Human pathologyPub Date : 2025-07-01DOI: 10.1016/j.humpath.2025.105867
Xueting Jin, Shunsuke Koga, Xiao Zhou, Niaz Z. Khan, Zubair W. Baloch
{"title":"Clinicopathologic characteristics of papillary thyroid carcinoma, tall cell subtype and subtype with tall cell features, an institutional experience","authors":"Xueting Jin, Shunsuke Koga, Xiao Zhou, Niaz Z. Khan, Zubair W. Baloch","doi":"10.1016/j.humpath.2025.105867","DOIUrl":"10.1016/j.humpath.2025.105867","url":null,"abstract":"<div><div>Papillary thyroid carcinoma (PTC) is categorized into various subtypes, including classic PTC (cPTC) with 0 % tall cell morphology, PTC with tall cell features (PTCtcf) with >0 but <30 % tall cells, and tall cell subtype of PTC (tcsPTC) having ≥30 % tall cells. This case-cohort study investigated the clinicopathologic characteristics of cPTC, PTCtcf, and tcsPTC. Patients with.</div><div>tcsPTC subtype were older (mean 50.2 years) than patients with cPTC (42.0 years) and PTCtcf (45.6 years). tcsPTC subtype presented with more advanced tumor stages than cPTC, indicating more aggressive tumor behavior. The frequency of extra-thyroidal extension in tcsPTC (60.1 %) and PTCtcf (39.7 %) was higher than in cPTC (23.6 %). Angioinvasion was more frequent in tcsPTC (15.1 %) than cPTC (7.6 %). Positive margins were more common in PTCtcf (12.4 %) and tcsPTC (23.9 %) than cPTC (4.9 %). tcsPTC and PTCtcf had more tumor foci than cPTC. Recurrent or persistent disease occurred more frequently in PTCtcf (13.2 %) and tcsPTC (6.7 %) compared with cPTC (1.5 %). Kaplan-Meier survival analysis demonstrated that all tcsPTC tumors and those tcsPTC tumors ≤1 cm had worse overall and disease-unrelated survival outcomes compared with cPTC, which was mostly due to second non-thyroid tumors. There were no differences in disease-related survival among the 3 PTC subgroups possibly due to efficacy of radioactive iodine therapy more frequently used for treating PTCtcf and tcsPTC compared with cPTC. In conclusion, the findings highlight the aggressive nature of tcsPTC and PTCtcf and emphasize the value of histologic subtyping in guiding management of thyroid carcinoma.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"161 ","pages":"Article 105867"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564676","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":"BSND: An emerging immunohistochemical marker that reliably distinguishes benign from malignant oncocytic salivary gland tumors","authors":"Arshi Tandon , Sabari Sinehaa , Sheeba Saifi , Amit Kumar Adhya , Kavneet Kaur , Aanchal Kakkar","doi":"10.1016/j.humpath.2025.105870","DOIUrl":"10.1016/j.humpath.2025.105870","url":null,"abstract":"<div><div>Oncocytic cells appear in various salivary gland lesions (SGLs) like oncocytic hyperplasia, metaplasia and several neoplasms. It is particularly challenging to distinguish oncocytoma and Warthin tumor from oncocytic and Warthin-like mucoepidermoid carcinoma (MEC) in the absence of molecular testing. A spectrum of oncocytic SGLs underwent immunohistochemistry for BSND, a novel marker of striated ducts and oncocytic tumor cells. <em>MAML2</em> fluorescence in situ hybridization (FISH) was performed in suspected MECs.</div><div>BSND immunoexpression was assessed in 138 SGLs, including 132 in-house and 4 consult cases. In-house cases comprised 5 non-neoplastic, 43 benign and 84 malignant SGLs. All nodular oncocytic hyperplasia (100 %) were BSND positive, while intercalated duct hyperplasia was negative. Among benign tumors, oncocytic cystadenomas (3/3), Warthin tumor (15/15), and oncocytoma (1/1) were BSND-positive (100 %). One clear cell oncocytoma reclassified as clear cell MEC on resection was BSND-negative. All remaining benign tumors were negative. Among all malignant tumors, one Warthin-like MEC was reclassified as infarcted metaplastic Warthin tumor on morphology and as it lacked <em>MAML2</em> rearrangement; it was BSND positive. All remaining 83 malignant neoplasms were BSND-negative (100 %). All consult cases submitted as oncocytoma and oncocytic carcinoma were reclassified on ancillary testing, with BSND reliably distinguishing benign from malignant SGLs. In 21 cases with <em>MAML2</em> FISH, <em>MAML2</em> rearrangement was mutually exclusive with BSND immunopositivity.</div><div>BSND is thus newly validated as an immunomarker to resolve diagnostic uncertainty in oncocytic SGLs. Use of BSND in routine practice could streamline the diagnostic process and improve patient management by reducing reliance on ambiguous morphological features, particularly in settings lacking molecular testing.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"161 ","pages":"Article 105870"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572022","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":"Neoplastic ductal plate malformation pattern rather than von Meyenburg complexes may be an early neoplastic lesion of small duct-type intrahepatic cholangiocarcinoma","authors":"Yasuni Nakanuma , Motoko Sasaki , Yuko Kakuda , Kenichi Harada , Yasunori Sato , Takashi Sugino .","doi":"10.1016/j.humpath.2025.105865","DOIUrl":"10.1016/j.humpath.2025.105865","url":null,"abstract":"<div><h3>Aims</h3><div>To characterize “neoplastic ductal plate malformation pattern (N-DPMP)” of intrahepatic cholangiocarcinoma (iCCA) and to evaluate whether or not von Meyenburg complexes (VMCs) and VMC-mimics characterized by dysplasia/carcinoma <em>in situ</em> were related to the development of iCCA.</div></div><div><h3>Materials and methods</h3><div>N-DPMP composed of low-grade neoplastic biliary epithelia and showing ductal plate malformation (DPM) features, VMCs, and VMC-mimics were surveyed in 144 small duct-type (SD)-iCCA cases and 47 large duct-type (LD)-iCCA cases. Genetic alterations were examined by direct sequencing and immunohistochemistry. 536 autopsied livers were used as controls.</div></div><div><h3>Results</h3><div>N-DPMP was found in 27 cases of SD-iCCA but not in LD-iCCA (p < 0.05). While a tumor totally composed of N-DPMP was found in 4 cases, a tumor composed of N-DPMP and anastomosing CCA and/or conventional CCA was found in the remaining 23 cases, with the latter being larger than the former (p < 0.05). Genetic alterations in N-DPMP parts were also found in anastomosing parts in two cases of N-DPMP with anastomosing CCA, supporting that anastomosing CCA may develop in N-DPMP. VMCs were found frequently in 49 cases of SD-iCCA than in 16 cases of autopsy livers (p < 0.01). VMC-mimics, which were found in 5 of 144 SD-iCCA cases, frequently showed mixture of atypical and benign epithelia with an abrupt transition, suggesting that VMC-mimics may reflect cancerization of VMCs by iCCA.</div></div><div><h3>Conclusions</h3><div>N-DPMP may be an early neoplastic lesion in approximately one-fifth of SD-iCCA. VMCs may be frequently associated with SD-iCCA, but there is no evidence that VMCs are a precursor of SD-iCCA.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"161 ","pages":"Article 105865"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560017","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}
Human pathologyPub Date : 2025-06-25DOI: 10.1016/j.humpath.2025.105862
Hyun Jung Lee , Farinaz Shokri , Maria S. Tretiakova
{"title":"Diagnostic accuracy of TRIM63 RNA-ISH in MiTF-rearranged renal cell carcinomas: Results from a 331-tumor validation cohort","authors":"Hyun Jung Lee , Farinaz Shokri , Maria S. Tretiakova","doi":"10.1016/j.humpath.2025.105862","DOIUrl":"10.1016/j.humpath.2025.105862","url":null,"abstract":"<div><div>The microphthalmia-associated transcription factor rearranged renal cell carcinoma (MiTF-rRCC) comprise very heterogenous group of tumors with variable histology mimiking other renal cell tumors and often present a diagnostic challenge. Tripartite Motif Containing 63 (TRIM63) has been proposed as a novel marker of MiTF-rRCC, but its sensitivity and specificity remain unknown. The study aimed to investigate TRIM63 expression in a large independent cohort of different renal cell tumors and determine its diagnostic value in detecting MiTF-rRCC.</div><div>TRIM63 RNA in situ hybridization (RNA-ISH) was performed on 331 renal cell tumors, including 15 TFE3-translocation RCCs (TFE3-tRCC), 3 TFEB-amplified RCCs (TFEB-aRCC), 113 clear cell RCCs, 66 papillary RCCs, 27 oncocytomas, 23 chromophobe RCCs, 13 eosinophilic solid and cystic (ESC)-RCCs, 10 collecting duct carcinomas, 6 tubulocystic RCC, 4 fumarate hydratase (FH)-deficient RCCs, 51 other types of RCCs.</div><div>TRIM63 overexpression was identified in 80 % (12/15) of TFE3-tRCC, 33.3 % (1/3) of TFEB-aRCC, while being positive only in 4 % of other renal cell tumor types (12/313). Among non-MITF-rRCC positive cases, significant incidence of TRIM63 overexpression was detected in 66.7 % of tubulocystic RCC (4/6), 38.5 % of ESC-RCC (5/13) and 25 % of FH-deficient RCC (1/4). The overall performance of TRIM63 RNA-ISH assay for detecting MITF-rRCC tumors showed high specificity (96.2 %) and negative predictive value (98.4 %) with relatively lower sensitivity (72.2 %) and positive predictive value (52.0 %).</div><div>In conclusion, TRIM63 RNA-ISH can be a useful diagnostic marker of MiTF-rRCC. TRIM63 RNA-ISH could improve the diagnostic accuracy of recognizing MiTF-rRCC in an adequate histologic background and distinguishing them from other renal cell tumors.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"161 ","pages":"Article 105862"},"PeriodicalIF":2.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490590","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}
Human pathologyPub Date : 2025-06-25DOI: 10.1016/j.humpath.2025.105861
Michael Kozak, Mahzad Azimpouran, Xiaomo Li , Danielle A. Hutchings, Keith Lai, Kevin M. Waters, Maha Guindi, Brent K. Larson
{"title":"Clinicopathologic findings in native liver biopsies after heart transplantation and total artificial heart implantation","authors":"Michael Kozak, Mahzad Azimpouran, Xiaomo Li , Danielle A. Hutchings, Keith Lai, Kevin M. Waters, Maha Guindi, Brent K. Larson","doi":"10.1016/j.humpath.2025.105861","DOIUrl":"10.1016/j.humpath.2025.105861","url":null,"abstract":"<div><div>Liver biopsy is common before heart transplantation to assess for advanced fibrosis that could require combined heart-liver transplantation. While congestive hepatopathy is common in these biopsies, little is known about what happens in the native liver after heart transplantation. In this study, 1300 adult heart explants were identified at a single institution, 38 of which had subsequent native liver biopsies (2.9 %), including 31 after orthotopic heart transplantation (OHT) and 7 after total artificial heart (TAH) implantation. Presentation was variable, but similar overall between post-OHT and post-TAH patients, with elevated liver function tests being the most common indication for liver biopsy (15/38; 39.5 %), and AST levels being significantly higher in post-TAH patients than post-OHT patients (mean: 172.4 vs. 59.8 U/L, respectively; p = 0.0077). A wide variety of histological patterns was seen, but the most common was a vascular outflow impairment pattern in 11/38 (28.9 %) patients. Fibrosis was predominantly mild (23/38; 60.5 %), with advanced fibrosis in 5 (13.2 %), no fibrosis in 6 (15.8 %), and insufficient parenchyma for evaluation in 4 (10.5 %). Fewer than half of patients with vascular outflow impairment pattern had a clinical diagnosis of heart failure, suggesting alternative etiologies of vascular injury in post-OHT/TAH patients.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"161 ","pages":"Article 105861"},"PeriodicalIF":2.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490589","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}
Human pathologyPub Date : 2025-06-18DOI: 10.1016/j.humpath.2025.105855
Neil D. Theise , Mehran N. Kohnehshahri , Luis A. Chiriboga , Billie Fyfe , Wenqing Cao , Sui Zee , Rami Imam , Simona Pichler-Sekulic , Rebecca G. Wells
{"title":"Evidence of interstitial continuity within and beyond the human pancreas","authors":"Neil D. Theise , Mehran N. Kohnehshahri , Luis A. Chiriboga , Billie Fyfe , Wenqing Cao , Sui Zee , Rami Imam , Simona Pichler-Sekulic , Rebecca G. Wells","doi":"10.1016/j.humpath.2025.105855","DOIUrl":"10.1016/j.humpath.2025.105855","url":null,"abstract":"<div><div>Bodies have continuous reticular networks, comprising collagens and other extracellular matrix components, through all tissues and organs. We recently validated fluid flow through human interstitium and demonstrated that they are filled with hyaluronic acid by staining with biotinylated hyaluronic acid binding protein. Their continuity across tissue boundaries (skin and subcutis), and between organs (colon and mesentery) and along vessels (within adventitia) and nerves (within perineurium) has been demonstrated in this manner. We aim to evaluate the continuity of interstitium within human pancreas and beyond into adjoining tissues. Tissue blocks of histologically normal pancreas from nine pancreatectomy specimens were sectioned in parallel for staining with hematoxylin and eosin, Picrosirius red, and biotinylated hyaluronic acid binding protein. Also, specimens of invasive pancreatic cancer were assessed for interstitial tumor invasion. Picrosirius red ensheathes all microscopic units of the endocrine and exocrine pancreas, including acini, islets, and ducts, adventitia of blood vessels and perineurium, and into adjacent duodenum. Interstitial spaces within the fibrous tissue are filled with hyaluronic acid by staining and are also continuous through all microscopic structures of the pancreas, into adjoining duodenum and along vessels (within adventitia) and nerves (within perineurium). Invasive carcinoma is seen spreading through pre-existing interstitial spaces. Interstitium of the human pancreas is continuous within and beyond the pancreas. This continuity suggests the capacity to be a route of molecular, microbiome, and cellular trafficking and communication. In particular, it is a route of cancer spread.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"161 ","pages":"Article 105855"},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336477","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}
Human pathologyPub Date : 2025-06-14DOI: 10.1016/j.humpath.2025.105854
Ruihe Lin, Huili Li, Ezra Baraban, Tamara Lotan, Angelo DeMarzo, Pedram Argani, Alexander Baras, Andres Matoso
{"title":"WITHDRAWN: Atypical Intraductal Proliferation (AIP) of the Prostate: Findings in Repeat Biopsy or Radical Prostatectomy in Patients who Met Pathologic Criteria for Active Surveillance","authors":"Ruihe Lin, Huili Li, Ezra Baraban, Tamara Lotan, Angelo DeMarzo, Pedram Argani, Alexander Baras, Andres Matoso","doi":"10.1016/j.humpath.2025.105854","DOIUrl":"10.1016/j.humpath.2025.105854","url":null,"abstract":"<p><p>The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.humpath.2025.105841\u0000The duplicate article has therefore been withdrawn.\u0000The full Elsevier Policy on Article Withdrawal can be found at <ce:inter-ref xlink:href=\"https://www.elsevier.com/about/policies-and-standards/article-withdrawal\" id=\"intref0015\">https://www.elsevier.com/about/policies-and-standards/article-withdrawal</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105854"},"PeriodicalIF":2.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309879","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}