Faculty Bibliography

Pigmented lesions of the oral cavity can present significant diagnostic challenges because of their diverse etiologies and similar clinical presentations. Understanding these lesions is crucial for correct diagnosis and management because the biologic behavior ranges from benign physiologic variations to aggressive malignancies. The spectrum of oral lesions can include melanin-associated and exogenous pigmented lesions such as physiologic pigmentation and an amalgam tattoo, reactive processes such as smoker's melanosis and post-inflammatory pigmentation, benign neoplasms such as melanocytic nevi, and malignant conditions such as oral mucosal melanoma. Unlike cutaneous malignant melanomas, mucosal melanomas show distinct molecular profiles, with a lower prevalence of BRAF^V600E mutations and a higher prevalence of c-KIT (CD117) mutations, which impacts therapeutic approaches. While most oral pigmented lesions are benign, they require a careful clinical evaluation, and when indicated, a biopsy for definitive diagnosis. This comprehensive review enables clinicians to navigate the complicated spectrum of oral pigmented lesions for optimal patient care.

PURPOSE OF REVIEW/OBJECTIVE: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. RECENT FINDINGS/RESULTS: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.

Radiology is essential in prosthodontics for diagnosis and treatment planning, utilizing intraoral radiographs, panoramic imaging, and cone beam computed tomography (CBCT) while adhering to the as low as reasonably achievable principle. CBCT provides 3 dimensional (3D) evaluations of bone quality, dimensions, and proximity to vital structures, aiding implant placement and reducing surgical risks. Artificial intelligence (AI) and computer-assisted surgery have transformed prosthodontics, improving treatment planning and implant precision and reducing complications. The future of prosthodontic radiology will increasingly integrate AI-driven imaging and robotic assistance to enhance precision and treatment success.

The oral mucosal calcified nodule (OMCN) is a rare soft tissue lesion with only 7 cases reported in the English literature. It typically presents in the pediatric population as an asymptomatic submucosal nodule of less than 2 cm size affecting the maxillary ridge or palate, though other sites are reported. The histopathology displays stratified squamous epithelium overlying fibrous connective tissue with embedded calcified aggregates bordered by variable numbers of multinucleated giant cells. Surgical excision is curative. In this report, we present a new case of OMCN, outline the characteristic histopathologic features and review the cases reported in the English literature.

Oral leiomyomatous hamartoma (OLH) is a rare lesion, with only 40 cases reported in the literature. It typically presents early in life as a nodule on the anterior maxillary alveolar tissues or the tongue. Its growth potential is limited, with few cases reaching dimensions >2.0 cm, and its microscopic composition includes an intact surface mucosa with an underlying fibrovascular stroma possessing an unencapsulated proliferation of smooth muscle fascicles. Excision is considered the definitive treatment. Here we describe the clinical, microscopic, histochemical, and immunohistochemical features and management of 3 cases of OLH and review the literature. The findings we present here can assist in performing differential diagnosis, particularly in discriminating between OLH and similar yet non-hamartomatous processes and in selecting appropriate management.

OBJECTIVES/OBJECTIVE:knockout mice were included to evaluate the effects of the conditional E-cadherin ablation onto tooth development. MATERIAL AND METHODS/METHODS:littermate controls. These litters were euthanized at postnatal day P2 to study the effects of conditional E-cadherin ablation in vivo. RESULTS:mice also displayed a smaller overall stature compared with heterozygotes and wild-type littermates. CONCLUSIONS:E-cadherin is important in tooth development, including the formation of enamel, the crown, pulp space, and the roots.

Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.

BACKGROUND:The effective detection and monitoring of potentially malignant oral lesions (PMOL) are critical to identifying early-stage cancer and improving outcomes. In the current study, the authors described cytopathology tools, including machine learning algorithms, clinical algorithms, and test reports developed to assist pathologists and clinicians with PMOL evaluation. METHODS:Data were acquired from a multisite clinical validation study of 999 subjects with PMOLs and oral squamous cell carcinoma (OSCC) using a cytology-on-a-chip approach. A machine learning model was trained to recognize and quantify the distributions of 4 cell phenotypes. A least absolute shrinkage and selection operator (lasso) logistic regression model was trained to distinguish PMOLs and cancer across a spectrum of histopathologic diagnoses ranging from benign, to increasing grades of oral epithelial dysplasia (OED), to OSCC using demographics, lesion characteristics, and cell phenotypes. Cytopathology software was developed to assist pathologists in reviewing brush cytology test results, including high-content cell analyses, data visualization tools, and results reporting. RESULTS:Cell phenotypes were determined accurately through an automated cytological assay and machine learning approach (99.3% accuracy). Significant differences in cell phenotype distributions across diagnostic categories were found in 3 phenotypes (type 1 ["mature squamous"], type 2 ["small round"], and type 3 ["leukocytes"]). The clinical algorithms resulted in acceptable performance characteristics (area under the curve of 0.81 for benign vs mild dysplasia and 0.95 for benign vs malignancy). CONCLUSIONS:These new cytopathology tools represent a practical solution for rapid PMOL assessment, with the potential to facilitate screening and longitudinal monitoring in primary, secondary, and tertiary clinical care settings.

AIMS: Ectomesenchymal chondromyxoid tumor (ECT) is a rare, benign intraoral neoplasm showing predilection for the anterior dorsum of the tongue. The World Health Organization (W.H.O.) includes ECT in the pathologic spectrum of soft tissue myoepithelioma. EWSR1 rearrangement is identified in 45% of cutaneous, soft tissue and bone myoepithelial neoplasms, while PLAG1 aberrations are found in 37% of EWSR1-negative soft tissue myoepitheliomas. The aim of this study was to evaluate the presence of EWSR1 and PLAG1 rearrangements in ECTs. METHODS AND RESULTS: Eleven formalin-fixed, paraffin-embedded ECTs were evaluated using FISH probes to EWSR1 (22q12) and PLAG1 (8q12). Among the 11 ECT cases tested, 3 (27.3%) showed EWSR1 rearrangement in >15% of tumor cells, while 8 (72.7%) cases did not show EWSR1 rearrangement. Eight of 9 (89%) ECTs demonstrated gain of EWSR1, likely representing gain of all or part of chromosome 22, in a varying proportion of neoplastic cells ranging between 1.4-27.9%. PLAG1 rearrangement was not detected in the successfully hybridized tissue sections (7/11). No correlation was observed between the molecular and histopathologic findings such as morphology of the neoplastic cells, presence of atypia, and matrical type. CONCLUSIONS: We identified EWSR1 rearrangement in > 25% of ECTs. These results suggest that some ECTs are at least genetically related to myoepithelioma of the soft parts. Finally, PLAG1 aberrations do not appear to be critical in the pathogenesis of ECT of the tongue