Histopathologic review of pineal parenchymal tumors identifies novel morphologic subtypes and prognostic factors for outcome.
Pineal parenchymal tumors (PPTs) are rare neoplasms of the central nervous system, and data concerning clinical outcomes are limited. The purpose of this study was to define the clinical behavior of PPT according to current histopathologic criteria and identify prognostic factors to guide therapeutic decisions.



Seventy-five patients treated for PPT at a single institution between 1992 and 2015 were retrospectively identified. Forty-five resection specimens were available and re-reviewed. Freedom from progression (FFP) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using log-rank tests.



Median follow-up was 4.1 years. All patients initially underwent surgery; 78% of patients with PPT of intermediate differentiation (PPTID) and all patients with pineoblastoma received adjuvant therapy. Pathologic re-review refined classification in 27% of cases, with the majority of these being adult patients with pineal tumors originally classified as pineoblastomas that more accurately resembled PPTID based on the 2007 WHO classification.



Our histologic review also identified that PPTIDs can be classified into small-cell and large-cell morphologic subtypes, which have distinct clinical outcomes. Tumor grade, extent of resection, and neuraxis spread were prognostic for FFP. PPTID subtype, extent of resection, and neuraxis spread were prognostic for OS. Genetic analysis of a pineoblastoma case identified somatic mutations of DICER1, ARID1A, and KDM5C genes.



PPTIDs can be classified into 1 of 2 novel morphologic subtypes that are associated with distinct clinical outcomes. Tumor grade, neuraxis spread, and extent of resection also influence outcome for patients with PPT.
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.).
David R
DR
Raleigh
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.).
David A
DA
Solomon
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.).
Shane A
SA
Lloyd
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.).
Ann
A
Lazar
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.).
Michael A
MA
Garcia
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.).
Penny K
PK
Sneed
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.).
Jennifer L
JL
Clarke
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.).
Michael W
MW
McDermott
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.).
Mitchel S
MS
Berger
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.).
Tarik
T
Tihan
Department of Radiation Oncology, University of California San Francisco, San Francisco, California (D.R.R., S.A.L., A.L., M.A.G., P.K.S., D.A.H.-K.); Division of Neuropathology, Department of Pathology, University of California San Francisco, San Francisco, California (D.A.S., T.T.); Department of Neurology, University of California San Francisco, San Francisco, California (J.L.C.); Department of Neurologic Surgery, University of California San Francisco, San Francisco, California (J.L.C., M.W.M., M.S.B.) dhaas-kogan@lroc.harvard.edu.
Daphne A
DA
Haas-Kogan
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D010870:Pineal Gland / Q000378:metabolism / Q000473:pathology*; D010871:Pinealoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
D014408:Biomarkers, Tumor
DICER1; pineal parenchymal tumor; pineal parenchymal tumor of intermediate differentiation; pineoblastoma; pineocytoma