Pub Date : 2026-01-22DOI: 10.1016/j.humpath.2026.106050
Annikka Weissferdt, Cesar A. Moran
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.
{"title":"Solid, cystic, and mucinous spindle cell thymomas (WHO type A): A clinicopathological and immunohistochemical study of 7 cases","authors":"Annikka Weissferdt, 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":"2026-01-22","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}
Pub Date : 2026-01-22DOI: 10.1016/j.humpath.2026.106051
Frank Rojas Alvarez , Eric I Nayman , Yi-Hua Chen , Qing Ching Chen , Pouya Jamshidi , Karan Dixit , Hamza Tariq
Background
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.
Methods
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).
Results
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).
Conclusion
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.
{"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 , Eric I Nayman , Yi-Hua Chen , Qing Ching Chen , Pouya Jamshidi , Karan Dixit , 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":"2026-01-22","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}
Pub Date : 2026-01-22DOI: 10.1016/j.humpath.2026.106054
Julia Gallardo, Emrah Gumusgoz, James M Mitchell, Suntrea Hammer, Zhikai Chi, Purva Gopal, Dipti M Karamchandani
Existing data characterize "classic" Epstein-Barr virus (EBV) positive gastric carcinoma (GC) histologically as GC with lymphoid stroma (or lymphoepithelioma-like or medullary) exhibiting sheets or syncytia of malignant cells with prominent intratumoral lymphocytes. This diagnosis has clinical implications, given the associated frequent programmed death-ligand 1 gene amplification, and clear benefit from immunotherapy. However, there appears to be a paucity of published data regarding characteristic histologic features of EBV-GC. We evaluated 19 EBV-GC specimens (11 biopsies; 8 resections) retrieved from 13 patients and found that a unique reticular pattern was identified in 17 of 19 (89 %) specimens, either as an exclusive pattern in 26 %, or as a mixed pattern in 63 % specimens. Most patients were male (85 %), with an average age of 61.5 years, mostly of Hispanic or Black (77 %) ethnicity, and showed a predilection for proximal stomach (69 %). Associated prominent intratumoral inflammation was seen in cases retrieved from all patients (lymphocytic: 7, mixed: 6). Although a similar lace-like pattern has been implicitly cited in association with early stage EBV-GC, we report a unique reticular pattern with intratumoral inflammation that was seen more commonly than widely known "classic" histology and was even seen in association with advanced pathologic stage. We propose that ancillary EBV testing be performed on all gastric tumors with this distinctive pattern, and with other patterns with prominent (including mixed) intratumoral inflammation, to screen for EBV-GC cases, thus detecting patients who may be eligible for immunotherapy with important therapeutic implications.
{"title":"Epstein-Barr virus associated gastric carcinoma: A clinicopathologic study with recognition of a distinctive reticular histologic pattern.","authors":"Julia Gallardo, Emrah Gumusgoz, James M Mitchell, Suntrea Hammer, Zhikai Chi, Purva Gopal, Dipti M Karamchandani","doi":"10.1016/j.humpath.2026.106054","DOIUrl":"10.1016/j.humpath.2026.106054","url":null,"abstract":"<p><p>Existing data characterize \"classic\" Epstein-Barr virus (EBV) positive gastric carcinoma (GC) histologically as GC with lymphoid stroma (or lymphoepithelioma-like or medullary) exhibiting sheets or syncytia of malignant cells with prominent intratumoral lymphocytes. This diagnosis has clinical implications, given the associated frequent programmed death-ligand 1 gene amplification, and clear benefit from immunotherapy. However, there appears to be a paucity of published data regarding characteristic histologic features of EBV-GC. We evaluated 19 EBV-GC specimens (11 biopsies; 8 resections) retrieved from 13 patients and found that a unique reticular pattern was identified in 17 of 19 (89 %) specimens, either as an exclusive pattern in 26 %, or as a mixed pattern in 63 % specimens. Most patients were male (85 %), with an average age of 61.5 years, mostly of Hispanic or Black (77 %) ethnicity, and showed a predilection for proximal stomach (69 %). Associated prominent intratumoral inflammation was seen in cases retrieved from all patients (lymphocytic: 7, mixed: 6). Although a similar lace-like pattern has been implicitly cited in association with early stage EBV-GC, we report a unique reticular pattern with intratumoral inflammation that was seen more commonly than widely known \"classic\" histology and was even seen in association with advanced pathologic stage. We propose that ancillary EBV testing be performed on all gastric tumors with this distinctive pattern, and with other patterns with prominent (including mixed) intratumoral inflammation, to screen for EBV-GC cases, thus detecting patients who may be eligible for immunotherapy with important therapeutic implications.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106054"},"PeriodicalIF":2.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044004","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}
Pub Date : 2026-01-22DOI: 10.1016/j.humpath.2026.106052
Zhenwei Zhang, M. Ruhul Quddus, C James Sung, Kamaljeet Singh
Objective
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.
Methods
After IRB approval, we retrieved 41 AdSq cases diagnosed at our institution between 2007 and 2024. H&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.
Results
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 (p = 0.49).
Conclusions
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.
{"title":"Morphologic and immunohistochemical study of HPV-related cervical adenosquamous carcinoma: Reappraisal of a poorly defined entity","authors":"Zhenwei Zhang, M. Ruhul Quddus, C James Sung, 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&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":"2026-01-22","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}
Pub Date : 2026-01-16DOI: 10.1016/j.humpath.2026.106049
Pingchuan Zhang, William R Sukov, Loren P Herrera Hernandez, John C Cheville, Sounak Gupta
{"title":"Metastatic thyroid-like follicular renal cell carcinoma with EWSR1::PATZ1 fusion: A case report and review of the literature.","authors":"Pingchuan Zhang, William R Sukov, Loren P Herrera Hernandez, John C Cheville, Sounak Gupta","doi":"10.1016/j.humpath.2026.106049","DOIUrl":"10.1016/j.humpath.2026.106049","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106049"},"PeriodicalIF":2.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997896","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}
Pub Date : 2026-01-13DOI: 10.1016/j.humpath.2026.106034
Yanping Zhang M.S., Enjie Liu Ph.D., Minglei Yang Ph.D., Guannan Wang Ph.D., Wugan Zhao Ph.D., Wencai Li Ph.D., Shenglei Li Ph.D.
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.
{"title":"Primary pulmonary Langerhans cell histiocytosis: comprehensive clinicopathologic and molecular genetic analysis of 13 cases","authors":"Yanping Zhang M.S., Enjie Liu Ph.D., Minglei Yang Ph.D., Guannan Wang Ph.D., Wugan Zhao Ph.D., Wencai Li Ph.D., 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":"2026-01-13","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}
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.
1-3A级的BCL2+滤泡性淋巴瘤（FLs）被定义为典型的FL，十二指肠和皮肤FLs被称为特殊亚型。为了阐明BCL2+ FLs的自然历史，我们分析了肿瘤部位、组织学分级和组织学转化率。我们分析了来自1389例患者的2260例1-3B级FL样本。BCL2在94%（2115/2260）的样本中呈阳性表达，其中胃肠道（GI）（98%[十二指肠，99%]）和骨髓（BM）（97%）的阳性表达高于淋巴结（LN）（92%）和结外（EN）（93%）的阳性表达（P = 3.41 e -06）。组织学分级依次为BM、十二指肠、GI（不含十二指肠）、EN、LN。在诊断为FL的同一活检样本中，胃肠道（不包括十二指肠）的组织学转化率最高（12%），其次是LN (10%), EN (5%)， BM（1%）和十二指肠（0.5%）。bcl2阳性率（P = 0.326）、组织学分级（P = 0.131）、组织学转化率（P = 0.408）在十二指肠组与BM组间均无显著差异。在EN部位，fl最常累及皮肤、眼附件、结缔组织、骨和椎旁。没有特定器官显示特别低的BCL2+百分比（范围，67%-100%）。由于原发性（88%）和继发性（95%）皮肤FLs的BCL2表达率都很高，因此大多数皮肤FLs可能代表BCL2+ FL的一个方面。这些研究结果表明，BM和十二指肠FLs可能代表早期BCL2+ FL，而EN、GI（不包括十二指肠）和LN FLs可能对应更晚期的BCL2+ FL。
{"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 , Yuto Kaimi , Yuka Takahashi , Tetsuro Ochi , Shinichi Makita , Noriko Iwaki , Suguru Fukuhara , Wataru Munakata , Koji Izutsu","doi":"10.1016/j.humpath.2026.106048","DOIUrl":"10.1016/j.humpath.2026.106048","url":null,"abstract":"<div><div>BCL2<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> FL. These findings suggest that BM and duodenum FLs may represent early-phase BCL2<sup>+</sup> 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":"2026-01-13","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}
The diagnosis of bone and soft tissue tumors is challenging due to their rarity, overlapping morphology, and limited access to specialized immunohistochemistry (IHC) in routine practice. Because many of these tumors are fusion-driven, targeted RNA sequencing may improve diagnostic accuracy, but its use is not yet established in Japan.
Methods
We retrospectively analyzed 90 cases of bone and soft tissue tumors, including benign lesions, using the TruSight RNA Pan-Cancer Panel (1385 genes) on FFPE samples. Fusion detection was combined with expression-based clustering. Diagnostic impact was assessed by comparing initial histological impressions with integrated diagnoses incorporating targeted RNA panel findings.
Results
Fusion transcripts were detected in 63 cases (69.2 %), of which 46 were in-frame. Twenty-five cases harbored well-characterized pathogenic fusions that directly contributed to diagnostic confirmation or refinement. Twenty-one cases showed fusion transcripts of uncertain significance, and ten of these were reclassified as likely pathogenic after additional validation. Three cases exhibited complex fusion patterns suggestive of chromothripsis or chromoplexy, warranting further genome-wide analysis. RNA expression clustering distinguished several tumor subtypes and provided complementary support for diagnostically challenging cases, such as undifferentiated pleomorphic sarcoma.
Conclusions
Targeted RNA panel testing enabled robust detection of clinically relevant fusions and provided expression-based insights into tumor classification. When integrated with histopathology, this approach improved diagnostic accuracy in rare tumors and offered a practical triage strategy for extended genomic analysis, highlighting its clinical utility in pathology practice.
{"title":"Targeted RNA sequencing enhances the integrated diagnosis of bone and soft tissue tumors","authors":"Harumi Nakamura , Yoji Kukita , Toru Wakamatsu , Sho Nakai , Hironari Tamiya , Kei Kunimasa , Toru Kumagai , Fumio Imamura , Kazumi Nishino , Satoshi Takenaka , Yoshiko Hashii , Toshinari Yagi","doi":"10.1016/j.humpath.2026.106036","DOIUrl":"10.1016/j.humpath.2026.106036","url":null,"abstract":"<div><h3>Background</h3><div>The diagnosis of bone and soft tissue tumors is challenging due to their rarity, overlapping morphology, and limited access to specialized immunohistochemistry (IHC) in routine practice. Because many of these tumors are fusion-driven, targeted RNA sequencing may improve diagnostic accuracy, but its use is not yet established in Japan.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 90 cases of bone and soft tissue tumors, including benign lesions, using the TruSight RNA Pan-Cancer Panel (1385 genes) on FFPE samples. Fusion detection was combined with expression-based clustering. Diagnostic impact was assessed by comparing initial histological impressions with integrated diagnoses incorporating targeted RNA panel findings.</div></div><div><h3>Results</h3><div>Fusion transcripts were detected in 63 cases (69.2 %), of which 46 were in-frame. Twenty-five cases harbored well-characterized pathogenic fusions that directly contributed to diagnostic confirmation or refinement. Twenty-one cases showed fusion transcripts of uncertain significance, and ten of these were reclassified as likely pathogenic after additional validation. Three cases exhibited complex fusion patterns suggestive of chromothripsis or chromoplexy, warranting further genome-wide analysis. RNA expression clustering distinguished several tumor subtypes and provided complementary support for diagnostically challenging cases, such as undifferentiated pleomorphic sarcoma.</div></div><div><h3>Conclusions</h3><div>Targeted RNA panel testing enabled robust detection of clinically relevant fusions and provided expression-based insights into tumor classification. When integrated with histopathology, this approach improved diagnostic accuracy in rare tumors and offered a practical triage strategy for extended genomic analysis, highlighting its clinical utility in pathology practice.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"168 ","pages":"Article 106036"},"PeriodicalIF":2.6,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922214","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}
Pub Date : 2026-01-07DOI: 10.1016/j.humpath.2026.106035
Ankur R Sangoi, Rohit Mehra, Lara R Harik
{"title":"RNA in situ hybridization based TRIM63 characterization in tubulocystic renal cell carcinoma.","authors":"Ankur R Sangoi, Rohit Mehra, Lara R Harik","doi":"10.1016/j.humpath.2026.106035","DOIUrl":"10.1016/j.humpath.2026.106035","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106035"},"PeriodicalIF":2.6,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145943406","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}
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