Objectives: While the incidence and prevalence of in situ follicular neoplasia (ISFN) and in situ mantle cell neoplasia (ISMCN) in adults are well documented, little is known about these early (precursor) lesions in pediatric populations. The aim of this study was to analyze so-called ‘reactive' lymph nodes harvested for the purpose of staging solid tumors, unexplained lymphadenopathies, or presumed inflammatory processes or in conjunction with other surgical interventions in children and adolescents aged <18 years, with special attention to ISFN and ISMCN. Methods: Formalin-fixed, paraffin-embedded reactive lymph node samples from an unselected pediatric population from two catchment areas in Switzerland were retrospectively analyzed for the presence of ISFN and ISMCN and specific reactive lymph node patterns. Results: While a diverse range of histopathological patterns of reactive lymph node changes with a particular periodic increase in mycobacterioses could be observed in this pediatric population, not a single case of ISFN or ISMCN was found. Conclusions: Early histological lymphomagenesis equivalents in the form of in situ lymphomas are exceedingly rare events in children and young adolescents. The spectrum of reactive lymph node changes is large, with differences possibly determined by regional variations in geography, demographics, catchment areas, seasons, and years, respectively.

Swerdlow S, Campo E, Pileri S, Harris N, Stein H, Siebert R, Advani R, Ghielmini M, Salles G, Zelenetz A, Jaffe E: The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375-2390.
Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, Thiele J, Vardiman J: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Geneva, WHO, 2008.
Schmatz AI, Streubel B, Kretschmer-Chott E, Püspök A, Jäger U, Mannhalter C, Tiemann M, Ott G, Fischbach W, Herzog P, Seitz G, Stolte M, Raderer M, Chott A: Primary follicular lymphoma of the duodenum is a distinct mucosal/submucosal variant of follicular lymphoma: a retrospective study of 63 cases. J Clin Oncol 2011;29:1145-1151.
Cong P, Raffeld M, Teruya-Feldstein J, Sorbara L, Pittaluga S, Jaffe ES: In situ localization of follicular lymphoma: description and analysis by laser capture microdissection. Blood 2002;99:3376-3382.
Nodit L, Bahler DW, Jacobs SA, Locker J, Swerdlow SH: Indolent mantle cell lymphoma with nodal involvement and mutated immunoglobulin heavy chain genes. Hum Pathol 2003;34:1030-1034.
Bassarova A, Tierens A, Lauritzsen GF, Fossa A, Delabie J: Mantle cell lymphoma with partial involvement of the mantle zone: an early infiltration pattern of mantle cell lymphoma? Virchows Arch 2008;453:407-411.
Tsujimoto Y, Gorham J, Cossman J, Jaffe E, Croce CM: The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science 1985;229:1390-1393.
Limpens J, Stad R, Vos C, de Vlaam C, de Jong D, van Ommen GJ, Schuuring E, Kluin PM: Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood 1995;85:2528-2536.
Dolken G, Illerhaus G, Hirt C, Mertelsmann R: BCL-2/JH rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases. J Clin Oncol 1996;14:1333-1344.
Liu Y, Hernandez AM, Shibata D, Cortopassi GA: BCL2 translocation frequency rises with age in humans. Proc Natl Acad Sci USA 1994;91:8910-8914.
Horsman DE, Gascoyne RD, Coupland RW, Coldman AJ, Adomat SA: Comparison of cytogenetic analysis, southern analysis, and polymerase chain reaction for the detection of t(14; 18) in follicular lymphoma. Am J Clin Pathol 1995;103:472-478.
Hockenbery D, Nuñez G, Milliman C, Schreiber RD, Korsmeyer SJ: Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 1990;348:334-336.
Aqel N, Barker F, Patel K, Naresh KN: In-situ mantle cell lymphoma - a report of two cases. Histopathology 2008;52:256-260.
Hirt C, Schuler F, Dolken L, Schmidt CA, Dolken G: Low prevalence of circulating t(11;14)(q13;q32)-positive cells in the peripheral blood of healthy individuals as detected by real-time quantitative PCR. Blood 2004;104:904-905.
Henopp T, Quintanilla-Martínez L, Fend F, Adam P: Prevalence of follicular lymphoma in situ in consecutively analysed reactive lymph nodes. Histopathology 2011;59:139-142.
Montes-Moreno S, Castro Y, Rodríguez-Pinilla SM, García JF, Mollejo M, Castillo ME, Bas-Vernal A, Barrionuevo-Cornejo C, Sanchez-Verde L, Menarguez J, Cigudosa JC, Piris MA: Intrafollicular neoplasia/in situ follicular lymphoma: review of a series of 13 cases. Histopathology 2010;56:658-662.
Bermudez G, Gonzalez de Villambrosia S, Martinez-Lopez A, Batlle A, Revert-Arce J, Cereceda Company L, Ortega Bezanilla, C, Piris M, Montes-Moreno S: Incidental and Isolated Follicular Lymphoma In Situ and Mantle Cell Lymphoma In Situ Lack Clinical Significance. Am J Surg Pathol 2016;40:943-949.
Adam P, Schiefer AI, Prill S, Henopp T, Quintanilla-Martínez L, Bösmüller HC, Chott A, Fend F: Incidence of preclinical manifestations of mantle cell lymphoma and mantle cell lymphoma in situ in reactive lymphoid tissues. Mod Pathol 2012;25:1629-1636.
Dölken G, Dölken L, Hirt C, Fusch C, Rabkin CS, Schüler F: Age-dependent prevalence and frequency of circulating t(14;18)-positive cells in the peripheral blood of healthy individuals. J Natl Cancer Inst Monogr 2008;39:44-47.
van Leeuwen MT, Turner JJ, Joske DJ, Falster MO, Srasuebkul P, Meagher NS, Grulich AE, Giles GG, Vajdic CM: Lymphoid neoplasm incidence by WHO subtype in Australia 1982-2006. Int J Cancer 2014;135:2146-2156.
Schmidt J, Salaverria I, Haake A, Bonzheim I, AdamP, Montes-Moreno S, Piris MA, Fend F, Siebert R, Quintanilla-Martinez L: Increasing genomic and epigenomic complexity in the clonal evolution from in situ to manifest t(14;18)-positive follicular lymphoma. Leukemia 2014;28:1103-1112.
Bell DA, Liu Y, Cortopassi GA: Occurrence of bcl-2 oncogene translocation with increased frequency in the peripheral blood of heavy smokers. J Natl Cancer Inst 1995;87:223-224.
Roulland S, Lebailly P, Lecluse Y, Briand M, Pottier D, Gauduchon P: Characterization of the t(14;18) BCL2-IGH translocation in farmers occupationally exposed to pesticides. Cancer Res 2004;64:2264-2269.
Quintanilla-Martinez L, Sander B, Chan JK, Xerri L, Ott G, Campo E, Swerdlow SH: Indolent lymphomas in the pediatric population: follicular lymphoma, IRF4/MUM1+ lymphoma, nodal marginal zone lymphoma and chronic lymphocytic leukemia. Virchows Arch 2016;468:141-157.
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