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.
The WHO classification of head and neck tumors over the past five decades were reviewed, highlighting the major conceptual and taxonomic changes that have shaped contemporary head and neck pathology. Major WHO classifications of head and neck tumors were reviewed, with a focus on changes in diagnostic concepts and taxonomic principles rather than individual additions or removals of tumor entities. WHO classifications have evolved from morphology-based, site-specific systems to an integrated clinicopathological and molecular taxonomy. Early editions emphasized histomorphology and presumed tissue of origin. Subsequent classifications, however, increasingly incorporated immunophenotypic and molecular findings. The recognition of virus-associated neoplasms and recurrent molecular alterations has contributed to defining new entities and refining existing categories. The fifth edition further standardized tumor taxonomy by introducing essential and desirable diagnostic criteria, reflecting a biology-driven approach to classification. The evolution of WHO classifications reflects major advances in tumor biology and has substantially influenced diagnostic practice and clinical interpretation. Future classifications will likely incorporate increasingly sophisticated molecular, digital, and computational approaches while maintaining standardized, reproducible, and clinically meaningful diagnostic criteria.
The Ki-67 labelling index is routinely performed by manual microscopic examination of tissue samples. Digital pathology has improved the efficiency of the diagnostic workflow, however discrepancies between automated and manual estimation of Ki-67 labelling index remain a concern. The present study compared conventional and DeepLIIF-extended global scoring methods for Ki-67 labelling index estimation across a broad spectrum of oral lesions. To our knowledge, this is the first study in oral and maxillofacial pathology to assess the diagnostic precision, reproducibility, and temporal efficiency using DeepLIIF-extended global scoring. High-power images of Ki-67 stained oral pathologies were analysed using an extended global scoring system by both manual and automated analysis. Manual scoring was performed by two independent pathologists blinded to the clinical diagnosis. Automated scoring was conducted by the DeepLIIF platform. Pearson's and Spearman's correlation coefficients were used to assess the relationship between the automated AI-derived and manual score. Bland–Altman analysis assessed the limits of agreement between the two methods. Agreement between the AI-derived and manual Ki-67 scores was poor (ICC = 0.389), with a consistent tendency for the AI platform to overestimate Ki-67 positivity (mean bias = − 10.27
Heterotopic ossification is characterized by the formation of mature bone within soft tissues and is most commonly associated with trauma, surgery, or chronic inflammation. The development of hematologic malignancies within heterotopic bone is exceedingly uncommon. We present a unique case of submandibular heterotopic ossification containing lymphoplasmacytic lymphoma and provide a review of calcified soft-tissue lesions encountered in the head and neck region. A 77-year-old man presented with a calcified nodule in the left submandibular region. Radiologic imaging demonstrated a well-circumscribed focus of soft-tissue ossification with no continuity to the mandible. The lesion was initially interpreted as a calcified lymph node, and watchful waiting was recommended. However, given the patient’s reports of gradual enlargement and increasing discomfort during cervical rotation, surgical excision was performed. Histopathological examination revealed mature lamellar bone and marrow infiltrated by an atypical lymphoplasmacytic B-cell population. Immunohistochemical and PCR analysis demonstrated findings supportive of lymphoplasmacytic lymphoma, including IgM kappa light-chain restriction. Subsequent hematologic evaluation showed a serum IgM paraprotein and sparse bone marrow involvement. To our knowledge, this represents the first documented case of lymphoplasmacytic lymphoma involving marrow-containing submandibular heterotopic ossification. As the lesion was the sole clinical manifestation of an otherwise occult lymphoproliferative disorder, this case underscores the importance of histopathological and molecular evaluation of excised calcified head and neck lesions, even when clinical and radiologic findings suggest a benign process.
