Key-words:
Cervical spinal cord - intramedullary metastasis - malignant mesothelioma - surgery
Introduction
Malignant mesothelioma is aggressive cancer arising from the mesothelial surfaces
of the pleural in 80% of all cases.[[1]] The prognosis of pleural malignant mesothelioma (PMM) is dismal even with multimodal
therapy; median survival is 12 months after symptom onset.[[1]],[[2]],[[3]],[[4]],[[5]] PMM has an increasing incidence due to environmental factors and has been strongly
related to inhalational exposure to asbestos[[1]],[[4]],[[6]],[[7]],[[8]] but also inhalation of other mineral fibers, such as erionite, a fibrous crystal
found in Turkey, has also been identified as a risk factor.[[3]] Although malignant mesothelioma is a rare disease, the lack of effectiveness in
treatment and the increasing incidence through the world have led to improve the clinical
research in this field.[[1]],[[9]]
Mesothelioma has a predilection for local spread into adjacent tissues.[[10]] Sites of spread are most thoracic lymph nodes, the contralateral pleura, the abdominal
cavity, and distant organs through hematogenous dissemination in the later stages
of the disease.[[2]],[[11]],[[12]],[[13]],[[14]]
Spinal involvement of a PMM is exceptional with only a few reported cases.[[11]],[[12]],[[13]],[[14]],[[15]],[[16]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]],[[23]],[[24]],[[25]],[[26]],[[27]],[[28]],[[29]],[[30]],[[31]],[[32]],[[33]]
The authors report a case of a hematogenous intramedullary metastasis to the cervical
spinal cord from malignant mesothelioma. Six articles with cranial or spinal meningeal
infiltration of a mesothelioma without intradural tumor were found in literature.[[28]],[[30]],[[34]],[[35]],[[36]] Ten reports [[Table 1]] were retrieved with one case of intradural mesothelioma each,[[12]],[[13]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]],[[23]],[[25]] two of which were in intradural extramedullary location,[[23]],[[24]] and eight of which showed intramedullary growth[[12]],[[13]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]],[[25]] [[Table 2]]. These eight cases were analyzed and together with the current case, serve as the
basis for the discussion of intradural intramedullary metastasis from PMM.
Table 1: Intradural spinal cord metastasis from pleural malignant mesothelioma
Table 2: Overall review of intramedullary metastasis from pleural malignant mesothelioma
Case Report
On March 2000, a 68-year-old, right-handed male with a history of malignant mesothelioma
was admitted to our department after 3 weeks of progressive mild bilateral low extremity
weakness, more pronounced on the left side. The patient had previous occupational
exposure to asbestos working at a fiber cement factory for 20 years, and in 1989,
he was diagnosed with asbestosis. He had undergone a left thoracotomy for tumor resection
and subsequently treated with local radiotherapy 1 year ago.
Neurological examination revealed a paraparesis of lower extremities (4/5 on the right
and 3/5 on the left side), decreased light touch, pain, and temperature sensation
on the right side below T1, without sphincter disturbance. Increased reflexes in the
lower extremities, while the joint position and vibration sense were normal. He had
upgoing toes bilaterally (partial Brown–Sèquard syndrome). Cervical X-rays film did
not show any bony abnormalities. Magnetic resonance imaging (MRI) of the cervical-thoracic
spine revealed a hypointense left intramedullary anterolateral lesion at the level
of C6–C7 strongly enhancing after gadolinium administration [[Figure 1]] and [[Figure 2]].
Figure 1: Coronal T1-weighted magnetic resonance images of the cervicothoracic spine after
gadolinium injection demonstrating a well-shaped enhancing mass in the spinal cord
at the C6-C7 level. Images showing no evidence of (a) perimedullary or paravertebral
(b) mass (yellow arrowheads)
Figure 2: Axial T1-weighted magnetic resonance images after gadolinium injection, showing intradural
enhancing mass, with no evidence of transdural extension or foramina involvement (yellow
arrows)
The patient underwent surgery through median posterior short incision and C6–C7 laminectomy.
Opening the dura and the arachnoid, the spinal cord appeared bulky on the left side
by an intramedullary grayish lesion that was completely removed, even though a clear
plane was difficult to identify between the tumor and surrounding spinal cord. No
intradural or extradural nerve involvement was seen. Pathological examination of the
specimen revealed malignant mesothelioma. The cells exhibited large irregular nuclei
with prominent nucleoli, small-to-moderate amounts of pale-staining cell cytoplasm,
and mitotic figures [[Figure 3]]. Immunohistochemical staining was positive for keratin, vimentin, epithelial membrane
antigen, and cytokeratin 5/6 and was negative for S100, CD15 (LeuM1), and carcinoembryonic
antigen. This staining profile was consistent with sarcomatous-type malignant mesothelioma.
Figure 3: Hematoxylin and eosin staining (a and b) showing mesothelioma cells with large irregular
nuclei and prominent nucleoli, pale staining cell cytoplasm, and mitotic figures
The postoperative course was favorable. The patient's neurological condition improved
and 20 days after surgery, he had completely regained normal lower extremity function.
Eight months after surgery, the patient died due to the progression of the thoracic
disease.
Materials and Methods
Intradural mesothelioma is highly uncommon and has been reported in 11 cases, including
the present case, so far[[12]],[[13]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]],[[23]],[[24]],[[25]] [[Table 1]] and [[Table 2]]. In two cases,[[23]],[[24]] the lesion was extramedullary. In one of those two cases,[[23]] a thoracic roots invasion by desmoplastic malignant mesothelioma without intramedullary
tumor localization were reported.
Discussion
Overhauling our analysis [[Table 1]] and [[Table 2]], spinal involvement of a malignant PMM is in general exceptional and occurs most
commonly as involvement of the vertebral body or epidural space.[[3]],[[11]],[[27]],[[33]],[[37]],[[38]] Spinal metastasis can be considered as a direct centrifugal extension into the
nerve root through the intervertebral foramen, or as a result of hematogenous spread
to the meninges through the intercostal arteries or the veins of Batson's plexus.[[21]],[[28]],[[30]] A characteristic way of spreading is perineural or “neurotropic” growth along nerve
roots due to primary tumors neurotropism.[[11]],[[24]] Extension along the pia matter or arachnoid membrane surrounding the nerve root,
known as leptomeningeal spread, can be interpreted as one of the hematogenous metastases.
Eight previous case reports document intramedullary spinal cord metastasis due to
PMM. Compared to all cases reported above, in only three cases (including our case),
intramedullary tumors were considered resulted from hematogenous or leptomeningeal
spread, without continuity with the pleural lesion.
Due to the paucity of cases, no prediction can be made for which histological type
of mesotheliomas has a tendency for intradural spread. Sarcomatous desmoplastic malignant
mesotheliomas constitute approximately 10% of malignant mesotheliomas[[1]],[[9]],[[33]] and have been more frequently associated with metastasis and shorter survival in
one series.[[1]]
In six[[17]],[[18]],[[19]],[[22]],[[25]] of the 11 cases reported so far, including the present case, a sarcomatous type
malignant mesothelioma was detected in the histological examination suggesting a strong
tendency of this type of mesothelioma for intradural spread.
However, it may be hypothesized that a protracted course of disease may leave enough
time for a mesothelioma to slowly transgress the dura and infiltrate the spinal cord;
concordantly, Lee's case has a 18-month history,[[38]] Hillard's case a 24-month history,[[12]] and Payer's case a 28-month history of pleural mesothelioma prior to spinal infiltration.[[19]] In our case, diagnosis of intradural mesothelioma occurred in a patient with a
14-month history of PMM. The median time from symptom/treatment of PMM to diagnosis
of intramedullary mesothelioma is 13.3 months, in the cases reported so far.
In our case, the tumor appeared as an intramedullary localized mass at the C6–C7 level
and like in Cooper[[15]] and Yamamoto et al.[[25]] reports, there is an evidence of direct hematogenous spread to the spinal cord
by the spinal branch of the intercostal arteries or the veins of Batson's plexus.
Hence, in our case, no leptomeningeal spread or neoplastic deposits to the arachnoid
sheath was found. Furthermore, no epidural spinal canal, no nerve roots, or extramedullary
involvement was found.
Intramedullary involvement is extremely rare,[[6]],[[12]],[[13]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]],[[25]] with nine cases including the present case. The majority of reports indicate that
the thoracic spinal cord is most often involved, followed by one case of the junction
cervical/thoracic cord. Our case is the second reported one of intramedullary cervical
spine cord metastasis from PMM[[6]],[[12]],[[13]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]],[[23]],[[24]],[[25]] [[Table 2]]. No multiple metastases to the spinal cord are reported so far.
Most patients present with rapid onset of symptoms referable to the spinal cord, including
pain, weakness, sensory loss, and incontinence. Weakness is the most common presenting
symptom and resembles a Brown–Sèquard syndrome. Sensory symptoms are often difficult
to characterize but are frequent and may be contralateral to the weak extremity. In
one case (Yamamoto et al.[[25]]), a Brown–Sèquard syndrome was associated to a C5 radiculopathy. Contrast-enhanced
spine MRI is the most sensitive and reliable radiographic means to diagnose intramedullary
mesothelioma.
As the disease progresses, patients often deteriorate and manifest a complete spinal
cord transection with paraplegia. In most patients reported with intramedullary metastatic
mesothelioma who underwent surgery did not achieve any improvement in their neurological
condition. In our case, a favorable surgical outcome was achieved with normal lower
extremity function. However, patient's preoperative neurological examination (partial
Brown–Sèquard syndrome without sphincter disturbance) and short-time diagnosis to
surgical treatment, were crucial for the outcome.
If the patient suffers neurological deterioration with possible preservable function,
and preoperative imaging not indicates definitively whether the intraspinal involvement
is intradural, surgical decompression with intradural exploration is recommended.
Extradural tumor can be removed safely in most cases. Intradural tumor's cleavage
plane of the tissue may determine whether successful gross total resection can be
achieved. In selected cases, partial spinal decompression may be sufficient to prevent
further neurological deterioration.[[6]]
The treatment of intramedullary metastasis from PMM is poorly defined, as there have
been no prospective trials due in large part to the infrequency of occurrence. As
a consequence, the literature reflects expert opinion, case series, and review of
the literature. Two general approaches have been suggested: resective surgery and
CyberKnife stereotactic radiotherapy. In the majority of the cases reported neither
of these approaches or improve function. Although not in all cases of intramedullary
metastasis due to PMM, a follow-up is available, an average survival period following
diagnosis and treatment of intramedullary mesothelioma is settled between 3 and 11
months [[Table 2]].
New concept management of patients with PMM has used antifolate (pemetrexed or raltitrexed)
platinum combinations and new radiotherapy techniques such as intensity-modulated
radiation therapy.[[39]]
There are some reports that radiation therapy only is an effective treatment for intramedullary
spinal cord metastasis in terms of clinical symptoms and radiological findings.[[17]],[[22]],[[40]],[[41]] However, there is no standard treatment for spinal cord metastasis. In case of
undiagnosed or limited cases such as radioresistant tumors and rapid neurological
deterioration, surgical resection is recommended. In our case, surgical resection
was undertaken due to the moderate neurological symptoms, rapidly progressive neurological
deterioration, and to confirm the definitive diagnosis.
Conclusions
Spinal metastasis must be considered if a patient with PMM shows neurological worsening,
and MRI shows an abnormal lesion in the cervical or more common in the thoracic cord.
Sarcomatous-type PMM should be considered propended for intradural metastasis.
Despite the natural history of the disease and the management of the intradural mesothelioma
both disappointing, we advocate surgical excision for the extradural localization.
However, if the patient has neurological deterioration with possible preservable function,
with a short time history of neurological sequelae, we recommend a neurologic decompression
with intradural exploration. The cleavage plane of the tissue may determine whether
a successful gross total resection can be achieved with a good outcome for the patient.
Declaration of patient consent
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