B-cell Lymphoma In Children Research Articles

MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma

Aggressive B-cell non-Hodgkin lymphomas (NHL) in children, adolescents, and young adults (CAYA) include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and a subset of high-grade tumors with features intermediate between these entities whose genetic and molecular profiles have not been completely elucidated. In this study, we have characterized 37 aggressive B-NHL in CAYA, 33 with high-grade morphology, and 4 DLBCL with MYC rearrangement (MYC-R), using targeted next-generation sequencing and the aggressive lymphoma gene expression germinal center B-cell-like (GCB), activated B-cell-like (ABC), and dark zone signatures (DZsig). Twenty-two tumors had MYC-R without BCL2 breaks, and two MYC-non-R cases had BCL6 translocations. MYC-R cases, including DLBCL, carried BL-related mutations and copy number alterations. Conversely, MYC-non-R lymphomas had alterations in the B-cell receptor signaling/NF-κB pathway (71%). DZsig was expressed in 12/13 of MYC-R tumors but only in 2/10 of MYC-non-R GCB tumors (P < 0.001). The 3-year event-free survival (EFS) of the whole cohort was 79.6%. TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL.

Evaluation of the Epstein–Barr virus occurrence at the present stage (literature review)

The purpose of this article is to review and analyze the foreign and domestic scientific papers to assess the Epstein-Barr virus (EBV) occurrence in the human population. &#x0D; A search of Russian and foreign publications in the PubMed and E-library databases was conducted. The high ecological and medical significance &#x0D; of EBV-infection is due to its global spread in the human population, lifelong persistence of EBV in the human body. Evidence has been collected EBV to be involved in the development of various somatic pathologies, such as rheumatic diseases and vasculitis, chronic kidney disease, cardiovascular pathologies, pathologies of the gastrointestinal tract, T- and B-cell lymphomas in children and adults, nasopharyngeal carcinoma. These diseases are the main causes of population disability and premature death not only in Russia, but also in the World. The deterioration of the ecological and epidemic situation for &#x0D; EBV-infection is associated with the other infectants spread that change the population immunological status. These include the human immunodeficiency virus, hepatitis B and C viruses, SARS-CoV-2, Mycobacterium tuberculosis. With the simultaneous persistence of these infectants, their synergistic or antagonistic effect on the human body occurs. In the modern World, the COVID-19 and the EBV-infection are simultaneously developing. It is difficult to say which infection is more significant in terms of medical, social. and economic losses of the human population. The EBV has been undeservedly given little attention. &#x0D; It is necessary to optimize preventive measures and epidemic surveillance for EBV-infection.

Development and validation of a nomogram for predicting cardiovascular mortality risk for diffuse large B-cell lymphoma in children, adolescents, and adults.

This study aimed to construct and validate a nomogram for predicting cardiovascular mortality (CVM) for child, adolescent, and adult patients with diffuse large B-cell lymphoma (DLBCL). Patients with only one primary tumor of DLBCL first diagnosed between 2000 and 2019 in the SEER database were extracted. We used the cumulative incidence function (CIF) to evaluate the cumulative rate of CVM. The outcome of interest was CVM, which was analyzed using a competing risk model, accounting for death due to other causes. The total database was randomly divided into a training cohort and an internal validation cohort at a ratio of 7:3. Adjustments were for demographics, tumor characteristics, and treatment modalities. Nomograms were constructed according to these risk factors to predict CVM risk at 5, 10, and 15 years. Validation included receiver operating characteristic (ROC) curves, time-dependent ROC, C-index, calibration curves, and decision curve analysis. One hundred four thousand six hundred six patients following initial diagnosis of DLBCL were included (58.3% male, median age 64 years, range 0-80, White 83.98%). Among them, 5.02% died of CVM, with a median follow-up time of 61 (31-98) months. Nomograms based on the seven risk factors (age at diagnosis, gender, race, tumor grade, Ann Arbor stage, radiation, chemotherapy) with hazard ratios ranging from 0.19-1.17 showed excellent discrimination, and calibration plots demonstrated satisfactory prediction. The 5-, 10-, and 15-year AUC and C-index of CVM in the training set were 0.716 (0.714-0.718), 0.713 (0.711-0.715), 0.706 (0.704-0.708), 0.731, 0.727, and 0.719; the corresponding figures for the validation set were 0.705 (0.688-0.722), 0.704 (0.689-0.718), 0.707 (0.693-0.722), 0.698, 0.698, and 0.699. Decision curve analysis revealed a clinically beneficial net benefit. We first built the nomogram model for DLBCL patients with satisfactory prediction and excellent discrimination, which might play an essential role in helping physicians enact better treatment strategies at the time of initial diagnosis.

Clinical and laboratory diversity of diffuse large B-cell lymphomas in children with Nijmegen breakage syndrome.

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Primary Mediastinal B-Cell Lymphoma in Children and Young Adults

Primary mediastinal B-cell lymphoma (PMBCL) is a rare but aggressive mature B-cell lymphoma that arises from thymic B cells and most commonly affects adolescents and young adults. PMBCL is now recognized by the WHO as a distinct entity from diffuse large B-cell lymphoma (DLBCL), not otherwise specified, with a unique clinical presentation and distinct morphologic features and molecular alterations. Similar to classic Hodgkin lymphoma, PMBCL tumors are characterized by alterations in the nuclear factor-κB and JAK/STAT pathways. These tumors also exhibit an immune evasion phenotype marked by upregulation of PD-L1 and loss of B2M. Historic data indicates that outcomes for pediatric patients with PMBCL are inferior compared with pediatric patients with DLBCL treated on the same protocols, and there is no current standard approach to initial treatment. Common regimens used for children with PMBCL include multiagent chemotherapy regimens designed for Burkitt lymphoma, such as Lymphomes Malins B (LMB)-based or Berlin-Frankfurt-Münster (BFM)-based chemotherapy ± rituximab. Based on initial data in adults showing excellent outcomes with the use of DA-EPOCH-R regimens, these regimens have also been adopted in pediatrics, although with mixed results. Novel agents are currently being studied in PMBCL with the goal of improving outcomes and reducing reliance on radiation and/or high-dose chemotherapy. Immune checkpoint blockade with PD-1 inhibition is of particular interest given the upregulation of PD-L1 in PMBCL and the known efficacy of these agents in the relapsed setting. Future efforts in PMBCL will also seek to determine the role of FDG-PET in evaluating response to therapy and the role of biomarkers in risk stratification.

Clinical analysis of 11 cases of high-grade B-cell lymphoma in children

Clinical analysis of 11 cases of high-grade B-cell lymphoma in children

Pediatric Aggressive Mature B-Cell Lymphomas, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.

Epi-O-08 - Primary cutaneous B-cell lymphomas in children and adolescents: a SEER population-based study

<h3>Background:</h3> The incidence of primary cutaneous B-cell lymphomas (PCBCL) in the pediatric population is unknown, and the information on pediatric PCBCL has mostly been gathered from individual case reports or series from single centers. <h3>Objective:</h3> To assess the incidence of PCBCL in the pediatric population (<20 years) compared with adult patients (≥20 years) and delineate its demographic and clinicopathologic characteristics. <h3>Methods:</h3> This was a population-based, retrospective cohort study of patients in 18 cancer registries in the United States diagnosed between 2000 to 2016 through the Surveillance, Epidemiology, and End Results (SEER) program. Age-adjusted incidence rates were calculated for PCBCL in pediatric and adult populations. Demographic, clinical, and pathological characteristics were compared between the two groups. <h3>Results:</h3> 5,128 adult and 48 pediatric PCBCL cases were included. The median age at diagnosis in the pediatric group was 16.5 years. The major histologic subtypes of pediatric cases were marginal zone lymphoma (77.1%), diffuse large B-cell lymphoma (12.5%) and follicle center lymphoma (10.4%), which significantly differed from the distribution in the adult group (p<0.001) where subtypes were equally distributed. The age-adjusted pediatric PCBCL incidence rate (per 1,000,000 person‐years) was 0.12 (95% CI 0.09-0.16) and incidence in the adult population was approximately 40-fold higher (IRR 41.4, 95% CI 31.2-56.2, P<0.001). All 48 pediatric cases were alive during a median follow-up time of 48 months. <h3>Conclusions:</h3> Pediatric PCBCL is a rare and indolent disease, which affects mostly adolescents of both sexes. Clinical presentation is similar to adults, but marginal zone subtype is significantly over-represented.

Primary Cutaneous B-Cell Lymphomas in Children and Adolescents: A SEER Population-Based Study

BackgroundAlthough primary cutaneous B-cell lymphomas (PCBCL) comprise 25% of all cutaneous lymphomas, their incidence in the pediatric population is unknown, and the information on pediatric PCBCL has mostly been gathered from individual case reports or series from single centers. Patients and MethodsThis was a population-based, retrospective cohort study of patients in 18 cancer registries in the United States diagnosed between 2000 to 2016 through the Surveillance, Epidemiology, and End Results (SEER) program. Age-adjusted incidence rates were calculated for PCBCL in pediatric (<20 years) and adult (≥20 years) populations. Demographic, clinical, and pathological characteristics of PCBCL were compared between the two groups. ResultsA total of 48 pediatric and 5128 adult PCBCL cases were included. Median age at diagnosis was 16.5 years and 65 years in the two groups, respectively. The major histologic subtypes of pediatric cases were marginal zone lymphoma (77.1%), followed by diffuse large B-cell lymphoma (12.5%) and follicle center lymphoma (10.4%), which were equally distributed in adults. The age-adjusted pediatric PCBCL incidence rate (per 1,000,000 person‐years) was 0.12 (95% CI 0.09-0.16). The incidence in the adult population was approximately 40-fold higher than the one observed in the pediatric group (IRR 41.4, 95% CI 31.2-56.2). All 48 pediatric cases were alive during a median follow-up time of 48 months. ConclusionsPediatric PCBCL is a very rare disease affecting mostly adolescents of both sexes. The major histologic subtype is marginal zone lymphoma, and the prognosis is favorable.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

Rare mature B‐cell lymphomas in children and adolescents

Pediatric-type follicular lymphoma (PTFL), pediatric nodal marginal zone lymphoma (pnMZL), and large B-cell lymphoma (LBCL) with IRF4 rearrangement have been introduced into the current World Health Organization (WHO) classification. They account for 5% to 10% of mature B-cell lymphomas in children and adolescents. Both PTFL and pnMZL predominantly affect male adolescents and usually present with localized lymphadenopathy in the head and neck region. The cells within the follicles of PTFL typically show high-grade cytology, IGH monoclonality and lack the t(14;18) chromosomal alteration. In contrast, pnMZL is characterized by progressive transformation of germinal center (PTGC)-like features and interfollicular proliferation of the cells with expansion of the marginal zones with diffuse areas. Watch and wait after complete resection seems an adequate therapy with chemotherapy restricted to incompletely resected disease. All children with PTFL and pnMZL reported, so far, survived. B-cell lymphomas presenting in the Waldeyer's ring are characterized by the expression of IRF4/MUM1 and often associated with IRF4 rearrangements. Because of the frequent diffuse component, treatment often follows current protocols for mature B-NHL. The prognosis is excellent.

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.

Paediatric cutaneous lymphomas: a review and comparison with adult counterparts.

Primary cutaneous lymphomas (CL) in children is rare. Only a few studies focused specifically on paediatric CL and therefore little is known whether primary CL in children are similar to or different from their adult counterparts with respect to the clinicopathological presentation, behaviour and prognosis. An extensive literature search using PubMed/MEDLINE from January 1995 through July 2014 was undertaken for articles reporting cases of paediatric CL. In addition, we identified 31 children with CL in our institutions. Mycosis fungoides and lymphomatoid papulosis are the two most prevalent lymphoma forms in children. A few entities of cutaneous lymphomas such as cutaneous diffuse large B-cell lymphoma leg type, and Sézary syndrome have not been reported so far in children. Other lymphoma entities such as hydroa vacciniforme-like lymphoma are mostly seen in certain geographic areas (Asia, Central and South America). In the paediatric population, low-malignant indolent forms such as primary cutaneous marginal zone lymphoma and primary cutaneous follicle centre lymphoma are very rare, whereas the more aggressive forms of B-cell lymphomas, precursor lymphoblastic lymphomas, and blastic plasmacytoid dendritic cell neoplasm are the most common forms in children, mostly involving the skin secondarily. Most paediatric lymphomas have similar clinicopathological features and course as their adults counterparts, particularly in the group of cutaneous T-cell lymphomas. The spectrum of cutaneous B-cell lymphomas in children significantly differs from the one in adults. Diagnostic work-up and treatment of paediatric patients with lymphomas are best achieved in close collaboration with paediatric haematopathologists and oncologists.

Epstein-Barr virus-positive diffuse large B-cell lymphoma in children: a disease reminiscent of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

Pediatric Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare disease in nonimmunocompromised hosts. In a review of 231 cases of malignant lymphoma (87 Hodgkin lymphoma and 144 non-Hodgkin lymphoma) occurring in Iraqi children, 7 cases (5% of NHLs) were classified as EBV+ DLBCL. Six children presented with nodal disease, and 1 presented with extranodal localization (bone). In all cases, the disease was at an advanced clinical stage (III/IV). Evidence of immunodeficiency (Evans syndrome and selective IgA deficiency) was observed in a single case. Two cases were "monomorphic" with immunoblastic histology, and 5 cases were "polymorphic" with histologic aspects reminiscent of nodular lymphocyte-predominant Hodgkin lymphoma (2 cases) and of CD30+ classical Hodgkin lymphoma (3 cases). In all cases, tumor cells were EBV infected (EBER+/LMP-1+), were medium-large B-cells (CD20+/CD79a+/PAX-5+/BOB-1+/OCT-2+) of non-germinal center (non-GC) origin (CD10-/MUM-1+), and had high proliferative activity (50%-70%). Chromosomal translocations involving BCL2, MYC, and IGH genes were not observed. IGH monoclonality could be demonstrated in 3 of 3 investigated cases. Six cases of EBV-negative DLBCL (4% of NHL) were present in the same series. All had monomorphic histology with centroblastic/immunoblastic morphology; 3 cases were of GC type and 3 of non-GC type. Our findings indicate that in Iraq, DLBCLs are 9% of NHLs. Moreover, 2 different types of the disease do exist; the EBV-positive cases, with strong histologic and immunohistochemical resemblance with EBV+ DLBCL of the elderly, and the EBV-negative cases, which are similar to the pediatric DLBCL usually observed in Western populations.

Antibody Therapy of Pediatric B-Cell Lymphoma

B-cell lymphoma in children accounts for about 10% of all pediatric malignancies. Chemotherapy has been very successful leading to an over-all 5-year survival between 80 and 90% depending on lymphoma type and extent of disease. Therapeutic toxicity remains high calling for better targeted and thus less toxic therapies. Therapeutic antibodies have become a standard element of B-cell lymphoma therapy in adults. Clinical experience in pediatric lymphoma patients is still very limited. This review outlines the rationale for antibody treatment of B-cell lymphomas in children and describes potential target structures on B-cell lymphoma cells. It summarizes the clinical experience of antibody therapy of B-cell lymphoma in children and gives an outlook on new developments and challenges for antibody therapy of pediatric B-cell lymphoma.

Clinical, pathological and genetic features of primary mediastinal large B-cell lymphomas and mediastinal gray zone lymphomas in children

Background Primary mediastinal large B-cell lymphoma is a rare lymphoma accounting for no more than 3% of all B-cell lymphomas in children and adolescents. However, patients in this young age group with this lymphoma have the shortest event-free survival of patients with any B-cell lymphoma under current standard chemotherapy protocols. Lymphomas with features intermediate between primary mediastinal large B-cell lymphoma and classical Hodgkin's lymphoma (mediastinal gray zone lymphomas) have been acknowledged in the latest World Health Organization classification. Recent studies suggest that mediastinal gray zone lymphomas have an aggressive clinical course whereas patients, at least adult ones, with primary mediastinal large B-cell lymphoma might respond very well to chemotherapy in combination with anti-CD20 antibody. We aimed to evaluate whether biological differences or so far unrecognized admixed mediastinal gray zone lymphomas might explain the relatively poor outcome of pediatric patients with apparent primary mediastinal large B-cell lymphoma. We, therefore, performed a retrospective histopathological, immunohistochemical and interphase cytogenetic analysis of 52 pediatric lymphomas. The childhood primary mediastinal large B-cell lymphomas (n=44) showed a similar pattern of histology, immunophenotype and gains at 9p (59%) and 2p (41%) as adult cases, as determined from published data. We identified only four so far unrecognized cases of mediastinal gray zone lymphoma among 52 lymphomas registered in previous trials. Conclusions Mediastinal gray zone lymphoma is very rare in children and adolescents. It does, therefore, seem unlikely that these lymphomas account for the unsatisfactory clinical results with current therapy protocols in pediatric patients. These data have major implications for the design of future treatment protocols for mediastinal lymphomas in children and adolescents.

Tissue Expression of Interleukin 2 (IL-2) and IL-2 Receptor (IL-2Rα/CD25) in non-Hodgkin B-cell Lymphomas in Children

The study aimed at analysis of tissue expression of interleukin 2 (IL-2) and subunit alpha of its receptor (IL-22R(alpha)/CD25) in B-cell non-Hodgkin lymphomas (B-cell NHLs) in children as related to selected clinical data. The studies were performed on an archival tissue material originating from children with B-cell NHLs (n=26) using avidin-biotin-peroxidase complex method and in-situ hybridization with biotinylated tyramine amplification signal (ImmunoMax technique). As compared with non-neoplastic lesions, in B-cell NHLs a significantly higher expression was noted of both IL-2 and IL-22R(alpha). In children with B-cell NHLs, frequency of IL-2 detection was 62%, and that of IL-22R(alpha), 46%. Using hybridocytochemistry, presence of mRNA for IL-2 could be detected, but not mRNA for IL-22R(alpha) in children with B-cell NHLs. A significant direct relationship was demonstrated between expressions of IL-2 and IL-22R(alpha) in children with B-cell NHLs. No significant relationships could be detected between expression of IL-2 and/or IL-22R(alpha) on one hand and histopathologic diagnosis, tumor location, age, or sex in B-cell NHLs on the other. The new element in the results involved demonstration of significant differences in shorter survival of children with B-cell NHLs, as related to cellular expression of IL-2 and IL-22R(alpha) (CD25). Comparing the expected percentage of patients at risk, children with CD25-positive tissue expression had a significantly lower chance to survive longer time than children with IL-2-positive tissue expression. The positive relationship between tissue expression of IL-22R(alpha) and the shorter survival of children with B-cell NHLs should prompt further investigations to identify other risk factors in patients with this type of tumors in children.

Nodal Diffuse Large B-cell Lymphomas in Children and Adolescents: Immunohistochemical Expression Patterns and c-MYC Translocation in Relation to Clinical Outcome

Diffuse large B-cell lymphoma (DLBCL) is a very infrequent neoplasm in the pediatric age group; therefore there are very few studies on the immunophenotype or genetics of these cases. We studied a series of 16 patients with nodal DLBCL occurring in patients between 10 and 18 years of age. The cases were classified according to the 2008 World Health Organization classification criteria, with application of immunohistochemistry for the detection of CD10, BCL-6, and MUM1 proteins to divide the lymphomas into germinal center and nongerminal center types. In addition, TCL1, BCL-2 expression, and the Ki-67 proliferation index were evaluated by immunohistochemistry, and c-MYC and BCL2 translocations were evaluated by fluorescence in situ hybridization. All these parameters were correlated with clinical features and outcome. Our study revealed that centroblastic morphology and the germinal center type of DLBCL are more prevalent in these young patients (63%), with 37% containing a c-MYC translocation. Only 1 case showed a BCL2 translocation, reflecting a double-hit case with features intermediate between DLBCL and Burkitt lymphoma. We found a higher frequency of BCL-2 expression than previously reported, with no direct influence on the outcome of the disease in univariate or multivariate analysis. The expression of TCL1 has not been specifically studied in nodal pediatric DLBCL before; we found a 31% incidence of TCL1 expression. MUM1 expression was observed in 44% of the cases and these positive cases showed a significant negative impact on clinical outcome. TCL1 is directly and significantly associated with the presence of c-MYC and a high proliferative index. The germinal center and nongerminal center subtypes showed significant differences for both overall survival and disease-free interval. c-MYC translocation was found in 37% of patients, and had a favorable impact on clinical outcome. We conclude that nodal pediatric and adolescent DLBCL are mainly of the germinal center type, with a generally good outcome despite the frequent expression of BCL-2 and the presence of c-MYC translocation. TCL1 expression seems to be associated with a good clinical outcome, whereas MUM1 expression predicts a poor clinical outcome.

Mature B-Cell Lymphoma in Children and Adolescents

In pediatric mature B-cell non-Hodgkin lymphoma, international pathologist diagnostic agreement was previously evaluated using the Revised European-American Lymphoma Classification. Surgical biopsy histology technical quality (HTQ) is variable and may affect diagnostic accuracy. This study evaluated diagnostic agreement correlated with HTQ. Surgical biopsies obtained from international protocol FAB LMB96 Treatment of Mature B-Cell Lymphoma/Leukemia for Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and high-grade B-cell lymphoma Burkitt-like (BLL), were independently reviewed by hematopathologists from 3 national groups (Children's Cancer Group, Société Française d'Oncologie Pédiatrique, and United Kingdom Children's Cancer Study Group) to determine each national diagnosis and a final diagnosis. HTQ grades for microscopic tissue sections included: good; medium; low; inconclusive. Final diagnoses in 187 cases included: BL 87 (47%); BLL 20 (11%); DLBCL 64 (34%); other 16 (9%). HTQ grades included: good 10 (5%); medium 100 (54%); low 75 (40%); inconclusive 2 (1%). The rate of uniform agreement between the national diagnoses was significantly higher with good or medium HTQ (62%) than with low HTQ (33%) (P = 0.001). In conclusion, in pediatric mature B-cell non-Hodgkin lymphoma, international pathologist diagnostic agreement is significantly higher in surgical biopsies with better HTQ. Poor HTQ may adversely impact diagnostic ability and affect prognosis and therapeutic management when different treatment regimens are employed for DLBCL versus BL/BLL.

Pediatric Follicular Lymphomas, Marginal Zone Lymphomas, and Marginal Zone Hyperplasia

Whereas most B-cell lymphomas in children are of diffuse large B-cell or Burkitt type, other B-cell lymphomas, including follicular and marginal zone B-cell lymphomas, rarely occur Pediatric follicular lymphomas (FLs) have many features indistinguishable from those seen in adults but demonstrate an increased proportion that are localized, lack bcl-2 protein expression, lack bcl-2 translocations, and are grade 3 but still indolent. They also tend to have large expansile follicles. Although usually at nodal or tonsillar sites, other extranodal involvement also occurs, with FL of the testis well described. Distinction from potentially clonal but reactive follicular hyperplasia is important. Marginal zone B-cell lymphomas of nodal and extranodal types are other indolent B-cell neoplasms that usually are seen in adults but also occur in children. The differential diagnosis must include the very recently reported lambda light chain class-restricted marginal zone hyperplasias of the tonsil or appendix that might closely mimic a lymphoma. Understanding the full spectrum of B-cell neoplasia in children and its unique features is important for diagnostic, therapeutic, and academic purposes.