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Neuroblastic tumors associated with opsoclonus-myoclonus syndrome: histological, immunohistochemical and molecular features of 15 Italian cases

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Abstract

The aim of this study was to investigate the histological, immunohistochemical and molecular features of a series of children with neuroblastic tumors (NTs) and opsoclonus-myoclonus syndrome (OMS). Of 1187 children (age 0–15 years) with previously untreated NTs registered between 1979 and 1995, 15 (1.3%) had OMS at presentation. The majority of patients showed favorable biological characteristics, such as lack of amplification of the neuroblastoma-associated avian myelocytomatosis homolog MYCN oncogene and aneuploid nuclear DNA content. Tumor histology was reviewed according to the International Neuroblastoma Pathology Classification. Histology of the 15 cases of NTs with OMS was ganglioneuroblastoma, intermixed, in 10 patients; ganglioneuroma, maturing, in 1; and neuroblastoma in 4. Of 15 tumors, 12 (10 ganglioneuroblastomas, 2 neuroblastomas) showed abundant interstitial or perivascular lymphoid infiltrates, the latter often organized in secondary lymphoid follicles. The three remaining cases had only minimal infiltrates. A review of 91 cases of age- and stage-matched neuroblastic tumors not associated with OMS tested as controls showed that the degree of lymphoid infiltration was significantly lower than that detected in OMS-related tumors. Furthermore, lymphoid follicles were always present in the latter tumors, whereas they were detected only in a few ganglioneuroma, intermixed tumors from the control group. In conclusion, ganglioneuroblastoma, intermixed subtype, lack of MYCN amplification, aneuploid DNA content and presence of lymphoid infiltrates may contribute to favorable prognosis in NTs associated with OMS.

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Acknowledgements

We thank Dr. Soldano Ferrone, Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, for the generous supply of the anti-HLA class-I monoclonal antibody TP 25.99, Marco Ciufferri for the help in tissue handling, and Luca Tedeschi for editing the pictures. This study was supported by grants from Ministero della Sanità, Roma (ICS 070.2/RF99.21) and Associazione Italiana per la Lotta al Neuroblastoma, Genova, Italy.

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Authors and Affiliations

  1. Service of Pathology, Giannina Gaslini Children's Hospital, Largo Gerolamo Gaslini 5, 16148, Genova, Italy

    Claudio Gambini, Adriana Morando & Francesca Negri

  2. The Department of Hematology-Oncology, Giannina Gaslini Children's Hospital, Genova, Italy

    Massimo Conte, Paola Angelini & Bruno De Bernardi

  3. The Division of Neuropsychiatry, Giannina Gaslini Children's Hospital, Genova, Italy

    Edvige Veneselli

  4. The Laboratory of Oncology, Giannina Gaslini Children's Hospital, Genova, Italy

    Lizzia Raffaghello, Anna Favre & Vito Pistoia

  5. The Division of Oncology, Bambino Gesù Children's Hospital, Roma, Italy

    Alberto Donfrancesco & Carlo Dominici

  6. Laboratory of Tumor Genetics, National Institute for Cancer Research, Genova, Italy

    Katia Mazzocco & Gian Paolo Tonini

  7. Division of Pediatrics, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

    Paolo Paolucci

  8. Department of Pediatrics, University of Bologna, Italy

    Andrea Pession

  9. Department of Pediatrics, University of Firenze, Italy

    Gabriella Bernini

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  1. Claudio Gambini
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Correspondence to Claudio Gambini.

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Gambini, C., Conte, M., Bernini, G. et al. Neuroblastic tumors associated with opsoclonus-myoclonus syndrome: histological, immunohistochemical and molecular features of 15 Italian cases. Virchows Arch 442, 555–562 (2003). https://doi.org/10.1007/s00428-002-0747-1

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