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

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.

Figure 1. A – Brain axial computed tomography shows brain masses with significant vasogenic edema; B – Brain magnetic resonance image weighted in T2 shows brain mass with a targetoid appearance and a central non-enhancing lesion, suggestive of necrosis, surrounded by vasogenic edema.

Figure 2. Photomicrography of the brain biopsy with all of the above images being at 400x magnification. A – H&E sections of the excisional biopsy show sheets of neoplastic epithelioid cells with round nuclei and variably prominent red nucleoli; By immunohistochemistry, the tumor cells are negative for CD43 – B; and diffusely positive for S100 – C; and Melan-A – D.

Figure 3. A, B – Flow cytometry of the bone marrow shows an abnormal CD19+/CD20++ /CD11c+ /dimCD25+ monotypic B-cell population, consistent with relapsed Hairy Cell Leukemia.

Figure 4. Photomicrography of the bone marrow A, B – H&E sections of bone marrow show mildly hypocellular (~30% cellularity) bone marrow with decreased trilineage hematopoiesis and increased abnormal interstitial lymphocytes; C – IHC staining for PAX5 shows positive staining in the abnormal B-cells; D – DBA-44 immunostain highlights the abnormal cells of the HCL.