Keywords
intradural metastasis - breast carcinoma - brachial plexus - brachial plexopathy -
perineural spread
Introduction
Primary cancers that are most typically associated with spinal metastasis are, in
descending order, prostate, breast, kidney, lung, and thyroid.[1] Breast cancer being one of the most common cancers worldwide also shows metastasis
to the central nervous system, with intracranial involvement more common than extracranial
sites. Here is a case report of a patient suffering from primary left breast carcinoma
presenting with neurological deficits due to intradural extramedullary metastasis
with spread along the brachial plexus.
Case Description
A 60-year-old woman, right-handed, known case of hypertension on regular medication,
was diagnosed with left brachial plexitis 2 years ago when she started having pain
in her left wrist and elbow joint associated with occasional numbness. She started
developing gradually progressive weakness in the left upper limb starting distally
with weakness in her grip, which later progressed to involve muscles of proximal joints
such as the elbow and shoulder. For the last 1 year, her left upper limb was non-functional
and she did not respond to any medications including steroids. She presented to us
with weakness in her left lower limb and difficulty in walking for 7 days. She did
not show any symptoms of cranial involvement. She also had a history of upper back
pain for the last 1 year which was on and off and relieved on medication and more
after lying down. There were no symptoms of bladder or bowel involvement. On neurological
examination, we found left upper limb LMN weakness with power 1/5 and left lower limb
power of 4/5. There was significant loss of pain, temperature sensation and joint
position sense, vibration sensation in the left upper limb and lower limb. There was
no local tenderness on the spine examination. On her physical examination, we found
a scar of healed ulcer on the left breast in the lower inner quadrant with fixed overlying
skin ([Fig. 1]). (Incidentally, this history was not known to her husband, son, sister, and neither
it was mentioned to us).
Fig. 1 External appearance of breast lesion.
FDG PET CT and MRI with gadolinium contrast studies were done ([Figs. 2]
[3]
[4]). PET CT revealed a primary hypermetabolic lesion in the left breast with metastasis
in the left supraclavicular lymph nodes, right lung middle lobe with lytic destructive
lesions of manubrium sterni and third rib of the left side, diffuse metastatic infiltration
of C6, C7, and C8 nerve root with infiltration of the adjacent part of the superior
trunk and posterior cord of brachial plexus, intraspinal extra-axial leptomeningeal
thickening involving the anterior, left lateral and posterior surface of the spinal
cord at C5, C6, C7 and D1 vertebral level with associated cord compression. MRI showed
well-defined heterogeneously enhancing intradural extramedullary lesion extending
from C5 to D1 with significant cord compression and edema mainly on the left side.
There was thickening of brachial plexus nerve roots on MRI giving it an appearance
of a clumped-up mass, which explained the left upper limb paresis. The pressure effect
of mass on ipsilateral side of the cord was so significant that it resulted in progressive
weakness in her left lower limb. Ultrasonography-guided trucut biopsy was taken from
the left breast lesion and was evaluated for histopathology, ER, PR status, and HER2NEU
status. For spinal lesion decompression was achieved by C5 to D1 laminectomy and subtotal
excision of the intradural lesion was done. The lesion was densely adhering to the
spinal cord and engulfing the nerve roots ([Figs. 5]
[6]). While the posterior lesion was excised precisely, the left lateral and anterior
parts of the lesion were very difficult to excise due to dense adhesions to the spinal
cord and undistinguishable nerve roots. Adequate decompression was achieved. Post-operatively,
the patient had improvement in her left lower limb power and back pain. Histopathology
revealed primary invasive ductal carcinoma, grade 3 of the left breast with ER, PR
positive, and HER2NEU equivocal status with Ki67 index of approximately 55% and metastatic
carcinoma (C5 to T1) ([Fig. 7A, B]). The patient was started on hormonal therapy and was advised for further adjuvant
therapy.
Fig. 2 (A, B) MRI with gadolinium contrast showing enhancing lesion from C5 to T1.
Fig. 3 (A, B) Axial sections showing significantly compressed cord mainly from left side with
encasement of nerve roots.
Fig. 4 (A, B) Coronal MRI images showing thickened brachial plexus roots and lesion extending
intradurally.
Fig. 5 Intraoperative image of lesion.
Fig. 6 Intraoperative image after decompression and subtotal excision of lesion.
Fig. 7 (A, B) Histopathology images of metastatic lesion at 100 um and 200 um respectively.
Discussion
Excluding lymph nodes, the skeleton is the third most frequent location for metastasis
after the liver and the lungs,[1]
[2]
[3]
[4] with the spinal column being the most common site.[3] The spinal metastatic disease involves the vertebral bodies (80%) more often than
the posterior elements (20%).[5]
[6] About 60% to 70% of metastases involve the thoracic, 20% to 30% the lumbosacral,
and 10% the cervical region.[7]
[8]
[9]
[10] Breast and lung cancers usually metastasize preferentially to the thoracic spine,
whereas prostate, colon, and pelvic cancers tend to arise in the lumbosacral spine.[7]
[8]
[10] Although spinal pathologic conditions are typically classified according to their
anatomical location (epidural or extradural, intradural extramedullary, or intradural
intramedullary), spinal metastases are regarded as arising from one of four compartments:
spinal skeleton (85%), paravertebral region (10–15%), epidural space (< 5%), and intradural
(extramedullary or intramedullary; remainder).[5]
There are four pathways for metastatic tumor spread to the spine: hematogenous dissemination
(via an artery), through the paravertebral plexus of veins (Batson's plexus), direct
invasion of the bone, and dissemination through cerebrospinal fluid.[11]
[12]
[13]
[14] Metastasis to the intradural space has five proposed routes of spread from outside
the central nervous system including direct invasion, Baton's venous plexus, perineural
lymphatics, CSF dissemination, and hematogenous spread through the arterial system.[15] Metastatic intracranial tumors are concomitantly detected in 90% of patients with
metastatic intradural spinal cord tumors.[16]
Spinal metastatic disease can have a wide variety of clinical manifestations, including
signs of systemic disease such as asthenia, anorexia, night sweats, and unintentional
weight loss, axial pain is the earliest and most common symptom.[9]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24] Patient can also present with radicular pain, sensory radiculopathy, myelopathy,
and autonomic dysfunction. Any patient suspected to have the metastatic spinal disease
should undergo a detailed and appropriately focused history and physical examination.
Magnetic resonance imaging (MRI) is the “gold standard” imaging technique for assessing
spinal metastasis. Intradural metastasis is the terminal stage of the disease and
the average survival is between 6 and 9.5 months.[25] Our patient was having progressive monoparesis starting 2 years ago and was being
treated as brachial plexitis. Her signs and symptoms did not improve with medications.
Her symptoms started with brachial plexus involvement and the patient came to us with
rapidly progressive weakness of the left lower limb and impending quadriparesis/plegia.
Metastatic breast and lung cancers are the most common non-traumatic causes of brachial
plexopathy, after radiation-induced fibrosis.[26] The incidence of brachial plexopathy due to breast carcinoma is approximately 0.5%.[26] Because one of the major lymphatic drainages of the breast is through the apex of
the axilla, it is not uncommon for metastatic breast cancer to invade the brachial
plexus.[27] The most likely pathway is via the intercostobrachial nerve, which may communicate
with the brachial plexus via the medial cord, the medial and posterior antebrachial
cutaneous nerves, or the T2 ventral ramus.[28] Other less likely possible routes include the lateral and medial pectoral nerves,
which originate from the lateral and medial cord, and the supraclavicular nerves,
which may communicate with the brachial plexus at the level of the suprascapular nerve
and C5 root.[28] The patient had multiple sites of metastatic spread, which were through the hematogenous
spread, but the intradural spread must have been perineural because the patient first
started having signs and symptoms of brachial plexus involvement, which then progressed
to show signs and symptoms of the nerve root and cord compression. MRI also showed
thickening of the brachial plexus giving it a mass-like appearance that was contiguous
with the intradural extension ([Fig. 4]). The absence of any other lesion in the CNS deters the CSF spread and the absence
of any local tissue destruction or active metabolic site on FDG-PET deters the direct
spread. By the review of current literature, until now, the perineural spread of breast
carcinoma to intradural extramedullary space has not been reported. There has been
one case of renal cell carcinoma spreading along the autonomic nerves to the aorticorenal,
celiac, and mesenteric ganglia and then along the thoracic and lumbar splanchnic nerves
to the corresponding spinal nerves to the intradural, extramedullary space.[29] Further research is necessary to identify factors that predispose neoplasms to metastasize
via specific routes to the intradural space. Intraoperatively also, the nerve roots
were completely encased by the mass. The main aim of surgical treatment-laminectomy
with decompression and subtotal resection was to help stop the further neurological
impairment and alleviate the pain. The surgery was strictly palliative and to increase
or maintain the quality of life for the remainder of the life. Considering the terminal
stage of the disease treatment options, prognosis, need for adjuvant therapy, and
risks and complications of surgery are of utmost importance while counseling the patient
and the family members. The presence of a pre-surgical neurological deficit is an
independent overall negative predictor of survival with one study reporting a hazard
ratio of 10.2.[30]
Conclusion
In advanced metastatic cancer, preservation of neurologic function is the goal of
surgical treatment. The surgical treatment is strictly palliative and to increase
or maintain the quality of life for the remainder of the life. Thorough evaluation
of patients presenting with a neurological deficit is always mandatory. Patient education
is equally important for palliative treatment as well as to help reduce the burden
of metastatic diseases. Further research is necessary to identify factors that predispose
neoplasms to metastasize via specific routes to the intradural space.
