Primary mucosal melanomas of the head and neck are characterised by overexpression of the DNA mutating enzyme APOBEC3B.

AIMS: Primary head/neck mucosal melanomas (MMs) are rare and exhibit aggressive biologic behaviour and elevated mutational loads. The molecular mechanisms responsible for high genomic instability observed in head/neck MMs remain elusive. The DNA cytosine deaminase APOBEC3B (A3B) constitutes a major endogenous source of mutation in human cancer. A3B-related mutations are identified through C-to-T/-G base substitutions in 5'-TCA/T motifs. Herein, we present immunohistochemical and genomic data supportive of a role for A3B in head/neck MMs. METHODS AND RESULTS: A3B protein levels were assessed in oral (n = 13) and sinonasal (n = 13) melanomas, and oral melanocytic nevi (n = 13) by immunohistochemistry using a custom rabbit α-A3B mAb (5210-87-13). Heterogeneous, selective-to-diffuse, nuclear only, A3B immunopositivity was observed in 12 of 13 (92.3%) oral melanomas (H-score range = 9-72, median = 40) and 8 of 13 (62%) sinonasal melanomas (H-score range = 1-110, median = 24). Two cases negative for A3B showed prominent cytoplasmic staining consistent with A3G. A3B protein levels were significantly higher in oral and sinonasal MMs than intraoral melanocytic nevi (P < 0.0001 and P = 0.0022, respectively), which were A3B-negative (H-score range = 1-8, median = 4). A3B levels, however, did not differ significantly between oral and sinonasal tumours (P > 0.99). NGS performed in 10 sinonasal MMs revealed missense NRAS mutations in 50% of the studied cases and one each KIT and HRAS mutations. Publicly available whole-genome sequencing (WGS) data disclosed that the number of C-to-T mutations and APOBEC3 enrichment score were markedly elevated in head/neck MMs (n = 2). CONCLUSION: The above data strongly indicate a possible role for the mutagenic enzyme A3B in head/neck melanomagenesis, but not benign melanocytic neoplasms.

Immediate inferior alveolar nerve reconstruction: Improving warfighter quality of life following mandibulectomy or traumatic avulsion of the mandible.

BACKGROUND: Mandibular reconstruction has historically been challenging due to the complex, highly functional, and esthetic nature of the anatomy. The most common etiologies of these defects requiring resection include trauma, benign tumors, and malignant pathology. Mandibular defects have been treated with little consideration for neural reconstruction, leaving patient's orally incompetent with associated social stigma. Although recent advances in reconstructive techniques improve oral rehabilitation, immediate inferior alveolar nerve (IAN) reconstruction has not been widely adapted. OBJECTIVE: Here-in we seek to discuss the innovations of neural reconstruction of large segment mandibular defects and associated IAN defects and present an example case performed at Naval Medical Center San Diego (NMCSD). METHODS: Pertinent literature discussing maxillofacial reconstruction and nerve repair using autogenous nerve harvest and allograft was queried from available online resources. RESULTS: Six patients have received immediate reconstruction of the IAN using processed nerve allograft over the past three years. All obtained sensation to S3 within six months of surgery. CONCLUSION: IAN repair using nerve allografts in conjunction with free flap reconstruction for large mandibular defects is a viable treatment and should be the new paradigm in maxillofacial reconstruction as it provides substantial quantifiable and qualitative improvements in social, functional, and esthetic outcomes of care.

Metastatic Tumors to the Oral Soft Tissues and Jawbones: A Retrospective Analysis of 40 Cases and Review of the Literature.

BACKGROUND: Metastasis to the oral soft tissues and jawbones is rare and frequently associated with wide spread disease and dismal prognosis. Herein, we report the clinicopathologic characteristics of 40 intraoral metastatic neoplasms and perform a comprehensive review of the pertinent literature. METHODS: Criteria for inclusion included: (a) archived cases from the UMN Oral Pathology laboratory with available tissue blocks and/or H&E-stained preparations diagnosed between 2003 and 2021, (b) proper documentation of the clinico-radiographic characteristics of oral metastasis along with confirmed history of primary malignancy, or (c) microscopic findings consistent with metastatic disease with or without discovery of the primary site. RESULTS: Intraoral metastases comprised 0.03% of all accessioned cases; 22 (55%) occurred in men and 18 (45%) in women (median age = 66.5; range = 18-94 years). Eighteen cases (45%) involved the gingiva, 16 (40%) the gingiva and jawbones, 5 (12.5%) were exclusively intraosseous, and 1 affected (2.5%) the tongue. The lung was the two most frequent primary site in both men (n = 6, 27.3%) and women (n = 5, 27.7%), followed by the colon (n = 4, 18.2%) and kidney (n = 3, 13.7%) in men, and colon (n = 4, 22.2%) and breast (n = 3, 16.6%) in women. Analysis of 1,084 metastatic cases from the literature (male-to-female ratio = 1.2; mean = 52.3; range = 0.6-90 years) indicated strong preference for the jawbones (69.5%) and significant site-specific predilection of certain primary malignancies. CONCLUSIONS: Oral and gnathic metastases are rare but demonstrate a clear predilection for the gingiva and mandible. Clinicians should remain cognizant of such lesions since they frequently mimic inflammatory, reactive or benign neoplastic processes and, in certain cases, are the first indication of occult disease.