title: 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.
authors.affiliation: Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Michelle W
authors.initials: MW
authors.lastname: Ma
authors.forename: Meng
authors.initials: M
authors.lastname: Qian
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lackaye
authors.forename: Russell S
authors.initials: RS
authors.lastname: Berman
authors.forename: Richard L
authors.initials: RL
authors.lastname: Shapiro
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
authors.forename: John G
authors.initials: JG
authors.lastname: Golfinos
authors.forename: Erik C
authors.initials: EC
authors.lastname: Parker
authors.forename: Farbod
authors.initials: F
authors.lastname: Darvishian
authors.forename: Eva
authors.initials: E
authors.lastname: Hernando
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Shao
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality* / Q000556:secondary*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000401:mortality* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult