Sarcoidosis in the setting of combination ipilimumab and nivolumab immunotherapy: a case report & review of the literature

Abstract

Background: We report a case of sarcoidosis in a patient with metastatic melanoma managed with combination ipilimumab/nivolumab. Sarcoid development has been linked with single agent immunotherapy but, to our knowledge, it has not been reported with combination ipilimumab/nivolumab treatment. This case raises unique management challenges for both the melanoma and the immunotherapy-related toxicity.

Case presentation: A 46 year old Caucasian female with M1c-metastatic melanoma was managed with ipilimumab/nivolumab combination. Patient experienced response in baseline lesions but developed new clinical and radiographic findings. Biopsy of new lesions at two different sites both demonstrated tumefactive sarcoidosis. Staining of the biopsy tissue for PD-L1 expression demonstrated strong PD-L1 staining of the histiocytes and lymphocytes within the granulomas. Monotherapy nivolumab was continued without progression of sarcoid findings or clinical deterioration.

Conclusions: Tissue biopsy for evaluation of new lesions on immunotherapy is an important step to help guide decision making, as non-melanoma lesions can mimic disease progression.

Keywords: Checkpoint inhibitor; Combination immunotherapy; Immune-related adverse event; Ipilimumab; Metastatic melanoma; Nivolumab; Sarcoidosis.

Fig. 1

Imaging at Time of Diagnosis Before Treatment. a Scout PET scan showing cervical/mediastinal/inguinal adenopathy and vertebral lesions. b Cross section of mediastinum with increased update in mediastinal nodes (SUV_max 10 in subcarinal node). c Cross section of knees with no increased uptake. d MRI brain with two right cerebellar metastases with vasogenic edema

Fig. 2

PET-CT of Hepatic Metastases Before and After Combination Immunotherapy. a PET-CT scan at times of diagnosis of with several hypermetabolic hepatic lesions consistent with metastases. b PET-CT scan after 4 cycles of nivolumab plus ipilimumab and 3 cycles of nivolumab maintenance

Fig. 3

PET-CT scan after Nivolumab + Ipilimumab Induction and on Maintenance Nivolumab. a Scout PET scan showing cervical/mediastinal/inguinal adenopathy and vertebral lesions. b Cross section of mediastinum with increased uptake in mediastinal nodes (SUV_max 16 in paratracheal node). c Cross section of knees with increased uptake in left soft tissue nodule (SUV_max 2.7). d MRI brain with interval improvement of right cerebellar metastases

Fig. 4

Hematoxylin and Eosin Staining of Pre-Tibial Soft Tissue Nodule. Microscopic hematoxylin and eosin (H&E) section showing (A) large, deep dermal collections of non-caseating granulomas (a, 2×) extending into the subcutaneous tissue (b, 2×). Higher magnification shows tightly formed granulomas containing multinucleated giant cells separated by fibrous connective tissue (c, 4×). Scattered mature appearing lymphocytes are seen surrounding the granulomatous inflammation (d, 10×)

Fig. 5

PD-L1 Staining of Pre-Tibial Soft Tissue Nodule. PD-L1 antibody stained section of the granulomatous inflammation shows strong membranous staining of the histiocytes within the granulomas and scattered positive lymphocytes (a, 4×; b, 20×)