Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement.

Pediatric follicular lymphoma (PFL) is a variant of follicular lymphoma (FL) presenting as localized lymphadenopathy in children. Unlike conventional adult FL, PFL typically does not recur or progress. Clear diagnostic criteria for PFL are lacking, and it is uncertain whether this indolent lymphoma is defined by age or may occur in adults. We analyzed 27 FL in patients < 40 years of age and found that all 21 cases that lacked a BCL2 gene abnormality (BCL2-N; P < .0001) and had > 30% Ki67 fraction (high proliferation index, HPI; P = .0007) were stage I and did not progress or recur; in comparison, all 6 cases with BCL2 rearrangement and/or PI < 30% were stage III/IV, and 5 of 6 recurred or progressed. In a separate cohort of 58 adult FL (≥ 18 years of age), all 13 BCL2-N/HPI cases were stage I, and none progressed or relapsed, whereas 11 of 15 stage I cases with BCL2 gene abnormality and/or LPI relapsed or progressed (P = .0001). The adult and pediatric BCL2-N/HPI FL cases had similar morphologic features. Our results confirm the highly indolent behavior of PFL and suggest that these are characterized by HPI and absence of BCL2 gene abnormality. PFL-like cases also occur in adults and are associated with indolent behavior in this patient population.

[1]  K. Maclennan,et al.  Primary Follicular Lymphoma of the Testis in Children and Adolescents , 2012, Journal of pediatric hematology/oncology.

[2]  A. Feldman,et al.  Clinicopathologic and Genetic Characterization of Follicular Lymphomas Presenting in the Ovary Reveals 2 Distinct Subgroups , 2011, The American journal of surgical pathology.

[3]  A. Rosenwald,et al.  Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles , 2011, Haematologica.

[4]  S. Perkins,et al.  Pediatric indolent lymphoma—would less be better? , 2011, Pediatric blood & cancer.

[5]  Dirk Hasenclever,et al.  Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults. , 2011, Blood.

[6]  R. Siebert,et al.  Follicular lymphoma grade 3B. , 2011, Best practice & research. Clinical haematology.

[7]  D. Mason,et al.  Pseudonegative BCL2 protein expression in a t(14;18) translocation positive lymphoma cell line: a need for an alternative BCL2 antibody , 2010, Pathology.

[8]  W. Klapper,et al.  Pediatric follicular lymphoma – a clinico-pathological study of a population-based series of patients treated within the Non-Hodgkin’s Lymphoma - Berlin-Frankfurt-Münster (NHL-BFM) multicenter trials , 2010, Haematologica.

[9]  A. Feller,et al.  BCL6-translocations affect the phenotype of follicular lymphomas only in the absence of t(14;18)IgH/BCL2. , 2009, Anticancer research.

[10]  Jun Wang,et al.  Pediatric follicular lymphoma: a rare clinicopathologic entity. , 2009, Archives of pathology & laboratory medicine.

[11]  M. Piris,et al.  Frequency of BCL2 and BCL6 translocations in follicular lymphoma: Relation with histological and clinical features , 2008, Leukemia & lymphoma.

[12]  L. Staudt,et al.  Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. , 2007, Blood.

[13]  A. Rohatiner,et al.  Primary Follicular Lymphoma of the Testis and Epididymis in Adults , 2007, The American journal of surgical pathology.

[14]  H. Tagawa,et al.  CD10-MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features. , 2007, Blood.

[15]  K. Karube,et al.  Bcl2‐negative follicular lymphomas frequently have Bcl6 translocation and/or Bcl6 or p53 expression , 2007, Pathology international.

[16]  N. Harris,et al.  Low Histologic Grade Follicular Lymphoma With High Proliferation Index: Morphologic and Clinical Features , 2005, The American journal of surgical pathology.

[17]  C. Massone,et al.  Primary cutaneous large B-cell lymphomas: clinicopathologic features, classification, and prognostic factors in a large series of patients. , 2005, Blood.

[18]  H. Kerl,et al.  Genetic Aberrations in Primary Cutaneous Large B-Cell Lymphoma: A Fluorescence In Situ Hybridization Study of 25 Cases , 2005, The American journal of surgical pathology.

[19]  D. de Jong,et al.  Lack of Bcl‐2 expression in follicular lymphoma may be caused by mutations in the BCL2 gene or by absence of the t(14;18) translocation , 2005, The Journal of pathology.

[20]  U. Surti,et al.  Clinicopathologic, Immunophenotypic, and Molecular Cytogenetic Fluorescence In Situ Hybridization Analysis of Primary and Secondary Cutaneous Follicular Lymphomas , 2005, The American journal of surgical pathology.

[21]  S. Swerdlow.  Pediatric follicular lymphomas, marginal zone lymphomas, and marginal zone hyperplasia. , 2004, American journal of clinical pathology.

[22]  P. Dubus,et al.  Neoplastic Cells Do Not Carry bcl2-JH Rearrangements Detected in a Subset of Primary Cutaneous Follicle Center B-cell Lymphomas , 2004, The American journal of surgical pathology.

[23]  J. Teruya-Feldstein,et al.  Primary follicular lymphoma of the testis: excellent outcome following surgical resection without adjuvant chemotherapy. , 2004, Journal of pediatric hematology/oncology.

[24]  G. Fleuren,et al.  Bcl‐2, Bcl‐6 and CD10 expression in cutaneous B‐cell lymphoma: further support for a follicle centre cell origin and differential diagnostic significance , 2003, The British journal of dermatology.

[25]  M Hummel,et al.  Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936 , 2003, Leukemia.

[26]  R. Gascoyne,et al.  Absence of t(14,18) chromosomal translocation in primary cutaneous B‐cell lymphoma , 2002, The British journal of dermatology.

[27]  F. Behm,et al.  Clinicopathologic analysis of follicular lymphoma occurring in children. , 2002, Blood.

[28]  R. Gascoyne,et al.  Primary cutaneous follicular lymphoma: an assessment of clinical, histopathologic, immunophenotypic, and molecular features. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  Atra,et al.  Conservative management of follicular non‐Hodgkin's lymphoma in childhood , 1998, British journal of haematology.

[30]  C. Meijer,et al.  bcl-2 protein expression in primary cutaneous large B-cell lymphoma is site-related. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  W. Chan,et al.  Prognostic value of cellular proliferation and histologic grade in follicular lymphoma. , 1995, Blood.

[32]  H. Kerl,et al.  bcl-2 protein expression and correlation with the interchromosomal 14;18 translocation in cutaneous lymphomas and pseudolymphomas. , 1994, The Journal of investigative dermatology.

[33]  C. Berard,et al.  Follicular lymphomas in pediatric patients. , 1990, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[34]  B. Nathwani,et al.  Follicular (nodular) lymphoma during the first two decades of life: A clinicopathologic study of 12 patients , 1981, Cancer.

[35]  M. Djokic.  BCL6 gene amplification/3q27 gain is associated with unique clinicopathological characteristics among follicular lymphoma without BCL2 gene translocation , 2009 .

[36]  R. Braziel,et al.  Prominent clonal B-cell populations identified by flow cytometry in histologically reactive lymphoid proliferations. , 2004, American journal of clinical pathology.

[37]  P. McKay,et al.  Primary Cutaneous Follicular Lymphoma A Clinicopathologic and Molecular Study of 16 Cases in Support of a Distinct Entity , 2002 .