Development of a molecular assay for multiomic detection of cfDNA signals in blood samples from skin cancer patients

Background: Malignant melanoma of the tongue is an exceptionally rare and aggressive neoplasm, accounting for less than 2% of oral melanomas [1,2].Its rarity and atypical presentation make diagnosis and management challenging.This systematic review aims to consolidate available evidence on the epidemiology, clinical characteristics, histopathological features, treatment strategies, and outcomes of tongue melanoma.Methods: A comprehensive literature search was conducted up to November 2024.Data were extracted on demographics, lesion characteristics, histopathology, treatment modalities, and outcomes.Results: Forty-seven cases of tongue melanoma were included.The male-to-female ratio among the included cases was 1.38:1.The mean age at diagnosis was 58.6 years, with a median of 62 years and a range of 7 to 90 years.Anatomically, 94.59% of lesions were on the body of the tongue.Lesion sizes varied widely, with a median diameter of 2.69 cm; 51.6% were larger than 3 cm.Histopathological findings were available for 23 cases, with spindle cell morphology observed in 34.78%, epithelioid in 13.04%, and mixed morphologies in another 34.78%.Common immunohistochemical markers included HMB45 (76.47%) and S100 (64.71%).Metastases were present in 38.46% of cases at diagnosis, primarily affecting the lungs and pleura.Nodal metastases were observed in 35.9% of cases, while 20.51% experienced local recurrence.Local invasion was reported in 12.82%, and treatment outcomes showed poor prognosis, with 38.46% of patients succumbing to the disease.Treatment approaches included wide local excision in most cases, sometimes combined with neck dissection, chemotherapy, or radiation therapy.Other therapies included immunotherapy (e.g., anti-PD-1/PD-L1) and interferon alfa-2b.Conclusions: Tongue melanoma is a rare but aggressive malignancy with significant diagnostic and therapeutic challenges.Early detection and a multidisciplinary approach are crucial.Despite its rarity, understanding its diverse clinical presentations, histopathological features, and aggressive behaviour is essential for timely diagnosis and effective management.Given the limited evidence base, collaborative efforts among clinicians, pathologists, and oncologists are vital to advancing diagnostic and therapeutic approaches.Future research focusing on larger case series, genetic pathways, and novel therapies is needed to bridge current knowledge gaps and improve outcomes for this rare and aggressive malignancy.