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Updated: Apr 21, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Primary cutaneous small/medium CD4+ T-Cell lymphoma occurring during treatment with vemurafenib for advanced melanoma
Maria C Garrido1, Erica Riveiro-Falkenbach, Yolanda Ruano
1Departments of *Pathology, and †Dermatology, Hospital Universitario 12 de Octubre, Universidad Complutense, Instituto de Investigación I+12, Madrid, Spain.
Abstract:
The discovery of BRAF mutations in 40%-60% of melanomas led to the development of BRAF inhibitors, which exhibit objective response in over 50% of patients. However, up to 98% of the patients develop at least 1 side effect. We report for the first time a patient with metastatic melanoma harboring BRAF V600E mutation that develops a primary, cutaneous small/medium CD4 T-cell lymphoma secondarily to the treatment with vemurafenib. A 54-year-old man with a history of metastatic melanoma treated with the oral BRAF inhibitor vemurafenib presents, 4 months after the initiation of the treatment, with multiple, nodular firm nonulcerated lesions on his back. Two skin biopsies from the lesions revealed a primary, cutaneous small/medium CD4 T-cell lymphoma.The extensive use of recently approved mutation-specific RAF inhibitors seems to be speeding up the emergence of unknown nonpreventable toxicities of these agents. Our patient developed a primary, cutaneous small/medium CD4 T-cell lymphoma, which presented 4 months after the commencement of vemurafenib. Although no treatment interruption is normally required, a close monitoring of the patients with advanced melanomas treated with vemurafenib seems imperative to optimize the management strategies.
Insights
BRAF inhibitors effectively treat melanoma but can cause side effects. This study reports a rare case of cutaneous T-cell lymphoma developing during vemurafenib treatment for metastatic melanoma.
Area of Science:
- Oncology
- Dermatology
- Hematology
Background:
- BRAF mutations are common in melanoma, leading to targeted therapies like BRAF inhibitors.
- BRAF inhibitors, such as vemurafenib, show high response rates but are associated with significant side effects.
Observation:
- A patient with metastatic melanoma and a BRAF V600E mutation was treated with vemurafenib.
- Four months into treatment, the patient developed multiple nodular skin lesions.
Findings:
- Skin biopsies confirmed a diagnosis of primary, cutaneous small/medium CD4 T-cell lymphoma.
- This represents a novel and previously unreported toxicity associated with vemurafenib therapy.
Implications:
- The emergence of rare toxicities highlights the need for vigilant monitoring of patients on BRAF inhibitors.
- Understanding and managing these unexpected side effects is crucial for optimizing melanoma treatment strategies.
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