<i>BRAF</i><sup>V600E</sup> Mutation in a Histiocytic Sarcoma Arising From Hairy Cell Leukemia
Authors: David Michonneau, Sophie Kaltenbach, Coralie Derrieux, Amelie Trinquand, Chantal Brouzes, Laure Gibault, Marie-Odile North, Richard Delarue, Bruno Varet, Jean-François Emile, Nicole Brousse, Olivier Hermine
Journal: Journal of Clinical Oncology (2014)

Case ReportOur patient, a white man with a 26-year history of hairy cell leukemia (HCL), was initially diagnosed in 1986 when he was 48 years old.He was first treated with splenectomy and interferon therapy.Two subsequent relapses, 17 and 20 years after the initial diagnosis, were successively treated with 2-chlorodeoxyadenosine (2-CdA) with a good response on the basis of hairy cell blood count and flow cytometry.Two years later, the patient relapsed for a third time.He was treated with three courses of rituximab (375 mg/m 2 per week for 3 weeks) without any response.He then received 10 courses of pentostatin and went into complete remission after a normal bone marrow evaluation.Complete remission was maintained for 3 years, after which a new relapse occurred.He was treated with an additional course of 2-CdA, which achieved a good response.One year later, the blood cell count was normal, and 0.13% of circulating hairy cells were detected by flow cytometry.The patient was 74 years old when he was hospitalized after a 3-month history of back pain, fever, and asthenia.A computed tomography scan revealed a voluminous retroperitoneal mass measuring 104 ϫ 91 ϫ 55 mm, with a lytic lesion of the L4 vertebra, para-aortic adenopathies, and multiple secondary lung lesions (Fig 1A, white arrowheads).Surgical biopsies of the retroperitoneal mass and lymph node were performed.A proliferation of large atypical pleomorphic cells with eosinophilic cytoplasm and hemophagocytosis was observed.Immunohistologic analysis showed strong positivity for CD163, CD68 (PG-M1 clone), and CD4, suggesting histiocytic differentiation and favoring the diagnosis of histiocytic sarcoma.Tumor cells were positive for CD45 but negative for other lymphoid markers (CD3, CD20) as well as Langerhans cell marker (CD1a), follicular dendritic cell marker (CD21), myeloid markers (CD34, MPO), epithelial marker (AE1/AE3), melanosome markers (human melanoma black 45 [HMB-45] and melanocyte antigen [Melan-A]), and for PS100 (Fig 1b; original magnification, ϫ200; HES, hematoxylin eosin saffron).The diagnosis was confirmed by three experienced hematopathologists (L.G., J.F.E., and N.B.).Moreover, the lymph node biopsy showed infiltration of leukemic hairy cells without histiocytic sarcoma.The patient was treated with two courses of cyclophosphamide, doxorubicin, vincristine, and prednisone without response.He then received four courses of dexamethasone 20 mg, thalidomide 50 mg, and vinblastine 10 mg.Despite these treatments, the tumor rapidly progressed, and the patient eventually died 9 months after the first clinical symptoms of histiocytic sarcoma.At that time, the BRAF V600E mutation was first being described in HCL, 1 and the following biologic exploration was mainly performed after the death of the patient.The BRAF V600E mutation is present in the cells of virtually all patients with hairy cell leukemias 1 and may therefore be an interesting