TUMORS O F THE PERIPHERAL NERVES
CHARLEB F. GESCHICKTER, M.D. 1
( F r o m the Surgical Pathological Laboratory, Department of Surgery, Johns Hopbins Hospital
and University)
The individual fiber of a peripheral nerve is composed of an axon
o r neurite, which is usually encased in a myelin sheath. Surrounding
this is a protoplasmic envelope, the sheath of Schwann. These elements, the neurite, the myelin sheath, and sheath of Schwann, are
neurogenic in origin (Fig. 1). The neurite is a prolongation of an
individual nerve cell, while the sheath of Schwann is composed of a
syncytium of cells which migrate out from the neural crest in early
embryonic life (Harrison). The myelin sheath is supposedly a product
of the nerve cell. The individual nerve fibers are embedded in connective tissue, the endoneurium, and are gathered into bundles enclosed
by fibrous tissue, the perineurium. The entire nerve, consisting of
these bundles of individual fibers, is overlaid by connective tissue, referred to as epineurium (Fig. 2).
Tumors of the peripheral nerves were divided by Virchow, in 1863,
into false neuromas, which include tumors of the nerve sheath, and
true neuromas including growths arising from nerve fibers or nerve
cells. Among the true neuromas are ganglioneuromas of the peripheral, spinal, and sympathetic nerves, and amputation neuromas, which
are a combination of nerve fiber and sheath regeneration following the
severing of a nerve trunk. Sporadic examples of neuro-epitheliomas
of the peripheral nerves have been reported.
The false neuromas or tumors of the nerve sheath are far more
common than tumors derived from nerve fibers. Tumors of the nerve
sheath occur on both spinal and sympathetic nerves, on both sensory
and motor nerves, centrally at their roots, peripherally on the deep
nerve trunks, and superficially near the terminal ramifications, particularly in the subepidermal tissues. According to one school these tumors are derived from the sheath of Schwann, i e . , are of neuro-ectodermal derivation ; another seeks their origin in the connective tissue
of the endoneurium and perineurium.
Clinical-anatomical classifications of nerve sheath tumors have been
attempted, the best defined clinical group being the multiple variety
described by von Recklinghausen. These tumors are sometimes hereditary and are extremely varied in their manifestations. Melanotic
plaques in the epidermis, subcutaneous multiple fibrous tumors, plexiform involvement of the nerves of an extremity with or without elephantiasis, and solitary nodules on the deep nerves, both benign and malignant, are among the varied findings.
Two varieties of solitary benign nerve sheath tumors are recognized, a differentiated and undifferentiated group. The more highly
1
Aided by a grant from The Anna Fuller Fund.
377
378
C H A R L E S I?. GESCHICIZTER
differentiated tumors arc rich in collagen and fibrous tissue and in one
o r more zones of the tumor a clumping of the nuclei in a characteristic
palisade arrangement ca.n be seen iiiider the microscope. These tumors
are surrounded by the perineurium except at the point of attachment
to the nerve and rarely uiidcrgo malignant change. “hey have been
variously termed perineural fibroblastomas, nenriiiomas, Schwannomas,
neurilemomas, and lemmomas. They occur most frequently in the subcutaneous tissues or centrally along the root,s of the cranial or spinal
nerves in adults.
The tumors of the undifferentiated group may o r may not be encapsulated and are prone t o recur and to undergo malignant change.
These tumors occur most frequently on the deep nerve trunks of the
upper or lower extremities and also superficially beneath the epidermis.
Both children and adults may be affected. The combination of multiple superficial and deep tumors of this type is part of the clinical
picture of von Reeklinghausen’s disease. Histologically these growths
are composed of reticulated myxomatous tissue often arranged in
bundles and sometimes extremely cellular. These tumors have been
variously referred to as fibromyxomas, fibroneuromas, and myxoicl
neurinomas.
Sarcoma of the nerve sheath may arise in either type of solitary
nerve tumor just mentioned. It is the most common form of sarcoma
of the soft parts. Usually this malignant change affects the deep nerve
trunks of the extremities, and it may complicate von Recklinghausen’s
disease.
The following table shows the classification and the incidence of
these tumors recorded in the Johns Hopkins Surgical Pathological
Laboratory.
Tumors of the Nerve Sheath (False Neurotnas).. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Palisaded neurinomas (Neurilemomas) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Peripheral (55 cases)
Spinal (25 cases)
Acoustic (70 cases)
Myxoid neurinomas (Neurilemoblastornas) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Subepidermal (240 cases)
Deep (70 cases)
von Recklinghausen’s, multiple (40 cases)
Sarcoma o f t h e n e r v e sheath . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
350 cases
Tumors of Nerve Fibers (True Neuromas) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
50 cases
Amputation neurom
....................
. . . . . . . . 40 cases
Ganglioneuronia
.......
........
8 cases
2 cases
Peripheral neuro-epitheliomas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
900 cases
TUMORS
OF THE NERVESHEATH:
FALSE
NEUROMAS
Palisaded Nezwinonias (NeurilPrnornas)
The palisaded neurinomas arise from the sheaths of the subcutaneous nerves or the roots of the spinal or cranial nerves. They are
encapsulated hy the pcrineurium, are solitary, and do not implicate
an entire nerve trunk. With the peripheral tumors a tender lump
FIQ.1.
PHOTOMICROGRAPH OF A NORMAL MEDULLATED
NERVEFIBER
TATION NEUROMA
ON TIIE SCIATIC NEWE
OCCURRING
I N AN
AMPU-
The axon courses through the center of the myelin, which stains in the form of small
droplets. The nucleated sheath of Schwann is seen above the fiber. Above a n d below are the
anastomosing columns and fibers of the Schwannian syncytium. Masson 's trichrome stain.
Path. No. 56853.
FIQ.2. PHOTOMICROQRAPH SHOWING THE CONNECTIVE-TISSUE SHEATHS 0% A NORMALNEltVE
Ep. Epineurium. Pe. Perineurium. En. Endoneurium. Laidlaw's silver stain. Path.
No. 60885.
379
380
CHARLES P. GESCHICKTER
may be palpated in the subcutaneous region, and pressure may provoke
pain referred along the distribution of the affected nerve. About onethird of these tumors lie immediately beneath the epidermis (Fig. 5).
Stout has reviewed the literature on the peripheral tumors of this
type, collecting 194 cases and adding 50 of his own. He has suggested
FIG. 3. DISTRIBUTIONOF SUBEPIDERMAL AND CENTRAL PALISADED NEURINOMAS
The location of the tumors was as follows:
Peripheral tumors
Head and neck, including facc, scalp, and eyelids ................................
Upper extremities .............................................................
Trunk .......................................................................
Lower extremities .............................................................
Central tumors
Acoustic nerve ................................................................
Spinal cord and cauda equiiia ..................................................
18
14
12
6
70
25
the term neurilemoma f o r these growths. I n the central tumors
involvement of the cranial nerves o r compression of the spinal cord is
the outstanding feature. Whether these tumors are central or peripliera1 in distribution the upper portion of the body and the upper extremities are affected more often than the lower. With the central tumors
the cranial nerves are involved more frequently than the spinal roots,
TUMORS O F THE PERIPHERAL NERVES
381
and in the subcutaneous regions the head and neck and upper extremities more frequently than the trunk and lower extremities (Fig. 3).
On the extremities the flexor surfaces are usually affected. Eighty
per cent of all cases occur in adults between the ages of thirty and
fifty years (Fig. 4).
FIG.4. AGEDISTRIBUTION
OF NERVESHEATH
TUMORS
Histologically these are benign, well differentiated tumors showing
varying degrees of fibrosis, which is maximal in the region of the
capsule. A few degenerating axons with myelin sheaths may be demonstrated by special stains but these are persisting normal structures
and not part of the new growth. The major portion of the tumor is
composed of wavy bands of collagen interspersed with elongated parallel fibrils (Fig. 6). Whorls of fibers may occur and in these zones
clumping of the nuclei to produce so-called palisades may be seen (Fig.
7A). This is referred t o by Antoni as Type A tissue. Interspersed
with the collagenous and palisaded structures there is a loose reticulated tissue containing cells with small nuclei, many fine radiating fibrils,
and minute cystic spaces. These reticulated o r loose-meshed areas,
termed by Antoni Type B, can be found in all of these growths, but the
palisading is a more helpful finding from the standpoint of diagnosis
(Fig. 7B).
Masson has studied in detail the cytological characteristics of the
predominating cells in these tumors, which he believes a r e sheath of
Schwann cells o r lemmocytes. The nuclei a r e fairly large with moderate amounts of chromatin arranged at the periphery. The cytoplasm
of the cell is abundant and forms syncytial columns of protoplasm
marked by numerous delicate fibrils arranged both longitudinally and
circularly. This syncytium stains pink with Masson’s trichrome stain;
it is encased in a reticulum of fibers which stain blue by this same
method. We have been able to confirm Masson’s findings i n the present
study. When a reticulum stain is used the entire tumor is seen to be
382
CHARLES F. GESCHICKTER
crowded with many fine fibrils, which Masson believes are derived from
the lemmocytes of the sheath of Schwann rather than from the connective tissue of the endoneurium.
These subcutaneous or peripheral neurilemomas may be trealed
by simple excision. Sacrifice of an important nerve is not necessary,
since the deep peripheral nerves are rarely involved and recurrence
after excision is extremely uncommon. Malignant change has occasionally been reported (Stewart and Copeland; Peers) in tumors in
the deeper tissues but not in those in the subcutaneous regions.
Acoustic Nerve !l'unzor.s : Tumors occupying the cerebelloporitine
angle and involving thc acoustic nerve comprise about 10 per cent of all
FIG.
5.
PHOTOMICROQRAPH OF SUREPIDERMAL PALISADED NEURINOMA.
P A T H . NO. 16620
intraeranial neoplasms. In the present series 105 cases were placed in
this group, on the basis of operative findings. Of this group 70 were
selected as typical after microscopic study. The majority of these
cases were from tlic surgical service of Dr. Walter E. Dandy, although
10 of the cases had been previously reported by Cnshing.
The acoustic tnmors in the present series, with two exceptions,
occurred in adults beyond the age of twenty years. The two younger
patients were eighteen and nineteen years of age. The duration of
symptoms is prolonged, extending beyond a five-year period in many
instances. A characteristic syndrome is usually present, beginning
with a roaring in the ears or dizziness, after which the hearing is
gradually lost 011 the affected side. There is loss of sensation over
the affected side of the face and occasionally in the anterior two-thirds
of the tonguc. The voice may become thick and the patient becomes
TUMORS O F T E E PERIPHERAL NERVES
383
ataxic, with a staggering gait. The symptoms relate to the eighth,
fifth, seventh, and ninth cranial iierves on the affected side and to the
cwebellum. They are f ollowed by signs of intracranial pressure including headache, impairment of vision, and vomiting.
The findings on examination include impairment of hearing,' loss
of vestibular response on caloric test (absence of nystagmus when the
ear is irrigated with hot or cold water), and absence of the corneal
reflex on the affected side. Facial asymmetry and anesthesia, nystagmus, ataxia, paralysis of the vocal cords, dysphagia, and hemiatrophy
of the tongue are among the other findings.
Grossly these tumors are encapsulatecl and vary in color from a
6.
FIG.
LOW-POWER
PIIOTOMICROGRAPII
OF
AN
ENCAPSULATED
PALISADED
NEURINOMA
OK
NEURILEMOMA.
PATIT. N O . 42721
From Lewis aiid Hart: Ann. Surg. 9 2 : 963, 1930.
grayish white to a yellow or red. They are usually fibrous but may
be quite vascular. They range in size from one t o several ceiitimeters
in diameter. At operation they are found just beneath the cerebellum,
which must either be lifted o r uncapped before the tumor presents.
Dandy prefers a complete enucleation of the tumor with the curettc,
followed by removal of the capsule, whereas Cushing is often content
with intracapsular enucleation, awaiting the possibility of recurrence
before more radical removal. The operative mortality is between 15
and 25 per cent. Paralysis of the facial nerve follows surgical removal
of these lesions and anastomosis is usually performed a t a second stage
between the peripheral portion of the seventh nerve and the central
portion of the eleventh.
2
I n rare iiistaiiees the hearing may be retained.
384
CHARLES F. GESCEIICKTER
These tumors show varying degrees of vascularity and fibrosis.
The more cellular growths resemble spongioblastomas o r glioblastomas
of the brain and the more fibrous lesions resemble meningiomas. I n
one or more portions the tumors show typical reticulated tissue and
elsewhere collagenous areas with clumping of the nuclei, They do not
differ as a group from the palisaded neurinomas found on the peripheral nerves (Fig. 8).
There have been various theories as t o the nature and origin of
these tumors. The frequency of their occurrence in the region of the
cerebellopontine angle has led Sternberg, Verocay and others to refer
them t o embryonic rests occurring in the complex development of this
FIG.7.
Two AREAS FROM THE TUMOR
~ I I O W NIN FIQ.6 : A. TYPEA TISSUE (LEFT)
B. RETICIJLATED
AKEA,OR TYPEB TISSUE (RIQHT)
PALISADING.
Fig, 7A from Lewis and Hart: Ann. Surg. 92: 964, 1930
SHOWING
region. These tumors, however, have been reported, also, on the
seventh nerve by Raymond, Huet and Alquier and on the fifth nerve
by Cohen and by Glaser. Cooper has reported two neurinomas invading the Gasserian ganglion. He was able t o collect from the literature records of 76 tumors affecting this structure. One of the cases
in the present series involved the tenth and another the twelfth cranial
nerve. A series of six tumors ranging from 1 t o 3 mm. in diameter
has been collected in Dr. Crowe's laboratory for otological research
at the Johns IIopkins Hospital, on the distal portion of the eighth nerve
within the internal auditory canal. The histology of these minute
tumors on the distal portion of the nerve, is identical with that of the
larger tumors at the cerebellopontine angle and of the tumors on
the peripheral spinal nerves. This substantiates the origin of these
tumors from the sheath of the acoustic nerve.
Ex;tramedullary Neurilemomas o f the Spi.na1 Cord: Tumors of the
palisaded neurinomatous type occur on the spinal cord in an extramedullary location. They may be intradural or estradural and occur
on the roots of the spinal nerves within the vertebral canal anywhere
TUMORS
OF THE PERIPHERAL NERVES
385
from the cervical region to the cauda equina. They are sometimes
multiple or associated with meningeal tumors in the presence of von
Recklinghausen’s disease. The symptoms produced vary with the
level of the tumor. The onset is usually insidious, indicating cord
compression with unilateral sensory and motor disturbances. Root
pains exacerbated by coughing o r sneezing occur. Girdle pains, weakness of the legs, progressive paralysis (at first spastic) below the painful area, and disturbance of the bladder and rectal functions, are
common findings. Diagnosis is much aided by the injection, in the
subarachnoid space above the lesion, of lipiodol and roentgenographic
demonstration of a block in its downward course.
FIG.
8.
PHOTOMICROGRAPH OF AN
ACOUSTICTUMORSHOWINQ TYPICALPALISADES.
No. 41391
PATH.
Tumors in the anterior portion of the cord are more difficult to
locate and to excise. The tumors are usually encapsulated and do not
invade the cord, but in one case in the present series associated with
von Recklinghausen’s disease there was definite invasion and a portion
of the tumor was left behind at the operation (Fig. 9 ) . In other cases
the growth may form an anterior extension (so-called hour-glass tumor), the major portion being found in the neck, mediastinum, o r in
the retroperitoneal spaces.
Tumors of the cauda equina present certain diagnostic difficulties.
The majority of tumors in this region are sheath tumors, the neurinomas being more common than the meningiomas. The pain, which
may be very prolonged, is frequently attributed t o sacro-iliac arthritis
or sciatica. There is flaccid paralysis with loss of reflexes and marked
disturbance of the bladder and rectal functions. An area of “ saddle ”
386
CHARLES I?. OESCHICKTER
anesthesia is present in the perineum. The exposure of these tumors
at operation is more difficult than those of the spinal cord, but the
prognosis is better. The distribution of these sheath tumors in the
spiiid cord and in the cauda equiiia, is as follows:
Cervical region.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Thoracic region. . :, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lumbar region . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Caudaequina . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
T ~ T A. .L. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
B’IG.
9.
6 cases
7 cases
2 cases
10 cases
25 cases
PHOTOMICROQRAPH O F A N EXTKAMEDLTLLARY NEURILELEOMA
O F THE S P I N A L CORD
CO~IIPLICATING A CASE OF VON R E C K L I N Q I I A U S E N ’S DISEASE
A portion of the tumor invaded the cord.
Path. No. 53373.
M y m id Neu r.il1.oI n as o r N e ir ril erii ob 1a d o m as
The myxoid neurinomas of the nerve sheath differ €rom the palisaded neurinomas both clinically and pathologically. The distribution
of these tumors is subepidermal and along the deeper nerve trunks, in
contrast to the subcutaneous and central location of the palisaded
neurinomas. These myxoid tumors also have a wider age distribution and occur more frequently in children. The majority of the tumors are not encapsulated. Histologically they are more undifferen-
387
TUMONS Oh’ THE I’EKIl’HEI<AL NEKVES
tiated and particularly in the deeper locations are prone t o uiitlergo
maligiiarit c>hnnge. Multiple nodnles a r e not an unusual finding and
hoth the snl)epidermal and tlcep lying iicr\-cs may he difffiisclpinvolved
by such tumors in voii Rccldiiighaiis~ii’s disease. WICaccompanying
t ahle (wntixsts the myxomalons iieiirinomas with tlic palisacled nenriiiom a s.
~~
TABLE
I: Coinparifion of Palisaded and Myxoid Neurinonias
~-_____._
_ _________-___--____
_ _ _ _ ~ -_
~ ~_ _ _
~
-
1
Kumber of
I
C:MS
Age peak
_
~
Children affected
_______~
_
-
~
~
_________
~
-
_
__
___--_
Behavior aftei tieatment
_
~
40-50
-
350
20 30
~
~
.
_
_
Majority encapsulated
Majority not eiicapsulated
~
__
-__
-~
Palisading arid hbrous Reticulation and myxomatous
tissue
tissue
~-
_ _
___
Common
Association 5% ith von Rechlingliausen’s Rare
disease
( ’ommori
__-
__ __--
-
No recurrence after qim- Tendency to recur ntter sirnple excision
ple excision
Rare
Malignant change
~
Neurilrmohlastoma~
20 pei cent
Sone
_____
Roots of eighth ciamal Subepidermal fibers, deep
and spinal nerves, subnerve tiiiiiks of upper and
cutaneous fibers, head
l o er~ extremities, visceral
and neck, at m, hand
syrnpathetics
~-
~~
Mici osropic findings
!
I
150
-~
~
Most frequent loratioti<
Enciipsulation
Nrurilrmomas
~
__-
~ . _ ~ _ _ _ _ _ _ _ _ _ _ - _ _ _ _ _ ~
Subcpidcrwnl JIyroitl Neririizo ~ u n s(No-rulletl N m v o f i b ro m a s ) : Subepitlcrmal ~iodulcsnssociatrd ivitli the ~ l i e a f hof~ tlic 1)criphcral nerves
are arnoiig the most Conimoii tumors. Nearly every patient examined
will bc found to have one or two of these pcduiicixlated lesions several
millimeters in diameter. They differ from the lcsious found in typical
von Becklinghausen’s disease in the absence of symptoms produced,
their small size, their rcstrictetl niimbei‘s, ant1 their failure lo follow
the entire cutaneons distribution of the nerve. hi tlic present series of
castis t1ici.e were 240 tumors of appreciahle size Tvhich hat1 been excised
and classcd as neiirofihromas after niicr.oscopic study. These growths
\vei-c usually removed for cosmetic reasons, although rarely increase
in size or cleepeiiing pigmentation w a s the indication for excision. I n
some cases the nodules had become iiicreasingly painful o r tender.
With few cmeptiorts orily a single turnor was removed from an inclividnal. The notlules were more f1~cqncntlysituated on the extremities
than on the Iicacl, neck o r trunk (Fig. 10).
Microscopic study discloses tlii*ce types of su1)epiclermal nodules
associated with bhc 1ien-c shcath. The most common form is charactcrizecl hy an increase in adult c~oriiiectivetissue ;uid is often considered,
erroneously, a simple fibroma (so-called fibi*omamolluscum). Another
foi*mis composed of bundles o r fasciculae of c~loiigtitetlcells wliich may
388
CHARLES Y. UESCIUCKTER
1)e arranged in whorls, some of which display marked cellularity. A
third type is cornposed of a diffuse proliferation of small spindle cells
vithout any characteristic arrangement. Any of these three histologic
types may be associiitetl with melanin pigment (Figs. 11-13), arid none
I’IO.
10. DISTRIBU~I’ION
OF KUPEHPICIAL A N D DEEP MYXOIDNEUKINOMAS
( NEUIULEM
O B IASTOMAS)
of them sl.iows complete encapsillation. They represent three stages
of differentiation in tlie same pathologic process. Tlie essential pathologic change is apparently a proliferation of sheath cells about onct
or more bundles of iierve fibers eiit eriiig tlic subepidermal region. Tlie
nodules cornposed of undifferentiated spindle cells represent the earliei.
phase of n process which tcrminntes with fibrosis after passing through
;i stage cliarncterized by bundles of eloilgated sheath cells.
Multiple nodules of this character are the outstanding feature of
von Recklinghauscn’s disease. Penfield as able to stain axons of
nerve fibers enteriiig tlie subcutaneous nodules, and interpreted
notlulcs a s a, reactionary fibrosis of probable neurotrophic origin.
r.ctained the term ncnrofibroma for these lesions, because of the axon
TUMORS O F T H E PERIPHERAL NERVES
389
found in the tumor area. F r o m the present study n o special significance can be attached to the demoiisti*ation of asonal fibers in these
nodulcs. They c a n IE demonstrated iii the normal skin and subcutaiwoiis regions anti their pel-sistciice in the tiffectecl area is not iieces-
FIG.11. LOW-POWER
AND
IIIGII-POWER PH O T O MI ( ' R 0 G R A P H S
NEURILE~~OI~LASTOMA
O F A SUBEPIDERMAL
Mature cwllngcnous fillers prrclomiiiatr. Path. No. 31502.
FIGS.1 2 AND 13. SUBEPI DERMA L P\TEURII~EMOBLASTOIIAS
The tumor in Fig. 12 (left), occurring in a child of seven months, is composed of interlacing bundles of collagenous fibrils (E'oot's reticulum stain). The tumor in Fig. 13 (right)
is composed of undifferentiated spindlc cells; a small deposit of melanin is seen in t h e lower
riglit Imid corner. Path. Nos. 547% and 3272!5.
sarily related to the pathologic changes (Figs. 14 and 15), but merely
indicates proximity to iicural structures. I n general neither axons iior
myelin arc found a s p a r t of the neoplastic process in tumors of thc
nerve sheath.
Subepidermal N e r v e Sheath Sarcoma, Grade I . : In the present
series there was a group of 30 very cellular spindle-cell tumors oc-
~’IG.
14.
~ 1 ~ O T O M I ~ ’ K O O K A I ’OI IF A SITREPIDERhrAL
A large
FIG.
15.
I K ~ W C ~fibri.
NODULEOCCURRING ON THE N E R V E SIIRATII
Path. No. 32414.
is wen cntciing t h c tumor.
PIlOTOhIICROORAP€€ O F AXONAL
m B E R S ENTERING
A SUBEPIDERMAL
(1~IELSClIOWSIZY’ S STAIN). P A T l I . NO. 54958
NODULE
TUMORS O F THE PERIPHERAL NERVES
39 1
curring immediately beneath the epidermis and apparently of nerve
sheath origin (Figs. 16 a i i t l 1 7 ) . These cases were formerly classed
in the lahomtory as siircomas of thc skin. With few clsccptions they
FIG.17.
~ H O r l ~ O ~ 3 1 < AAI N
~D
I I ~ I I O T O A l I ( ' K 0 U R A P HOF A 8 U B E P I D E R l I A L S P I N D L E - C E L L SARUOMA O F
'1'IIIlC N E R V E H I I E A l ' I I ItECURKE:NT AFTEK. I k C I S I O N A N D IKRADIATION
The characteristic cc,lls of Srhwann are shown ill the ~ ~ l i o t o i i i i c r o g r awith
~ ~ h , large amount
of collagen. Path. No. 53380.
occurred about the liead aiid face and o n the upper extremities. All
of them liad been treated by simple excision, inc*luding a margin of
licalthy skin and the siihcutaneous tissues down to the underlying fascia.
392
CHAEIJES 17. GESCHICKTER
llistologically the majority of tlicsc tumors arc Grade I, when coml)arcd with snrcom:t of the tlecp nerve trunks, although some of them
i ~ r oQratlc 11, 111 or 1 V in maligiitmc~y. This group of tumors is singled
o i i t 1)cc:iiisc of tlic rcwilt s follo\viiig trcatmciit. Of 18 paticrits followed for more thnii five years after cscision of the tiimor, 16 r*~niihied
wcll arid only t\vo clictl of metastasis (Fig. 18). The curability of these
sul)cq,iclcrmal nodiilcs is f a r highcr tlinn that of sarcoma af’fccting the
shcatlis of tlie ttccpcr I I C ~ I + V C ~:iri(I
S,
they wirrmit a. lrcttci. prognosis than
1hey arc llsnnlly 2 l C c o l Y l ( ~ t l .
TUMORS O F T H E PERIPHERAL NERVES
393
give the impression of being encapsulated, but they frequently extend
without any ticfinite boundary above o r below, up and down the nerve
trunk. These tumors are usually larger a t the time of their clinical
rec.ognitioii tliaii the other varieties of nerve sheath tumor, varying
from the size of a u7al11ut to that of a grapefruit. ‘I’hey tciitl to have
a somewhat gelatinous consistency and a gray, translucent appcaraiice.
Althoiigh pain and tingling along the distribution of tlie iicrvc may hc
coinplairietl of by the patient, the fairly rapid growth of the swelling
is often the only significant finding in the history.
b’l0. 19.
LOW POWER A N D IIlGIf POWER I’IIOT03II(‘KOGKAPIIS
O F A LfYXOlD NE UR INOMA I N T l l E
WALL OF mI.: S T O ~ I A C H
Tlici tumor is undergoing malignant cl-inngc. P a t h . No. 55320.
The outstmclirig cliiiictil fcaturc in this groiq) of tnmors is the
iendency to reciii-reiice. Thii*ty rxr ceiit of the tumors in t lie present
ant1 of the iwinwiit giwwths slightly moi-c than half
series i*c~ciirrc~4
nnderweiit m;digiiani t (~haiige,nwiltiiig- iii the death of the patieiit.
Whcrcas siml~leewisioit siiffices iii the t i w t m e n t of the sulwpidermal
nodules an(1 the pdisaded iicwi.iiiorrias, thc mysoitl iiciu.iiiomns should
without c.sc.eptioii he clscisetl \\.it11 a rn;ii.giii of liedthy tissue. If a
major nerve trunk m i s t be sac.rificct1, this should be done with an
tumors i n oiir ospci.icnce
attempt at sitbsequciit iiei-ve s u t u i ~ ~These
.
have not p ~ r v e t rdioseusitivcl.
l
Histologically, 11ic~sogiwwths a r e composed of intci*lac*iiigstralitls
of eloilgated or s1ioi.t spiiitlle cells with varying amonnts of collagciious
and mysomatous iiiterc~e1liil;tr sn1)staiice. Reticulated arcas in which
small brniichirig cells lie free in a traiisluceitt matrix arc a prominent
feature. Marlied filirosis ant1 definite palisading v e r e iiot presciit i n
the sections examiiied. From the standpoint of treatmciit ally nerve
394
CHARLES F. (iESC’IIICK‘l‘ER
sheath tumor occurring on the deeper nei’ve ti.iinks or on the sympathetic nerves of the viscera. should be r.cscctecl rather than excised on
imptive cvitlcw+cthat it 1)clloilgs to this group (Figs. 20-22).
I 1
1nmors of this t y p o exwediiig 2 em. it1 diameter arc usually malignant.
Nr)ii.ofiOi.onintosis.-TTon Bec~ltliti~:.h;inscn
’s disetisc o r ncurofibromntosis is a c o i i ~ * ~ i l i ttlisturbancc
al
of the nerve sheaths resulting in
?
multiple subcpitlermal riocliilcs d o n g the distribution of the peripliernl
~ i ~ ~ r vtumors
cs,
of the drepei. iiervc triiiiks an(l roots, ant1 clistur1)anecs
in pigmcii tation. Mciiingcal tiimoix, angiomas, lipomas, and tropl-iic
tiisturlmiccs, such a s hypertrophy of a limb 01’ spiiia hifitla, are often
ikssocil-ttd coiiditioiis. Typical c;~sesiii \vliich tumor nodules are widely
( i i s t r i h t e d over tlic Iwdy are iiot cornmoil, I)ut atypical cases (so-callctt
), iil which oiic 01’ more areas of the h t l y sliow pigmentation and tumor 110(1111cs, are see11 more f rcqueiitly. ‘l’he present
study is 1,ascd npoii 40 typical cases in which tissue was available for
study followiiig snrFica1 excision or autopsy.
Although c i ~ s c s111 wliic*h the cliscasc shows licrctlitury or familial
features a r e not rare in the 1iteratui.e (Stulmann), in tlic present series
of 40 c~ascsiio iiisttince is recordctl in which memhers of the patient’s
family were laiown t o he affcctcil. The diseuse pnrsucs a slow, insidious
course, approsimatc~lyoiic-third of the I>aticntsbciiig in the third decaclc
before disability or disfigurcmeiit brings them to 1lie physician. Although the majority of tlie p t i e i i t s were between tlie ages of twenty a i d
fifty years, 11 of the 40 eases were congenital in onset, 7 began in chililliood, arid iii 5 nodules had been observed more than ten years previously.
L’rcsumably all eitses are congenital in origin. Multiple nodules (0.5
b’l0.
22.
I ~ I G l I - P O Elt
l ~ ~ ’ ~ I O ‘ l ’ O A l I ( ’ R 0 G K A P I I O F AX EDEMATOUS hfYXOID ~ E U K I N O M A
Thc cells aic arranged in parallel
395
~ 0 ~ 8 Path.
.
No. 47077.
396
OHAELES F. GESCHICKTER
to 1em. in diameter), freely movable and tender t o pressure, situated
on the trunk and extremities and accompanied by pigmentation were
the outstanding features in most cases (Figs. 23 and 24). Involvement
of the head and face was promiiient in 6 cases, and in an equal number
nodules were found on the feet and hands. The tumors follow the
distribution of the peripheral nerves and are often pedunculated. In
one o r more locatioris larger nodules, from 3 t o 5 em. in diameter, may
be palpated. The tumors along deeper nerves may give rise to rheumatic pains f o r many years before becoming palpable. Thirty of the
40 patients in the present series had demonstrable involvement of the
deep nerves o r central tumors within the skull or along the spinal cord.
Subcutaneous angiomatous lesions were present in 4 cases, spina bifids
in 2 instances, curvature of both wrists in one, congenital club foot in
FIG.23.
P A T I E N T WITH VON RE('ICLINGIiAlJ8EN '8
DISEASE.
P A TII.
NO. 4607
another, and hypertrophy of an extremity with plexiform neuromas
three times.
Nine of the 40 patielits with von Recklirighitusen's disease in the
present series had sarcoma of a deep nerve trunk, proving fatal in
each case. I n 6 other patients tumors of the acoustic nerve, of the
meninges, of the spinal roots within the vertebral caiial, or tumors
within the mediastinum resulted in death.
Ihtologically the superficial tumors are similar to the solitary
subepidermal nodules of the nerre sheath (Figs. 2 - 2 7 ) . The deeper
tumors are myxoid neurinomas or sarcomas of the nerve sheath. Typical palisaded neurinomas, however, were not observed in von Recklinghausen's disease in this series except within the craiiiill cavity or
along the spinal cord.
Plelciforrn fieuiwtna or elephantiasis nervorum is coiisidered a form
of congenital elephantiasis, since in the region affected the nerves, connective tissue, arid vessels may all show enlargement. I n this type of
FIG.24.
PATIENT
WITH VON RECRLINQHAUSEN ' s DISEASE. PATH.
No. 37818
From LLcwis and Hart: Ann. Surg. 9 2 : 969, 1930.
FIG. 25. PHOTOMICROGRAPHS SHOWING MELANOTIC(LEFT) AND NEURINOMATOUS (RIGHT)
PORTIONS
OF A SUBEPIDERMAL NODULE I N VON RECKLINGHAUSEN
'S DISEASE.
PATH.No. 20339
397
398
CHARLES F. GESCHICKTER
nerve involvement, usually seen in von Recklinghausen’s disease, a
limited part of the nerve is thickened and elongated as the result of an
overgrowth of the sheath and connective tissue along the tortuous and
PHOTOMICROGRAPH OF EORMAL FIBERS
ENTERINQ TIIE BEADED
AND THICKENED P O&TION OF THE NERVE I N A CASE O F VON ~ E C K L I N Q l I A U S E N ’ SDISEASE. P A T H . NO. 30078
FIG.26.
FIG.27.
PHOTOMICROGRAPH
OF A SARCOMA
DEVELOPING
BELOW POUPART’S
LIGAMENT
IN
ANTERIOR
PORTION OF T H E THIGH I N TIIE CASE SHOWN I N FIG.26
‘
THE
beaded course of the fibers. Lewis has reviewed the literature and
discussed in detail this phase of the disease under the heading “ Elephantiasis Nervorum.” Bruns was the first to analyze a series of
these cases, collecting 42 from the literature and adding 8 of his own.
Lewis described 5 cases and stressed the enlargement of the part (Fig.
TTJMORS O F T H E P E R I P H E R A L NERVES
399
28) and the association of vascular and connective-tissue disturbances
and a tendency for malignant tumors t o develop on the involved nerve.
These plexiform neuromas are essentially a forme fruste of von Reck-
FIG.28. PATIENT
AND GROSSSPECINENS
FROM A CASE OF ELEPHANTIASIS
NERVORUM
The left loner extremity is enlarged and the iiiultiple iiodules along the iierve which arc
shown i n the excised specimens were definitely palpable. From Lewis and H a r t : Ann. Surg.
92: 976, 1930.
linghausen's disease, since similar enlargements of the spinal nerves
at their roots are often an outstanding feature in the more generalized
form. The following ease is characteristic :
A colored male, aged seventeen, was admitted to the hospital in August 1933, having
noticed multiple nodules beneath the skin over the surface of the body f o r a little more
than one year. I I e complained of pain in the left chest accompanied by increasing
shortness of breath. A decided right scoliosis was present, with drooping of the left
shoulder. The skin nodules, the largest of which were about 4 em. in diameter, followed
the distribution of thc superficial nrrves about the body and down the extremities. The
face, palms of the hands, and soles of the feet' were the only portions of the body free
from these nodules. All of them were tender to pressure. The main physical findings
pertained to consolidation in the left chest. X-ray revealed a large tumor in the mediastinuni comprcssing the left lung. The neurological examination was essentially negative. I n January 1934 death occurred from respiratory embarrassment.
Autopsy revealed in addition to the superficial nodules a lobulated tumor mass
18 X 12 X 12 cm. in the left chest. Numerous tumor nodules 1 em. in diameter followrd
the distribution of the nerves along the trachea and esophagus. The sympathetic nerve
chains anterior to the abdominal spine were thickened and beaded by tumor formation.
Both the brachial plexus and the sciatic nerves were markedly thickened and beaded by
numerous tumors. The roots of the thoracic and lumbar nerves showed bilateral tumor
nodules. Nearly every spinal nerve at the intervertebral angle contained a tumor nodule
slightly in excess of five mm. in diameter. Microscopic examination showed the nerve
fibers of the'various spinal nerves separated by loose myxomatous tissue. The axis cylinders and myclin sheaths were visible in specially stained preparations in scattered fibers
only. The mediastinal mass showed two types of tumor, one of these was typical nerve
sheath sarcoma composed of interlacing strands of spindle cells, the other portion was
epithelial in appearance and resembled a paraganglioma of the adrenal or, in places, parathyroid tissue (Fig. 29).
400
CHARLES F. GESCHICKTER
Sarcoma of the Nerve Sheath
Sarcoma of the nerve sheath arises most commonly along the deep
nerve trunks of the upper and lower extremities. The sites of occurrence correspond very closely to the distribution of the benign deep
myxoid neurinomas previously described. The lower extremity is more
often affected than the upper, and the region of the popliteal space and
the anterior arid posterior portion of the thigh are the most common
PHOTOMICLtOGRAPH OF ~PI'PHEXJAI.-LII<ECELLS EMBEDDED
I N A N OTHERWISE TYPIC'AL
SARCOMA OF T H E NERVE
BHEATII OCCURRING I N A CASE OF VON RECKLINGHAUSEN
'S
FIG.29.
DISEASE. PATH.No. 13470
sites (Fig. 30). The iiicidencc of these tumors reaches its peak in the
decade between thirty and forty ';years with approximately 10 per cent
of the patients under twenty years (Fig. 4). The average duration of
symptoms was slightly under one year in 75 per cent of the cases ; the
remainder of the patients had known of a swelling o r pain from five to
fifteen years. The results of both the clinical and pathological study
of the cases in the present series iiidicate that it large percentage of
these sarcomas represent malignant change in pre-existing benign myxoitl neurinomas.
Histologically there is a remarkable degree of uniformity in the
majority of these tumors. They are composed of tightly interlacing
strands of plump spindle cells which may occasionally be elongated
with wavy fibrils and at other times show enlarged nuclei with mitotic
figures arid tumor giant cell formation. From this typical picture,
which can be eoiieitlered Grade 11 or I11 sarcoma (Figs. 32 and 33),
the tumors vary 011 the one hand toward the benign myxoid neurinomas,
merging imperceptibly with the histological forms of this benign group
TUMORS OF THE PERIPHERAL NERVES
401
(Fig. :Xi), which may be termed the Grade I sarcomas, and on the other
hand a group showing ~ i u m e ~ ~ tumor
o u s giant cells and epithelioid forms,
C r i w l c ) I V iii mdigiiniicy (Fig. 34). I n 9 of the cases of
i*cpi*esc~iitiiig
this series, the malig~iaiic~y
complicated von Becklinghausen’s disease.
h i iiii cqual iinmlwr of w s w the nialigii~iitcliaiige occnrred in palisatled
neiiriiioqas (Fig. 3 5 ) .
‘I’hescl tumors recur after excision a i d esteiid along the perineum1
lymphatic spaccs. Traiisplanitatioii by this route, rather than thc fo1.-
FIG.30.
TIIE (’OAIMON SITESOF NEKVESHEATH
SAXCOMA
matioii of iicw t iimory, seems Ihc most likely cxplaiiation of recurrciice.
13ccuusc of the local invasiveiiess aiitl the deep-seated location of thesc
growths, bone iiivolveniciit (so-callccl parostcal sarcoma) is not an
ii~i(~ornrnoii
fiiicliiig ((+cscliicktci~). 1)ist;uit metastasis to lung or scalp
or l m ~ i nrather than t o the regional lymph notlcs is o1)served in the
fatal crises,
Thi*cc ontstaiitling observatioiis a s to trcatmciit a r e worth noting.
First, the cured c w m i i t this series either m i * e treated l y ampiitstion
or were snpci-ficial tumors formc~rlyclassed as sar(*oma of the skin.
b’W. 32.
PHOTOMICROGRAPH OF (;KADE
11
S A K ( ‘ O N A OF THE hTERVE SFIEATII.
402
PATH.
NO. 31775
b’IG.
33.
FIG.34.
PIIOTOBIICROGIRAPH OF
GRADE111 SARCOMA OF
TEE
NERVE
SHEATH.
PATH.
NO. 39696
PHOTOYICROGRAPE
OF GRADE 1V SAIWOAIA
OF T I I E NERVE
SHEATH.PATH.No. 13152
403
404
ClIAltLES F. OESCHICKTER
Second, irradiation did iiot produce a permanent cure when u s c d alone,
but in tlic recurrent tumors apparently delayed mettistasis or the spread
of tlic disease in a small percentage of cases. Third, where the tumoi*s
had invaded bone, o r deeper structures such as the pelvis, no curw
were effected. The prognosis of this form of sarcoma of the soft parts,
arising from the nerve sheath, is f a r worse than that of fibrospindlc-wll
siircorna of fascia1 origin, with which it is easily confiixecl histologicdy.
Hist o
p i csis
An interpretation of the histogenesis of these ncoplusms of tlic
pei~ipliel*ul
mi-ves s;houlcl account for the histologic diffeiwices hetween
tlie palisticled iieui-iiiomas tuid the myxoicl form. It should also accon1it
for the pcriplieral and central distribution of the tumors showing p.alisuding, f o r their differentiation and fibrosis, for their encapsulatio~i,
t heir occurrciicc i n adults, and their benign clinical course. It should
likewise explain the distribution of the myxoid neurinomas su1)epitlermally and on the deep nerve trunks, their lion-ciicapsulation, t2iei 1’
teridency to be multiple and congenital in von Rcckliiighauscii’s d i s w w ,
their recurrence af
excision, and frequent malignant change.
These fundamental differences iii behavior in the two groups 01’
tumors of the nerve sheath arc apparently relatcd t o the presence or
abseiice of a myclin sheath o n the nerve fibers affected. 14ccor(ling to
Nageotte, the myeliii exerts a. physiological cwiitrol over the cliartict(1r
of the sheath of Sch\vaiiii. I n the presence of mycliii individual tubular
film-,and small binidles of fihers
sheaths arc forrricel about each iie~*ve
ai*e surromided by pcrilieurium. 111 lion-myclinatcrl nei*vesin the syrnImthetic system, in the skin, and iii the coriiea, the sheath of Schwanri
is multitubular, enclosiiig ;I. community of fibers in ii syricytial network.
This is well il1ustr;itctl in the iierves of the corneal 1)lexus. I11 the chick
ernbryo the nerves iiivide the cornea ill the form of a syricytial ar1)ol.ization. The network lying outside of the corzicti at the time of myclinization becomes mctlullated and is provided with iridiviclual sheaths.
On tlie other hand, the neiiritcs of tlic cornea, i i i older to maiiitairi tEic
traiisparcncy of that organ, (lo not hecome metlnllatccl, aiitl n syncytial
network or collective sheath iwriiiilis iil)oiit the c~)i*iical
plexus of fi1)ci.s.
This intimate relationship which exists bctwcwi tlic m y ellin aiid tlicl
slicath of Sc~liwaiiiialso exists l~e~tweeii
tlic mycliii a i i d lhe pcrincurium.
Not only is the re-ari-augcmciit of the sheath of Scliwaiiii c o n c u ~ - ~ + c ~ i t
wit21 the appearance of mycliri, hiit the periiicui*inm also forms at the
time that myelin tipi)cvii*s. 111 the s1)seiice of myelinixiitioii a. commuiiity
of riel-vc film-s within a syiicytium of Sch\vanii cells persists without a
tlefiiiitc~priiicwrwl cii\do1)c, tlic c~oiinective-tissueslic~utliof tliesc?fibers
remaining incomplete.
rl ih e pnlisiitletl iieiii*iiiomas il~)l)~1*(~litly
arise in connection with
rnedullatcd nerves, tho slieatli of S(chwaiiii foi*miiig definite coluniris
within the tumor a t its inceptioii aiid bciiig eiicasccl by perineuriurn.
The fibrous reaction of tlie peririenrinm accounts for the eiictipsulatioii
-
TUMORS O F THE PERIPHERAL NERVES
405
and relatively bcriigri c~hai~acter
of these growths. The coiitact of the
tumor ;it its periphery with mycliiiatetl nerve fibers accounts for the
1)alisatlctl cficct. 11s tlic tumor grows, iieitlicr axoiis nor myelin participate ; liciice, tlic i i i v t i r i a b l ~~ ~ i ~ ~ sof~ syiicytial
~ i i c c or reticulated areas
I N A PALISADED NEIJRINOMA
$'IG. 35. ~ I i O l ' O h lI('ltOGILAPI1 O F SARCOMA DEVELOPING
The tumor occurred in the popliteal spare and thc Icg was amputated. Previously published by Gcachic~kter. Path. No. 35248.
within the center of the tumor. This relationship of the palisaded
neurinomas to myelinatccl nerves accounts f o r their distribution in the
subcutaneous pei*iphci*alnen-es and on the roots of the cranial and
spiiial nerves.
406
CHAHLES E’.
UESCIIICKTEH
The myxoici neurinomas, on the other hand, tend to form in the
subepidermal nerve fibers which a r e normally non-myelinated at their
terminal ramifications. These tumors also occur on the non-medullatetl visceral sympathctics, ant1 o n the deep iierve trunks at the site
of the larger iiww plexuses of the a r m and leg. These plesuscs during
cimbryonic life and early childhoot1 represent a syncytial network of
sheath cells ~ i i dfibeias, where myelinizatiori is delayed. The origin of
these tumoi-s in a syncytinm of Rchw;inn cells acconnts for their rcticnltitcd and iioii-r)alisatlctl iiixziigemeiit, for their failure to be erwiipsnlatcci by perinewiurn, anti for their tciitlciicy t o irivaclc the more definite
iubular strnctaiw in the nerve above a11d below tlie site of origin when
they occur 0x1 the tlcbep nwves. In the snhcpidermaS tissue the conricctive tissue of the corinm i-each to siirromicl the tumor, acting as a form
of encapsulation.
The assoc+iationof the mysoitl iieiiriiiomns with childhood is probably related t o dc1:iyc~tlmyclinization of the iierves. The occurrence
of mu1tir)lc noclulcs of‘ this type iii the siq)erfic*ialand deep nerves in
( ~ i s wof voii 12cckli~igliaiiscn’stliscasc is liliewise prolmbly related to
ii congenital c1isturl)aiicc in myclliiiizatioii at tlic sites of tumor formntion. That such ;tl)normalities iii mycliiiization occur in von Rec*kliiigliaiiscii’s disease is tlcmoiist~~itctl
hy the finding of mcclulluted nerve
Gbcrs in tlic retina (Copeluxid, ct al).
The interpretation just presented accepts the origiii of these tumors
from the cells of the sheath of Scli\i~.aiin.Masson’s cytologicizl studies
h i v e sliowi that the cdls in these tumors RI’C iclentical with the cells of
the sheath of Schrvaiiii which piwlifcratc in the so-called cspei~irnenta1
scli~vaiinomits,first studied hy Nngeottc. I f the sciatic nerve of it
rabbit is cut thci*c is observcti 1 1 ~ 7 the foiirtli day clcgciicration of t h ~
distal films with mitotic proliferation of thc Scliwiiiii c ~ l l s . If the
proximal cnrS of the IICI*VC is removed, so ihat it c ~ i i i i i o tiniicrvatc the
distal segment aiiti it’ ;Lscmntl cut is made in this c1ist:tl scgmciit, hypchi*ti*opliy ant1 mitotic proliferation continue in the slicath of Schuwiiu.
‘l’hcsc ancnritic I)uiidlcs of i*egeiicratioii in the distal segmeiit aw
iei*med c~xI)cr.irncxit:ils ~ h w ~ ~ i ~ i o and
m a stlie
, indivithinl ccblls res;cmhl(i
those seen iii the iiciiriiiomas of both the pidist-ltleti and noii-palisadevl
varieties. Massori ldicivcls the collagen presciit to be a product of
tlie Rchwaiin sllcatll rather thaii of fihroblilsts. Ilc llas suggested that
palisading occiirs iii tlic tnmorx forming on seiisory iiervcs (simulatiiig
\V;igiic~r-Mcissiicr tactile eoi+piiscles) and that rion-palisatlcti ncuritiomas occiir on motor iiei-vcs.
In 1he Tissiie C’iilturc L a b o r a t o r y of the Surgical Pathologicyd L a b
oixtory Dr. G. 0. Gey h a s maintaiiicci for months cultuiw of malignimi
nerve rslieatli tumors removed a l operation. Tliesc cultures hehare
cmtii-cly difTcreiitly and are histologically easily distinguished from
cultures of IiorEiilI Iiuman fibroblasts (Figs, 3(j and 37).
Besides tlic histological features of these tumors the1.c. are otllpr
groiiiids for Idieving them of iicun*ogeiiic rather than of con~lcctivelt
tissue origin. The association of both lmiigii mid m a l i g ~ i a ~tumors
FIG.30. TISSUECIJLTUREFROM A SAIEO?,IA
OF THE KERVESHEATH
’l’hr cells :in’ groniiig out iii a syiicytium. LTote the large vesicular nuclei. Compare mith
E’igurc 37. Path. No. 45016.
FIG.37. TISSIJECIJLTUREOF NORMAL
FIROBLASTS
Notc tlir iiiterlacing network of cells and the dciise elongate nuclei. Goniparc with Fig
w e 36. Rlagiiific:ition same as in Fig. 36.
407
of this gi*oupwith melanoma, tlie fact that t h y are associated anatomically with tlie iicrves illid tliat similar tumors do not occnr in the
fascia1 striictiwes, aiid thcir maligiitint 1)chavior clinically, which exccctls tlitit of fnscial tiimcws, :we in favor of a iicurogcnic origin. F e r gi~son(cited by (hpclancl) has rcymrtccl the finding of intermediii in
the hlootl of patients with rrinligiiaiit mclaiiomas, with von Reeklingliaiiscii’s disease, aiitl with nerve sheath sarcoma. The firiilirig of this
mcliliiophorc-espaiidiiigIiormonc of tlic pituitary in these patients is
iii 1teey)ing with tlic nciurogeiiic origin of the tumors.
In tlic pi’esc”nt scricis of cases 110 sharp dividing liiic csists bc4wccii
tlich palisaclcd aiitl myxoid iieurinomas ant3 between the benign antl
r n i d i p n i t tumors, all of thcrri 1-epreseiiting various phases of iicoplastic growth in tlic slitvith of Sc1i~v:~nii.T h e contention of Pcrifieltl
and others that tlic sul)cpidei.nial notlnlcs tire true ncurofibi*omas ant1
tliffcroiit in origin from tlie palisaded ticwriiiomas docs not seem
jnstifia1)le. 111 s ~ v c ~ r iiistaiiccs
al
iii this sei*ics a siiiglc noclnlch in tlic:
su1)cpidcimal aiitl siilrciitaneoiis regioiis coritaiiictl lmth t ypcs of tissue.
l*’iii~thermoi~,
tho c~)iiceptionof ;L sepai*iitc group of tumors as tisollit1
~ n i ( lfil)i*omatous in iiatiire (iwurofihroma) is contradicted hy tissue
ciilture cxpci*imnits. 1t is ~vcllrccogiiixctl that ciiltares are easily
m u l e of tlie wlls of tlic sheath of St’li\viiiiii, lint that without the PITSc i i c * c of sucli wlls tlic iieiii*iteswill not grow arid caiiriot he maiiitaiiietl
i i i c+iiltiit.c. ‘L’Ii(~ proliferation of siwh iwilrites, therefore, in the prescmcc of coiiiicctivc tissue oiily is liiglily hypothctical. It is doubtf i l l
wlicltlici- any iiciu*itcs iii the peripheral iiervoiis system exist without
; ~ iaccompiiiigiiig
i
sheath of Seliw\.;irin(Nageottc).
r1
i UMOHS
I Y ~ ) ~ ~N E
i ~l W~ E
VIRERS
~ ~ ~: ~
TRUE:
( : NEUR~MAS
Anap?ctcifiovi A r c i ~ ~ ~ o wTi’ollo\ving
ns:
the division of a main n e r w by
;Irrlputiitioii or ii\tjiii*ya iieiiiwma forms on tlic proximal critl of tlic
tlivitlctl iici’vc~. ‘l’liis m
of i*cgeiiei~:ithgtissue (lifers from tumors
of t lie i i c ~ ~ vslicatli,
e
coiit;iiiiiii(~*
rcgciicixtiiig iiciirit cs as wcll as shcntli
h
of Schmmii cdls ;iii(i fihrous tissiic. ‘l’li~physiological details of ~ici*ve
rcgeiieration leading t o i i c i i iwma formation havc Iweri st utlicd in gi-cat
dctail. ‘I‘hc followiiig tlesciiption is l ~ s c t llaiyyly on the studies of
Nagco t t c.
Wli(’i1 R pei*iplicixl i i c r v ~t riiiik is scvci~ed,iicw cwllatcral sproiits
1)iwacetliiig fi.orn1 thci iicui+itcs (asoris) above tlic lesion appear R few
lioiii*s aftcia thc i1i.jni.y. ‘l’hcy sooii form a plesus of non-mcdullatccl
f i h r s c~iicii~+lcd
1)s’ ii syiicytiiim o f piwlifcrating cells of the sheaths of
S c l i w i i i i i o i i tlic ~ ) i ~ ) s i n isitlcl
n l of thcl division. Newly formed co1111ectivcb tissnc. from t lic ciitloiiciii-iuni :uit’i pcririeiu*ium snpplies it stroma
;iiitl a fil)i~)us
ca;tl)snlcb c~iivc~lops
the rcgcncratiiig mass, which is tcymecl
a iit~iii~nria
(li’ig. 1 ). l ’ h c growth of’ tlicl iichiiiwmtl is rapid ant1 tliso i . t l ~ i ~ 1 -ayt fii-st h i t giaatliially a i101~1~ill
oi*gnnizntion is rcsnmctl \trhcll
thc tlonii-growiiig iicliiiitcs ciittLrt lie prolifcir:~tiiigsheaths of Schwann
~)i+oc*c~ctIirig
fi.on1 tlic distal p i ‘ t i o i i of tlic sc\~crcdt ruiili. 1~lvclitually
the ortlci*c~tliienritcs I w o m c mycliiiatcd. If, a s in amputations, tile
TUMORS O F THE PERJPHEHAL NERBES
409
ricuroma forming on the proximal stump fails to firid the channels of
the sheath elements of the distal fragments and encounters instead
resistant scar tissue, the proliferation of neurites, Schwain cells, antl
coiiiiective tissue of the iieiiroma continue without myeliriization t o
form a typical painful ‘‘ amputation neuroma. ” Similar iieiiromas
follow nerve injuries where scar tissue forms an impecliment to the
regericrating fibers. The painful masses are treated by escision. I n
pcrfoi*ming amputation, injection of the iierre stump with alcohol
prewnts the formation of these neuromas.
hrewo-cpithelinl T u m o r s of the Peripheral Nerces: Tumors showiiig
a primitive neuroblastic structure, while riot uncommoii in the neui*al
structures of the sympathetic system, a r e cixtremely rare 011 the peripheral spinal nerves. (kh1 1-cported a recnrreiit ncuro-epithelial
tumor on the median nerve i n a case of von Rccl\-lingli~nscii’sdisease
in a man of thirty-five. Peiifield has illustrated a casc of Stout’s illvolviiig the uliiar i i c n e antl showing definite rosette formation. These
tnmors may represent undifferentiated forms of gaiiglioiicuroma, to
which they are undoubtedly 1-elated. They do not \\rarrant a separate
classification in view of the f a c t that the majority of all shcnth tnmors
arisiiig from the Sclinmiii cells of the pcripheral U C ~ V C Sai’c liltcwise
iieuro-ectoclei.mN1i n origin. Sarcomas of the nerve shcath, \vhich a r e
liiglily maligiiaiit tiirnoi’s, are not iiifrccyueiitly see11 in which cells have
; L I ~ cipitliclit-il-like form or arrangemelit (Fig. 29). These cpi tliclioid
l‘eaturcx of iieurogenic sarcoma wer*c noted in approsimat ely 10 per
cent of thc cases of sarcoma i n the present series. Stewart and Ckq~cland fouiid similar microscopic variants in their cnses of sarcoma of
the i i e r ~ esheath. Tlicsc epitlielioicl features in sarcoma of tlic nerve
sheath tire additional cvidcncc in favor of tlic origin of these tumors
from tlic sheath of kC(11Iwallll.
Ga,/~~Zio~ieuro??7as:
These are among the rarest tumors of the iiei*vous
system. The majority of the 150 tumors recorded in the literntiire
d the sympathetic nerves, most fiwluen tly in the regioii
have o c ~ ~ i i r r con
of the suprarenal glands. The 8 cases in the present sci-icls have been
previously reported (1,ewis and Geschickter). They o c c n r ml in the
~ o u s t i nerve,
c
mid-hrairi, cervieiil region ( 2 ) , tl(lr~tli~1,
thigh, aiitl finger.
McFarlaiicl and Sappington have rcccrit 1- 1-cportetl a case and made
a complete survey of the litcratixre. They were able t o collect 143
C;LSCR,~ of wliich 41 n.cre r.citi.operitoiie;11or within the acli*enals,18 were
in the cei’vicvl, aiitl 10 iii the mcdittstiiial rcgioii. Fifteen cases were
intracraiiial m t l 13 occurred on the craiiial nerves. Sis cases showed
multiple snbcutaiicoiis t i i n i ~ r s the
, maximum number of a single patient
heing 160. One of the C ; ~ S C S was associated with vori Rcckliiighausen’s
disease. Many of tlw cases showed immature iienroblasts o r iieuroc’ytes, 10 of such cases being recoidetl a s maligiiant.
These tumors itre emhedded in a stroma of Sc~hwaiiiicells, and palisading may occasioiially be sec‘ii. Tlic giiiglioii cells vary from small
to large mati1i.e forms aiitl occasioual ncnrites arc found.
3
These do not inc*luile the
C : L S C ~ pre\,iouslg
Icported by Lewis and Gcschicktcr.
410
CHAELES I?.
GESCHlCKTER
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