The patient was a 66-year-old man with a 1.15-mm thick, nonulcerated primary melanoma on the upper back diagnosed in October 2011 who had undergone wide local excision and left axillary sentinel lymph node dissection, revealing 1 lymph node positive for metastatic melanoma. In May 2015, he had a locoregional recurrence with 3 new hypermetabolic subcutaneous metastases in the left axilla and the left upper back confirmed by cytology. His tumor did not harbor a BRAF mutation. He started treatment with a combination of ipilimumab and nivolumab in July 2015. A positron emission tomography (PET)/computed tomography (CT) scan of the body in September 2015 showed resolution of the subcutaneous nodules in the left axilla. However, after 2 doses, a grade 3 diffuse papular skin rash and grade 3 hepatitis developed, and the combination therapy was discontinued. After his rash and hepatitis resolved with corticosteroid treatment, he started treatment with nivolumab alone in September 2015, without recurrence of the severe rash or hepatitis.
In December 2015, a PET/CT scan showed ill-defined subcutaneous fat stranding in the medial left lower extremity, without apparent skin abnormalities on physical examination. In January 2016, he presented with small skin nodules in the left calf that were mildly tender to palpation. In March 2016, he noted an increasing number of diffuse erythematous nontender subcutaneous nodules on his bilateral lower extremities (Fig 1, A). A PET/CT scan at that time showed interval development of approximately 50 hypermetabolic subcutaneous nodules in the upper extremities, pelvis, and lower extremities, mostly concentrated in the lower extremities below the knees (Fig 1, B), raising a high suspicion for disease progression in the subcutaneous tissue. Results of blood tests at the time showed elevated erythrocyte sedimentation rate at 100 mm/h (normal range, 0-20 mm/h), slightly elevated rheumatoid factor at 17 IU/mL (normal, <15 IU/mL), and C-reactive protein at 9.0 mg/L (normal, 0-8.0 mg/L). Complete blood counts, liver function results, and serum creatinine level were within normal limits, and antinuclear antibody titer was negative. Excisional biopsy of 3 of the subcutaneous nodules on his lower extremities and the forearm found a robust lobular, septal, and paraseptal lymphohistiocytic infiltrate that was overtly granulomatous in nature in some areas in which multinucleate histiocytes were noted. No vasculitis was observed, and no bacterial, fungal, or mycobacterium tuberculosis DNA was detected in the samples. On the basis of pathologic evaluation, a diagnosis of granulomatous panniculitis was made.
Nivolumab treatment was discontinued at the time of panniculitis diagnosis, and the patient was observed clinically without corticosteroid treatment. However, by May 2016, an increasing number of subcutaneous lesions developed throughout his body, more prominently in the lower legs. Although some of the existing lesions had resolved, some of the lesions became tender. C-reactive protein was further elevated (36.1 mg/L), but erythrocyte sedimentation rate was normal. A PET/CT scan showed further progression of the subcutaneous nodules throughout the body. He was started on 20 mg of oral prednisone daily, and his subcutaneous nodules regressed quite rapidly. Prednisone was slowly tapered off over the next 3 months. A follow-up PET/CT scan performed in August 2016 showed near complete resolution of the subcutaneous lesions.