{"title":"Spatial Transcriptome Analysis of B7-H4 in Head and Neck Squamous Cell Carcinoma: A Novel Therapeutic Target for Anti-Immune Checkpoint Inhibitors.","authors":"Yuri Noda, Masao Yagi, Koji Tsuta","doi":"10.1007/s12105-025-01815-w","DOIUrl":"10.1007/s12105-025-01815-w","url":null,"abstract":"<p><strong>Purpose: </strong>A significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) are ineligible for immune checkpoint inhibitors (ICIs) because of low programmed cell death protein-ligand 1 (PD-L1) expression. The therapeutic potential of B7-H4 (VTCN1) was investigated using immunohistochemistry (IHC) and spatial transcriptomics (ST).</p><p><strong>Methods: </strong>IHC analysis of B7-H4, PD-L1, CD3, CD4, and CD8 was performed using a tissue microarray [94 HNSCC, 94 adjacent squamous intraepithelial neoplasia (SIN), and 69 adjacent normal oral mucosa (NOM) samples]. B7-H4 and PD-L1 expression levels were assessed using tumor cell score (TC; positive, TC > 1%), immune cell score, and combined positive score. ST was performed on six HNSCCs with paired SINs and NOMs to confirm the expression and distribution of B7-H4 (CTVN1), PD-L1 (CD274), CD4 (DC4A), and CD8 (CD8).</p><p><strong>Results: </strong>In HNSCCs, TCs revealed a mutually exclusive B7-H4/PD-L1 expression pattern in 55% of samples (p < 0.05). B7-H4 positive TCs were more frequent in HNSCCs (79%) than in SINs (10%) and NOMs (2%). ST analysis confirmed mutually exclusive VTCN1/CD274 upregulation in 83% of samples (n = 6) and demonstrated co-localization of B7-H4 protein and VTCN1 in IHC-positive areas. B7-H4 was significantly correlated with low-CD8<sup>+</sup> T-cell infiltration (n = 94, p = 0.009), and CD8A mRNA was down-regulated in the VTCN1<sup>+</sup> area compared with that in the VTCN1<sup>+</sup> area.</p><p><strong>Conclusion: </strong>B7-H4 is a promising antibody-drug conjugate target in ICI-resistant HNSCC. IHC combined with TCs enabled the reliable assessment of B7-H4, given its co-localization with VTCN1 in IHC-positive areas and association with low-CD8<sup>+</sup> T-cells.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"19 1","pages":"78"},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of SOX10, and micro-RNA 221 and Micro-RNA 222 in Oral Squamous Cell Carcinoma and Correlation with Clinicopathological Characteristics.","authors":"Soroor Shahedi, Narges Gholizadeh, Hadiseh Mohammadpour, Neda Kardouni Khoozestani, Nafiseh Sheykhbahaei","doi":"10.1007/s12105-025-01809-8","DOIUrl":"10.1007/s12105-025-01809-8","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma is the most prevalent head and neck cancer. Cancer stem cell markers are crucial for early diagnosis and targeted treatment, as they provide insight into the molecular biology of cancer. One such marker, SOX10, plays a vital role in epithelial-mesenchymal transition in adult cells. This research aims to assess the expression levels of SOX10, miR-221, and miR-222 in oral squamous cell carcinoma tissue.</p><p><strong>Methods: </strong>In this case-control study, 28 oral squamous cell carcinoma and 28 tumor-free margin tissue samples from the same individuals were gathered as the control group. Real-time quantitative Polymerase Chain Reaction was conducted on affected and control samples to assess the expression of SOX10, miR-221, and miR-222 genes. Immunohistochemistry analysis with an anti-SOX10 antibody was performed on oral squamous cell carcinoma samples.</p><p><strong>Results: </strong>The results showed that SOX10 gene expression was significantly upregulated in the oral squamous cell carcinoma specimens, whereas the expression of miR-221 and miR-222 was significantly lower in the tumoral tissue compared to the control tissue. Additionally, SOX10 protein expression was undetectable in the oral squamous cell carcinoma specimens. A positive and significant correlation was also observed between miR-222 expression, smoking, and the clinical stage of oral squamous cell carcinoma. The ROC analysis demonstrated that SOX10, miR-221, and miR-222 had significant diagnostic ability for detecting Oral squamous cell carcinoma.</p><p><strong>Conclusions: </strong>The findings suggest that the expression levels of the SOX10 gene in oral squamous cell carcinoma were significantly higher than in tumor-free margin samples. However, the IHC results did not confirm the protein expression of SOX10. The under-expression of miR-221 and miR-222 genes in oral squamous cell carcinoma samples may indicate a potential tumor suppressor role for these genes. Furthermore, these genes may serve as potential genetic biomarkers for the diagnosis of oral squamous cell carcinoma.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"19 1","pages":"76"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rethinking Ameloblastic Fibroma and Fibro-odontoma: A Serie of 6 Cases and Reclassification Proposal.","authors":"Jonas Ver Berne, Reinhilde Jacobs, Esther Hauben","doi":"10.1007/s12105-025-01818-7","DOIUrl":"10.1007/s12105-025-01818-7","url":null,"abstract":"<p><strong>Purpose: </strong>The classification of mixed odontogenic tumors-specifically ameloblastic fibroma (AF), ameloblastic fibro-odontoma (AFO), and odontoma-remains controversial. The current WHO classification emphasizes the presence of dental hard tissues but overlooks the distinction between aberrant inductive activity and maturation resembling normal odontogenesis. This has led to diagnostic ambiguity and inconsistent management strategies. This study aims to propose a biologically grounded reclassification based on histological, developmental, and molecular criteria.</p><p><strong>Methods: </strong>We conducted a conceptual reassessment of AF, AFO, and odontoma, using six cases from our pathology archives. Histological slides were reviewed with focus on the type and organization of mineralized tissue (tubular dentin, osteodentine, enamel) and its epithelial-mesenchymal context. Clinical and radiological data were evaluated, and BRAF V600E mutation status was retrieved when available. A targeted literature review was performed to integrate findings on histology, genetic alterations, and malignant transformation risk.</p><p><strong>Results: </strong>Two distinct lesion types were identified: (1) Ameloblastic fibroma with aberrant inductive activity, showing irregular osteodentine and enameloid deposits without odontoblast differentiation, harboring BRAF mutations; and (2) odontomas, characterized by mature tubular dentin and enamel formation, indicating a hamartomatous nature, despite significant clinical growth. Historical descriptions support this biological dichotomy, emphasizing the difference between aberrant inductive activity and processes resembling normal odontogenesis.</p><p><strong>Conclusion: </strong>We propose abandoning AFO as a distinct diagnostic entity. Instead, lesions could be classified based on the presence of organized, mature dental hard tissues. AF with aberrant inductive activity represents a benign neoplasm with low malignant potential, while odontoma is a hamartomatous lesion sometimes with large growth capacity but no malignant risk. This binary classification would align histological criteria with biological behavior, integrate molecular data, and restore diagnostic clarity. The validity of this framework should be investigated in future cohorts.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"19 1","pages":"77"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ian T Lagerstrom, David T Danielson, Jeannie M Muir, Robert D Foss, Aaron Auerbach, Nadine S Aguilera
{"title":"A Comprehensive Review of Kimura Disease.","authors":"Ian T Lagerstrom, David T Danielson, Jeannie M Muir, Robert D Foss, Aaron Auerbach, Nadine S Aguilera","doi":"10.1007/s12105-025-01812-z","DOIUrl":"10.1007/s12105-025-01812-z","url":null,"abstract":"","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"19 1","pages":"75"},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prokopios P Argyris, Gabrielle R Dennis, Rajaram Gopalakrishnan, Ioannis G Koutlas, Kristin K McNamara, John R Kalmar
{"title":"Oral Soft Tissue and Jawbone Sarcomas: A Retrospective Clinicopathologic Analysis of 128 Cases from Two Institutions and Comprehensive Literature Review.","authors":"Prokopios P Argyris, Gabrielle R Dennis, Rajaram Gopalakrishnan, Ioannis G Koutlas, Kristin K McNamara, John R Kalmar","doi":"10.1007/s12105-025-01811-0","DOIUrl":"10.1007/s12105-025-01811-0","url":null,"abstract":"<p><strong>Purpose: </strong>Oral soft tissue and jawbone sarcomas (OSTJS) are rare neoplasms accounting for only 1% of all intraoral malignancies. As a result, robust epidemiologic data pertaining to OSTJS are limited. Here, we present a collaborative, retrospective analysis of the clinicopathologic characteristics of 128 cases of OSTJS, together with a comprehensive review of the literature.</p><p><strong>Methods: </strong>Archived OSTJS cases (2000-2022) were retrieved from the electronic laboratory databases of the oral pathology services at The Ohio State University and University of Minnesota. Patient age and sex, anatomic site and histopathologic diagnosis were recorded.</p><p><strong>Results: </strong>Among 128 OSTJS, 123 (96.1%) were primary and 5 (3.9%) metastatic (M: F = 1.5:1; mean age = 43.7 years, range = 4-102 years). Most OSTJS presented in adults (113, 88.3%; mean age = 47.8 years) with only 15 pediatric cases (11.7%; mean age = 13 years). Favored sites included the mandible (48, 37.5%), maxilla (39, 30.4%), gingiva (15, 11.7%), palate (13, 10.2%), and tongue (4, 3.1%). In adults, osteosarcoma represented the predominant OSTJS (58, 51.3%), followed by Kaposi sarcoma (18, 15.9%), leiomyosarcoma (7, 6.2%), chondrosarcoma (6, 5.3%), low-grade myofibroblastic sarcoma (5, 4.4%), and 4 each (3.5%) of angiosarcoma, rhabdomyosarcoma and undifferentiated pleomorphic sarcoma. Similarly, osteosarcoma comprised the most common OSTJS histotype in the pediatric population (8, 53.3%), followed by Ewing sarcoma (4, 26.7%) and 1 each (6.7%) of TFCP2::EWSR1-rearranged rhabdomyosarcoma, mesenchymal chondrosarcoma, and alveolar soft part sarcoma.</p><p><strong>Conclusion: </strong>OSTJS represent an uncommon, histopathologically diverse, subset of mesenchymal malignancies. In our series, most patients were adults in their 4th - 5th decade with a broad age range and a slight male predilection. Overall, jawbone osteosarcoma and Kaposi sarcoma accounted for two-thirds of OSTJS cases in this cohort. While the diagnosis of OSTJS relies heavily on routine light microscopic findings, ancillary immunohistochemistry and/or cytogenetic studies are frequently warranted.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"19 1","pages":"74"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Branchioma: A Classic Example.","authors":"Melad N Dababneh, Kaitlyn Ooms","doi":"10.1007/s12105-025-01805-y","DOIUrl":"10.1007/s12105-025-01805-y","url":null,"abstract":"<p><p>Branchioma is a very rare benign neoplasm of the neck. This case highlights its classic clinical presentation, histomorphology and immunoprofile.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"19 1","pages":"72"},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joud Y Omari, Marc L Nevins, Gideon P Smith, Reshma S Menon, Sook-Bin Woo
{"title":"Erdheim-Chester Disease of the Jaws: A Case Report and Review of the Literature.","authors":"Joud Y Omari, Marc L Nevins, Gideon P Smith, Reshma S Menon, Sook-Bin Woo","doi":"10.1007/s12105-025-01803-0","DOIUrl":"10.1007/s12105-025-01803-0","url":null,"abstract":"","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"19 1","pages":"71"},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Traumatic Ulcerative Granuloma with Stromal Eosinophilia: From Reactive Process to Low Grade CD30 + lymphoproliferative Disorder.","authors":"Rachelle Wolk, Denise Trochesset","doi":"10.1007/s12105-025-01802-1","DOIUrl":"10.1007/s12105-025-01802-1","url":null,"abstract":"<p><strong>Purpose of review: </strong>Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a rare, benign ulcerative lesion of the oral mucosa that exists in both adult and infantile (Riga-Fede) forms. This review examines TUGSE by exploring its clinical presentation, pathogenesis, histopathological features, and treatment approaches. It briefly discusses oral CD30+ T-cell lymphoproliferative disorders (TLPDs) and their potential relation with TUGSE lesions.</p><p><strong>Recent findings: </strong>While traditionally considered reactive in nature, some recent evidence suggests TUGSE may share features with CD30+ T-cell lymphoproliferative disorders (TLPDs), potentially representing a spectrum of lesions and thereby complicating diagnosis and treatment approaches. Although some TUGSE cases demonstrate CD30 positivity and monoclonality of the T-cell receptor gamma (TCRγ) chain gene, no cases have progressed to widespread or systemic lymphoma. The rarely reported CD30+ TLPDs of the oral cavity appear to share features with their cutaneous counterparts, demonstrating indolent biologic behavior and excellent prognosis, with complete or partial regression frequently occurring after incisional biopsy. TUGSE presents as a slow-healing ulcer with raised borders and induration, commonly affecting the tongue and potentially mimicking squamous cell carcinoma. While trauma appears to be an important factor, the exact pathogenesis remains unclear. Histopathologically, lesions show ulceration with polymorphous infiltrate rich in eosinophils extending into the submucosa, with characteristic muscle fiber degeneration and variable presence of atypical mononuclear cells. The condition generally follows a self-limiting course with excellent prognosis, responding well to conservative management. Aggressive treatment and extensive follow-up may be unnecessary even for CD30+ cases with monoclonal TCRγ chain genes. Further research is needed to clarify the relationship between oral CD30+ TLPDs and TUGSE.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"19 1","pages":"70"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Eosinophilic Angiocentric Fibrosis: An Uncommon Entity in the Spectrum of IgG4-related Disease.","authors":"Sarah E Gradecki, Edward B Stelow","doi":"10.1007/s12105-025-01795-x","DOIUrl":"10.1007/s12105-025-01795-x","url":null,"abstract":"<p><strong>Background: </strong>Eosinophilic angiocentric fibrosis (EAF) is a rare, tumefactive inflammatory process of the sinonasal and upper respiratory tract and orbit. Numerous histologic mimickers of EAF occur in these locations.</p><p><strong>Methods: </strong>A comprehensive literature review focused on EAF and its histologic mimickers was performed.</p><p><strong>Results: </strong>This manuscript serves as an overview of the histopathological characteristics of EAF and its histologic mimickers, including granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), sinonasal inflammatory polyps, epithelioid hemangioma, invasive fungal rhinosinusitis, Langerhans cell histiocytosis, rhinoscleroma, inflammatory myofibroblastic tumor, and fibromatosis.</p><p><strong>Conclusion: </strong>A correct diagnosis of EAF can be reached by identifying the classic histopathologic features of prominent eosinophilia, lymphoplasmacytic inflammation, and concentric perivascular fibrosis. Additionally, as EAF sometimes lies on the spectrum of IgG4-related disease, immunohistochemistry and serologic studies can be used to aid in diagnosis.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"19 1","pages":"67"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}