Human pathology最新文献

{"title":"Metastatic renal cell carcinoma with fibromyomatous stroma associated with tuberous sclerosis or MTOR, TSC1/TSC2-Mutations: A Series of 4 cases and a review of the literature","authors":"Sounak Gupta ,&nbsp;Michael R. McCarthy ,&nbsp;Melissa Y. Tjota ,&nbsp;Tatjana Antic ,&nbsp;John C. Cheville","doi":"10.1016/j.humpath.2024.105680","DOIUrl":"10.1016/j.humpath.2024.105680","url":null,"abstract":"<div><div>Renal cell carcinoma with fibromyomatous stroma (RCCfms) are characterized by a constellation of morphologic findings that include elongated tubules lined by cells with clear to pale eosinophilic cytoplasm and intersecting bands of smooth muscle stroma. Consistent immunohistochemistry findings in RCCfms include diffuse positivity for carbonic anhydrase 9 and variable expression of keratin 7. Molecular profiling of such tumors show either pathogenic alterations of the <em>ELOC</em> (<em>TCEB1</em>) gene, or alterations of <em>MTOR</em>, <em>TSC1</em>, and <em>TSC2</em>. <em>MTOR</em>, <em>TSC1</em>/<em>TSC2</em>-altered RCCfms (M/TSC-RCCfms) has been reported both in the sporadic setting and in association with tuberous sclerosis complex (TSC). The importance of accurate diagnosis of M/TSC-RCCfms includes prompting germline testing in the appropriate clinical context. In addition, it can lead to patient management strategies that are focused on the preservation of renal function, as TSC patients often have multifocal and bilateral disease. As diagnostic criteria for M/TSC-RCCfms have only been recently established, additional data are needed to understand the natural history of this disease. Herein, we report 6 patients with metastatic M/TSC-RCCfms, including four patients from our institutional archives (four males, aged 36–58 years at nephrectomy), and two additional cases reported in the literature. Five patients had TSC, and the sixth had an <em>MTOR</em>-altered RCCfms. The majority of patients (5/6, 83%) presented with regional lymph node involvement and one patient developed metastases to the lung. All patients were alive at last follow up (median follow-up of 85 months). Our report is intended to raise awareness regarding rare instances of metastatic behavior for M/TSC-RCCfms.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105680"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multinucleated tumor cells and micropapillary morphology appear to be predictors of poor prognosis in renal cell carcinoma with papillary and oncocytic features","authors":"Ting Zhao,&nbsp;Thomas Denize,&nbsp;Hanzhang Wang,&nbsp;Adam S. Fisch,&nbsp;Shulin Wu,&nbsp;Chin-Lee Wu,&nbsp;Kristine M. Cornejo","doi":"10.1016/j.humpath.2024.105677","DOIUrl":"10.1016/j.humpath.2024.105677","url":null,"abstract":"<div><div>Renal cell carcinoma with papillary and oncocytic features (RCC-PO) are poorly understood, partially due to conflicting results in multiple studies. The histological features that predict behavior of RCC-PO have not been elucidated. The aim is to review clinicopathologic features and to correlate clinical outcomes of patients with RCC-PO to further expand our knowledge on these heterogeneous tumors. An archival search was done for “RCC” and “papillary,” and tumors with &gt;50% papillary and oncocytic features were included. Clinicopathologic data including tumor size, grade, stage, molecular and immunohistochemical testing when performed, and follow-up data were collected. Using multivariate analyses, correlation between histological features, tumor stage and prognosis were analyzed. Sixty-one patients with RCC-PO were identified of which 49 (80%) were male with a median age of 65 (range: 36–93) years, and a mean tumor size of 5.2 (range: 1–21.5) cm. Micropapillary features were seen in 4, bizarre nuclei (at least 3 times larger or with irregular shape) in 6, multinucleated tumor cells (MTC) in 15, single or small clusters (SSC) (made of 2–3 tumor cells) located away from areas of necrosis in 16, and striking eosinophilic cytoplasmic inclusions in 3 tumors, respectively. Thirty-six (59%) tumors were high-grade (WHO/ISUP grade 3–4), and 23 (38%) had a high stage (≥pT3 or pN1). Tumors were positive for AMACR (15/16) and CK7 (13/17), with preserved FH (7/7) staining and were all negative for CD117 (0/7), ALK, TFE3, cathepsin K, Melan A, and HMB45 (0/4, each). Three tumors underwent chromosomal microarray (CMA) plus gene fusion assay, and FISH and germline testing for <em>FLCN</em> and <em>MET</em> gene alterations by PCR were done on 1 each. Ten (16%) patients had a local recurrence (LR) or metastasis after nephrectomy; 4 died of disease (2 had tumors with micropapillary features), with a median follow-up of 7 (range: 0.01–19) years. Tumors with micropapillary features showed significantly higher RCC-PO-related mortality (50% vs. 3.5%, p &lt; 0.001). In multivariable analysis, SSC correlated with a higher stage (HR: 11.95; p = 0.005); micropapillary features (HR: 18.42; p = 0.017) and MTC (HR: 180.22; p = 0.036) with presence of metastasis/LR; and micropapillary features with a higher RCC-PO-related mortality (HR: 60.35; p = 0.036). RCC-PO are cytogenetically heterogeneous with overlapping features of various renal neoplasms. Micropapillary features and MTC appear to be independent predictors of poor outcomes in these tumors.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105677"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinically aggressive follicular cell-derived thyroid carcinoma: A comprehensive series with histomolecular characterization and discovery of novel gene fusions","authors":"Ziyad Alsugair ,&nbsp;Francoise Descotes ,&nbsp;Jonathan Lopez ,&nbsp;Hélène Lasolle ,&nbsp;Françoise Borson Chazot ,&nbsp;Jean-Christophe Lifante ,&nbsp;Myriam Decaussin-Petrucci","doi":"10.1016/j.humpath.2024.105674","DOIUrl":"10.1016/j.humpath.2024.105674","url":null,"abstract":"<div><div>Thyroid cancer rates are increasing, mostly with a good prognosis and less than 2 % of cases are more aggressive. Recent efforts focus on understanding molecular events predicting tumor aggressiveness and treatment targets in advanced thyroid cancer. This study concerned 57 patients with aggressive metastatic, and/or radioiodine-refractory thyroid carcinomas, excluding anaplastic cases. Molecular profiling, including next-generation sequencing and RNA sequencing, was conducted to dissect the complex molecular landscape of these aggressive tumors. Histopathological analysis indicated that papillary carcinomas and high-grade thyroid carcinomas were predominant. The molecular analysis revealed a spectrum of mutations, with prevalent occurrences of BRAF V600E, TERT promoter, and RAS mutations. RNA sequencing identified ten gene fusions, such as <em>NTRK</em> and <em>RET</em> fusions. Three novel fusions were discovered: <em>UGGT1::TERT</em>, <em>BTBD9::TERT</em>, and <em>TG::IGF1R</em>, potentially driving aggressive behavior. <em>UGGT1::TERT</em> was linked to radioiodine-refractory tall cell PTC, <em>BTBD9::TERT</em> to high-grade follicular PTC, and <em>TG::IGF1R</em> to oncocytic carcinoma. These findings underscore the importance of <em>TERT</em> alterations in aggressive phenotypes and offer insights into molecular mechanisms guiding targeted therapies. Further research is necessary to confirm their significance as diagnostic and prognostic markers in thyroid cancer.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105674"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging Clinicopathologic Features and Genetics in Follicular Lymphoma: Towards Enhanced Diagnostic Accuracy and Subtype Differentiation.","authors":"Jan Bosch-Schips, Xenia Parisi, Fina Climent, Francisco Vega","doi":"10.1016/j.humpath.2024.105676","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.105676","url":null,"abstract":"<p><p>Follicular lymphoma (FL) is a neoplasm that originates from germinal center B cells and typically forms at least a partial follicular pattern. Approximately 85% of FL cases harbor the t(14;18)(q32;q21)/IGH::BCL2 which leads to the overexpression of BCL2. These cases are referred to as classic FL in the current World Health Organization classification [1]. These neoplasms often exhibit hallmark epigenetic deregulation due to recurrent mutations in genes such as KMT2D, CREBBP, and EZH2, with KMT2D and CREBBP considered founding events in FL lymphomagenesis. In contrast, about 15% of FL cases are negative for the t(14;18), which could present diagnostic challenges. These cases may lack the typical genetic markers and require careful pathological and molecular analysis for accurate diagnosis. This review aims to provide an up-to-date pathology resource on FL, focusing on the pathological and molecular characteristics of these neoplasms. We will detail the diagnostic criteria for FL and emphasize the importance of genetic and mutational analyses in accurately characterizing and distinguishing FL subtypes. Furthermore, we will propose methodologies and best practices for the diagnostic work-up of FL to enhance diagnostic accuracy.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105676"},"PeriodicalIF":2.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SALL4 expression is very rare in endometrial endometrioid and serous carcinoma.","authors":"Meline Brouard, Mousa Mobarki, Michel Péoc'h, Georgia Karpathiou","doi":"10.1016/j.humpath.2024.105675","DOIUrl":"10.1016/j.humpath.2024.105675","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105675"},"PeriodicalIF":2.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelioid trophoblastic tumor in male patients with germ cell tumor: A clinicopathologic analysis of five cases","authors":"Georges C. Tabet ,&nbsp;Lan Zheng ,&nbsp;Hossein Hosseini ,&nbsp;John Ward ,&nbsp;Louis Pisters ,&nbsp;Matthew T. Campbell ,&nbsp;Shi-Ming Tu ,&nbsp;Bogdan Czerniak ,&nbsp;Charles C. Guo","doi":"10.1016/j.humpath.2024.105673","DOIUrl":"10.1016/j.humpath.2024.105673","url":null,"abstract":"<div><div>Epithelioid trophoblastic tumor (ETT) is an extremely rare chorionic-type neoplasm in the testis, with only seven cases reported in the literature. Here, we report five cases of testicular ETT from a single institution, constituting the largest series of this rare tumor to date. The patients had a mean age of 44 years (range, 20–68 years). Four patients had a previous history of testicular germ cell tumor (GCT) treated with chemotherapy, and they developed ETT in metastatic sites in a mean of 11 years (range, 3–15 years) after the initial diagnosis of testicular GCT. Only one patient had ETT in the testis. Three patients had a normal serum beta–human chorionic gonadotropin (β-hCG) level, and two patients had a level that was slightly elevated, but far below that typically seen in patients with choriocarcinoma. ETT was characterized by a proliferation of intermediate trophoblastic cells with abundant eosinophilic cytoplasm, and the tumors frequently had coagulative necrosis with eosinophilic debris, mimicking keratinizing squamous cell carcinoma. The trophoblastic phenotype of ETT was supported by its immunoreactivity for trophoblastic markers, including GATA-3 (3 of 3 cases tested), α-inhibin (3/4), p63 (3/5), and β-hCG (3/4). ETT was also positive for cytokeratin (4/4) and GCT marker SALL4 (3/3). Despite surgery and chemotherapy, two patients died of disease 17 months after ETT diagnosis, and three patients were alive with metastatic disease at a mean of 20 months (range, 15–28 months). Our results demonstrate that ETT may be an aggressive disease associated with distinct pathologic features and poor clinical outcome.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105673"},"PeriodicalIF":2.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intramuscular hemangioma capillary type with HRAS mutation: Expanding the molecular genetic spectrum with an emphasis on overlap with arteriovenous malformations and distinct from infantile hemangioma","authors":"Shuang Xue ,&nbsp;Mei Li ,&nbsp;Xijun Zhang ,&nbsp;Peigang Ning ,&nbsp;Changxian Dong ,&nbsp;Xiaonan Guo ,&nbsp;Qiuyu Liu","doi":"10.1016/j.humpath.2024.105672","DOIUrl":"10.1016/j.humpath.2024.105672","url":null,"abstract":"<div><h3>Aims</h3><div>Intramuscular hemangioma capillary type (IHCT) is a rare entity that refers to fast-flow vascular lesions. This study aims to elucidate the relationships between clinicopathological, radiological, and molecular characteristics in IHCT patients.</div></div><div><h3>Methods and results</h3><div>We reviewed all IHCT cases which were treated surgically in our pathology database from 2014 to 2023. Ten cases were analyzed via next-generation sequencing (NGS) and Sanger sequencing. The cohort consisted of 10 patients (6 males, 4 females) with a median age of 18 years (range: 1–37). Disease lesions were located in the trunk (n = 4), upper extremity (n = 2), lower extremity (n = 2), shoulder (n = 1), and neck (n = 1). IHCT is most commonly a progressively increasing painless mass. Histopathologically, all lesions exhibited aggregates, lobules, and anastomosing cords of capillary-type vessels separating or infiltrating the skeletal muscles. Four cases exhibited irregularly dilated vessels with thick walls, such as arteriovenous malformations (AVM) in the lesion's periphery. MRI findings commonly demonstrated a well-delineated, homogeneous mass. Somatic mutations were detected in seven of the ten IHCT cases. Four cases harbored mutations in <em>MAP2K1</em> (p.Q58_E62del, p.K57_G61del, p.K57 N), two cases harbored mutations in <em>KRAS</em> (p.Q61R and p.L56V, p.G13R), and one case harbored a mutation in <em>HRAS</em> (p.D69_Q70insRWYSAMRD). Mutant allele frequencies detected by sequencing ranged from 9.98% to 15.97%.</div></div><div><h3>Conclusions</h3><div>The hemodynamic and molecular genetic phenotypes of IHCT closely resemble those observed in AVMs. Newly identified <em>KRAS</em> missense mutations, including cases with coexisting mutation types, and <em>HRAS</em> insertion mutations offer valuable insights into the genetic basis of vascular anomalies. These findings may also present potential targets for the development of novel pharmacotherapeutic interventions.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105672"},"PeriodicalIF":2.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic ALK-negative anaplastic large cell lymphoma: Insights into morphologic, immunophenotypic, genetic and molecular characteristics.","authors":"Wei Xie, L Jeffrey Medeiros, Guang Fan, Shaoying Li, Jie Xu","doi":"10.1016/j.humpath.2024.105671","DOIUrl":"https://doi.org/10.1016/j.humpath.2024.105671","url":null,"abstract":"<p><p>Anaplastic large cell lymphoma (ALCL) is a mature T-cell neoplasm characterized by large pleomorphic cells, often with horseshoe- or kidney-shaped nuclei and abundant cytoplasm (hallmark cells), and uniformly strong CD30 expression. Based on ALK expression or ALK rearrangement, ALCL is further classified into ALK-positive (ALK+) and ALK-negative types. This review focuses on the clinicopathologic, immunophenotypic, cytogenetic and molecular features of systemic ALK-negative ALCL. These patients are usually older adults who present with advanced stage disease and often a poor prognosis. ALK-negative ALCL is morphologically indistinguishable from the common pattern of ALK+ ALCL, but some cases show non-common morphology, such as \"donut cells\", Hodgkin-like features. ALK-negative ALCL is often negative for T-cell antigens (so-called \"antigen loss\") and in some cases can have a \"null\" immunophenotype and be confused with other hematopoietic and non-hematopoietic neoplasms. Recurrent genetic/molecular alterations have been identified in systemic ALK-negative ALCL, including rearrangements of DUSP22, TP63, JAK2, FRK, MYC, ROS1 and TYK2; mutations of JAK1, STAT3 and MSCE; and aberrant expression of ERBB4. Some of these alterations may have prognostic significance and/or provide potential therapeutic targets. Data support the idea that ALK-negative ALCL with DUSP22 rearrangement is a distinctive variant due to its unique morphologic, immunophenotypic and molecular features. Gene expression profiling data have shown that ALK-negative ALCL has distinctive molecular signatures, different from ALK+ ALCL and other T-cell lymphomas. Better understanding of the morphologic, immunophenotypic, genetic and molecular features of ALK-negative ALCL will help establish the correct diagnosis, guide therapeutic strategies and improve patient outcomes.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105671"},"PeriodicalIF":2.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of the large amino acid transporter SLC7A5/LAT1 on immune cells is enhanced in primary sclerosing cholangitis-associated cholangiocarcinoma and correlates with poor prognosis in cholangiocarcinoma","authors":"Vittorio Branchi ,&nbsp;Racha Hosni ,&nbsp;Lukas Kiwitz ,&nbsp;Susanna Ng ,&nbsp;Gemma van der Voort ,&nbsp;Neila Bambi ,&nbsp;Eileen Kleinfelder ,&nbsp;Laura K. Esser ,&nbsp;Leona Dold ,&nbsp;Bettina Langhans ,&nbsp;Maria A. Gonzalez-Carmona ,&nbsp;Saskia Ting ,&nbsp;Glen Kristiansen ,&nbsp;Jörg C. Kalff ,&nbsp;Kevin Thurley ,&nbsp;Michael Hölzel ,&nbsp;Hanno Matthaei ,&nbsp;Marieta I. Toma","doi":"10.1016/j.humpath.2024.105670","DOIUrl":"10.1016/j.humpath.2024.105670","url":null,"abstract":"<div><div>Biliary tract cancers (BTC) are rare lethal malignancies arising along the biliary tree. Unfortunately, effective therapeutics are lacking and the prognosis remains dismal even for patients eligible for surgical resection. Therefore, novel therapeutic approaches along with early detection strategies and prognostic markers are urgently needed. Primary sclerosing cholangitis (PSC) is a chronic disease of the bile ducts leading to fibrosis and ultimately cirrhosis. Patients with PSC have a 5–20% lifetime risk of developing BTC; yet the molecular mechanisms that underpin the development of PSC- associated biliary tract cancer (PSC-BTC) have not been fully elucidated. SLC7A5/LAT1, a large amino acid transporter, has been shown to modulate cell growth and proliferation as well as other intracellular processes in solid tumors. In this study, we evaluated <em>SLC7A5</em> expression in PSC-BTC and in sporadic BTC (sBTC) and its role as a prognostic factor. Analysis of the TGCA cohort showed a significantly higher expression of <em>SLC7A5</em> in tumor tissue compared with adjacent normal tissue (p = 0.0002) in BTC. In our cohort (comprised of 69 BTC patients including 16 PSC-BTC), SLC7A5/LAT1 expression was observed in both tumor and intratumoral immune cells. A significantly higher percentage of SLC7A5/LAT1 positive intratumoral immune cells was observed in PSC-BTC compared with sBTC (p = 0.004). Multiplex immunofluorescence co-detection by indexing (CODEX) analysis identified CD4⁺ regulatory T lymphocytes and CD68⁺ macrophages as the largest immune cell populations expressing LAT1.</div><div>SLC7A5/LAT1 expression as well as a higher intratumoral infiltration of SLC7A5/LAT1-positive immune cells (≥2%) were associated with a shorter overall survival in our cohort (LogRank test, p = 0.04 and p = 0.008; respectively). SLC7A5/LAT1 expressing tumors are higher staged tumors (pT3/4 versus pT1/2, p = 0.048).</div><div>These results underline the potential use of SLC7A5/LAT1 as a prognostic marker in BTC. Furthermore, the higher frequency of SLC7A5/LAT1 positive immune cells in PSC-BTC compared to sBTC may hint at the potential role of SLC7A5/LAT1 in inflammation-driven carcinogenesis.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105670"},"PeriodicalIF":2.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological and molecular genetic insights into EBV-positive inflammatory follicular dendritic cell sarcoma","authors":"Siqi Chen ,&nbsp;Zhijie You ,&nbsp;Xin Chen,&nbsp;Chen Wang","doi":"10.1016/j.humpath.2024.105668","DOIUrl":"10.1016/j.humpath.2024.105668","url":null,"abstract":"<div><div>Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell (FDC) sarcoma (EBV + IFDCS) is a rare entity, and its histopathological characteristics have not been fully described. This study aimed to investigate the clinical characteristics, pathological features, and molecular genetic profiles of EBV + IFDCS to improve our understanding of these lesions. A total of 12 EBV + IFDCS specimens were obtained from patients in our pathology diagnostic center. The clinical data, morphology, immunohistochemistry, in situ hybridization, and high-throughput DNA-targeted sequencing data were collected, and follow-up data were analyzed. These data were compared with those of 6 patients with traditional FDCS. The patients with EBV + IFDCS ranged from 21 to 84 years old, with a mean age of 52.3 years and a male-to-female ratio of 1:5. At the last follow-up, all patients were alive, with 2 experiencing recurrence and metastasis. In these cases, four were classified as the classical subtype, four as the angiomatoid/sclerosing subtype, and four as the lymphoma-like subtype, with two cases also exhibiting epithelioid granulomas. All patients exhibited heterogeneous expression of follicular dendritic cell markers (CD21, CD23, CD35, and CXCL13) alongside the fibroblast marker SMA, with significantly higher expressions of IgG4, EBER, and SMA in EBV + IFDCS patients compared to FDCS patients (P &lt; 0.05). Conversely, SSTR2, EGFR, and STAT3 expression were significantly lower in the EBV + IFDCS group (P &lt; 0.05). The average value of EBER was significantly higher in the classical subtype group (P = 0.022). Among the four cases of EBV + IFDCS analyzed for molecular genetic features, one patient exhibited germline mutations in the <em>CDKN1C</em>, <em>PDGFRA</em>, <em>MSH2</em>, <em>FANCG</em>, <em>MLH1</em>, <em>ALK</em>, and <em>RUNX1</em> genes; three exhibited simultaneous <em>SNP</em> variations in the <em>MTHFR</em> gene; and two exhibited simultaneous <em>SNP</em> variations in the <em>NQO1</em> gene. We conducted <em>KEGG</em> pathway analysis on the mutant genes, revealing significant enrichment in the <em>cAMP</em> signaling pathway, which plays a crucial role in tumor development. Survival analysis demonstrated that the median PFS rates were not reached (NR) for EBV + IFDCS patients, compared to 5 months (HR = 7.76) for FDCS patients. The 3-year PFS rates were 66.67% and 16.67%, respectively. Compared with the FDCS group, EBV + IFDCS patients had a significantly longer median PFS time (p &lt; 0.05). In conclusion, EBV + IFDCS represents a group of tumors with unique clinical, morphological, immunological, prognostic, and molecular cytogenetic characteristics.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105668"},"PeriodicalIF":2.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}