Autopsy and Case Reports
http://autopsyandcasereports.org/article/doi/10.4322/acr.2017.032
Autopsy and Case Reports
Article / Clinical Case Report

An extremely rare case of concurrent BRAF V600E mutation driven hairy cell leukemia and melanoma: case report and review of literature

Amir Ghorbani-Aghbolaghi; Mirna Lechpammer; Saba F. Ali; Nam K. Ku; Denis M. Dwyre; Hooman H. Rashidi

Downloads: 2
Views: 486

Abstract

BRAF protein is a serine/threonine kinase with 766 amino acids. Approximately 15% of human cancers harbor BRAF mutations as well as other BRAF anomalies (amplifications, fusions). Somatic mutations mainly occur in the catalytic kinase domain (CR3), and the predominant mutation is p.V600E which is the substitution of glutamic acid (E) for valine (V) as result of a mutation at codon 600 of the kinase domain. To our knowledge, the vast majority of the cancers have non-germline BRAF mutations. Here we describe a case of a 60-year-old female with a history of hairy cell leukemia (HCL) who presented with aphasia and forgetfulness. A follow-up Brain CT scan showed three distinct brain lesions which were found to be diagnostic of melanoma (confirmed by immunohistochemistry) with no evidence of a concurrent brain involvement by a B-cell neoplasm. Molecular studies confirmed the same BRAF p.V600E mutation in both malignancies (hairy cell leukemia and melanoma). Thereafter the patient was started on BRAF inhibitor treatment and is now symptom-free after one year of follow up. Having two concurrent malignancies with a shared BRAF mutation is extremely rare and makes this an excellent example of a genomic marker-driven treatment in two histologically and immunophenotypically distinct tumors.

Keywords

Leukemia, Hairy Cell, Melanoma, Proto-Oncogene Proteins B-raf

References

Sithanandam G, Druck T, Cannizzaro LA, Leuzzi G, Huebner K, Rapp UR. B-raf and a B-raf pseudogene are located on 7q in man. Oncogene. 1992;7(4):795-9.1565476

Blachly JS, Lozanski G, Lucas DM, Grever MR, Kendra K, Andritsos LA. Cotreatment of hairy cell leukemia and melanoma with the BRAF inhibitor dabrafenib. J Natl Compr Canc Netw. 2015;13(1):9-13, quiz 13.25583765 10.6004/jnccn.2015.0004.

Sithanandam G, Kolch W, Duh FM, Rapp UR. Complete coding sequence of a human B-raf cDNA and detection of B-raf protein kinase with isozyme specific antibodies. Oncogene. 1990;5(12):1775-80.2284096

Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949-54.12068308 10.1038/nature00766.

Tanami H, Imoto I, Hirasawa A, et al. Involvement of overexpressed wild-type BRAF in the growth of malignant melanoma cell lines. Oncogene. 2004;23(54):8796-804.15467732 10.1038/sj.onc.1208152.

Ross JS, Wang K, Chmielecki J, et al. The distribution of BRAF gene fusions in solid tumors and response to targeted therapy. Int J Cancer. 2016;138(4):881-90.26314551 10.1002/ijc.29825.

Sarkozy A, Carta C, Moretti S, et al. Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Hum Mutat. 2009;30(4):695-702.19206169 10.1002/humu.20955.

Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949-54.12068308 10.1038/nature00766.

Su F, Bradley WD, Wang Q, et al. Resistance to selective BRAF inhibition can be mediated by modest upstream pathway activation. Cancer Res. 2012;72(4):969-78.22205714 10.1158/0008-5472.CAN-11-1875.

Pakneshan S, Salajegheh A, Smith R, Lam AK-Y. Clinicopathological relevance of BRAF mutations in human cancer. Pathology. 2013;45(4):346-56.23594689 10.1097/PAT.0b013e328360b61d.

Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507-16.21639808 10.1056/NEJMoa1103782.

Dietrich S, Glimm H, Andrulis M, von Kalle C, Ho AD, Zenz T. BRAF inhibition in refractory hairy-cell leukemia. N Engl J Med. 2012;366(21):2038-40.22621641 10.1056/NEJMc1202124.

Hauschild A, Grob J-J, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, openlabel, phase 3 randomized controlled trial. Lancet. 2012;380(9839):358-65.22735384 10.1016/S0140-6736(12)60868-X.

Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012;483(7387):100-3.22281684 10.1038/nature10868.

Corcoran RB, Atreya CE, Falchook GS, et al. Combined BRAF and MEK inhibition with dabrafenib and trametinib in BRAF V600-mutant colorectal cancer. J Clin Oncol. 2015;33(34):4023-31.26392102 10.1200/JCO.2015.63.2471.

Turski ML, Vidwans SJ, Janku F, et al. Genomically driven tumors and actionability across histologies: BRAF-Mutant cancers as a paradigm. Mol Cancer Ther. 2016;15(4):533-47.27009213 10.1158/1535-7163.MCT-15-0643.

 

 

 

 

 

 

 

59ca36b00e882503407c305b autopsy Articles

Autops Case Rep

Share this page
Page Sections