Early diagnosis of extranodal NK/T lymphoma presenting with oral ulcer and lip swelling by metagenomics next-generation sequencing: a case report

BACKGROUND: Extranodal natural killer/T-cell lymphoma, is a rare, aggressive lymphoma strongly associated with Epstein-Barr virus infection. Its clinical manifestations are often non-specific, and atypical presentations outside the nasal cavity, such as lip swelling or oral ulcers, can mimic benign oral conditions, leading to delayed diagnosis. Histological variability and tissue necrosis further hinder early diagnosis. Metagenomic next-generation sequencing (mNGS) has emerged as a useful adjunct for detecting pathogen-specific nucleic acids when conventional pathology is inconclusive. CASE PRESENTATION: A 39-year-old man presented with a one-month history of recurrent upper lip swelling and a persistent labial and hard palate ulcer. Examination revealed firm swelling of the upper lip, a U-shaped ulcer on the upper labial mucosa, and an ulcer on the right hard palate. Laboratory tests were normal. Considering the patient's recollection of a prior fish bone injury to the oral mucosa, we performed mNGS on biopsy tissue in addition to routine histopathology. mNGS revealed a high load of Epstein-Barr virus DNA, prompting targeted immunohistochemistry and in situ hybridization, which confirmed the presence of Epstein-Barr virus-encoded RNA in atypical lymphocytes, establishing the diagnosis of extranodal NK/T-cell lymphoma. PET/CT showed a hypermetabolic upper-lip mass without systemic spread. The patient was classified as Ann Arbor stage IE, group A. Treatment with two cycles of pegaspargase, gemcitabine, and oxaliplatin resulted in complete healing of oral lesions, followed by localized radiotherapy. No recurrence was observed at the eight-month follow-up. CONCLUSIONS: This case illustrates that extranodal NK/T-cell lymphoma can present with isolated oral lesions, posing significant diagnostic challenges. Incorporating mNGS into the evaluation of suspicious or infection-like oral lesions expedite Epstein-Barr virus detection, guide targeted pathological workup, and reduce diagnostic delays, ultimately improving patient outcomes.