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Hairy cell leukemia (HCL), an uncommon cancer affecting B-lymphocytes primarily in the bone marrow and spleen, is identified by abnormal projections on malignant B cells, which give the illness its name. This condition is less frequently observed in Asian populations compared with individuals from American and European backgrounds and tends to be diagnosed around the age of 55 years. The leading genetic association of this ailment is linked to the BRAFV600 mutation. Diagnosing HCL poses challenges due to its similarity to other conditions involving excessive lymphocyte growth. Here, we present a distinctive case of an aggressive disease course in a 46-year-old male.

Hairy cell leukemia (HCL) is a rare mature B-cell lymphoproliferative disorder and most often presents as classic hairy cell leukemia. This entity is characterized by an indolent course and the presence of the BRAF V600E mutation. We report the case of an 80-year-old man with a history of classical hairy cell leukemia who presented with fatigue, dizziness, shortness of breath, blurring of vision, and headache. His initial diagnosis was 9 years prior, and he received treatments with cladribine, pentostatin, and rituximab. The workup showed an elevated white blood cell count with atypical lymphocytes, anemia, and thrombocytopenia. A peripheral blood smear confirmed HCL relapse, and a magnetic resonance imaging (MRI) of the brain showed diffuse, nonenhancing masses in the supratentorial and infratentorial regions of the brain. He was initiated on treatment with vemurafenib, with improvements in his white blood cell count and a recovery of his platelet count and hemoglobin. A repeat MRI of the brain after 3 months showed complete resolution of the lesions. Vemurafenib was discontinued after 6 months, with bone marrow biopsy showing no evidence of residual hairy cell leukemia. There have only been limited reports of HCL involvement in the central nervous system in the literature. Due to the rarity of the condition, it is not clear which treatments can be effective for intracranial disease control. Our report shows the successful use of vemurafenib, resulting in complete remission of relapsed HCL with CNS involvement. [ABSTRACT FROM AUTHOR]

Hairy cell leukemia (HCL) is a rare mature B-cell lymphoproliferative disorder and most often presents as classic hairy cell leukemia. This entity is characterized by an indolent course and the presence of the BRAF V600E mutation. We report the case of an 80-year-old man with a history of classical hairy cell leukemia who presented with fatigue, dizziness, shortness of breath, blurring of vision, and headache. His initial diagnosis was 9 years prior, and he received treatments with cladribine, pentostatin, and rituximab. The workup showed an elevated white blood cell count with atypical lymphocytes, anemia, and thrombocytopenia. A peripheral blood smear confirmed HCL relapse, and a magnetic resonance imaging (MRI) of the brain showed diffuse, nonenhancing masses in the supratentorial and infratentorial regions of the brain. He was initiated on treatment with vemurafenib, with improvements in his white blood cell count and a recovery of his platelet count and hemoglobin. A repeat MRI of the brain after 3 months showed complete resolution of the lesions. Vemurafenib was discontinued after 6 months, with bone marrow biopsy showing no evidence of residual hairy cell leukemia. There have only been limited reports of HCL involvement in the central nervous system in the literature. Due to the rarity of the condition, it is not clear which treatments can be effective for intracranial disease control. Our report shows the successful use of vemurafenib, resulting in complete remission of relapsed HCL with CNS involvement.

This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status. Among 80 patients (79% males; median age, 60.0 years), durable complete response (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial response) was 75%; 64 patients (80%) achieved hematologic remission. Among complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and generally manageable with supportive care and treatment discontinuation (6 patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of independently assessed durable response and MRD eradication in heavily pretreated patients with HCL, with acceptable tolerability.

Introduction. Although secondary malignancies usually occur at different times after hairy cell leukemia (HCL) treatment, the occurrence of HCL and other malignancies at the same time is very rare. Synchronous HCL and diffuse large B-cell lymphoma (DLBCL) have not been described so far. Case report. The report presents a 62-year-old female patient with intense constitutional symptoms, hypercalcemia, pancytopenia, and osteolytic destruction of the left shoulder joint. Immunohistochemical analysis of the bone marrow revealed the presence of two cell populations: a population of HCL cells and a population of DLBCL cells with the expression of CMYC and BCL-2 proteins ("double expressor" DLBCL) and high proliferative activity (Ki-67+cells > 90%). Fluorescence in situ hybridization (FISH) analysis showed amplification of the BCL-2 gene. In addition, BRAF gene V600E mutation was detected. After intensive treatment with immunochemotherapy, radiotherapy, and bisphosphonates, the patient achieved complete remission, lasting for more than two years. Conclusion. As the association of HCL and lymphoma is very rare, diagnosis of synchronous occurrence of two lymphoproliferative diseases is a diagnostic and therapeutic challenge. It remains unclear whether DLBC and HCL originated from two different malignant clones or DLBCL developed by the transformation of HCL as the result of clonal evolution of the Bcell clone. [ABSTRACT FROM AUTHOR]

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.

Nucleoside analogues are highly active in patients with hairy cell leukaemia (HCL); however, patients continue to relapse. This phase II study evaluated the efficacy and safety of cladribine followed by rituximab in patients with untreated HCL (N = 59), relapsed HCL (N = 14) and HCL variant (HCLv, N = 7). Cladribine 5·6 mg/m(2) was given intravenously (IV) daily for 5 d and was followed approximately 1 month later with rituximab 375 mg/m(2) IV weekly for 8 weeks. Complete response rate in patients with untreated HCL, relapsed HCL and HCLv was 100%, 100% and 86%, respectively. With a median follow up of 60 months, 5-year failure-free survival (FFS) in patients with untreated HCL, relapsed HCL and HCLv was 95%, 100% and 64%, respectively. Median duration of response to the cladribine followed by rituximab was significantly longer than the first-line cladribine single agent in patients who received this treatment as second-line treatment (72 months vs not reached, P = 0·004). Almost all patients (94%) achieved negative minimal residual disease (MRD) after the treatment. Positive MRD during the follow up did not necessarily result in clinically relevant relapse. Cladribine followed by rituximab is highly effective even in patients with relapsed disease and HCLv, and can achieve durable remission.

A 75-year-old male evaluated for pancytopenia. Abnormal lymphocytes with hairy projections noted on peripheral blood. Bone marrow examination showed diffuse proliferation of CD20+ B-lymphocytes. Flowcytometry revealed monoclonal lambda-restricted B-cells expressing CD19, CD20, CD11c, CD103, CD25 and CD123, negative for CD5 and CD10. Additional staining showed positivity for cyclin-D1, Annexin-A1 and TRAP. FISH identified t(11;14). PCR was positive for BRAF V600E. Given the above findings, nonspecificity of t(11;14) and the presence of BRAF V600E; the diagnosis of HCL was favored. Patient achieved CR with infusional cladribine. Herein, we report the co-occurrence of CCND1/IGH and BRAF V600E in HCL, a rare scenario that could characterize a new subtype of HCL.

Splenic B-cell lymphomas comprise a heterogeneous group of entities that either arise in or show a conspicuous involvement of the spleen, usually accompanied by bone marrow and peripheral blood involvement. The lack of lymphoid tissue available for diagnosis due to the decrease in splenectomies is a challenge for the hematopathologist for the correct classification. The current WHO classification recognizes five distinct entities which are systematically reviewed for the practising pathologist. [ABSTRACT FROM AUTHOR]

Objective: To review the literature for the treatment of classical and variant hairy cell leukemia (HCL, HCLv), evaluating efficacy, safety, and supportive care involved in the use of purine analogues (PAs), interferon, BRAF inhibitors, monoclonal antibodies, Bruton's tyrosine kinase inhibitors, and new immunotoxin, moxetumomab pasudotox-tdfk (MPT). An electronic literature search of PubMed (January 1958 to January 2019) was conducted in PubMed using the MESH terms hairy cell leukemia, hairy cell leukemia variant, cladribine, pentostatin, rituximab, interferon, vemurafenib, moxetumomab pasudotox. Study Selection and Data Extraction: Studies written in the English language were considered for this article. The significance of each article was determined by authors independently. Data Synthesis: HCL and HCLv are rare B-cell lymphoproliferative disorders, each with distinct biologies. Symptoms are characterized by pancytopenia and splenomegaly. Initial treatments for HCL were suboptimal, leading to minimal and transient remissions. PAs significantly improved outcomes, inducing remission in most patients. However, those with purine-resistant disease were left with a dearth of options, leading to implementation of vemurafenib for BRAF V600 mutated disease and chemoimmunotherapy with rituximab. Despite these advances, some HCL and a majority of HCLv patients experience relapse. Newer targeted agents offer promise for relapsed and refractory patients, including the recently approved MPT. Relevance to Patient Care and Clinical Practice: This review provides a comprehensive update on the pharmacological management of HCL and HCLv for clinicians who encounter patients with this rare disease. Conclusion: HCL and HCLv are uncommon lymphoid neoplasms that lead to a characteristic constellation of symptoms. The emergence of PAs and novel targeted agents have improved the likelihood and durability of responses for these patients. [ABSTRACT FROM AUTHOR]

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

Objectives: To report the experience and the importance of flowcytometry immunophenotyping by measuring the positivity andantigenic expression intensity in the diagnosis of 48 patients withhairy cell leukemia (HCL). Methods: From November 1991 to June2005, 4318 cases were analyzed by flow cytometry, 3556 (82.3%) ofwhich were oncohematological diseases. Forty-eight cases of hairycell leukemia (1.3%) were diagnosed. Morphological analysis wasperformed on slides stained with Grunwald Giemsa panchromaticdye, analyzed by two experienced professionals. The cytochemicalanalyses made were for acid phosphatase and tartrate-resistant acidphosphatase (TRAP). For antigenic expression analysis, the monoclonalantibodies used were: CD2, CD3, CD5, CD7, CD10, CD11c, CD19,CD20, CD22, CD23, CD25, CD38, HLA-DR, FMC-7, CD79b, CD103,IgM, IgG, IGD, kappa and lambda. Results: By analyzing positivity andmonoclonal antibody expression intensity in the forward scatter vs.side scatter histograms (used between 1991 and 2001), and in CD19vs. SSC histograms with sequential histograms (after 2001), it waspossible to confirm this pathology and to discriminate residual cellsafter the specific therapy. Conclusion: Diagnostic confirmation of hairycell leukemia by flow cytometry is a fast and accurate method that isuseful in the clinical laboratory. The option for an initial CD19 vs. SSChistogram and an analysis of antigenic expression intensity in the bonemarrow showed to be statistically more efficient.

PURPOSE: CD5 is a T cell marker, aberrantly express in B cell chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma (MCL). Other chronic B cell malignancies including hairy cell leukemia (HCL) and B cell prolymphocytic leukemia (B-PLL) are CD5 negative or express this antigen in a weak way. In this study, CD5 expression was investigated in leukemic cells from 42 patients with chronic B cell lymphoproliferative disease. METHODS: We studied the CD5 expression in leukemic cells from 42 patients with chronic B-cell malignancies by flow cytometry. Demographic features such as age, sex and clinical date were also analyzed. RESULTS: There were 22 males and 20 females. The immunophenotyping showed that 35 cases were B-CLL, 3 B-PLL and HCL and one patient was MCL. CD5 expression was present in all B-CLL and MCL. Low expression of CD5 was observed in one patient with B-PLL and negative in all cases of HCL. CONCLUSION: Our date demonstrated that CD5 expression can help distinguish among B-CLL from HCL and B-PLL, but is similar expressed in MCL.OBJETIVOS: CD5 é um marcador normalmente expresso nas células T e de forma aberrante nas células B da leucemia linfocítica crônica (LLC) e no linfoma de células do manto (LCM). Outras doenças linfoproliferativas crônicas como a hairy cell leukemia (HCL) e leukemia prolinfocítica de células B (LPL-B), são geralmente CD5 negativas ou expressam fracamente este antígeno. Neste trabalho investigou-se o padrão de expressão do CD5 em 42 pacientes com doenças linfoproliferativas crônicas de células B (DLC-B). METODOS: Investigamos a expressão de CD5 em células leucêmicas de 42 pacientes com DLC-B através da citometria de fluxo. Dados demográficos, tais como idade e sexo, bem como dados clínicos e laboratoriais também foram analisados. RESULTADOS: A imunofenotipagem mostrou que 35 casos foram LLC, 3 LPL-B, 3 HCL e um caso de LMC. O CD5 mostrou-se fortemente expresso em todos os casos de LLC e LMC. Baixa expressão desse antígeno foi observada em um caso de LPL-B, mostrando-se negativamente expresso em todos os casos de HCL. CONCLUSÃO: Nossos resultados demonstram que o padrão de expressão do CD5 pode auxiliar na distinção entre LLC da HCL e LPL-B, sendo no entanto similares na HCL e LCM.

Dear Editor-in-Chief A 28 yr male was presented in October 2015 at Medicine Outpatient Department, Safdarjung Hospital, New Delhi- India with generalized weakness, fever and cough for preceding 15 days. Clinicoradiologic examination revealed pallor, firm, non-tender splenomegaly measuring 13.7 cm and hepatomegaly (liver span - 16.9 cm). However, no lymphadenopathy was found.