Case Report: Differential Genomics and Evolution of a Meningeal Melanoma Treated With Ipilimumab and Nivolumab

Abstract

Primary melanocytic tumors of the CNS are extremely rare conditions, encompassing different disease processes including meningeal melanoma and meningeal melanocytosis. Its incidence range between 3-5%, with approximately 0.005 cases per 100,000 people. Tumor biological behavior is commonly aggressive, with poor prognosis and very low survivability, and a high recurrence rate, even after disease remission with multimodal treatments. Specific genetic alterations involving gene transcription, alternative splicing, RNA translation, and cell proliferation are usually seen, affecting genes like BRAF, TERT, GNAQ, SF3B1, and EIF1AX. Here we present an interesting case of a 59-year-old male presenting with neurologic symptoms and a further confirmed diagnosis of primary meningeal melanoma. Multiple therapy lines were used, including radiosurgery, immunotherapy, and chemotherapy. The patient developed two relapses and an evolving genetic makeup that confirmed the disease’s clonal origin. We also provide a review of the literature on the genetic basis of primary melanocytic tumors of the CNS.

Pediatric Primary Intracranial Malignant Melanoma: Case Report and Literature Review

“…Recent insights demonstrate that PIMMs are triggered by overexpression of the neuroblastoma RAS viral oncogene ( NRAS ) in melanocytes of the leptomeninges during embryogenesis and that somatic mutations in the NRAS oncogene are risk factors to develop PIMM in children [21]. Also, additional alterations affecting BRAF (v-raf murine sarcoma viral oncogene homolog B1), TERT (telomerase reverse transcriptase), GNAQ (G protein subunit alpha Q), SF3B1 (splicing factor 3b subunit 1), and EIF1AX (eukaryotic translation initiation factor 1A X-linked) genes have also been observed [36]. Furthermore, advances in molecular profiling demonstrate that the genetic drivers of PIMM tend to involve mutations in GNAQ in adults [37], while somatic mutations in NRAS are more common in children [21].…”

A case of primary meningeal melanocytosis treated with combination therapy with nivolumab and ipilimumab

“…3,4 In summary, we experienced a very rare case with meningeal melanocytosis. Although there are anecdotal case reports successfully treated with combination therapy with nivolumab and ipilimumab, 5 the patient did not respond to the treatment regimen. Dermatologists have to think about the disease when seeing patients with giant congenital nevi.…”

Clinicopathological features, current status, and progress of primary central nervous system melanoma diagnosis and treatment

“…Of the 92 primary CNS melanoma cases in our compilation, 13 patients reported their genetic status (Burgos et al., 2021; de la Fouchardière et al., 2015; El Habnouni et al., 2018; Fortin Ensign et al., 2020; Goldman‐Lévy et al., 2016; Hanft et al., 2022; Kinsler et al., 2017; Schäfer et al., 2013) (Table 1). This included three cases with GNAQ mutations, five cases with NRAS mutations, one case with BAP1 deletion, one case with INPP4B Q204R mutation, and one case with BRAF V600E mutation.…”

“…However, only a few cases of primary CNS melanoma have been treated with immunotherapy. To address this gap, we collected data from Chakib, Remberto, Ashley, Heidi, and Kentaro on five cases of primary CNS melanoma treated with immunotherapy (Aaroe et al., 2021b; Burgos et al., 2021; El Habnouni et al., 2018; Fujimori et al., 2018; Küsters‐Vandevelde et al., 2017) (Table 3). These patients achieved a median OS of 58 months (5–63 months).…”