TUEDAY SURGICAL PATHOLOGY Thymoma: an update DR CESAR MORAN TUEDAY SURGICAL PATHOLOGY Glial and Glial-Neuronal Tumors DR ARIE PERRY GLIAL AND GLIO- NEURONAL TUMORS Arie Perry, M.D. DISCLOSURES (Arie Perry, MD) • I have no financial relationships to disclose. - and - • I will not discuss off label use or investigational use in my presentation School of Medicine NEUROPATHOLOGY AND REAL ESTATE • Location • Location • Location • Patient Age • Neuroimaging School of Medicine GLIOMAS • Astrocytomas (A) • Oligodendrogliomas (O) • [Mixed oligoastrocytomas (MOA)] • Ependymomas • Diffuse glioma = A, O, or MOA School of Medicine GLIOMA GRADING: WHO 2016 • Grade I = Benign • Grade II = Low-grade • Grade III = “Anaplastic” • Grade IV = High-grade malignant, e.g. “GBM” School of Medicine Distribution of Primary Malignant Brain and Other CNS Tumors by CBTRUS Histology Groupings and Histology and Behavior (N = 121,277) CBTRUS Statistical Report: NPCR and SEER, 2011–2015. Gliomas account for 26% of all primary CNS tumors, but 81% of all malignant CNS tumors Neuro Oncol. 2018;20(suppl_4):iv1-iv86. doi:10.1093/neuonc/noy131 © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. ASTROCYTOMAS • Diffuse (75%) • Circumscribed / Favorable (25%) – Fibrillary – Pilocytic – Gemistocytic – PXA – Giant Cell – SEGA – Small Cell – DIA – Granular Cell – Epithelioid School of Medicine ASTROCYTOMA, IDH-mutant, WHO GRADE II • Age 30-40 • Insidious / Slow growing • Non-enhancing • Often progress to grades III or IV • Survival ~10 years School of Medicine DIFFUSE ASTROCYTOMA (WHO II) School of Medicine ASTROCYTOMA (WHO GRADE II) School of Medicine DIFFUSE ASTROCYTOMA (II) School of Medicine SECONDARY STRUCTURES OF SCHERER School of Medicine ANAPLASTIC ASTROCYTOMA, IDH- mutant, WHO GRADE III • Age 40-50 • More rapid onset • Frequent progression to grade IV • Survival ~5-10 years School of Medicine ANAPLASTIC ASTROCYTOMA, WHO III School of Medicine IDH-mutant astrocytomas IDH1 p53 ATRX GLIOBLASTOMA (GBM), WHO GRADE IV • Age 50-60 • Rapid onset and progression • Rim (or ring)-enhancing • IDH-wildtype (“primary”): ~90%; Survival ~1-year • IDH-mutant (“secondary”): ~10%; Survival 2-3-years School of Medicine GLIOBLASTOMA (WHO GRADE IV) School of Medicine GLIOBLASTOMA (WHO GRADE IV) School of Medicine GBM VARIANTS / PATTERNS • Fibrillary (Classic) • Granular Cell • Gemistocytic • Small Cell • Giant Cell • GBM with primitive • Gliosarcoma neuronal component • Adenoid / Epithelioid / • Epithelioid Metaplastic • Molecular variants • Lipidized • Inflammation-rich School of Medicine GIANT CELL GBM School of Medicine GIANT CELL GBM Reticulin GFAP GIANT CELL GBM PATTERN IDH1 ATRX p53 GC-GBM in CMMRD MLH1 MSH2 MSH6 PMS2 GLIOSARCOMA Reticulin GFAP SMA CD34 OLIGODENDROGLIOMA, IDHm and 1p19q-codel (WHO GRADE II or III) • Average age 30-40 years • Corticotropism / seizures common • Cerebral, especially frontal lobe • Slow progression • Survival ~15-25 years for oligo (grade II); 10-15 years for anaplastic oligo (grade III): microvascular proliferation, high mitotic index, and/or necrosis School of Medicine OLIGODENDROGLIOMA School of Medicine OLIGODENDROGLIOMA, WHO GRADE II N N N School of Medicine OLIGODENDROGLIOMA School of Medicine GFAP ANAPLASTIC OLIGODENDROGLIOMA School of Medicine SYN IDH-mutant + 1p/19q-codeleted oligos IDH1 p53 ATRX Astro, IDHm IDHwt GBM, IDHwt EGFR‐amp IDHm Preneoplastic TERTm TP53m Cell (H3 G34R/V) ATRXm IDHm TERTm CICm 9p (CDKN2A/B) LOH 1p19q‐codel FUBP1m AA, IDHm Oligo, IDHm, Diffuse midline 1p19q‐codel glioma, H3‐K27Mm PIK3R1/PIK3CAm 4q LOH? PIK3CAm? GBM, IDHm AO, IDHm, 1p19q‐codel Note: no oligoastro! PILOCYTIC ASTROCYTOMA PILOCYTIC ASTROCYTOMA Nat Genet 45: 927-932, 2013 MAPK pathway BRAF KIAA1549 PILOMYXOID ASTROCYTOMA, WHO? Komotar et al. Neurosurgery 54:72, 2004 School of Medicine LONG-TERM EPILEPSY ASSOCIATED TUMORS (LEAT) • Glioneuronal – Ganglioglioma (GG), WHO I – Dysembryoplastic neuroepithelial tumor (DNET), WHO I – Others: mixed GG/DNET, PGNT, EVN • Gliomas – Pleomorphic xanthoastrocytoma (PXA), WHO II/III – Diffuse LGGs, WHO II – Pilocytic astrocytoma, WHO I School of Medicine GANGLIOGLIOMA (WHO I) • Most common LEAT • Children/young adults • Temporal lobe • Benign/surgically curable • Anaplasia rare: definition? – WHO grade III (grade II eliminated in 2007) • BRAF V600E in up to half School of Medicine GANGLIOGLIOMA (WHO I) School of Medicine GANGLIOGLIOMA (WHO I) School of Medicine SYN NFP Neu-N CD34 Ganglioglioma BRAF V600E ANA GG, WHO GRADE III DNET (WHO I) • LEAT of children/young adults • Temporal lobe • Benign/surgically curable • Tumor vs. hamartoma • Simple, complex, ‘non-specific’ variants • BRAF V600E: 0-50%; FGFR1-alt: 58%?, IDHwt, no 1p19q-codeletion School of Medicine GFAP PXA, WHO II-III School of Medicine PXA, WHO GRADE II PXA, WHO GRADE II PXA, WHO GRADE II PXA, WHO GRADE II Reticulin PXA, WHO GRADE II GFAP PXA, WHO GRADE II SYN NFP PXA, WHO GRADE II CD34 PXA c ANA transformation, WHO GRADE III PXA c ANA transformation, WHO GRADE III Ki-67 BRAF-V600E EPENDYMOMA (WHO GRADE I, II, III) • Kids: 4th ventricle, supratentorial • Adults: spinal cord • Prognostic Variables – Extent of resection / location – Patient age (poor if <2 years old) – Histologic grade? • Subependymoma or MPE, WHO grade I • Ependymoma, WHO grade II • Anaplastic ependymoma, WHO grade III – Molecular subgroups School of Medicine Subependymoma, WHO GRADE I MPE, WHO GRADE I MPE, WHO GRADE I PAS Trichrome Ependymoma, WHO GRADE II NFP Ependymoma, WHO GRADE II Ependymoma, WHO GRADE II Tanycytic ependymoma GFAP EMA CD99 EPENDYMOMA: PROGNOSIS Tihan T, et al., Mod Pathol 2008: 21, 165–177 School of Medicine Pajtler et al., 2015, Cancer Cell 27, 728–743 Clear cell ependymoma Clear cell ependymoma Clear cell (RELA fusion+) ependymoma L1CAM UCSF 500 NGS PF-A Ependymoma PF-B Ependymoma H3K27me3 Oligodendroglioma Music to Ave Maria by F. Schubert, Lyrics by Arie Perry, MD O----ligodendroglio-oh-oh-ma, diffuse cerebral tumor of adults Invading cortex, causing epilepsy; on imaging, often you are calcified And although, you tend to progress over time, for long periods your fine You're famous for your rounded nuclei, Clear haloes look like honeycombs or fried eggs With branching chicken wire capillaries, and perineuronal satellitosis O----ligodendroglio-oh-oh-ma, genetically, you are quite unique With 1p and 19q deletions, from translocation with loss of one derivative Represents a genetically favorable set, when FISH criteria are met Anaplastic cases grow more rapidly, assigned a W.H.O. grade III With microvascular proliferation, or increased mitotic activity O----ligodendroglio-oh-oh-ma School of Medicine TUEDAY SURGICAL PATHOLOGY Pleural Mespthelloma DR CESAR MORAN TUEDAY SURGICAL PATHOLOGY Germ Cell tumors of the Ovary DR BLAKE GILKS 8/9/19 Germ Cell Tumors of the Ovary Blake Gilks Dept of Pathology, Vancouver General Hospital [email protected] Case 1 Secondary information Clinical presentation n22F nPreviously fit and well nMedical history - nil nRecently completed degree nRecent travel to Nigeria (April) nFever and ear pain 2 weeks prior – treated with antibiotics by GP nTwo weeks of altered sense of smell, odd taste, poor appetite 1 8/9/19 Clinical presentation nAttended hospital 21 Sept with generalised seizures starting focally in the right arm, non-sensical speech, confusion and agitation nTemperature of 38 nInterictally odd behaviour and not verbalising nInitial CT and EEG normal nKept in for observation nFurther 7 seizures in next 24 hrs Course nIntubated and ventilated, loaded with phenytoin nTreated for encephalitis/meningitis empirically and malaria nTests subsequently came back negative • normal MRI brain • CSF protein 0.28, 4 WC, opening pressure 40 Secondary information 2 8/9/19 nDeveloped pneumonia and acute renal failure requiring haemofiltration nBedside ultrasound of abdomen revealed a pelvic mass. Investigations n EEG 21/9/2012 • The EEG is within normal limits. No focal abnormalities or epileptiform discharges are seen. n EEG 24/9/2012 • The EEG shows mild generalised slow activity suggestive of mild global cortical dysfunction. • No focal abnormalities, epileptiform discharges or periodic complexes are seen. n EEG 27/9/2012 • The EEG is abnormal with generalised slowing in keeping with mild- moderate encephalopathy. • No focal abnormalities, periodic complexes or epileptiform discharges are seen. n MRI Brain • Normal n CSF • Prot 0.28, WCC 5 (4 LC), lactate normal • OP 40 n Bloods • Routine bloods normal, ESR 30 • Lupus anticoagulant, ANA and ANCA negative • C3 and C4 in normal limits, Ammonia <13 Investigations • NMDA Receptor antibodies POSITIVE • NMDA Receptor antibody was first found in young female patients with ovarian tumours and prominent psychiatric symptoms, amnesia, seizures, dyskinesias, autonomic dysfunction and decreased levels of consciousness. The antibodies are now also found in males or females with no known tumour and in children. Their presence suggests an immunotherapy-responsive condition. • Dalmau J et al Lancet Neurology 2008 7(12) p1091 3 8/9/19 Treatment nIVIG contraindicated because of renal failure nIV Methylprednisolone, then Prednisolone 60mg nTransferred to RLH for plasma exchange nArrived intubated and ventilated nRenal function improved – not requiring haemodialysis Secondary information Pathology • Intact cystic and solid ovarian mass • 1214g • 165 x 90 x 70 mm • Externally smooth • Internally multiloculated, 60% solid areas, soft, grey to haemorrhagic 4 8/9/19