Challenging the current paradigm of melanoma progression: brain metastasis as isolated first visceral site

Abstract

Melanoma brain metastasis that develops as the isolated first visceral site challenges the current paradigm of tumor progression in which brain metastasis is regarded as the final stage. Here we test the hypothesis that melanoma patients who develop brain metastasis as the isolated first visceral site have distinct clinicopathological features at the time of primary melanoma diagnosis. Cutaneous melanoma patients enrolled in 2 prospectively collected databases were studied (Cohort 1: 1972-1982, Cohort 2: 2002-2009). Patients who developed brain metastasis as isolated first visceral site were compared with (1) all other patients, (2) patients who developed visceral metastasis: extracranial only or extracranial and brain, and (3) patients who progressed to other isolated visceral sites first. Two hundred seven of 2280 (9.1%) patients developed brain metastasis (median follow-up, 5.2 y). Seventy-four of 207 (35.7%) brain metastasis patients progressed to brain metastasis as the isolated first visceral site. These patients presented with primaries that were thinner and had no mitosis compared with all other visceral metastasis patients (Fisher's combined P = .02, .05, respectively), and there was a significant difference in American Joint Committee on Cancer stage distribution at initial melanoma diagnosis (combined P = .02). Post-visceral metastasis survival, however, was shorter in patients with brain metastasis as isolated first visceral site than in patients with visceral metastasis: extracranial and brain (combined P = .03). Brain metastasis as isolated first visceral site is a distinct clinicopathological entity. Studies are needed to better understand the biological factors driving this phenotype at the time of primary melanoma diagnosis and to determine its clinical implications.

A miRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis

“…Our group recently identified a subgroup of 36% of melanoma brain metastasis patients whose tumors spread to the brain as the isolated, first site of visceral metastasis(24). This subset of patients suggests that some melanomas may be clinicopathologically and/or molecularly distinct and may develop molecular alterations that dictate tissue tropism of metastatic cells.…”

Systemic Tolerance Mediated by Melanoma Brain Tumors Is Reversible by Radiotherapy and Vaccination

“…One potential explanation is that metastasis to the brain is a relatively late event and thus a harbinger for widely disseminated disease. This hypothesis is challenged, however, by the finding that patients presenting with isolated melanoma brain metastases have shorter life expectancies than patients presenting with visceral metastases or synchronous brain and visceral lesions (27). A hypothesis consistent with these clinical data is that brain metastases accelerate systemic disease progression, potentially through an immune-mediated mechanism.…”

In vivo Modeling and Molecular Characterization: A Path Toward Targeted Therapy of Melanoma Brain Metastasis

“…Moreover, in melanoma patients, a higher proportion of B-Met represent the only site of metastatic disease compared to other solid tumors that frequently metastasize to the brain (Thompson et al, 2004). Strikingly, in a retrospective analysis of more than 2000 melanoma patients our group showed that 36% of melanoma B-Met represent the first and isolated site of metastasis (Ma et al, 2012). Primary tumors of patients from this subgroup displayed distinct clinicopathological features with thinner (mostly stage 1), non-mitotic lesions.…”