A 56-year-old man is brought to the emergency department with new-onset tonic-clonic seizures. His past medical history is unremarkable. The patient recently has had right-sided headaches and has taken acetaminophen with some relief. MRI of the brain reveals several round lesions in the right temporal lobe. After initial evaluation, a stereotactic biopsy of one of the lesions is performed. The biopsy results show neoplastic tissue containing a mutation in the gene that encodes BRAF, a protein kinase. The point mutation results in a valine → glutamic acid substitution at position 600 of the protein. Which of the following is the most likely diagnosis?

Question

A 56-year-old man is brought to the emergency department with new-onset tonic-clonic seizures.  His past medical history is unremarkable.  The patient recently has had right-sided headaches and has taken acetaminophen with some relief.  MRI of the brain reveals several round lesions in the right temporal lobe.  After initial evaluation, a stereotactic biopsy of one of the lesions is performed.  The biopsy results show neoplastic tissue containing a mutation in the gene that encodes BRAF, a protein kinase.  The point mutation results in a valine → glutamic acid substitution at position 600 of the protein.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec160b_38fe_d9f4_9249_4916ee52b3eb_MD0001_00 The main environmental risk factor for cutaneous melanoma is increased exposure to ultraviolet radiation (eg, solar or tanning bed sources), which can cause malignant transformation of melanocytes. The risk of melanoma is also increased by mutations in specific genetic factors, most commonly tumor suppressor genes and various oncogenes. BRAF is a protein kinase involved in activating the signaling pathways of melanocyte proliferation. BRAF mutation V600E (valine → glutamic acid), seen in 40%-60% of patients with melanoma, leads to greatly increased activation of the signaling pathways for melanocyte growth, survival, and metastasis. Vemurafenib, a potent inhibitor of mutated BRAF, has significant anti-tumor effects with improved survival and long-term outcomes in advanced stage V600E-positive melanoma patients. The presence of this BRAF mutation in this patient's tissue sample most likely indicates a diagnosis of metastatic melanoma. (Choice A) Glioblastoma is more likely to present as a single lesion; BRAF mutations are less common than with melanoma. (Choice C) Prostate cancer is associated with BRCA1 and BRCA2 mutations, not BRAF mutations. BRCA mutations also increase the risk of breast cancer. (Choices D and E) Renal cell carcinoma and small cell lung cancer appear to be multifactorial in origin, involving many different genes and environmental factors. However, BRAF has not been associated with either malignancy. Educational objective: BRAF is a protein kinase involved in activation of signaling pathways for melanocyte proliferation; the BRAF V600E mutation is seen in 40%-60% of patients with melanoma. __________ References: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. (http://www.ncbi.nlm.nih.gov/pubmed/21639808) Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. (http://www.ncbi.nlm.nih.gov/pubmed/20630094)

A 56-Year-Old Man Is Brought to the Emergency Department with New-Onset