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Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder characterized by pancytopenia, splenomegaly and increased susceptibility to infections. In 2011, BRAF gene mutation was identified in almost all the patients with the classical type of HCL. The purine analogs cladribine and pentostatin induce long-term remission in the majority of patients, and they remain the standard treatment for this type of leukemia. However, more than half of patients in complete response relapse over the long term, with a quarter of them relapsing within the first five years. Recently, new drugs have been developed and have demonstrated efficacy in refractory or relapsed HCL. The immunotoxin Moxetumomab pasudotox was registered for HCL in 2018. The BRAF kinase inhibitors vemurafenib and dabrafenib, as well as the Bruton kinase inhibitor ibrutinib, are also proven highly effective in clinical trials.

Reproducible expert-independent flow-cytometric criteria for the differential diagnoses between mature B-cell neoplasms are lacking. We developed an algorithm-driven classification for these lymphomas by flow cytometry and compared it to the WHO gold standard diagnosis. Overall, 662 samples from 662 patients representing 9 disease categories were analyzed at 9 laboratories using the previously published EuroFlow 5-tube-8-color B-cell chronic lymphoproliferative disease antibody panel. Expression levels of all 26 markers from the panel were plotted by B-cell entity to construct a univariate, fully standardized diagnostic reference library. For multivariate data analysis, we subsequently used canonical correlation analysis of 176 training cases to project the multidimensional space of all 26 immunophenotypic parameters into 36 2-dimensional plots for each possible pairwise differential diagnosis. Diagnostic boundaries were fitted according to the distribution of the immunophenotypes of a given differential diagnosis. A diagnostic algorithm based on these projections was developed and subsequently validated using 486 independent cases. Negative predictive values exceeding 92.1% were observed for all disease categories except for follicular lymphoma. Particularly high positive predictive values were returned in chronic lymphocytic leukemia (99.1%), hairy cell leukemia (97.2%), follicular lymphoma (97.2%), and mantle cell lymphoma (95.4%). Burkitt and CD10 diffuse large B-cell lymphomas were difficult to distinguish by the algorithm. A similar ambiguity was observed between marginal zone, lymphoplasmacytic, and CD10 diffuse large B-cell lymphomas. The specificity of the approach exceeded 98% for all entities. The univariate immunophenotypic library and the multivariate expert-independent diagnostic algorithm might contribute to increased reproducibility of future diagnostics in mature B-cell neoplasms., This work was supported by the EuroFlow Consortium, which received support from the FP6-2004-LIFESCIHEALTH-5 program of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP). The EuroFlow Consortium is part of the European Scientific Foundation for Hemato-Oncology (ESLHO), a Scientific Working Group (SWG) of the European Hematology Association (EHA).

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

Patients with CD5-expressing lymphomas presenting with splenomegaly are frequently diagnosed with chronic lymphocytic leukemia. The most important differential diagnosis is mantle cell lymphoma, both in its classical and leukemic, non-nodal forms, given its prognostic and therapeutic implications. Other small B-cell neoplasms that frequently involve the spleen and occasionally express CD5 include the splenic marginal zone lymphoma, hairy cell leukemia and, rarely, lymphoplasmacytic lymphoma. The frequency of CD5 positivity depends in part on the sensitivity of the detection methods employed. Usually, a combination of morphological, immunophenotypic and molecular findings allows for a precise sub-classification of CD5-positive, low-grade B-cell lymphomas of the spleen. Some of these tumors may display a mixture of small and larger B cells, raising the possibility of more aggressive lymphomas, such as diffuse large B-cell lymphomas (DLBCL). Approximately 5–10% of DLBCL are CD5-positive and some may manifest as primary splenic lesions. When available, the morphology of DLBCL in the splenic tissue is distinctive and a leukemic picture is very rare. In conclusion, the appropriate morphological and clinical context assisted by flow cytometry panels and/or immunohistochemistry allows the differential diagnosis of CD5-positive, non-Hodgkin, B-cell lymphomas involving the spleen.

DISEASE OVERVIEW Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders characterized by the identification of hairy cells, a specific genetic profile, a different clinical course, and the need for appropriate treatment. DIAGNOSIS Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAFV600E somatic mutation. RISK STRATIFICATION Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood, and the immunoglobulin heavy chain variable region gene mutational status. VH4-34-positive HCL cases are associated with a poor prognosis. TREATMENT Patients should be treated only if HCL is symptomatic. Chemotherapy with risk adapted therapy purine analogs (PNAs) are indicated in first-line HCL patients. The use of chemo-immunotherapy combining PNAs and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/refractory disease is based on the use of BRAF inhibitors (BRAFi) plus rituximab or MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22 or Bruton Tyrosine Kinase inhibitors (BTKi). However, the optimal sequence of the different treatments remains to be determined. The Bcl2-inhibitors (Bcl-2i) can play a major role in the future.

Objectives To assess the efficacy of a method to circumvent CD20-positive antigen masking by rituximab for flow cytometry analysis of B-cell malignancies in hematology patients. Methods Mononuclear cells (MNCs) from 10 healthy individuals and 5 untreated patients with B-cell malignancies were sensitized with rituximab. Patients’ diagnoses included chronic lymphocytic leukemia, hairy cell leukemia, and follicular lymphoma. MNCs were isolated by gradient density centrifugation. An EDTA/glycine acid (EGA) elution method was used to dissociate CD20-rituximab complexes; afterwards, CD20-positive immunoreactivity was assessed by flow cytometry. A saturation curve was built based on serial dilutions of rituximab. Median fluorescent intensities of CD20-positive signals were obtained before sensitization with rituximab and after its elution with EGA. Results CD20-positive signals were not detectable by flow cytometry after rituximab sensitization of B cells. CD20-sensitized vs CD20-unsensitized, CD20-sensitized vs CD20-eluted, and CD20-eluted vs CD20-negative control (NC) MNC populations exhibited statistical differences (P = .001), while CD20-sensitized vs CD20-NC populations did not (P = .499), confirming CD20 antigen masking by rituximab. Conclusions Rituximab interfered with the flow cytometry protocol for CD20 determination on normal and neoplastic B cells. The EGA method efficiently eluted rituximab, allowing for accurate identification of CD20-positive B cells.

Background: Hairy cell leukemia (HCL) responds well to purine analogs with an overall median relapse free survival of 11-16 years. Most patients can be retreated with the same or a different purine analog however a subset of patients will become resistant or develop cumulative toxicities. Novel agents such as Vemurafenib (BRAF kinase inhibitor), Bendamustine/Rituximab (BR), Moxetumomab pasudotox (anti CD-22 recombinant immunotoxin) and Ibrutinib have emerging roles in patients with relapsed HCL. Methods: Five databases (PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov) were searched using the following search terms: “hairy cell leukemia” or “leukemia, hairy cell” AND “relapse” or “recurrence”. We included only prospective clinical trials with outcome data. Results: Vemurafenib monotherapy was evaluated in two separate arms of a phase 2 trial. In the US arm (n=24), the ORR was 100% (CR 42%; PR 58%). In the Italian arm (n=26), the ORR was 96% (CR 35%; PR 62%). In a phase 2 study (n=25), the combination of vemurafenib and rituximab showed CR of 100%. The combination of BR achieved an ORR of 100% whereas CR was 50% and 67% at a bendamustine dose of 70mg/m2 (n=6) and 90 mg/m2 (n=6) respectively. In a phase 3 trial, moxetumomab pasudotox (n=80) had an ORR of 75% (CR 41%). Single agent Ibrutinib (n=37) had an ORR of 54%. Therapies were generally well tolerated. Conclusion: Novel agents have good efficacy in HCL in patients with multiple relapses.

Hairy Cell Leukemia (HCL) is a lymphoproliferative B cell abnormality dominated by mature lymphocytes with cytoplasmic projections and often misunderstood as Chronic Lymphocytic Leukemia (CLL). Misdiagnosis can be caused by errors in the preparation of peripheral Blood Smear Evaluation (BSE). Immunophenotyping is an option to differentiate HCL from CLL. A 56-year-old female presented with complaints of weakness. Physical examination showed conjunctival anemia 3 3 and hepatosplenomegaly. Hematological test results were as follows: Hb 7.4 g/dL; WBC 131.24x10 /uL; and Plt 61x10 /uL. BSE And Bone Marrow Aspiration (BMA) showed predominantly mature lymphocytes with cytoplasmic projections and suspected CLL with HCL as the differential diagnosis. Immunophenotyping with peripheral blood samples showed CD19+, CD20+, CD79a+, HLA-DR+, CD5-, and CD7- suggesting an increasing mature lymphocytes population (74.16%) that expressed B lymphoid lineage. White Precursor Cell (WPC) channel test showed an abnormal lymphocytes population. The differential diagnosis of patients with dominant mature lymphocytes BSE with cytoplasmic projections was CLL and HCL. Immunophenotyping of CLL showed positive results on B cell markers (CD19, CD20, CD79a, and HLA-DR) with aberrant CD5. However, in such an HCL case like this, there were strongly positive results on B cell markers but the absence of aberrant CD5. This study was supported by the presence of abnormal lymphocytes population in the WPC test. The diagnosis of HCL in this patient was based on interpretation of BSE and immunophenotyping, supported by the WPC test.

Objective/background B-cell neoplasms are clonal tumors of B cells at various stages of maturation, including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic lymphoma (CLL), Burkitt lymphoma (BL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom’s macroglobulinemia (WM), splenic marginal zone lymphoma (SMZL), nodal marginal zone lymphoma (NMZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and hairy cell leukemia (HCL). In this study, we analyzed the frequency of MYD88 L265P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasms. Methods A total of 110 consecutive cases of B-cell neoplasms showing peripheral blood and/or bone marrow infiltration were included. MYD88 L265P mutation was detected by polymerase chain reaction amplification of exon 5 of MYD88 gene, followed by restriction fragment length polymorphism analysis. Results Among the 110 cases, the major group was of CLL (54.5%, n = 60), followed by HCL. Other cases included MCL, LPL, DLBCL, SMZL, NMZL, FL, and BL. MYD88 L265P mutation was seen in 21 (19.1%) cases of B-cell neoplasm, whereas 89 (80.9%) cases were negative for MYD88 L265P mutation. It was most commonly seen in LPL/WM cases followed by HCL, SMZL, CLL, and MCL cases. No case of DLBCL, FL, and BL showed MYD88 L265P mutation. Statistically significant difference was seen for hemoglobin level in CLL cases, with MYD88 L265P mutated cases showing higher mean hemoglobin levels than MYD88 wild-type cases (p = .001). For other parameters, no statistically significant difference was noted between mutated and unmutated cases. Conclusion MYD88 L265P mutation is seen in various B-cell neoplasms; it is most commonly seen in LPL/WM cases but not specific for it.

Hairy cell leukemia is a rare form of leukemia: three hundred new cases are diagnosed each year in France. The diagnosis is based on: (1) morphological examination of the blood and bone marrow smear, (2) analysis by flow cytometry of hairy cells, which express three or the four following markers: CD11c, CD25, CD103 and CD123, (3) identification of the BRAFV600E mutation, a true molecular marker of the disease. The management of treatment has evolved considerably in recent years. As of today, the purine analogues remain the standard treatment in the first line. Relapses are however observed in about 40% of cases. In the event of a first relapse, the preferred option is treatment with immunochemotherapy i.e. a combination of cladribine plus rituximab. Subsequent relapses are treated with moxetumomab pasudotox or BRAF inhibitors which provide indisputable benefits if third-line treatment is required. We will discuss in patients with relapsed/refractory hairy cell leukemia the needs for personalized medicine and the advantages and disadvantages of each treatment modality. The good prognosis for LT requires treatments that are not immunosuppressive, non-myelotoxic, and do not increase the risk of secondary cancers.

Hematological malignancy in pregnancy is a rare condition which leads to lack of prospective study and randomized control trial. Nevertheless, it has own challenge to the medical field in term of managing patient with the said condition. The dilemma is to decide among the necessities of continuation of pregnancy, the choice of diagnostic tools and chemotherapeutic drugs, and the timing of initiation treatment without disregarding the women's wish and preferences. The process often has a profound psychological burden on patients and family members. Furthermore, delays in diagnosis and intervention will adversely affect the outcomes of pregnancy and the disease itself. The effect of teratogenicity of chemotherapeutic drugs on the fetus and the progression of the disease during pregnancy are the main concern in treating this group of patients. This article will review the management and outcomes of 6 cases of hematological malignancy in pregnancy in one center (3 Hodgkin lymphoma, 1 chronic myeloid leukemia, 1 hairy cell leukemia, and 1 myeloproliferative neoplasms). The outcomes of the pregnancy cases in this article were five successful live births with one case of early neonatal death due to prematurity with a history of second-trimester loss. The treatment was initiated during the second trimester to reduce the risk of chemotherapy to the fetus. Even though a few cases had fetal growth compromise but the fetal outcomes seem to be good with early interventions and multidisciplinary approached.

Objective: BRAF V600E mutation has several implications in hairy cell leukemia (HCL). The prevalence of This mutation has been investigated in various populations, but not in Iran. In this study, we evaluated the prevalence of BRAF V600E mutation in an Iranian HCL population as well as its association with the patients’ characteristics.Methods: In a retrospective (archival) study, 20 HCL patients with the confirmed immunophenotypic and morphologic diagnosis were included. Paraffin-embedded blocks of bone marrow aspirate were used to investigated BRAF V600E mutation using amplification refractory mutation system (ARMS) PCR. Demographic, clinical, laboratory, and immunophenotypic characteristics of patients were extracted from the patients medical profiles.Result: BRAF V600E mutation was present in 17 (85%) HCL patients and absent in three (15%) patients. The mean age of the patients was 44.76 ± 8.69 years in mutation-positive and 62.33 ± 8.69 in mutation-negative patients. This difference was statistically significant (p=0.013). No significant difference was found between the laboratory indices of the mutation-positive and mutation-negative groups. The clinical, morphologic, and immunophenotypic characteristics of the two groups were also statistically comparable.Conclusion: BRAF V600E mutation is present in the majority of the Iranian HCL patients and is associated with younger age of presentation.

A Leucemia de Células Pilosas (LCP) é uma doença rara, de origem desconhecida, de curso indolente, e que se apresenta no hemograma associada a pancitopenia e linfócitos com projeções citoplasmáticas. No presente estudo apresentamos o relato de caso de um paciente de 31 anos, masculino, hipocorado, sem esplenomegalia, admitido no Hospital Municipal de Rondon do Pará, Amazônia, no dia 31.12.2018 para a realização de exames laboratoriais em função de rebaixamento do estado geral. O hemograma revelou: anemia (7.5g/dL de hemoglobina e 20% de hematócrito), plaquetopenia (28.200/mm3) e hiperleucocitose (179.000/mm3) as custas de 88% de linfócitos com projeções citoplasmáticas finas e alongadas sugestivas de células pilosas. No dia 07.01.2019 houve piora do quadro do paciente com evolução a óbito antes mesmo da confirmação diagnóstica pelo exame de imunofenotipagem que revelou tratava-se de população clonal de 68,3% de células pilosas com expressão dos antígenos: CD19, CD20, CD79b, CD23, IgM, CD200, CD38, FMC-7, CD25 e CD103. Não tendo sido possível a determinação de quais fatores foram determinantes para esse quadro.

Hairy cell leukemia (HCL), a rare, chronic B-cell leukemia, first described as a distinct entity in 1958, was recognized as an entity by the World Health Organization in 2008. The disease accounts for 2% of all leukemias and is more frequent in middle-aged to older men. The diagnosis is based on the hairy lymphoid cells in the peripheral smear and the bone marrow aspiration cytology and the bone marrow biopsy showing a monotonous interstitial infiltrate with a fried egg appearance. The classic immunophenotypic profile in the flow cytometry and the BRAF V600E mutation confirm the diagnosis. Herein we report a 52- year-old male patient presented with pancytopenia, high-grade fever, and weight loss. The characteristic histomorphological and the flow cytometry features of this leukemia will be used to discuss further the recent updates on the distinct clinicopathologic features, differential diagnosis, treatment, and prognosis of the entity. Keywords: Hairy cell leukemia, Monotonous, Fried egg, Flow cytometry, Pancytopenia.

Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.

Hairy cell leukemia variant (HCL-v) is a rare B-cell lymphoproliferative disorder with distinct immunophenotypic and molecular characteristics when compared to classical hairy cell leukemia (HCL-c). In contrast to the enormous progress in therapeutic options for HCL-c, HCL-v remains a therapeutic challenge due to inferior outcomes with standard chemoimmunotherapy and BCR signaling pathway inhibitors, and due to the fact that HCL-v has limited molecular therapeutic targets. In addition, because of the rarity of the disease, there is a paucity of later phase studies or multicenter trials to guide treatment decisions. In this article, we briefly review the diagnostic criteria and clinical characteristics of HCL-v and present a comprehensive overview of current therapeutic options in HCL-v.

Background: Polycythemia vera (PV) is one of the Philadelphia-negative myeloproliferative neoplasms (MPN), characterized by a pan-myelosis with an erythroid-predominant proliferation mainly driven by somatic JAK2V617F gain-of-function mutation. Hairy cell leukemia (HCL) is a rare B-cell lineage lymphoproliferative disease (LPD) with a typic immunophenotypic profile. BRAFV600E, leading to constitutive activation of the RAF/MEK/ERK signalling pathway and increased cell proliferation, is identified as the driver mutation in almost all cases. Although the risk of developing an LPD is significantly increased in patients with MPN compared with the general population, few cases of co-occurring PV and HCL are reported to date. BRAF is one of the most frequently mutated oncogenes in human cancer and some point mutations were identified in multiple neoplasms in addition to HCL, including follicular and papillary thyroid adenoma and carcinoma. Case presentation: Here we report a molecular diagnostic challenge in a woman with a concomitant diagnosis of JAK2V617F PV, BRAFV600E HCL, and HRASQ61K thyroid follicular adenoma. Conclusion: In the age of molecular and precision medicine, this case underlines the importance of integrating molecular results with clinical, radiologic, cytologic, and histopathologic investigations.

Morphological analysis of the bone marrow is an essential step in the diagnosis of hematological disease. The conventional analysis of bone marrow smears is performed under a manual microscope, which is labor-intensive and subject to interobserver variability. The morphological differential diagnosis of abnormal lymphocytes from normal lymphocytes is still challenging. The digital pathology methods integrated with advances in machine learning enable new diagnostic features/algorithms from digital bone marrow cell images in order to optimize classification, thus providing a robust and faster screening diagnostic tool. We have developed a machine learning system, Morphogo, based on algorithms to discriminate abnormal lymphocytes from normal lymphocytes using digital imaging analysis. We retrospectively reviewed 347 cases of bone marrow digital images. Among them, 53 cases had a clinical history and the diagnosis of marrow involvement with lymphoma was confirmed either by morphology or flow cytometry. We split the 53 cases into two groups for training and testing with 43 and 10 cases, respectively. The selected 15,353 cell images were reviewed by pathologists, based on morphological visual appearance, from 43 patients whose diagnosis was confirmed by complementary tests. To expand the range and the precision of recognizing the lymphoid cells in the marrow by automated digital microscopy systems, we developed an algorithm that incorporated color and texture in addition to geometrical cytological features of the variable lymphocyte images which were applied as the training data set. The selected images from the 10 patients were analyzed by the trained artificial intelligence-based recognition system and compared with the final diagnosis rendered by pathologists. The positive predictive value for the identification of the categories of reactive/normal lymphocytes and abnormal lymphoid cells was 99.04%. It seems likely that further training and improvement of the algorithms will facilitate further subclassification of specific lineage subset pathology, e.g., diffuse large B-cell lymphoma from chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma or even hairy cell leukemia in cases of abnormal malignant lymphocyte classes in the future. This research demonstrated the feasibility of digital pathology and emerging machine learning approaches to automatically diagnose lymphoma cells in the bone marrow based on cytological-histological analyses.

Mature B cell neoplasms, previously indolent non-Hodgkin lymphomas (iNHLs), are a heterogeneous group of malignancies sharing similar disease courses and treatment paradigms. Most patients with iNHL have an excellent prognosis, and in many, treatment can be deferred for years. However, some patients will have an accelerated course and may experience transformation into aggressive lymphomas. In this review, we focus on management concepts shared across iNHLs, as well as histology-specific strategies. We address open questions in the field, including the influence of genomics and molecular pathway alterations on treatment decisions. In addition, we review the management of uncommon clinical entities including nodular lymphocyte-predominant Hodgkin lymphoma, hairy cell leukemia, splenic lymphoma and primary lymphoma of extranodal sites. Finally, we include a perspective on novel targeted therapies, antibodies, antibody–drug conjugates, bispecific T cell engagers and chimeric antigen receptor T cell therapy.

Introduction: Infectious complications represent a major cause of morbidity and mortality in hairy cell leukemia (HCL) patients. Due to the immunosuppressive nature of the disease, these patients are frequently affected by opportunistic infections and rare pathogens. Furthermore, cytotoxic chemotherapy might lead to poor or even fatal outcomes in the setting of an active infection. Case Presentation: We report the case of a 62-year-old HCL patient who presented with recurrent fever episodes, pancytopenia, and mediastinal lymphadenopathy. A treatment decision against purine analogs and for rituximab mono was made as lymph node tissue revealed disseminated Mycobacterium kansasii infection. Together with specific antimycobacterial treatment, rituximab mono led to complete hematologic remission after 6 months without aggravating the accompanying infection. Conclusion: Here, we demonstrate successful treatment of HCL with rituximab in a patient with concomitant disseminated M. kansasii infection.

We report a case of an uncommon presentation of Epstein-Barr virus (EBV)-associated plasma cell neoplasm in a patient with a history of prostate cancer and hairy cell leukemia (HCL) in remission after chemotherapy. The diagnosis of an EBV-associated plasma cell neoplasm was challenging as initially the findings were also compatible with a recurrence of HCL. We highlight the value of diagnostic vitrectomy to achieve the diagnosis. Our particular case demonstrates the importance of diagnostic pars plana vitrectomy and aqueous analyses in patients with uveitis of an unknown cause to confirm the diagnosis.

Background Lymphoproliferative disorders (LPDs) are a heterogeneous group of diseases characterized by an uncontrolled production of monoclonal lymphocytes. RECAF is the receptor for alpha-fetoprotein, which is re-expressed on malignant cells, thus serving as a broad-spectrum tumor marker. Methods The current study is a retrospective study carried out on 200 archival bone marrow trephine biopsy specimens [60 normal control (NC), 38 pathological control (PC) and 102 lymphoproliferative diseases (LPD) specimens]. RECAF expression was assessed using immunohistochemistry. Results The percentage of cells that are positive for RECAF was significantly higher in the LPD group than in the NC group (P=0.007), while there was no significant difference between non-Hodgkin lymphoma (NHL) patients and PC regarding the number of RECAF positive cells (P=0.1). RECAF showed a unique expression pattern among the different subtypes of LPD. None of the hairy cell leukemia (HCL) expressed RECAF, while the highest percentage was seen in follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) (P=0.001). Compared to routine histopathology, RECAF was more sensitive in detecting bone marrow (BM) infiltration in FL, mantle cell lymphoma (MCL), and DLBCL (P=0.01). Conclusion RECAF is significantly expressed in the BM of NHL/chronic lymphocytic leukemia (CLL) patients. RECAF shows a unique expression pattern among the different subtypes of LPD. Furthermore, RECAF may help to detect bone marrow infiltration in lymphoma cells. This may help in the diagnosis, follow-up, and targeting of LPD.

We present a case of multifocal cutaneous alternariosis in a 69-year-old man with hairy cell leukemia. The patient presented with painful, violaceous nodules of the lower extremities and left forearm. His physical examination was otherwise normal. Biopsy specimens were submitted first for histopathological examination, followed by microbiological testing. Histopathology showed epidermal hyperplasia, intraepidermal abscess formation, and intracellular and extracellular fungal elements. Subsequent microbiological investigations, including fungal culture and polymerase chain reaction (PCR), isolated Alternaria alternata. The patient was treated for cutaneous alternariosis with itraconazole for 12 weeks and demonstrated significant improvement of the lesions. This case highlights the role of dual histopathological and microbiological laboratory investigation in suspected opportunistic cutaneous mycoses.

Purpose of the study. To make an informed assessment of comorbidity in patients with lymphoproliferative diseases. To evaluate the effectiveness of comorbidity scales CCI and CIRS-G in patients with lymphoproliferative diseases under treatment. To evaluate the effect of the conducted immunochemotherapy on the general comorbidity in this category of patients.Material and methods. Two scales were used for calculations: Charlson Comorbidity Index (CCI) and Cumulative Illness Rating Scale for Geriatrics (CIRS-G). 127 primary patients with lymphoproliferative diseases aged 19 to 95 years old (the average age was 51.4) were examined from January 2018 till October 2019. The distribution of patients was based on the types of diseases: non-Hodgkin’s lymphomas — 59 (46.46%), Hodgkin’s lymphoma — 35 (27.56%), multiple myeloma — 20 (15.77%), chronic lymphocytic leukemia — 7 (5.51%) people, Waldenstrom’s macroglobulinemia — 3 (2.36%); each of the following diseases: hairy cell leukemia, T-cell leukemia of large granular lymphocytes, T-cell prolymphocytic leukemia - 1, amounted to 0.78% each.Results. Comorbidity was detected in 46 patients who received immunotherapy, chemotherapy, combined chemoradiotherapy, which amounted to 36.22% of the total number of patients. Lesions of the peripheral and central nervous system — 20 (43.48%) patients, were diagnosed most frequently. Immunodefi ciency states — 19 (41.30%) people, came next, and diseases of the cardiovascular system — 12 (26.08%) patients, appeared to be least frequent.Conclusions. When recalculating comorbidity on the CCI and CIRS-G scales, a significant aggravation of comorbidity after treatment, an increase in moderate and severe comorbidity were noted. According to the effectiveness of the CCI and CIRS-G scales in the treated patients, comorbidity is evaluated only approximately, since the Charlson Comorbidity Index does not include polyneuropathy, immunodeficiency states, thrombosis, ischemic heart disease, cardiac arrhythmias, gastritis, and thromboembolic complications and immunodeficiency states are absent in the CIRS-G scale. It is advisable to develop scales for assessing comorbidity, free from disadvantages mentioned above.

Coronavirus disease 2019 (COVID-19) pandemic has been a serious threat and has been reported with different presentations and complications. Older age, along with comorbidities such as diabetes, hypertension, or cardiac disease, increases the risk factors for COVID-19 severity and death [N Engl J Med. 2020;382(18):1708–20 and Lancet Respir Med. 2020 05;8(5):475–81]. It is proposed that cancer patients have a significantly higher incidence of severe incidents including admission to the intensive care unit, the necessity for assisted ventilation, and even death after catching the virus compared with non-cancer patients [Lancet Oncol. 2020;21(3):335–7]. It is also described that cancer patients appear to be twice as likely to contract infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [JAMA Oncol. 2020;6(7):1108–10]. Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder, with patients typically presenting with cytopenias, marked splenomegaly in 80–90% of patients, circulating leukemia cells, bone marrow infiltration and the presence of BRAF V600E somatic mutation [Indian J Hematol Blood Transfus. 2014;30(Suppl 1):413–7]. Leukemic cells classically have central nuclei and abundant cytoplasm with hairy-like projections and express CD11c, CD25, CD103, and CD123 [Indian J Hematol Blood Transfus. 2014;30(Suppl 1):413–7]. Loss of CD123 in HCL has been rarely reported in the literature [Am J Hematol. 2019;94(12):1413–22]. We describe a unique case of a COVID-19-positive male who presented with severe respiratory symptoms, deteriorated quickly, and was intubated. Workup of severe progressive pancytopenia and bone marrow examination revealed HCL without splenomegaly and with atypical unusual loss of CD123. To our knowledge, this is the first case of CD123-negative HCL without splenomegaly associated with COVID-19 infection as the initial presentation.

Skin lesions have been reported in about 10–12% of hairy cell leukemia (HCL) patients. Most are etiologically related to autoimmune or infectious processes, although secondary cutaneous neoplasms and drug-induced lesions are also reported. However, leukemia cutis with the direct infiltration of the skin by leukemic cells is extremely rare in HCL patients. This paper reviews the epidemiology, pathogenesis, clinical symptoms, diagnosis, and approach to treating skin lesions in HCL. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skin lesions, leukemia cutis, adverse events, infectious, cutaneous, drug reactions, neutrophilic dermatoses, secondary neoplasms, and vasculitis was conducted via PubMed. Publications from January 1980 to September 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.

A 49-year-old male patient who had been diagnosed with variable hairy cell leukemia (HCL-V) was treated with interferon for half a year but exert no obvious effect. After two courses of chemotherapy with cladribine, he achieved remission, and splenomegaly significantly improved (the length in craniocaudal dimension decreased from 15.8cm to 11.8cm). Four years later, the patient got disease relapse and was recommended for another cycle of cladribine (6mg for 7 days). On the last day of cladribine, the patient developed fever with needle-like red rashes on the face, limbs, and trunk. At the very beginning, the rash was lighter in color, sparsely distributed, and without obvious itching. Three days later, the rash gradually darkened, expanded and merged, with itching. With the application of high dose gamma globulin and corticosteroids (prednisolone combined with dexamethasone), the rash finally faded, and the patient was discharged. Rash caused by cladribine is not uncommon, such serious and widespread drug-induced rash is rare, and there are few reports. This article reviewed relevant studies and treatments.

Background Hairy cell leukemia is a rare B-cell lymphoproliferative disorder. It has an indolent course with relapse and remission periods. The aim of this study was to investigate the clinical characteristics and risk factors affecting the outcome of patients with hairy cell leukemia. Patients and Methods The retrospective data of 65 patients were evaluated according to initial hematologic and biochemical parameters, response rates, progression-free survival, and overall survival. Factors effecting response and survival rates were analyzed. Results The median follow-up duration was 62.8 months (range, 5.7-229.3 months). The result of the analysis showed that the patients with relapse/progressive disease had higher lactate dehydrogenase (LDH) levels at the time of diagnosis than patients without relapse/progression (median [range], 243 [137-540] vs. 179 [99-334] U/L, P = .01). Patients with LDH ≥ 200.5 IU at the time of diagnosis were demonstrated to have a shorter progression-free survival than those with LDH Conclusion Serum LDH level is significantly associated with relapse/progression in hairy cell leukemia patients. Patients with higher LDH levels at diagnosis should be monitored closely even if they experience complete remission.

Absztrakt: A nemszteroid gyulladáscsökkentők (NSAID-ok) lokális és szisztémás formában történő alkalmazása egyre elterjedtebbé vált, az ezzel kapcsolatos adverz reakciók gyakoriak. A szerzők egy 49 éves férfi beteg esetét ismertetik, aki lábszárak fájdalma miatt etofenamáttartalmú lokális készítményt alkalmazott, majd az alkalmazás helyén, UV-expozíciót követően, haemorrhagiás, atípusos, kontaktdermatitisnek megfelelő bőrtünetek jelentek meg. Tüneteinek rapid terjedése miatt sürgősségi fekvőbeteg-ellátásra szorult. Fizikális vizsgálata során az etofenamátexpozíció helyén, mindkét lábszáron, valamint azon túlmenően a karokon, valamint a törzsön és az arcon bevérzett, konfluáló, erythemás seropapulákat és maculákat láttunk, melyek mellett testszerte és a buccalis nyálkahártyán petechiák voltak megfigyelhetők. A nagy kiterjedésű és aspecifikus bőrtünetek, a fizikális vizsgálattal észlelt splenomegalia, valamint a perifériás vérképeltérés miatt indított onkohematológiai kivizsgálás során hajas sejtes leukaemia diagnózisa igazolódott. Epicutan tesztelés (ET) során az etofenamáttartalmú gélre adott, erősen pozitív reakció mellett fakátrány-, propilén-glikol-, propolisz-, ’fragrance mix I’, metilizotiazolinon-, benzoesav- és perubalzsam-poliszenzibilizáció volt verifikálható. Az etofenamát hatóanyaggal elvégzett lymphocytatranszformációs teszt (LTT) és CD69-expresszió-vizsgálat negatív eredményt adott. Orv Hetil. 2020; 161(38): 1646–1651.

Skeletal involvement is a rare complication of hairy cell leukemia (HCL) with an incidence of approximately 3%. Bone lesions are commonly lytic, and the most common sites of involvement are the femoral head and neck. Skeletal involvement is typically associated with high tumor burden and bone marrow infiltration. However, isolated cases of skeletal disease without splenomegaly or bone marrow involvement are occasionally reported. This review focuses on skeletal lesions in HCL, particularly the pathogenesis, clinical symptoms, diagnostic methods, and treatment approach. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skeletal symptoms, bone involvement was conducted via PubMed. Publications from January 1970 to May 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.

Multiparameter flow cytometry is a useful tool for the diagnostic evaluation of chronic lymphoproliferative disorder recently, it has been shown that CD200 may improve the distinction between chronic lymphocytic leukemia and mantle cell lymphoma, but the role of CD200 expression in atypical chronic lymphocytic leukemia and other chronic lymphoproliferative disorder remains to be established. Methods: A total of 200 samples were evaluated by Flow cytometry over a period of 2 years from august 2017 to October 2019. Cases were diagnosed according to WHO classification of tumours of hematopoietic and lymphoid tissues, 2017. Results: CD200 was strongly expressed in chronic lymphocytic leukemia and was revealed to be an excellent marker to distinguish chronic lymphocytic leukemia from mantle cell lymphoma, even in cases of atypical chronic lymphocytic leukemia. However, lack of CD200 was not an exclusive finding of mantle cell lymphoma, being also observed in other chronic lymphoproliferative disorder. Conclusion: CD200 was expressed by all cases of chronic lymphocytic leukemia as well as atypical chronic lymphocytic leukemia cases while it is negative in MCL thus it is particularly useful in distinguishing chronic lymphocytic leukemia/small lymphocytic lymphoma from other CD5+ B-cell neoplasms. CD200 is also expressed in most of the cases of hairy cell leukemia, splenic marginal zone lymphoma, and follicular lymphoma. CD200 is a useful addition to Moreau et al. panel for analysis of B cells in lymphoid tissue in Bone Marrow aspirates, and Peripheral Blood.

Introduction. Hairy cell leukemia (HCL) is an uncommon B-cell lymphoproliferative disorder characterized by distinctive cells present in bone marrow, peripheral blood and spleen. Treatment of relapsed and/or refractory (R/R) HCL remains a challenge. Case report. A 28-year-old male was treated with cladribine +/- rituximab for his newly diagnosed BRAF-V600 mutated HCL. A year later leukemia relapsed and he received interferon alfa with poor response. Subsequently, vemurafenib was continued for 5 months but this treatment also failed. Then, he received bendamustine with rituximab but significant response was not achieved. Finally, he was found eligible for allogeneic stem cell transplantation (Allo-SCT) from a 9/10-matched unrelated donor. He was conditioned with total body irradiation (TBI) and cyclophosphamide. Cyclosporine and methotrexate were used as graft-versus-host prophylaxis (GVHD). He engrafted and achieved full donor chimerism. There were 0.4% of hairy cells in bone marrow sample by flow cytometry at discharge. 3 months after transplantation he developed neurological and psychiatric deficits which remained unexplained despite a detailed work-up. The symptoms partly resolved after steroids implementation. At the last contact, 14 months after transplantation he remained in complete remission and his neurological condition improved substantially. Conclusions. Allo-SCT seems to be a promising treatment option for R/R HCL.