Diverse therapeutic approaches including immunotherapy are utilized for patients with occult squamous cell carcinomaMen and women show different patterns in squamous cell carcinoma

An occult squamous cell carcinoma (SCC) is a rare subtype of SCC for which standard radiological protocols are often unable to identify the primary tumour. We describe our patient’s history and provide a systematic review of the literature. To review the clinical characteristics, treatment strategies, and outcomes of patients with occult SCC presenting with lymph node (LN) metastases and to report a rare case of a patient with occult SCC metastasizing to the inguinal and iliac LNs. A systematic literature search was conducted in PubMed, Scopus, and Embase, covering the period from 2000 to 2025. The inclusion criteria for eligible studies comprised case reports and case series documenting patients with occult SCC presenting with LN metastases. Data were extracted at the individual-patient level and synthesised descriptively. A 75-year-old man suffering from myelodysplastic syndrome presented with inguinal lymphadenopathy. Pathological analysis of a core needle biopsy revealed metastases of poorly differentiated SCC. Positron emission tomography-computed tomography (18F-fluorodeoxyglucose PET-CT) showed isolated glucose uptake in the iliac LNs without a potential site of primary disease. Consequently, an iliac lymphadenectomy was performed, followed by adjuvant radiotherapy. The patient remained asymptomatic with no signs of cancer for 15 months following treatment; however, follow-up PET-CT imaging revealed retroperitoneal lymphatic recurrence. Metastases to cervical LNs were observed in a significantly higher proportion of males than of females (63.4% vs. 39.5%; p = 0.033). On the contrary, inguinal LN metastases were more frequently observed in females than in males (39.5% vs. 17.1%; p = 0.026). Within the assessed cohort, systemic therapy was administered to 62% of patients, radiotherapy to 68.4%, and surgical intervention to 59.5%. Notably, five patients (6.3%) received immunotherapy. The diversity of therapeutic approaches documented in the literature emphasizes the importance of individualised treatment strategies, including immunotherapy. Genomic profiling may help implement molecular-based therapy; however, no genetic testing has been reported for the patients included in this cohort.