Tumoral melanosis associated with combined BRAF/MEK inhibition (dabrafenib/trametinib) in metastatic melanoma

Laino, Antonia; Shepherd, Benjamin; Atkinson, Victoria; Fu, Hong; Soyer, H. Peter; Schaider, Helmut

doi:10.1016/j.jdcr.2018.06.024

Cited by 7 publications

(14 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2,7,9,[11][12][13] Two cases have also been reported in the setting of dabrafenib, a BRAF inhibitor. 14,15 In all cases of tumoral melanosis reported after immunotherapy except in the study by Laino et al, tumor regression due to treatment has been associated with a favorable clinical response. 3,9,[11][12][13][14][15] We had a single patient in our case series who continued to have disease progression despite developing tumoral melanosis.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 In all cases of tumoral melanosis reported after immunotherapy except in the study by Laino et al, tumor regression due to treatment has been associated with a favorable clinical response. 3,9,[11][12][13][14][15] We had a single patient in our case series who continued to have disease progression despite developing tumoral melanosis. The mechanism of regression has not been completely defined, but for anti-PD-1 inhibitors and with CTLA-4 antibodies, it is believed to occur through increased T-cell-mediated apoptotic cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Typically, histopathology of tumoral melanosis demonstrates a large, nodular collection of melanin-laden macrophages and melanin pigment in the dermis and/or subcutaneous tissue in the absence of melanocytes. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Alternatively, regression typically displays additional features of fibrosis, lymphocytic inflammation, remaining viable melanocytes, and in some cases, a prior history of preceding melanocytic lesion. [16][17][18][19][20][21][22] Most recently, tumoral melanosis has been described in the context of immunotherapy with ipilimumab (a monoclonal antibody targeting CTLA-4) as well as nivolumab and pembrolizumab (humanized monoclonal antibodies against programmed death 1 receptor) and has been believed to be associated with improved prognosis.…”

Section: Introductionmentioning

confidence: 99%

“…Tumoral melanosis represents a rare presentation of completely regressed melanoma with only 18 cases reported to date. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] There is limited guidance in the literature regarding diagnostic criteria for tumoral melanosis, and it is difficult to distinguish from partial regression.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tumoral Melanosis in the Setting of Targeted Immunotherapy for Metastatic Melanoma—A Single Institutional Experience and Literature Review

Jurgens¹,

Guru

Guo

et al. 2020

The American Journal of Dermatopathology

View full text Add to dashboard Cite

Background: Tumoral melanosis clinically resembles metastatic melanoma, occurs in the context of regressed disease, and requires evaluation to rule out underlying melanoma and metastatic disease. Histopathology demonstrates a nodular infiltrate of melanophages in the dermis, subcutaneous tissue, deep soft tissue, or lymph nodes in the absence of viable melanocytes. Recent limited reports of tumoral melanosis in the context of immunotherapy with ipilimumab (monoclonal antibody targeting CTLA-4) as well as nivolumab and pembrolizumab (humanized monoclonal antibodies against programmed death 1 receptor) highlight a unique presentation representative of treatment-related tumor regression and an association with a favorable clinical response.Objective: To describe our experience with tumoral melanosis in the setting of immunotherapy for metastatic melanoma and elucidate the clinical and histopathological features.Methods: Retrospective case series from a single tertiary care institution. Results:We describe 10 cases of patients with metastatic melanoma who received treatment with immunotherapy before the development of tumoral melanosis. Length of time between the initiation of therapy and the onset of tumoral melanosis ranged from 2 to 20 months with a mean time of 10 months. At the end of the follow-up period, 8 patients were classified as having a complete or partial response to treatment with immunotherapy. One patient had progression of visceral and cutaneous disease on ipilimumab despite developing tumoral melanosis, and 1 patient had yet to undergo repeat imaging. Furthermore, at the end of follow-up, 3 patients were alive with no evidence of active disease, 5 patients were alive with disease, and 1 patient was deceased, although this patient died of a cardiovascular event unrelated to his underlying melanoma. Of the patients who were classified as alive with disease, 2 patients had minimal remaining disease, and 2 patients had an almost complete response on immunotherapy with recurrence of visceral metastases after immunotherapy was discontinued. One patient developed new peritoneal and cutaneous metastases on pembrolizumab despite development of tumoral melanosis. Conclusions:The underlying biologic mechanisms and prognostic implications of tumoral melanosis in the setting of immunotherapy remain to be elucidated. Further prospective studies with a larger cohort and prolonged follow-up are necessary to better understand the incidence, prevalence, and oncologic outcomes in patients with tumoral melanosis who receive immunotherapy.

show abstract