title: Integrated Genomic Characterization of a Pineal Parenchymal Tumor of Intermediate Differentiation.
abstract: BACKGROUND
  Pineal parenchymal tumors of intermediate differentiation (PPTIDs) are rare lesions. The differential diagnosis and management strategy for PPTIDs can be challenging because of the variable prognostic and pathologic characteristics of these tumors.
  
  
  METHODS
  A 24-year-old man presented with progressive headaches, gait abnormalities, and abulia. Magnetic resonance imaging revealed a large T1-hypointense, T2-isointense, contrast-enhancing, partially cystic mass of the pineal and tectal region. Near-total resection was achieved in a 2-stage operation followed by focal and craniospinal irradiation and adjuvant chemotherapy.
  
  
  RESULTS
  Immunohistochemical analysis including use of pineal lineage marker confirmed a diagnosis of PPTID. Targeted exome sequencing showed mutations in TSC1(L388P) and IKZF3(F206C), whereas high-resolution array cytogenetics revealed losses in chromosomes 2, 3, 4, 8, 10, 11, 17, and 20, leading to single-copy loss of PTEN and TP53.
  
  
  CONCLUSIONS
  Pineal parenchymal tumors reflect a broad spectrum of malignancy potential and prognoses, which mandate better understanding of the disease mechanism for rational therapeutic strategies. We present a case of PPTID and report several mutations and chromosomal abnormalities previously unrecognized in this tumor subtype. Review of the literature highlights a need for surgical resection followed by adjuvant chemoradiation. Further investigation of these novel variants may improve understanding of the pathogenesis underlying pineal parenchymal tumors.
authors.affiliation: Center for Molecular Oncologic Pathology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Yun Jee
authors.initials: YJ
authors.lastname: Kang
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Wenya Linda
authors.initials: WL
authors.lastname: Bi
authors.affiliation: Division of Cytogenetics, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Dubuc
authors.affiliation: Hôpital Universitaire de Mirebalais, Mirebalais, Haiti.
authors.forename: Louine
authors.initials: L
authors.lastname: Martineau
authors.affiliation: Division of Cytogenetics, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Azra H
authors.initials: AH
authors.lastname: Ligon
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Berkowitz
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ayal A
authors.initials: AA
authors.lastname: Aizer
authors.affiliation: Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Eudocia Q
authors.initials: EQ
authors.lastname: Lee
authors.affiliation: Center for Molecular Oncologic Pathology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Division of Neuropathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.affiliation: Center for Molecular Oncologic Pathology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Division of Neuropathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Shakti H
authors.initials: SH
authors.lastname: Ramkissoon
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: idunn@partners.org.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Dunn
mesh_terms: D000328:Adult; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D002872:Chromosome Deletion; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004252:DNA Mutational Analysis; D059472:Exome; D005819:Genetic Markers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010870:Pineal Gland / Q000473:pathology / Q000601:surgery; D010871:Pinealoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy*; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D005819:Genetic Markers; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Clinical management; Genomics; Pineal parenchymal tumor; Pineal tumor