Orbital mucosa-associated lymphoid tissue (MALT) lymphoma as the initial presentation in patients with hepatitis C virus infection

ABSTRACT Hepatitis C virus infection may be implicated in 12.7% of ocular adnexal marginal zone lymphomas. We present the first case of an orbital-systemic mucosa-associated lymphoid tissue lymphoma that responded to hepatitis C virus medical treatment. A 62-year-old male with a right-sided orbital mass was diagnosed with stage IIA orbital marginal zone lymphoma in addition to hepatitis C virus infection based on clinical, imaging, laboratory, and histological examinations. The systemic and orbital responses were achieved 1 year after undergoing hepatitis C virus treatment with glecaprevir/pibrentasvir. The association between the hepatitis C virus infection and orbital-systemic mucosa-associated lymphoid tissue lymphoma is relevant. Accordingly, patients with orbital mucosa-associated lymphoid tissue lymphoma should be assessed for hepatitis C virus seroreactivity for therapeutic and prognostic purposes.

Primary central nervous system lymphoma: Comprehension of cell-of-origin subtypes

Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is an uncommon extranodal lymphoma that accounts for more than 95% of all the CNS lymphomas. Unlike its systemic/nodal counterpart, which is currently subtyped into cell-of origin (COO) subtypes, its feasibility and utility are largely debatable in PCNS-DLBCL. Objectives: To classify PCNS-DLBCL into COO-subtypes based on immunohistochemical algorithms by Hans and Choi and evaluate concordance between the two. A further aim is to investigate the clinicoradiological and histomorphological parameters of the subtypes thus obtained. Materials and Methods: As many as 143 cases of primary CNS lymphoma were evaluated by immunohistochemistry for CD10, BCL6, MUM1, GCET, and FOXP1 and based on which the said 143 cases were further classified into COO subtypes using Hans and Choi algorithms. Results: Mean age was 53.8 years with marginal male preponderance and predominantly centroblastic morphology (75.5%). CD 10 was positive in 8.9% of the cases, BCL6 in 58.6%, MUM1 in 89.9%, GCET in 32.9%, and FOXP1 in 79.5%. As much as 84.9% cases were of non-germinal center B-cell (GCB) subtype and 15.1% cases were of GCB subtype as determined based on Hans algorithm. Furthermore, 90.7% cases were of activated B-cell (ABC) subtype and 9.3% cases were of GCB subtype according to Choi algorithm. A 91.8% concordance was observed between Hans and Choi algorithms. Among the 6 discordant cases, 5 cases were subtyped as GCB by Hans and ABC by Choi and 1 case as ABC by Hans and GCB by Choi. Conclusion: Most of PCNS-DLBCLs are of non-GCB/ABC COO subtype, but inconsistences abound in the utility of IHC algorithms in PCNS-DLBCL COO subtypes.

Linfoma no Hodgkin difuso de células B grande como linfoma primario de ovario. Presentación de caso / Diffuse large B-cell non-Hodgkin's lymphoma as primary ovarian lymphoma. Case presentation

Fundamento: Los linfomas primarios de ovario son poco frecuentes; el 1 % de estos se presenta en ovario y el 1.5 % de los tumores malignos de ovario son linfomas. Los tipos histológicos más frecuentes es el linfoma no Hodgkin difuso de células B grande y el BurKitt; el tratamiento consiste en cirugía combinada con quimioterapia. Objetivo: Reportar un caso de un linfoma no Hodgkin difuso de células B grande primario de ovario. Presentación de caso: Se presentó el caso de una paciente de 39 años de edad, con antecedentes patológicos personales de salud; la cual fue al cuerpo de guardia de ginecología por presentar dolor abdominal difuso que no se aliviaba con analgésicos. En la exploración física presentaba dolor a la palpación superficial y profunda en hipocondrio y fosa ilíaca derecha con masa tumoral palpable. Ecografía hacia proyección anexial derecha se observó una imagen de baja ecogenicidad y en la laparoscopia de urgencia se concluyó como una formación de aspecto tumoral que parecía corresponderse con ovario derecho. Se le realizó una histerectomía con doble anexectomía. El diagnóstico anatomopatológico fue un linfoma no Hodgkin primario de ovario. Conclusiones: La paciente del caso presentado tuvo una clínica oligosintomática y la confirmación de la enfermedad fue a partir de una muestra quirúrgica, lo que expresa que el diagnóstico del linfoma no Hodgkin de células B es difícil y aunque es poco frecuente siempre se debe tener en cuenta en el diagnóstico diferencial de las tumoraciones unilaterales de ovario.

Background: Primary ovarian lymphomas are uncommon, 1% of these malignancies occur in the ovary, and 1.5% of all ovarian malignancies are lymphomas. The most common histologic types are diffuse large B-cell non-Hodgkin's lymphoma and BurKitt's lymphoma; treatment consists of surgery combined with chemotherapy. Objective: To report a case of primary ovarian diffuse large B-cell non-Hodgkin lymphoma. Case presentation: A 39-year-old female case is presented, with a personal pathological history; she went to the gynecology emergency service because she presented diffuse abdominal pain that was not relieved by analgesics. Physical examination revealed superficial and deep pain on palpation in the hypochondrium and right illiac fossa with a palpable tumor mass. Right adnexal ultrasound showed an image of low echogenicity and at the emergency laparoscopy, it was diagnosed as a tumor-like formation that appeared to correspond to the right ovary. She underwent a hysterectomy with double adnexectomy. The anatomopathologic diagnosis was primary ovarian non-Hodgkin's lymphoma. Conclusions: The patient in the presented case had an oligosymptomatic clinical presentation. Confirmation of the disease was obtained from a surgical sample, which means that B-cell non-Hodgkin's lymphoma is difficult to diagnose and although it is uncommon, it should always be considered in the differential diagnosis of unilateral ovarian tumors.

Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B. Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana. Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años. Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/ µl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa. Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados, lo que sugiere que no existe afectación de genes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.

Introduction. Monoclonal B-cell lymphocytosis generally precedes chronic lymphocytic leukemia, affecting about 12% of the healthy adult population. This frequency increases in relatives of patients with chronic B-cell lymphoproliferative disorders. Objective. To determine the frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic B-cell lymphoproliferative disorders, their immunophenotypic/ cytogenetic characteristics, a possible relationship with infectious agents, and short-term follow-up in the Colombian population. Materials and methods. Fifty healthy adults with a family history of chronic B-cell lymphoproliferative disorders were studied using multiparametric flow cytometry, cytogenetic/serological testing, lifestyle survey, and 2-year follow-up. Results. The frequency of monoclonal B-cell lymphocytosis found was 8%, with a predominance of female gender and advanced age, increasing to 12.5% for individuals with a family history of chronic lymphocytic leukemia. Three out of four individuals presented chronic lymphocytic leukemia-type immunophenotype, all with low counts. In turn, a significantly higher number of cells/µΙ is observed in these individuals in T lymphocyte subpopulations, together with a greater predisposition to the disease. The described clonal populations increase over time in a non-significant manner. Conclusions. The frequency and behavior of monoclonal B-cell lymphocytosis in patients with family history of chronic B-cell lymphoproliferative disorders are like those found in related studies, which suggests that there is no involvement of more relevant genes that can trigger uncontrolled clonal proliferation, but that generates immunological deregulation that could justify a greater risk of serious infection in these individuals.

The B-cell non-Hodgkin’s lymphoma: An enigma to diagnose

Non-Hodgkin’s lymphoma is a heterogeneous group of malignancies characterized by an abnormal clonal proliferation of T-cells, B-cells, or both. Sometimes, tuberculosis and lymphoma presentation can share common symptoms and features. In this case report, we present the case of a 28-year-old female patient who came with a chief complaint of swelling on the right side of the face for the past 6 months. Initially, it was not associated with pain but gradually developed severe pain over the region and reduced salivary flow. The patient was planned for surgery with a differential diagnosis of salivary gland pathology. Post-operatively, the histopathological report showed atypical cells which were diffusely positive for cluster of differentiation (CD)20. Focally positive for CD45 and CD3 which was positive in reactive T lymphocytes. Immunohistochemistry pattern favors the diagnosis of B-cell type NHL. Through this case report, we want to share our experience in treating an aggressive tumor that mimics salivary gland pathology.

ASIA and BIA-ALCL as adverse reactions to silicone breast implants / ASIA e BIA-ALCL como reações adversas aos implantes mamários de silicone

Adjuvant-induced autoimmune/inflammatory syndrome leads to capsular contracture and fibrosis from the oxidation that takes place in silicone. Anaplastic large cell lymphoma occurs through the development of a seroma, with the formation of a periprosthetic effusion, or through the infiltration of the condition itself. To analyze these conditions, a review of the literature was carried out on the symptoms and pathophysiology of the autoimmune/inflammatory syndrome induced by adjuvants and anaplastic large cell lymphoma, searched using the terms "ASIA breast silicone," "Lymphoma," "Adjuvants" "Immunologic" " Breast Implants" on the PubMed platform. Analyzing the data obtained, it was noted that the symptoms of the autoimmune/inflammatory syndrome induced by adjuvants are nonspecific, such as fatigue, myalgia, arthralgia, morning stiffness, and night sweats, and therefore need attention. Anaplastic large cell lymphoma presents with breast pain, periprosthetic effusion, and palpable mass, among other characteristics. Because of these aspects, it is concluded that a good investigation should be carried out when nonspecific symptoms appear, regardless of the time the surgery was performed since these complications can occur years later.

A síndrome autoimune/inflamatória induzida por adjuvantes leva à contratura capsular e fibrose pela oxidação que acontece no silicone. O linfoma anaplásico de grandes células ocorre através do desenvolvimento de um seroma, com a formação de derrame periprotético ou por uma infiltração da própria afecção. Para análise destes acometimentos, foi realizada uma revisão da literatura acerca da sintomatologia e fisiopatologia da síndrome autoimune/inflamatória induzida por adjuvantes e linfoma anaplásico de grandes células, pesquisada através dos termos "ASIA breast silicone" "Lymphoma" "Adjuvants" "Immunologic" "Breast Implants" na plataforma PubMed. Analisando os dados obtidos, notou-se que os sintomas da síndrome autoimune/inflamatória induzida por adjuvantes são inespecíficos, como fadiga, mialgia, artralgia, rigidez matinal e suores noturnos, e, portanto, necessitam de atenção. Já o linfoma anaplásico de grandes células se apresenta com dor mamária, derrame periprotético, massa palpável, dentre outras características. Em vista destes aspectos, conclui-se que uma boa investigação deve ser realizada ao surgirem sintomas inespecíficos, independentemente do tempo que a cirurgia foi realizada, uma vez que estas complicações podem ocorrer anos após a cirurgia.

Association between statin use & risk of diffuse large B-cell lymphoma: A systematic review & meta-analysis

Background & objectives: Statin use has been shown to be associated with a decreased risk of several types of cancer, however, the data on diffuse large B-cell lymphoma (DLBCL) are still inconclusive. This study aimed to systematically summarize all available data on this association and conduct a meta-analysis on the same. Methods: A systematic review was performed using EMBASE and MEDLINE databases from inception upto October 2019 with a search strategy that included terms such as ‘statin’ and ‘DLBCL’. Eligible studies included either case–control or cohort studies that reported the association between statin use and the risk of DLBCL. Relative risk, odds ratio (OR), hazard: risk ratio or standardized incidence ratio of this association and standard error were extracted and combined for calculating the pooled effect estimate using random-effects, generic inverse variance method. Results: A total of 1139 articles were screened. Of these six studies satisfied the inclusion criteria and were included for the meta-analysis. Statin use was associated with a significantly reduced risk of DLBCL with the pooled OR of 0.70 (95% confidence interval, 0.56-0.88; I2=70%). The funnel plot (fairly symmetric) was not suggestive of the presence of a publication bias. Interpretation & conclusions: The present systematic review and meta-analysis found that statin use is associated with a 30 per cent reduced odds of DLBCL. However, the pooled analysis utilized data from observational studies so causation cannot be concluded upon. Hence, it suggested that randomized-controlled studies are still needed to confirm this potential benefit.

Linfoma de células B de alto grado de malignidad con morfología blastoide durante el embarazo: reporte de un caso / High-grade malignant B-Cell lymphoma with blastoid during pregnancy: a case report

Resumen ANTECEDENTES: Durante el embarazo es más común el linfoma de Hodking que el no Hodking; afecta, en promedio, a mujeres de 30 años (18-44 años) y más. Suele diagnosticarse alrededor de las 28 semanas de embarazo y está documentado que puede llegarse al término. Los esquemas de tratamiento pueden iniciarse en el posparto inmediato o, incluso, antes. La incidencia mundial del linfoma no Hodking es de 0.8 por cada 100,000 mujeres; se desconoce la supervivencia durante el embarazo. CASO CLINICO: Paciente de 34 años, con antecedentes obstétricos de tres embarazos, una cesárea y un aborto y el embarazo actual en curso de las 29 semanas, referida de la ciudad de Colima debido a un reporte de BI-RADS 3 en el ultrasonido de mama y un nódulo mamario palpable, con evidencia de múltiples tumoraciones en la zona hepática, esplénica y peripancreática. La biopsia tomada de las zonas de la lesión reportó: linfoma de células B de alto grado de malignidad, con morfología blastoide y expresión de C-MYC y BCL2. Además, la paciente se encontró con: anemia, dolor abdominal, múltiples nódulos hepáticos y adenopatías abdominales. Se decidió la interrupción del embrazo a las 30 semanas, con la obtención de un recién nacido, sin complicaciones. Enseguida se inició el tratamiento con rituximab-etopósido-prednisolona-vincristina-ciclofosfamida-doxorrubicina (R-EPOCH) con adecuada adaptación por la paciente. CONCLUSION: Puesto que la información bibliográfica de linfoma y embarazo es escasa el caso aquí reportado es relevante por su aporte. La atención multidisciplinaria favorecerá siempre el pronóstico de las pacientes.

Abstract BACKGROUND: Hodking's lymphoma is more common during pregnancy than non-Hodking's lymphoma; it affects, on average, women aged 30 years (18-44 years) and older. It is usually diagnosed around 28 weeks of pregnancy and is documented to be carried to term. Treatment regimens can be initiated in the immediate postpartum period or even earlier. The worldwide incidence of non-Hodking's lymphoma is 0.8 per 100,000 women; survival during pregnancy is unknown. CLINICAL CASE: 34-year-old patient, with obstetric history of three pregnancies, one cesarean section and one abortion and the current pregnancy in progress at 29 weeks, referred from the city of Colima due to a report of BI-RADS 3 on breast ultrasound and a palpable breast nodule, with evidence of multiple tumors in the hepatic, splenic and peripancreatic area. Biopsy taken from the lesion areas reported: high grade malignant B-cell lymphoma, with blastoid morphology and expression of C-MYC and BCL2. In addition, the patient was found to have: anemia, abdominal pain, multiple hepatic nodules and abdominal adenopathies. It was decided to terminate the pregnancy at 30 weeks, with the delivery of an uncomplicated newborn. Rituximab-Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (R-EPOCH) therapy was started immediately with adequate adaptation by the patient. CONCLUSION: Since bibliographic information on lymphoma and pregnancy is scarce, the case reported here is relevant for its contribution. Multidisciplinary care will always favor the prognosis of patients.

Biomarcadores genéticos de la leucemia linfoide aguda de linaje B / Genetic biomarkers of B - cell acute lymphoid leukemia

Introducción: La leucemia linfoide aguda es una proliferación y transformación maligna de las células progenitoras linfoides en la médula ósea, la sangre y los sitios extramedulares. Es la neoplasia más frecuente en la infancia. Constituye el 80 % de todas las leucemias agudas de la edad pediátrica y la más frecuente de las que se originan a partir del linaje de células B. Desde el punto de vista genético se presentan múltiples alteraciones moleculares y cromosómicas que son utilizadas para la estratificación pronóstica. Objetivo: Describir los biomarcadores genéticos de la leucemia linfoide aguda de linaje B y su implicación pronóstica. Métodos: Se realizó una revisión de la literatura en los idiomas inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico, de artículos publicados en los últimos cinco años. Se efectuaron un análisis y resumen de la bibliografía revisada. Conclusiones: En la leucemia linfoide aguda de linaje B se detectan múltiples alteraciones citogenéticas como las traslocaciones t(9;22) y la t(12;21), rearreglos en 11q23 que generan genes de fusión, así como otras aberraciones cromosómicas y mutaciones génicas. Este espectro genético involucra genes que participan en el desarrollo de las células linfoides y en la regulación del ciclo celular. El conocimiento de su biología, a partir del estudio de las alteraciones genéticas como biomarcadores predictivos, permite la estratificación de la leucemia linfoide aguda y la aplicación de tratamientos más personalizados para evitar recaídas.

Introduction: Acute lymphoid leukemia is a proliferation and malignant transformation of lymphoid progenitor cells in the bone marrow, blood and extramedullary sites. It is the most common neoplasm in childhood; it constitutes 80% of all acute leukemias in children; and the most frequent of those that originate from the B cell lineage. From the genetic point of view, there are multiple molecular and chromosomal alterations. Objective: To describe the genetic biomarkers of the disease and its prognostic implication. Methods: A review of the literature in English and in Spanish was carried out, in the PubMed website and using the search engine of Google Scholar, for articles published in the last five years. We performed analysis and summary of the reviewed bibliography. Conclusions: In acute lymphoid leukemia, multiple cytogenetic alterations are detected, such as translocation t(9;22), t(12;21), rearrangements in 11q23 that generate fusions genes as well as other chromosomal aberrations and gene mutation. This genetic spectrum involves genes that participate in the development of lymphoid cells and in the regulation of the cell cycle. Knowledge of its biology, based on the study of genetic alterations as predictive biomarkers, allows the stratification of Acute lymphoid leukemia and the application of more personalized treatments to avoid relapses.

Diagnostic Efficacy of 18F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma / 生物医学与环境科学（英文）

OBJECTIVE@#Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL.@*METHODS@#A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.@*RESULTS@#The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively.@*CONCLUSION@#18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.

Based on CT radiomics model for predicting the response to first-line chemotherapy of diffuse large B-cell lymphoma / 中华肿瘤杂志

Objective: To investigate the potential value of CT Radiomics model in predicting the response to first-line chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods: Pre-treatment CT images and clinical data of DLBCL patients treated at Shanxi Cancer Hospital from January 2013 to May 2018 were retrospectively analyzed and divided into refractory patients (73 cases) and non-refractory patients (57 cases) according to the Lugano 2014 efficacy evaluation criteria. The least absolute shrinkage and selection operator (LASSO) regression algorithm, univariate and multivariate logistic regression analyses were used to screen out clinical factors and CT radiomics features associated with efficacy response, followed by radiomics model and nomogram model. Receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the models in terms of the diagnostic efficacy, calibration and clinical value in predicting chemotherapy response. Results: Based on pre-chemotherapy CT images, 850 CT texture features were extracted from each patient, and 6 features highly correlated with the first-line chemotherapy effect of DLBCL were selected, including 1 first order feature, 1 gray level co-occurence matrix, 3 grey level dependence matrix, 1 neighboring grey tone difference matrix. Then, the corresponding radiomics model was established, whose ROC curves showed AUC values of 0.82 (95% CI: 0.76-0.89) and 0.73 (95% CI: 0.60-0.86) in the training and validation groups, respectively. The nomogram model, built by combining validated clinical factors (Ann Arbor stage, serum LDH level) and CT radiomics features, showed an AUC of 0.95 (95% CI: 0.90-0.99) and 0.91 (95% CI: 0.82-1.00) in the training group and the validation group, respectively, with significantly better diagnostic efficacy than that of the radiomics model. In addition, the calibration curve and clinical decision curve showed that the nomogram model had good consistency and high clinical value in the assessment of DLBCL efficacy. Conclusion: The nomogram model based on clinical factors and radiomics features shows potential clinical value in predicting the response to first-line chemotherapy of DLBCL patients.

Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Mechanism of Ethyl Acetate Extract of Gentianopsis paludosa in Treatment of Ulcerative Colitis Based on Bcl-2/Bax Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of ethyl acetate extract of Tibetan medicine dampness bud Gentianopsis paludosa in the prevention and treatment of recurrent ulcerative colitis （UC） in rats with dampness-heat in large intestine syndrome based on the apoptotic pathway mediated by the B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）. MethodUsing the disease-syndrome combination method， a recurrent UC model of dampness-heat in large intestine syndrome was constructed in rats. Seventy SPF-grade male SD rats were randomly divided into control group， model group， high-， medium-， and low-dose ethyl acetate of G.paludosa groups （150， 75， 37.5 mg·kg-1）， and mesalazine group （135 mg·kg-1）. The rats were orally administered with respective drugs for 14 days. The general conditions of the rats were recorded， and colon length and mucosal damage were observed. The colon wet weight index and organ coefficients of the liver， spleen， and thymus were calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-6 （IL-6） and interleukin-1β （IL-1β） in the serum of each group. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in the colon. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect apoptosis in colonic epithelial cells. Western blot was used to measure the expression levels of Bcl-2， Bax， Caspase-3， Caspase-9， Zona Occludens-1 （ZO-1）， Claudin3， and Occludin in colonic tissue. Immunohistochemistry （IHC） was used to observe the expression of Bax and Caspase-3 in colonic epithelial cells. ResultCompared with the control group， the model group showed significant increases in the disease activity index （DAI） score， colonic mucosal damage index （CMDI）， intestinal epithelial apoptosis， liver and spleen indexes， and levels of inflammatory factors IL-1β and IL-6 in the serum （P<0.01）， decreased expression of intestinal mucosal protective proteins ZO-1， Claudin3， and Occluding （P<0.01）， increased expression of pro-apoptotic proteins Bax， Caspase-3， and Caspase-9 （P<0.01）， and decreased expression of anti-apoptotic protein Bcl-2 （P<0.01）. Compared with the model group， the high-， medium-， and low-dose ethyl acetate of G.paludosa groups all significantly improved the general condition of the rats， reduced colonic lesions， decreased intestinal epithelial cell apoptosis， reduced liver and spleen indexes， upregulated the expression of ZO-1， Claudin3， Occludin， and Bcl-2 proteins， and downregulated the expression of Bax， Caspase-3， and Caspase-9 proteins， with the high- and medium-dose ethyl acetate of G.paludosa groups showing the superior effects （P<0.05， P<0.01）. ConclusionEthyl acetate of G.paludosa can alleviate colonic mucosal damage and exert a therapeutic effect on UC by regulating the Bcl-2/Bax signaling pathway.

Plasmodium knowlesi circumsporozoite protein: genetic characterisation and predicted antigenicity of the central repeat region

@#Circumsporozoite protein (CSP) central repeat region is one of the main target regions of the RTS,S/AS01 vaccine for falciparum infection as it consists of immunodominant B cell epitopes. However, there is a lack of study for P. knowlesi CSP central repeat region. This study aims to characterise the CSP repeat motifs of P. knowlesi isolates in Peninsular Malaysia. CSP repeat motifs of 64 P. knowlesi isolates were identified using Rapid Automatic Detection and Alignment of Repeats (RADAR). Antigenicity of the repeat motifs and linear B cell epitopes were predicted using VaxiJen 2.0, BepiPred-2.0 and BCPred, respectively. A total of 35 dominant repeat motifs were identified. The repeat motif “AGQPQAQGDGANAGQPQAQGDGAN” has the highest repeat frequency (n=15) and antigenicity index of 1.7986. All the repeat regions were predicted as B cell epitopes. In silico approaches revealed that all repeat motifs were antigenic and consisted of B cell epitopes which could be designed as knowlesi malaria vaccine.

Prognostic Predictive Value of ITPKB Mutation's Variant Allele Frequency in Diffuse Large B-cell Lymphoma / 肿瘤防治研究

Objective To investigate the correlation between ITPKB mutation's variant allele frequency (VAF) and prognosis of diffuse large B-cell lymphoma (DLBCL). Methods This study included 155 patients with DLBCL initially diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from June 2014 to December 2020. Paraffin-embedded tumor tissue specimens were obtained, and tumor tissue DNA was extracted. A total of 475 hotspot genes including ITPKB were detected by the next generation sequencing to analyze the relationship of the VAF of high-frequency mutant gene with progression-free survival (PFS) and overall survival (OS). Results The mutation frequency of ITPKB was 18.71%. The PFS was significantly shorter in the patients with ITPKB mutations than in those without mutations (37 months vs. 108 months; HR=1.643, 95%CI: 0.920-2.934, P=0.093). The R-language based web tool was used to find the best VAF cutoff to differentiate prognosis. The patients were divided into two groups (VAF High vs. VAF Low+Wt) according to their VAF values. The optimal VAF threshold for ITPKB was 27.48% (HR=3.480, 95%CI: 1.70-7.13, P=0.00027). Multivariate Cox analysis was conducted using clinical indicators such as age, gender, COO classification, IPI, and LDH, and the results showed that PFS was associated with high ITPKB VAF (≥28%) (HR=3.592, 95%CI: 1.738-7.425, P < 0.001) which was an independent adverse predictor of PFS. Conclusion The high load of ITPKB mutation is an independent risk factor for the PFS of patients with DLBCL, and the VAF of ITPKB mutation has a prognostic predictive value for patients with DLBCL.

A Case of Lymphoma with Multiple Identities

@#Discordant lymphoma (DL) is the coexistence of two or more distinct subtypes in separate anatomic sites. There are limited reports on DL cases especially involving more than two subtypes in more than two sites. We report a 76-year-old man who presented with constitutional symptoms, flank mass and painless lymphadenopathies for six months. Laboratory tests revealed moderate anaemia, markedly elevated serum IgM (13400 mg/dL), IgM Lambda paraproteinemia and Lambda light chain paraproteinuria with unmeasurable serum lactate dehydrogenase due to hyperviscous sample. CT scan showed multiple subcutaneous masses over chest wall and retroperitoneum, with lytic bone lesions, and hepatosplenomegaly. Further biopsy findings with morphological, immunohistochemical and molecular analysis of the tissue sections revealed diffuse large B-Cell lymphoma in the chest wall mass, follicular lymphoma in the inguinal lymph node and lymphoplasmacytic lymphoma in the bone marrow. This case highlights the rare DL. The importance of histopathological evaluation of lymphoma despite the availability of PET-CT scans for disease staging is undeniable.

Diagnostic efficacy comparison between CLLflow score and Moreau score for chronic lymphocytic leukemia / 中华检验医学杂志

Objective:To explore the diagnostic efficacy difference and clinical diagnostic value of chronic lymphocytic leukemia flow (CLLflow) score and Moreau score (MS) in the diagnosis of chronic lymphocytic leukemia (CLL).Methods:According to the latest international and national diagnosis criteria for CLL, 133 patients with B-cell chronic lymphoproliferative diseases and uncertain immunophenotypes (B-CLPD), diagnosed by Zhengzhou Jinyu Comprehensive Haematological Pathology Diagnosis Centre from March 2020 to May 2021, were included in this study. Above patients were divided into the CLL group ( n=83) and non-CLL group ( n=50). The expression of clusters of differentiation (CD)5, CD10, CD20, CD19, κ light chain, λ light chain, FMC7, CD23, CD22, surface immunoglobulin M, CD200 and CD79 were detected by flow cytometry, and CLLflow score and MS score were calculated respectively according to the scoring rules. A fourfold table was used to compare the diagnostic efficacy of the two scoring systems, and the Kappa test and McNemar test were used to compare the consistency and superiority of the systems. Results:The rate of negative and positive CLLflow score were 4.8% (4/83) and 95.2% (79/83) in the CLL group and were 80.0% (40/50) and 20.0% (10/50) in the non-CLL group, and respectively (both P<0.001). The MS score (≤2, =3 and≥4) was 1.2% (1/83), 10.8% (9/83) and 88.0% (73/83) in the CLL group and was 86.0% (43/50), 14.0% (7/50) and 0 in the non-CLL group, there were significant statistical difference between the two groups ( P<0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the CLLflow score were 95.2% (79/83), 80.0% (40/50), 88.8% (79/89) and 90.9% (40/44), respectively and those of MS score were 98.8% (82/83), 86.0% (43/50), 92.1% (82/89) and 97.7% (43/44) respectively. The overall coincidence rate, positive and negative coincidence rate between the CLLflow score and MS score were 91.0% (121/133), 93.3% (83/89) and 86.4% (38/44) respectively. Besides, the McNeamr dominance test presented no significant difference ( P>0.05) and high consistency (Kappa=0.796) between the two scoring systems. With MS≤2 and MS≥4, the sensitivity and the specificity of the MS score were 100% (73/73) and 97.7% (43/44) respectively, and for the CLLflow score, the sensitivity and the specificity were 97.3% (71/73) and 86.4% (38/44) in this MS range. With MS = 3, the sensitivity and specificity of the MS score were 100% (9/9) and 0 (0/7), and CLLflow was 88.9% (8/9) and 57.1% (4/7). Conclusions:The diagnostic efficacy is similar and presents high consistency between the CLLflow score and MS score in CLL diagnosis. For CLL patients with MS = 3, the specificity of MS is relatively low, combined assessment with CLLflow score could improve the diagnosis efficacy for CLL in these patients.

The effect and safety of first-line autologous hematopoietic stem cell transplantation in elderly patients with moderate/high-risk diffuse large B-cell lymphoma / 中华老年医学杂志

Objective:To investigate the efficacy and related influencing factors of autologous hematopoietic stem cell transplantation(auto-HSCT)as first-line consolidation therapy for newly diagnosed elderly patients with diffuse large B cell lymphoma(DLBCL).Methods:Retrospective study of clinical characteristics, therapeutic effect, and prognostic factors of newly diagnosed DLBCL elderly patients with an International Prognostic Index(IPI)score≥3 who underwent auto-HSCT in the Affiliated People's Hospital of Ningbo University from January 2015 to August 2020.Results:Among the 31 patients, 18 were males and 13 were females, with a median age of 65(60-75)years.The 13 cases(41.9%)were involved in 2 sites outside lymph nodes, and 13 cases(41.9%)were involved in bone marrow.IPI medium and high risk(IPI=3 points)was found in 21 cases(67.7%), high risk(≥4 points)in 10 cases(32.2%). Before transplantation, 21(67.7%)patients achieved complete remission(CR), and the other 10(32.3%)patients were in the partial remission(PR). All patients after transplantation achieved hematopoietic reconstitution.The median time for neutrophil and platelet engraftment were 10(9-16)days and 12(8-58)days respectively.During a median follow-up of 20.9(3.1 to 73.0)months after transplantation, transplant-related mortality within 100 days was 3.2%(1/31). The 2-year overall survival(OS)and progression-free survival(PFS)were(77.2±8.4)% and(72.7±8.3)%, respectively.Multivariate Cox analysis showed that the achieved partial remission status before auto-hematopoietic stem cell transplantation[OS( HR=30.064, 95% CI: 2.231-405.209, P=0.010), PFS( HR=9.165, 95% CI: 1.926-43.606, P=0.005)], and CD34 + cell count in graft <3×10 6/kg[OS( HR=12.004, 95% CI: 1.234-116.807, P=0.032), PFS( HR=6.115, 95% CI: 1.325-28.221, P=0.020)]were the independent poor prognostic factor affecting both OS and PFS in elderly lymphoma patients. Conclusions:Auto-HSCT may improve the survival rate of carefully selected elderly patients with DLBCL.Pretransplant disease status and the number of CD34 + cells in the graft are important factors to predict the efficiency of auto-HSCT of the patients.

Predictive value of multi-parameter model incorporating PET-based radiomics features for survival of older patients(≥60 years) with diffuse large B-cell lymphoma / 中华核医学与分子影像杂志

Objective:To explore the prognostic value of 18F-FDG PET-based radiomics features by machine learning in older patients(≥60 years) with diffuse large B-cell lymphoma (DLBCL). Methods:A total of 166 older patients (88 males, 78 females, age: 60-93 years) with DLBCL who underwent pre-therapy 18F-FDG PET/CT from March 2011 to November 2019 were enrolled in the retrospective study. There were 115 patients in training cohort and 51 patients in validation cohort. The lesions in PET images were manually drawn and the obtained radiomics features from patients in training cohort were selected by the least absolute shrinkage and selection operator (LASSO), random forest (RF), and extreme gradient boosting (Xgboost), and then classified by support vector machine (SVM) to build radiomics signatures (RS) for predicting overall survival (OS). A multi-parameter model was constructed by using Cox proportional hazard model and assessed by concordance index (C-index). Results:A total of 1 421 PET radiomics features were extracted and 10 features were selected to build RS. The univariate Cox regression analysis showed that RS was a predictor of OS (hazard ratio ( HR)=5.685, 95% CI: 2.955-10.939; P<0.001). The multi-parameter model that incorporated RS, metabolic metrics, and clinical risk factors, exhibited significant prognostic superiority over the clinical model, PET-based model, and the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in terms of OS (training cohort: C-index: 0.752 vs 0.737 vs 0.739 vs 0.688; validation cohort: C-index: 0.845 vs 0.798 vs 0.844 vs 0.775). Conclusions:RS can be used as a survival predictor for older patients(≥60 years) with DLBCL. Furthermore, the multi-parameter model incorporating RS is able to successfully predict prognosis.

Predictive value of 18F-FDG PET/CT metabolic parameters combined with inflammatory markers for medium-term outcome in patients with primary gastrointestinal diffuse large B cell lymphoma / 中华核医学与分子影像杂志

Objective:To explore the predictive value of 18F-FDG PET/CT metabolic parameters combined with inflammatory markers for the medium-term efficacy of chemotherapy in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL). Methods:From April 2011 to May 2020, 67 patients (37 males, 30 females, age: 28-85 years) with PGI-DLBCL examined by 18F-FDG PET/CT before chemotherapy in Changhai Hospital, Navy Medical University were retrospectively analyzed. All patients were treated with cyclophosphamide+ doxorubicin+ vincristine+ prednisone (CHOP) or rituximab+ CHOP (R-CHOP) regimens, and the medium-term efficacy was evaluated after 2-4 cycles of chemotherapy. The effect outcome was divided into complete remission (CR) group and non-CR (NCR) group based on the Lugano lymphoma response evaluation criteria. Mann-Whitney U test was used to compare the differences of SUV max, peak of SUV (SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) between two groups. The independent risk factors of NCR were analyzed by multivariate logistic regression and the binary logistic regression model was established according to the results. The model was tested with external validation data ( n=15). Results:Of 67 PGI-DLBCL patients, 28(41.8%) were CR and 39(58.2%) were NCR. SUV peak, MTV, TLG, PLR and NLR in NCR group (17.3(12.3, 28.1), 73.8(42.9, 141.7) cm 3, 887.5(300.9, 2 075.3) g, 203.9(155.7, 297.1), 3.9(3.0, 4.9)) were significantly higher than those in CR group (9.5(6.2, 15.2), 11.3(4.7, 23.2) cm 3, 85.2(35.5, 214.6) g, 149.3(102.8, 173.1), 2.2(1.8, 4.6); z values: from -6.41 to -2.33, all P<0.05). The logistic regression model was as follows: P=1/(1+ e - x), x=0.100×MTV+ 0.024×PLR-8.064. The prediction accuracy for NCR risk was 86.57%(58/67), with the accuracy of 13/15 tested by external validation data. Conclusion:MTV combined with PLR has a good predictive value for medium-term efficacy of CHOP/R-CHOP chemotherapy in patients with PGI-DLBCL.