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Case Report: Pseudomeningeosis and Demyelinating Metastasis-Like Lesions From Checkpoint Inhibitor Therapy in Malignant Melanoma.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have considerably expanded the effective treatment options for malignant melanoma. ICIs revert tumor-associated immunosuppression and potentiate T-cell mediated tumor clearance. Immune-related neurologic adverse events (irNAEs) manifest in the central (CNS) or peripheral nervous system (PNS) and most frequently present as encephalitis or myasthenia gravis respectively. We report on a 47-year old male patient with metastatic melanoma who developed signs of cerebellar disease five weeks after the start of ICI treatment (ipilimumab and nivolumab). Magnetic resonance imaging (MRI) of the brain and spine revealed multiple new contrast enhancements suggestive of parenchymal and leptomeningeal metastasis. Cerebral spinal fluid (CSF) evaluation showed a lymphomononuclear pleocytosis in the absence of tumor cells. Subsequent stereotactic brain biopsy confirmed demyelinating disease. High-dose corticosteroid treatment resulted in immediate improvement of the clinical symptoms. MRI scans and CSF re-evaluation were conducted six weeks later and showed a near-complete remission. The strong resemblance to neoplastic CNS dissemination and irNAEs is a particularly difficult diagnostic challenge. Treating physicians should be aware of irNAEs as those can be effectively treated with high-dose steroids.

SUBMITTER: Schmidt T

PROVIDER: S-EPMC8081911 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The incidence of malignant melanoma is increasing worldwide and is one of the major causes of skin cancer deaths in the United States. Although melanoma has the potential to metastasize to any organ, the incidence of bone metastasis is low (~25%) compared to liver or lung metastasis. However, when a bone is involved, metastasis occurs to the axial skeleton in most cases (80%-90%), and involvement of the appendicular skeleton is relatively rare. We here describe the case of a patient who presented with a pathological fracture due to extra-axial skeletal metastasis of a widespread malignant melanoma. A 45-year-old female with an unremarkable past medical history presented to the ED with acute left hip pain. X-ray demonstrated left intertrochanteric femur fracture with an abnormal, suspicious lesion at the fracture site. Detailed physical examination revealed various skin nodules on the anterior chest wall, right upper back, and left cheek. CT of the chest/abdomen/pelvis (CT C/A/P) showed multiple lytic bone lesions and metastatic lesions in lungs, soft tissue, and mediastinal lymph nodes. She underwent surgical stabilization of the fracture, and a biopsy of the bone lesion revealed metastatic malignant melanoma with BRAF V600E mutation. She was started on localized radiotherapy followed by targeted therapy (dabrafenib and trametinib) and denosumab for her stage IV (cTX, cN2, cM1b(1)) (American Joint Committee on Cancer [AJCC] cancer staging 8th edition) disease. Despite treatment, her disease progressed as evidenced by the presence of new metastatic foci on a positron emission tomography-computed tomography (PET-CT) scan performed at a three-month follow-up. Her clinical course was complicated by hemoperitoneum due to bleeding from metastatic liver lesions and respiratory failure requiring a prolonged stay in the ICU before she was deceased. In most cases, malignant melanoma presents with skin lesions at an early stage. Very few patients (4%) have metastatic disease at presentation. Although metastasis to bone is known to occur in advanced disease, involvement of the extra-axial skeleton is relatively rare. Malignant melanoma, initially presenting as pathological fracture of the appendicular skeleton, is not commonly encountered. Our case emphasizes the aggressive nature of malignant melanoma with an aim to raise physicians' awareness of this uncommon presentation. A brief review of the literature exploring prognosis and currently available treatment options is discussed.

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Case Report: Pseudomeningeosis and Demyelinating Metastasis-Like Lesions From Checkpoint Inhibitor Therapy in Malignant Melanoma.

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