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

W. Klapper; I. Oschlies

doi:10.1055/s-0032-1306358

Klinische Pädiatrie, Inhaltsverzeichnis

Klin Padiatr 2012; 224(03): 183-190
DOI: 10.1055/s-0032-1306358

Übersicht

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

Specifics of Histopathological and Genetical Diagnosis and Classification of Lymphomas in Children and Adolescents

W. Klapper

¹Department of Pathology, Hemopathology Section and Lymph Node Registry, Christian-Albrecht University, Kiel

,

I. Oschlies

¹Department of Pathology, Hemopathology Section and Lymph Node Registry, Christian-Albrecht University, Kiel

› Institutsangaben

Abstract

Zusammenfassung

Lymphome machen im Kindes-und Jugendalter gemeinsam mit den Leukämien fast die Hälfte aller malignen Erkrankungen aus. Die korrekte gewebebasierte Diagnostik und daraus resultierende therapeutische Einordnung der Lymphomerkrankungen bedarf einer engen Zusammenarbeit zwischen pädiatrischen Onkologen und Hämatopathologen. Wir beschreiben hier relevante Charakteristika der im Kindesalter auftretenden Lymphome speziell das Hodgkin-Lymphom, das Burkitt-Lymphom, die Vorläufer-/lymphoblastischen Lmphome, das großzellig anaplastische Lymphom und das diffuse großzellige B-Zell-Lymphom sowie das primär mediastinale B-Zell-Lymphom und das seltene pädiatrische follikuläre Lymphom. Das Augenmerk richtet sich dabei auf spezielle diagnostische Schwierigkeiten sowie neue Erkenntnisse zu den biologischen Besonderheiten dieser Lymphome in Abgrenzung zu gleichnamigen Lymphomen des Erwachsenenalters. Zusätzlich werden neu definierte Lymphomentitäten der WHO-Klassifikation 2008 wie beispielsweise Grauzonenlymphome in ihrer Relevanz für die junge Altersgruppe diskutiert.

Abstract

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.

Schlüsselwörter

Burkitt-Lymphom - diffuses großzelliges B-Zell- Lymphom - follikuläres Lymphom - großzellig anaplastisches Lymphom - lymphoblastisches Lymphom - Hodgkin-Lymphom

Key words

Burkitt lymphoma - Hodgkin lymphoma - anaplastic large cell lymphoma - follicular lymphoma - diffuse large B-cell lymphoma - lymphoblastic lymphoma

Volltext

Referenzen

Literatur
1 Ait-Tahar K, Damm-Welk C, Burkhardt B et al. Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor dissemination and relapse risk. Blood 2010; 115: 3314-3319
2 Asano N, Yamamoto K, Tamaru J et al. Age-related Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders: comparison with EBV-positive classic Hodgkin lymphoma in elderly patients. Blood 2009; 113: 2629-2636
3 Aukema SM, Siebert R, Schuuring E et al. Double-hit B-cell lymphomas. Blood 2011; 117: 2319-2331
4 Barreca A, Lasorsa E, Riera L et al. Anaplastic lymphoma kinase (ALK) in human cancer. J Mol Endocrinol 2011;
5 Bauer K, Skoetz N, Monsef I et al. Comparison of chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for patients with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst Rev 2011; CD007941
6 Bene MC. Biphenotypic, bilineal, ambiguous or mixed lineage: strange leukemias!. Haematologica 2009; 94: 891-893
7 Bonzheim I, Geissinger E, Roth S et al. Anaplastic large cell lymphomas lack the expression of T-cell receptor molecules or molecules of proximal T-cell receptor signaling. Blood 2004; 104: 3358-3360
8 Campo E, Swerdlow SH, Harris N et al. The 2008 WHO Classification of Lymphoid Neoplasms and Beyond – Evolving Concepts and Practical Applications. Blood 2011; 117: 5019-5032
9 Corao DA, Biegel JA, Coffin CM et al. ALK expression in rhabdomyosarcomas: correlation with histologic subtype and fusion status. Pediatr Dev Pathol 2009; 12: 275-283
10 Damm-Welk C, Busch K, Burkhardt B et al. Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK positive anaplastic large cell lymphoma. Blood 2007; 110: 670-677
11 Damm-Welk C, Klapper W, Oschlies I et al. Distribution of NPM1-ALK and X-ALK fusion transcripts in paediatric anaplastic large cell lymphoma: a molecular-histological correlation. Br J Haematol 2009; 146: 306-309
12 Dave SS, Fu K, Wright GW et al. Molecular diagnosis of Burkitt’s lymphoma. N Engl J Med 2006; 354: 2431-2442
13 Dojcinov SD, Venkataraman G, Raffeld M et al. EBV positive mucocutaneous ulcer – a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol March 2010; 34: 405-417
14 Dunleavy K, Pittaluga S, Tay K et al. Comparative Clinical and Biological Features of Primary Mediastinal B-Cell Lymphoma (PMBL) and Mediastinal Grey Zone Lymphoma (MGZL). Blood (ASH Annual Meeting Abstracts) 114 (22) 2009; Ref Type: Abstract
15 Engert A, Plutschow A, Eich HT et al. Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med 2010; 363: 640-652
16 Fan Z, Natkunam Y, Bair E et al. Characterization of variant patterns of nodular lymphocyte predominant hodgkin lymphoma with immunohistologic and clinical correlation. Am J Surg Pathol 2003; 27: 1346-1356
17 Gérard-Marchant R, Hamlin I, Lennert K et al. Letter: Classification of non-Hodgkin’s lymphomas. Lancet 1974; 2: 405-408
18 Gesk S, Gascoyne RD, Schnitzer B et al. ALK-positive diffuse large B-cell lymphoma with ALK-Clathrin fusion belongs to the spectrum of pediatric lymphomas. Leukemia 2005; 19: 1839-1840
19 Gobel U, Creutzig U, Klingebiel T et al. Adolescents with cancer – administrative, clinical and scientific implications. Klin Padiatr 2011; 223: 311-314
20 Herbst C, Rehan FA, Skoetz N et al. Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma. Cochrane Database Syst Rev 2011; CD007110
21 Hummel M, Bentink S, Berger H et al. A biologic definition of Burkitt’s lymphoma from transcriptional and genomic profiling. N Engl J Med 2006; 354: 2419-2430
22 Klapper W, Szczepanowski M, Burkhardt B et al. Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials. Blood 2008; 112: 1374-1381
23 Klapper W. Pathobiology and diagnosis of follicular lymphoma. Semin Diagn Pathol 2011; 28: 146-160
24 Kluge R, Korholz D. Role of FDG-PET in Staging and Therapy of Children with Hodgkin Lymphoma. Klin Padiatr 2011; 223: 315-319
25 Korholz D, Claviez A, Hasenclever D et al. The concept of the GPOH-HD 2003 therapy study for pediatric Hodgkin's disease: evolution in the tradition of the DAL/GPOH studies. Klin Padiatr 2004; 216: 150-156
26 Lamant L, McCarthy K, d’Amore E et al. Prognostic Impact of Morphologic and Phenotypic Features of Childhood ALK-Positive Anaplastic Large-Cell Lymphoma: Results of the ALCL99 Study. J Clin Oncol 2011;
27 Mareschal S, Lanic H, Ruminy P et al. The proportion of activated B-cell like subtype among de novo diffuse large B-cell lymphoma increases with age. Haematologica 2011; 96: 1888-1890
28 Morton LM, Wang SS, Devesa SS et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006; 107: 265-276
29 Oschlies I, Burkhardt B, Chassagne-Clement C et al. Diagnosis and immunophenotype of 188 pediatric lymphoblastic lymphomas treated within a randomized prospective trial: experiences and preliminary recommendations from the European childhood lymphoma pathology panel. Am J Surg Pathol 2011; 35: 836-844
30 Oschlies I, Burkhardt B, Salaverria I et al. Clinical, pathological and genetic features of primary mediastinal large B-cell lymphomas and mediastinal gray zone lymphomas in children. Haematologica 2011; 96: 262-268
31 Oschlies I, Klapper W, Zimmermann M et al. Diffuse large B-cell lymphoma in pediatric patients belongs predominantly to the germinal-center type B-cell lymphomas: a clinicopathologic analysis of cases included in the German BFM (Berlin-Frankfurt-Munster) Multicenter Trial. Blood 2006; 107: 4047-4052
32 Oschlies I, Salaverria I, Mahn F et al. Pediatric follicular lymphoma – a clinico-pathological study of a population-based series of patients treated within the NHL-BFM (Berlin-Frankfurt-Munster) multicenter trials. Haematologica 2010; 95: 253-259
33 Pileri S, Falini B, Delsol G et al. Lymphohistiocytic T-cell lymphoma (anaplastic large cell lymphoma CD30+/Ki-1+ with a high content of reactive histiocytes). Histopathology 1990; 16: 383-391
34 Pileri SA, Agostinelli C, Bacci F et al. Pathobiology of ALK-negative anaplastic large cell lymphoma. Pediatr Rep 2011; 3 (Suppl. 02) e5
35 Pillay K, Govender D, Chetty R. ALK protein expression in rhabdomyosarcomas. Histopathology 2002; 41: 461-467
36 Pulford K, Lamant L, Morris SW et al. Detection of anaplastic lymphoma kinase ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. Blood 1997; 89: 1394-1404
37 Purz S, Mauz-Korholz C, Korholz D et al. [18F]Fluorodeoxyglucose positron emission tomography for detection of bone marrow involvement in children and adolescents with Hodgkin’s lymphoma. J Clin Oncol 2011; 29: 3523-3528
38 Rizzo KA, Streubel B, Pittaluga S et al. Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR. Mod Pathol 2010; 23: 866-873
39 Rudiger T, Jaffe ES, Delsol G et al. Workshop report on Hodgkin’s disease and related diseases (‘grey zone’ lymphoma). Ann Oncol 1998; 9 (Suppl. 05) S31-S38
40 Salaverria I, Philipp C, Oschlies I et al. Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults. Blood 2011; 118: 139-147
41 Salaverria I, Siebert R. The gray zone between Burkitt’s lymphoma and diffuse large B-cell lymphoma from a genetics perspective. J Clin Oncol 2011; 29: 1835-1843
42 Scholtysik R, Kreuz M, Klapper W et al. Detection of genomic aberrations in molecularly defined Burkitt’s lymphoma by array-based, high resolution, single nucleotide polymorphism analysis. Haematologica 2010; 95: 2047-2055
43 Song JY, Eberle FC, Xi L et al. Coexisting and clonally identical classic hodgkin lymphoma and nodular lymphocyte predominant hodgkin lymphoma. Am J Surg Pathol 2011; 35: 767-772
44 Stein H, Foss HD, Durkop H et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood 2000; 96: 3681-3695
45 Swerdlow SH, Campo E, Harris N et al. WHO Classification of Tumors of the Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008
46 Swerdlow SH. Pediatric follicular lymphomas, marginal zone lymphomas, and marginal zone hyperplasia. Am J Clin Pathol 2004; 122 (Suppl) S98-S109
47 Thunberg U, Amini RM, Linderoth J et al. BCL2 expression in de novo diffuse large B-cell lymphoma partly reflects normal differences in age distribution. Br J Haematol 2009; 146: 683-684
48 Woessmann W, Zimmermann M, Lenhard M et al. Relapsed or refractory anaplastic large-cell lymphoma in children and adolescents after Berlin-Frankfurt-Muenster (BFM)-type first-line therapy: a BFM-group study. J Clin Oncol 2011; 29: 3065-3071