Late development of splenic sarcoidosis-like lesions in a patient with metastatic melanoma and long-lasting clinical response to ipilimumab

Abstract

A male patient with Stage IV melanoma was treated with ipilimumab resulting in a long-lasting partial response according to RECIST criteria. However, twenty months after ipilimumab treatment, routine follow-up CT scan revealed new splenic lesions initially interpreted as indicative of progressive disease. Nevertheless, a biopsy was performed and histologic evaluation showed that the lesions did not contain malignant cells but rather constituted non-caseating epithelioid cell granulomas consistent with sarcoidosis. As the patient was asymptomatic no treatment was initiated and over the following months the splenic lesions slowly disappeared and to date the patient remains in remission. Ipilimumab is now widely used in the treatment of melanoma patients. Our case-report illustrates that physicians should consider the possibility of ipilimumab induced visceral sarcoidosis-like reactions, mimicking metastatic lesions, developing even many months after ipilimumab treatment. Thus, biopsy of such suspicious lesions is advisable to avoid misinterpretation as disease progression and unnecessary resumption of cancer therapy.

Keywords: CT, computed tomography; CTLA-4, cytotoxic T-lymphocyte associated protein 4; FDG-PET, fluorodeoxyglucose positron emission tomography; RECIST, response evaluation criteria in solid tumors; anti-CTLA-4 monoclonal antibody; ipilimumab; malignant melanoma; metastatic; splenic sarcoidosis.

Figure 1.

Sarcoidoisis-like lesions occurring in melanoma cancer patient following ipilumumab therapy. Horizontal sections of the brain with melanoma metastatic tumor imaged by magnetic resonance imaging (MRI) and horizontal sections of thorax and abdomen by computed tomography (CT); red arrows indicate isolated sarcoidosis-like granulomas; yellow arrows indicate metastases in the right lung and mediastinum; green arrows indicate residual metastatic burden. Longitudinal imaging: (A) November 2010, pre-ipilimumab; (B) March 2011, after 4 courses of ipilimumab; (C) April 2011, 6 weeks after Ipilimumab; (D) August 2011, 5 months after ipilimumab; (E) November 2012, 20 months after ipilimumab and (F) December 2013, 2 y and 10 months after ipilimumab.

Figure 2.

Development of splenic sarcoidosis-like lesions in melanoma patient with durable response to ipilimumab. Ultrasound guided biopsy and histological examination of the hypodense lesions in the spleen of ipilimumab treated melanoma patient showing several non-caseating epithelioid cell granulomas (black arrows) consistent with sarcoidosis (hematoxylin-eosin stain; original magnification × 20, scale bar 500 μm).