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Atypical Ganglion Cell Tumor of the Sciatic Nerve
Dominick J. H. McCabe, MB, MRCPI;
Gerard P. McCarthy, MB;
Finbarr Condon, FRCSI;
Sean Connolly, MD;
Paul Brennan, FRCR;
Francesca M. Brett, FRCPath;
Brian Hurson, FRCSI;
Kieran Sheahan, MRCPath;
Janice Redmond, MD
Arch Neurol. 2002;59:1179-1181.
ABSTRACT
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Context Although herniation of a lumbosacral intervertebral disk is a major
cause of sciatic distribution pain, relentlessly progressive symptoms or signs
should alert one to the possibility of a tumor involving the nerve.
Objective To describe the clinical, neurophysiological, and histological features
of a pathologically unique tumor involving the sciatic nerve.
Setting Tertiary referral university hospital.
Patient A 36-year-old woman was seen with a 6-year history of increasingly severe
symptoms in the distribution of the left sciatic nerve.
Results Electromyography indicated a sciatic nerve lesion in the region of the
greater sciatic notch. Magnetic resonance imaging demonstrated a tumor involving
the left sciatic nerve in this area. Light microscopy, electron microscopy,
and immunohistochemistry results confirmed the presence of an atypical ganglion
cell tumor of the sciatic nerve that exhibited prognostically conflicting
clinical and histological features.
Conclusions To our knowledge, this is the first report of an atypical ganglion cell
tumor affecting the sciatic nerve, and illustrates the value of detailed neurophysiological
examination in localizing the site of peripheral nerve injury to facilitate
focused neuroimaging when standard investigations are uninformative. Longer
follow-up is required to determine the true biologic potential of this lesion.
INTRODUCTION
HERNIATION OF a lumbosacral intervertebral disk is a major cause of
chronic or recurrent low back and sciatic distribution leg pain.1
Less common diagnoses should be considered when the clinical presentation
is atypical. Cyclical sciatica, that varies in intensity in a catamenial pattern,
can be caused by endometriosis affecting the nerve,2-3
whereas relentlessly progressive symptoms or signs in the affected limb should
alert one to the possibility of a tumor4-7
or an arteriovenous malformation involving the sciatic nerve.8
REPORT OF A CASE
A 36-year-old woman had a 6-year history of increasingly severe left
leg pain. She had initially reported intermittent aching pain in the left
posterior thigh after waking. After a 2-year period, the pain radiated from
the left buttock down the posterior aspect of the left leg to the ankle during
the first 5 days of the patient's menstrual cycle. Subsequently, she also
experienced less severe symptoms during the remainder of the menstrual cycle.
Four years after the onset of symptoms, the patient developed numbness and
hyperesthesia over the left outer calf and foot, with intermittent shooting
pains radiating from the sole of the foot to the left calf and thigh. The
pain was exacerbated by prolonged sitting or exercise, unchanged by coughing
or sneezing, and there was mild intermittent foot drop when the symptoms intensified.
Laparoscopy around that time revealed a retroverted uterus, but no evidence
of endometriosis.
The clinical features persisted until 2 months prior to presentation
when the patient became pregnant. Her symptoms improved between the sixth
and eighth week of gestation, but then, she developed a constant, severe,
throbbing pain affecting the left buttock, calf, and foot, necessitating inpatient
care and opiate analgesia. There was progressive wasting of the left gluteal
and calf muscles over the next 2 months, and by 20 weeks' gestation, the patient
walked with a complete left foot drop, avoiding all contact of the left foot
with the ground. Clinical examination of the left lower limb revealed marked
muscle wasting of the glutei, left tibialis anterior and gastrocnemius muscles,
decreased muscle tone, and severe weakness of ankle and toe dorsiflexion and
plantarflexion. The knee jerk was brisk but the ankle jerk was reduced. The
left plantar response was not assessed because of hyperpathia, but the right
plantar response was flexor. There was altered soft touch, pin prick, and
temperature sensation, with allodynia and hyperpathia over the left L5 and
S1 dermatomes. The remainder of the neurological examination was normal.
RESULTS
The clinical findings were suggestive of a high sciatic nerve lesion,
but standard axial and sagittal T2- and T1-weighted magnetic resonance imaging
scans of the lumbosacral spine showed no abnormality. The results of routine
hematological and biochemical investigations showed no abnormality; the autoantibody
tests, treponemal serologic studies and cerebrospinal fluid analysis were
normal. To facilitate localization of the lesion, nerve conduction studies
and concentric-needle electromyography were performed using standard techniques.
No sensory nerve action potentials were recorded from the left sural or superficial
peroneal nerves, indicating pathologic abnormality at, or distal to, the dorsal
root ganglion. There were positive sharp waves and fibrillations (evidence
of denervation) in the left gluteus maximus and tibialis anterior muscles,
and large amplitude polyphasic motor unit potentials (evidence of reinnervation)
in the left gluteus maximus, semitendinosus, short head of biceps femoris,
and tibialis anterior muscles. Concentric-needle electromyography of the L4
to S1 paraspinal muscles was normal. These studies indicated a partial lesion
of the left sciatic and inferior gluteal nerves, and the site of pathologic
abnormality was felt to be in the region of the greater sciatic foramen because
of the close proximity of the 2 nerves in this area.9
A T1-weighted magnetic resonance imaging scan of the pelvis subsequently demonstrated
a 2-cm hypointense soft tissue mass at the greater sciatic notch, enveloping
the proximal left sciatic nerve, and associated with gluteal muscle wasting;
the lesion enhanced with gadolinium Gd 64 (Figure 1). A second series of magnetic resonance imaging scans 3
weeks later showed enlargement of the mass; therefore, a percutaneous needle
biopsy under ultrasound guidance was performed. This showed a focally necrotic
tumor of indeterminate origin and the patient proceeded to have an open diagnostic
biopsy via a posterior approach. The roots of the sciatic nerve exited the
greater sciatic notch in 4 separate bundles, emerging through the substance
of the piriformis muscle before joining to form the sciatic nerve proper,
1 cm distal to the greater sciatic notch. The proximal 10 cm of the sciatic
nerve proper was indurated, red-purple, and approximately 2 cm in diameter.
The posterior femoral cutaneous nerve and the portion of the piriformis muscle
in proximity to the sciatic nerve were also firm and thickened. The sciatic
nerve was decompressed at the sciatic notch and multiple biopsy specimens
were obtained.
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Figure 1. Coronal T1-weighted magnetic resonance
imaging scan of the pelvis. Hypointense soft tissue mass (upper thin arrow)
at the greater sciatic notch associated with marked gluteal muscle wasting
(lower thick arrow).
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Light microscopic examination revealed nodules of atypical ganglion
cells in a background infiltrate of mononuclear round and spindle cells; Schwann
cells were not seen (Figure 2A).
The tumor cells had moderately pleomorphic nuclei, prominent nucleoli, and
abundant acidophilic cytoplasm with extensive vacuolar alteration. Mitotic
figures were not present, but focal areas of necrosis, perineural infiltration,
and muscle invasion were identified. Results of immunocytochemistry studies
showed that the tumor cells were positive for neuronal markers such as PGP
9.5, chromogranin, synaptophysin, and neuron-specific enolase. Glial (glial
fibrillary acid protein), epithelial (CAM 5.2, AE 1, AE 3), melanoma (HMB
45), and smooth muscle (smooth muscle actin, desmin) markers were negative.
In addition, staining for progesterone receptors was positive, but estrogen
receptor positivity was not identified. Electron microscopy confirmed that
the tumor was of ganglion cell origin (Figure
2B).
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Figure 2. A, Light micrograph of a section
of the tumor mass. Note atypical ganglion cells (thin arrow) with scattered
intralesional lymphocytes (thick arrow) (hematoxylin-eosin, original magnification
x400). B, Electron micrograph of a neoplastic ganglion cell. The presence
of abundant intermediate filaments (left arrow) and Nissl substance (right
arrow) confirm the neuronal origin of the sciatic nerve lesion (original magnification
x75 000).
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On the basis of these findings, a diagnosis of an atypical ganglion
cell tumor of the proximal portion of the sciatic nerve was made. Six weeks
postoperatively, the severity of the patient's pain had decreased, the numbness
over the lateral foot and toes improved, but the clinical features were otherwise
unchanged. The patient subsequently was delivered of a normal healthy infant.
Three years postoperatively, she was ambulatory with no evidence of disease
progression but declined further investigations.
COMMENT
This patient had an unusual clinical history of sciatic distribution
pain secondary to a histologically unique tumor involving the proximal sciatic
nerve. The case emphasises the value of detailed neurophysiological examination
in localizing the site(s) of peripheral nerve injury, to facilitate focused
neuroimaging when standard investigations are uninformative. It also demonstrates
the importance of considering rarer causes of sciatica, especially tumors
involving the nerve, when the clinical history is atypical. Tumors with a
neoplastic ganglion cell component include gangliocytomas and gangliogliomas
in the central nervous system, and ganglioneuromas in the peripheral nervous
system, although the latter occasionally occur within the central nervous
system.10 Gangliocytomas are rare tumors composed
of neoplastic neurons with a ganglion cell phenotype in a background stroma
of nonneoplastic astrocytes, whereas gangliogliomas contain an admixture of
both atypical ganglion cells and neoplastic glia. Ganglioneuromas are characterized
by atypical ganglion cells interspersed among sheaths of Schwann cells and
a variable collagenous stroma that does not contain glial cells. This lesion
is histologically unique in that it does not fulfill the diagnostic criteria
for any of the typical ganglion cell tumors because glial cells and Schwann
cells were absent,10 it was highly cellular,
and there was an infiltrative growth pattern with areas of necrosis. The location
of the tumor is also unusual. In a clinicopathologic study of 35 neurogenic
tumors of the sciatic nerve, 21 (60%) were classified as neurofibrosarcomas,
7 (20%) as schwannomas, and 7 (20%) as neurofibromas, but no ganglion cell
tumors were identified.4 Although it is uncertain
whether the ganglion cells are of autonomic or dorsal root origin, one would
not expect to find ganglion cells at this point along the course of the sciatic
nerve. We postulate that the delayed union of the component roots of the sciatic
nerve distal to the greater sciatic notch raises the possibility of a neuronal
migration abnormality that could account for their peripheral location in
this case. The initial catamenial variation in symptom intensity and subsequent
enlargement of the tumor in pregnancy suggests a degree of hormonal sensitivity,
and staining for progesterone receptors was positive. The role of progesterone
in the patient's catamenial symptom variablity is unclear, because one would
have predicted more pronounced symptoms during the second half of the menstrual
cycle when progesterone levels are higher. However, the dramatic increase
in symptoms during pregnancy may have been secondary to increased tumor vascularity
associated with the vasodilatory effects of rising levels of progesterone.
The prognosis in this case is unknown. From a histological viewpoint,
the lack of mitotic activity is reassuring, but the infiltrative growth pattern
with multiple microscopic areas of necrosis may worsen the prognosis. Although
the prolonged duration of symptoms for 6 years prior to presentation and the
favorable clinical course following surgery suggest a benign clinical lesion,
there was a dramatic clinical and radiological deterioration over a 3-week
period during pregnancy. Longer follow-up is required to determine the true
biologic potential of this lesion.
AUTHOR INFORMATION
Accepted for publication December 7, 2001.
This research is funded in part by a grant from the Brain Research Trust,
London, England (Dr McCabe).
Corresponding author: Dominick J. H. McCabe, MB, MRCPI, Department
of Clinical Neurology, Institute of Neurology, University College London,
The National Hospital for Neurology and Neurosurgery, Queen Square, London
WC1N 3BG, England (e-mail: d.mccabe{at}ion.ucl.ac.uk).
From the Departments of Neurology (Drs McCabe and Redmond) and Pathology
(Dr Brett), St James' Hospital, the Departments of Pathology (Drs McCarthy
and Sheahan), Orthopaedic Surgery (Drs Condon and Hurson), and Clinical Neurophysiology
(Dr Connolly), St Vincent's University Hospital, and the Department of Neuroradiology,
Beaumont Hospital (Dr Brennan), Dublin, Ireland; and the Department of Clinical
Neurology, Institute of Neurology, The National Hospital for Neurology and
Neurosurgery, London, England (Dr McCabe).
REFERENCES
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1. Adams RD, Victor M. Pain in the back, neck, and extremities. In: Adams RD, Victor M, eds. Principles of Neurology. 5th ed. New York, NY: McGraw-Hill Co; 1993:171-196.
2. Cottier J-P, Descamps P, Sonier CB, Rosset P. Sciatic endometriosis: MR evaluation. AJNR Am J Neuroradiol. 1995;16:1399-1401.
PUBMED
3. Zager EL, Pfeifer SM, Brown MJ, Torosian MH, Hackney DB. Catamenial mononeuropathy and radiculopathy: a treatable neuropathic
disorder. J Neurosurg. 1998;88:827-830.
ISI
| PUBMED
4. Thomas JE, Piepgras DG, Scheithauer B, Onofrio BM, Shives TC. Neurogenic tumours of the sciatic nerve: a clinicopathologic study
of 35 cases. Mayo Clin Proc. 1983;58:640-647.
PUBMED
5. Hruban RH, Shiu MH, Senie RT, Woodruff JM. Malignant peripheral nerve sheath tumors of the buttock and lower extremity:
a study of 43 cases. Cancer. 1990;66:1253-1265.
FULL TEXT
|
ISI
| PUBMED
6. Harrison MJ, Leis HT, Johnson BA, MacDonald WD, Goldman CD. Hemangiopericytoma of the sciatic notch presenting as sciatica in a
young healthy man: case report. Neurosurgery. 1995;37:1208-1212.
PUBMED
7. Kanamori M, Matsui H, Yudoh K. Solitary T-cell lymphoma of the sciatic nerve: case report. Neurosurgery. 1995;36:1203-1205.
ISI
| PUBMED
8. Cusimano MD, Shedden PM, Hudson AR, Bilbao JM. Arteriovenous malformation of the pyriformis muscle manifesting as
a sciatic nerve tumor. Neurosurgery. 1992;31:151-153.
PUBMED
9. Williams PL, Warwick R. Arthrology. In: Williams PL, Warwick R, eds. Gray's Anatomy. 36th ed. Edinburgh, Scotland: Churchill Livingstone; 1980:420-503.
10. Lantos PL, Vandenberg SR, Kleihues P with contributions from Lopes MBS. Tumours of the nervous system. In: Graham DI, Lantos PL, eds. Greenfield's Neuropathology. Vol 2. 6th ed. New York, NY: Oxford University Press Inc; 1997:583-879.
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