium as a reference sequence. Somatic variants involving amino acid substitutions were detected in 61 and 125 locations in LEGH and GAS, respectively. Seven variants were common in both lesions, of which the pathogenic variant was GNAS only (c.2531G>A, p.R844H), a mutation frequently reported in pancreatic and colorectal cancers. LEGH had no other pathogenic variants; another pathogenic variant in GAS was found only at the same amino acid site as GNAS (c.2530C>T, p.R844C). In the present case, LEGH and GAS shared the same pathogenic variant of GNAS , indicating that both lesions had a common origin. Furthermore, the current results showed that the second GNAS variant is associated with the progression of LEGH to GAS. Further studies are required to elucidate GAS's pathogenesis and biological characteristics.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"125-129"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125674","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}

{"title":"Eosinophilic Salpingitis.","authors":"Badr AbdullGaffar, Amal Almulla","doi":"10.1097/PGP.0000000000001104","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001104","url":null,"abstract":"<p><p>Chronic salpingitis presents with various inflammatory patterns due to different causes. Eosinophil-rich salpingitis is rare and primarily associated with parasitic infestations. We aim to report our findings of eosinophil-rich salpingitis in a series of women who presented with ruptured hemorrhagic ovarian corpus luteum cysts and tubal schistosomiasis accompanied by ectopic tubal pregnancies. Eight women (age range: 31-40 yr, average age: 34 yr) met the inclusion criteria for eosinophil-rich salpingitis. The tubes showed a dense eosinophilic infiltrate throughout the tubal wall with edema and hemosiderin pigment deposition. The mucosal plicae were broadened due to vascular congestion, edema, and conspicuous eosinophilic infiltrates with siderophages. Luminal hemorrhage was present. Six patients had ipsilateral ruptured hemorrhagic ovarian corpus luteum cysts with ruptured tubal ectopic pregnancies, whereas 2 patients had Schistosoma ova in the tube. The close proximity of the tubal fimbriae to the ovary suggests that the tubal cavity is a potential reservoir of the extruded contents from ruptured hemorrhagic luteal cysts. Theoretically, the engulfed contents could move down the tubal lumen, adhere to the epithelium, and elicit an allergic inflammatory reaction in the tubal mucosa and mural wall. This phenomenon may play a role in postinflammatory fibrous adhesion and ectopic pregnancies. Eosinophilic salpingitis is a rare, unilateral, localized, secondary inflammatory reaction of the fallopian tubes. Apart from parasitic infestations, an inflammatory response to ruptured hemorrhagic corpus luteum cysts should be considered as a potential association when other causes are excluded. Certain histopathologic features may provide clues to this association. Further validation is warranted to determine whether these findings are associations or mere coincidences.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468166","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}

{"title":"β-catenin, PAX2, and PTEN Aberrancy Across the Spectrum of Endometrioid Ovarian Lesions.","authors":"Maria M Del Mundo, Mitzi Aguilar, Hao Chen, Shuang Niu, Subhransu S Sahoo, Sambit Roy, Wenxin Zheng, Elena Lucas, Diego H Castrillon","doi":"10.1097/PGP.0000000000001046","DOIUrl":"10.1097/PGP.0000000000001046","url":null,"abstract":"<p><p>Endometriosis is a common condition, with the ovary being the most common anatomic site. Endometriosis-particularly in the ovary-is associated with a risk of malignant progression, with a histologic spectrum of lesions from benign to malignant. Recently, a panel of 3 markers consisting of β-catenin, PAX2, and PTEN has been described as a potentially useful diagnostic adjunct in the diagnosis of intrauterine endometrioid neoplasia, where aberrancy for one or more of the markers is strongly associated with neoplasia. Here, we applied the panel to ovarian endometrioid lesions, including endometriosis, endometriosis with flat cytologic atypia, endometrioid borderline tumors, and endometrioid adenocarcinoma (n=85 cases in total). The incidence of aberrancy for the 3 markers increased along this putative neoplastic spectrum, arguing for a role of each of the markers in the neoplastic transformation of ovarian endometriosis. Just 1/32 (3%) of cases of nonatypical endometriosis was marker-aberrant, and this case was aberrant only for PAX2. One of 5 cases (20%) of endometriosis with atypia was marker-aberrant (both PAX2 and PTEN), supporting prior findings that some cases of flat atypia may represent bona fide precursor lesions. Of 19 endometrioid borderline tumors, 10 (53%) were aberrant for one or more markers, with PAX2 being the most frequently aberrant. Of 29 endometrioid adenocarcinomas, 28 (96.6%) were aberrant for at least 1 marker, with PAX2 again the most frequently aberrant. Patterns of aberrancy were well-preserved in areas of nonatypical endometriosis adjacent to borderline tumor or adenocarcinoma, supporting a biological origin in a common marker-aberrant precursor. The findings show that the biomarker panel could be of some diagnostic utility in the characterization of ovarian endometrioid neoplasia, such as in the diagnosis of endometrioid borderline tumor, distinguishing endometrioid from nonendometrioid lesions, or in identifying other types of early precursors at a higher risk of malignant transformation.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"79-87"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792468","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}

{"title":"Human Papilloma Virus-Independent/p53abnormal Keratinizing Squamous Cell Carcinoma of the Uterine Cervix Associated With Uterine Prolapse.","authors":"Lars-Christian Horn, Christine E Brambs, Bahriye Aktas, Astrid Dannenmann, Jens Einenkel, Michael Höckel, Irene Krücken, Sabine Taubenheim, Gero Teichmann, Ulrike Obeck, Mathias Stiller, Anne Kathrin Höhn","doi":"10.1097/PGP.0000000000001040","DOIUrl":"10.1097/PGP.0000000000001040","url":null,"abstract":"<p><p>Knowledge about the morphologic and molecular characteristics of cervical squamous cell carcinomas (CSCCs) associated with uterine prolapse is very limited. Detailed histopathological and immunohistochemical (p16, p53, and cytokeratin 17), as well as molecular evaluation for human papillomavirus (HPV)-DNA and p53-mutational analyses in 4 consecutive CSCCs associated with uterine prolapse with definition of a hitherto not well-described HPV-independent/p53abnormal precursor lesion (HPV-independent cervical intraepithelial neoplasia [CIN; differentiated CIN]) and molecular tumorigenetic pathway. Cases diagnosed within 7 years with a mean age of 75 (range: 69-83) years and a mean tumor size of 7.3 cm (range: 5.2-9.4 cm). All patients presented with locally advanced disease, and 1 woman died of the disease within 4, and another within 14 months of follow-up. All CSCCs and their adjacent precursor lesions were negative for p16, with aberrant p53-expression and diffuse and strong staining for cytokeratin 17. Both the CSCCs and their precursors were negative for HPV-DNA but harbored a TP53 mutation. The precursor lesions were characterized by epithelial thickening with superficial keratinization, and the presence of basal and parabasal keratinocytes with mitotic figures beyond the basal layer, thus showing features similar to those seen in differentiated types of vulvar intraepithelial lesions (vulvar intraepithelial neoplasia [VIN] syn. HPV-independent/p53abn VIN), suggesting the terminology of differentiated CIN or HPV-independent/p53abn CIN. An HPV-independent pathogenetic pathway with a p53-alteration was identified for these cases. CSCC associated with uterine prolapse represents HPV-independent tumors harboring a TP53 mutation. For the first time, a precursor lesion of HPV-independent CSCC of the uterine cervix is described with a differentiated VIN-like morphology, and a separate tumorigenic pathway defined.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"2-14"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498002","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}