Concomitant BRAF Mutation in Hairy Cell Leukemia and Papillary Thyroid Cancer
Authors: Mohamed Shehab , Yassin Mohamed A , Nashwan Abdulqadir Jeprel , El Omri Halima , Ibrahim Firyal , El akiki Susana 
Published: October 2019

Abstract
Hairy cell leukemia (HCL) is an uncommon but distinct form of mature B-cell neoplasm that originates from activated late B-cells. It represents only 2% of all adult lymphoid leukemia; patients are predominantly middle-aged to elderly males with a median age of 50 years and is characterized by pancytopenia, monocytopenia and usually associated with massive splenomegaly.
HCL associated with BRAF mutation 100% of cases, it's associated with hematological and oncological malignancies such as melanoma and papillary thyroid cancer with positive BRAF in 40 % of cases.
Although the association of both cancers (HCL & papillary thyroid cancer) with BRAF mutation is well established in the literature, up to our knowledge, this specific combination has not been previously reported in one patient.
Here we report a case of 48-year old Lebanese male, who presented to with bilateral hip pain and found to have lytic bone lesions on both x-ray and MRI. HIS CBC were normal and abdominal US didn't show any splenomegaly. Work-up for myeloma were negative.
Bone marrow examination and flow cytometry results confirmed the diagnosis of hairy cell leukemia. The patient treated with cladrabine.
Patient responded but have continues fever, PUO included Piston tomography showed abnormal uptake in thyroid. Ultrasound and final needle aspiration diagnose him as case of papillary thyroid cancer. He was treated with total thyroidectomy and followed up with RAI 30 micori.
We sent BRAF from both bone marrow biopsy and thyroid tissue which turn out positive in both. The mutation results in substitution of adenine for thymine at position 1799 in exon 15 of the BRAF that replaces Valine (V) by glutamate (E) at amino acid 600(BRAF V600E).
Although the BRAF V600E mutation is frequently present in different neoplasms, such as melanoma, papillary thyroid cancer, non-small cell lung cancer, colorectal cancer and Langerhans cell histiocytosis (X), within the lymphoid neoplasms, the BRAFV600E mutation is found to be highly specific for HCL and testing for this mutation is particularly useful in differentiating classic HCL from other B- cell neoplasm with overlapping features, such as HCL variant
Mutation in BRAF (particularly V600E) in HCL remarkably increase the BRAF kinase activity renders the protein constitutively active, phosphorylating then ERK as a monomers independent from upstream regulatory signals or in a RAS-independent manner leading to constitutive activation of RAF-MEK-ERK signaling pathway and enhanced survival of leukemic hairy cells, similar to what occurs in other BRAF-mutated tumors as papillary thyroid carcinomas
Other BRAF mutations outside exon 15 were rarely reported as exon 11 F468C and D449E mutations.
We emphasize on the link of BRAF mutation in HCL and papillary thyroid cancer. The biology has been established but never in real clinical case. We recommend having high clinical suspicion and sending BRAF mutation in those types of cancers and link it with other possible abnormal findings, as might detect more cases of similar association.

Disclosures
No relevant conflicts of interest to declare.