Key-words:
Carney complex - melanotic schwannoma - nerve sheath tumor - psammoma bodies
Introduction
Melanotic schwannoma is a rare form of nerve sheath tumor with <200 cases reported
worldwide. It accounts for <1% of all peripheral nerve sheath tumors and has a predilection
for spinal nerves.
Melanotic schwannomas can be divided into psammomatous or nonpsammomatous, a discordance
that is important due to the former's association with Carney complex. This is a rare
genetic disorder characterized by multiple benign tumors, most often affecting the
endocrine system, heart, and skin.
In the past, melanotic schwannoma was thought to be an entity with a predominantly
benign course, but in more recent literature, the condition has been demonstrated
to be more aggressive in nature.
It is imperative that clinicians are aware of this malignant entity, despite its possible
presentation with radiological features of a chronic, benign process. Unusual characteristics
should be treated with a high index of suspicion.
Case Report
A 38-year-old female presented to our neurosurgical department with a sudden-onset
dull ache in her lower back region followed by sharp radicular pain radiating down
from her left gluteal region to the foot while attempting to move a dresser. The patient
reported a progression in both frequency and intensity of radicular pain over the
following weeks with sleep disruption by the time of presentation. The pain was associated
with intermittent paresthesia and numbness in the sole of her left foot, but she denied
any weakness or other concerning symptoms.
The patient's general practitioner commenced her on nortriptyline, but this provided
little symptom relief despite fine dosage titration.
On examination, gait was normal. Tandem walking was intact. The patient was able to
walk on tiptoes and the ball of her heels. There was no evident muscle wasting in
her lower limbs. Romberg's test was negative. She was able to straight leg raise up
to 90° bilaterally, albeit with slight apprehension on the movement of her left leg.
There was normal power in all muscles of her lower limbs, and the sensation was intact.
Reflexes were preserved, and plantars were flexor bilaterally.
The patient had a lumbosacral X-ray, which showed scalloping of the left L5/S1 neural
exit foramen typical of a chronic, benign process. A magnetic resonance imaging (MRI)
of the spine confirmed this and demonstrated the presence of a well-circumscribed
lesion within the foramen with some extraforaminal extension [[Figure 1]] and [[Figure 2]]. Some high T2 signal changes were noted within the lesion, suggesting recent intralesional
hemorrhage likely precipitating her symptom onset and progression.
Figure 1: Sagittal and axial T2-weighted magnetic resonance imaging of the lumbosacral spine
demonstrating the lesion in the left L5/51 neural foramen with some extraforaminal
extension. It appears to be a well-circumscribed solid lesion with a central liquid
core. Remodeling of the neural exit foramen is noted, suggesting a chronic, benign
process
Figure 2: Coronal T2-weighted magnetic resonance imaging of the lumbosacral spine demonstrating
the lesion
Following a multidisciplinary discussion, the provisional diagnosis was a benign nerve
sheath lesion arising from the left L5 nerve root, which gradually increased in size
and became symptomatic post hemorrhage and rapid expansion. Surgical resection was
recommended and carried out through a paramedian extraforaminal approach.
Intraoperatively, the lesion was noted to be encapsulated and hyperpigmented (grayish)
with a hematoma present in its core. Internal debulking was performed, and the tumor
was excised piecemeal. It appeared to be arising eccentrically from the nerve root,
which was adequately decompressed by the end of the procedure.
Histopathology sections demonstrated tumor along with fragments of the adjacent dura
and nerve root. There was a mixture of spindle and epithelioid cells arranged in fascicles,
sheets, and nests. These cells contained abundant intracytoplasmic pigment and had
prominent nucleoli [[Figure 3]] and [[Figure 4]]. A vaguely lobular and palisading pattern of arrangement was noted [[Figure 4]]. There were also psammoma bodies which coalesced in some foci forming areas of
calcification [[Figure 3]]. Tumor was seen infiltrating dura with ganglion cells adjacent to it. Scattered
mitotic activity was seen, including focal areas where up to five mitotic figures
were identified in 10 high-power fields. No areas of necrosis were identified. While
there were overlapping histologic features between a melanoma and schwannoma, the
entity appeared to be biologically distinct from both. Immunohistochemistry confirmed
the presence of both SOX10 and HMB45 positive tumor cells [[Figure 5]] and [[Figure 6]] and loss of PRKAR1A staining. The morphology and immunophenotype were consistent
with a psammomatous melanotic schwannoma. Differentials included malignant melanoma
and meningeal melanocytoma, both of which were ruled out due to the presence of psammoma
bodies.[[1]]
Figure 3: Psammoma body (orange arrow). Pigmented spindle cells (green arrow) demonstrating
nuclear enlargement with vesicular chromatin and distinct nucleoli
Figure 4: Spindle cells demonstrating palisading arrangement (green arrows). Both spindle and
epithelioid cells show abundant intracytoplasmic pigment deposition
Figure 5: Immunohistochemistry confirming SOXIO-positive tumor cells. SOXIO is a sensitive
and specific marker of malignant melanoma
Figure 6: Immunohistochemistry confirming HMB45-positive tumor cells (yellow arrows). HMB 45
is a monoclonal antibody used as a common marker to confirm melanoma
Postoperatively, the patient recovered well with improvement in both her back and
radicular pain. A postoperative MRI of the spine showed satisfactory resection of
the lesion, and a staging computed tomography showed no evidence of extraspinal lesions.
As part of investigations for Carney complex, she had blood tests which demonstrated
no endocrinopathy.
The patient was discharged home 3 days later and remains under close surveillance
for local and distant metastasis with an echocardiogram and genetic testing for Carney
complex pending at the time of this report.
Discussion
Melanotic schwannoma is a rare form of nerve sheath tumor. Less than 200 cases have
been reported worldwide. It accounts for <1% of all peripheral nerve sheath tumors
and has a predilection for spinal nerves.[[2]] It has no sex predisposition with a mean age of presentation of the 38-year-old
female.[[3]]
On a cellular level, lesions are composed of cells possibly derived from the multipotent
neural crest cells of origin that also differentiate to form melanocytes. It often
exhibits hybrid microscopic and ultrastructural features of both melanocytes and Schwann
cells. The classic morphological features of melanotic schwannomas were demonstrated
in our patient's histology, including spindle and epithelioid cells with lightly eosinophilic,
somewhat fibrillar-appearing cytoplasm growing in fascicles, sheets, and nests with
variably abundant melanin pigmentation. In most cases reported in the literature,
spindle cells dominated the composition of tumor.[[4]] Melanotic schwannomas can be divided into psammomatous or nonpsammomatous, a discordance
that is important due to the former's association with Carney complex. Psammoma bodies
are round collections of calcium deposits appreciated under the microscope.[[5]] In one of the largest case series to date, Torres-Mora et al. noted the occasional
hemorrhagic core in some melanotic schwannomas, but only one out of the 40 cases reported
an encapsulated tumor like ours.[[4]]
Fifty percent of patients with psammomatous melanotic schwannoma have a Carney complex.
This is a rare genetic disorder characterized by multiple benign tumors, most often
affecting the endocrine system, heart, and skin. Abnormalities in skin pigmentation
result in a spotty appearance of affected areas, which is most commonly caused (70%)
by a mutation in the PRKAR1A gene within chromosome 17 (Locus 17q23-24).[[6]]
A patient's presenting complaint is often dependent on the location of the lesion.
Our patient developed radicular pain as a result of the L5 nerve root involvement.
She had remained asymptomatic till a mechanical injury provoked a small volume hemorrhage
likely, causing a rapid expansion in the size of the lesion and contributing to the
symptoms that lead to its discovery. Posterior spinal nerve roots are one of the more
common sites for these lesions, along with cranial nerve roots and the sympathetic
chain. Less common primary sites include the peripheral nerves and the gastrointestinal
tract.[[7]],[[8]]
MRI remains the diagnostic imaging of choice in neurological and spinal disease. To
date, there have been no large reviews of imaging characteristics for melanotic schwannomas,
but it is widely acknowledged to exhibit signal hyperintensity on T1-weighted sequences
and hypointensity/isointensity on T2-weighted sequences due to the presence of melanin
within.[[8]] These characteristics were demonstrated in our patient's imaging along with a T2
signal hyperintensity representing a central liquid core, which was the hematoma noted
intra-operatively.
Previously, melanotic schwannoma was thought to be an entity with a predominantly
benign course. The metastatic potential was only demonstrated in up to 26% of cases.[[9]] In more recent literature, the condition has been demonstrated to be more aggressive
in nature, with local recurrence noted in 35% and evidence of distant metastases in
42% of cases.[[4]] Of note, only three cases within the review documented a positive Carney complex
status, and of these, only one (33%) had metastatic disease.
Given these figures, aggressive treatment is recommended. The aim of surgical intervention
should be to achieve gross total resection. Postoperatively, the patient should be
kept under close surveillance with interval imaging looking for potential recurrence
of the disease. There are currently no formal recommendations with regard to the duration
of surveillance.
Conclusion
Clinicians should be aware of this malignant entity, despite its possible presentation
with radiological features of a chronic, benign process. Unusual characteristics such
as hemorrhage should be treated with a high index of suspicion.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot bechrological order guaranteed.
