Pediatric Follicular Lymphoma Research Articles

편도선 절제술 후 진단된 소아 모낭 림프종 1례

Follicular lymphoma is a characteristic clinicopathologic term of centrioles and centroblasts of germinal center B cell origin. Pediatric follicular lymphoma is a variant type of follicular lymphoma in children. Unlike follicular lymphoma, pediatric follicular lymphoma is an indolent lymphoma that rarely recurs and progresses to other organs, but has no clear diagnostic criteria. The authors report and review a case of pediatric follicular lymphoma diagnosed by tonsillectomy for recurrent tonsillitis. (J Clinical Otolaryngol 2021;32:291-295)

A Case of Pediatric Follicular Lymphoma in the Parotid Gland

Pediatric follicular lymphoma (PFL) is rare, and it has distinctive characteristics compared to adult-type follicular lymphoma. PFL mainly occurs in males and is likely to be localized to cervical lymph nodes and tonsils. Extranodal type PFL also occurs in the testis, epididymis, skin, gastrointestinal tract, and parotid gland, etc. The prognosis of PFL is better than adulttype follicular lymphoma. Surgical excision is a good option, and the majority of PFL cases show complete remission after surgery. We have encountered a case of PFL of the parotid gland in a 12-year-old boy. Here, we report this case with a review of the literature.

IRF4 translocation status in pediatric follicular and diffuse large B-cell lymphoma patients enrolled in Children's Oncology Group trials.

Large B-cell lymphoma with IRF4 rearrangement is a provisional entity in the 2017 World Health Organization classification. In order to characterize these lymphomas in children from the United States, IRF4 FISH and immunohistochemical stains were performed on 32 follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) from Children's Oncology Group studies. Two DLBCLs (6%) had IRF4 rearrangements, one involving the ileocecal valve and another involving the tonsil and cerebrospinal fluid. Both cases had strong, diffuse IRF4/MUM1 immunohistochemical staining, which may be a pathologic clue to the diagnosis. Reclassification of these cases may have prognostic and therapeutic implications.

A high definition picture of key genes and pathways mutated in pediatric follicular lymphoma

Mature B-cell lymphomas in childhood are a welldefined group of B-cell neoplasms, encompassing both aggressive and indolent tumors. Biologically, indolent pediatric B-cell lymphomas derive from either germinal center B cells [follicular lymphoma (FL)] or B cells outside the germinal center (marginal

Pediatric follicular lymphoma of the parotid gland.

Primary malignant lymphoma rarely presents as a mass in the salivary gland. It accounts for about 1% of salivary gland tumors. The lymphomas of the parotid gland are mainly non-Hodgkin’s lymphoma of B-cell follicular type. It usually occurs in male adults and is very rare in children. In contrast to the intractable disease course of adult parotid follicular lymphoma, when occurred in children or adolescent, its prognosis is very good when it is first treated with surgical excision. Thus, a solitary follicular lymphoma in an extranodal site that has occurred in children is termed separately as pediatric follicular lymphoma (PFL). We share our treatment experience of a 16-year-old PFL patient through surgical removal combined with superficial parotidectomy. In line with the few previous case reports of PFL, we suggest that active surgical removal should be undertaken for solitary, extranodal follicular lymphoma of the pediatric and adolescent population.

Pediatric follicular lymphoma in Japan.

Follicular lymphoma (FL) is quite rare in children. There have been only two major reports on pediatric FL. The present retrospective study on pediatric FL in Japan, including FL with diffuse large B cell lymphoma (DLBCL), analyzed data from 1991 to 2014. Twenty-two patients with pediatric FL were analyzed. Sixteen patients were boys and six were girls. Median age of onset was 9years (range 4-17years). In 11 patients, DLBCL co-existed with FL. The initial lesions involved cervical lesions in 16 patients, and the abdomen in six. With regard to stage of disease at diagnosis, 17 patients were at stage I or II, four were at stage III, and one was at stage IV. Chemotherapy was administered in 18 patients, and only resection was performed in four patients. Mature B lymphoma regimens were selected for 17 patients who received chemotherapy. Although two patients relapsed, all patients are currently alive and disease free. The median follow-up period was 54.5months (range 6-126months). Patients having FL with DLBCL were younger compared with those having FL, and this disease was more frequently observed in female patients. Our data revealed that FL in Japanese children is a tumor with good prognosis, as in reports from the United States and Europe.

Clinical, Biological Characteristics and Outcome of Pediatric Follicular Lymphoma at Children's Cancer Hospital - Egypt: A Single Center Experience

Background: Pediatric follicular lymphoma is a rare entity that had been provisionally included in the WHO classification of hematologic malignancies. Unlike adults, pediatric follicular lymphoma patients usually presents with localized nodal disease, are translocation (14; 18) and BCL2 negative. It shows different clinical behavior and thus distinct outcome. We analyzed the three pediatric follicular lymphoma cases presented to Children's Cancer Hospital- Egypt (CCH-E) during the period from July 2007 to December 2014.Results: All patients presented with localized stage II disease, responded well to R-CHOP chemotherapy (Rituximab target therapy with conventional CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). One of them received involved field radiotherapy in addition. All patients are in continuous complete remission. The first case: A male patient 7 years old who presented with left upper deep cervical lymph node with B symptoms (fever and night sweets). Biopsy was taken, partial effacement of the nodal structure and obliteration of the sub-capsular sinus by confluent follicles, intermediate and large cells were seen microscopically. Immunohistochemical staining showed positivity to CD20 and BCL6 and negative reaction to CD3 and BCL2. MIB-1 index was high (80%). The diagnosis of diffuse large cell B-cell lymphoma in 40% of cells and pediatric follicular lymphoma grade 3a in the remaining 60% was made. The patient received 8 cycles of R-CHOP and placed under follow up from July 2011 till now.He is in complete remission. The second case: A male patient 8 years old who presented in March 2013 with recurrent right pre-auricular lymph node. Repeated biopsies were done, all revealed atypical lymphoid hyperplasia. The patient was placed under follow up till April 2014 when he presented with large right parotid mass from which another biopsy was taken. Microscopic examination revealed effaced nodal architecture by evenly distributed large uniform, crowded follicles & nodules, populated by centroblasts intermixed with centrocytes consistent with grade 3a follicular lymphoma. Some foci displayed diffuse pattern with evident extra nodal extension. Immunohstochemical staining showed positive reaction to CD20 and BCL6 while negative reaction to BCL2 and low expression of Ki-67. The diagnosis of pediatric follicular NHL, predominantly grade 3a was made. He received 6 cycles of R-CHOP, evaluation post 3rd cycle was in complete remission by CT and PET scan He completed 6 courses of R-CHOP followed by involved field radiotherapy. He is under follow up since April 2015 till now ; alive and in complete remission. The third case is also for a male patient 12 years old who presented with left parotid and bilateral cervical lymph node enlargement. Initial PET-CT was negative. Cervical lymph node biopsy showed partial effacement of lymph node architecture with observed vague follicular pattern as well as diffuse infiltrate dominantly composed of centroblastic neoplastic lymphoid cells admixed with centrocytes . Immunohostochemical staining revealed positive reaction to CD20 in the neoplastic large cells. BCL2 highlighted mainly the neoplastic cells mainly of diffuse pattern. BCL6 and CD10 highlighted the deformity of neoplastic follicles by growth of neoplastic cells. CD21 stained admixed follicular dendritic cells. Ki-67 labeling index was high (60%). The diagnosis of follicular NHL, mixed follicular and diffuse, grade 3 a was made. He received 6 cycles of R-CHOP, was in complete remission post the third cycle by CT evaluation and is currently under follow up since March 2015.In conclusion, pediatric follicular lymphoma patients presented to our center had localized disease, responded well to R-CHOP chemotherapy and had durable complete remission. DisclosuresNo relevant conflicts of interest to declare.

Bilateral conjunctival pediatric follicular lymphoma

Follicular lymphoma (FL) is the most common type of B cell non-Hodgkin lymphoma in Western counties. FL is usually seen in adults and is very uncommon in pediatric population. Pediatric follicular lymphoma (PFL) is a rare indolent lymphoma characteristically seen in pediatric population, usually involving cervical lymph nodes, Waldeyer ring, and testis. They pose significant diagnostic challenges due to morphologic overlap with much more common florid follicular hyperplasia and lack of typical t(14;18)IgH/BCL2 fusion and BCL-2 protein expression. We present the case of a 10-year-old male with bilateral conjunctival nodules, showing characteristic morphologic and immunophenotypic features of PFL with demonstrated clonal B cell immunoglobulin heavy chain gene rearrangement. Of note, the neoplastic cells expressed MUM1, MYC, and IgM, suggestive of a different disease pathogenesis from adult FL.

Clinical analysis of 14 cases of rare non-Hodgkin lymphoma in children

Objective To analyze the clinical characteristics and prognosis of 4 rare types of non-Hodgkin lymphoma(NHL) in children, and to discuss the progress in treatment. Methods Clinical data of 14 patients with rare types of NHL at Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine between January 2004 and December 2014 were retrospectively analyzed, and their clinical features, treatment and prognosis were discussed. Results Fourteen cases were reported including 6 subcutaneous panniculitis-like T-cell lymphoma(SPTCL), 3 hydroa vacciniforme-like cutaneous lymphoma(HVLL), 2 pediatric follicular lymphoma(PFL) and 3 extranodal NK/T-cell lymphoma, and nasal type(ENKTL). Ten patients (71.4%) primarily presented with skin lesions and underwent a long course of illness before they were finally diagnosed (the median was 10 months), 71.4%(10/14 cases) of them associated with fever and 50.0%(7/14 cases) with liver and spleen enlargement, and no evidence of central nervous system (CNS) and bone marrow (BM) involvement was observed, while 28.6% patients (4/14 cases) had more than two lines' abnormalities in peripheral blood examination.Since there were no standard treatment guidelines, most patients received CHOP (Cyclophosphamide+ Adriamycin+ Vincristine+ Prednisone) and/or mature B-cell NHL-like therapy, and 50.0%(7/14 cases) of them received interferon therapy in addition, while 1 patient received allogeneic hematopoietic stem cell transplantation after recurrence.The complete remission was achieved in 71.4%(10/14 cases) of all the patients.Two of them died, 3 lost follow-up, and 1 relapsed.The 3-year overall survi-val and event free survival rates were 0.84 and 0.57, respectively, after a median follow-up of 26 months (range 12-64 months). Conclusions Pediatric rare types of NHL show atypical clinical manifestation, low incidence of CNS/BM infiltration and long course.It is hard to make pathological diagnosis and differentiation.It is also inappropriate to apply the commonly used staging system to these rare types of NHL.No standard treatment has been found by now.SPTCL, HVLL and PFL have relatively good outcomes when treated with mature B-cell NHL-type therapy plus interferon therapy. Key words: Subcutaneous panniculitis-like T-cell lymphoma; Hydroa vacciniforme-like cutaneous lymphoma; Pediatric follicular lymphoma; Extranodal NK/T-cell lymphoma, nasal type; Child

Whole Exome Sequencing Defines the Genetic Differences Between Pediatric and Adult Follicular Lymphoma

Follicular lymphoma (FL) is the most common low grade lymphoma in adults, but uncommon in children. While the two diseases are similar in morphology and immunophenotype, pediatric-type FLs manifest higher grade histology with most cases being localized and curable with standard therapy. Pediatric-type FLs are thought arise from germinal center B cells and typically demonstrate higher expression of the germinal center B cell markers BCL6 and CD10.While the genetic basis of adult FL has been studied previously, the genetic basis of pediatric-type FL remains largely unknown. In this study, we sought to define the gene coding mutations occurring in pediatric FL and compared them to those of 48 adult FLs, as well as other adult lymphomas derived from germinal center B cells including 88 GCB DLBCLs and 67 cases of BL that we, and others, have published previously.We obtained a total of 32 pediatric-type FLs along with paired normal tissue. The median age wa 8 years with 62% male patients. We performed whole-exome sequencing for these cases using the Agilent solution-based system of exon capture, which uses RNA baits to target all protein coding genes (CCDS database), as well as ~700 human miRNAs from miRBase (v13). In all, we generated over 6 GB of sequencing data using high throughput sequencing on the Illumina platform.Using bioinformatics approaches that we have described previously, we identified 26 candidate cancer genes that were recurrently somatically mutated in pediatric FL. We found that the genes mutated in pediatric FLs were from three predominant ontologies/pathways. These included DNA damage repair (40%, ATM, RB1), chromatin modification (34%, SETD2, SMARCA4 and TET2) and alternative splicing (12%, SF3B1). We also noted IRF4 translocations and TNFRSF14 mutations in 10% of the cases as has been described previously.We further compared pediatric FLs to other germinal center B cell derived lymphomas and, in particular, FLs occurring in adults. We found that the mutations that characterize adult FLs including MLL2, CREBBP, and GNA13 were absent in pediatric FLs. There was only one pediatric FL case with an EZH2 mutation, which otherwise occur commonly in germinal center B cell derived lymphomas.Thus, pediatric FLs are genetically unlike both adult FLs and other germinal center B cell derived lymphomas. Our data provide new clues to the distinctive genetic basis of these tumors and their clinical behavior. DisclosuresNo relevant conflicts of interest to declare.

Burkitt Lymphoma Has Lower CD58 Expression Than Other B Cell Malignancies in Children

Introduction: Burkitt Lymphoma (BL) is a highly aggressive mature B cell neoplasm comprising 30% of Non-Hodgkin lymphoma in children. BL can be difficult to discriminate from other mature B cell lymphomas, and distinguishing BL from Diffuse Large B Cell Lymphoma (DLBCL) is a commonly encountered diagnostic dilemma. While c-myc translocation as detected by fluorescence in situ hybridization is more often associated with BL, DLBCLs may also have the translocation, and therapy is often started prior to obtaining this result. Early and rapidly obtained diagnostic clues would therefore be helpful to establish the appropriate therapeutic regimen. CD58 (aka LFA-3) is a cell adhesion molecule typically found on antigen presenting cells and is highly overexpressed in B-lymphoblastic leukemia (B-LL)(Chen et al, Blood 2001). In contrast, CD58 expression decreases as physiologic B cells mature in the bone marrow (Lee et al, Am J Clin Pathol 2005). Despite findings of abnormal CD58 expression in B-LL, CD58 expression by flow cytometry in BL and other mature B lymphomas, including DLBCL, has not been previously described in children or adults. Thus our objective was to investigate quantitative CD58 expression in BL and other pediatric B cell malignancies by flow cytometry.Methods: CD58 has been included in the flow cytometry diagnostic panel for all hematopoietic malignancies at our institution since 2009. In a single center retrospective study, we reviewed flow cytometry data from clinical specimens obtained at initial diagnosis of BL (n=18) and other mature B lymphomas (n=16) from 2009-2015. The "other mature B lymphomas" group consisted of DLBCL (n=6), post-transplant lymphoproliferative disorder (n=3), primary mediastinal large B cell lymphoma (n=2), pediatric follicular lymphoma (n=2), B-cell lymphoma unclassifiable with features intermediate between DLBCL and BL (n=2), and extranodal marginal zone lymphoma (n=1). We also investigated CD58 expression of consecutive initial diagnostic bone marrow aspirates of B-LL (n=20) and Stage I-III hematogones (n=25) from bone marrow aspirates of patients with benign hematologic conditions (all from 2014). All samples included in this analysis were from patients 18 years of age or younger. CD58 expression was quantified as arbitrary mean fluorescence intensity (MFI) units. Initial comparisons were performed using a Kruskal-Wallis test, with post-hoc pairwise comparisons computed with the Nemenyi test.Results: CD58 expression by BL was found to be low (median MFI 427). In contrast, other mature B lymphomas and B-LL had significantly higher expression of CD58 when compared to BL (median MFI 1480 and 2342 respectively, p<0.0001 for both). Specifically, BL had lower CD58 expression than the DLBCL subgroup (n=6, median MFI 2142, p=0.0008). CD58 expression in BL was similar to that of Stage III hematogones/mature B lymphocytes (median MFI 569).Conclusions: Our data suggest that CD58 expression is significantly lower in BL compared to DLBCL, other mature B lymphomas, B-LL, and maturing B cells in pediatric patients. CD58 expression may be a useful diagnostic tool to discriminate BL from other pediatric B cell malignancies. Consistent with our data, low expression of cell adhesion molecules LFA-1 and CD58/LFA-3 in cultured Burkitt cell lines has been demonstrated previously (Billaud et al, Blood 1990), and our findings support the previous data. The authors also hypothesized that decreased expression of CD58 may serve as a mechanism of immune escape in BL. Correlation of CD58 surface proteins with RNA expression may be a first step to elucidate mechanistically why BL cells have decreased CD58, and how that may provide a survival advantage. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Metachronous/concomitant B-cell neoplasms with discordant light-chain or heavy-chain isotype restrictions: evidence of distinct B-cell neoplasms rather than clonal evolutions.

Metachronous/concomitant B-cell neoplasms with distinct morphology are usually considered clonally related. We retrospectively analyzed 4 cases of metachronous/concomitant B-cell neoplasms with discordant light-chain/heavy-chain restrictions. The primary diagnoses included chronic lymphocytic leukemia (CLL; n = 2), lymphoplasmacytic lymphoma (n = 1), and pediatric follicular lymphoma (FL; n = 1). The respective secondary diagnoses included diffuse large B-cell lymphoma (DLBCL; n = 2), plasmablastic myeloma, and pediatric FL. The secondary B-cell neoplasm occurred after the primary diagnosis in 3 cases, with the median interval of 120 months (range, 21-216), whereas the remaining 1 case had the 2 neoplasms (CLL/DLBCL) diagnosed concurrently. Histology suggested aggressive transformation in 3 cases and recurrence in 1 case (FL). Nonetheless, 3 cases showed discordant light-chain restrictions between the 2 B-cell neoplasms, whereas in the remaining case (lymphoplasmacytic lymphoma/plasmablastic myeloma), the 2 neoplasms shared κ light-chain restriction but expressed different heavy-chain isotypes (IgM versus IgA). The 2 CLL/DLBCL cases had polymerase chain reaction-based IGH/K gene rearrangement study and amplicon sequence analysis performed, which demonstrated distinct clonal amplicons between the 2 B-cell neoplasms in each case. Concomitant/metachronous B-cell neoplasms may be clonally unrelated, which can be confirmed by immunoglobulin isotype analysis and/or genotypic studies. We advocate analysis of clonal identities in large cell transformation or recurrent disease compared with primary indolent B-cell neoplasm because of a potential difference in prognosis between clonally related and unrelated secondary B-cell neoplasms.

Pathology of follicular lymphoma.

Follicular lymphoma (FL) is a heterogeneous disease, and there are many different subgroups, such as in terms of age of onset, involved organ (especially extranodal sites such as gastrointestinal tract) and genetic abnormality. Grade 3B is currently regarded as a distinct entity by molecular genetic analyses, but the independence of Grade 3A remains unclear. Variations of clinical course are known in FL. Some cases are very indolent, but others are not. The latter cases show histological transformation to diffuse large B-cell lymphoma (DLBCL) (high-grade transformation) and an aggressive course. Histological transformation to DLBCL is reported to occur in about 30-40% of patients, at a rate of about 3% each year. However, it reaches a plateau at about 16 years, so the stratification of patients in whom transformation would or would not occur is very important for the therapeutic strategy. From genome-wide analysis by next-generation sequencing, EZH2, CREBBP and MLL2, which are histone-modifying genes, have been shown to be frequently mutated in FL and to have an important role in lymphomagenesis. IGH-BCL2 translocation and CREBBP mutations are early events, whereas MLL2 and TNFSFR14 mutations represent late events during disease evolution. In the 2008 WHO classification, three new variants: (1) pediatric follicular lymphoma, (2) primary intestinal follicular lymphoma and (3) in situ follicular lymphoma, are included. Pathologists and clinicians should consider these new developments when deciding on the diagnostic and therapeutic strategy.

Small B-cell lymphomas. Diagnosis of malignant lymphomas in 2014

The 2008 WHO classification of tumors of hematopoietic and lymphoid tissues has adopted consensus guidelines for the definition of well-defined entities. The major principle of the classification is the recognition of distinct diseases according to a combination of morphology, immunophenotype, genetic, molecular and clinical features. These disease entities are stratified according to their cell lineage and their derivation from precursor or mature lymphoid cells. Although the new 2008 WHO classification intentionally does not divide lymphomas by grade, traditionally mature B-cell lymphomas composed mainly of small lymphocytes have been called low-grade lymphomas. These small B-cell lymphomas include chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL), follicular lymphoma (FL), nodal marginal zone lymphoma (MZL), MALT lymphoma, hairy cell leukemia, and lymphoplas-macytic lymphoma (LPL). An entity that should be included in the differential diagnosis of lymphomas composed mainly by small lymphocytes but with a rather aggressive behaviour is mantle cell lymphoma (MCL). As a consequence of new and better available techniques in routine diagnosis, an increased recognition of early and precursor lesions of lymphoid neoplasms has emerged. This talk aims to review the morphological and phenotypic characteristics of the most frequent small B-cell lymphomas and expand on emerging concepts like, BCL2 negative FL, grading of EL, Pediatric FL, and indolent and cyclin Dl negative MCL, differential diagnosis of CD5+ low-grade lymphomas and more.

Children and adolescents with follicular lymphoma have an excellent prognosis with either limited chemotherapy or with a “watch and wait” strategy after complete resection

Data on clinical features and outcome in pediatric follicular lymphoma (pFL) are scarce. The aim of this retrospective study including 13 EICNHL and/or i-BFM study group members was to assess clinical characteristics and course in a series of 63 pFL patients. pFL was found to be associated with male gender (3:1), older age (72% ≥10years old), low serum LDH levels (<500U/l in 75%), grade 3 histology (in 88%), and limited disease (87% stage I/II disease), mostly involving the peripheral lymph nodes. Forty-four out of sixty-three patients received any polychemotherapy and 1/63 rituximab only, while 17/63 underwent a "watch and wait" strategy. Of 36 stage I patients, 30 had complete resections. Only one patient relapsed; 2-year event-free survival and overall survival were 94 ± 5 and 100%, respectively, after a median follow-up of 2.2years. Conclusively, treatment outcome in pFL seems to be excellent with risk-adapted chemotherapy or after complete resection and an observational strategy only.

„In-situ-Lymphome“ und andere Frühstadien maligner Non-Hodgkin-Lymphome

The increasing use of immunohistochemical and molecular investigations of lymphatic tissues results in more frequent detection of early lymphoid proliferations. These show some but not all features of malignant lymphomas without fulfilling the diagnostic criteria for the diagnosis of lymphoid malignancy. In addition to well-known premalignant B-cell proliferations, such as monoclonal gammopathy of unknown significance (MGUS) and monoclonal B-cell lymphocytosis (MBL), so-called in situ lymphomas have recently been described with minimal infiltrates of clonal B-cells in morphologically reactive lymphoid tissues which show the phenotypic and genetic features of specific B-cell lymphoma subtypes and often show a characteristic topographical distribution. This article addresses a group of clonal lymphoproliferations with usually localized disease and excellent clinical prognosis, such as pediatric follicular lymphoma and nodal marginal zone lymphoma. Another group of early lesions not addressed in this review are virally induced lymphoproliferations which represent a grey zone between purely reactive lesions and malignant lymphomas and may pose significant diagnostic as well as clinical problems. In this review diagnostic criteria for early or in situ lesions and their distinction from partial infiltration by malignant lymphoma are described.

Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas

Pediatric follicular lymphoma is a rare disease that differs genetically and clinically from its adult counterpart. With the exception of pediatric follicular lymphoma with IRF4-translocation, the genetic events associated with these lymphomas have not yet been defined. We applied array-comparative genomic hybridization and molecular inversion probe assay analyses to formalin-fixed paraffin-embedded tissues from 18 patients aged 18 years and under with IRF4 translocation negative follicular lymphoma. All evaluable cases lacked t(14;18). Only 6 of 16 evaluable cases displayed chromosomal imbalances with gains or amplifications of 6pter-p24.3 (including IRF4) and deletion and copy number neutral-loss of heterozygosity in 1p36 (including TNFRSF14) being most frequent. Sequencing of TNFRSF14 located in the minimal region of loss in 1p36.32 showed nine mutations in 7 cases from our series. Two subsets of pediatric follicular lymphoma were delineated according to the presence of molecular alterations, one with genomic aberrations associated with higher grade and/or diffuse large B-cell lymphoma component and more widespread disease, and another one lacking genetic alterations associated with more limited disease.

Early lesions in lymphoid neoplasia

The increasing use of immunophenotypic and molecular techniques on lymphoid tissue samples without obvious involvement by malignant lymphoma has resulted in the increased detection of "early" lymphoid proliferations, which show some, but not all the criteria necessary for a diagnosis of malignant lymphoma. In most instances, these are incidental findings in asymptomatic individuals, and their biological behaviour is uncertain. In order to better characterize these premalignant conditions and to establish diagnostic criteria, a joint workshop of the European Association for Haematopathology and the Society of Hematopathology was held in Uppsala, Sweden, in September 2010. The panel reviewed and discussed more than 130 submitted cases and reached consensus diagnoses. Cases representing the nodal equivalent of monoclonal B-cell lymphocytosis (MBL) were discussed, as well as the "in situ" counterparts of follicular lymphoma (FL) and mantle cell lymphoma (MCL), topics that also stimulated discussions concerning the best terminology for these lesions. The workshop also addressed the borderland between reactive hyperplasia, and clonal proliferations such as pediatric marginal zone lymphoma and pediatric FL, which may have very limited capacity for progression. Virus-driven lymphoproliferations in the grey zone between reactive lesions and manifest malignant lymphoma were covered. Finally, early manifestations of T-cell lymphoma, both nodal and extranodal, and their mimics were addressed. This workshop report summarizes the most important conclusions concerning diagnostic features, as well as proposals for terminology and classification of early lymphoproliferations and tries to give some practical guidelines for diagnosis and reporting.

Besonderheiten der histopathologisch-genetischen Diagnose und Klassifikation von Lymphomen im Kindes- und Jugendalter

Malignant lymphoma along with leukemias account for nearly half of all malignancies arising in childhood and adolescence. The correct tissue-based histopathological diagnosis of lymphomas results from a close interdisciplinary exchange between pediatric oncologists and hematopathologists. We describe here relevant features of lymphoma subtypes arising in the young age group, Burkitt lymphoma, precursor/lymphoblastic lymphomas, anaplastic large cell lymphoma and diffuse large B-cell lymphoma as well as primary mediastinal B-cell lymphoma and the rare pediatric follicular lymphomas. Special focus is put on specific diagnostic difficulties as well as new insights into biological features of pediatric lymphomas in comparison with their adult counterpart. In addition the relevance of newly defined lymphoma entities of the WHO-classification 2008, e.g. greyzone lymphomas, will be discussed for the young age group.

Pediatric Follicular Lymphoma: A Report of the First 3 Cases From Taiwan and Literature Review

Follicular lymphoma (FL) is a common lymphoma entity in adults but is rare in children. As opposed to adult cases, pediatric FL is characterized by a high-grade histology, low-stage disease, a lower frequency of both bcl-2 protein expression and BCL2 gene rearrangement, and a more favorable prognosis. During the authors’ previous study of pediatric Burkitt lymphoma, they identified 3 cases of pediatric FL. Here the authors present the first series of pediatric FL from Taiwan. The patients were 2 boys and 1 girl, aged from 7 to 14. The presentation sites were cervical lymph node in 2 and tonsil in 1. All cases showed large neoplastic nodules comprising sheets of centroblasts, corresponding to grade 3b FL. Two of the 3 tumors weakly expressed bcl-2 protein. Fluorescence in situ hybridization for IGH, BCL2, BCL6, CCND1, and MYC loci showed that the only chromosomal translocation was rearranged IGH in 1 case. Two patients were at stage I, and 1 at stage III. All were treated with combination chemotherapy and achieved long-term complete remission. Literature review including the current cases showed that 45% cases of pediatric FL expressed bcl-2 protein and 9% cases carried BCL2 gene rearrangement, suggesting an alternate molecular pathogenesis of pediatric FL as compared to their adult counterparts.