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Posterior
Fossa Tumors
in Children
M. Memet Özek
Giuseppe Cinalli
Wirginia Maixner
Christian Sainte-Rose
Editors

123
Posterior Fossa Tumors in Children
M. Memet Özek • Giuseppe Cinalli
Wirginia Maixner • Christian Sainte-Rose
Editors

Posterior Fossa Tumors

in Children
Editors
M. Memet Özek Giuseppe Cinalli
Neurosurgery Pediatric Neurosurgery
Acıbadem University Santobono Children's Hospital
Istanbul Naples, Napoli
Turkey Italy

Wirginia Maixner Christian Sainte-Rose

Department of Neurosurgery Pediatric Neurosurgery
Royal Childrens Hospital Hopital Necker-Enfants Malades
Melbourne, Victoria Paris
Australia France

ISBN 978-3-319-11273-2 ISBN 978-3-319-11274-9 (eBook)

DOI 10.1007/978-3-319-11274-9

Library of Congress Control Number: 2015937189

Springer Cham Heidelberg New York Dordrecht London

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To my wife for 32 years, Eren, for her support and patience
throughout my life.
M. Memet Özek

To my mother.
To Fabrizia, Francesco, and Maria Allegra because the time
spent with them is the only real happiness.
and
To Roberta Migliorati who devoted her whole life to the care of
children affected by Brain Neoplasms.
Giuseppe Cinalli

To my mentors and students and the children for whom we care.

Wirginia Maixner

To all the young colleagues whom I have helped to progress in

pediatric neurosurgery.
Christian Sainte-Rose
Preface

Tumors of the posterior fossa are one of the most challenging pathologies a
neurosurgeon is called upon to deal with. The anatomical complexity of the
region and the amazing variety of possible histologies of neoplastic lesions in
this area in children make the therapeutic challenges even more difficult for
the pediatric neurosurgeon. The frequent association with hydrocephalus and
the options for its management before, during, or after the surgical procedure
on the posterior fossa have given rise to significant controversies during
recent years, and a consensus is still far from being obtained. During the last
few years, we have witnessed impressive progress in the genetic and genomic
profiling of some tumor lesions, allowing the identification of specific and
very different prognostic subgroups previously labeled with the same name
and often treated with the same protocols. With this new approach, we are
entering an era in which we shall be able to tailor treatment protocols very
precisely in order to avoid unnecessary procedures or therapeutic regimens,
thus limiting the possible collateral effects that have always burdened the
long-term prognosis and quality of life of survivors.
We have tried to group into different sections the main pathologies encoun-
tered in this age range. For each pathology, recognized experts thoroughly
analyze all aspects of genetics, radiology, surgery, pathology, oncology, and
radiotherapy. Although all of the editors are surgeons, only Section II is dedi-
cated solely to surgical approaches and techniques, and a strong effort was
made when profiling the book plan to offer a real multidisciplinary view of
these pathologies. We hope that the final results will reflect this effort.
Treatment of posterior fossa tumors in children is never a single person’s
work. Classification is complex, deeper expertise is demanded of actors in
many different fields, and very strong and reliable teamwork is not simply an
option but a real obligation.
An entire section has been dedicated to rare pathologies where early rec-
ognition may modify the therapeutic approach from the earliest stages, and
the final section is devoted to an analysis of different standards of immediate
postoperative care and the long-term general implications of follow-up and
treatment.
The final result explains why gestation was long and complex, and we are
very grateful to all contributors for their patience and to the Springer editorial
staff, who believed in this project.

vii
viii Preface

The final acknowledgment always goes to our patients and to their families,
who are called upon to face something bigger than themselves and from
whose terrible endurance and tribulations the cold scientific aspects of these
pages are derived.

Istanbul, Turkey M. Memet Özek

Naples, Italy Giuseppe Cinalli
Parkville, VIC, Australia Wirginia June Maixner
Paris, France Christian Sainte-Rose
Contents

Part I General Principles of Treatment in Pediatric

Posterior Fossa Tumors

1 History of Posterior Fossa Tumor Surgery . . . . . . . . . . . . . . . . 3

James Tait Goodrich
2 Development of the Posterior Fossa Structures . . . . . . . . . . . . . 61
Martin Catala
3 The Anatomy of the Posterior Cranial Fossa . . . . . . . . . . . . . . . 75
Aşkın Şeker and Albert L. Rhoton Jr.
4 Anatomical Connection of the Cerebellum. . . . . . . . . . . . . . . . . 101
Akin Akakin and Albert L. Rhoton Jr.
5 Clinical Presentation and Neurologic Evaluation
in Posterior Fossa Tumors in Children . . . . . . . . . . . . . . . . . . . . 119
Ugur Işık and M. Memet Özek
6 Principles of Molecular Biology in Posterior
Fossa Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Yuzo Terakawa, Jong Hee Chang, Christian Smith,
and James T. Rutka
7 Radiation Therapy in Posterior Fossa Tumors . . . . . . . . . . . . . 147
Thomas E. Merchant

Part II Surgical Approaches to Pediatric Posterior Fossa Tumors

8 Median Suboccipital Approach . . . . . . . . . . . . . . . . . . . . . . . . . . 177

Benoit Jenny and Wirginia June Maixner
9 Paramedian Approaches to the Posterior Fossa. . . . . . . . . . . . . 189
Giuseppe Mirone, Pietro Spennato,
and Giuseppe Cinalli
10 Skull Base Approaches in Children . . . . . . . . . . . . . . . . . . . . . . . 209
Bernard George and Damien Bresson
11 Anterior Skull Base Approaches to the Posterior Fossa . . . . . . 219
Dominic N.P. Thompson

ix
x Contents

12 Hydrocephalus in Pediatric Patients with Posterior

Fossa Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
Mustafa Güdük and M. Memet Özek
13 Intraoperative Neurophysiological Monitoring
in Posterior Fossa Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
Francesco Sala, Pasquale Gallo, Vincenzo Tramontano,
and Massimo Gerosa

Part III Pathologies in Pediatric Posterior Fossa Tumors:

Medulloblastoma

14 Molecular Biology and Genetics of Medulloblastoma . . . . . . . . 265

Pasquale De Antonellis, Livia Garzia, Antonio Verrico,
Michael D. Taylor, and Massimo Zollo
15 Imaging of Medulloblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
Anna Nastro, Maria Consiglio Buonocore, Domenico Cicala,
Emilio Cianciulli, Daniele Cascone, and Maria Rita Panico
16 Medulloblastoma: Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Pietro Spennato, Claudio Ruggiero, and Giuseppe Cinalli
17 Medulloblastoma: Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
Giuliana Di Martino, Elia Guadagno,
and Maria Laura Del Basso De Caro
18 Treatment of Medulloblastoma: Chemotherapy . . . . . . . . . . . . 349
Lucia Quaglietta, Virginia Vitale, Antonio Verrico,
and Roberta Migliorati
19 Radiotherapy in Medulloblastoma . . . . . . . . . . . . . . . . . . . . . . . 363
Maurizio Mascarin, Francesca Maria Giugliano,
and Elisa Coassin

Part IV Pathologies in Pediatric Posterior Fossa Tumors:

Ependymoma

20 Ependymomas: Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383

Stephanie Puget and Guillaume Bergthold
21 Neuroimaging of Posterior Fossa Ependymoma
in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
Andrea Rossi
22 Ependymomas: Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407
Stephanie Puget and Christian Sainte-Rose
23 Ependymoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
Pascale Varlet and Felipe Andreiuolo
24 Oncological Management of Ependymomas . . . . . . . . . . . . . . . 423
Jacques Grill and Maria-Jesus Lobon Iglesias
Contents xi

Part V Pathologies in Pediatric Posterior Fossa Tumors:

Cerebellar Astrocytoma

25 Genetics of Cerebellar Low-Grade Astrocytomas . . . . . . . . . . . 431

Adam J. Fleming and Mark W. Kieran
26 Neuroimaging of Posterior Fossa Astrocytoma in Children . . . 447
Daniele Cascone, Maria Rita Panico, Maria Consiglio Buonocore,
Domenico Cicala, Anna Nastro, and Emilio Cianciulli
27 Approaches to Cerebellar Astrocytoma in Pediatric Patients . 457
Erica Jacobson, Grace K. Lai, and Wirginia June Maixner
28 Cerebellar Astrocytomas: Pathology. . . . . . . . . . . . . . . . . . . . . . 467
Christian H. Rickert
29 Cerebellar Astrocytoma: Oncological Care . . . . . . . . . . . . . . . . 487
Pratiti Bandopadhayay, Peter A. Downie, and David M. Ashley
30 Radiotherapy for Cerebellar Astrocytomas . . . . . . . . . . . . . . . . 495
Greg C. Wheeler

Part VI Pathologies in Pediatric Posterior Fossa Tumors:

Brain Stem Tumors

31 Imaging of the Brainstem Tumors . . . . . . . . . . . . . . . . . . . . . . . . 511

Charles Raybaud and Abeer Almehdar
32 Surgical Approach to Mesencephalic Tumors . . . . . . . . . . . . . . 545
Bahattin Tanrıkulu, Gurmit Singh, and M. Memet Özek
33 Surgery of the Pons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557
Pablo F. Recinos, Violette Renard Recinos, and George I. Jallo
34 Surgery of Medulla Oblongata Tumors . . . . . . . . . . . . . . . . . . . 571
M. Memet Özek and Ulaş Yener
35 4D: Brain Stem Tumors – Pathology. . . . . . . . . . . . . . . . . . . . . . 585
Aydin Sav and Pınar Karabağlı
36 Radiotherapy Options of Brainstem Tumors . . . . . . . . . . . . . . . 595
Hale Başak Caglar
37 Oncologic Treatment of Pediatric Brainstem Tumors . . . . . . . . 609
Cengiz Canpolat

Part VII Pathologies in Pediatric Posterior Fossa Tumors: AT/RT

38 Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 629
Su Gulsun Berrak
39 Imaging Findings of CNS Atypical
Teratoid/Rhabdoid Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 633
Alp Dinçer
xii Contents

40 Atypical Teratoid/Rhabdoid Tumor: Surgery . . . . . . . . . . . . . . 643

Concezio Di Rocco and Luca Massimi
41 Atypical Teratoid/Rhabdoid Tumor . . . . . . . . . . . . . . . . . . . . . . 651
Pınar Karabağlı
42 Atypical Teratoid/Rhabdoid Tumors: Current Chemotherapy
and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 657
Cengiz Canpolat
43 Radiation Therapy in Atypical Teratoid/Rhabdoid Tumors . . 667
Hale Basak Caglar

Part VIII Pathologies in Pediatric Posterior Fossa Tumors:

Chordoma

44 Molecular Biology and Genetics of Chordomas. . . . . . . . . . . . . 675

Mustafa Güdük and M. Memet Özek
45 Imaging Findings of the Pediatric Clivus Chordomas . . . . . . . 683
Alp Dincer
46 Chordomas: Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 693
Aydin Sav and Pinar Karabağli
47 Chordomas and Their Management . . . . . . . . . . . . . . . . . . . . . . 703
Kevin Beccaria, Stephanie Puget, Bernard George,
and Christian Sainte-Rose

Part IX Pathologies in Pediatric Posterior Fossa Tumors:

Rare Tumors

48 Posterior Fossa Choroid Plexus Tumor . . . . . . . . . . . . . . . . . . . 723

Nobuhito Morota, Toshihiro Kumabe, and Akiyoshi Kakita
49 Medical Management of Choroid Plexus Tumors . . . . . . . . . . . 745
Johannes E. Wolff, Mical Bahar, Anita Mahajan,
and Su G. Berrak
50 Vestibular Schwannoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 761
Martin U. Schuhmann and Marcos S. Tatagiba
51 Posterior Fossa Gangliogliomas . . . . . . . . . . . . . . . . . . . . . . . . . . 771
Federico Di Rocco, Pascale Varlet, Nathalie Boddaert,
Jacques Grill, Thomas Roujeau, Stephanie Puget,
Bertrand Baussard, Michel Zerah, and Christian Sainte-Rose
52 Dermoid Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 783
M. Memet Özek and Saeed Kohan
53 Epidermoid Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
Saeed Kohan, Joachim Oertel, and M. Memet Özek
Contents xiii

54 Lhermitte–Duclos (Section Rare Tumors) . . . . . . . . . . . . . . . . . 805

Pietro Spennato, Vincenzo Trischitta, Ferdinando Aliberti,
and Giuseppe Cinalli
55 Meningioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
Saeed Kohan and M. Memet Özek

Part X Pre- and Postoperative Care of Pediatric Posterior

Fossa Tumors

56 Immediate Postoperative Care. . . . . . . . . . . . . . . . . . . . . . . . . . . 825

Martina Messing-Jünger, Michael Ehlen,
and Ehrenfried Schindler
57 Postoperative Care Following Surgery for Posterior
Fossa Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 841
Vasilios Tsitouras and Spyros Sgouros
58 Immediate Postoperative Care. . . . . . . . . . . . . . . . . . . . . . . . . . . 847
Stephanie Puget, Antonio Vecchione,
and Philippe Meyer
59 Immediate Postoperative Care: Istanbul Experience . . . . . . . . 849
Nigar Baykan and M. Memet Özek
60 Posterior Fossa Tumors: Immediate Postoperative Care . . . . . 853
Il-Woo Lee
61 Immediate Postoperative Care. . . . . . . . . . . . . . . . . . . . . . . . . . . 857
Pietro Spennato, Anna Dolcini, Alessandra Alifuoco,
and Giuseppe Cinalli
62 Surgical Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 861
Ram Kumar and Conor Mallucci
63 Postoperative Vertebral Column Complications . . . . . . . . . . . . 885
Bahattin Tanrıkulu, M. Memet Özek,
and Deniz Konya
64 Endocrinologic Complications and Late Sequela
of Childhood Posterior Fossa Tumors . . . . . . . . . . . . . . . . . . . . . 897
Abdullah Bereket
65 Rehabilitation for Children with Posterior Fossa Tumors . . . . 907
Adam M. Scheinberg
66 Psychosocial Coping with Neurosurgery:
Children and Their Families . . . . . . . . . . . . . . . . . . . . . . . . . . . . 917
Banu Çankaya and M. Kemal Kuşcu

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 931
Contributors

Akin Akakin Department of Neurosurgery, Bahcesehir University,

Beşiktaş, Istanbul, Turkey
Ferdinando Aliberti, M.D. Division of Pediatric Neurosurgery,
Department of Neuroscience, Santobono-Pausilipon Children’s Hospital,
Naples, Italy
Alessandra Alifuoco Department of Pediatric Anesthesiology,
Santobono-Pausilipon Children’s Hospital, Naples, Italy
Abeer Almehdar, M.D. Department of Medical Imaging, King Abdulaziz
Medical City, Jeddah, Saudi Arabia
Felipe Andreiuolo, M.D. Department of Neuropathology, Sainte-Anne
Hospital, University Paris Descartes, Paris, France
David M. Ashley, M.D. Andrew Love Cancer Centre and Children’s
Cancer Centre, Barwon Health and Royal Children’s Hospital, Melbourne,
VIC, Australia
Pratiti Bandopadhayay, M.B.B.S., Ph.D. Pediatric Neuro-Oncology
Program, Dana-Farber Cancer Institute, Boston Children’s Hospital and
Harvard Medical School, Melbourne, VIC, Australia
Bertrand Baussard, M.D. Department of Paediatric Neurosurgery, Necker
Enfants Malades Hospital, Paris, France
Nigar Baykan, M.D. Department of Anesthesiology, Acıbadem University,
School of Medicine, Istanbul, Turkey
Kevin Beccaria, M.D. Division of Pediatric Neurosurgery, Department of
Neurosurgery, Hopital Necker Enfants Malades, Université Paris Decartes,
Paris, France
Abdullah Bereket, M.D. Division of Pediatric Endocrinology, Marmara
University Hospital, Istanbul, Turkey
Guillaume Bergthold, M.D. Department of Vectorology and Anticancer
Therapeutics, CNRS UMR 8203, University Paris sud XI, Institut Gustave
Roussy, Villejuif, France

xv
xvi Contributors

Su Gulsun Berrak, M.D. Division of General Pediatrics, LINCS,

Children’s Hospital at Montefiore, Albert Einstein College of Medicine,
Bronx, NY, USA
Department of Pediatric Hematology Oncology, Marmara University
Medical Center, Istanbul, Turkey
Nathalie Boddaert, M.D. Department of Radiology, Hopital Necker-
Enfants Malades, Université Paris Decartes, Paris, France
Damien Bresson Department of Neurosurgery, Hôpital Lariboisère,
Paris, France
Maria Consiglio Buonocore, M.D. Division of Pediatric Neuroradiolgy,
Department of Neurosciences, Santobono-Pausilipon Children’s Hospital,
Naples, Italy
Hale Basak Caglar, M.D. Department of Radiation Oncology, Medipol
University, Istanbul, Turkey
Banu Çankaya, Ph.D. Department of Psychology, Koç University,
Istanbul, Turkey
Cengiz Canpolat, M.D. Division of Pediatric Oncology, Department of
Pediatrics, Acıbadem University, School of Medicine, Istanbul, Turkey
Daniele Cascone, M.D. Division of Pediatric Neuroradiolgy, Department
of Neurosciences, Santobono Pausilipon Children’s Hospital, Naples, Italy
Martin Catala, M.D., Ph.D. Faculté de Médecine Pitié-Salpêtrière
(Université Paris 6), UMR CNRS and Paris VI 7622, Paris Cedex 05,
France
Fédération de Neurologie, Hôpital Pitié-Salpêtrière, Paris Cedex 13, France
Jong Hee Chang, M.D. Division of Neurosurgery, Department of Surgery,
The Hospital for Sick Children, The University of Toronto, Toronto, ON,
Canada
Emilio Cianciulli, M.D. Division of Pediatric Neuroradiolgy, Department
of Neurosciences, Santobono-Pausilipon Children’s Hospital, Naples, Italy
Domenico Cicala, M.D. Division of Pediatric Neuroradiolgy, Department
of Neurosciences, Santobono-Pausilipon Children’s Hospital, Naples, Italy
Giuseppe Cinalli, M.D. Division of Pediatric Neurosurgery, Department of
Neuroscience, Santobono-Pausilipon Children’s Hospital, Naples, Italy
Department of Neurosurgery, University of L’Aquila, L’Aquila, Italy
Elisa Coassin, M.D. Pediatric Radiotherapy Unit, Department of Radiation
Oncology, IRCCS – CRO Aviano Cancer Center (Italy), Aviano, Italy
Pasquale De Antonellis, M.D. Department of Molecular Medicine and
Medical Biotechnologies, “Federico II” University of Naples, Naples, Italy
Maria Laura Del Basso De Caro, M.D. Department of Advanced
Biomedical Sciences, University Federico II Naples, Naples, Italy
Contributors xvii

Giuliana Di Martino, M.D. Division of Pediatric Neurosurgery,

Department of Neuroscience, Santobono-Pausilipon Children’s Hospital,
Naples, Italy
Concezio Di Rocco, M.D. Division of Pediatric Neurosurgery, Catholic
University, Medical School-Rome, Rome, Italy
Federico Di Rocco, M.D. Department of Paediatric Neurosurgery, Hopital
Necker-Enfants Malades, Université Paris Decartes, Paris, France
Alp Dinçer, M.D. Department of Radiology, Acibadem University,
School of Medicine, Istanbul, Turkey
Anna Dolcini Department of Anesthesiology, Santobono-Pausilipon
Children’s Hospital, Naples, Italy
Peter A. Downie, M.D. Children’s Cancer Centre, Royal Children’s
Hospital and Southernhealth, Melbourne, VIC, Australia
Michael Ehlen, M.D. Department of Pediatric Intensive Care and
Neonatology, Asklepios Klinik Sankt Augustin, University-Hospital
of Bonn, Bonn, Germany
Adam J. Fleming, M.A.Sc., M.D. Pediatric Hematology/Oncology,
McMaster Children’s Hospital, McMaster University, Hamilton, ON,
Canada
Pasquale Gallo, M.D. Pediatric Neurosurgery Unit, Institute of
Neurosurgery, University Hospital, Verona, Italy
Livia Garzia, M.D. Arthur and Sonia Labatt Brain Tumor Research
Centre, The Hospital for Sick Children, Toronto, ON, Canada
Bernard George Department of Neurosurgery, Hôpital Lariboisère,
Paris, France
Massimo Gerosa Intraoperative Neurophysiology Unit, Institute of
Neurosurgery, University Hospital, Verona, Italy
Francesca Maria Giugliano, M.D. Department of Radiation Oncology,
II University of Naples (Italy), Aviano, Pordenone, Italy
Pediatric Radiotherapy Unit, Department of Radiation Oncology,
IRCCS – CRO Aviano Cancer Center (Italy), Aviano, Italy
James Tait Goodrich, M.D., Ph.D., D.Sci. (Honoris Causa) Leo Davidoff
Department of Neurological Surgery, Albert Einstein College of Medicine,
Children’s Hospital at Montefiore, Bronx, NY, USA
Jacques Grill, M.D., Ph.D. Pediatric and Adolescent Oncology,
Institut Gustave Roussy, Villejuif, Ile de France, France
Elia Guadagno, M.D. Department of Advanced Biomedical Sciences,
University Federico II Naples, Naples, Italy
Mustafa Güdük, M.D. Department of Neurosurgery, Acibadem University,
School of Medicine, Istanbul, Turkey
xviii Contributors

Maria-Jesus Lobon Iglesias, M.D. Pediatric and Adolescent Oncology,

Institut Gustave Roussy, Villejuif, Ile de France, France
Ugur Işık, M.D. Division of Pediatric Neurology, Department of
Pediatrics, Acibadem University, Istanbul, Turkey
Erica Jacobson, M.D. Department of Neurosurgery, Prince of Wales
Hospital, Randwick, NSW, Australia
George I. Jallo, M.D. Division of Pediatric Neurosurgery, Johns Hopkins
University School of Medicine, Baltimore, M.D., USA
Benoit Jenny Department of Neurosurgery, Royal Children’s Hospital
Melbourne, Parkville, VIC, Australia
Akiyoshi Kakita, M.D., Ph.D. Department of Pathology and Resource
Branch for Brain Disease Research CBBR, Brain Research Institute,
University of Niigata, Chuo-ku, Niigata, Japan
Pınar Karabağlı, M.D. Department of Pathology, Selçuk University,
Selçuklu School of Medicine, Konya, Turkey
Mark W. Kieran, M.D., Ph.D. Pediatric Neuro-Oncology, Dana-Farber
Children’s Hospital Cancer Center, Harvard Medical School,
Boston, MA, USA
Saeed Kohan, MBBS, FRACS Department of Neurosurgery,
Sydney Children’s Hospital, Sydney, Australia
Deniz Konya, M.D. Department of Neurosurgery, Marmara University,
School of Medicine, Istanbul, Turkey
Toshihiro Kumabe, M.D. Department of Neurosurgery, Tohoku University
Graduate School of Medicine, Sagamihara, Kanagawa, Japan
Ram Kumar, M.D. Department of Neurology, Alder Hey Children’s NHS
Foundation Trust, Liverpool, UK
M. Kemal Kuşcu, M.D. Department of Psychiatry, Marmara University,
School of Medicine, Istanbul, Turkey
Grace K. Lai, M.D. Department of Neurosurgery, Prince of Wales
Hospital, Randwick, NSW, Australia
Il-Woo Lee, M.D., Ph.D. Department of Neurosurgery, Catholic University
of Korea, Seoul, South Korea
Anita Mahajan, M.D. Department of Radiation Oncology, MD Anderson
Cancer Center, Houston, TX, USA
Wirginia June Maixner, M.D. Department of Neurosurgery, Royal
Children’s Hospital Melbourne, Parkville, VIC, Australia
Conor Mallucci, M.D. Department of Neurosurgery, Alder Hey Children’s
NHS Foundation Trust, Liverpool, UK
Contributors xix

Maurizio Mascarin, M.D. Pediatric Radiotherapy Unit, Department of

Radiation Oncology, IRCCS – CRO Aviano Cancer Center (Italy),
Aviano, Italy
Luca Massimi, M.D. Division of Pediatric Neurosurgery, Catholic
University, Medical School-Rome/INI-Hannover, Rome, Italy
Thomas E. Merchant, D.O., Ph.D. Department of Radiation Oncology,
St. Jude Children’s Research Hospital, Memphis, TN, USA
Martina Messing-Jünger, M.D., Ph.D. Department of Pediatric
Neurosurgery, Asklepios Klinik Sankt Augustin, University-Hospital of
Bonn, Bonn, Germany
Philippe Meyer, M.D. Department of Anesthesiology, Necker Hospital,
Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Roberta Migliorati, M.D. Department of Oncology, Division of Pediatric
Oncology, A.O.R.N. Santobono-Pausilipon Children’s Hospital,
Naples, Italy
Giuseppe Mirone Division of Neurosurgery, Department of
Neurosciences, Santobono-Pausilipon Children’s Hospital, Naples, Italy
Nobuhito Morota, M.D. Division of Neurosurgery, National Medical
Center for Children and Mothers, National Center for Child Health and
Development, Setagaya, Tokyo, Japan
Anna Nastro, M.D. Service of Pediatric Neuroradiolgy, Department of
Neurosciences, Santobono-Pausilipon Children’s Hospital, Naples, Italy
Joachim Oertel, M.D. Department of Neurosurgery, Universitätsklinikum
des Saarlandes, Homburg-Saar, Germany
M. Memet Özek, M.D. Division of Pediatric Neurosurgery, Department of
Neurosurgery, Acibadem University, School of Medicine, Istanbul, Turkey
Department of Neurosurgery, Acibadem University, Istanbul, Turkey
Maria Rita Panico, M.D. Division of Radiology, Department of
Neurosciences, Federico II University, Naples, Italy
Ove Peters, M.D. Department of Pediatric Oncology, University of
Regensburg, Regensburg, Germany
Stephanie Puget, M.D., Ph.D. Department of Pediatric Neurosurgery,
Necker Hospital, Université Paris Descartes, Sorbonne Paris Cité, Paris,
France
Lucia Quaglietta, M.D. Department of Oncology, Division of Pediatric
Oncology, Santobono-Pausilipon Children’s Hospital, Naples, Italy
Charles Raybaud, M.D. Division Head of Neuroradiology, Hospital for
Sick Children and University of Toronto, Toronto, ON, Canada
Pablo F. Recinos, M.D. Division of Pediatric Neurosurgery, Johns Hopkins
University School of Medicine, Baltimore, M.D., USA
xx Contributors

Violette Renard Recinos, M.D. Department of Neurosurgery, Cleveland

Clinic, Cleveland, OH, USA
Albert L. Rhoton Jr., M.D. Department of Neurosurgery, Florida
University, Gainesville, FL, USA
Christian H. Rickert, M.D., Ph.D., FRCPath, FFSc(RCPA) Department
of Neuropathology and Paediatric Pathology, Vivantes Clinics Berlin,
Berlin, Germany
Andrea Rossi, M.D. Department of Pediatric Neuroradiology, G. Gaslini
Children’s Hospital, Genoa, Italy
Thomas Roujeau, M.D. Department of Paediatric Neurosurgery, Necker
Enfants Malades Hospital, Paris, France
Claudio Ruggiero, M.D. Division of Pediatric Neurosurgery, Department
of Neuroscience, Santobono-Pausilipon Children’s Hospital, Naples, Italy
James T. Rutka, M.D., Ph.D. Division of Neurosurgery, Department of
Surgery, The Hospital for Sick Children, The University of Toronto,
Toronto, ON, Canada
Christian Sainte-Rose, M.D. Department of Paediatric Neurosurgery,
Necker Hospital, Université Paris Descartes, Sorbonne Paris Cité, Paris,
France
Francesco Sala, M.D. Pediatric Neurosurgery Unit, Institute of
Neurosurgery, University Hospital, Verona, Italy
Aydin Sav, M.D. Department of Pathology, Acıbadem University, School
of Medicine, Istanbul, Turkey
Adam M. Scheinberg, M.D. Victorian Paediatric Rehabilitation Service,
Royal Children’s Hospital, Murdoch Children’s Research Institute, Faculty
of Medicine, Monash University, Parkville, VIC, Australia
Ehrenfried Schindler, M.D. Department of Anesthesiology and Critical
Care Medicine, Asklepios Klinik Sankt Augustin, University-Hospital of
Bonn, Bonn, Germany
Martin U. Schuhmann, M.D Section of Pediatric Neurosurgery,
Department of Neurosurgery, Eberhart Karls University Hospital of
Tübingen, Tübingen, Germany
Aşkın Şeker, M.D. Department of Neurosurgery, Marmara University,
Istanbul, Turkey
Mariasavina Severino, M.D. Department of Pediatric Neuroradiology,
G. Gaslini Children’s Hospital, Genoa, Italy
Spyros Sgouros, M.D., F.R.C.S. (S.N.) Department of Paediatric
Neurosurgery, “Mitera” Children’s Hospital, Athens, Greece
Department of Neurosurgery, University of Athens Medical School,
Athens, Greece
Contributors xxi

Gurmit Singh, M.D. Department of Neurosurgery, Penang General

Hospital, Penang, Malaysia
Christian Smith, Ph.D. Division of Neurosurgery, Department of Surgery,
The Hospital for Sick Children, The University of Toronto, Toronto, ON,
Canada
Pietro Spennato, M.D. Division of Pediatric Neurosurgery, Department of
Neuroscience, Santobono-Pausilipon Children’s Hospital, Naples, Italy
Bahattin Tanrıkulu, M.D. Department of Neurosurgery, Marmara
University, School of Medicine, Istanbul, Turkey
Marcos S. Tatagiba, M.D. Department of Neurosurgery, Eberhart Karls
University Hospital of Tübingen, Tübingen, Germany
Michael D. Taylor, M.D. Arthur and Sonia Labatt Brain Tumor Research
Centre, The Hospital for Sick Children, Toronto, ON, Canada
Yuzo Terakawa, M.D. Division of Neurosurgery, Department of Surgery,
The Hospital for Sick Children, The University of Toronto, Toronto,
ON, Canada
Department of Neurosurgery, Osaka City University Graduate School of
Medicine, Osaka, Japan
Dominic N.P. Thompson, M.D., MBBS, BSc, FRCS (SN) Department of
Pediatric Neurosurgery, Great Ormond Street Hospital for Children NHS
Trust, London, UK
Vincenzo Tramontano Intraoperative Neurophysiology Unit, Institute of
Neurosurgery, University Hospital, Verona, Italy
Vincenzo Trischitta, M.D. Division of Pediatric Neurosurgery, Department
of Neuroscience, Santobono-Pausilipon Children’s Hospital, Naples, Italy
Vasilios Tsitouras, M.D. Department of Pediatric Neurosurgery, “Mitera”
Children’s Hospital, Athens, Greece
Pascale Varlet, M.D. Department of Neuropathology, Sainte-Anne
Hospital, University Paris Descartes, Paris, France
Department of Pathology, Sainte-Anne Hospital, Paris, France
Antonio Vecchione, M.D. Department of Anesthesiology, Necker Hospital,
Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Antonio Verrico, M.D. Department of Molecular Medicine and Medical
Biotechnologies, “Federico II” University of Naples, Naples, Italy
Department of Oncology, Division of Pediatric Oncology,
A.O.R.N. Santobono-Pausilipon Children’s Hospital, Naples, Italy
Virginia Vitale, M.D. Department of Oncology, Division of Pediatric
Oncology, Santobono-Pausilipon Children’s Hospital,
Naples, Italy
xxii Contributors

Greg C. Wheeler, M.D. Radiation Oncology and Cancer Imaging, Peter

MacCallum Cancer Centre, East Melbourne, VIC, Australia
Johannes E. Wolff, M.D. Tufts Medical Center, Floating Hospital for
Children, Boston, MA, USA
Department of Pediatrics, MD Anderson Cancer Center, Houston, TX, USA
Department of Pediatric Oncology, University of Regensburg, Regensburg,
Germany
Department of Pediatric Hematology Oncology and Blood and Marrow
Transplantation, Cleveland Clinic Children’s, Cleveland, OH, USA
Brigitte Wrede, M.D. Department of Pediatric Oncology, University of
Regensburg, Regensburg, Germany
Ulaş Yener, M.D. Department of Neurosurgery, Acibadem University,
School of Medicine, Istanbul, Turkey
Michel Zerah, M.D. Department of Paediatric Neurosurgery, Necker
Enfants Malades Hospital, Paris, France
Massimo Zollo, M.D. Department of Biochemistry and Medical
Biotechnologies, “Federico II” University of Naples, Naples, Italy
Department of Molecular Medicine and Medical Biotechnologies, “Federico
II” University of Naples, Naples, Italy
General Principles of Treatment in
Pediatric Posterior Fossa Tumors
 History of Posterior Fossa Tumor
Surgery 1
James Tait Goodrich

1.1 Introduction a brief look at antiquity and then quickly move to

the Renaissance and the pioneering work of the
Development of surgical techniques for the treat- anatomists of the sixteenth century. This chap-
ment of posterior fossa disorders is, in the terms ter will review how the anatomy of the posterior
of historical events, very recent. In the sense of fossa was first understood. The evolution of sur-
“modern” surgical techniques, we are only look- gical technique and the individuals who provided
ing at a period that developed in the late quarter us with these new ideas will be discussed.
of the nineteenth century. In looking back at the In the twenty-first century, neurosurgeons
historical literature, surgeons since the time of now enter an operating room with an environ-
antiquity avoided any kind of surgical interven- ment much more advanced and technically
tion within the posterior fossa. Early surgeons more complex than what was available to their
quickly realized that this region of the brain is colleagues just 30 years ago. In the 1970s, the
extremely sensitive to any type of manipulation. surgical microscope revolutionized operative
Loss of respiration, sudden death, and distortion approaches with much improved visualization
of the brain stem, all could lead to a rapid demise assisted by better illumination, and as a result,
of the patient. As we shall see, surgery of the pos- surgeons could now operate more safely on areas
terior fossa really only came in being with the ori- of the brain previously considered unapproach-
gins of the twentieth century. A review of surgical able. Looking to the future, likely within the next
textbooks in the latter half of the nineteenth cen- decade, with the advance in computer-assisted
tury reveals only a minimal discussion of surgery devices, the “hands-on surgeon” will become a
in the posterior fossa. In the last 25 years, there relic of the past. The next generation of neuro-
has been a virtual explosion of techniques and surgeons will be “data suppliers,” i.e., a techni-
equipment related to what is now called frameless cian who makes entries into a database and then
surgical technology. To provide a historical per- sits back and watches the robotics, e.g., the “da
spective on this subject, the author will review the Vinci” perform the surgical operation.
development of posterior fossa surgery with only Having said that, we have made enormous
progress in surgical technique and the operative
management of patients with complex posterior
J.T. Goodrich, M.D., Ph.D., D.Sci. (Honoris Causa) fossa disorders. To provide a comparison, I would
Leo Davidoff Department of Neurological Surgery, like to present a scenario of a 1930s era operat-
Albert Einstein College of Medicine,
ing room, what was then considered a “mod-
Children’s Hospital at Montefiore,
111 East 210th Street, Bronx, NY 10467, USA ern” operating theater. Paul Bucy, a pioneer in
e-mail: [email protected] American neurosurgery, described the following

M.M. Özek et al. (eds.), Posterior Fossa Tumors in Children, 3

DOI 10.1007/978-3-319-11274-9_1, © Springer International Publishing Switzerland 2015
4 J.T. Goodrich

scene at the Queens Square Hospital in London, mid-portion of the suboccipital bone is a large
where he was working as a visiting surgeon: trephination with healed margins indicating the
…[A]t the National Hospital were Sir Percy individual survived the surgical procedure. The
Sargent and Mr. Donald Armour. They were both reason for the trephination is not clear and it does
poor surgeons, unbelievably crude in their surgical not appear that it was done for trauma. In review-
procedures. On one occasion (Gordon) Holmes ing a number of trephined skulls over the years,
told me to go with a patient to the operating theatre
and tell Sargent that because the lesion was prob- the vast majority was performed over the convex-
ably an arteriovenous malformation, he should use ity, and trephinations of the posterior fossa are
great care in exposing it. I did tell Sargent, but he actually quite rare Fig. 1.1.
paid no attention and proceeded to open the dura The only accounts of posterior fossa surgery
mater with a pair of sharp pointed scissors. In
doing so he ripped the malformation wide open, from the Greco-Roman era appear in the writ-
resulting in a severe hemorrhage and the patient’s ings of Galen of Pergamon (130–200 A.D.), from
death. On another occasion Armour performed an an area of what is now Turkey [3–6]. In Galen’s
occipital craniectomy with hammer and chisel. writings on anatomical procedures, he describes a
This patient also did not survive the operation.
There was a story current at the National Hospital series of animal dissections in which he exposed
that Denny-Brown, then a house officer, when the cerebellum and the fourth ventricle, investi-
assisting Armour in an operation would often gations which were done in the second century
remark that the blood had reached the drain in the A.D. Using primarily the rat, he made a linear
floor on the far side of the room and that perhaps it
would be wise to terminate the operation. [1] incision from the inion down to the foramen mag-
num. Galen studies were done in living animals
This historical vignette clearly shows how far with bleeding being controlled by finger pressure
we have come in a fairly short period of time. A and scalp retractors. The craniectomy was done
more complete anatomical foundation with a bet- with a series of chisels, especially designed for
ter understanding of the disease processes com- this operation. After the skull bone was removed,
bined with computer technology has clearly led Galen described the pulsating brain, especially
to better surgical outcomes and results in treating seeing it rise up out of the craniectomy when the
disorders of the posterior fossa. Understanding animal was agitated. Galen’s technique of opening
how we have managed to get to this point over the dura was no different than what we do today.
time makes for an interesting historical review of Galen used a small hook to elevate the dura away
our field. from the cerebellum and then incised it with a
This review will trace the origins of poste- sharp knife carefully avoiding any of the venous
rior fossa surgery from its antecedents in the sinuses, overlying cortical vessels, and the cer-
Renaissance to the 1940s. Unfortunately, only a ebellum. Galen pointed out in his discussion of
sampling of themes and personalities can be pro- the surgery that problems like cessation of breath-
vided due to page constraints. Other authors in ing could occur along with motor or sensory loss.
this monograph will deal with the developments The voice could become hoarse and even death
in posterior fossa surgery from the 1940s forward. could occur. From experimentation, Galen noted
that compression of the fourth ventricle could lead
to severe impairments and even death. It is well
1.2 Antiquity known that Galen was a surgeon to the gladiators,
so it is possible that he was involved in the treat-
Surgical operations on the posterior fossa have ment of traumatic injuries to the posterior fossa;
been dated back to antiquity [2]. From skulls whether he ever operated on these types of inju-
excavated from around the world are examples of ries is open to conjecture. Interestingly, Galen
trephinations of the posterior fossa, most of describes in his anatomical dissections splitting
which were done for trauma or other unknown the vermis to expose the fourth ventricle in living
reasons. In my own collection is a skull obtained animals. Galen carefully adds his comment that
from Peru in the 1950s that originates from a severe neurological impairments can happen with
graveyard that dates back to 600 A.D. In the this technique; nevertheless, it was a useful way to
1 History of Posterior Fossa Tumor Surgery 5

a b

Fig. 1.1 (a) A human skull from Peru dating to about 600 trephination done for unknown reasons. Along the lower
A.D. In the occipital bone is a trephination done for edge of the trephination are signs that show healing, so it
unknown reasons. The well-healed bony margins indicate is likely the patient survived this procedure. Courtesy of
the “patient” survived the operation. From the author’s the Museum of Man collection, San Diego, California
collection. (b) A skull with a large right occipital

expose the floor of the fourth ventricle. Galen was

the first to describe the calamus scriptorius, which
is seen on the floor of the fourth ventricle using
this surgical exposure. Galen, throughout his writ-
ings, noted that knowledge of the surgical anatomy
was absolutely key for the surgeon; without this
knowledge, the surgeon would be prone to serious
errors and bad outcomes. Unfortunately, much of
Galen’s animal anatomy was incorrectly transliter-
ated into human anatomy and then carried forward
by various translations (e.g., Latin, Greek, and
Arabic) to the time of the Renaissance. As we shall
see, it was the Renaissance artist that led the drive
to first understand and describe human anatomy
from hands-on dissections of humans Fig. 1.2.

1.3 The Sixteenth Century:

The Origins of Modern
Anatomy and Surgical
Investigation

At the end of the fifteenth century, the intellec-

tual currents in Europe were undergoing pro-
found changes. With the introduction of the
printing press and moveable type, books could Fig. 1.2 An early English translation of Galen’s writing
including his “office of a chirurgion” in which he details
be more easily and cheaply produced. As the his surgical techniques along with general works on medi-
intellectual shackles of the Middle Ages were cine [5]
6 J.T. Goodrich

being removed, physicians were beginning to rely tion to “human” anatomy. Ironically, it was the
more on what their eyes taught them at the bed- Renaissance artist followed by sixteenth-century
side. The previously held concepts of the early anatomists and surgeons that led the movement
anatomists like Galen of Pergamon and others in anatomy away from subservience to the medi-
would be challenged in their accuracy. One of evalists. With great figures like Leonardo da
the most important intellectual currents in sur- Vinci (1452–1519), Berengario da Carpi (1470–
gery and medicine at this time were the schools 1550), Johannes Dryander (1500–1560), Andreas
of anatomical studies like Michelangelo, Titian, Vesalius (1514–1564), and others that was to lead
and Leonardo da Vinci among others [7, 8]. In to a new movement based on a hands-on anatomi-
an attempt to provide more realistic surface anat- cal dissection of the human body. As a result, pre-
omy of the human, these individuals were doing vious codified anatomical errors, many ensconced
hands-on dissection unencumbered with the ear- since the Greco-Roman era, were to be slowly
lier medieval anatomical texts and doctrines that corrected over the next several centuries. These
were rife with errors. The “typical” surgeon at changes in studies from codified manuscripts to
the beginning of the sixteenth century was noth- a new and more accurate human anatomy also led
ing more than an unskilled and poorly educated to a surge of interest in surgery. The Renaissance
barber surgeon. This surgeon could cut your hair, surgeon, like the artist, became interested in try-
remove a tooth, and repair a hernia. There were a ing to unravel the intricacies of the human body –
very few surgeons with either prominent person- without this foundation of knowledge, it would
alities or formal education. The “educated” sur- be impossible to correctly treat a disease much
geon having learned medieval dogma remained less perform a surgical resection. In the area of
buried in conjecture and training from centuries posterior fossa anatomy and surgery, a number
of beliefs based on earlier Greco-Roman and later of important Renaissance figures played pivotal
Byzantine teachers and translators who continued roles in bringing forward posterior fossa surgery
to translate and repeated the errors of the past sur- as both an art and a science.
gical history. In learning and then following these While neither a surgeon nor a physician,
antiquated surgical writings, medieval surgeons Leonardo da Vinci (1452–1519) made enormous
often found themselves in conflict with their own contributions to both medicine and surgery.
bedside observations. As a result of these com- Leonardo was the quintessential Renaissance
mon conflicts of written text versus what was man. Recognized as an artist, an anatomist, and a
actually being seen in the anatomical amphithe- scientist, Leonardo learned human anatomy, both
ater, a number of innovative personalities dually surface and deep to better provide more realistic
learned their surgical material not only as sur- artistic creations. Leonardo’s anatomical studies
geons but also as anatomists. Within the origins were extremely important in providing an early
of the intellectual climate of the Renaissance, we emancipation from the previous medieval teach-
begin to see profound changes in learning, par- ings. Leonardo’s output in anatomical studies
ticularly in the anatomical investigations of the led to some 750 separate anatomical drawings.
human body. To modern scholars, Leonardo is now consid-
With the early origins of the Renaissance, we ered the founder of iconographic and physiologic
see a renewed interest in human anatomical dissec- anatomy [9–11].
tion, anatomical dissections and drawings which at Some of the earliest anatomical drawings on
this point had been almost frozen in time for some posterior fossa anatomy appear in Leonardo’s
1400 years dating to the time of the Alexandrians. anatomical studies [9]. To Leonardo we owe
From the Byzantine era and through the Middle the earliest surviving illustrations of the cranial
Ages, anatomy was based on the previous writ- nerves. Figures 1.3 and 1.4, Leonardo did not
ings of the giants such as Galen of Pergamon who describe all 12 of the cranial nerves though he was
performed their anatomical dissections on non- the first to provide some reasonably accurate dia-
human subjects and then morphing this informa- grams. To Leonardo we owe the first illustrations
1 History of Posterior Fossa Tumor Surgery 7

a b

Fig. 1.3 (a) An early copper engraving of Leonardo da There are the earliest known anatomical drawings of the
Vinci (from the collection of author). (b) Leonardo’s cerebral ventricles – for the first time demonstrating the
sketches of the “wax casting” of the ventricles of the third ventricle, aqueduct of Sylvius and the fourth
brain. In these drawings, the third and fourth ventricles are ventricle [9]. (d) Leonardo’s “layered” anatomical studies
anatomically outlined for the first time. In the bottom on the skull, brain, and cranial nerves, what would appear
image is an early and rudimentary drawing of the cerebel- to be the earliest “realistic” anatomical demonstrations of
lum and brain stem [9]. (c) Da Vinci anatomical illustra- the cranial nerves [9]
tions of the ventricular system – enlarged from b.

of the ventricular system. Using a uniquely removing the brain from the skull and injecting
designed “wax casting” of the ventricular sys- melted wax through the fourth ventricle. Mental
tem, Leonardo was able to detail the anatomical tubes were placed in each of the lateral ventricles
landmarks of these cavities including the fourth to allow air to be released. Once the injected wax
ventricle (see Fig. 1.3c). Leonardo’s “wax cast- hardened, the brain was removed leaving behind
ing” technique was quite innovative and involved a wax casting of ventricles.
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laxity
lay
Layard
layer
layers
laying
layman
lays
Lazaro
Lazear
Lazes
lazuli
lazy
lb
le
lead
leader
leaders
leadership
leading
leadingstrings
leads
leaf
leafy
LEAGUE
leagued
leagues
leaked
Lean
Leander
leaned
leaning
leanings
Leao
leap
leaped
leaps
learn
learned
Learning
learns
learnt
lease
leased
leasehold
leases
leash
leasing
Least
leathern
leave
leavened
leaves
leaving
Lebanon
Lebel
Leblois
Lebrun
Lebœuf
LECHER
lecherous
lecture
lectured
lecturers
Lectures
lecturing
Led
ledges
Lee
Leech
Leeds
Lees
Leeward
left
leg
legacy
legal
legality
legalized
legally
Legaria
Legaspi
legation
legations
legend
legendary
legends
Legge
legion
legions
legislate
legislated
legislating
LEGISLATION
Legislative
legislators
Legislature
Legislatures
Legitimate
legitimately
legs
Lehigh
Lei
LEICHAU
Leighton
Leipsic
Leipzig
leisure
leisurely
Leite
Leland
Lemercier
Lena
Lenard
lend
lenders
lending
length
lengthened
lengthening
lengths
lengthy
leniency
lenient
leniently
Lenox
lens
lent
Lentilhon
Leo
Leon
Leonard
LEONE
Leonora
Leopold
leper
Lerner
Leroy
les
Leslie
less
lessees
lessen
lessened
lessening
Lesseps
Lesser
lesson
lessons
lessor
lest
let
lethargy
Letran
Letter
letters
Letting
Leucocytes
Levant
level
leveled
levelled
levelling
lever
Levering
Levi
leviable
levied
levies
Levis
levy
levying
Lewis
Lewiston
LEX
Lexicon
Lexow
Leyba
Leyden
Leyds
Leydsdorp
Leyte
Lezo
li
liabilities
Liability
Liable
Liang
Liao
Liaotung
libel
libellous
libels
liberal
liberalism
liberality
liberalized
liberalizing
liberally
Liberals
liberated
liberating
liberation
liberators
Liberia
liberties
liberty
libidinous
Libog
Librarian
librarians
libraries
Library
LIBRE
Libyan
Libyans
libérateur
libéré
licence
Licences
licencia
license
licensed
licensee
licenses
licensing
licentious
lichens
licked
lid
Liddell
lie
Liebig
Liebknecht
Liechtenstein
Liefsting
Liege
lien
liens
lies
lieu
lieutenancy
Lieutenant
lieutenants
life
lifeless
lifelong
lifetime
lift
lifted
lifter
light
lighted
lightened
lightening
lightens
lighter
lighters
lightest
Lighthouse
lighthouses
Lighting
lightly
lightning
lights
lightships
LII
LIII
Like
liked
likelihood
likely
liken
likened
likeness
likes
Likewise
likin
liking
Likipia
lil
Liliuokalani
Lille
Lima
Limantour
limb
Limbancauyan
Limbourg
limbs
lime
limes
limit
limitation
limitations
limited
limiting
limits
limply
Limpopo
Lin
Linapacan
Linares
LINCOLN
Linde
Lindsay
line
lineage
lineal
linear
lined
linen
Linens
LINES
Lingay
Lingayen
lingering
Lingey
Linivitch
link
linked
links
linotype
Linton
lion
Lionel
lioness
lionised
lions
lip
Lippett
Lippincott
lips
Liquefaction
liquefy
liquefying
liquid
liquidated
liquidating
liquidator
liquids
liquor
liquors
Lisbon
Liscum
lisière
list
listen
listened
listening
lists
lit
literacy
literal
literally
Literary
literati
Literature
litigants
litigation
Littell
litters
LITTLE
Littmann
littoral
LIU
LIV
live
lived
liveliest
livelihood
lively
liver
Liverpool
lives
livestock
Living
Livingstone
LIX
LL
Lloyd
lo
Loa
load
loaded
Loading
loads
loafers