Grading of oral epithelial dysplasia (OED) suffers from poor interobserver agreement and limited accuracy for predicting malignant transformation. We assessed the potential value of incorporating p53 abnormalities into the grading framework for OED, with particular attention to 24-month progression risk and interobserver agreement. In this retrospective nested case–control study, 103 OED lesions, including 21 cases progressing to squamous cell carcinoma within 24 months and 82 controls, were independently reviewed by three pathologists using a two-tier system, first with H E alone and after a 2-month washout with H E plus p53 immunohistochemical stain (IHC). Lesions with high-grade morphology and/or abnormal p53 expression were upgraded as integrated high-grade dysplasia (i-HGD) in the second round. Interobserver agreement was assessed by Fleiss' kappa. Associations with rapid progression were assessed by logistic regression, and discrimination was compared using the C-index. Cases were older than controls (median 63 vs. 52 years, p < 0.01). i-HGD was associated with 24-month progression (age-adjusted OR = 9.17, 95
CRTC1::TRIM11 cutaneous melanocytic tumors are a recently described uncommon entity almost exclusively reported as arising in the skin with fewer than 70 described cases and no dedicated reports of tumors arising in the sinonasal cavity (SNC). We identified 3 cases arising in the SNC with similar morphology and immunophenotype, all harboring CRTC1::TRIM11 fusion. We present the clinical, histological, immunophenotype, and molecular profile of these tumors and compare our tumors with those previously reported in the literature and provide practical guidance for evaluating tumors in the SNC with undifferentiated, neuroendocrine, or melanocytic phenotype. Formalin-fixed, paraffin embedded tissue sections of the patients’ tumors were examined and compared with routinely stained sections and by immunohistochemistry. Whole exome/whole transcriptome sequencing revealing CRTC1::TRIM11 fusions in each case was performed at Caris® Life Sciences. The patients were 34, 48, and 69 years of age, 2 females and 1 male. All tumors originated in the nasal cavity and hard palate. Original diagnoses were S100-negative granular cell tumor, poorly differentiated carcinoma and mucosal melanoma. All tumors demonstrated highly cellular proliferations of round/ovoid cells arranged in vague organoid clusters. Individual cells had moderate eosinophilic granular cytoplasm and round nuclei containing dispersed and granular chromatin with visible nucleoli resembling neuroendocrine tumors. The neural markers synaptophysin and chromogranin were negative, however, tumors expressed PGP9.5 and NCAM in 2 cases. All cases expressed SOX10 in a diffuse fashion but negative for S100, Melan-A, HMB-45. CRTC1::TRIM11 fusion was detected in all cases. This recently described CRTC1::TRIM11 fusion-driven tumor almost exclusively described in cutaneous sites, hence the current designation as cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT), can arise in the nasal cavity and should be considered in the differential diagnoses of aggressive tumors with similar morphologies in the SNC that include mucosal melanoma, sinonasal undifferentiated carcinoma, and neuroectodermal and neuroendocrine carcinomas.
Pleomorphic adenoma (PA) is the most common salivary gland neoplasm and is histologically benign, yet it poses two problems that current practice cannot resolve prospectively: local recurrence after incomplete excision and malignant transformation to carcinoma ex pleomorphic adenoma (CXPA). These are distinct outcomes, the first determined largely by surgical and capsular factors and the second by the acquisition of additional genetic alterations, and they are considered separately throughout. This narrative review appraises candidate biomarkers by the pathologist’s decision they are intended to inform, at fine-needle aspiration, intraoperative consultation and examination of the resection specimen. Each candidate is assigned an intended-use category (lineage, diagnostic of established transformation, progression-associated, risk-predictive or therapy-predictive), a developmental evidence grade and a label recording whether the evidence came from benign disease or was extrapolated from malignant cohorts. PLAG1 and HMGA2 immunohistochemistry, fusion detection and the second edition of the Milan System now give the cytopathologist practical tools for recognising PA. Androgen receptor and HER2 expression, Ki-67, MDM2 amplification, copy-number and DNA methylation profiles and the HMGA2::WIF1 fusion are associated with the sequence from PA through atypical PA to invasive CXPA, but this evidence is cross-sectional: these markers help recognise transformation that has occurred, not predict it in a benign tumour. No tissue, cytological or biofluid marker has been validated for predicting either recurrence or transformation. We summarise practical reporting recommendations for current practice and the longitudinal study designs and reporting standards needed before any marker can be used to predict outcome in benign PA.
To characterize the clinicopathologic and molecular spectrum of kinase fusion-positive spindle cell neoplasms arising in the oral and maxillofacial region and to evaluate the patient-level contribution of molecular testing to diagnosis, classification, and therapeutic stratification. A systematic review was conducted according to PRISMA 2020. PubMed/MEDLINE, Embase, and Scopus were searched from inception through July 31, 2026, supplemented by Google Scholar screening, reference checking, and citation tracking. Eligible reports described primary oral or maxillofacial spindle cell neoplasms harboring oncogenic kinase fusions or rearrangements. Overlapping publications were reconciled through patient-level deduplication. Clinicopathologic, immunophenotypic, molecular, diagnostic, treatment, and outcome data were synthesized descriptively. Molecular evidence was categorized into three prespecified tiers, and methodological quality was assessed using design-appropriate Joanna Briggs Institute tools. Fifteen eligible reports contained 22 report-level tumor occurrences, which were reduced to 15 unique patients after deduplication. Median age was 8 years (range, neonatal period–65 years), and 9 patients (60.0
This study aims to characterize sialadenopapillary ductal tumors—a rare and recently described clinicopathologic spectrum of minor salivary gland neoplasms with prominent submucosal ductal proliferation. This spectrum includes lesions reported as sialadenoma papilliferum-like intraductal papillary tumor, tubulopapillary hidradenoma-like tumor of the mandible, papillary cystadenocarcinoma, and other entities. Herein we report three additional cases of sialadenopapillary ductal tumor and review the English-language literature to identify previously reported cases with features of this tumor type. Inclusion criteria include the following: (1) neoplasm of likely minor salivary gland origin with prominent submucosal ductal proliferation, and (2) multiple bilayered to multilayered cystic structures with a peripheral myoepithelial cell layer. Excluded from our review were tumors with diagnostic features of intraductal carcinoma, salivary duct carcinoma, or epithelial-myoepithelial carcinoma (as per WHO criteria) as well as cases with inadequate documentation of histopathologic features. The current case series includes two patients with posterior mandibular tumors treated by marginal resection and one patient with a palatal tumor treated by simple excision. Review of the English-language literature reveals 37 previously reported cases with features of sialadenopapillary ductal tumor. Clinicopathologic findings for the current and previously reported cases include the following: mean age 64 years (range: 33–89 years), male-to-female ratio 1.5, most frequently involved sites: mandible and/or retromolar mandibular gingiva (n = 22) and palate (n = 11), mean tumor size 1.7 cm (range 0.2–4.2 cm), bone involvement (n = 21), surface involvement (n = 14), BRAF V600E immunohistochemistry positive (23 of 27 cases), surgical treatment ranging from curettage/excision/enucleation to resection, cervical lymph node metastasis (n = 1), recurrence (n = 3, ranging from 1 to 5 years after treatment). Current data regarding this rare tumor type are limited to case series and individual case reports; our review of 40 documented cases in the existing literature and current series suggests that sialadenopapillary ductal tumors may represent low-grade adenocarcinomas amenable to surgical treatment and long-term surveillance. However, further studies are needed for improved characterization and development of evidence-based treatment guidelines. Awareness of this extremely rare entity is essential to ensure appropriate diagnosis.
