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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

Oschlies, Ilske MD*; Burkhardt, Birgit MD, PhD; Chassagne-Clement, Catherine MD; d'Amore, Emanuel S. MD§; Hansson, Ulrika MD; Hebeda, Konnie MD; Mc Carthy, Keith MD; Kodet, Roman MD**; Maldyk, Jadwiga MD††; Müllauer, Leonhard MD‡‡; Porwit, Anna MD§§; Schmatz, Ana-Iris MD∥∥; Tinguely, Marianne MD¶¶; Abramov, Dimitry MD*; Wotherspoon, Andrew FRCPath♯♯; Zimmermann, Martin PhD; Reiter, Alfred MD; Klapper, Wolfram MD*

The American Journal of Surgical Pathology: June 2011 - Volume 35 - Issue 6 - p 836–844
doi: 10.1097/PAS.0b013e318213e90e
Original Articles

The majority of lymphoblastic (precursor cell) neoplasms presents as leukemias. Consequently, the guidelines for lineage determination and subtyping of precursor cell neoplasms were primarily established for flow cytometry methods. Large-scale studies of nonleukemic lymphoblastic lymphomas are lacking so far. We analyzed a large series of pediatric patients with lymphoblastic lymphoma treated within a prospective randomized trial (the Euro-LB 02 study). Among 193 lymphomas, in which a detailed immunohistochemical analysis was carried out, there were several unusual and diagnostically challenging morphologic and immunophenotypical variants. These included 11 lymphomas with mixed phenotypes expressing markers of at least 2 hematopoietic lineages, 7 terminal deoxynucleotide transferase-negative lymphoblastic lymphomas, and 3 undifferentiated hematopoietic neoplasms that could not be assigned to any lineage with certainty. Our data indicate that World Health Organzation guidelines for lineage determination and subtyping of precursor cell leukemia need to be adapted before they can be applied to immunohistochemical diagnosis of lymphoma. Using the experience from this cohort we suggest a resource-saving diagnostic staining panel for the immunohistochemical analysis of precursor cell neoplasms in formalin-fixed paraffin-embedded tissue.

*Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian-Albrecht University, Kiel

NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen

∥∥Departments of Pediatric Hematology and Oncology, University of Hannover, Germany

Department of Biopathology, Centre Léon Bérard, Lyon, France

§Department of Pathology, Ospedale San Bortolo, Vicenza, Italy

Avdehingen för Patologi, Sahlgrenska Universitetssjukhuset, Gothenburg

§§Department of Pathology, Karolinska University Hospital and Institute, Stockholm, Sweden

Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Department of Pathology, Chettenham General Hospital, Chettenham

♯♯Department of Histopathology, Royal Marsden Hospital, London, United Kingdom

**Department of Pathology and Molecular Medicine, 2nd Medical School and Faculty Hospital, Charles University, Prague, Czech Republic

††Department of Pathology, Childrens Hospital, Warsaw, Poland

¶¶Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland

‡‡Department of Pathology, Medical University Vienna, Vienna, Austria

Supported by the Deutsche Krebshilfe Bonn (projekt Nr. 102595 and 107813) and national study groups of participating centers. D.A. was supported by the TransAid foundation. W.K. and I.O. were supported by the Kinderkrebsinitiative Buchholz, Holm-Seppensen, Germany.

Supported by the Kinder-Krebs-Initiative Buchholz, Holm-Seppensen and the national study groups for pediatric Non-Hodgkin Lymphoma of the participating pathologists. The NHL-BFM study center as the international coordination center of the trial was supported by the Deutsche Krebshilfe (grant No.107813).

Ilske Oschlies, MD and Wolfram Klapper, MD are supported by the Kinderkrebsinitiative Buchholz, Holm-Seppensen.

Correspondence: Wolfram Klapper, MD, University Hospital Schleswig-Holstein, Hematopathology Section and Lymph Node Registry Kiel, Arnold-Heller-Straβe 3, Haus 14, 24105 Kiel, Germany (e-mail:

© 2011 Lippincott Williams & Wilkins, Inc.