{"title":"Histopathology of Chronic Rhinosinusitis and Sinonasal Inflammatory Polyps.","authors":"Mena Mansour, Juan C Hernandez-Prera","doi":"10.1007/s12105-025-01760-8","DOIUrl":"10.1007/s12105-025-01760-8","url":null,"abstract":"<p><p>Sinus content specimens from patients with chronic rhinosinusitis (CRS) are commonly encountered by surgical pathologists across various practice settings. The inflammatory cellular component of CRS often includes eosinophil-rich inflammation, and the specimens frequently contain polyps. Moreover, noninvasive forms of fungal rhinosinusitis can also be identified in the sinus contents of patients with CRS. This article provides a succinct review of the histopathology of CRS and sinonasal inflammatory polyps.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"35"},"PeriodicalIF":3.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634224","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}
Justin A Bishop, Masato Nakaguro, Doreen Palsgrove, Jeffrey Gagan, Prasad Koduru, Lisa Rooper, Molly Housely Smith, Jared Shows, Yuichiro Tada, Hirotake Nishimura, Mei Matsuno, Yoshitaka Utsumi, Toshitaka Nagao
{"title":"12q Amplification Characterizes a Distinctive Salivary Gland Tumor with Bizarre Myoepithelial Atypia.","authors":"Justin A Bishop, Masato Nakaguro, Doreen Palsgrove, Jeffrey Gagan, Prasad Koduru, Lisa Rooper, Molly Housely Smith, Jared Shows, Yuichiro Tada, Hirotake Nishimura, Mei Matsuno, Yoshitaka Utsumi, Toshitaka Nagao","doi":"10.1007/s12105-025-01770-6","DOIUrl":"10.1007/s12105-025-01770-6","url":null,"abstract":"<p><strong>Background: </strong>Over the past two decades, an increased understanding of molecular alterations has greatly refined salivary gland tumor classification. Many tumors that were previously difficult or impossible to classify have been recognized to represent emerging entities based on shared histologic, immunophenotypic and molecular characteristics. While initial attention was given to carcinomas, more recently molecular discoveries have shed light on salivary gland adenomas as well. We present a series of biphasic salivary gland tumors characterized by striking bizarre myoepithelial atypia, unified at the genetic level by evidence of 12q amplification.</p><p><strong>Methods: </strong>Salivary gland tumors demonstrating bizarre but degenerative-appearing atypia were identified. Immunohistochemistry, MDM2 and HMGA2 fluorescence in situ hybridization (FISH), and/or targeted next-generation sequencing (NGS) were attempted on the cases.</p><p><strong>Results: </strong>Seven cases were identified. The tumors arose in the parotid gland (3 of 7), oral cavity (3 of 7) and submandibular gland (1 of 7). The patients were 5 women and 2 men, ranging from 53 to 83 years (mean, 65.7 years). Histologically, the tumors appeared well-circumscribed and partially encapsulated. They were highly cellular and solid, with no chondromyxoid stromal component. The tumors were biphasic, with a population of eosinophilic ducts in a background of basaloid cells with variable clear cell change and spindling. The most striking feature in all cases was the presence of scattered cells with bizarrely atypical nuclei with smudgy chromatin. These bizarre cells maintained low nuclear:cytoplasmic ratios and lacked mitotic activity. The biphasic nature of the tumors was demonstrated by the basaloid cells staining with S100, p63 and p40, while the ducts were positive for CD117 and AE1/AE3 (strong). The bizarre cells had a myoepithelial immunophenotype. The Ki67 index ranged from 1 to 10%, with most of the markedly atypical cells not labeling. DNA NGS was successful in 4 cases, demonstrating 12q copy number increase and 5q copy number loss in all 4 cases. RNA sequencing was able to identify increased MDM2 and HMGA2 expression in one additional case, while amplification of MDM2 and/or HMGA2 was also demonstrated in 6 of 7 cases by FISH. In summary, all 7 cases exhibited evidence of 12q amplification by at least one technique.</p><p><strong>Conclusion: </strong>Salivary gland neoplasms with bizarre myoepithelial atypia are consistently associated with evidence of 12q amplification. Although this histologic alteration may be alarming, the smudgy nature of the chromatin and paucity of mitotic activity and Ki67 labeling suggest that this finding may not necessarily be indicative of malignancy.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"31"},"PeriodicalIF":3.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634926","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":"Oncocytic Mucoepidermoid Carcinoma of the Parotid Gland.","authors":"Prokopios P Argyris, Paul E Wakely","doi":"10.1007/s12105-025-01768-0","DOIUrl":"10.1007/s12105-025-01768-0","url":null,"abstract":"<p><strong>Case presentation: </strong>A 30-year-old man presented with a multilobulated left parotid mass measuring 5.2 × 4.1 × 2.4 cm by imaging, and numerous enlarged left cervical lymph nodes, suspicious for metastasis. FNA cytopathology of the mass showed loose clusters of large cells displaying increased N/C ratios and ample granular oncocytic cytoplasm. A superficial left parotidectomy with radical resection of the cheek and cervical lymphadenectomy was performed. Histopathologic examination disclosed a circumscribed, unencapsulated neoplasm exhibiting a solid growth pattern composed of infiltrative islands and nests of cohesive, polygonal, oncocytoid cells in a densely fibrous stroma. Lesional cells exhibited enlarged, oval, open-face nuclei with coarse chromatin and a single acidophilic macronucleolus, voluminous eosinophilic granular cytoplasm and distinct cell membrane borders. Mitotic activity and necrosis were absent. Microcystic architecture was noted solely in a single tumor nest at the periphery. These spaces contained mucinous secretions and were lined by cuboidal oncocytic and intermediate cells with interspersed mucocytes, highlighted by mucicarmine stain. Immunohistochemically, oncocytic cells were strongly and diffusely positive for cytokeratin AE1/AE3, p63 and p40, and uniformly negative for androgen receptor, GATA3, S100, SOX10 and Her-2. A MAML2 rearrangement was identified by FISH, thus confirming the diagnosis of oncocytic variant of mucoepidermoid carcinoma.</p><p><strong>Conclusion: </strong>In this illustrative example, we present the clinicoradiologic, cytologic, histopathologic, and immunophenotypic characteristics of this rare variant of mucoepidermoid carcinoma, together with molecular documentation.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"30"},"PeriodicalIF":3.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634208","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":"Laryngeal Coccidioidomycosis Mimicking Squamous Cell Carcinoma.","authors":"Chuying Su, James S Lewis","doi":"10.1007/s12105-025-01769-z","DOIUrl":"10.1007/s12105-025-01769-z","url":null,"abstract":"<p><p>Coccidioidomycosis is a rare fungal infection that can closely mimic squamous cell carcinoma (SCC) clinically and radiologically when presenting in the larynx, leading to potential misdiagnosis. This case highlights the importance of considering fungal infections in the differential diagnosis of laryngeal lesions, particularly in endemic regions.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"29"},"PeriodicalIF":3.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524810","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":"Langerhans Cell Histiocytosis and Other Histiocytic Lesions.","authors":"Reed A McKinney, Guanghua Wang","doi":"10.1007/s12105-025-01766-2","DOIUrl":"10.1007/s12105-025-01766-2","url":null,"abstract":"<p><strong>Background: </strong>Histiocytoses, including Langerhans cell histiocytosis (LCH), comprise a diverse group of histiocytic disorders characterized by the abnormal accumulation and proliferation of histiocytes in various tissues or organs throughout the body, ranging from benign, self-limited conditions to aggressive malignancies and systemic inflammatory syndromes. These lesions present unique diagnostic challenges due to their broad spectrum of clinical presentations, overlapping histopathological and immunophenotypical features, and genetic complexity.</p><p><strong>Methods: </strong>This review analyzes major histiocytic lesions, focusing on their epidemiology, clinical presentations, histologic and immunophenotypic features, and genetic characteristics to facilitate accurate diagnosis and differentiation among these histiocytoses.</p><p><strong>Results: </strong>LCH, a well-recognized lesion, can affect various organ systems and necessitates differentiation from other types of histiocytoses such as Erdheim-Chester disease (ECD), Rosai-Dorfman-Destombes disease (RDD), and cutaneous and mucocutaneous non-Langerhans cell histiocytoses. Some histiocytic lesions, such as histiocytic sarcoma, are inherently malignant, while others, like hemophagocytic lymphohistiocytosis (HLH), manifest as severe, potentially life-threatening systemic inflammatory syndromes. Recent molecular genetic studies revealed recurrent genetic alterations in the MAPK pathway, such as BRAF V600E and MAP2K1 in LCH and ECD, and KRAS, NRAS, and MAP2K1 mutations in a subset of RDD. Malignant histiocytoses frequently show alterations in tumor suppressor genes like TP53 and CDKN2A.</p><p><strong>Conclusion: </strong>Precise classification of histiocytic lesions relies on a comprehensive diagnostic approach that integrates clinical, histologic, immunophenotypic, and genetic data. Recent genetic advances shed light on these conditions' unique but occasionally overlapping pathogenic mechanisms. Molecular genetics advancements continue to refine diagnostic accuracy and present new therapeutic targets, especially for aggressive or treatment-resistant cases.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"26"},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494263","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}
David T Danielson, Ian Lagerstrom, Zachary Wary, Aaron Auerbach, David S Cassarino
{"title":"Dermatologic Lesions with Eosinophilia in the Head and Neck.","authors":"David T Danielson, Ian Lagerstrom, Zachary Wary, Aaron Auerbach, David S Cassarino","doi":"10.1007/s12105-025-01757-3","DOIUrl":"10.1007/s12105-025-01757-3","url":null,"abstract":"<p><strong>Background: </strong>Dermatologic lesions with notable eosinophilic infiltration of the head and neck region represent a diverse group of conditions, ranging from benign to malignant proliferations.</p><p><strong>Methods: </strong>We performed a comprehensive literature review focusing on head and neck dermatologic conditions that commonly present with a prominent eosinophilic infiltrate.</p><p><strong>Results: </strong>This review provides an overview of common entities showing prominent associated eosinophilic inflammatory infiltrates in this region, including epithelioid hemangioma, eosinophilic cellulitis (Wells syndrome), eosinophilic folliculitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), granuloma faciale, and Langerhans cell histiocytosis (LCH).</p><p><strong>Conclusion: </strong>Eosinophils play a key role in the pathogenesis of these disorders, although the exact mechanisms remain poorly understood. Accurate diagnosis is crucial for differentiating these conditions, as they can share similar histologic features. This review aims to enhance understanding of these eosinophilic dermatologic conditions, improving diagnostic accuracy and treatment strategies.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"27"},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494253","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":"Eosinophils and the Head and Neck.","authors":"Henok Eskinder, Yang Zhang","doi":"10.1007/s12105-025-01765-3","DOIUrl":"10.1007/s12105-025-01765-3","url":null,"abstract":"<p><p>Tissue eosinophilia is a common finding during histopathologic evaluation and recognizing its presence oftentimes aids pathologists in arriving at the correct diagnosis. The head and neck region is an anatomic location where an abundance of eosinophil-rich disorders occur. In this review, we seek to provide an overview of eosinophil morphology, production, regulation, lifecycle, recruitment, function, and mediators. We will also summarize the most commonly diagnosed eosinophil-rich disorders, both non-neoplastic and neoplastic, occurring in the head and neck.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"24"},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494262","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}
Julia Gresky, Melina Frotscher, Sophia Thiem, Alexander Stoessel, Alexey Kalmykov, Natalia Berezina
{"title":"Cemento-Osseous Dysplasia in a Female Bronze Age Skeleton (North Caucasus).","authors":"Julia Gresky, Melina Frotscher, Sophia Thiem, Alexander Stoessel, Alexey Kalmykov, Natalia Berezina","doi":"10.1007/s12105-025-01767-1","DOIUrl":"10.1007/s12105-025-01767-1","url":null,"abstract":"<p><strong>Purpose: </strong>The earliest known case of cemento-osseous dysplasia could be detected in a Bronze Age skeleton, dating back 4500 years ago in the region of the North Caucasus. Although the soft tissue was missing, sufficient diagnosis could be achieved by using different methods that prove the existence of fibro-osseous processes already in prehistory. Skeletal remains provide a direct view of such changes which cannot be obtained from a living patient without compromising.</p><p><strong>Methods: </strong>A skeleton of a 30-40-year-old female individual from the burial mound of Budyonnovsk 10 (including 19 individuals) in Southern Russia was investigated using macroscopic, radiographic, and microscopic methods.</p><p><strong>Results: </strong>In the mandible, destruction of the labial wall of the alveoli 32 and 31 is already visible macroscopically. At the base of the lesion, the original bone is replaced by fine porous bone including small dense particles: plain radiography and computed tomography evidence localized processes to the periapical areas of all lower incisors. The lesions are mainly radiolucent, only the particles in alveolus 32 have a radiopaque appearance. Microscopy shows woven bone as filling of the lesions and additional hypocellular materials in alveolus 32, which can best be explained as cementum-like structures.</p><p><strong>Conclusions: </strong>The lesion´s location in the periapical areas of the lower incisors, the woven bone, and cementum-like structures fit the diagnosis of periapical cemento-osseous dysplasia. The presence of a second individual with focal cemento-osseous dysplasia in this burial mound is an interesting co-occurrence that requires further genetic analysis.</p><p><strong>Limitations: </strong>The diagnosis is solely based on the skeletal remains, soft tissue components are missing.</p><p><strong>Suggestions for further research: </strong>Genetic analyses are planned to detect the underlying mutation for the two individuals.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"28"},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494252","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}
Michael T Wotman, Weihong Xiao, Robyn R Du, Bo Jiang, Keiko Akagi, Suyu Liu, Maura L Gillison
{"title":"Development and Validation of an Assay to Quantify Plasma Circulating Tumor Human Papillomavirus DNA for 13 High-Risk Types that Cause 98% of HPV-Positive Cancers.","authors":"Michael T Wotman, Weihong Xiao, Robyn R Du, Bo Jiang, Keiko Akagi, Suyu Liu, Maura L Gillison","doi":"10.1007/s12105-025-01752-8","DOIUrl":"10.1007/s12105-025-01752-8","url":null,"abstract":"<p><strong>Purpose: </strong>Plasma circulating tumor HPV DNA (ctHPVDNA) persistence after curative-intent treatment may identify patients with HPV-positive cancers at risk for recurrence. Technical validation is required for use as an integral biomarker in a prospective clinical trial.</p><p><strong>Methods: </strong>Development and analytical validation of a digital droplet PCR assay for detection and quantification of 13 high-risk HPV types (i.e., Cell-Free 13) was performed with oligonucleotides/plasmids encoding type-specific E6/E7 coding regions. Clinical performance, determinants of detection/quantification, and associations of pre-treatment ctHPVDNA with progression-free survival (PFS) were also evaluated in a prospective cohort of 272 head and neck cancer patients.</p><p><strong>Results: </strong>Limit of detection, limit of quantification, and linear range of quantification were 5, 16 and 16-200,000 virus copies for all 13 high-risk HPV types. No cross-reactivity was detected across all 13 HPV types. At 10,000 copies, inter-assay coefficients of variation ranged from 0.3 to 4.6%. Multiplexing, DNA purification method, input plasma volume, total input cell-free (< 1800 ng) or genomic (< 700 ng) DNA did not affect HPV detection or quantification. The assay had a sensitivity of 91.7% (95%CI 87.3-94.9%) and specificity of 97.7% (95%CI 87.7-99.9%) for ctHPVDNA detection in the setting of newly diagnosed HPV-positive oropharyngeal cancer. Tumor and nodal stage categories, tumor viral load (ρ = 0.41, p < 0.05), and HPV integration status were associated with ctHPVDNA quantitative level. Pre-treatment ctHPVDNA greater than the median (231 copies/ml) was associated with worse PFS (HR = 2.14, 95%CI 1.16-3.97, p = 0.0156) in univariate analysis. However, this was no longer significant after adjustment for clinical covariates (HR<sub>adj</sub> = 1.81, 95%CI 0.97-3.37, p = 0.0635).</p><p><strong>Conclusion: </strong>Cell-Free 13 demonstrated excellent analytical performance and clinical sensitivity/specificity in HPV-positive oropharyngeal cancer. Pre-treatment ctHPVDNA may be associated with oncologic outcomes.</p>","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"25"},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494261","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":"Reevaluating Histopathologic and Molecular Insights in Ameloblastoma Management: A Call for Methodological Refinement.","authors":"Carlos M Ardila, Pradeep K Yadalam","doi":"10.1007/s12105-025-01764-4","DOIUrl":"10.1007/s12105-025-01764-4","url":null,"abstract":"","PeriodicalId":47972,"journal":{"name":"Head & Neck Pathology","volume":"19 1","pages":"23"},"PeriodicalIF":3.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450678","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}