Journal Article

Multiorgan Sarcoidosis-Like Reaction Mimicking Metastatic Disease in Microsatellite Instability-High Melanoma Patient Treated With Checkpoint Inhibitor Nivolumab

Jagannathan, Geetha, Tuluc, Madalina, Bernabeu, Belen Quereda

2019

Overview

Abstract Introduction Melanomas and tumors with high microsatellite instability (MSI-H) carry heavy tumor mutation burden. The resulting neo-antigens elicit a host immune response in an attempt to contain the tumor. Immune checkpoint pathways (PD-1/PD-L1 and CTLA-4) downregulate T-cell activation, limiting damage to healthy tissue during physiologic immune response. Tumors take advantage of these pathways as a mechanism of immune escape. Checkpoint inhibitors (CPIs) such as Nivolumab (PD-1 inhibitor) and others inhibit these pathways, allowing immune-mediated destruction of tumor cells. Unsurprisingly, these drugs are associated with a spectrum of immune-related adverse effects (irAEs). We report a case of a patient with MSI-H metastatic melanoma who developed an unusual irAE during nivolumab immunotherapy. Case Report A 35-year-old man with a history of ocular melanoma presented with omental metastasis. The metastatic focus was MSI-H by NGS with deficient MSH1/PMS2 by immunohistochemistry. Nivolumab therapy was initiated. Initial follow-up imaging showed complete response. At 7 months, clinical exam and PET imaging showed new skin nodules, hypermetabolic mediastinal lymphadenopathy, and a hypermetabolic vertebral (L3) lesion concerning for disease progression. Biopsies from all three sites revealed sarcoidosis-like granulomatous inflammation. Special stains for fungus and mycobacteria and microbial cultures were negative. The patient was asymptomatic and did not require antisarcoid treatment. He remains in remission for melanoma. Conclusion Sarcoidosis-like reaction is a rare irAE of CPIs that can clinically/radiologically mimic metastatic disease. Bone involvement as seen in our patient is extremely rare. Importantly, biopsy/histopathological examination is required to rule out disease progression. Infectious causes for granulomas should be excluded as these patients are immunocompromised. Evidence suggests that irAE with CPIs may be associated with better outcomes. MSI-H status is infrequent in melanomas but is hypothesized to be a predictive biomarker for CPI response. Our patient is predicted to do well.

• Publisher: Oxford University Press
• Subject: Antigens / Biopsy / Case reports / Cell activation / CTLA-4 protein / Fungi / Immune response / Immunohistochemistry / Immunosuppressive agents / Immunotherapy / Lymphadenopathy / Lymphocytes T / Melanoma / Metastases / Metastasis / Microsatellite instability / Mimicry / Monoclonal antibodies / Nodules / Patients / PD-1 protein / PD-L1 protein / Remission / Sarcoidosis / Targeted cancer therapy / Tumor cells / Tumors / Vertebrae