Cutaneous squamous cell carcinoma (cSCC) is the most frequent malignancy in solid-organ transplant recipients, promoted by chronic immunosuppression and oncogenic viral mechanisms. Post-transplant lymphoproliferative disorder (PTLD) may coexist or alternate with epithelial neoplasms, complicating follow-up. FDG PET/CT plays a pivotal role in differentiating recurrence, metastasis, and inflammation.

To describe sequential FDG PET/CT findings in a renal-transplant recipient with overlapping cSCC and PTLD, highlighting the role of metabolic imaging in disease monitoring.

Clinical, histopathological, and imaging data were retrospectively reviewed. Serial FDG PET/CT scans (2022–2025) were analyzed for SUVmax, anatomic distribution, and temporal evolution.

A 54-year-old woman, 12 years post-renal transplant under tacrolimus and prednisone, had multiple cSCCs, Merkel-cell carcinoma, vulvar carcinoma (2021) and PTLD-DLBCL (2022) treated with mini-CHOP + rituximab. The PET/CT in Nov 2023 revealed FDG-avid subcutaneous lesions in the right leg (SUVmax 33) and a lingular pulmonary nodule (SUVmax 4.1). Biopsy confirmed poorly differentiated SCC, leading to transtibial amputation (Jun 2024, clear margins). PET/CT May 2024 showed postoperative uptake and bone-marrow activation; the pulmonary nodule remained stable. PET/CT Mar 2025 demonstrated absence of progression and stable pulmonary lesion, consistent with controlled disease.

Chronic immunosuppression predisposes to multiple synchronous malignancies. Serial PET/CT was decisive for distinguishing inflammation from recurrence, preventing overtreatment, and confirming metabolic stability after surgery. Recent evidence shows PET/CT enhances early relapse detection and guides immunosuppression adjustment in transplant oncology. In this case, sustained metabolic stability underscored the effectiveness of multimodal management and the integrative value of PET/CT in long-term surveillance of immunosuppressed patients.