A Comprehensive Immunophenotypic Marker Analysis of Hairy Cell Leukemia in Paraffin-Embedded Bone Marrow Trephine Biopsies-A Tissue Microarray Study

Hairy cell leukemia (HCL) is an uncommon B cell lymphoproliferation characterized by a unique immunophenotype. Due to low number of circulating neoplastic cells and 'dry tap' aspiration, the diagnosis is often based on BM trephine biopsy. We have performed a consecutive immunohistochemical analysis to evaluate diagnostic usefulness of various HCL markers (CD11c, CD25, CD68, CD103, CD123, CD200, annexin A1, cyclin D1, DBA.44, HBME-1, phospho-ERK1/2, TRAP, and T-bet) currently available against fixation resistant epitopes. We analyzed tissue microarrays consisting of samples gained from 73 small B-cell lymphoma cases, including hairy cell leukemia (HCL) (n = 32), HCL variant (HCL-v) (n = 4), B-cell chronic lymphocytic leukemia (B-CLL) (n = 11), lymphoplasmacytic lymphoma (LPL) (n = 3), mantle cell lymphoma (MCL) (n = 10), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n = 2), splenic B cell marginal zone lymphoma (SMZL) (n = 8), and splenic B cell lymphoma/leukemia, unclassifiable (SBCL) (n = 3) cases. The HCL cases were 100 % positive for all but 2 (DBA.44 and CD123) of these markers. Annexin A1 showed 100 % specificity and accuracy, which was followed by CD123, pERK, CD103, HBME-1, CD11c, CD25, CD68, cyclin D1, CD200, T-bet, DBA.44, and TRAP, in decreasing order. In conclusion, our results reassured the high specificity of annexin A1 and pERK, as well as the diagnostic value of standard HCL markers of CD11c, CD25, CD103, and CD123 also in paraffin-embedded BM samples. Additional markers, including HBME-1, cyclin D1, CD200, and T-bet also represent valuable tools in the differential diagnosis of HCL and its mimics

Comparison of Follicular Helper T-Cell Markers with the Expression of the Follicular Homing Marker CXCR5 in Peripheral T-Cell Lymphomas—A Reappraisal of Follicular Helper T-Cell Lymphomas

Peripheral T-cell lymphomas (PTCLs) expressing multiple follicular T helper (TFH) cell-related antigens are now classified as TFH lymphomas (TFHL), including angioimmunoblastic, follicular, and not otherwise specified (NOS) types. CXCR5 is the TFH cell-defining chemokine receptor that, together with its ligand CXCL13, plays a critical role in the development of follicles and the positioning of TFH and B cells within follicles. A comprehensive immunomorphologic study was performed to investigate the expression pattern of CXCR5 in a large cohort of nodal PTCLs, particularly those with a TFH cell phenotype, and to compare its expression with six other TFH cell-related antigens. We found that CXCR5 is widely expressed in neoplastic TFH cells, except in TFHL-NOS, and represents a specific marker of this lymphoma entity. Our results suggest that CXCR5 directs the distribution of neoplastic T cells in the affected lymph nodes and may influence the formation of the pathognomic pathological FDC network

Valós idejű polimeráz láncreakció alkalmazása cytomegalovirus-fertőzés és -reaktiváció nyomon követésére malignus hematológiai betegségek kemoterápiás kezelése során és autológ őssejt-transzplantációt követően | Monitoring cytomegalovirus infection and reactivation using quantitative real-time polymerase chain reaction in patients with haematological malignancies during chemotherapy and after autologous stem cell transplantation

Absztrakt Bevezetés: A hematológiai betegek kemo-immun terápiás kezelése és az őssejt-transzplantáció során fellépő fertőzéses komplikációk egyikét képezi a cytomegalovirus-infekció és -reaktiváció. Célkitűzés: A szerzők célja a cytomegalovirus-fertőzés és -reaktiváció követése kvantitatív valós idejű polimeráz láncreakció módszerével. Módszer: A szerzők intézetében 2012–2014 között kezelt 96 beteg dokumentációját elemezték retrospektív vizsgálatban. A betegeket az alapbetegség szerint csoportosították (lymphoproliferativ betegségek, akut leukaemiák), valamint megkülönböztették aszerint, hogy történt-e autológ őssejt-transzplantáció vagy sem. Eredmények: Lymphoproliferativ betegség miatt kezeltek 83 beteget, közülük 63 (76%) részesült autológ őssejt-transzplantációban. A 604 plazmamintából 46 mintában (7,6%) igazolódott valós idejű polimeráz láncreakcióval cytomegalovirus-pozitivitás összesen 25 betegből (6 nem transzplantált [18%], 19 transzplantált [30,2%]). A valós idejű polimeráz láncreakcióval cytomegalovirus-pozitivitás kétszeres gyakorisággal fordult elő a transzplantált betegcsoportban, azonban 68%-ukban a reaktiváció tünetmentes volt és spontán oldódott. Következtetések: Rutinszerű cytomegalovirus-monitorozás nem szükséges a fenti betegcsoportban, azonban jól meghatározott betegcsoportban klinikai gyanú esetén elvégzett molekuláris teszt lehetővé teszi a korai preemptív kezelést, ezáltal csökkentve a mortalitást. Orv. Hetil., 2016, 157(35), 1403–1409. | Abstract Introduction: Because of the use of chemo-immunotherapeutic drugs, cytomegalovirus infection is one of the most important infectious complications among patients with haematological malignancies. Aim: The aim of the authors was to detect cytomegalovirus infection and reactivation using quantitative real-time polymerase chain reaction. Method: Between 2012 and 2014, the authors retrospectively analysed 96 patient’s medical history hospitalised in haematology Unit. Patients were grouped on the basis of their underlying diseases (lymphoprolipherative malignancies, acute leukaemias), and the following groups were created: autologous stem cell transplanted and non-transplanted groups. Results: Eighty-three patients were treated with lymphoprolipherative disorders, and 63 (76%) of them underwent autologous stem cell transplantation. Out of the 604 plasma specimens 46 (7.6%) were positive for the cytomegalovirus desoxyribonucleic acid collected from 25 patients [6 non-transplanted (18%) and 19 from the transplanted group (30.2%)]. The frequency of cytomegalovirus positivity was doubled in the transplanted patient group, however, reactivation was asymptomatic in 68% of the cases. Conclusions: The routine use of cytomegalovirus monitoring is not necessary in this patient group. In case of suspected cytomegalovirus infection, molecular tests allow early preemptive antiviral therapy, which may decrease the mortality attributed to cytomegalovirus infection. Orv. Hetil., 2016, 157(35), 1403–1409

Monoclonal antibody HBME-1 reacts with a minor subset of B cells with villous surface and can be useful in the diagnosis of hairy cell leukemia and other indolent lymphoproliferations of villous B lymphocytes

The Hector Battifora mesothelial epitope-1 (HBME-1) monoclonal antibody has been generated against human mesothelioma cells and recognizes a biochemically unknown membrane epitope. We have accidentally found that the HBME-1 reacts with scattered lymphocytes showing villous surface in hyperplastic lymphoid tissue. To evaluate its reactivity pattern, we have performed a consecutive immunohistochemical study in nonneoplastic bone marrow and lymphoid samples (n = 40), as well as in malignant lymphoproliferations (n = 427), including hairy cell leukemia (HCL) (n = 72), HCL variant (HCL-v) (n = 13), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n = 8), splenic B cell marginal zone lymphoma (SMZL) (n = 59), and splenic B cell lymphoma/leukemia, not further classifiable on bone marrow morphology (SBCL) (n = 37) cases. The staining pattern of HBME-1 was compared to DBA.44. HBME-1+ villous lymphocytes were constantly detected in low number in nonneoplastic lymphoid tissues. With multicolor immunofluorescence staining, HBME-1+ lymphocytes showed a CD20+/CD79a+/IgM+ B cell phenotype. In B cell lymphoproliferations of villous lymphocytes, HBME-1 reactivity was demonstrated in 96 % of HCL, 39 % of HCL-v, 50 % of SDRPL, 12 % of SMZL, and 19 % of SBCL cases. Nodal and extranodal marginal zone lymphoma cases were positive in 12 % of the cases. A small minority (4 %) of the other B cell lymphomas and no T cell lymphoma revealed tumor cell reactivity with HBME-1. In conclusion, our study has established that HBME-1 reacts with a minor subset of B lymphocytes and a small proportion of B cell lymphomas, which has not been described previously. We suggest that HBME-1 can be a useful marker in the diagnosis of HCL and other indolent lymphoproliferations of villous B lymphocytes

COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA)

COVID-19; Acute myeloid leukemia; SurveyCOVID-19; Leucemia mieloide aguda; EncuestaCOVID-19; Leucèmia mieloide aguda; EnquestaPatients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by Gilead Science, USA (Project 2020-8223). The funder of the study had no role in the study design, data analysis, interpretation, or writing of the report. All authors had full access to the data and had final responsibility for the decision to submit for publication

Fatal cases of disseminated nocardiosis: challenges to physicians and clinical microbiologists – Case report

Despite the development in the identification of Nocardia spp., common challenges exist in the laboratory diagnosis and management of nocardiosis. We report two cases of disseminated nocardiosis in a patient with hematologic disorder and in a patient with systemic lupus erythematosus, where the cooperation between various specialists was essential to set up the adequate diagnosis of disseminated nocardiosis

Nasalis típusú extranodalis natural killer T-sejtes lymphoma hazai előfordulása és kezelésével szerzett tapasztalatok | Incidence and treatment of extranodal natural killer/T-cell lymphoma, nasal type. Hungarian experiences

Absztrakt: Bevezetés: Az extranodalis nasalis típusú natural killer/T (NK/T) sejtes lymphoma (ENKTL) a T-sejtes lymphomák egyik ritka agresszív megjelenésű formája, amely elsősorban sinonasalis és nasopharynx kiindulású. Bár előfordulása ritka a fejlett nyugati országokban, kezelése a hagyományos, agresszív lymphomákban alkalmazott antraciklintartalmú kemoterápiával csekély hatékonyságú. Célkitűzés: ENKTL-esetek előfordulása hazai hematológiai centrumok által gondozott non-Hodgkin-lymphomás betegek között. Módszer: A szerzők négy magyarországi hematológiai centrumban 2003–2015 között kezelt 20 ENKTL-beteg klinikai adatait elemezték. A betegek között 12 férfi és 8 nő volt, medián életkor 49,5 év (22–84 év). Eredmények: Tíz esetben a betegség lokalizált (I–II. stádiumban) volt a diagnózis idején. Kemoterápiás kezelésben részesült 17 beteg (11 CHOP, CHOP-szerű, kettő hyper-CVAD, egy ProMACECytaBom, egy SMILE, kettő egyéb), amelyet hat esetben érintett mezős besugárzással (IFRT) egészítettek ki (40–46 Gy). Az első vonalbeli kezelésre kilenc beteg komplett (CR), három parciális remisszióba (PR) került, három progrediált, két esetben stabil volt a betegség. A medián követési idő 32 (3–113) hónap volt. Öt beteg progresszió, recidíva miatt második vonalban újabb kezelésben részesült (kettő DHAP, egy VIM, egy hyper-CVAD, egy ProMACECytaBom). Második vonalbeli kezelésre CR nem jött létre egy betegben sem. Két esetben első CR-ben autológ őssejt-transzplantáció történt. Következtetés: Az ENKTL kezelésében hatékonyabbak a nem antraciklintartalmú kemoterápiás kezelések. Elsősorban L-aszparagináz-alapú kombinált kemoterápia és egyidejű vagy szekvenciális kemo-radioterápia alkalmazásával a túlélés és CR aránya javítható. Orv Hetil. 2017; 158(41): 1635–1641. | Abstract: Introduction: Extranodal natural killer/T (NK/T) cell lymphoma, nasal type (ENKTL) represents a rare subtype of T-cell lymphomas with aggressive clinical behavior according to WHO 2016 classification. Aim: ENKTL has distinctive geographic distribution with higher incidence in Asia and Latin America (10% of all non-Hodgkin lymphoma cases), than in Europe and North America (<1%). ENKTL tipically origins from nasopharynx and upper aerodigestive tract. Anthracycline-based chemotherapy regimens are largely ineffective in the treatment of ENKTL. Method: Our aims were to evaluate the incidence and treatment strategies of ENKTL patients in Hungarian Haematological Centres between 2003 and 2015. Altogether 20 patients with ENKTL were treated in the 4 haematological hospitals (male:female ratio 12:8, with median 49.5 years of age). Results: Ten patients had localized (stage I–II) disease at the time of the diagnosis. Seventeen patients were treated with chemotherapy (11/CHOP, CHOP-like, 2/HyperCVAD, 1/ProMACECytaBom, 1/SMILE, 2/others), which was completed with involved-field radiation therapy (IFRT) (40–46 Gy) in 6 cases were used. After first-line therapy 9 patients achieved complete remission (CR), 3 patients had partial remission (PR), 3 patients had progressive disease (PD), and 2 patients had stable disease (SD). Median follow-up was 32 (3–113) months. Five patients received second-line therapy for progressive or recurrent disease [2/DHAP, 1/VIM, 1/HyperCVAD, 1/ProMACECytaBom]. None of the patients achieved CR after second-line therapy. Two patients have undergone autologous hematopoietic stem cell transplantation (HSCT) after the first CR. Conclusion: ENKTL treatment is more effective with nonanthracycline-containing regimens. L-asparaginase containing chemotherapy and concurrent or sequential chemo-radiotherapy improves survival and CR rates. Orv Hetil. 2017; 158(41): 1635–1641