Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.
Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.
Department of Pediatrics, Medical University Vienna, Vienna, Austria.|Department of (Neuro) Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Angelika
A
Mühlebner
Department of (Neuro) Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Jackelien
J
van Scheppingen
Department of Pediatric Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Hanna M
HM
Hulshof
Department of Pediatrics, Medical University Vienna, Vienna, Austria.
Theresa
T
Scholl
Department of (Neuro) Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Anand M
AM
Iyer
Department of (Neuro) Pathology, Academic Medical Center, Amsterdam, The Netherlands.
Jasper J
JJ
Anink
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Ans M W
AM
van den Ouweland
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Mark D
MD
Nellist
Department of Pediatric Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Floor E
FE
Jansen
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Wim G M
WG
Spliet
Department of Pediatric Neurology, Charles University, Second Medical School, Motol University Hospital, Prague, Czech Republic.
Pavel
P
Krsek
Department of Pediatric Neurology, Charles University, Second Medical School, Motol University Hospital, Prague, Czech Republic.
Barbora
B
Benova
Department of Pathology and Molecular Medicine, Charles University, Second Medical School, Motol University Hospital, Prague, Czech Republic.
Josef
J
Zamecnik
Shriners Hospital Pediatric Research Center and Department of Neurology, Temple University, Philadelphia, United States of America.
Peter B
PB
Crino
Department of Radiology, Medical University Vienna, Vienna, Austria.
Daniela
D
Prayer
Department of Neurosurgery, Medical University Vienna, Vienna, Austria.
Thomas
T
Czech
Institute of Neurology, Medical University Vienna, Vienna, Austria.
Adelheid
A
Wöhrer
Institute of Neurology, Medical University Vienna, Vienna, Austria.
Jasmin
J
Rahimi
Institute of Neurology, Medical University Vienna, Vienna, Austria.
Romana
R
Höftberger
Institute of Neurology, Medical University Vienna, Vienna, Austria.
Johannes A
JA
Hainfellner
Department of Pediatrics, Medical University Vienna, Vienna, Austria.
Martha
M
Feucht
Department of (Neuro) Pathology, Academic Medical Center, Amsterdam, The Netherlands.|Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.|Stichting voor Epilepsie in Nederland (SEIN), Hemstede, The Netherlands.
Eleonora
E
Aronica
D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology* / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000150:complications* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D005911:Gliosis / Q000150:complications / Q000473:pathology; D006801:Humans; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000032:analysis / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism; D014402:Tuberous Sclerosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D055815:Young Adult
D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases