Head and neck pathology最新文献

{"title":"Pattern-Anchored Diagnosis of Oral Epithelial Dysplasia: A Position Paper From COST Action INTERCEPTOR Working Group 2.","authors":"Syed Ali Khurram, Keith D Hunter, Edward W Odell, Merva Soluk Tekkeşin, Mark Lingen, Pablo Agustín Vargas, Omar Kujan, Daniela Elena Costea, Paolo Bossi, Pierre Saintigny, Senada Koljenović","doi":"10.1007/s12105-026-01963-7","DOIUrl":"10.1007/s12105-026-01963-7","url":null,"abstract":"<p><strong>Purpose: </strong>Oral epithelial dysplasia (OED) is the principal histopathological marker for malignant risk stratification in oral potentially malignant disorders (OPMDs). Current World Health Organisation (WHO) three-tier and other binary grading systems are limited by modest inter-observer reproducibility and suboptimal prognostic discrimination, particularly for architecture-predominant lesions where cytological atypia is inconspicuous. The most clinically consequential failure of current practice is not mis-grading but non-recognition of dysplasia altogether, with direct implications for patient surveillance and management.</p><p><strong>Methods: </strong>This position paper, arising from Working Group 2 of COST Action CA21140 INTERCEPTOR, synthesises evidence from inter-observer reproducibility studies, feature-based prognostic models, under-recognition studies, outcome data and computational pathology analyses to propose and contextualise a pattern-anchored, grade-retaining diagnostic framework for OED.</p><p><strong>Results: </strong>Five recognisable histological patterns are proposed: conventional/basaloid, keratinising/differentiated, verrucous, papillomatous, and HPV-associated, functioning as diagnostic anchors that capture the full morphological spectrum of OED, including architecture-predominant phenotypes that are disproportionately under-recognised in routine practice. Feature-based prognostic models demonstrate that architectural traits characterising these patterns (bulbous rete ridges, AUROC 0.74; cohesion loss, AUROC 0.73) predict malignant transformation more effectively than grade alone. Independent computational pathology analyses identify corresponding immune microenvironment and architectural signals as the strongest prognostic variables, providing convergent support.</p><p><strong>Conclusion: </strong>A two-step approach i.e. first identifying the dominant morphological pattern and then assigning grade within that pattern using existing WHO or binary criteria, offers a pragmatic, grade-retaining refinement compatible with current diagnostic frameworks and clinical pathways. The proposal is hypothesis-driven and requires prospective multicentre validation before wider adoption.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889854","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":"Inflammatory Rhabdomyoblastic Tumor with Malignant Progression of the Neck: Unique Copy Number Profile Identified by Nanopore Sequencing.","authors":"Kengo Shiraishi, Naohiro Makise, Ryuta Kojima, Tsukasa Takahashi, Akiko Odaka, Mariko Oikawa, Yusuke Amano, Akinobu Araki, Sawato Fukuda, Yukiyoshi Mita, Ichiro Fukumoto, Takashi Kinoshita, Masahito Kawazu, Toyoyuki Hanazawa","doi":"10.1007/s12105-026-01960-w","DOIUrl":"10.1007/s12105-026-01960-w","url":null,"abstract":"<p><p>Inflammatory rhabdomyoblastic tumors (IRMT) are newly described entities characterized by a near-haploid karyotype. Most IRMTs exhibit indolent behavior; however, rare malignant transformation has been reported. We report a case of IRMT with malignant progression.</p><p><strong>Case presentation: </strong>A 67-year-old man presented with a painless mass in the left neck. Radiology revealed a 40-mm tumor in the left sternocleidomastoid muscle, with no evidence of distant metastasis.</p><p><strong>Results: </strong>Core needle biopsy showed densely proliferating polygonal cells with pleomorphic nuclei, necrosis, and atypical mitoses. Based on histology, a preliminary diagnosis of pleomorphic rhabdomyosarcomas was made, although the clinical behavior seemed atypical. Nanopore DNA sequencing was subsequently performed and, within days, revealed characteristic molecular features, including relative gains of chromosomes 5, 7, and 22, a TP53 mutation, and DNA methylation profiling consistent with IRMT with malignant progression. The tumor was surgically resected, and pathological examination of the resected specimen confirmed a minor conventional IRMT component. Furthermore, infiltration of CD163-positive histiocytes was prominent, and fluorescence in situ hybridization analysis revealed two red signals (COL1A1 on chromosome 17) and four green signals (PDGFB on chromosome 22) in most tumor cells. Collectively, these histopathological, immunohistochemical, cytogenetic, and epigenetic findings established a final diagnosis of IRMT with malignant progression.</p><p><strong>Conclusions: </strong>Given the small tumor size, chemotherapy and radiotherapy were not administered. Nevertheless, the long-term behavior of IRMT with malignant progression remains unclear; thus, careful follow-up is warranted.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148858065","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":"Pathogenesis of Warthin's Tumors: A Critical Synthesis of the Evidence.","authors":"John D Cramer, Fulvio Lonardo","doi":"10.1007/s12105-026-01961-9","DOIUrl":"10.1007/s12105-026-01961-9","url":null,"abstract":"<p><strong>Purpose: </strong>Warthin tumor (WT) is the second most common benign parotid neoplasm, and its reported incidence has risen over recent decades, with a narrowing male predominance that parallels tobacco exposure trends. Whether WT is a true clonal neoplasm or a metaplastic process remains contested. We synthesize contemporary evidence on WT pathogenesis into a unified framework and articulate its diagnostic implications.</p><p><strong>Methods: </strong>Critical narrative synthesis. We searched PubMed/MEDLINE, Embase, and Web of Science from inception through May 16, 2026 for \"Warthin tumor\" and its synonyms combined with subtopic terms spanning pathogenesis, embryology, smoking, radiation, oncocytic and mitochondrial biology, cellular senescence, IgG4-related disease, viral association, clonality, malignant transformation, and synchronous neoplasia, with hand-searching of reference lists. No formal eligibility criteria, dual independent screening, or quantitative pooling were applied. Reporting follows the Scale for the Assessment of Narrative Review Articles (SANRA).</p><p><strong>Results: </strong>Three converging lines of evidence account for WT pathogenesis: (1) an anatomic-embryologic substrate unique to the late-encapsulating parotid, in which salivary ductal epithelium is entrapped within intraparotid lymph nodes; (2) extrinsic-stressor-induced cellular injury and oncocytic metaplasia driven by tobacco, ionizing radiation, IgG4-mediated inflammation, or age-related mitochondrial decline; and (3) a permissive lymphoid microenvironment derived from pre-existing nodal parenchyma and actively remodeled by epithelium-derived chemokines. Clonality testing of conventional WT has been polyclonal, no recurrent oncogenic driver has been identified, and CRTC1-MAML2 has been reattributed to misclassified mucoepidermoid carcinoma.</p><p><strong>Conclusion: </strong>The available evidence favors conventional WT as a metaplastic-proliferative lesion of ductal epithelium entrapped within intraparotid lymph nodes and modulated by extrinsic stressors, rather than as a true clonal neoplasm. Whether a KRAS-mutant subset is genuinely neoplastic remains unresolved, since a single activating mutation does not by itself establish malignancy. The absence of a consistent oncogenic driver, the histologic heterogeneity of rare associated malignancies spanning multiple epithelial and lymphoid subtypes, and the synchronous occurrence of WT with oral and aerodigestive carcinomas favor a carcinogen-driven field effect over clonal progression.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815510","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":"Correction: Biphenotypic Sinonasal Sarcoma with a Novel PAX3::FOXO6 Fusion: A Case Report and Review of the Literature.","authors":"Meredith M Nichols, Fatimah Alruwaii, Mohamad R Chaaban, Yu-Wei Cheng, Christopher C Griffith","doi":"10.1007/s12105-026-01957-5","DOIUrl":"10.1007/s12105-026-01957-5","url":null,"abstract":"","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805172","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":"Discrepancies with Final Diagnosis in Head and Neck Intraoperative Frozen Section.","authors":"Scott Albright, Alexandra Isaacson, Robert Robinson","doi":"10.1007/s12105-026-01959-3","DOIUrl":"https://doi.org/10.1007/s12105-026-01959-3","url":null,"abstract":"<p><strong>Purpose: </strong>Creating a frozen section slide and crafting an interpretation is a multistep process with multiple possible points of failure. Head and neck frozen section pathology presents particular technical and diagnostic challenges. The aim of our study was to identify discrepancies between head/neck intraoperative and final diagnoses, determine the site of process failure, and assess the potential causes.</p><p><strong>Methods: </strong>Concordance data from head and neck intraoperative and final diagnoses (2020-2023) were queried from our LIS-embedded quality assurance system. Discrepancies were categorized as major and minor, with major defined as those that would have altered the surgical procedure.</p><p><strong>Results: </strong>We found 71 total discrepancies out of 1844 head and neck cases (3.9%). Major discrepancies accounted for 48/1844 (2.7%). Only major errors were considered for further study and were classified primarily into three categories: (1) inadequate gross sampling by the prosector, usually involving mucosal tissues of excised large specimens for evaluation of margins for dysplasia/carcinoma (14/48 cases; 29%), (2) insufficient sectioning into the block leaving undetected tissue unexamined (9/48 cases; 19%), and (3) interpretative errors (23/48 cases; 48%). The most common major interpretative errors involved the diagnosis of squamous dysplasia (9 cases), failure to identify minimally invasive squamous carcinoma (4 cases), failure to identify parathyroid and thyroid tissues (5 cases), and incorrect diagnoses of non-squamous neoplasms (5 cases). Two errors (4%) were ascribed to processing artifact issues in the frozen section.</p><p><strong>Conclusion: </strong>Half of diagnostic discrepancies occurred at steps prior to microscopic interpretation. Management of specimen grossing and tissue selection in large specimens, adequate block sectioning, and adherence to diagnostic criteria for difficult but common issues such as squamous dysplasia, minimally invasive carcinoma and thyroid/parathyroid morphology may help reduce intraoperative/final diagnosis discrepancies.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764241","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":"Clinical Utility of Molecular Testing in Ameloblastoma: A Systematic Review with Functional Meta-synthesis and Exploratory Meta-analysis.","authors":"Carlos M Ardila, Eliana Pineda-Vélez, Alejandro I Díaz-Laclaustra","doi":"10.1007/s12105-026-01955-7","DOIUrl":"10.1007/s12105-026-01955-7","url":null,"abstract":"<p><strong>Purpose: </strong>This systematic review with functional meta-synthesis and exploratory meta-analysis evaluated the clinical utility of molecular testing in ameloblastoma, focusing on diagnostic, genotype-phenotype, prognostic, liquid-biopsy, and precision-therapy implications.</p><p><strong>Methods: </strong>PubMed/MEDLINE, Scopus, and Embase were searched from inception to April 2026. Eligible studies were full original articles evaluating direct molecular or molecularly interpretable testing in human ameloblastoma. Data were synthesized using functional meta-synthesis. Exploratory random-effects meta-analyses were performed when sufficient study-level data were available.</p><p><strong>Results: </strong>Twenty-nine studies met the inclusion criteria. Molecular testing was most consistently informative for defining the molecular landscape and supporting diagnosis. BRAF V600E was the dominant alteration across the evidence base, but additional alterations in SMO, FGFR2, RAS-family genes, CTNNB1, PIK3CA, EGFR, and ROS1 were reported, particularly in selected or BRAF-wild-type tumors. Exploratory meta-analysis of 19 studies showed a pooled BRAF V600E prevalence of 69.1% (95% CI: 62.1%-75.3%; I2 = 80.3%). Four studies provided complete site-specific data, showing strong enrichment of BRAF V600E in mandibular versus maxillary tumors (OR = 20.13; 95% CI: 7.65-52.95; I2 = 0.0%). BRAF VE1 immunohistochemistry showed high exploratory pooled sensitivity (96.6%; 95% CI: 84.1%-99.4%) and specificity (89.8%; 95% CI: 71.5%-96.8%) when compared with molecular reference methods. Prognostic evidence was inconsistent: BRAF V600E was not a reliable stand-alone recurrence marker, although VEGF mRNA and broader molecular profiles may have prognostic relevance. Plasma cfDNA testing did not reliably detect tissue-positive BRAF V600E. Targeted therapy evidence suggested radiologic response and organ-preservation potential in selected BRAF V600E-mutated tumors, but remained limited to non-randomized series.</p><p><strong>Conclusions: </strong>Molecular testing provides clinically relevant diagnostic and genotype-phenotype information in ameloblastoma and may guide targeted therapy in selected cases. Prognostic and liquid-biopsy applications remain insufficiently validated.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681995","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":"DNA Methylation Signatures of Upper Aerodigestive Tract Squamous Cell Carcinoma and Sarcomatoid Squamous Cell Carcinoma Are Similar: A Potential Novel Diagnostic Tool for the Diagnosis of Sarcomatoid Squamous Cell Carcinoma.","authors":"Josephine K Dermawan, Christopher C Griffith, Jennifer Starbuck, Sheila Shurtleff, Travis Hattery, Joy Nakitandwe, Shauna Campbell, John S A Chrisinger, Mark J Chen, Elizabeth M Azzato, Karen J Fritchie","doi":"10.1007/s12105-026-01958-4","DOIUrl":"10.1007/s12105-026-01958-4","url":null,"abstract":"<p><strong>Purpose: </strong>Upper aerodigestive tract squamous cell carcinoma (UATSCC) is often easy to recognize in its conventional form. However, a subset of tumors loses histologic evidence of squamous differentiation and, instead, become sarcomatoid (spindled). These cases may be difficult or impossible to appropriately classify on biopsy material, even with immunohistochemistry. DNA methylation has emerged as a tool to help in classifying undifferentiated malignancies. We sought to explore whether conventional and sarcomatoid UATSCC harbor the same epigenetic signature.</p><p><strong>Methods: </strong>Cases of sarcomatoid UATSCC were collected and reviewed. The conventional and sarcomatoid components were documented. Only specimens with concomitant epithelial dysplasia and/or invasive SCC were included. A panel of keratins (CK AE1/3, CAM5.2 and CK5/6) was performed on the sarcomatoid component of each tumor and scored as follows: 0, < 1%; 1+, 1-25%; 2+, 26-50%, 3+, > 50%. DNA methylation profiling was performed and compared with profiles from publicly available UATSCC and a control cohort of pleomorphic malignancies including undifferentiated sarcoma, leiomyosarcoma, angiosarcoma, atypical fibroxanthoma/pleomorphic dermal sarcoma, and melanoma, as well as sarcomatoid carcinoma of cutaneous origin.</p><p><strong>Results: </strong>21 UATSCC samples from 15 patients were retrieved (9 M, 6 F; 47-88 years, median 71 years) from sites including tongue (7), larynx (5), pharynx (3), maxillary/mandibular alveolar ridge (3), \"neck\" (2), and nasal cavity (1). 12 samples were entirely sarcomatous, while six were conventional SCC and three contained both sarcomatoid and conventional components. Of the sarcomatous components, six were entirely negative (score = 0) for all keratins performed. Using dimensionality reduction analysis of DNA methylation data by Uniform Manifold Approximation and Projection (UMAP) and unsupervised hierarchical clustering, 11 of 12 sarcomatoid UATSCC samples, were positioned with conventional UATSCC. Methylomes of sarcomatoid carcinoma of upper aerodigestive tract and cutaneous origin overlapped. Copy number profile analysis did not show significant differences between conventional and sarcomatoid histologies or tumor time point.</p><p><strong>Conclusion: </strong>The epigenetic signatures of conventional and sarcomatoid UATSCC are similar, even in cases that lack expression of multiple keratins. DNA methylation profiling may be leveraged in biopsies and entirely sarcomatoid UATSCC to accurately diagnose these cases and differentiate them from pleomorphic sarcomas and melanoma.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674444","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":"Early-Stage Oral Squamous Cell Carcinoma in Adolescents and Young Adults Compared with Older Patients Exhibits Distinct Clinicopathological Features.","authors":"Sawako Ono, Katsutoshi Hirose, Hotaka Kawai, Tatsuya Abe, Shintaro Sukegawa, Masanori Masui, Chihoko Ikeda, Madoka Isomura, Yuri Tachibana, Junya Ono, Katsumitsu Shimada, Hitoshi Nagatsuka, Hidetaka Yamamoto","doi":"10.1007/s12105-026-01944-w","DOIUrl":"10.1007/s12105-026-01944-w","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to compare the clinicopathological features of stage I-II oral squamous cell carcinoma (OSCC) between adolescents and young adults (AYAs) and older patients, and to identify prognostic factors in AYA OSCC.</p><p><strong>Methods: </strong>Forty-eight AYA patients aged 15-39 years and 69 older patients aged ≥ 65 years with surgically treated stage I-II OSCC were retrospectively analyzed. Histological evaluation, survival analysis, immunohistochemistry for p53, p16, and MTAP, high-risk HPV RNA in situ hybridization, and fluorescence in situ hybridization for CDKN2A and MTAP were performed.</p><p><strong>Results: </strong>Compared with older patients, OSCCs in AYAs were more frequently located on the tongue (93.7% vs. 47.8%) and more often exhibited a superficial spreading growth pattern (60.4% vs. 31.8%). AYA tumors more frequently showed modified WPOI-1, high tumor budding, and abnormal p53 immunophenotypes (85.4% vs. 68.1%). AYA patients showed significantly better overall and disease-free survival than older patients. Within the AYA group, depth of invasion (DOI) > 5 mm was associated with distant metastasis and poorer overall and disease-free survival. Postoperative lymph node metastasis occurred in 31.2% of AYAs. Univariable analysis suggested that clinical stage II, tumor thickness > 5 mm, DOI > 5 mm, and tumor budding scores 1-2 were associated with postoperative lymph node metastasis. Molecular status, including p53, p16/CDKN2A, and MTAP, did not provide robust prognostic stratification.</p><p><strong>Conclusion: </strong>Early-stage AYA OSCC exhibits distinct clinicopathological features. DOI was the strongest prognostic indicator, whereas clinical stage, tumor thickness, and tumor budding may provide additional prognostic information regarding the risk of late nodal metastasis.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633601","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":"Pleomorphic Adenoma of the Palate with Bizarre Ductal and Myoepithelial Cells: A Case Image.","authors":"Katsutoshi Hirose, Masato Nakaguro, Kohei Kawamura, Taisuke Mori, Satoru Toyosawa","doi":"10.1007/s12105-026-01953-9","DOIUrl":"10.1007/s12105-026-01953-9","url":null,"abstract":"<p><strong>Background: </strong>Pleomorphic adenomas (PAs), the most common salivary gland tumors, are comprised of ductal epithelial and myoepithelial cells within a stromal background. A rare subset of PAs exhibits bizarre cells and 12q amplification involving HMGA2 and MDM2; in reported cases, bizarre cells have been confined to the myoepithelial component. We report the first case of a PA with bizarre-cytological features in both the ductal and myoepithelial components.</p><p><strong>Case presentation: </strong>A 75-year-old woman presented with a palatal mass. Histology revealed a well-circumscribed biphasic tumor with marked nuclear pleomorphism in both luminal ductal and non-luminal myoepithelial cells. Despite the alarming atypia, mitotic activity was low, and neither necrosis nor invasive growth was observed. Immunohistochemically, luminal bizarre cells exhibited ductal characteristics, whereas non-luminal bizarre cells exhibited myoepithelial characteristics. Tumor cells were negative for androgen receptor and HER2 and showed a p53 wild-type expression pattern. The Ki-67 labeling index was < 5%, and the bizarre cells rarely tested positive. Molecular analysis demonstrated amplification of HMGA2 and MDM2, whereas no other pathogenic variants related to salivary gland tumors were detected. Complete excision was performed; no evidence of recurrence or metastasis was observed after 10 months.</p><p><strong>Conclusion: </strong>Marked cytological atypia of bizarre cells in PA, even when involving ductal cells, may not necessarily indicate malignancy. This case highlights the value of integrating clinicopathological and genetic findings to better define PAs with bizarre cells and prevent overdiagnosis of carcinoma based on atypia alone.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148595368","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":"Lenalidomide-Associated Oral Pigmentation: A Case Report.","authors":"André Luis Santana de Freitas, Fabiana Gomes Cardoso Pereira de Sousa, Cleverson Teixeira Soares, Rosane Rezende de Souza Giuliani, Andresa Borges Soares","doi":"10.1007/s12105-026-01954-8","DOIUrl":"10.1007/s12105-026-01954-8","url":null,"abstract":"<p><strong>Background: </strong>Lenalidomide is an immunomodulatory agent widely used in the treatment of multiple myeloma and is generally associated with a favorable safety profile. Although pigmentary alterations such as cutaneous hyperpigmentation and hair repigmentation have been reported, oral mucosal involvement remains poorly documented.</p><p><strong>Case presentation: </strong>An 80-year-old Black female with multiple myeloma undergoing lenalidomide therapy presented with asymptomatic brown macules on the tongue, hard palate, bilateral buccal mucosa and gingiva. Histopathological examination of an incisional biopsy on the tongue revealed many fine granular, brownish pigmentation of approximately the same size throughout all epithelial layers, as well as collagen fibers, vascular walls, neural tissue, and skeletal striated muscle. These findings represent an unusual pattern of pigment distribution not previously described in patients under lenalidomide therapy.</p><p><strong>Conclusion: </strong>This case emphasizes the need for thorough oral examination in patients undergoing lenalidomide therapy, as early recognition of drug-induced pigmentation is essential for proper diagnosis and management.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148582092","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}