Human pathology最新文献

{"title":"The molecular profile of ovarian struma ovarii","authors":"Iris Calejero ,&nbsp;Mousa Mobarki ,&nbsp;Shaqraa Musawi ,&nbsp;Michel Péoc'h ,&nbsp;Georgia Karpathiou","doi":"10.1016/j.humpath.2026.106069","DOIUrl":"10.1016/j.humpath.2026.106069","url":null,"abstract":"<div><h3>Introduction</h3><div>Struma ovarii is a rare type of ovarian teratoma consisting predominantly of thyroid tissue and showing a usually benign clinical course which cannot be predicted by its histology. Thus, their molecular analysis could help to better classify these tumors. However, the molecular profile of struma ovarii, especially the benign one, has been rarely studied.</div></div><div><h3>Material and methods</h3><div>We performed a retrospective, non-interventional study of 23 benign ovarian struma ovarii using formalin-fixed paraffin-embedded tissues for DNA extraction and next-generation sequencing.</div></div><div><h3>Results</h3><div>Two tumors harbored interesting molecular alterations. The first tumor, diagnosed in an adult patient, harbored two <em>DICER1</em> variants: c. 4738 C &gt; T and c. 5429 A &gt; T. The second one was a struma ovarii harboring a <em>POLD1</em> c.961G &gt; A, p.(Gly321Ser) variant. None of the tumors harbored <em>BRAF</em> mutations.</div></div><div><h3>Conclusion</h3><div>Benign struma ovarii do not harbor <em>BRAF</em> alterations. <em>DICER1</em> and <em>POLD1</em> variants need further investigation in this tumor pathology.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"171 ","pages":"Article 106069"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142251","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":"GRHL-rearranged sebaceoma: expanding the clinical and morphologic spectrum","authors":"Anum Dileep ,&nbsp;Christine J. Ko ,&nbsp;Robert E. LeBlanc ,&nbsp;Gauri G. Panse ,&nbsp;Jeffrey M. Cloutier","doi":"10.1016/j.humpath.2026.106058","DOIUrl":"10.1016/j.humpath.2026.106058","url":null,"abstract":"<div><div>Sebaceoma is a benign sebaceous neoplasm with broad architectural variability, and outside of mismatch repair (MMR)-deficient tumors, its molecular features have remained poorly defined. Recent work identified recurrent <em>GRHL1/GRHL2</em> rearrangements in a subset of sebaceomas, suggesting the presence of a molecularly distinct group. We report three additional sebaceomas harboring <em>RCOR1::GRHL2</em> fusions identified by RNA-based next-generation sequencing and integrate the clinical, morphologic, and molecular features of all 11 currently known <em>GRHL</em>-rearranged sebaceomas. Patients ranged from 40 to 84 years; two tumors arose on the head and neck, and one represented the first documented extracranial example (axilla). All tumors were macronodular to multinodular basaloid proliferations with variably complex corded (“organoid”) architecture; infundibulocystic structures were present in one case. One tumor demonstrated partially cystic growth and rounded basaloid nests, expanding the recognized morphologic spectrum. All three tumors were microsatellite stable without pathogenic MMR gene alterations. Across the combined cohort, no recurrences have been reported. These findings broaden the clinicopathologic spectrum of <em>GRHL</em>-rearranged sebaceoma and support this group as a sporadic, MMR-proficient subset characterized by distinctive organoid-patterned architecture. Further studies are needed to determine whether <em>GRHL</em> rearrangements represent a unifying driver of organoid morphology in sebaceoma.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"170 ","pages":"Article 106058"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043979","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":"The evolving landscape of pathologic interpretation in metabolic dysfunction-associated steatotic liver disease.","authors":"Daniela S Allende","doi":"10.1016/j.humpath.2026.106112","DOIUrl":"10.1016/j.humpath.2026.106112","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. This article discussed updates in diagnosis and emerging issues. Key histologic findings include steatosis, lobular inflammation, and hepatocyte ballooning. Updated histologic guidance, with more detailed definitions, has recently been published for features in the histologic spectrum. Studies in portal changes seen in MASLD have shown the importance of this finding in relation to fibrosis and outcome. Among the emerging issues, the importance of incidental findings and regression of fibrosis features is described. Digital pathology/machine learning algorithms, stain-free technologies, and molecular testing are being integrated into the diagnosis of MASLD, still mostly in the research setting but rapidly capturing the attention of the clinical community with the intent of aiding pathologists.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106112"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615999","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":"Solid, cystic, and mucinous spindle cell thymomas (WHO type A): A clinicopathological and immunohistochemical study of 7 cases","authors":"Annikka Weissferdt,&nbsp;Cesar A. Moran","doi":"10.1016/j.humpath.2026.106050","DOIUrl":"10.1016/j.humpath.2026.106050","url":null,"abstract":"<div><div>Seven cases of an unusual thymoma subtype are presented. Patients included five men and two women, aged 43–57 years (mean: 50). Five patients presented with non-specific symptoms of cough, chest pain and shortness of breath; two patients were asymptomatic. Diagnostic imaging revealed anterior mediastinal masses in all patients and surgical resection was accomplished via thoracotomy. Grossly, the tumors were well circumscribed with focal cystic changes, measuring 2.7 cm–4.8 cm. Six tumors were encapsulated; one was minimally invasive. Histologically, the tumors exhibited cystic changes and solid areas composed of bland spindle cells with scant thymocytes, consistent with spindle cell thymomas (WHO type A). Notably, focal mucinous differentiation was observed, including glandular structures with mucinous epithelium, scattered mucinous cells, extracellular mucin, and partial cyst wall lining by mucinous epithelium. Immunohistochemistry demonstrated that the spindle cell component was positive for pancytokeratin, CK5/6, p63 and CD20 and negative for CK7, CK20, PAX8, GATA-3, TTF-1, CDX2, STAT6 and SS18-SSX while the mucinous cells were variably positive for CK7, CK20 and CDX2; mucicarmine histochemical staining confirmed mucin content. Four patients remained alive and well at 18 months postoperatively while 3 patients were lost to follow-up. The current cases represent a previously undescribed variant of spindle cell thymoma that may pose diagnostic challenges and give rise to a wide differential diagnosis.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"170 ","pages":"Article 106050"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043928","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":"Polymorphic central nervous system (CNS) immune deficiency/dysregulation-associated lymphoproliferative disorders show a uniquely aggressive clinicopathologic profile compared to their extra-CNS counterparts","authors":"Frank Rojas Alvarez ,&nbsp;Eric I Nayman ,&nbsp;Yi-Hua Chen ,&nbsp;Qing Ching Chen ,&nbsp;Pouya Jamshidi ,&nbsp;Karan Dixit ,&nbsp;Hamza Tariq","doi":"10.1016/j.humpath.2026.106051","DOIUrl":"10.1016/j.humpath.2026.106051","url":null,"abstract":"<div><h3>Background</h3><div>Primary central nervous system immunodeficiency/dysregulation-associated lymphoproliferative disorders (PCNS-IDD-LPDs) are a rare and heterogeneous group of lymphoid lesions that arise within the CNS of immune compromised patients. Among PCNS-IDD-LPDs, monomorphic IDD-LPDs are relatively well studied; however, data regarding PCNS polymorphic IDD-LPDs is very limited. It remains unclear whether polymorphic PCNS IDD-LPDs follow a similarly indolent clinical course as observed in their systemic polymorphic counterparts, or whether the unique immune microenvironment of the CNS imparts a more aggressive disease biology.</div></div><div><h3>Methods</h3><div>In this study, we compared the clinical, pathologic, and survival profile of PCNS polymorphic IDD-LPDs (N = 15) with extra-CNS polymorphic IDD-LPDs (N = 21) as well as PCNS monomorphic IDD-LPDs (N = 12).</div></div><div><h3>Results</h3><div>Compared to extra-CNS polymorphic IDD-LPDs, patients with PCNS polymorphic IDD-LPDs showed a significantly stronger association with kidney transplants, longer latency, worse performance status, more frequent monoclonal populations and necrosis, and a greater need for aggressive chemoimmunotherapy in addition to reduction in immunosuppression and/or rituximab. The overall survival (OS) of PCNS polymorphic IDD-LPDs was significantly inferior to that of extra CNS polymorphic IDD-LPDs (median survival: 7.1 years vs. not reached; log-rank p = 0.023) and not significantly different from PCNS monomorphic IDD-LPDs (median survival: 7.1 vs. 3.6 years; log-rank p = 0.852).</div></div><div><h3>Conclusion</h3><div>We conclude that PCNS polymorphic IDD-LPDs have a uniquely aggressive clinicopathologic and prognostic profile compared to their systemic counterparts and are comparable to their monomorphic PCNS counterparts. CNS localization supersedes the histological subtype as the primary determinant of disease biology in IDD-LPDs, likely ascribed to the immune sanctuary status of the CNS.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"170 ","pages":"Article 106051"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043962","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":"Long-term outcomes of prostate cancer patients with metastases in the anterior fat pad and pelvic lymph nodes: Nodal upstaging without worse long-term outcomes","authors":"Bo Yu ,&nbsp;Xiao Zhou ,&nbsp;Fang Bian ,&nbsp;Feng Yan ,&nbsp;Fogt Franz","doi":"10.1016/j.humpath.2026.106033","DOIUrl":"10.1016/j.humpath.2026.106033","url":null,"abstract":"<div><h3>Background</h3><div>The frequency and prognostic significance of prostate cancer (PCa) metastasis to the prostatic anterior fat pad (PAFP) remain unclear. We evaluated the incidence of lymph nodes and metastatic involvement within the PAFP and assessed the impact of PAFP lymph node metastasis on nodal staging accuracy and long-term outcomes in patients undergoing radical prostatectomy.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 4028 patients who underwent radical prostatectomy with concurrent PAFP and pelvic lymph node (PLN) dissection between January 2010 and May 2021. Lymph nodes within the PAFP and PLN specimens, along with relevant histopathologic features, were evaluated. Patients were stratified into three groups based on the location of lymph node metastasis: (Group 1) PAFP-only metastasis, (Group 2) PLN-only metastasis, and (Group 3) metastasis involving both regions. Biochemical recurrence-free survival and overall survival were compared, and Kaplan-Meier analysis and multivariable Cox regression were used.</div></div><div><h3>Results</h3><div>Among all patients, lymph nodes were identified in the prostatic anterior fat pad in 295 cases (7.30 %), of those, 23 patients had isolated PAFP lymph node metastasis (0.57 % of the entire cohort and 7.80 % of patients with PAFP lymph nodes). PLNs were reported in 3874 patients (96.18 %), of whom 70 patients had isolated PLN metastasis (1.73 % of the entire cohort and 1.8 % of patients with PLN). Nine patients (0.22 % overall) demonstrated metastatic involvement of both PAFP and PLN. The metastatic positivity rate for isolated metastasis was significantly higher in PAFP lymph nodes than in PLN (Z = 6.7), with a relative risk of 4.32 (95 % CI, 2.73–6.75). Biochemical recurrence occurred in 77.8 % of patients in Group 1, 72.7 % in Group 2, and 66.7 % in Group 3. All-cause mortality was observed in 21.7 %, 7.2 %, and 22.2 % of patients in Groups 1, 2, and 3, respectively. Kaplan-Meier analysis and multivariable Cox regression demonstrated no significant differences in biochemical recurrence-free survival or overall survival between groups. Excision of the prostatic anterior fat pad resulted in lymph node upstaging in approximately 1 % of all patients. Biochemical recurrence-free survival and overall survival were comparable between patients with isolated PAFP and isolated PLN metastases.</div></div><div><h3>Conclusions</h3><div>Routine excision and pathological evaluation of the prostatic anterior fat pad during radical prostatectomy improve nodal staging by identifying otherwise unrecognized N1 disease, without an associated adverse impact on oncologic outcomes, compared with pelvic lymph node evaluation alone.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"170 ","pages":"Article 106033"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915106","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":"Primary pulmonary Langerhans cell histiocytosis: comprehensive clinicopathologic and molecular genetic analysis of 13 cases","authors":"Yanping Zhang M.S.,&nbsp;Enjie Liu Ph.D.,&nbsp;Minglei Yang Ph.D.,&nbsp;Guannan Wang Ph.D.,&nbsp;Wugan Zhao Ph.D.,&nbsp;Wencai Li Ph.D.,&nbsp;Shenglei Li Ph.D.","doi":"10.1016/j.humpath.2026.106034","DOIUrl":"10.1016/j.humpath.2026.106034","url":null,"abstract":"<div><div>Primary pulmonary Langerhans cell histiocytosis (PLCH) is a rare entity. To characterize its clinicopathological and molecular features, 13 cases (15 specimens) were retrospectively analyzed, incorporating clinical information, imaging findings, histopathological features, immunohistochemical results, BRAFV600E mutation status, and DNA-based next-generation sequencing data. The patients ranged in age from 17 to 59 years (mean, 30 years), with a male-to-female ratio of 12:1; all male patients were smokers. Computed tomography demonstrated multiple pulmonary cysts in 12 cases, including pneumothorax in 3 cases, and a solitary nodular mass in 1 case. Histologically, 11 cases exhibited classic morphological features, whereas two small biopsy specimens showed subtle nuclear grooves and sparse background eosinophils, leading to an initial misdiagnosis of reactive lesions. Immunohistochemical analysis confirmed expression of S-100 (15/15), CD1a (15/15), Langerin (15/15), and cyclin D1 (3/3) in all cases. BRAFV600E mutation analysis was positive in one of four tested cases. Next-generation sequencing performed in six cases (seven lesions) revealed a non-frameshift BRAF deletion in one case, concurrent MAP2K1 and DUSP4 missense mutations in one case, an isolated DUSP4 missense mutation in one case, and RRAS mutations in two separate specimens from one patient. Four cases exhibited abnormalities in genes associated with DNA damage repair. Additional alterations involved multiple other signaling pathways, as well as abnormalities in hematopoietic regulation, epigenetic modulation, and related molecules. At a median follow-up of 23 months, all twelve patients were alive, although one patient developed extrapulmonary lesions. In conclusion, PLCH predominantly affects adult smokers, shows a marked male predominance, and generally carries a favorable prognosis. In cases with atypical morphology, immunohistochemical and molecular analyses should be integrated with characteristic imaging findings to avoid misdiagnosis. Furthermore, this study provides additional insights into the molecular pathogenesis of PLCH.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"170 ","pages":"Article 106034"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989024","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":"Consideration of the natural history of BCL2-positive follicular lymphoma: based on tumor site, histological grade, and histological transformation rate","authors":"Akiko Miyagi Maeshima ,&nbsp;Yuto Kaimi ,&nbsp;Yuka Takahashi ,&nbsp;Tetsuro Ochi ,&nbsp;Shinichi Makita ,&nbsp;Noriko Iwaki ,&nbsp;Suguru Fukuhara ,&nbsp;Wataru Munakata ,&nbsp;Koji Izutsu","doi":"10.1016/j.humpath.2026.106048","DOIUrl":"10.1016/j.humpath.2026.106048","url":null,"abstract":"<div><div>BCL2⁺ follicular lymphomas (FLs) of grades 1–3A are defined as classic FL, and duodenal and skin FLs are known as special subtypes. To clarify the natural history of BCL2⁺ FLs, we analyzed the tumor site, histological grade, and histological transformation rate. We analyzed 2260 FL grade 1–3B samples from 1389 patients. BCL2 expression was positive in 94 % (2115/2260) of the samples, with higher positivity in gastrointestinal (GI) (98 % [duodenum, 99 %]) and bone marrow (BM) (97 %) FLs than in lymph node (LN) (92 %) and extranodal (EN) (93 %) FLs (P = 3.4E-06). Histological grade increased in the order of BM and duodenum, GI (excluding duodenum) and EN, and LN. The histological transformation rate in the same biopsy sample diagnosed with FL was the highest in GI (excluding duodenum) (12 %), followed by LN (10 %), EN (5 %), BM (1 %), and duodenum (0.5 %). No significant differences were observed between duodenal and BM FLs regarding BCL2-positivity rate (P = 0.326), histological grade (P = 0.131), and histological transformation rate (P = 0.408). In EN sites, FLs most commonly involved skin, ocular adnexa, connective tissue, bone, and paravertebra. No specific organ showed a particularly low BCL2⁺ percentage (range, 67 %–100 %). Because both primary (88 %) and secondary (95 %) skin FLs showed a high incidence of BCL2 expression, most skin FLs may represent one aspect of BCL2⁺ FL. These findings suggest that BM and duodenum FLs may represent early-phase BCL2⁺ FL, whereas EN, GI (excluding duodenum), and LN FLs may correspond to more advanced phases.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"170 ","pages":"Article 106048"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989072","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":"Morphologic and immunohistochemical study of HPV-related cervical adenosquamous carcinoma: Reappraisal of a poorly defined entity","authors":"Zhenwei Zhang,&nbsp;M. Ruhul Quddus,&nbsp;C James Sung,&nbsp;Kamaljeet Singh","doi":"10.1016/j.humpath.2026.106052","DOIUrl":"10.1016/j.humpath.2026.106052","url":null,"abstract":"<div><h3>Objective</h3><div>Current WHO criteria require distinct glandular and squamous differentiation for diagnosis of adenosquamous carcinoma (AdSq). However, a subset of poorly differentiated cervical carcinoma exhibits ambiguous morphology with diffuse growth pattern. The current study explores whether these tumors belong to the adenosquamous subtype.</div></div><div><h3>Methods</h3><div>After IRB approval, we retrieved 41 AdSq cases diagnosed at our institution between 2007 and 2024. H&amp;E slides were reviewed. Immunohistochemical staining for p16, p40, p63, BerEP4, and Claudin-4 was performed. IHC was scored. Statistical analysis was performed with Python packages.</div></div><div><h3>Results</h3><div>Based on morphology only, out of the 41 AdSq cases, 11 fulfilled the WHO proposed criteria for classic AdSq (cAdSq). Twenty cases were classified as non-classic AdSq (nAdSq). All the rest also exhibited a solid growth pattern, but were reclassified as endocervical (3), endometrioid (6), and squamous carcinoma (1). Histologically, nAdSq lacked distinct spatially separate components of squamous or glandular differentiation. Instead, tumor cells exhibited ambiguous morphology with diffuse growth or, less frequently, in nests, characteristic vacuolated/foamy cytoplasm, pleomorphic nuclei, and inflamed stroma. All nAdSq showed block positivity for p16 like cAdSq. Significant portion of AdSq cases expressed the squamous marker p40 (58 % in nAdSq vs. 50 % in cAdSq). In contrast to pure adenocarcinomas or squamous cell carcinomas, 47 % (7/15) of nAdSq cases expressed both squamous and adenocarcinoma markers (p40 and BerEP4), with 5 (33 %) cases showing positivity for all four markers. Similarly, two cAdSq cases (22 %) showed universal positivity for all four markers, though p40 positivity was more focal and weaker in other instances. Despite morphological differences, the overall survival outcomes between nAdSq and cAdSq was not significantly different (<em>p</em> = 0.49).</div></div><div><h3>Conclusions</h3><div>Many cervical carcinomas with diffuse growth pattern are likely the non-classic AdSq that do not contain spatially separate squamous and glandular components. Immunostaining may help in identifying this “non-classic” subtype of AdSq.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"170 ","pages":"Article 106052"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043954","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":"Every day a new fusion? – An update on recent discoveries in dermatopathology","authors":"Eric C. Honaker ,&nbsp;Ruifeng (Ray) Guo ,&nbsp;Carina A. Dehner","doi":"10.1016/j.humpath.2025.106011","DOIUrl":"10.1016/j.humpath.2025.106011","url":null,"abstract":"<div><div>The expanding integration of molecular diagnostics into dermatopathology has transformed the recognition and classification of cutaneous neoplasms, revealing an increasingly diverse landscape of oncogenic gene fusions across melanocytic, mesenchymal, and adnexal tumors. These fusion-driven entities often display distinctive histopathologic, immunophenotypic, and clinical features that can directly inform diagnostic accuracy, prognostication, and, in select cases, therapeutic decision-making. In this review, we summarize recent advances in fusion-associated cutaneous tumors encountered in routine practice, highlighting emerging molecular subsets within Spitz neoplasms, MITF pathway–activated tumors, fusion-driven mesenchymal neoplasms, and adnexal tumors characterized by recurrent kinase or transcriptional regulator rearrangements. We discuss key morphologic correlations that may provide clues to the underlying fusion, the value and limitations of ancillary immunohistochemical surrogates, and the expanding role of next-generation sequencing in resolving diagnostically challenging cases. As the catalog of identified fusions continues to grow, an updated understanding of these entities is essential for accurate classification and for anticipating potential therapeutic vulnerabilities. This review aims to provide a practical, contemporary reference for the diagnostic pathologist navigating the rapidly evolving field of fusion-driven dermatopathology.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"169 ","pages":"Article 106011"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751802","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}