Primary cutaneous squamous cell carcinoma of the neck mimicking tuberculous lymphadenitis

Abstract Background Neck lymphadenopathy is frequently associated with infectious etiologies such as tuberculosis (TB); however, malignant conditions can present with similar clinical and radiological features, leading to diagnostic uncertainty and potential misdiagnosis. Case presentation We describe a 35-year-old immunocompetent man who presented with persistent fever and a progressively enlarging right neck mass. Initial fine-needle aspiration (FNA) revealed multinucleated giant cells consistent with granulomatous inflammation, prompting a presumptive diagnosis of tuberculous lymphadenitis and initiation of anti-TB therapy. Despite treatment, the mass continued to enlarge with no meaningful clinical improvement. A diagnostic surgical (incisional) biopsy was subsequently performed, and histopathology demonstrated poorly differentiated squamous cell carcinoma (SCC) infiltrating the subcutaneous tissues. PET-CT revealed a solitary hypermetabolic lesion without evidence of distant metastasis, supporting a final diagnosis of primary subcutaneous cutaneous SCC. Conclusion This case underscores the diagnostic challenges of distinguishing TB from malignancy when clinical, cytological, and radiological features overlap. In patients with persistent neck masses and atypical or inadequate response to empirical anti-TB therapy, early reconsideration of the diagnosis—including repeat tissue sampling or excisional biopsy—is essential. Prompt identification of malignant mimics is critical to prevent delays in treatment and improve clinical outcomes.