Diagnostic Assessment and Treatment of Peripheral Nerve

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Editors
Fernando Guedes Eric L. Zager
WFNS Peripheral Nerve Surgery WFNS Peripheral Nerve Surgery
Committee Committee
Division of Neurosurgery Department of Neurosurgery
Department of Surgery University of Pennsylvania
Gaffrée e Guinle University Perelman School of Medicine
Hospital (HUGG) Philadelphia, PA
School of Medicine USA
Federal University of Rio de
Janeiro State (UNIRIO) Lukas Rasulic
Rio de Janeiro WFNS Peripheral Nerve Surgery
RJ Committee
Brazil Faculty of Medicine University of
Belgrade
Debora Garozzo Clinic for Neurosurgery, University
WFNS Peripheral Nerve Surgery Clinical Center of Serbia
Committee Department of Peripheral Nerve
Department of Neurosurgery Surgery, Functional Neurosurgery and
Mediclinic Parkview Hospital Pain Management Surgery
Dubai Belgrade
UAE Serbia

Mariano Socolovsky
WFNS Peripheral Nerve Surgery
Committee
Peripheral Nerve & Brachial Plexus
Surgery Program
Department of Neurosurgery
University of Buenos Aires
School of Medicine
Buenos Aires
Argentina

ISBN 978-3-030-77632-9    ISBN 978-3-030-77633-6 (eBook)

https://doi.org/10.1007/978-3-030-77633-6

© Springer Nature Switzerland AG 2021

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Dr. Fernando Guedes:
I dedicate this book to my lovely wife Elizabeth and our dear
son Thiago.
I’d like to thank my dear fellow coeditors and also my dear
colleagues from many parts of the world who contributed with
their expertise in several chapters.
I cannot forget to thank the people in Springer, particularly Ms.
Niveka Somasundaram, for the incredible support they gave us
throughout this project.
To all patients suffering from peripheral nerve tumors: that
they may benefit from this work.
Dr. Eric L. Zager:
I dedicate this book to my loving family:
To my parents, Daniel and Florence, and my sister, Robin, all
of blessed memory.
To my wonderful wife, Marirosa, for her love and support.
To my fabulous children, Camila, David, and Daniel.
To my mentors in nerve surgery, Professors David Kline and
Alan Hudson.
And to my larger family of colleagues, residents, students, and
especially to my patients and their families.
Dr. Debora Garozzo:
To the everlasting memory of Lauris Muischneek and to what
we were for each other.
Dr. Lukas Rasulic:
I dedicate this book to my driving force, my family: my wife
Katarina, our daughter Milica, and our son Mihailo;
my parents: my father Grujica and my mother Dusanka;
my sister Katarina;
my mentor, Prof. Dr. Miroslav Samardzic, and my associates;
and last but not the least, my patients with peripheral nerve
disorders.
Dr. Mariano Socolovsky:
I dedicate this book to the wonderful team I have the honor to
work with: Gilda di Masi, Danilo Battaglia, Verónica
Brandolin, Gonzalo Bonilla, Karina Barillaro, Ana Lovaglio,
Daniela Binaghi, and Rafael Barousse.
Foreword

It is a great pleasure and honor to write the Foreword for this book on periph-
eral nerve tumors, written and edited by distinguished colleagues and dear
friends from the WFNS Peripheral Nerve Surgery Committee.
The activity of the WFNS PNS Committee has been outstanding over the
past few years. A continuous effort from the group of devoted neurosurgeons,
with their compassionate endeavors in the preservation of peripheral nerve
surgery within neurosurgery, once again led to the most comprehensive book
on peripheral nerve tumors to date.
These lesions (accounting for only about 1% of all soft tissue tumors)
demand a dedicated and meticulous approach. With the era of “life-saving,”
functional or even extremity sacrifice having passed, contemporary approaches
to peripheral nerve tumors include basic principles, a deep understanding of
pathophysiology and pathomorphology, as well as modern surgical techniques
and tricks. With the development of chemotherapeutics and radiation-­oncology,
with targeted therapies taking their rightful place, we now have all the best tools
at our disposal, and this book is here to guide new generations of neurosurgeons
and peripheral nerve surgeons. The book is also aimed at all physicians dealing
with these complex lesions, however with the emphasis on young neurosur-
geons, as well as those expected to solve the most demanding cases.
This book will help in educating general neurosurgeons and beyond. On
the other hand, it should inspire experts to expand knowledge and to improve
patient outcomes. The field of peripheral nerve surgery is considered one of
the less represented areas in any average neurosurgical department world-
wide. I am confident that this book will raise awareness about the importance
of this field and contribute to its visibility and increasing interest.
I would like to congratulate the editors of this book, Fernando Guedes,
Mariano Socolovsky, Lukas Rasulic, Eric L. Zager, and Debora Garozzo, as well
as all chapter authors for publishing a very useful book to support all surgeons
involved in the diagnostic assessment and treatment of peripheral nerve tumors.

Franco Servadei
Department of Neurosurgery, Humanitas
University and Research Hospital Milano, Milan, Italy
WFNS, Milan, Italy
Italian Society of Neurosurgery (SINCh), Milan,Italy

vii
Foreword

What a pleasure it is to be asked to write a foreword for this book on periph-

eral nerve tumors. One of the great challenges and sometimes the joy of
working with surgical nerve lesions are managing patients with nerve tumors.
The editors Fernando Guedes (Brazil), Eric L. Zager (USA), Debora Garozzo
(Italy and UAE), Lukas Rasulic (Serbia), and Mariano Socolovsky (Argentina)
as well as 30 chapters from North, Central, and South America, Europe,
India, and UAE have created a fascinating compendium covering epidemiol-
ogy, genetics, pathology, clinical assessment, neurophysiology, ultrasound,
MRI, biopsy, surgical resection, intraoperative monitoring, complications,
pain management, radiotherapy and chemotherapy, neurofibromatosis,
schwannomatosis, and malignancies, and I imagine a number of other tumor
types in addition to the most common benign neural sheath tumors, schwan-
nomas, neurofibromas, and others such as perineuriomas—localized hyper-
trophic neuropathy (LHN), hemangiomas, ganglion cysts, desmoids, triton
tumors, and more. The different loci of tumors such as the brachial and pelvic
plexus are also delineated. You will enjoy both consulting and reading this
new and up-to-date book on peripheral nerve tumors.
As a minor historic addendum—when we began to operate on nerve
tumors in the late 60s, 70s, and 80s, we already had experience with operative
recordings of CNAPs (Compound Nerve Action Potentials) for injured nerves
in continuity. It became evident that what was very important was to expose
both the proximal and distal poles of schwannomas and neurofibromas
because there were fascicles or groups of fibers entering and leaving both
poles (more in neurofibromas than schwannomas) and when entering fasci-
cles were stimulated proximally and recordings done on exiting fascicles dis-
tally, the traces were flat on these rather globular tumors. By comparison,
fascicles or groups of fibers more superficial in the capsule or pseudocapsule
conducted an NAP as did the nerve as a whole even when fascicles or fiber
groups entering and leaving the mass of the tumor were sectioned. Histological
examination of the entering and leaving fascicles or fibers from the tumor
mass itself showed a rudimentary array of immature poorly developed, small
axons in a very disorganized background. As one Ochsner pathologist com-
mented—the entering and exiting fascicles had an embryonic appearance.
This was also confirmed by Masson, Bodian, and Luxol fast blue as well as
HandE stains in our own neurohistology laboratory at LSUHSC NS (Louisiana
State University Health Sciences Center, Department of Neurosurgery).

ix
x Foreword

These observations were made not only on sporadic neurofibromas but those
associated with neurofibromatosis.

• Donner TR, Voorhies RM, Kline DG. Neural sheath tumors of major
nerves. J Neurosurg. 1994;81:362–73
• Kim DH, Hudson AR, Kline DG. Surgical techniques for nerve tumors. In
Atlas of peripheral nerve surgery. 2nd Ed. Philadelphia: Saunders-­Elsevier;
2013. p. 235–40.
• Kline DG, Hudson AR, Kim DH. Benign neural sheath tumors. In Atlas of
peripheral nerve surgery. Philadelphia: Saunders-Elsevier; 2001.
p. 190–6.

David G. Kline
LSUHSC-NS
New Orleans, LA, USA
Preface

We are pleased to present this text Diagnostic Assessment and Treatment of

Peripheral Nerve Tumors to the medical community. This work was con-
ceived by the Peripheral Nerve Surgery Committee of the World Federation
of Neurosurgical Societies and follows upon the previous text Manual of
Peripheral Nerve Surgery: From the Basics to Complex Procedures,
which was published in 2018. We are very fortunate to have received superb
contributions from many of the leading nerve surgeons in the world, along
with our colleagues in neuroradiology, neuropathology, and neurology.
Peripheral nerve tumors comprise a fascinating group of heterogeneous
lesions that challenge our diagnostic and therapeutic capabilities. Our man-
agement of these lesions has progressed substantially in recent decades
through the pioneering efforts of our colleagues in many disciplines, but
many controversies and challenges remain. No longer do we accept the rou-
tine sacrifice of functional nerve fascicles when resecting benign nerve sheath
tumors. However, even the most experienced and skillful nerve surgeons do
inadvertently injure nerves occasionally when removing certain difficult
lesions, even when benign. Recognizing and dealing with potentially malig-
nant lesions is even more challenging, and we have not even reached uniform
agreement as to when a biopsy is mandatory prior to tumor resection. Imaging
has improved substantially for these tumors, but is still incapable of reliably
diagnosing malignancy in many cases without a tissue diagnosis. Once a
malignant lesion is diagnosed, there is still major controversy regarding opti-
mal management in terms of the type and timing of adjuvant therapy and
reconstructive options.
In this text, we present first the general principles of clinical and surgical
approaches to nerve tumors. This section includes chapters on epidemiology,
genetics and pathology of nerve tumors, the clinical and radiological assess-
ment of these patients, indications and techniques for biopsy, the fundamental
aspects of surgical technique along with intraoperative neurophysiological
monitoring, and recognition and management of the inevitable and unfortu-
nate complications which accompany any surgical endeavors. We also dis-
cuss the indications for adjuvant therapy of malignant tumors. The second
and third parts of this book include chapters that deal with specific tumor
types and locations in the body in both the general population and in specific
genetic disorders.
Our goal here is to provide a readable collection of chapters that cover this
fascinating topic comprehensively for both the generalist and the specialist,

xi
xii Preface

with contemporary and classic references for further reading. Our target audi-
ence is broad and includes neurosurgeons, neurologists, hand surgeons in
orthopedic and plastic surgery, surgical oncologists, radiation therapists,
physiatrists, physical and occupational therapists, and even vascular and gen-
eral surgeons who often collaborate and provide operative exposure for us.
We wish to thank our authors for their expertise and eloquence, and our pub-
lisher for their support in this endeavor. Most importantly, we wish to thank
our patients for their trust and confidence that we are constantly striving to
improve our care for their neurological disorders.

Rio de Janeiro, Brazil Fernando Guedes

Philadelphia, PA, USA  Eric L. Zager
Dubai, UAE  Debora Garozzo
Belgrade, Serbia  Lukas Rasulic
Buenos Aires, Argentina  Mariano Socolovsky
Contents

Part I General Clinical and Surgical Principles in Peripheral

Nerve Tumors

1 Epidemiology of Peripheral Nerve Sheath Tumors����������������������   3

Andrew S. Jack, Charlotte J. Huie, and Line G. Jacques
2 Genetics of Nerve Tumors �������������������������������������������������������������� 17
Kimberly Harbaugh, Neel T. Patel, and Elias Rizk
3 Pathological Basis for Classification (Cytomolecular Aspects)���� 29
Gustavo Sevlever
4 Clinical Assessment�������������������������������������������������������������������������� 43
Thomas Kretschmer, Christian Heinen, and Jakob Kraschl
5 Preoperative Neurophysiological Evaluation�������������������������������� 49
Ricardo de Amoreira Gepp and Ênio Comerlato
6 Ultrasound Imaging ������������������������������������������������������������������������ 59
Maria Teresa Pedro and Ralph Werner König
7 Magnetic Resonance Neurography������������������������������������������������ 65
Daniela Binaghi
8 X-Ray, Computed Tomography (CT), Positron Emission
Tomography (PET) Imaging, and Intraoperative
Imaging Adjuncts in the Evaluation and Treatment
of Peripheral Nerve Tumors������������������������������������������������������������ 85
Adela Wu, Thomas J. Wilson, and Michel Kliot
9 Indications and Techniques for Preoperative Biopsy
in Peripheral Nerve Tumors������������������������������������������������������������ 95
Fernando Guedes, Gabriel Elias Sanches,
Rodrigo Salvador Vivas Cardoso, and Martijn J. A. Malessy
10 Fundamental Aspects of the Surgical Techniques for
the Resection of Peripheral Nerve Tumors������������������������������������ 105
Harley Brito da Silva, Francisco Flávio Leitão de Carvalho Filho,
and Rajiv Midha
11 Neurophysiological Monitoring during Surgery�������������������������� 115
Carlos Alberto Rodríguez Aceves and Armando Tello Valdés

xiii
xiv Contents

12 Complications after Tumor Resection�������������������������������������������� 125

Javier Robla Costales, Mariano Socolovsky,
and Fernando Martínez Benia
13 Management of Painful Conditions Associated with
Nerve Tumors ���������������������������������������������������������������������������������� 129
Anna C. Filley and Christopher J. Winfree
14 Indications for Radiotherapy and Chemotherapy
in Malignant Tumors ���������������������������������������������������������������������� 141
James Feghali, Daniel Lubelski, and Allan J. Belzberg

Part II Peripheral Nerve Tumors in the General Population

15 Schwannomas of the Extremities���������������������������������������������������� 151

Mario Siqueira, Roberto Martins, and Luciano Foroni
16 Neurofibromas���������������������������������������������������������������������������������� 167
Lukas Rasulic, Milan Lepić, Andrija Savić,
and Miroslav Samardžić
17 Perineuriomas���������������������������������������������������������������������������������� 177
Christine Brand and Gregor Antoniadis
18 Non-neurogenic Tumoral and Pseudotumoral Lesions
Affecting Peripheral Nerve ������������������������������������������������������������ 181
Tomas Marek, Kimberly K. Amrami, and Robert J. Spinner
19 Malignant Peripheral Nerve Sheath Tumors�������������������������������� 193
Fernando Guedes, Gabriel Elias Sanches, Stephanie Bulhões,
Ana Caroline Siquara-de-­Sousa,
and Karin Soares Gonçalves Cunha
20 Management of Brachial Plexus Tumors�������������������������������������� 223
Sophie Y. Su, Martijn J. A. Malessy, Line G. Jacques,
and Eric L. Zager
21 Management of Lumbosacral Plexus Tumors������������������������������ 241
Fernando Guedes, Gabriel Elias Sanches,
Rosana Siqueira Brown, and Rodrigo Salvador Vivas Cardoso
22 Management of Paraspinal Nerve Sheath Tumors ���������������������� 259
Christopher F. Dibble and Wilson Z. Ray
23 Nerve Tumors of Childhood and Infancy�������������������������������������� 273
Svetlana Kvint, Zarina S. Ali, Line G. Jacques,
Gregory Heuer, and Eric L. Zager

Part III Peripheral Nerve Tumors in Genetic Diseases

24 Epidemiology of Genetic Diseases with Peripheral

Nerve Tumors ���������������������������������������������������������������������������������� 303
Robert B. Kim and Mark A. Mahan
Contents xv

25 A General Introduction to Neurofibromatosis������������������������������ 313

Sumit Sinha, Nishant Yagnick, and Harsh Deora
26 Genetic Aspects of Peripheral Nervous System Tumors�������������� 331
Marcela Ferrer, Patricia Ciavarelli, and Mariano Socolovsky
27 Clinical Management of NF1 and Indications for Surgery���������� 347
Debora Garozzo
28 Plexiform Tumors���������������������������������������������������������������������������� 355
Debora Garozzo
29 Management of MPNST in Neurofibromatosis���������������������������� 361
Debora Garozzo, Zarina S. Ali, and Eric L. Zager
30 Schwannomatosis: Review of Diagnosis and Management���������� 371
Zach Pennington, Daniel Lubelski, Ravi Medikonda,
and Allan J. Belzberg
 Part I
General Clinical and Surgical Principles in
Peripheral Nerve Tumors
 Epidemiology of Peripheral Nerve
Sheath Tumors 1
Andrew S. Jack, Charlotte J. Huie,
and Line G. Jacques

The first description of what was likely a peripheral peripheral nerve sheath tumors) alike. By under-
nerve tumor was published by Cheselden in 1741 standing the respective epidemiology of these rare
[1]. Since that time, not only has management of tumors, a better appreciation for their clinical bur-
peripheral nerve tumors obviously changed dra- den will hopefully prevail.
matically, but so has their reported epidemiology
(as summarized in Table 1.1). With the advent of
newer and more readily accessible imaging modal- 1.1 Schwannomas
ities such as magnetic resonance imaging (MRI)
and MR neurography, reported peripheral nerve Schwannomas are a benign PNST originating
tumor incidence has increased substantially. from Schwann cells encasing and insulating
Peripheral nerve tumors can be subdivided into nerve fibers. They are the most common benign
nerve sheath and non-nerve sheath tumors. As their PNST, a category that also includes neurofibro-
name implies, peripheral nerve sheath tumors mas (NF), perineuriomas, and granular cell
(PNSTs) are tumors arising from cells surrounding tumors (to be discussed elsewhere). However,
an axon or nerve fascicle(s), which may include, they can be quite heterogeneous in nature with
for example, Schwann cells, fibroblasts, and histio- respect to their reported epidemiology, including
cytic or macrophage-like cells, among others. They incidence and/or prevalence, location, and natu-
can also be further subdivided into benign or malig- ral history, among others. Values and statistics for
nant. In this chapter, we will compare and contrast the aforementioned tumor characteristics will
the different epidemiological characteristics of the also vary substantially depending on the context
most frequently encountered PNST—both benign in which they are being discussed. More specifi-
(schwannomas, neurofibromas, perineuriomas, cally, reported values will vary depending on
granular cell tumors, ganglioneuromas) and malig- whether they are occurring sporadically or in
nant (malignant granular cell tumors and malignant association with a genetic syndrome (e.g., neuro-
fibromatosis 1 versus 2 (NF-1 and NF-2, respec-
A. S. Jack (*) tively), schwannomatosis, or Carney’s complex).
Division of Neurosurgery, University of Alberta, How the incidence and prevalence of schwan-
Edmonton, AB, Canada nomas are qualified (the context or circumstance
e-mail: [email protected] in which they are being described) will ultimately
C. J. Huie · L. G. Jacques dictate how common or uncommon they are
Department of Neurosurgery, University of reported to be. Because schwannomas can poten-
California San Francisco (UCSF), San Francisco,
CA, USA tially arise from any nerve throughout the body
e-mail: [email protected] (or anywhere Schwann cells may be found for
© Springer Nature Switzerland AG 2021 3
F. Guedes et al. (eds.), Diagnostic Assessment and Treatment of Peripheral Nerve Tumors,
https://doi.org/10.1007/978-3-030-77633-6_1
 4

Table 1.1 Summary table of the epidemiological characteristics of peripheral nerve sheath tumors
Malignant granular
Schwannoma Neurofibroma Peri-neurioma Granular cell tumor Ganglio-­neuroma MPNST cell tumor
Incidence 20/million/year 5% of soft tissue 1% of nerve 0.5% of soft tissue 1/million/year [21, 44] 1/100,000/year 1–3% of granular
[127] tumors [70, 115] sheath tumors tumors [128] general cell tumors [128,
[80, 89, 93, 145] population vs 141]
1/3500/year
NF-1 [12, 13,
26, 27, 61, 74,
86, 101]
Age (years) 20–50 20–30 Intraneural: 30–50 Childhood 30–50 (mean 41 30–50
adolescence to vs 28 in NF-1)
adulthood
Extraneural:
adulthood
Sex Females = Males Females = Males No clear sex Females > Males No clear sex predilection No clear sex Females > Males
predilection predilection
Location Central: Anywhere: any Intraneural: Anywhere: Anywhere: neural crest Superficial Lower extremity,
intracranial, nerve lower > upper commonly head and cell derivatives (cutaneous) or nuchal region,
intraspinal, extremities neck deep (plexiform) chest wall,
intracerebral and/ Extraneural: gastrointestinal
or intramedullary trunk or tract, head, and
Peripheral extremities neck
Classification Conventional Dermal: localized or Intraneural Benign Neuroblastic tumor: Low grade Low grade
Ancient diffuse Extraneural Atypical ganglioneuroma, High grade High Grade
Cellular Intraneural localized Malignant ganglioneuroblastoma,
Plexiform Plexiform ganglioneurobalstoma
Melanotic Atypical intermixed, neuroblastoma
Intermediate Massive soft-tissue
Epithelioid type
A. S. Jack et al.
1 Epidemiology of Peripheral Nerve Sheath Tumors 5

that matter), most reports will classify ies have characterized the incidence of schwan-
schwannomas in context of their histology or
­ nomas based on location and tissue of origin or
based on their location. For example, schwanno- age. For example, in a radiological study examin-
mas are often categorized as being peripheral ing the most common soft tissue tumors of the
(occurring predominantly in the head and neck upper extremity, Hoglund et al. found 5% of
area or flexor aspects of the extremities) or cen- benign soft tissue tumors in their series to be
tral (affecting the cranial nerves or spinal nerve schwannomas [26]. In keeping with their preva-
rootlets and/or roots). Their prevalence is also lence and incidence, gender and age peaks may
often described on the basis of location, intracra- also vary based on the schwannoma location.
nial, intraspinal, intracerebral, and/or intramedul- Although it is generally accepted that schwanno-
lary, or in the context of other soft tissue or nerve mas generally affect adults more than children
sheath tumors. These schwannoma qualifiers will (usually occurring in patients between 20 and
then determine and affect the specific values 50 years of age) [21, 27–31], whether or not a sex
reported. For example, schwannomas are reported predilection exists for schwannomas remains
to be the most common benign PNST (as high as controversial. Some studies state no difference in
80% in some reports) [2–4]; however, they only tumor incidence between males and females [2,
account for 8% of all soft tissue tumors [1]. They 10, 16, 27, 28, 30, 32–35], while others state
have also been reported to represent 33% of pri- females are more affected [1].
mary spinal tumors [5–8], 8–10% of primary The natural history of schwannomas with
brain tumors [9–12], and 5.8% of foot and ankle respect to their growth rate is an important ele-
peripheral nerve tumors [13]. Moreover, the mat- ment to consider when trying to determine the
ter of tumor symptomatology (asymptomatic or best patient management strategy. This can often-
incidental diagnosis versus diagnosis based on times be difficult as the reported growth rate for
symptomatic investigations) and how the tumors these tumors is very heterogeneous depending on
are being diagnosed (cadaveric study versus the study (likely related to the heterogeneity in
radiological cross-sectional study) will also methods used for tumor size and growth mea-
greatly affect the prevalence reported. For exam- surements, the presence of extrinsic factors
ple, in earlier studies using cadaveric dissection affecting tumor growth, as well as the tumor biol-
for diagnosis, the prevalence of vestibular ogy and histological subtype itself). For example,
schwannomas (VS, incidental) was reported to be sporadic growth rates have been said to vary from
0–2.4% [10, 14–17]. However, with the increas- 1–2 mm/year up to 17 mm/year. In their review,
ing use of MRI, other studies have found the VS Paldor et al. found an average growth rate of
prevalence to be 0.02–0.07% [16, 18–20]. approximately 1 mm/year; however, it can be
In a similar vein, the incidence that is reported 3 mm/year in those tumors demonstrating growth
with respect to these tumors can also vary sub- at early follow-up [34]. Furthermore, approxi-
stantially depending on how it is defined (the mately one-third of newly diagnosed sporadic VS
context of the reported incidence). For example, had grown within 1–3 years and 50% after 5 years
in one prospective epidemiological database of follow-up. And finally, factors determined to
from Denmark, the incidence of diagnosed VS increase growth rate or predict tumor growth
was reported to have increased from 8/million/ included hormonal therapy (specifically, erythro-
year at its inception to more recently 20/million/ poietin), hemorrhagic or cystic tumor features,
year [21]. The rapid increase in the incidence of and early demonstrated growth on follow-up.
VS is likely related to increasing awareness of Age, sex, location, symptomatic status, and size,
these tumors and improved diagnostic investiga- however, did not predict growth. In another study
tions such as audiological testing and MRI tech- examining schwannomas of other cranial nerves,
niques. In keeping with this latter value, other growth rate was again noted to be quite variable
studies have found an incidence for VS to be (0.7 mm–2.6 mm/year, average 1.4 mm/year)
between 0.01 and 0.1% [16, 22–25]. Other stud- [36, 37]. Although many of these extrinsic factors
6 A. S. Jack et al.

may influence schwannoma growth patterns, as schwannomas in the context of genetic diseases
mentioned above, perhaps a more likely explana- and syndromes such as NF-1, NF-2, Carney’s
tion for the varied growth rates reported is that complex, or schwannomatosis. Although dis-
different histological subtypes (as shown in cussed here are mainly sporadic schwannoma
Fig. 1.1) of schwannomas [38] (subcategorized characteristics, their occurrence in diseases such
as cellular, conventional, intermediate, ancient, as those just mentioned will ultimately lead to
melanotic (1% of PNST) [39], plexiform (5% of different epidemiological and behavioral charac-
schwannomas) [40], epithelioid) simply have dif- teristics (to be discussed in later chapters).
ferent genotypes. The specific genetic or epigen-
etic mutations and factors will then result in
similar phenotypic tumors potentially behaving 1.2 Neurofibromas
much differently. For example, cellular schwan-
nomas (approximately 20–30% of retroperito- Neurofibromas are benign PNSTs originating
neal schwannomas) which are still considered a from Schwann cells, with admixed fibroblasts,
benign PNST have been shown to have a higher perineurial cells, hematopoietic cells, and nerve
growth rate and rate of recurrence compared to fascicles also being seen on histopathological
other subtypes [38, 41–43]. Although beyond the section [46, 47]. They are the second most com-
scope of this chapter, the advent of more targeted mon type of benign PNST after schwannomas
therapies has led to more and more research with a reported prevalence of 10–24% of all iso-
being done investigating these specific molecular lated nerve tumors and making up 5% of all soft
mechanisms that may be responsible for different tissue tumors [32, 48]. These can be classified as
schwannoma growth characteristics [23, 44, 45]. solitary (or sporadic, not occurring in the context
The latter is highlighted when considering of NF-1 and existing as a solitary nodule emanat-
ing from a single peripheral nerve) or plexiform
(seen almost exclusively in the context of NF-1 in
which multiple neoplastic tumors from individ-
ual nerves or nerve fascicles coalesce into a
plexiform-like “bag of worms”). As shown in
Fig. 1.2a, neurofibromas can be subclassified
based on location and gross pathology: dermal/
cutaneous (which can then also be subcatego-
rized as localized dermal neurofibromas which
are more common than their counterpart, diffuse
Fig. 1.1 Histological classification of schwannomas

a b

Fig. 1.2 Classification of neurofibromas (a) and photograph of a patient with a massive soft tissue-type neurofibroma
(b)