Virchows Archiv最新文献

{"title":"Proficiency test of BRAF immunohistochemistry as a surrogate marker of p.V600E mutation: Assessment of staining and interpretation quality in Taiwan.","authors":"Yun-An Chen, Jyie-Yu Lai, Chih-Yi Hsu, Huang-Chun Lien, Jen-Fan Hang","doi":"10.1007/s00428-025-04192-5","DOIUrl":"https://doi.org/10.1007/s00428-025-04192-5","url":null,"abstract":"<p><p>BRAF immunohistochemistry (IHC) serves as a surrogate for BRAF p.V600E but shows variable performance across tumor types and institutions. This study evaluated BRAF IHC staining quality and interpretation in general pathology laboratories through a nationwide proficiency test (PT) in Taiwan, focusing on the most commonly encountered thyroid neoplasm and colorectal cancer. This PT was organized by the Taiwan Society of Pathology using a tissue microarray, containing six tumor cores with confirmed BRAF mutation status and one positive control. Participating laboratories performed BRAF IHC staining and interpretation independently, with results centrally reviewed for concordance, accuracy, and staining quality. Twenty-six pathology laboratories participated. Two laboratories failed the initial control check. Among the remaining 24, 17 (70.83%) demonstrated optimal staining, while 5 (20.83%) showed over-staining and 2 (8.33%) under-staining. No significant associations were found between staining quality and antibody clones, platforms, dilution folds, or assay types. Interpretation was highly concordant (100% agreement and accuracy) for tissues with 3 + or negative staining. However, discrepancies arose in tissues with 2 + intensity (50% positive, 41.67% negative, 8.33% equivocal) and 1 + intensity (83.33% disagreement with test results). The overall accuracy was 79.2%, with sensitivity at 58.3% and specificity at 100%. Under-calling was frequent in cases with 1 + staining (33 cores across 23 laboratories) and 2 + staining (3 cores across 3 laboratories). Our study highlights the importance of optimizing staining quality and reinforcing education on interpretation criteria. To minimize false-negative results, we recommend molecular confirmation for all cases exhibiting diffusely weak staining.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP1::MAML2, YAP1::NUTM1, and RNF13::PAK2 rearrangements in trichoblastomas and adnexal tumors with panfollicular differentiation: expanding the spectrum of YAP1/PAK-fused skin adnexal tumors.","authors":"Thibault Kervarrec, Nicolas Macagno, Aurelie Houlier, Daniel Pissaloux, Brice Thamphya, Baptiste Louveau, Samia Mourah, Maxence Mancini, Dmitry Kazakov, Kim Harnisch, Franck Tirode, Gerardo Cazzato, Pierre Sohier, Arnaud de la Fouchardière, Maxime Battistella, Eduardo Calonje","doi":"10.1007/s00428-025-04175-6","DOIUrl":"https://doi.org/10.1007/s00428-025-04175-6","url":null,"abstract":"<p><p>In 2019, YAP1::MAML2 and YAP1::NUTM1 rearrangements were demonstrated in the majority of poromas and in porocarcinomas. Recently, our group demonstrated recurrent fusions of PAK (p21 (RAC1) activated kinase) 1/2/3 genes in a subset of poromas and porocarcinomas frequently harboring hair follicle and sebaceous differentiation. To expand the spectrum of YAP1/PAK-fused tumors, we report six adnexal neoplasms with follicular differentiation with in frame YAP1::MAML2, YAP1::NUTM1, or RNF13::PAK2 fusion transcripts. Four cases of trichoblastoma and two neoplasms with panfollicular differentiation were included. Median age was 66 (range 39-76). Two patients were female. Tumors were located on the head (n = 4), chest (n = 1), or leg (n = 1). Microscopically, tumors were located in the dermis (n = 4) and/or subcutaneous tissue (n = 5), and showed macro (n = 6), micronodular (n = 5), and cystic (n = 4) structures. A delicate fibrillar stroma was present in 5 cases. Infundibulocystic structures, cell balls, and sebocytes were observed in 5, 1, and 3 cases, respectively. Immunohistochemistry revealed BerEP4 expression and Merkel cell hyperplasia in 5 and 2 cases, respectively. YAP1 (C-terminal) loss was observed in 5 cases. Accordingly YAP1::MAML2 (n = 2), YAP1::NUTM1 (n = 1), or RNF13::PAK2 (n = 1) inframe fusion transcripts were detected in the four trichoblastomas. YAP1::MAML2 fusions were also detected in the two tumors with panfollicular differentiation. In conclusion, we report six cases of follicular tumors with YAP1::MAML2, YAP1::NUTM1, or RNF13::PAK2 fusions and therefore suggest that in addition to poroid tumors, YAP1 and PAK2 fusions might be the oncogenic driver in a subset of adnexal tumors with prominent follicular differentiation.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranodal palisaded myofibroblastoma shows a unique epigenetic profile-first molecular study of their epigenetic and copy number variation profile.","authors":"Sandra Leisz, Maximilian Scheer, Uwe Hildebrandt, Merle Wiegers, Christian Strauss, Christian Scheller, Thomas Mentzel, Andreas von Deimling, Anja Harder","doi":"10.1007/s00428-025-04170-x","DOIUrl":"https://doi.org/10.1007/s00428-025-04170-x","url":null,"abstract":"<p><p>Intranodal palisaded myofibroblastomas with amianthoid fibers (IPM) are rare mesenchymal neoplasms showing a myofibroblastic differentiation. Histopathologically, they might be difficult to distinguish from schwannoma or other neoplasia with spindle cell morphology, especially on limited biopsies. CTNNB1 gene variants have been detected in at least 50% of tumors. In this study, we determined the methylation profile including the copy number variation profile in a series of six patients. These analyses enabled genes with the highest gains or losses compared to myoblasts and fibroblasts to be identified. We identified a new methylation cluster that is not included in the Heidelberg Sarcoma Classifier so far. Furthermore, significantly differentially hypo- and hypermethylated genes compared to normal myoblasts and fibroblasts were detected in all samples, e.g., ARID5A, MIB2, TRIM58, and others were > 17-fold hypomethylated, while NEDD4, RUNX1, SLC8A1, and others were > 75-fold hypermethylated. Additionally, when combining positive ß-catenin expression and sequencing results, the aberrant/mutant CTNNB1 gene was shown in three tumors (75% of analyzed cases) in this IPM series. The present data provides additional support/adjunct to establish the rare diagnosis of intranodal palisaded myofibroblastomas with amianthoid fibers by molecular testing in diagnostically challenging cases.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indirect clinical validation for predictive biomarkers in oncology: International Quality Network for Pathology (IQN Path) Position Paper.","authors":"Emina E Torlakovic, Raed Al Dieri, Tony Badrick, Zongming Eric Chen, Carol C Cheung, Zandra Deans, Andrew Dodson, Francesca Fenizia, Hiroshi Kijima, Joerg Maas, Antonio Martinez, Søren Nielsen, Simon Patton, Etienne Rouleau, Peter Schirmacher, Tanuja Shet, Tracy Stockley, Nicola Normanno","doi":"10.1007/s00428-025-04169-4","DOIUrl":"https://doi.org/10.1007/s00428-025-04169-4","url":null,"abstract":"<p><p>Validation of biomarker assays is mandatory not only for their applications in clinical trials but also for their subsequent transfer to clinical laboratories in routine clinical care. There are two critical components relevant to their transfer to clinical practice: regulatory oversight and methodology transfer. Both aspects are simplified where companion diagnostic (CDx) assays relevant to a given indication are being implemented in clinical laboratories. However, when laboratory developed tests (LDTs) are being used either because CDx is not available or because LDT is preferred, both aspects need special consideration from regulatory agencies as well as clinical laboratories. The key component that links these two aspects is evidence of validation of the new LDTs. For predictive and prognostic biomarkers in oncology, clinical validation is feasible only in clinical trials. This approach is not available or feasible to clinical laboratories that develop LDTs. While clinical laboratories routinely perform technical/analytical validation, depending on the type of biomarker, this may not be sufficient to provide evidence of the LDT's clinical relevance. Laboratories must perform and document their assessment for the need for indirect clinical validation. When indirect clinical validation is required, it must be performed according to existing guidelines for this purpose. This paper provides expert consensus guidance and recommendations on how to assess for the need for indirect clinical validation and how to perform indirect clinical validation where required. This paper also provides a conceptual framework to regulatory agencies for determining requirements for validation of predictive and prognostic biomarkers in oncology.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare occurrence of penoscrotal basal cell carcinoma: Clinicopathologic findings from a single institution cohort and comprehensive literature review.","authors":"Bethany Batson, Tiarra Price, Dimitrios Korentzelos, Melissa Russell, Arivarasan Karunamurthy, Siobhan I Telfer, Gabriela M Quiroga-Garza","doi":"10.1007/s00428-025-04188-1","DOIUrl":"https://doi.org/10.1007/s00428-025-04188-1","url":null,"abstract":"<p><p>Basal cell carcinoma (BCC) is a frequently diagnosed cancer often associated with increased cumulative sun exposure. BCCs rarely occur on sun-protected areas, such as the external genitalia. Herein, we present the largest single-institution case series and comprehensive literature review of penoscrotal BCC. We performed a retrospective analysis of penoscrotal BCC cases diagnosed between 2000 and 2023 and collected information regarding demographics, risk factors, clinicopathologic features, treatment, and outcome. Available slides were reviewed by an experienced dermatopathologist and a genitourinary pathologist, and risk categories were assigned based on histologic subtype in accordance with the current World Health Organization (WHO) classification guidelines. Twenty cases of scrotal BCC and two cases of penile BCC were diagnosed during the study period. Reported risk factors included other non-melanoma skin cancer involving sun-exposed areas (42.9%) and sun-protected areas (9.5%), tobacco use (42.9%), chronic kidney disease (19%), moderate to severe sun exposure (14%), immunosuppressive/modulatory medication (9.5%), external beam radiation, and psoriasis. The median age at time of diagnosis, time to presentation, and lesion size were 69 years, 0.5 years, and 1.5 cm, respectively. Among the recognized subtypes, nodular BCC occurred most frequently (68.4%) and overall most cases (63%) were categorized as low risk. All nineteen cases with available treatment information had been treated with either Mohs (21%), excision (74%), or both (5%). No metastases were reported, and 75% of patients were alive without recurrence at follow-up. Our case series highlights important insights regarding penoscrotal BCC and increases knowledge and awareness of an unusual presentation of a common entity.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Composite gangliocytoma/neuroma and neuroendocrine tumor: a clinicopathologic, immunohistochemical, and molecular genetic study of 11 cases.","authors":"M Lisa Zhang, David M Meredith, Andrew M Bellizzi, Jonathan A Nowak, David J Papke","doi":"10.1007/s00428-025-04167-6","DOIUrl":"https://doi.org/10.1007/s00428-025-04167-6","url":null,"abstract":"<p><p>Composite gangliocytoma/neuroma and neuroendocrine tumor (CoGNET, previously \"gangliocytic paraganglioma\"), is a rare tumor type of uncertain pathogenesis in the ampulla/periampullary duodenum. Here, we present 11 CoGNETs in 6 females (55%) and 5 males (median age: 55 years; range: 28-69 years), all in the ampulla or duodenum. Tumors were triphasic with variable proportions of (1) neuroendocrine nests, (2) spindle cell nerve sheath regions, and (3) ganglion-like cells. By immunohistochemistry, ganglion-like cells expressed broad-spectrum keratins, somatostatin, NFP, and islet-1, and they lacked expression of PHOX2B. Neuroendocrine nests diffusely expressed ARX, islet-1, pancreatic polypeptide, and somatostatin, and they lacked expression of CDX2 and PDX1. Spindle cells expressed NFP and S-100. Targeted DNA sequencing of four tumors demonstrated 15q loss in two and multiple copy number alterations in one. Whole-exome DNA sequencing of five tumors showed borderline evidence of an NF1 frameshift mutation in one. Clinical follow-up was available for 8 patients (73%; median length: 7.0 years; range: 1.3 months-13.9 years). One Whipple resection showed regional lymph node metastases in a patient who remained disease-free 12.3 years later. No patients experienced recurrence or metastasis following surgery. The expression pattern of endocrine hormones and transcription factors distinguished CoGNET from other pancreatic and duodenal neuroendocrine tumor subtypes. The ganglion-like cells expressed keratins and not PHOX2B, demonstrating immunophenotypic divergence from true ganglion cells. Therefore, we propose that alternative nomenclature \"gangliocytoid neuroendocrine neoplasm\" or \"composite gangliocytoid neuroendocrine neoplasm\" be considered. The relative lack of pathogenic mutations raises the possibility that these tumors might harbor epigenetic drivers.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential expression of PTEN, pAKT1, pRPS6, and mismatch repair proteins in pituitary neuroendocrine tumors.","authors":"Mehmet Arda Inan, Melike Urganci, Berkay Simsek, Meric Coskun, Melih Sahin, Emrah Celtikci, Aylar Poyraz","doi":"10.1007/s00428-025-04176-5","DOIUrl":"https://doi.org/10.1007/s00428-025-04176-5","url":null,"abstract":"<p><p>Pituitary neuroendocrine tumors (PitNETs), formerly known as adenomas, are heterogeneous neoplasms that can result in significant clinical morbidity. The molecular pathogenesis of these tumors has been linked to mutations in genes such as GNAS, MEN1, and USP8, with their roles in tumor development well characterized. However, the potential contributions of the phosphatase and tensin homolog (PTEN) and microsatellite instability (MSI)-related genes remain insufficiently elucidated. This study aimed to investigate the immunohistochemical expression profiles of PTEN, phosphorylated protein kinase B (pAKT1), phosphorylated ribosomal protein S6 (pRPS6), and DNA mismatch repair (MMR) proteins in PitNETs. In this retrospective analysis, archived formalin-fixed, paraffin-embedded tumor samples from 154 patients were stained for PTEN, pAKT1, and pRPS6, and H-scores were calculated based on the three most intensely stained high-power fields. Additionally, MMR protein expression (PMS2, MLH1, MSH2, and MSH6) was assessed to evaluate MSI status. Gonadotroph tumors were the most common subtype (45.5%). Statistical analysis revealed a significant loss of PTEN expression in lactotroph tumors, along with a sex-based association with tumor type. Notably, pRPS6 expression was significantly elevated in tumors exhibiting PTEN loss. No cases showed loss of MMR protein expression, indicating MMR proficiency across the cohort. Our findings suggest that dysregulation of the PTEN pathway may contribute to lactotroph tumorigenesis, underscoring its potential as a therapeutic target. In contrast, despite its established role as a tumor-agnostic biomarker, MMR status does not appear to hold clinical relevance for alternative treatment strategies in PitNETs.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An epithelioid hemangioendothelioma with a novel RREB1::TFE3 gene fusion.","authors":"Thomas Schumacher, Baptiste Ameline, Alexander Vogetseder, Beata Bode, Teodor Svantesson","doi":"10.1007/s00428-025-04183-6","DOIUrl":"https://doi.org/10.1007/s00428-025-04183-6","url":null,"abstract":"<p><p>Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of intermediate malignant potential. Most cases are characterized by a WWTR1::CAMTA1 gene fusion, with YAP1::TFE3 being the second most common. We present a case of EHE in a 78-year-old woman with an RREB1::TFE3 gene fusion, which, to our knowledge, has not previously been described. The tumor was detected incidentally as a subpectoral soft tissue mass during imaging for a simultaneously diagnosed metastatic pulmonary adenocarcinoma. Aside from this, the patient's presentation was consistent with common clinical findings in EHE. Histologically, however, the tumor partly revealed an uncommon morphology: on one hand, solid areas of monomorphic epithelioid tumor cells with abundant eosinophilic cytoplasm, and on the other, regions with considerable and unusual pleomorphism and multinucleation, thus not clearly aligning with the prototypical phenotypes of the classical molecular subtypes. In summary, this case expands the molecular spectrum of EHE and supports further investigation into its molecular heterogeneity.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desmoid fibromatosis in a child with DICER1-related tumor predisposition.","authors":"Paul Scott Thorner, Anne-Laure Chong, Sung Mi Jung, Gabriel P P Fox, Martin Corbally, William D Foulkes","doi":"10.1007/s00428-025-04180-9","DOIUrl":"https://doi.org/10.1007/s00428-025-04180-9","url":null,"abstract":"<p><p>DICER1-related tumor predisposition is an inherited disorder, generally pediatric in onset, featuring a characteristic array of mainly mesenchymal tumors. We report a chest wall desmoid fibromatosis, occurring in a child who uniquely carries a germline \"hotspot\" DICER1 variant that likely leads to impaired miRNA biogenesis in all cells. This lesion contained a hotspot CTNNB1 c.134C > T, (p.S45F) exon 3 somatic mutation and immunohistochemistry showed nuclear accumulation of β-catenin. Desmoid fibromatosis is known to be associated with dysregulation of β-catenin, resulting from altered APC or CTNNB1, leading to increased WNT pathway signaling. In fetal lung tumors linked to DICER1 hotspot variants, APC and/or CTNNB1 somatic mutations are found in most cases, suggesting a synergistic effect with DICER1 hotspot mutation to increase WNT pathway signaling. We postulate a similar mechanism is involved in this case and that desmoid fibromatosis is a rare mesenchymal lesion that could be part of DICER1-related tumor predisposition.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The morphological spectrum of Castleman disease and related disorders: a report from the Lymphoma Workshop of the 22nd Meeting of the European Association of Hematopathology.","authors":"Gorana Gasljevic, Arturo Bonometti, Ioannis Anagnostopoulos, Olga Balaguè, Michiel Van den Brand, James R Cook, Camille Laurent, Maurilio Ponzoni, Leticia Quintanilla-Martinez, Birgitta Sander, Stefan Dirnhofer","doi":"10.1007/s00428-025-04171-w","DOIUrl":"https://doi.org/10.1007/s00428-025-04171-w","url":null,"abstract":"<p><p>Castleman disease (CD) is an intriguing and complicated group of local and systemic disorders mainly affecting lymph nodes with heterogeneous presentation and therapeutic needs. These disorders were the topic of Session 1 of the Lymphoma Workshop at the 2024 EA4HP in Dubrovnik, Croatia. In this report, we summarize the features of the 85 submitted cases and review the differential diagnosis, pitfalls, and advances for all CD subtypes. Specifically, the molecular landscape of unicentric CD and its relationship with follicular dendritic cell proliferations and indolent T-lymphoblastic proliferation will be discussed. The spectrum of idiopathic multicentric CD (MCD), TAFRO syndrome, as well as the clinical and histopathological peculiarities of POEMS-CD, is reviewed. Cases of Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV8) + MCD were the most complicated and well demonstrated the difficulties and overlaps in the differential diagnosis of KSHV/HHV8 + lymphoproliferative disorders. Finally, the important topic of CD mimickers will be addressed, demonstrating how the integration of clinical, laboratory, histopathological, and molecular data is mandatory to confirm a diagnosis of CD and how to distinguish it from the many neoplastic, autoimmune, and infective mimickers.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}