Aggressive Squamous Cell Carcinoma of Unknown Primary: Isolated Inguinal Metastasis and Uncommon Progression.

BACKGROUND Carcinoma of unknown primary (CUP) is a rare malignancy, accounting for less than 5% of all cancers. Inguinal lymph node (LN) metastasis is an uncommon presentation, with squamous cell carcinoma (SCC) comprising a small subset of CUP cases. CASE REPORT A 65-year-old woman presented with a left inguinal mass, which was confirmed as SCC. Comprehensive diagnostics, including PET-CT, failed to identify a primary tumor. Following initial surgical resection, she experienced local recurrence and was treated with chemoradiotherapy (CRT), receiving 45 Gy to potential primary and nodal sites, followed by a 59.4 Gy boost and concurrent cisplatin. Despite an initial response to treatment, the disease progressed aggressively, leading to lung metastases and a subcutaneous metastatic nodule in the pubic region. After chemotherapy with cisplatin and 5-fluorouracil, 2 nodular lesions were identified in the right breast as new metastases - a finding not previously documented in the literature. Despite plans for a biopsy of the right breast lesions, the patient died due to respiratory complications 12 months after diagnosis. CONCLUSIONS This case of isolated inguinal LN metastasis from SCC of an unknown primary highlights the unpredictable and aggressive nature of CUP, even in subtypes typically considered favorable. The findings suggest that more aggressive multimodal treatment approaches may be warranted to manage and control potential microscopic disease effectively. Reevaluating standard treatment protocols for such presentations is essential to improve patient outcomes.