Overview

As a pediatric Neuropathologist, I am charged with the diagnosis and study of diseases of the nervous system in children. I examine abnormal tissues that are sampled from patients undergoing surgery or autopsy. These clinically derived tissues form the basis of my laboratory based practice and largely guide my research. Chiefly via microscopy, I am able to distinguish the culprit disease process(es) that is(are) affecting a patient; in turn, this information is then relayed to the primary care clinicians (eg, neurologists, neurosurgeons, oncologists etc.) and used to guide patient care.

One form of brain cancer has particularly captured my attention: Atypical Teratoid Rhabdoid Tumor (ATRT). My research into ATRT is aimed at re-examining BCCH’s experience with this tumor and using this information to guide the treatment of future patients. In addition, in a BCCH Telethon funded project, I am investigating the microscopy and genetics of Anencephaly, most common congenital brain malformation which is considered to reside amongst the ‘neural tube disorders’.

Publications

Phenotypic evolution of UNC80 loss of function.
Valkanas E, Schaffer K, Dunham C, Maduro V, du Souich C, Rupps R, Adams DR, Baradaran-Heravi A, Flynn E, Malicdan MC, Gahl WA, Toro C, Boerkoel CF
PubMed: 27513830
08/2016

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.
Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler KW, Jones DT, Luu B, Cavalli FM, Aldape K, Remke M, Mynarek M, Rutkowski S, Gururangan S, McLendon RE, Lipp ES, Dunham C, Hukin J, Eisenstat DD, Fulton D
DOI: 10.1200/jco.2015.65.7825
PubMed: 27269943
07/2016

Histopathology of the filum terminale in children with and without tethered cord syndrome with attention to the elastic tissue within the filum.
Hendson G, Dunham C, Steinbok P
PubMed: 27236780
05/2016

Uncommon pediatric tumors of the posterior fossa: pathologic and molecular features.
Dunham C
DOI: 10.1007/s00381-015-2735-1
PubMed: 26351226
10/2015

Assessing the accuracy of death records and pre-mortem clinical diagnoses in children diagnosed with brain tumors: A retrospective chart review of children in British Columbia, Canada.
Hasan H, Hendson G, Howard AF, Hukin J, Dunham C, Ahmed T, Lo AC, Goddard K
DOI: 10.1016/j.prp.2015.06.008
PubMed: 26342938
10/2015

Radiological features of infantile glioblastoma and desmoplastic infantile tumors: British Columbia's Children's Hospital experience.
Bader A, Heran M, Dunham C, Steinbok P
DOI: 10.3171/2014.10.peds13634
PubMed: 25955808
08/2015

EZH2 expression is a prognostic factor in childhood intracranial ependymoma: a Canadian Pediatric Brain Tumor Consortium study.
Li AM, Dunham C, Tabori U, Carret AS, McNeely PD, Johnston D, Lafay-Cousin L, Wilson B, Eisenstat DD, Jabado N, Zelcer S, Silva M, Scheinemann K, Fryer C, Hendson G, Fotovati A, Hawkins C, Yip S, Dunn SE, Hukin J
DOI: 10.1002/cncr.29198
PubMed: 25586788
05/2015

Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis.
Torchia J, Picard D, Lafay-Cousin L, Hawkins CE, Kim SK, Letourneau L, Ra YS, Ho KC, Chan TS, Sin-Chan P, Dunham CP, Yip S, Ng HK, Lu JQ, Albrecht S, Pimentel J, Chan JA, Somers GR, Zielenska M, Faria CC
DOI: 10.1016/s1470-2045(15)70114-2
PubMed: 25882982
05/2015

The role of resection alone in select children with intracranial ependymoma: the Canadian Pediatric Brain Tumour Consortium experience.
Ailon T, Dunham C, Carret AS, Tabori U, Mcneely PD, Zelcer S, Wilson B, Lafay-Cousin L, Johnston D, Eisenstat DD, Silva M, Jabado N, Goddard KJ, Fryer C, Hendson G, Hawkins C, Dunn S, Yip S, Singhal A, Hukin J
DOI: 10.1007/s00381-014-2575-4
PubMed: 25391979
01/2015

Fatal congenital hypertrophic cardiomyopathy and a pancreatic nodule morphologically identical to focal lesion of congenital hyperinsulinism in an infant with costello syndrome: case report and review of the literature.
Sheffield BS, Yip S, Ruchelli ED, Dunham CP, Sherwin E, Brooks PA, Sur A, Singh A, Human DG, Patel MS, Lee AF
DOI: 10.2350/14-07-1525-cr.1
PubMed: 25668678
2015

Evolution of a Pediatric Primary Cerebral ALK-1-Positive Anaplastic Large Cell Lymphoma on Serial MRI.
Dunbar MJ, Singhal A, Rassekh SR, Dunham C
DOI: 10.1159/000380769
PubMed: 25896198
2015

MEDULLOBLASTOMA.
06/2014

EPENDYMOMA.
06/2014

ATYPICAL TERATOID RHABDOID TUMOUR.
06/2014

Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations.
Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M, Morrison A, Lewis P, Bouffet E, Bartels U, Zuccaro J, Agnihotri S, Ryall S, Barszczyk M, Chornenkyy Y, Bourgey M, Bourque G, Montpetit A, Cordero F, Castelo-Branco P
DOI: 10.1038/ng.2936
PubMed: 24705254
05/2014

Granulomatous herpes simplex encephalitis in an infant with multicystic encephalopathy: a distinct clinicopathologic entity?
Schutz PW, Fauth CT, Al-Rawahi GN, Pugash D, White VA, Stockler S, Dunham CP
DOI: 10.1016/j.pediatrneurol.2013.12.008
PubMed: 24485930
04/2014

Overcoming resistance to Sonic Hedgehog inhibition by targeting p90 ribosomal S6 kinase in pediatric medulloblastoma.
Pambid MR, Berns R, Adomat HH, Hu K, Triscott J, Maurer N, Zisman N, Ramaswamy V, Hawkins CE, Taylor MD, Dunham C, Guns E, Dunn SE
DOI: 10.1002/pbc.24675
PubMed: 23940083
01/2014

Magnetic resonance imaging in the encephalopathic term newborn.
Chau V, Poskitt KJ, Dunham CP, Hendson G, Miller SP
DOI: 10.2174/157339631001140408120336
PubMed: 25055861
2014

Pleomorphic xanthoastrocytoma of the spinal cord: case report and literature review.
Das S, Yip S, Hukin J, Cochrane D, Dunham C
DOI: 10.5414/np300689
PubMed: 24495348
2014

FoxG1 interacts with Bmi1 to regulate self-renewal and tumorigenicity of medulloblastoma stem cells.
Manoranjan B, Wang X, Hallett RM, Venugopal C, Mack SC, McFarlane N, Nolte SM, Scheinemann K, Gunnarsson T, Hassell JA, Taylor MD, Lee C, Triscott J, Foster CM, Dunham C, Hawkins C, Dunn SE, Singh SK
DOI: 10.1002/stem.1401
PubMed: 23592496
07/2013

Pediatric rhabdoid tumors of kidney and brain show many differences in gene expression but share dysregulation of cell cycle and epigenetic effector genes.
Birks DK, Donson AM, Patel PR, Sufit A, Algar EM, Dunham C, Kleinschmidt-DeMasters BK, Handler MH, Vibhakar R, Foreman NK
DOI: 10.1002/pbc.24481
PubMed: 23382118
07/2013

Fetal progeria: prenatal sonographic findings in petty syndrome.
Pugash D, Schrader KA, Dunham CP, Popescu OE, Sargent MA, Lehman AM, Yong SL, Clarke LA
DOI: 10.7863/ultra.32.5.881
PubMed: 23620331
05/2013

Cribriform neuroepithelial tumor or atypical teratoid/rhabdoid tumor?
Dunham C, Yip S
DOI: 10.3171/2012.3.peds12168
PubMed: 23394355
04/2013

Malignant desmoplastic infantile astrocytoma? a case report and review of the literature.
Al-Kharazi K, Gillis C, Steinbok P, Dunham C
DOI: 10.5414/np300548
PubMed: 23149336
2013

Sonographic assessment of normal and abnormal patterns of fetal cerebral lamination.
Pugash D, Hendson G, Dunham CP, Dewar K, Money DM, Prayer D
DOI: 10.1002/uog.11164
PubMed: 22610990
12/2012

Infant brain tumors: a neuropathologic population-based institutional reappraisal.
Dunham C, Pillai S, Steinbok P
DOI: 10.1016/j.humpath.2011.12.011
PubMed: 22497851
10/2012

Atypical teratoid rhabdoid tumors (ATRTs): the British Columbia's Children's Hospital's experience, 1986-2006.
Fleming AJ, Hukin J, Rassekh R, Fryer C, Kim J, Stemmer-Rachamimov A, Birks DK, Huang A, Yip S, Dunham C
DOI: 10.1111/j.1750-3639.2011.00561.x
PubMed: 22188464
09/2012

Polo-like kinase 1 inhibition kills glioblastoma multiforme brain tumor cells in part through loss of SOX2 and delays tumor progression in mice.
Lee C, Fotovati A, Triscott J, Chen J, Venugopal C, Singhal A, Dunham C, Kerr JM, Verreault M, Yip S, Wakimoto H, Jones C, Jayanthan A, Narendran A, Singh SK, Dunn SE
DOI: 10.1002/stem.1081
PubMed: 22415968
06/2012

Possible differentiation of cerebral glioblastoma into pleomorphic xanthoastrocytoma: an unusual case in an infant.
Yang MM, Singhal A, Rassekh SR, Yip S, Eydoux P, Dunham C
DOI: 10.3171/2012.1.peds11326
PubMed: 22546030
05/2012

Intracranial tumors in infants: long-term functional outcome, survival, and its predictors.
Pillai S, Metrie M, Dunham C, Sargent M, Hukin J, Steinbok P
DOI: 10.1007/s00381-012-1707-y
PubMed: 22307825
04/2012

High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival.
Birks DK, Donson AM, Patel PR, Dunham C, Muscat A, Algar EM, Ashley DM, Kleinschmidt-Demasters BK, Vibhakar R, Handler MH, Foreman NK
DOI: 10.1093/neuonc/nor140
PubMed: 21946044
12/2011

Congenital stridor in the context of Chiari malformation type II: the etiological role of vernix caseosa granulomatous meningitis.
Stritzke AI, Dunham CP, Smyth JA, Steinbok P
DOI: 10.3171/2011.7.peds11208
PubMed: 21961543
10/2011

Diffusion-weighted imaging and pathological correlation in pediatric medulloblastomas-"They are not always restricted!".
Pillai S, Singhal A, Byrne AT, Dunham C, Cochrane DD, Steinbok P
DOI: 10.1007/s00381-011-1499-5
PubMed: 21732119
09/2011

Microfibrillar collagen hemostat-induced necrotizing granulomatous inflammation developing after craniotomy: a pediatric case series.
Apel-Sarid L, Cochrane DD, Steinbok P, Byrne AT, Dunham C
DOI: 10.3171/2010.8.peds10248
PubMed: 20887115
10/2010

Pediatric brain tumors: a histologic and genetic update on commonly encountered entities.
Dunham C
DOI: 10.1053/j.semdp.2010.04.003
PubMed: 20919607
08/2010

Neuronal Intranuclear Inclusion Disease presenting as juvenile Parkinsonism.
Wiltshire KM, Dunham C, Reid S, Auer RN, Suchowersky O
PubMed: 20437931
03/2010

Hypotonia and infantile spasms: a new phenotype of coenzyme Q10 deficiency?
Huntsman RJ, Lemire EG, Dunham CP
PubMed: 19294900
01/2009

Malignant transformation of an intraaxial-supratentorial neurenteric cyst - case report and review of the literature.
Dunham CP, Curry B, Hamilton M
PubMed: 19919821
2009

Congenital gliosarcoma: detailed clinicopathologic documentation of a rare neoplasm.
Hocwald O, McFadden D, Osiovich H, Dunham C
DOI: 10.2350/09-01-0592-oa.1
PubMed: 19883237
2009

Answer to case of the month # 132. Adult ileocolic intussusception secondary to a submucosal lipoma.
Marshall GB, Dunham C, Wiemer C, Lautner D, Gray RR
PubMed: 18533399
04/2008

Primary intracerebral angiomatoid fibrous histiocytoma: report of a case with a t(12;22)(q13;q12) causing type 1 fusion of the EWS and ATF-1 genes.
Dunham C, Hussong J, Seiff M, Pfeifer J, Perry A
DOI: 10.1097/pas.0b013e3181453451
PubMed: 18300800
03/2008

Research

Current Project
“Atypical Teratoid Rhabdoid Tumour” (ATRT) is relatively rare and deadly form of brain cancer that primarily occurs in children less than 2 years old. Despite intensive treatment, most patients only survive 1 year. Until recently, ATRTs were notoriously difficult to diagnose. Armed with a new diagnostic immunohistochemical test called INI-1, my colleagues and I set out to reassess the past incidence of ATRT at BCCH.

Amongst 10 previously unrecognized cases of ATRT in our pathology archives, we identified 3 rare long term survivors. Recently, colleagues at the University of Colorado in Denver discovered a new sensitive marker of ATRTs called claudin-6. Claudin-6 appears specifically overexpressed in ATRT as opposed to other central nervous system tumours. In collaboration with our American colleagues, we found that 11 of our 15 BCCH ATRTs stained positively with claudin-6. Interestingly, amongst the 4 negative cases were all three of our long term survivors. As such, we proposed that claudin-6 may also act as a prognostic marker, wherein immunohistochemical positivity identifies patients likely to incur a poor outcome. Currently, we are attempting to unravel the presumptive biological underpinnings of long term survivorship in ATRT, and in turn translate these findings into improved patient care.

Anencephaly is the most common congenital brain malformation, affecting up to 1% of all pregnancies. Anencephaly is considered to be one of the “neural tube defects” (NTDs), a group of disorders that involve early faulty closure of the fetal neural tube. In particular, anencephaly is thought by some to represent a combination of a lack of closure (by 28 days of gestation) of the rostral neural tube and a lack of formation of the skull cap (ie, calvarium). According to this hypothesis, the bony skull defect exposes the open neural tube to toxic amniotic fluid. The developing brain subsequently erodes, leaving behind a mass of residual tissue called the “area cerebrovasculosa” (AC).

The abundance of autopsy cases at BCCH enticed me to investigate anencephaly more closely. There are no large modern studies that document the microscopic appearance of anencephaly; in particular, an immunohistochemical profile of the “AC” is currently lacking. As such, part of my research is to elucidate the histology of anencephaly using modern techniques.

Although the cause of anencephaly is not known, treatment with folic acid has been found to reduce the incidence of NTDs in general. As such, environmental influences appear partially causal in anencephaly. However, familial cases in the literature also point to a genetic component to anencephaly. Unfortunately, a putative genetic defect is yet to be discovered. In a large series, Norman et al. (1995) stated that routine cytogenetic analysis of anencephaly often reveals a normal chromosomal complement. Using more modern genetic techniques, rare case reports have suggested the potential role for partial chromosome 2p duplication in anencephaly. As such, my colleagues at BCCA and I have sought out to genetically study a large series of anencephalics using single nucleotide polymorphism (ie, SNP) arrays. The SNP platform is a very sensitive technique that can be used to scan the genome (beyond the ability of routine cytogenetics) for characteristic chromosomal abnormalities. Our work is ongoing, and our goal is to uncover any underlying genetic etiology in anencephaly.

Grants

Michael Cuccione Childhood Cancer Research Program Brain Tumour Grant - Project: “Personalizing the treatment of pediatric medulloblastoma”

Honours & Awards

1999- Millennium Scholarship, Government of Canada

2000- Association of Professors of the University of Ottawa (APUO) Bursary

2000- Millennium Scholarship, Government of Canada