ALK-positive large B-cell lymphomas: A clinicopathologic study

Background and Aim: Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphomas (ALK+-LBCLs) are aggressive CD20-negative lymphomas, accounting for <1% of diffuse LBCLs. Being rare and with peculiar immunophenotypic characteristics, these can be easily misdiagnosed. We present 11 cases of ALK+-LBCLs diagnosed over a period of 11 years at a tertiary care hospital in South India to analyze the clinical, morphological, and immunophenotypic profile of these tumors. Subjects and Methods: ALK+-LBCL cases diagnosed from September 2009 to August 2020 were included. Clinical details were obtained from stored electronic records and summarized. Available hematoxylin and eosin (H and E) stained slides and immunohistochemistry slides were reviewed and observations tabulated. Results: Eleven patients (nine males and two females) were diagnosed with ALK+-LBCLs in the study period with seven presenting primarily with extranodal disease manifestations. Tumors in the lymph nodes showed diffuse architecture effacement and variable sinusoidal invasion. All tumors showed immunoblastic and plasmablastic-type large lymphoid cells with scattered anaplastic/multinucleate large cells, including rare Reed–Sternberg-like cells. Cytoplasmic granular ALK-1 staining, CD20 negativity, and immunohistochemical features of plasmablastic differentiation were noted in all. Of eight patients treated, only one achieved remission with multi-agent chemotherapy but relapsed after 6 months. Two patients died of disease and five others had progressive/persistent disease and were lost to follow-up. Conclusion: Although rare, these tumors should always be in the differential diagnoses of tumors with plasmablastic and immunoblastic morphology, especially in extranodal sites to avoid diagnostic delay/misdiagnosis.

Linfoma no Hodgkin primario de vagina o cuello uterino. Un diagnóstico en ocasiones incierto: a propósito de un caso / Primary non-Hodgkin´s lymphoma of vagina or cervix. A diagnosis sometimes uncertain: about a case

Resumen ANTECEDENTES: La afectación primaria del aparato genital femenino por un linfoma no Hodgkin es excepcional, se reporta en 0.2 a 1.1% de los casos. Los órganos afectados con más frecuencia son los ovarios, seguidos del cuello uterino; el endometrio y la vagina son los menos aquejados. Debido a su baja frecuencia aún no se llega a un consenso del tratamiento más adecuado de estos linfomas; hasta ahora, por lo general, se ha individualizado para cada caso en concreto. CASO CLÍNICO: Paciente de 29 años que consultó por sangrado genital anómalo e incapacidad para la inserción de tampones vaginales. En la exploración se encontró una masa pélvica, palpable a través de la vagina, que impresionaba al infiltrar toda la luz vaginal y la parte media e izquierda de la vulva. En los estudios de imagen se objetivó una gran masa pélvica de hasta 10 centímetros que parecía depender del cuello del útero y que se extendía e infiltraba el canal vaginal, la vulva y el tercio inferior de la vejiga. El reporte anatomopatológico de la biopsia fue: infiltración de pared vaginal por un linfoma no Hodgkin B difuso de células grandes. Se le indicaron seis ciclos de quimioterapia con ciclofosfamida, vincristina, adriamicina y prednisona con los que se consiguió la remisión metabólica completa. CONCLUSIÓN: El diagnóstico del linfoma genital primario puede resultar complejo por la posibilidad de simular una neoplasia ginecológica. En casos de enfermedad avanzada, la manifestación clínica más frecuente es el sangrado genital anómalo. El esquema de tratamiento más aceptado en la actualidad es con rituximab-ciclofosfamida, vincristina, adriamicina, prednisona seguido de radioterapia de consolidación.

Abstract BACKGROUND: Primary involvement of the female genital tract by non-Hodgkin's lymphoma is exceptional, reported in 0.2 to 1.1% of cases. The most frequently affected organs are the ovaries, followed by the cervix; the endometrium and vagina are the least affected. Due to their low frequency, there is still no consensus on the most appropriate treatment of these lymphomas; until now, it has generally been individualized for each specific case. CLINICAL CASE: A 29-year-old female patient consulted for abnormal genital bleeding and inability to insert vaginal tampons. On examination a pelvic mass was found, palpable through the vagina, which impressed by infiltrating the entire vaginal lumen and the middle and left side of the vulva. Imaging studies showed a large pelvic mass of up to 10 centimeters that appeared to be dependent on the cervix and that extended and infiltrated the vaginal canal, the vulva and the lower third of the bladder. The anatomopathological report of the biopsy was: infiltration of the vaginal wall by diffuse large cell non-Hodgkin's B lymphoma. She was prescribed six cycles of chemotherapy with cyclophosphamide, vincristine, adriamycin and prednisone with which complete metabolic remission was achieved. CONCLUSION: The diagnosis of primary genital lymphoma can be complex because of the possibility of simulating a gynecologic neoplasm. In cases of advanced disease, the most frequent clinical manifestation is abnormal genital bleeding. The most accepted treatment scheme at present is rituximab-cyclophosphamide, vincristine, adriamycin, prednisone followed by consolidation radiotherapy.

Hepatitis B virus infection in patients with aggressive B-cell non-Hodgkin lymphoma, indolent B-cell non-Hodgkin lymphoma and multiple myeloma / 白血病·淋巴瘤

Objective To analyze the infection rate of hepatitis B virus (HBV) in aggressive B-cell non-Hodgkin lymphoma (B-NHL), indolent B-NHL and multiple myeloma (MM) and its relationship with clinicopathological features. Methods The clinical data of 293 aggressive B-NHL, 181 indolent B-NHL and 261 MM patients in Tianjin Medical University Cancer Institute and Hospital from January 2009 to April 2017 were retrospectively analyzed. The difference of HBV infection was compared among three groups. Serum samples from all patients were tested for HBV markers, including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb) and hepatitis B core antibody (HBcAb) by using chemiluminescence immunoassay. Results The positive rate of HBsAg was 9.2% (27/293), 5.5% (10/181) and 3.8% (10/261), respectively in the aggressive B-NHL group, indolent B-NHL group and MM group. The positive rate of HBsAg in the aggressive B-NHL group was higher than that in the indolent B-NHL group and MM group (χ2＝6.987, P＝0.030), and there was no statistical difference of HBsAg positive rate between the indolent B-NHL group and MM group (P ＞ 0.05). The positive rate of HBsAg, HBeAg, HBcAb in the aggressive B-NHL group was higher than that in the indolent B-NHL group and MM group [4.1% (12/293), 0, 0.8% (2/261); χ2＝ 14.976, P＝ 0.001], and there was no significant difference in the positive rate of HBsAg, HBeAg and HBcAb between the indolent B-NHL group and MM group (P ＞ 0.05). Compared with HBsAg negative aggressive B-NHL patients, HBsAg positive aggressive B-NHL patients showed, higher ratio of stage Ⅲ-Ⅳ [70.4% (19/27) vs. 49.2% (131/266), χ 2 ＝ 4.377, P＝0.036], more frequent involvement of spleen [51.9% (14/27) vs. 23.7% (63/266), χ 2＝ 10.039, P＝ 0.002], more frequent of B symptom [55.6% (15/27) vs. 32.0% (85/266), χ 2 ＝ 6.073, P＝ 0.014], more frequent of elevated total bilirubin [29.6% (8/27) vs. 14.3% (38/266), χ 2 ＝ 4.360, P ＝ 0.037] and more frequent of reduced albumin [55.6% (15/27) vs. 35.7% (95/266), χ 2＝ 4.115, P＝ 0.042]. Conclusions The infection rate of HBV in aggressive B-NHL patients is higher than that in the indolent B-NHL and MM patients. HBsAg positive aggressive B-NHL patients are associated with adverse clinical characteristics.

Chimeric Antigen Receptor T-Cell Therapy for Diffuse Large B-Cell Lymphoma / 대한내과학회지

CD19 chimeric antigen receptor T-cell (CAR-T) therapy, a genetically engineered cell therapy, showed unprecedented efficacy in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Two agents, axicabtagene ciloleucel and tisagenlecleucel, were approved by the Food and Drug Administration in 2017. However, CAR-T therapy is a treatment with complex logistics and high costs, as well as inherent adverse events, including cytokine-release syndrome and neurotoxicity. In addition, predictive biomarkers for efficacy and toxicity are lacking. Industry-academy cooperation is urgently required to develop CAR-T therapy that is effective, safe, and affordable for patients in Korea.

Progress in the treatment of aggressive B-cell non-Hodgkin lymphoma / 白血病·淋巴瘤

The 23rd Congress of the European Hematology Association (EHA) was held in Stockholm, Sweden from June 14-17, 2018. The latest analysis of three chimeric antigen receptor T-cell treatments for diffuse large B-cell lymphoma and clinical data from a number of immunotargeting drugs were presented at this congress, all showing encouraging results. The recent progress of aggressive B-cell non-Hodgkin lymphoma is briefly introduced in this paper.

Correlation analysis of indolent B-cell non-Hodgkin lymphoma and hepatitis virus / 中国肿瘤临床

Objective:To differentiate hepatitis B virus (HBV) infection from hepatitis C virus (HCV) infection among different indolent B-cell non-Hodgkin lymphoma (B-NHL) subtypes. The correlation between indolent B-NHL and hepatitis viral infection was also investi-gated. Methods:A total of 733 indolent B-NHL patients from January 1994 to January 2014 with integrated clinical information were retrospectively investigated. We compared the hepatitis viral infection between the general population and indolent B-NHL patients. We analyzed the infection rate of hepatitis virus in the different indolent B-NHL subtypes and examined their correlations. Results:The HBs-Ag positive rate of the indolent B-NHL was 7.9%, which was not significantly different with that of the general population (7.9%vs. 7.2%, P=0.548). Among the different indolent B-NHL subtypes, the 48 splenic marginal zone lymphoma (SMZL) patients exhibited the highest HBs-Ag positive rate, which was significantly higher than those of the general population (18.8%vs. 7.2%, P=0.002), other indo-lent B-NHL subtypes (18.8%vs. 7.2%, P=0.004), and other marginal zone B-cell lymphoma (MZL) patients (18.8%vs. 7.1%, P=0.005). The HBs-Ag positive rates between other B-NHL subtypes and the general population were not significantly different. The coexpression of HBs-Ag, HBe-Ag, and anti-HBc-Ab exhibited no significant difference among the various B-NHL subtypes. However, the co-expres-sion of HBs-Ag, HBe-Ab, and anti-HBc-Ab was significantly higher in the SMZL group than the other B-NHL subtypes (16.7%vs. 4.7%, P<0.001).The positive rate of the anti-hepatitis C virus antibody (HCV-Ab) was 1.9%in 733 indolent B-NHL patients, which was significant-ly higher than in the general population (1.9%vs. 0.4%, P<0.001). The HCV-Ab positive rates in the chronic lymphocytic leukemia, lym-phoplasmacytic lymphoma/Waldenstr?m macroglobulinemia, SMZL, hairy cell leukemia, nodal marginal zone B-cell lymphoma group were 2.2%, 2.5%, 4.2%, 3%, and 3.7%, respectively. These values were significantly higher than those of the general population. Preva-lence rates of HCV in B-cell lymphoproliferative disorders, unclassified, extranodal marginal zone B-cell lymphoma of mucosa-associat-ed tissue lymphoma, B-cell prolymphocytic leukemia, and follicular lymphoma groups were not significantly different compared with the general population. Conclusion:Prevalence rate of HBV was higher in the SMZL group than other indolent B-NHL groups, which suggests that HBV infection may play an etiologic role in SMZL.

Efficacy of rituximab combined with CHOP chemotherapy for 35 patients with aggressive B cell non-Hodgkin’s lymphoma / 中国生化药物杂志

Objective To analyze efficacy of rituximab combined with chemotherapy for 35 patients with aggressive B cell non-Hodgkin’s lymphoma.Methods 70 patients with aggressive B cell non-Hodgkin’s lymphoma were chosen from Hematology Department of First Affiliated Hospital of Liaoning Medical University and divided into observation group and control group at random, each group with 35 cases.The control group were treated with CHOP chemotherapy, and the observation group were treated with anti-CD20 monoclonal antibody rituximab combined with CHOP chemotherapy. The efficacy and toxicity of two group were compared.Results The total effective rate of observation group was significantly higher than that of control group (80.0%vs.37.1%;χ2 =13.246,P<0.001).Fever cases of observation group were significantly more than those of control group (15vs.4;χ2 =8.741,P=0.003), while the other adverse reactions of leucopenia and gastrointestinal reaction between two groups were not significantly different. Conclusion For patients with aggressive B cell non-Hodgkin’s lymphoma, rituximab combined with CHOP chemotherapy has better short-term effects and its adverse reactions are tolerable, which helps patients to improve the quality of life.

Expression of BAFF and its specific receptor BAFF-R in patients with B-cell non-Hodgkin′s lympho-ma and their significance / 中华微生物学和免疫学杂志

Objective To investigate the expression of B-cell activating factor ( BAFF ) and its specific receptor BAFF-R in patients with B-cell non-Hodgkin′s lymphoma ( B-NHL) and to analyze the cor-relations between BAFF and the development of B-NHL.Methods RTQ-PCR and Western blot assay were used to measure the expression of BAFF and its specific receptor BAFF-R in patients with B-NHL.Fluores-cence immunocytochemical staining was used to determine the localization of BAFF and BAFF-R in Raji cells, a B-NHL cell line.The expression of BAFF in tumor tissues from patients with B-NHL of different his-tologic subtypes was measured by immunohistochemistry.WST proliferation and TUNEL assays were used to evaluate the effects of BAFF and BAFF-R on the proliferation, survival rate and apoptosis of Raji cells.Lin-ear correlations between the concentrations of lactate dehydrogenase ( LDH) and the expression of BAFF and BAFF at mRNA and protein levels in patients with B-NHL were analyzed.Results BAFF and its specific receptor BAFF-R were expressed in Raji cells and played an important role in the survival and proliferation of B-NHL cell line.The expression of BAFF in tumor cells from patients with B-NHL varied with the different histologic subtypes of B-NHL.Patients with small B-cell malignant lymphoma, large B-cell lymphoma ( LBCL) , mucosa-associated lymphoid tissue lymphoma ( MALT lymphoma) and follicular lymphoma showed higher levels of BAFF, while those with mantle cell lymphoma showed lower levels of BAFF.Compared with the healthy subjects, patients with B-NHL showed significantly increased expression of BAFF at mRNA and protein levels.The levels of LDH were closely related to the expression of BAFF at mRNA and protein lev-els.Conclusion BAFF and its specific receptor BAFF-R might play an important role in the growth and survival of malignant B cells.

Linfoma não Hodgkin primário da coluna vertebral / Primary non-Hodgkin's lymphoma of the vertebral column

O linfoma primário do osso (LPO) é uma condição extremamente rara, habitualmente confundida com outras lesões ósseas primárias. É responsável por cerca de 3 por cento-5 por cento de todos os tumores malignos no osso e 4 por cento-7 por cento de todos os linfomas nãoHodgkin extranodais. Caracteriza-se pelo envolvimento de um ou vários locais ósseos, com ou sem comprometimento de linfonodos regionais e vísceras. Histopatologicamente, o linfoma non Hodgkin de grandes células B representa a maioria dos casos de LPO. Ossos longos são mais frequentemente comprometidos, e o fêmur é o sítio mais acometido. Osso ilíaco e da coluna vertebral também podem ser atingidos. Relatamos um caso raro de linfoma não Hodgkin da vértebra em mulher de 41 anos. A imuno-histoquímica revelou CD20 e CD45 positivos. Ela foi diagnosticada com linfoma primário difuso de grandes células B da coluna vertebral. O estudo histopatológico da medula óssea não detectou infiltração por hemopatia linfoide. A paciente foi tratada com quimioterapia CHOP juntamente com etoposide, seguida de radioterapia (dose total = 3600cGy) na região tóraco-lombar. Não houve evidência de recidiva em um período de vinte meses de acompanhamento.

Primary bone lymphoma (PBL) is an extremely rare condition, commonly confused with other primary bone injuries. It accounts for approximately 3-5 percent of all malignant bone tumors and 4-7 percent of all extranodal non-Hodgkin's lymphomas. It is characterized by the involvement of one or multiple bone locations, with or without the involvement of regional lymph nodes and viscera. Histopathologically, diffuse large-B-cell lymphomas account for the majority of cases of PBL. Long bones are usually involved, with the femur being the most commonly affected site. Pelvic bones and the vertebral column can also be involved. We report on a rare case of PLB of the vertebra in a 41-year-old woman. Immunohistochemistry examinations revealed CD20 and CD45 positive cells. She was diagnosed with primary diffuse large B-cell lymphoma presenting as a vertebral column tumor. The histopathologic analysis of the bone marrow did not show lymphoproliferative disorders. The patient was treated with a CHOP plus etoposide regimen. Systemic chemotherapy was followed by radiotherapy (total dose = 3600 cGy) in the thoracolumbar region. There was no evidence of recurrence in the 20-month follow up.

A Case of Splenic Non-Hodgkin's Lymphoma in Rheumatoid Arthritis / 대한류마티스학회지

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder of unknown etiology. Inflammation may usually extend beyond the joints and involve other organs. Clinically detectable splenomegaly is present in 5~10% of RA. Methotrexate (MTX) is a structural analog of folic acid that inhibits the enzyme dihydrofolate reductase, so cellular proliferation is reduced. MTX has been proven to be effective in treating RA and is believed to be nononcogenic at low, weekly dose employed in the patients with RA. However, recently there has been increased concern about the oncogenic potential of MTX because of several case reports describing the occurrence of non-Hodgkin's Lymphoma (NHL) in the patients with RA treated with MTX. A 65-year-old woman with RA was treated with low dose MTX (i.e. 10 mg/week) for 3 years. Because of prolonged left upper abdominal pain and thrombocytopenia associated with huge splenomegaly, splenectomy was performed. Biopsy revealed splenic B-cell NHL. We report a case of RA with splenomegaly who developed B-cell NHL in spleen during low dose MTX therapy.

Treatment of B-cell Acute Lymphoblastic Leukemia and B-cell Lymphoma / 대한소아혈액종양학회지

PURPOSE: We report here the improved survival rate of B-cell acute lymphoblstic leukemia (B-ALL) and B-cell non-Hodgkin's lymphoma (B-NHL) treated with a short, intensive multiagent chemotherapy and the treatment related toxicities and complications. METHODS: From Oct. 1997 to Apr. 2002, 10 patients were enrolled. Patients were classified into three groups (Group A, B, C) according to tumor burden and were treated with CCG 5961, UKCCSG 9600, and LMB96 protocol. Induction chemotherapy included cyclophsophamide, vincristine, prednisolone, doxorubicin and high dose (HD) methotrexate (COPADM). Consolidation chemotherapy included HD methotrexate, HD cytarabine and etoposide (CYM; group B, CYVE; group C). In one patient, HD chemotherapy with stem cell rescue was used because residual disease was detected after consolidation chemotheapy. RESULTS: Four patients were B-ALL and six patients were B-NHL (A; 1, B; 2, C; 7). Regimen was changed in 1 patient because of residual disease (B--