Precursor B-cell Lymphoblastic Lymphoma Research Articles

Precursor B-sejtes lymphoblastos lymphoma cutan tünetei

The case of a 15-year-old boy diagnosed with cutaneous and subcutaneous infiltration of precursor B-cell lymphoblastic lymphoma is presented. The patient’s first skin symptoms appeared 4 months prior to the first hospitalization. According to the parents, it was diagnosed as lipoma by his family doctor and his dermatologist. The differential diagnosis of the case and the clinical features of the pediatric dermatological conditions presenting in nodular form are briefly reviewed.

Precursor B-cell Lymphoblastic Lymphoma in Children: Hacettepe Experience.

The purpose of the study was to review the clinical and pathologic characteristics and treatment results of children with precursor B-cell lymphoblastic lymphoma. Of 530 children diagnosed with non-Hodgkin lymphomas between 2000 and 2021, 39 (7.4%) were identified as having precursor B-cell lymphoblastic lymphoma. Clinical characteristics, pathologic, radiologic, laboratory data, treatments, responses, and overall outcomes were recorded from hospital files and analyzed. The median age of 39 patients (males/females, 23/16) was 8.3 years (range 1.3 to 16.1). The most common sites of involvement were the lymph nodes. At a median follow-up of 55.8 months, 14 patients (35%) had a recurrence of disease (11 stage IV, 3 stage III); 4 were in complete remission with salvage therapies, 9 died of progressive disease and one died due to febrile neutropenia. Five-year event-free survival and overall survival rates were 65.4% and 78.3% for all cases, respectively. Survival rates were higher in patients with a complete remission at the end of induction therapies. The survival rates were lower in our study compared with other studies, which could be explained by the high relapse rate and higher incidence of advanced-stage disease due to bone marrow involvement. We demonstrated a prognostic impact of treatment response at the end of the induction phase. Cases with a disease relapse have poor prognosis.

Clinicopathological Spectrum of B-Cell Non-Hodgkin Lymphoma in Pakistan Population: A Single-Center Study.

Background B-cell non-Hodgkin lymphoma (NHL) is a common malignancy worldwide and in the Pakistani population. In our population, there was limited information regarding the clinicopathological characteristics of B-cell NHL. This study assessed the disease spectrum and most prevalent subtypes of B-cell NHL. Methodology An analysis of 548 cases was conducted in this cross-sectional study between January 2021 and September 2022, using a non-probability consecutive sampling approach. Patient age, gender, site of involvement, and diagnosis were documented according to the 5th edition of the World Health Organization (WHO)Classification of Tumors of Hematopoietic and Lymphoid Tissue, published in 2018. Data were entered and analyzed using Statistical Product and Service Solutions (SPSS) (IBM SPSS Statistics for Windows, Version 26.0, Armonk, NY). Results The mean age of the patients was 47.73±20.44 years. There were 369 males (67.34%) and 179 females (32.66%). The most prevalent type of B-cell NHL was diffuse large B-cell lymphoma (DLBCL) (58.94%), followed by chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (13.14%), Burkitt lymphoma (9.85%), and precursor B-cell lymphoblastic lymphoma (5.11%). In contrast to low-grade B-cell NHL (22.99%), high-grade B-cell NHL was more common (77.01%). Nodal involvement was observed in 62.04% of cases. The cervical region was the most common nodal site of involvement (62.04%), and the gastrointestinal tract (GIT) was the most common extranodal site (48.29%). Conclusion The incidence of B-cell NHL is higher in older age groups. The most common nodal site was the cervical region, whereas the extranodal site was the GIT. The most reported subtype was DLBCL, followed by CLL/SLL, and Burkitt lymphoma. The prevalence of high-grade B-cell NHL is higher than that of low-grade B-cell NHL.

Precursor B-cell lymphoblastic lymphoma presenting as a primary solitary skull bone tumor

1Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 2Post Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3School of Medicine. College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Address for correspondence: Dr. Ann-Shung Lieu, Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan. E-mail: [email protected]. Data availability statement: Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest. Submitted: 31-Aug-2022, Accepted: 01-Sep-2022 This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Recurrent Germline Variant in the Cohesin Complex Gene RAD21 Predisposes Children to Lymphoblastic Leukemia and Lymphoma

Introduction: Cohesin complex genes are commonly mutated in cancer particularly in myeloid malignancies. Yet patients with germline mutations in cohesin genes, leading to cohesinopathies like Cornelia-de-Lange syndrome (CdLS) are generally not known to be tumor-prone. The complex plays a major role in chromosome alignment and segregation (Uhlmann, Nature Reviews Molecular Cell Biology, 2016), homologous recombination-driven DNA repair (Ström et al., Molecular Cell, 2004) and regulation of gene expression (Busslinger et al., Nature, 2017). To deepen the understanding of cohesin variants in cancer predisposition, we performed TRIO Sequencing in two independent pediatric cancer cohorts. Thereby, we identified a novel recurrent heterozygous germline variant in the cohesin gene RAD21 not described in CdLS patients , located in the binding domain of the cofactors WAPL and PDS5B .Methods: Whole exome sequencing (WES) in a TRIO (child-parent datasets) setting was carried out in two independent, unselected cancer cohorts (TRIO-D, n=158 (Wagener et al., European Journal of Human Genetics, 2021) and TRIO-DD, n=60). To investigate the oncogenic potential of the novel RAD21 variant molecular and functional assessment was performed focusing on potential implications on the complex.Results: The newly identified RAD21 variant at amino acid position 298 resulting in a Proline to Serine (p.P298S) and a Proline to Alanine exchange, respectively, (p.P298A) is only rarely mutated in the general population (gnomAD database n=118,479; RAD21 p.P298S MAF <10 -6 and RAD21 p.P298A MAF <10 -5). While both patients did not show any signs of CdLS, they both have a remarkable family history of cancer. Patient 1 (13y) was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) whose father had died from breast cancer (41y), while patient 2 (2y) presented with precursor B-cell lymphoblastic lymphoma (pB-LBL) whose uncle had died from pediatric cancer of unknown subtype (8y).To assess the influence of RAD21 p.P298S/A on the binding capacity of the complex, RAD21 variants and the wildtype (WT) were cloned and transfected into HEK293T cells, respectively. Immunoprecipitation analysis of RAD21 with the cofactors WAPL and PDS5B showed no differential binding between the WT and the variants, suggesting that RAD21 p.P298S/A does not impact the formation of the complex.Nevertheless, on a transcriptional level 83 genes were significantly differentially expressed in RAD21 p.P298S and p.P298A compared to the wildtype (fc>1.5, adj. p-value <0.05) with enrichment of genes in p53 signaling pathways. We further observed an increased number of γH2AX and 53BP1 co-localized foci compared to the WT (p≤0.01; Student's t-test). In line, following ionizing radiation, primary patients' samples showed increased cell cycle arrest at G2/M cell-cycle stage compared to a healthy control (p.P298S: p=0.0049 [6Gy]; p=0.0026 [10Gy]; p.P298A: p=0.0054 [6Gy]; p=0.0006 [10Gy]; Student's t-test).For cross-validation of the germline variant RAD21 p.P298S/A and its potential role in pediatric lymphoblastic malignancies, we analysed a third cohort of 150 children with relapsed ALL (IntReALL) for RAD21 p.P298S/A. We again identified RAD21 p.P298A in a boy (12y) with B-cell precursor acute lymphoblastic leukemia. To compare our data to a non-pediatric cancer setting, a cohort of 2300 young adults (<51 years) with cancer was mined (MASTER program). Here, one patient carrying RAD21 p.P298A with a solid tumor was identified. Therefore, amongst all cohorts, RAD21 p.P298S/A was found to be enriched in pediatric vs. adult cancers (3/479 vs. 1/2299; Fisher's exact test; p=0.018).Conclusion: Taken together, we present for the first time the potential role of RAD21 germline variants in pediatric lymphoblastic malignancies. This may shed new light on the many roles of the cohesin complex and its implication outside the typical syndromal presentation. DisclosuresNo relevant conflicts of interest to declare.

Rare ovarian neoplasm: Primary precursor B-cell Lymphoblastic Lymphoma involving bilateral ovaries

The involvement of the ovary in lymphomatous processes is rare. However, in the female genital tract, the ovary is a frequent site to be involved by the hematological malignancies. Involvement of the ovary by malignant lymphoma can be primary or secondary and is discovered incidentally during a workup for abdominal or pelvic complaints. Most commonly occurring ovarian lymphoma is diffuse large B cell type, whereas the Precursor B Cell Lymphoblastic Lymphomas are extremely rare and previously only 5 cases have been reported. Here, we report a case of clinically suspected malignant ovarian tumor involving bilateral ovaries, which was diagnosed as a primary precursor B-LBL after surgery in a young female. This case highlights the need for careful evaluation of radiologic and morphologic features along with an extensive immunohistochemical panel to arrive at the correct final diagnosis to guide the chemotherapy. Keywords: Non-Hodgkin Lymphoma; Primary Ovarian Precursor B-Cell Lymphoblastic Lymphoma; Primary ovarian lymphoma; Primary ovarian tumors

SALL4 is a useful marker for pediatric yolk sac tumors.

SALL4 is a zinc finger transcription factor that exerts its physiological role during embryo-fetal development. Analyses of SALL4 expression have shown its oncogenic role in precursor B-cell lymphoblastic lymphoma, acute and chronic myeloid leukemia, gastrointestinal, breast, and lung cancers. The aim of this study was to determine the immunohistochemical profile of SALL4 in pediatric yolk sac tumors (YSTs). Immunohistochemistry detection of SALL4 was performed in 22 cases of pediatric YSTs and 10 mature teratomas. The percentage of tumor cells stained was scored as 0, 1+ (1-30% cells), 2+ (31-60%), 3+ (61-90%), and 4+ (> 90%). To compare its sensitivity and specificity with Glypican-3 and α-fetoprotein (AFP), we also stained tumors from these cases for Glypican-3 and AFP. In contrast to AFP and glypican-3, SALL4 staining in more than 90% of the tumor cells was seen in all 22 pediatric YSTs (100% sensitivity) (P < 0.001 for both SALL4 vs. AFP and SALL4 vs. glypican-3). SALL4 is a sensitive marker for pediatric YSTs and it can be used to distinguish them from mature teratomas. SALL4 is likely to become a new and valuable biomarker for the diagnosis of pediatric YST.

Precursor B-cell Lymphoblastic Lymphoma of Bone in Children: A Close Mimicker of Ewing's Sarcoma

AbstractPrecursor B-cell lymphoblastic lymphoma (LBL) occurring as a primary bone tumor is a rare clinical presentation in children, and data regarding this condition are limited to small case series or a few individual case reports. We report two pediatric cases of precursor B-cell LBL of the bone. The tumor cells from bone biopsies of both patients were seen to be positive for leukocyte common antigen (LCA), terminal deoxynucleotidyl transferase, CD10, CD20 and weakly positive for CD99. Bone marrow studies were normal. They were treated according to the modified Berlin-Frankfurt-Münster acute lymphoblastic leukemia high-risk protocol. The first patient has completed treatment including local radiotherapy and has been disease free for the past 10 years. The second patient has recently completed treatment and shows good response.

A Case of Precursor B-cell Acute Lymphoblastic Leukemia Occurre d with Rapid Hip Bone Destruction and Femoral Neck Fracture

Background: Precursor B-cell lymphoblastic lymphoma is a rare subtype of acute lymphoblastic lymphoma and sometimes presents as lytic bone lesions. Diagnosis and treatment of lytic bone lesions are always challenging. This is a rare case of delayed leukemic change of precursor B-cell acute lymphoblastic lymphoma presented with a rapid hip bone destruction.Case presentation: A 12-year-old Japanese girl presented with progressive left hip pain, and bone destruction of her left hip two months after the onset of symptoms. She had no past medical or family history of malignancy and had no genetic abnormality. Radiograph and MRI examination showed bone destruction and osteolytic lesions in her left femoral neck and pelvis. Blast cells were not found in our initial examination of the peripheral blood and aspirated bone marrow cells. The case was finally diagnosed as Precursor B-cell lymphoblastic lymphoma as the results of bone biopsy, and blast cells were then detected after preforming multiple bone marrow aspirations. She also had pathological femoral neck fracture, but after treatment regimen by chemotherapy, her osteolytic lesions cured with obtainment of femoral neck fusion. She could walk at the final period.Conclusion: This case highlights the importance of early diagnosis of this disease for greater curing rates. Diagnosis of Precursor B-cell lymphoblastic lymphoma was finally made based on the results of biopsy of tissues because of the delayed appearance of leukemic changes. Orthopaedic surgeons should be aware of Precursor B-cell lymphoblastic lymphoma, when making diagnosis of patients exhibiting a rapid hip bone destruction.

Chronic Myeloid Leukemia with Cryptic Philadelphia Translocation Presenting Initially As Extramedullary Lymphoid Blast Phase

Abstract We report an adult male diagnosed as chronic myeloid leukemia (CML) - chronic phase when he was shortly presented with treatment-naive extramedullary lymphoid blast crises involving multiple lymph nodes, with no features of acceleration or blast crises in the peripheral blood (PB) and bone marrow (BM). In addition the patient has Philadelphia negative (Ph -ve) BCR/ABL-1 - positive CML. Up to our knowledge; this is the first report of CML with extramedullary lymphoid blast phase (as initial presentation) that shows cryptic Ph translocation. This is a 45 year- old male who presented with one month history of swelling of medial canthus of his left eye, and left sided neck swelling for three days. His initial physical examination showed bilateral cervical lymphadenopathy and splenomegaly. CBC showed marked leukocytosis (WBC: 159x10^3/ul (4.0-10.0), with Hb of 12.2gm/dl (13.0-17.0) and thrombocytopenia (123x10^3/ul (150-400)). BM biopsy was markedly hypercellular with granulocytic hyperplasia and prominent eosinophils. Reticulin stain showed focal increase reticulin fibrosis (grade 1-2 out of 3). FISH analysis revealed BCR/ABL1 rearrangement, t(9;22) in 97% of the cells analyzed with deletion of ABL1 as confirmed by metaphase FISH analysis: der(9)t(9;22),del(9)(q34q34)(ABL1+,BCR+),der(22)t(9;22)(BCR+,ABL1-)[10]. (fig 1 B). The fusion signal was formed on chromosome 9 instead of 22. Conventional cytogenetics confirmed the presence of cryptic BCR/ABL1 rearrangement. and normal karyotype: 46,XY. (fig1 c). BCR/ABL1 transcript confirmed by PCR.The overall findings consistent with CML- chronic phase. Immunohistochemical studies showed positivity for CD45, CD20, CD79a and BCL2 with strong and diffuse positive staining for Tdt. Ki67 shows high expression of about 90% of cellular nuclei. T-cell markers including CD3, CD5, CD4 and CD8 are negative in tumor cells. The morphological and immunohistochemical features are consistent with nodal involvement by precursor B-cell lymphoblastic lymphoma. FISH analysis performed on nodal tissue and confirmed the presence of BCR/ABL-1 rearrangement confirming that nodal involvement is lymphoid blast phase (BP) of CML and excluding the possibility of denovo ALL as second pathology. The patient started on hyper CVAD chemotherapy and Dasatinib .Still under treatment . In the great majority of CML; BCR/ABL is cytogenetically visualized as t(9;22); giving rise to the Ph chromosome, harboring the chimeric gene. Cryptic or masked translocation occurs in 2-10% patients with no cytogenetic evidence for the BCR/ABL rearrangement but are positive by FISH and/or (RT-PCR. Cryptic BCR/ABL rearrangements can be found in cases with a normal karyotype and in cases with complex karyotype in which the t(9;22) is not detected by conventional cytogenetics. These latter patients are described as CML Ph-ve/ BCR/ABL1 +ve with the chimeric gene present on the derivative chromosome 22, as in most CML cases, or alternatively on the rivative 9 as in our case. The prognostic significance of cryptic Ph translocations has been discussed in previous reports, some authors reported a worse prognosis associated with location of BCR/ABL on the der (9). Data regarding the outcome of Ph-neg CML patients treated with TKIs are limited, only 10 Ph-neg CML cases treated with imatinib have been described in 6 previous reports . The prevalence of extramedullary blast phase (BP) has been reported to be 7-17% in patients with BP . Extramedullary BP in the newly diagnosed patients is extremely rare as the prevalence of an accelerated phase and BP as initial presentations has been reported to be only 5-10% in CML patients . Conclusion: This is a report of a case of (CML) with a combination of a couple of unusual events including cryptic Philadelphia (Ph) translocation together with extramedullary lymphoid blast crisis as an initial presentation We aim in this report to highlight this case with unusual features, to describe clinical features and disease out come and to focus that the absence of hematologic blast proliferation in PB or BM in cases of CML doesn't by all means exclude the possibility of concomitant extramedullary blast crisis as an initial event. The combined cytogenetic, molecular and clinical studies in CML cases can bring to light the frequency of this event and disease out come. Although rare; this possibility should be raised and thoroughly investigated whenever clinically suspected. Download : Download high-res image (336KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.

Aches and Pain in a child- An unusual cause

Precursor B-cell lymphoblastic lymphoma presenting with severe pain and extensive skeletal lesions as an initial presentation is very rare. We report a nine year old boy who presented with lower backache and difficulty in walking of 2 months duration. He neither had lymphadenopathy nor organomegaly. His peripheral blood picture and bone marrow examination were normal. MRI revealed multiple lytic lesions in the spine and PET scan revealed metabolically active lytic lesions in the axial skeletal system and bilateral femurs and humerus. Biopsy of the vertebra revealed the diagnosis of precursor B cell lymphoma. A diagnosis of malignancy should never be missed in a patient with musculoskeletal pain, having ruled out infectious and traumatic etiologies especially when they present with several skeletal radiolucencies.

A case of precursor B-cell lymphoblastic lymphoma with bilateral multiple nodular renal and multiple spinal involvements

A case of precursor B-cell lymphoblastic lymphoma with bilateral multiple nodular renal and multiple spinal involvements

A Pediatric Primary Renal Lymphoma Case Presenting with Acute Renal Failure Findings

▪Lymphomatous involvement of the kidneys is a common manifestation of systemic non-Hodgkin’s lymphoma (NHL). In contrast, lymphoma originating within the kidneys is a rare event in children. In this study we report a case of primary renal lymphoma presenting with acute renal failure in a 14-years-old boy. According to histopathological and immunohistochemical examinations, the diagnosis of B-cell renal lymphoma was established.A fourteen years old boy presented to our Pediatric Hematology - Oncology Unit, with 4-month history of weakness and anorexia. He had mild abdominal pain. Physical examination revealed no significant abdominal or systemic. The laboratory data were white blood cell count 4100/mm3; hemoglobin level 10.8 g/dL, mean corpuscular volume 107 fL; mean corpuscular hemoglobin concentration 33.6 g/dL); platelet count 179,000/mm3;erytrocyte sedimentation rate 50mm/h; blood urea nitrogen level 142 mg/dL; creatinine level 4.85 mg/dL; lactate dehydrogenase level 465 IU/L. There were no pyuria or hematuria, and urinary culture and stain results were negative. An abdominal ultrasonography revealed an increase in bilateral kidney sizes. Abdomen computed tomography scan showed an increase in thickness of renal parenchyma with hypodense appearance and with bilateral mild ectasia in pelvicalyceal system.An ultrasonography guided renal biopsy demonstrated precursor B-cell lymphoblastic lymphoma. Hematoxylin and eosin section of these renal masses revealed neoplastic lymphoma cells with increased nuclear-cytoplasmic ratio, prominent nucleoli and mitotic figures.The lymphoma cells stained positivie for terminal deoxynucleotydyl transferase and B-lymphocyte marker CD10 and CD20 immuno-histochemical stain. Extrarenal abdominal involvement was excluded by imaging techniques. Bone marrow examination was normal. He was diagnosed as non-Hodgkin’s lymphoma, pre B-cell type and was treated with multidrug chemotherapy (induction regimen of prednisolone, vincristine, daunorubicin and L-asparaginase) and prophlactic intratecal methotrexate according to British-French-Munster (BFM) protocol. After the initial therapy, renal function test were improved rapidly and during consolidation and maintenance chemotherapy, they continud as normal. The patient is still in complete remission and was followed normal renal function with no sign of disease recurrence 5 years later diagnosis..In conclusion, diagnose of PRL is difficult. Percutaneous kidney biopsy is the most expeditious method towards the establishment of an early diagnosis for appropriate chemotheraph. Early diagnosis and urgent therapy, with supporting therapy are necessary for good prognosis. DisclosuresNo relevant conflicts of interest to declare.

Precursor B-Cell Lymphoblastic Primary Cardiac Lymphoma – Case report and Review of Literature

Primary cardiac lymphoma (PCL) is an extremely rare malignancy and an uncommon presentation of Non-Hodgkin’s Lymphoma. We report the first case of Precursor B-cell lymphoblastic PCL. A 44 year old Caucasian woman presented to our institution with one week history of worsening dyspnea, leg swelling and a weight gain of 12 pounds. Urgent echocardiography revealed pericardial effusion with tamponade physiology. Subsequent imaging showed a mass in the right atrio-ventricular groove. Pericardiocentesis was performed and cytopathology showed malignant appearing immature lymphocytes. Immunophenotypic analysis revealed 85% of the cells to be CD19 and CD10 positive. The cells were negative for CD20, surface light chains, CD3 and CD5 consistent with immature B-cells. Terminal deoxynucleotidyl Transferase (TDT) was strongly positive confirming Precursor B-cell Lymphoblastic Lymphoma. Clinical presentation of PCL can be varied and can mimic non-neoplastic primary cardiac problems. When PCL is suspected and a pericardial effusion is present, pericardial fluid analysis can be a reasonable first step. If diagnostic, it can avoid further invasive procedures. Chemotherapy remains the standard treatment and should be initiated early given the aggressive nature of these high grade lymphomas. Surgery is needed only in selected cases with obstructive features.

Neoplastic skin lesions of the scalp in children: A retrospective study of 265 cases in Taiwan

The preferential occurrence of certain skin neoplasms on the scalp of children raises concerns from their parents and warrants special diagnostic and therapeutic approaches. To explore the demographic and clinical characteristics of scalp neoplasms in the pediatric population, with attention to malignant tumors and systemic syndromes. Scalp neoplasms in patients aged 12 years or younger were retrospectively collected in 1990-2010 from two tertiary referral centers in Taiwan. A total of 267 scalp neoplasms in 265 pediatric patients were recruited. Among the 209 neoplasms with a histopathological diagnosis, nevus sebaceus was the most common (67.9%), followed by melanocytic nevus (6.2%) and juvenile xanthogranuloma (6.2%). Most of the scalp neoplasms (77.9%) were seen at birth or before 1 month of age. Infantile hemangioma was clinically diagnosed without histology in 41.4% of cases. Malignant scalp tumors were identified in two patients (0.95%), with one basal cell carcinoma and one precursor B-cell lymphoblastic lymphoma, respectively. Scalp neoplasms in association with systemic syndromes were found in two cases. One had neurofibromatosis type I with juvenile xanthogranuloma and the other basal cell nevus syndrome with basal cell carcinoma. Most pediatric scalp neoplasms in our study were hamartomas or teratomas. Malignant scalp tumors and malignant transformation of nevus sebaceus were rare. A detailed medical history taking and complete physical examinations are needed to exclude possible associations with systemic syndromes or malignancies.

Clinical outcome of childhood lymphoblastic lymphoma in Shanghai China 2001–2010

This retrospective cohort study analysed the clinical characteristics and outcomes of patients with childhood lymphoblastic lymphoma (LBL) treated in Shanghai, China. From 2001 to 2010, 108 evaluable patients ≤16 years of age who were newly diagnosed with biopsy-proven LBL were treated with one of three treatment protocols: CCCG-99, SCMC-T-NHL-2002, or LBL-CHOF-2006. Two patients had Stage I disease, 5 had Stage II, 55 had Stage III, and 46 had Stage IV. The immunophenotype was T-cell LBL in 92 patients (85.2%) and precursor B-cell LBL in 16 (14.8%). The abandonment rate was 11.5%. Twenty-five patients (23.2%) suffered from resistant disease, including 1 with isolated central nervous system (CNS) relapse. At a median follow-up of 40.4 months (range, 0-114 months), the 5-year probability of event-free survival (pEFS) was 63.9 ± 4.6% in all patients. The 5-year pEFS for patients with pB-LBL was better than for patients with T-LBL (100% vs. 61.3 ± 5.1%, P = 0.007). Patients who had achieved complete remission on day 33 of induction had significantly better pEFS than those who had not (78.8 ± 4.6% vs. 28.2 ± 9.0%, P = 0.000). Three of 25 patients who experienced resistant disease were alive at the end of the study period. The abandonment rate was lower for patients with LBL than for patients with acute lymphoblastic leukemia. Prophylactic cranial radiation can be omitted for patients with LBL even when advanced-stage disease is present, as intensive systemic chemotherapy with intrathecal therapy is sufficient to prevent CNS relapse. The survival of patients with resistant disease was very poor.

Pediatric precursor B-cell lymphoblastic lymphoma presenting with extensive skeletal lesions

Lymphoblastic lymphoma (LL) of the B cell type is uncommon, and extranodal presentation is even rarer. It is difficult to suspect this diagnosis without clinically obvious lymph nodal mass or bone marrow involvement. A 3-year-old girl presented with progressive pain and swelling of the right knee joint of 3 months duration. Radiograph revealed expansile lytic lesion at the supracondylar area of the right femur; with pathological fracture and multiple lytic areas in both femora. She neither had lymphadenopathy nor organomegaly. Her blood counts, peripheral smear examination and bone marrow examination were normal. Right supracondylar biopsy revealed diagnosis of a precursor B cell LL. Computerized tomography scan revealed a hypodense, poorly enhancing lesion in the left adnexal region. Although rare, precursor B-cell LL may present with extensive bone lesions. Early and accurate diagnosis of this entity is very important due to its high cure rates.

Precursor B-cell lymphoblastic leukemia of the arm mimicking neurogenic tumor: case report

Precursor B-cell lymphoblastic lymphoma (PBLL) is an infrequent subtype of lymphoblastic lymphoma (LBL) that commonly affected site for the diagnosis is the skin, followed by the head and neck. In this report, we presented a special case of PBLL located at the left arm and detected with magnetic resonance imaging (MRI) and ultrasonography (US). This kind of PBLL is similar to a peripheral nerve tumor in clinical and radiographic manifestation.

Fatal hepatic sinusoidal obstruction syndrome in a child with primary CNS lymphoma during induction therapy

Hepatic sinusoidal obstructive syndrome (HSOS) is a lifethreatening syndrome characterized by painful liver enlargement, weight gain, and jaundice, and generally occurs as a complication of hematopoietic stem cell transplantation (HSCT) [1] and chemotherapy in Wilm’s tumor [2]. HSOS after conventional chemotherapy for malignant disease other than Wilm’s tumor is unusual. Here, we report the first case to our knowledge of a 9-yearold boy with PCNSL who developed fatal HSOS during induction therapy. A 9-year-old boy presented with a 4-month history of hyperphagia. He was admitted to our department because of headache. The patient’s body weight was 40 kg (28 % obesity compared to ideal body weight). He had gained 15 kg in body weight over the previous 4 months. A physical examination revealed left-sided hemiparesis with a decreased mental status. The Eastern Cooperative Oncology Group performance status (ECOG-PS) was 3. Laboratory and coagulation tests showed the following: AST, 20 U/L; ALT, 21 U/L; LDH, 384 IU/L; total bilirubin, 0.3 mg/dl; activated partial thromboplastin time (aPTT), 33.2 s (normal 26–36 s); prothrombin time (PT), 10.8 s (normal 10–15 s), prothrombin time in international normalized ratio (PT-INR), 1.05 (normal 0.9–1.1); AT III activity level, 115 % (normal 80–120 %). Magnetic resonance imaging of the brain showed a mass with a homogeneous enhancement located in the right frontal lobe, and this lesion reached the hypothalamus (Fig. 1a). As the leftsided hemiparesis progressed rapidly, a sub-total excision of the tumor was performed. A pathological examination of the surgical specimen revealed a monotonous population of small-sized mononuclear lymphoblastic cells (Fig. 1b). Flow cytometry analysis revealed that lymphoblasts expressed TdT, cytoplasmic CD79a, CD10, and HLA-DR, leading to the diagnosis of precursor B-cell lymphoblastic lymphoma of the right cerebral hemisphere. A bone marrow examination revealed 6 % lymphoblasts. Cerebrospinal fluid (CSF) revealed 81 cells/mm leukocytes, with 82 % lymphoblasts. He showed no evidence of immunodeficiency, and a serological test for HIV was negative. Although optimal treatment of PCNSL in children has not yet been established, the effectiveness of combination chemotherapy for lymphoblastic lymphoma has been studied [3, 4]. We decided to treat the patient according to the protocol of pediatric advanced lymphoblastic lymphoma (ALBNHL03). An induction therapy regimen based on prednisone (60 mg/m daily for 5 weeks), vincristine (VCR) (1.5 mg/m on days 8, 15, 22, and 29), cyclophosphamide (1.0 g/m on day 8), daunorubicin (40 mg/m on days 8, 15, and 22), L-asparaginase (6,000 U/m on days 9, 11, 13, 16, 18, 20, 23, 25, and 27), and triple intrathecal therapy (methotrexate, cytarabine, and hydrocortisone, 12.5, 25, and 25 mg, respectively, on days 1, 15, and 29) (Fig. 2). Although he had shown rapid-onset obesity, no dose modification was made. His left-sided hemiparesis did not change; however, his mental status improved, and CSF tumor cells became negative on day 15. On day 27 of induction therapy, he developed peripheral neuropathy with pain. We stopped the induction therapy other than prednisone thereafter. However, the total bilirubin level was elevated to 2.1 mg/dl, with massive abdominal effusion and pain in the right upper quadrant on day 29. S. Yamamoto (&) K. Akiyama N. Oyama M. Hayashi Y. Fujimoto H. Ikeda K. Isoyama Division of Pediatrics, Department of Showa University Fujigaoka Hospital, 1-30 Fujigaoka Aoba-ku, Yokohama 227-8501, Japan e-mail: shohei-y@med.showa-u.ac.jp

Cutaneous Precursor B-Cell Lymphoblastic Lymphoma in Association With Epstein–Barr Virus

Precursor B-cell lymphoblastic lymphoma (B-LBL) is a rare high-grade neoplasm of immature B cells. Most of the reported cases in the literature represent cutaneous involvement in an existing systemic precursor B-LBL or leukemia rather than primary cutaneous disease. We report a rare case of primary cutaneous precursor B-LBL in an elderly male patient who presented with swelling and ulceration of his leg. Biopsy of the skin lesion showed precursor B-LBL. Immunohistochemistry was positive for terminal deoxytransferase, CD20, CD10, CD79a, and in situ hybridization was positive for Epstein-Barr virus. To our knowledge, this is the first report that shows an association between primary cutaneous precursor B-LBL with Epstein-Barr viral infection.