New-Onset Mediastinal and Central Nervous System Sarcoidosis in a Patient with Metastatic Melanoma Undergoing CTLA4 Monoclonal Antibody Treatment

Abstract

SummaryBackground: Ipilimumab, a cytotoxic monoclonal antibody that inhibits cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), has been established as an effective therapy in the management of advanced melanoma. Immune-mediated adverse events are a common side effect. Case Report: A 37-year-old male patient was diagnosed with nodal and osseous metastatic melanoma 15 months after the initial surgical treatment for lower limb melanoma. Therapy with the anti-CTLA-4 antibody, ipilimumab, was started. Follow-up staging imaging after treatment initiation showed symmetrical bihilar adenopathy. Transbronchial biopsy showed sarcoidosis. The patient had associated systemic symptoms of fatigue, joint pains, anorexia and weight loss. Brain magnetic resonance imaging (MRI), which was performed for the investigation of headaches, showed abnormal enhancing tissue in the sella turcica and adjacent to the pituitary infundibulum, consistent with neurosarcoidosis. The condition was successfully treated with corticosteroids. Conclusions: We report a case of immunotherapy-induced mediastinal/hilar sarcoidosis, with pituitary involvement, mimicking tumour progression. This highlights the need for awareness amongst radiologists and oncologists of the mechanism of action and potential side effects of new immunotherapies.

Characteristics of Sarcoidosis in Patients with Previous Malignancy: Causality or Coincidence?

“…There are several reports trying to connect anticancer therapy with the development of sarcoidosis [24,25,32,33] , with the most common postulated causative agent being the biological modifier alpha interferon [26,27,34] . We, however, did not identify a clear correlation between a specific agent and the subsequent appearance of sarcoidosis (with alpha interferon only seldom used), and a larger cohort would be required to address this issue.…”

“…There is also some evidence to suggest that either malignancy itself [18][19][20][21][22][23] or specific chemotherapy agents, such as alpha interferon, may be predisposing factors for the development of sarcoidosis [24][25][26][27] and there is ongoing debate as to whether the finding of noncaseating granulomatous disease after malignancy is analogous to idiopathic sarcoidosis [28] . Routine use of computed tomography (CT) and positron emission tomography (PET) in the follow-up of patients with previous malignancy has led to the identification of patients with intrathoracic lymphadenopathy [14][15][16][17] , in whom biopsies are suggestive of sarcoidosis.…”

Immune-mediated adverse events of anticytotoxic T lymphocyte–associated antigen 4 antibody therapy in metastatic melanoma

“…Ipilimumab-induced sarcoidosis has also been described by other authors (35-38), with skin and pulmonary lesions resolving or improving after discontinuation of ipilimumab. Sarcoidosis is an important adverse effect for clinicians to be aware of because it can mimic tumor progression and distant metastasis (39, 40). …”

PET/CT, MR, and PET/MR in Lymphoma and Melanoma

“…129 Especially sarcoidlike patterns must not be misjudged as disease progression. [130][131][132][133] There are no prospective MR or PET/MR studies dealing with tumor response patterns in patients with melanoma treated with targeted therapies. However, in the preclinical field, Beloueche-Babari et al 134 investigated tumor response after therapy with the MEK1/2 (mitogen or extracellular signalregulated kinase) inhibitor selumetinib in nude mice bearing melanoma tumors.…”