title: Primary leptomeningeal ALK+ lymphoma in a 13-year-old child.
abstract: A distinct pathologic entity characterized by expression of the anaplastic lymphoma kinase (ALK) protein (hence described as ALK lymphoma) has emerged within the heterogeneous group of CD30 anaplastic large-cell lymphomas. Central nervous system (CNS) involvement is extremely rare in anaplastic large-cell lymphoma. In children, only isolated cases have been reported, mainly as secondary CNS involvement. We report on a 13-year-old boy presenting with headaches and diplopia. Cerebrospinal fluid was infiltrated with atypical large granular lymphocytes. Magnetic resonance imaging of the brain revealed leptomeningeal enhancement. A frontal lobe biopsy showed a pleomorphic neoplasm diffusely infiltrating the meninges composed of large cells with bizarre nuclei similar to those evidenced in cerebrospinal fluid. Immunohistochemical stains showed diffuse strong positivity for CD8, CD30, anaplastic lymphoma kinase protein: p80 and negative monocyte-macrophage and B cell markers. TCR gamma was clonally rearranged. This finding was confirmed by reverse transcription-polymerase chain reaction analysis of the NPM/ALK fusion protein. Epstein-Barr virus was not detected. No evidence of extra-CNS disease was found by imaging study, cytologic examination, or molecular studies. The patient underwent complete remission with polychemotherapy followed by a CNS irradiation. At +10 months from onset, he suffered a full relapse. After a short-term remission with vinblastine, he underwent nonmyeloablative allogeneic bone marrow transplantation, but unfortunately died from multiple organ failure. This case is the first reported occurrence of a primary meningeal ALK lymphoma in a child.
authors.affiliation: CHU Clermont-Ferrand, Centre Régional de Cancérologie et Thérapie Cellulaire Pédiatrique, Hôtel-Dieu, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Merlin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chabrier
authors.forename: Virginie
authors.initials: V
authors.lastname: Verkarre
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cramer
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Stéphan
mesh_terms: D000293:Adolescent; D000077548:Anaplastic Lymphoma Kinase; D004273:DNA, Neoplasm / Q000032:analysis; D017809:Fatal Outcome; D015321:Gene Rearrangement; D019675:Genes, T-Cell Receptor gamma / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D017728:Lymphoma, Large-Cell, Anaplastic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009102:Multiple Organ Failure; D011505:Protein-Tyrosine Kinases / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases
chemical_list: D004273:DNA, Neoplasm; C107023:p80(NPM-ALK) protein; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases