American Journal of Surgical Pathology最新文献

{"title":"Validation of Congestive Hepatic Fibrosis Score in Pediatric and Adult Fontan-Associated Liver Disease.","authors":"Robyn C Reed, Matthew M Yeh, Matthew D Files, Joshua Price, Humera Ahmed, Evelyn K Hsu, Xing Wang, Brian Mau, M Cristina Pacheco","doi":"10.1097/PAS.0000000000002418","DOIUrl":"10.1097/PAS.0000000000002418","url":null,"abstract":"<p><p>Fontan-associated liver disease is a unique form of congestive hepatopathy occurring after Fontan palliation of single functional ventricle congenital heart disease. Although congestive hepatic fibrosis post-Fontan has been scored with various histologic systems, none have been validated in this population. The Congestive Hepatic Fibrosis Score (CHFS) was developed to assess liver disease in congestive hepatopathy secondary to chronic right heart failure and is a promising tool for staging congestive hepatic fibrosis post-Fontan. We sought to validate the CHFS in this setting and to examine clinical, laboratory, and hemodynamic parameters impacting the development of Fontan-associated liver disease. Three pathologists reviewed liver biopsies from 42 pediatric and adult post-Fontan patients, with review of clinical, laboratory, and hemodynamic parameters. CHFS and METAVIR fibrosis scores divided biopsies into identical clusters of low stage (stages 0, 1, and 2) and high stage (stages 3 and 4) fibrosis. Interobserver variability for both scores was moderate. Patients with high-stage fibrosis had significantly longer mean time since Fontan. Female patients were more likely to have high-stage fibrosis. Hemodynamic variables had no significant differences between the groups. We conclude that CHFS is a valid scoring method in pediatric and adult patients post-Fontan. Time since Fontan is the best predictor of severe hepatic fibrosis, but much interpatient variation is not explained by any of the identified clinical, laboratory, or hemodynamic parameters. Liver biopsy, therefore, remains the best means of assessing liver fibrosis in post-Fontan patients.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"942-947"},"PeriodicalIF":4.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Immunohistochemistry With Fluorescence In Situ Hybridization for Assessment of CCND1 Rearrangement in Plasma Cell Myeloma.","authors":"Maria Y Chen, Anna B Rider, Judith A Ferry, Robert P Hasserjian, Valentina Nardi, Abner Louissaint, Aliyah R Sohani, Lisa D Yuen","doi":"10.1097/PAS.0000000000002421","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002421","url":null,"abstract":"<p><p>More than half of patients with plasma cell myeloma (PCM) relapse after treatment and require novel therapies. Venetoclax, a highly specific and effective oral BCL2 inhibitor, has a favorable risk-benefit ratio for PCM patients with t(11;14)/IGH::CCND1. Standard of care for new or relapsed cases of PCM incorporates fluorescence in situ hybridization (FISH) analysis for the detection of IGH::CCND1. However, FISH requires a high-quality bone marrow (BM) aspirate sample and plasma cell (PC) purification. Immunohistochemical (IHC) staining to detect overexpressed cyclin D1 protein resulting from IGH::CCND1 is lower cost, more widely available, and has a faster turnaround time than FISH. However, a predictive cyclin D1 IHC cutoff has yet to be established for correlation with IGH::CCND1. We evaluated a testing cohort of 85 BM biopsy cases diagnosed as PCM with adequate core biopsies and corresponding myeloma FISH results (43 fusion positive and 42 fusion negative) to develop a multitiered classification system for cyclin D1 IHC expression in plasma cell myeloma that can predict IGH::CCND1 fusion status with high confidence in the majority of cases. Using H-score to predict fusion status yielded positive and negative predictive values of 97% and 100%, respectively. A validation cohort consisting of 50 additional cases (24 fusion negative and 26 fusion positive) had 93% positive and 100% negative predictive values for fusion status. We find that cyclin D1 IHC has high concordance with FISH for IGH::CCND1 fusion status and is a valuable alternative when FISH is suboptimal or unavailable.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic and Whole Exome Sequencing Analyzes of High-Grade Serous Carcinoma-Like Carcinoma of the Breast Reveal Unique Genetic Profile and Poor Clinical Outcome.","authors":"Wen-Yu Hsiao, Thi Truc Anh Nguyen, Wei Yang, Hu Yan, Zaibo Li, Linsheng Zhang, Jingjing Yang, Xiaoxian Li","doi":"10.1097/PAS.0000000000002423","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002423","url":null,"abstract":"<p><p>We identified 9 cases of primary high-grade serous-like carcinoma (HG-SL-Ca) of the breast that displayed the morphology of high-grade serous carcinoma of Müllerian origin. These cases could represent a new entity of breast carcinoma. This study included 9 cases of HG-SL-Ca of the breast. Extensive clinicopathologic features and outcome data were available and evaluated in 8 cases. We, for the first time, performed whole exome sequencing (WES) on 6 of these cases to identify pathogenic germline and somatic genetic mutations and conducted gene pathway enrichment analyses. Six cases were triple negative; 2 were HER2 positive, and 1 was ER+/PR+/HER2-. Eight of the 9 cases had high nuclear grade and the other 1 had intermediate nuclear grade. Six patients received chemotherapy; the patient with ER+/PR+/HER2-cancer received hormonal therapy only, and 1 patient with dementia did not receive any systemic therapy. Follow-up data showed 2 patients had distant metastasis and 1 had chest wall recurrence. Two patients died of disease, including 1 patient receiving palliative care and 1 with lung and pleural metastasis. Most of the cases were positive for GATA3 immunohistochemistry (IHC) staining and all were negative for PAX8. All except for 1 case (focally positive) were negative for WT1 nuclear stain. Aberrant p53 IHC staining patterns were observed in 6 cases. WES analyses showed 26 genes with pathogenic germline mutations and 28 genes with pathogenic somatic mutations in these cases that were in the ACR GENIE mutated gene list. Pathway analyses showed that these genes with pathogenic germline or somatic mutations were enriched in the PI3K-AKT-mTOR pathway, WNT pathways, and death receptor pathway. TP53 was recurrently mutated, containing somatic variants in 4 cases, and all these 4 cases had aberrant p53 IHC staining patterns. We, for the first time, performed WES analyses on HG-SL-Ca of the breast. The majority of HG-SL-Ca were triple negative or HER2 positive with high nuclear grade. Patients with HG-SL-Ca of the breast had a poor prognosis. Our pathway analyses showed that genes containing pathogenic germline or somatic mutations were enriched in the PI3K-AKT-mTOR pathway, WNT pathways, and death receptor pathway, which could provide potential targeted treatment options. TP53 was recurrently mutated in 4 cases and all these 4 cases had aberrant p53 IHC staining patterns.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dominant Negative PTEN Alterations in Endometrial Carcinoma Are Associated With Retained Immunohistochemical PTEN Expression.","authors":"Kianoosh Keyhanian, Aurelia Busca, Brooke Howitt, Phoebe Hammer, Leandra Kingsley, Bryan Lo","doi":"10.1097/PAS.0000000000002412","DOIUrl":"10.1097/PAS.0000000000002412","url":null,"abstract":"<p><p>PTEN immunohistochemistry (IHC) is considered complimentary for assessment of PTEN abnormality in endometrial carcinoma (EC), since PTEN IHC staining pattern does not entirely correlate with the presence and absence of mutations on sequencing. A set of functionally defective PTEN variants with stable protein levels are known to act in a dominant-negative manner to suppress wild-type PTEN activity. Our objective was to evaluate PTEN IHC patterns in ECs with dominant-negative (DN) PTEN mutations. ECs with next-generation sequencing (NGS, using Oncomine Comprehensive Assay v3) over a 3-year period were enrolled. PTEN IHC was scored as loss, subclonal loss, reduced, and intact (the last 3 considered retained). Of 182 EC cases, 114 (62.6%) were identified to have PTEN mutation(s), the majority of endometrioid histotype (87.7%) from all EC molecular classes. Forty-seven cases (41.2%) harbored DN mutations which were of endometrioid (FIGO 1 [n=15, 31.9%], FIGO 2 [n=23, 48.9%], FIGO 3 [n=3, 6.4%]), dedifferentiated (n=2, 4%), carcinosarcoma (n=3, 6%), mixed endometrioid and clear cell carcinoma (n=1, 2%) histotype; with representatives from all molecular classes. PTEN IHC showed retained expression in 95.8% (45/47) of DN-mutated cases (intact staining in 36 [76.6%], reduced staining in 6 [12.5%], and subclonal loss in 3 [6.4%]) cases. Two cases showed loss of expression (4.2%). In the PTEN wild-type group, loss and subclonal loss of expression were seen in 12.5% and 9.4%, respectively. Our results indicate that DN PTEN mutations are common in EC, and are associated with retained IHC staining (intact, reduced, or subclonal loss). These results highlight that IHC and NGS are both required in capturing the full spectrum of PTEN-abnormal EC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"923-930"},"PeriodicalIF":4.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dublin International Society of Urological Pathology (ISUP) Consensus Conference on Urachal Neoplasms and Urinary Bladder Glandular Lesions: It's About Time!","authors":"Gladell P Paner, Glen Kristiansen, Henning Reis","doi":"10.1097/PAS.0000000000002404","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002404","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic and Predictive Value of SARIFA-status Within Molecular Subgroups of Colorectal Cancer: Insights From the Netherlands Cohort Study.","authors":"Nic G Reitsam, Kelly Offermans, Colinda C J M Simons, Bianca Grosser, Jessica Zimmermann, Heike I Grabsch, Bruno Märkl, Piet A van den Brandt","doi":"10.1097/PAS.0000000000002408","DOIUrl":"10.1097/PAS.0000000000002408","url":null,"abstract":"<p><p>We recently proposed Stroma AReactive Invasion Front Areas (SARIFA), defined as direct tumor-adipocyte interaction at the invasion front, as a novel hematoxylin-and-eosin (H&E)-based histopathological prognostic biomarker in various cancers. Given that microsatellite instability, BRAF , and RAS mutation status are routinely tested for colorectal cancers (CRC), studying SARIFA's additional prognostic value within these molecular subgroups is crucial. In addition, exploring whether the survival benefit from adjuvant therapy differs according to SARIFA-status may enhance patient treatment and outcome. SARIFA-status, BRAF , RAS , and DNA mismatch repair (MMR) status were available for 1726 CRC patients from the prospective Netherlands Cohort Study (NLCS, 1986-2006). In this study, we investigated (1) the relationship between SARIFA-status and CRC molecular characteristics, (2) the prognostic value of SARIFA-status within these molecular subgroups, and (3) whether SARIFA-status was associated with survival benefit from adjuvant therapy. SARIFA-positive CRCs more frequently showed a BRAF mutation compared to SARIFA-negative CRCs ( P <0.001). BRAF -mutant/MMR-proficient CRCs were enriched in SARIFA-positive cases. SARIFA-positivity was associated with poor CRC-specific (HR range : 1.47 to 1.78) and overall survival (HR range : 1.35 to 1.70) within all molecular subgroups except MMR-deficient CRCs. Patients with SARIFA-positive CRC showed a CRC-specific survival benefit from adjuvant therapy compared to surgery alone (HR CRC-specific : 0.59; 95% CI: 0.44-0.79), while no CRC-specific survival benefit was observed for patients with SARIFA-negative CRC. To conclude, our results indicate that SARIFA-positivity is more common in the aggressive subset of BRAF -mutant and BRAF -mutant/MMR-proficient CRCs. Moreover, SARIFA-positivity provides additional prognostic value within molecular subgroups based on BRAF , RAS , and MMR status, suggesting that it may enhance prognostic stratification of CRC patients.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"956-969"},"PeriodicalIF":4.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult Granulosa Cell Tumors of the Ovary With Tubular Differentiation: A Report of 80 Examples of an Underemphasized Feature With Clinicopathologic and Genomic Differences From Other Sex Cord-Stromal Tumors.","authors":"Lauren J Ray, Robert H Young, Mark F Sabbagh, Adam S Fisch, Esther Oliva, Kyle M Devins","doi":"10.1097/PAS.0000000000002407","DOIUrl":"10.1097/PAS.0000000000002407","url":null,"abstract":"<p><p>Occasional ovarian sex cord-stromal tumors exhibit features suggestive of more than 1 subtype, including some with areas of both \"female\" (granulosa) and \"male\" (Sertoli and/or Leydig) cell types. These tumors, historically often referred to as \"gynandroblastomas,\" are frequently difficult to classify due to considerable clinical and morphologic heterogeneity. Herein, we describe a particular pattern of differentiation in which tubules occurred within tumors whose overall clinicopathologic features indicate that they are best characterized as adult granulosa cell tumors (AGCT). Eighty tumors were identified. Patient ages ranged from 15 to 87 (median: 52) years, and 28 had endocrine manifestations (25 estrogenic; 3 androgenic). Follow-up was available in 13 patients and ranged from 10 to 266 (median: 60) months, disclosing recurrence in 2. Microscopically, all tumors not only contained areas of typical granulosa cell morphology (diffuse, trabecular, corded, and others), which often dominated, but also contained variable amounts of hollow and/or solid tubules resembling those seen in Sertoli cell tumors. Next-generation sequencing was successful in 11 tumors. Two of these harbored FOXL2 p.C134W variants, and 2 others had FOXL2 copy number gains; none had DICER1 mutations. On the basis of the average age of the patients, frequency of estrogenic manifestations, abundance of standard AGCT morphology, and occasional late recurrences, we suggest that these tumors form a distinct group and propose the term \"AGCTs with tubular differentiation\" to denote them.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"770-780"},"PeriodicalIF":4.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Early\" Clear Cell Proliferations (Clear Cell Carcinoma in Situ) in Ovarian Endometriotic Cysts: Report of a Case Series With Recommendations for Terminology.","authors":"Nesa S Karunadhas, Mark Catherwood, Helen Stringfellow, Rupali Arora, W Glenn McCluggage","doi":"10.1097/PAS.0000000000002415","DOIUrl":"10.1097/PAS.0000000000002415","url":null,"abstract":"<p><p>Clear cell carcinoma (CCC) is an uncommon malignancy accounting for ∼12% of ovarian carcinomas. Most cases arise from endometriosis, frequently an endometriotic cyst. We report a series of 6 cases where clear cell proliferations, morphologically, and immunophenotypically consistent with CCC, involve the epithelial lining of an endometriotic cyst without invasion into the surrounding stroma. The patients were aged 29 to 63 years (mean 45). In all cases, epithelial proliferations composed of cells with atypical nuclei, sometimes with a hobnail morphology, and clear or eosinophilic cytoplasm involved the epithelial lining of an ovarian endometriotic cyst. In areas, the proliferations comprised a monolayer, but in all cases, there was also significant epithelial stratification and multilayering, sometimes with a pseudopapillary architecture. There was no invasion of the atypical cells into the surrounding ovarian stroma. The proliferations were positive for Napsin A (6 of 6; 4 diffuse, 2 focal), racemase (5 of 5; 3 diffuse, 2 focal), hepatocyte nuclear factor 1-beta (5 of 5; all diffuse), oestrogen receptor (5 of 6; 2 diffuse, 3 focal), and PAX8 (3 of 3; all diffuse). p53 was wild-type in all 6 cases and WT1 and progesterone receptor were negative in the 4 and 6 cases tested, respectively. Mismatch repair immunohistochemistry was retained in the 3 cases tested. Next-generation sequencing was performed in 2 cases. In 1 case, a sole pathogenic MSH6 variant (p.Ser65fs) was identified. Follow-up (2 to 24 months) was available in 5 cases and there was no tumour recurrence. In reporting these \"early\" clear cell proliferations in endometriotic cysts, we provide recommendations for the reporting pathologist regarding the most appropriate terminology, which is important in patient management. We suggest that these proliferations be termed \"CCC in situ\" and that identification of such a lesion should prompt extensive sampling in order to exclude an invasive CCC component within the stroma outside the endometriotic cyst lining. We also stress the importance of close dialogue between the pathologist and the clinician and between the clinician and the patient in order to avoid overtreatment in such cases.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"901-908"},"PeriodicalIF":4.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Confocal Laser Microscopy for Intraoperative Margin Assessment in Breast-Conserving Surgery: A New Procedure in the Pathology Laboratory Workflow.","authors":"Julien Colard-Thomas, Antonia Pialoux-Guibal, Pierre Gemival, Aurélie Maran-Gonzalez, Lakhdar Khellaf, Cristina Leaha, Evelyne Verdanet, Anne Mourregot, Marian Gutowski, Didier Pourquier","doi":"10.1097/PAS.0000000000002409","DOIUrl":"10.1097/PAS.0000000000002409","url":null,"abstract":"<p><p>One of the breast-conserving surgery goals is to achieve negative resection margins and avoid reoperation. Therefore, accurate intraoperative margin assessment is essential, but still challenging. Recently, confocal microscopy devices, such as Histolog Scanner (HS), have shown promise for intraoperative margin assessment. The aim of this study was to assess HS for the intraoperative examination of lumpectomy specimens by the pathologists of our institute. Intraoperative margin assessment was performed by macroscopic assessment and by HS imaging to provide information for re-excision decision-making. The specific contribution of HS was evaluated by comparing the HS-based findings with the final pathology reports based on formalin-fixed paraffin-embedded tissue analysis. The study population included 20 women with histologically confirmed invasive breast carcinoma who underwent breast-conserving surgery (mean age of 62.9 y; 41 to 88 y; 21 tumors in total). HS led to the same decision as macroscopic examination in 76.2% of cases and prompted additional re-excisions in 19% of cases. Compared with the pathology reports, the accuracy rates of the macroscopic and HS assessments were 81% (58.1 to 94.6) and 95.2% (76.2 to 99.9), respectively. Moreover, 5 cases are described to illustrate HS practical contribution and limitations. In conclusion, HS is user-friendly, generally reliable, and enhances the routine macroscopic examination by providing detailed imaging of lumpectomy specimens. In combination with macroscopic examination, HS is an effective tool for intraoperative margin assessment, assisting both pathologists and surgeons in making accurate intraoperative decisions regarding margin re-excision, thereby preventing the need for new surgical operations.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"909-922"},"PeriodicalIF":4.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinically Sporadic Folliculin -mutated Renal Epithelial Neoplasms Represent a Mixture of True Somatic Folliculin -mutated and Occult Birt-Hogg-Dubé Syndrome-associated Cases : Morphologic and Molecular Overlap With TSC/MTOR -mutated Eosinophilic Renal Neoplasms and MiT Family Translocation Renal Cell Carcinoma.","authors":"Pedram Argani, Ezra Baraban, Oksana Yaskiv, Huili Li, Swati Bhardwaj, Katya Dombrowski, Tamara L Lotan, Ying S Zou, Sunil H Patel, Betina Katz, Qi Cai, Rohit Mehra, Norman Barker, Jonathan Dudley, Doreen N Palsgrove","doi":"10.1097/PAS.0000000000002413","DOIUrl":"10.1097/PAS.0000000000002413","url":null,"abstract":"<p><p>Germline mutations in the folliculin ( FLCN ) gene define Birt-Hogg-Dubé syndrome, which is associated with a variety of renal neoplasms; however, the role of FLCN mutations in sporadic renal neoplasms has not been well-defined. We identified 8 oncocytic/cystic renal neoplasms that presented as sporadic tumors and harbored FLCN mutations and no other genetic alterations characteristic of another established subtype. On further workup, 5 seem to harbor true somatic FLCN mutations, whereas the other 3 represent neoplasms associated with occult Birt-Hogg-Dubé syndrome. Patients were all females ranging in age from 25 to 77 years, and all neoplasms were confined to the kidney. The neoplasms overlapped morphologically with TSC/MTOR -mutated eosinophilic renal neoplasms and TFE3/TFEB -rearranged renal cell carcinoma. All neoplasms extensively expressed GPNMB, a downstream marker of TFE3/TFEB pathway activation, which is logical given the known molecular interplay of folliculin with TSC/MTOR/TFE3/TFEB. All 3 occult syndromic cases demonstrated multiple chromosome losses and gains not seen in the 5 sporadic neoplasms. In conclusion, diffuse GPNMB expression in the absence of TSC/MTOR/TFE3/TFEB alterations, particularly when the morphology suggests the presence of the latter, is a clue to FLCN -mutated renal epithelial neoplasms, which in a subset of cases may be a clue to occult Birt-Hogg-Dubé syndrome.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"859-872"},"PeriodicalIF":4.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}