When Clinical Suspicion Outweighs a Negative Biopsy: Early Tongue Squamous Cell Carcinoma Diagnosed After Persistent Oral Leukoplakia.

Oral leukoplakia is the most common oral potentially malignant disorder and represents a well-recognized precursor of oral squamous cell carcinoma (OSCC). Although incisional biopsy remains the diagnostic gold standard, false-negative results may occur because of sampling error and lesion heterogeneity, creating a potential discordance between histopathological findings and clinical evolution. We report the case of a 67-year-old former heavy smoker who presented with a two-year history of persistent leukoplakia involving the right lateral border of the tongue, accompanied by an unintentional 20-kg weight loss over the same period. An initial incisional biopsy demonstrated no epithelial dysplasia, and the lesion was attributed to chronic mechanical irritation related to a dental implant. Despite adjustment of the dental prosthesis, the lesion remained unchanged, prompting further diagnostic evaluation. Following exclusion of metabolic causes, continued clinical suspicion prompted referral to a tertiary head and neck oncology center, where partial glossectomy revealed a moderately differentiated invasive squamous cell carcinoma (pT1N0M0). The patient underwent curative surgical treatment and remained free of recurrence after one year of follow-up. This case highlights the importance of integrating histopathological findings with the patient's evolving clinical picture and demonstrates that persistent clinicopathological discordance should prompt diagnostic reassessment. Ultimately, a negative biopsy should not represent the endpoint of investigation when clinical suspicion remains high.