Cutaneous Melanoma with Brain Metastasis: Report of 193 Patients with New Observations

Abstract

BackgroundBrain metastasis is a common endpoint in patients suffering from malignant melanoma. However, little is known about factors that predispose to brain metastases.ObjectiveWe performed a retrospective clinical and pathological investigation of melanoma patients with brain metastases in order to better characterise this patient population.Methods193 melanoma patients with brain metastasis histologically diagnosed between 1990 and 2015 at the University Hospital Zurich were retrospectively identified and further specified for sex, age at diagnosis and detection of brain metastasis, and localisation. In addition, data were extracted regarding the subtype of primary melanoma, Breslow tumour thickness, Clark Level, mutation status, extent of metastatic spread and history of a second melanoma.ResultsWe found a significant male predominance (n = 126/193; 65%; p < 0.001). Breslow tumour thickness showed a wide range from 0.2 to 12.0 mm (n = 99; median 2.3 mm). 14 of 101 melanomas (14%) were classified as T1, thereof 11 (79%) were found in men. In 32 of 193 patients (17%), the primary melanoma was unknown.ConclusionsOf special interest in our series is the high incidence of male predominance (79%) in cases of thin metastasing melanoma (14%), implicating genetic or epigenetic (hormonal) gender differences underlying tumour progression. Additionally, the high percentage of unknown primary melanoma (17%), at least partly representing completely regressed melanomas, indicates the importance of immune surveillance in melanoma progression.

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

“…Although other studies [8,25] found that NM histologic type was associated with BM development, we did not see this when corrected for tumor depth. Our patients with BM were predominantly male, as seen in other studies [8,12,17,26], although our stage-matched control group was similarly male-predominant. A review of multiple studies concluded that male patients with BM have a poorer prognosis [18], although we did not address that issue here.…”

“…Prior retrospective studies of melanoma patients with BM examined cohorts ranging in size from 49 to 670 patients [5,6,8-12]. The rate of BM in these cohorts was approximately 10% [5,6,8,9,11,13], which corresponds to the expected risk of developing BM after a diagnosis of primary cutaneous melanoma [2].…”

“…In fact, we were able to confirm development of stage IV disease in only 10/237 (8.4%) of our control patients and lack of distant metastasis in only 79/237 (33.3%); for the remainder of our control patients (100/237, 42.2%), we did not have recent follow-up to ascertain this information. In reviewing the literature, we note that of nine studies examining melanoma BM, four had no control group [4,12,26,29], four had a control group similarly constructed as ours [5,6,8,9], and only one had a control group with non-brain distant metastasis [10]. …”

Regressive melanoma in a female patient: A case report

“…Few cases of fully regressive melanomas are described in the literature. Regarding the metastatic sites, brain is the commonest with an incidence of 91% in cutaneous melanoma due to the capacity of tumoral cells to migrate along the external surfaces of vascular channels without extravasation (11). The majority of regressive melanomas were described after the occurrence of metastases, being one of the reasons that regression is considered to be a negative prognostic factor in melanoma (12).…”

Combination of Immunotherapy and Brain Radiotherapy in Metastatic Melanoma: A Retrospective Analysis

“…Complications of brain lesions (e.g., bleeding, stroke, epilepsy) are the direct cause of death in most of these cases. On the other hand, prognosis of melanoma patients with brain metastases is poor, with median survival ranging from 4 to 10 months in different studies [1, 2]. Significant therapeutic advances have been seen in the field of MM in recent years.…”