Key-words:
Epithelioid sarcoma - infection - lumbar spine
Introduction
Epithelioid sarcoma is a rare soft-tissue neoplasm of mesenchymal origin characterized
by epithelioid cell-like features accounting for <1% of all soft-tissue sarcomas.[[1]],[[2]] The condition was first described in 1961 by Laskowski and clearly characterized
by F. M Enzinger. He reported 62 cases of a peculiar form of sarcoma that has been
confused with a chronic inflammatory process, a necrotizing granuloma in 1970.[[3]] It commonly presents in the extremities of young adults[[4]] and very rarely in the axial skeleton. Its diagnosis is often difficult as it mimics
a benign reactive granuloma and resembles a chronic inflammatory process.[[3]],[[5]],[[6]],[[7]],[[8]],[[9]] Epithelioid sarcomas have no definitive cell of origin, but are alleged to show
ultrastructural and immunophenotypic evidence of epithelial differentiation with myofibroblastic
characteristics.[[2]],[[10]] This mixed differentiation of the tumor can make the differential diagnosis challenging.
Epitheloid sarcoma has a poor prognosis due to its aggressive behavior and is known
for its high recurrence.[[5]] It is also capable of lymphatic and hematogenous metastasis making the prognosis
unpredictable.[[5]],[[6]],[[7]] These events, as well as progression and aggressiveness, are predictive of an overall
worse outcome. The overall 5-year survival rate for Epitheloid sarcoma is anywhere
from 25% to 78%.[[11]] 10-year and 15-year survival rate is significantly low.[[12]],[[13]] Positive outcome factors are younger age, female gender, proximal location, smaller
tumor size, and negative margins upon tumor resection.[[3]],[[13]],[[14]] To our knowledge, only very few case reports of epithelioid sarcoma of the spine
(lumbosacral junction, sacrum, lumbar, and thoracic spine) has been reported in the
literature. Epithelioid sarcoma involving lumbar spine is extremely rare and here
we report a similar case presenting as an infection that threw challenges in early
diagnosis and management.
Case Report
A 42-year-old previously asymptomatic healthy male presented to our outpatient department
with complaints of diffuse Lower back pain which started 15 days earlier and suddenly
increased for the past 2 days. The pain was constant dull aching without diurnal variations,
radiating to bilateral lower limbs affecting his daily routine. He gave no other significant
contributing history. On physical examination, he was well built and nourished with
no gait or postural abnormalities and visible deformities. On palpation, mild tenderness
was present over L3, L4, L5 vertebral spinous processes along with adjacent Paraspinal
muscle spasms. The neurological status was normal. His blood examination revealed
raised erythrocyte sedimentation rate of 84 mm/h. Rest of the blood parameters were
normal. Plain radiograph of the lumbosacral spine revealed a mild reduction in the
height of the L4 vertebral body with sclerosis [[Figure 1]]. Magnetic resonance imaging (MRI) of the lumbosacral spine showed heterogeneous
signal intensity and fracture of L4 vertebral body with associated epidural and paravertebral
abscess collections causing mass effect on Cauda Equina and filum terminale [[Figure 2]]a,[[Figure 2]]b,[[Figure 2]]c,[[Figure 2]]d. Contrast MRI showed homogenous enhancement of the lesion in the L4 body and the
canal [[Figure 3]]a,[[Figure 3]]b,[[Figure 3]]c. He underwent L3-5 posterior spinal instrumentation with pedicle screws and rods
and posterior spinal decompression at stenotic level [[Figure 4]]. Biopsy samples were obtained from the L4 vertebral body through transpedicular
approach and from the intracanalicular tissue. Biopsy samples and fluid collected
were subjected to histopathological and microbiological analysis. Intra-operative
and immediate postoperative periods were uneventful. Tissue staining and cultures
were negative. Polymerase chain reaction (PCR) for tuberculosis (TB) was negative.
Histopathological examination of the biopsy material showed bony spicules interspersed
with fibro collagenous tissue, marrow elements along with areas of focal congestion
and foci of mild chronic inflammation. No evidence of malignancy was traced and immunohistochemistry
(IHC) studies were negative. Based on clinical and radiological evidences, impression
of tuberculous spondylitis was made since TB is very common in our region though PCR
was negative and medical treatment for the same was initiated. The patient was functionally
better for 1 month until he developed sudden onset of progressive weakness with no
associated sensory disturbances of both the lower extremities. On examination, the
power was Grade 1 in bilateral L4, L5, and S1. Bowel and bladder were spared and had
normal bilateral lower extremities sensations. MRI of the lumbar spine revealed increase
in the soft tissue component compared to the previous report extending from L3 to
L5 vertebra causing complete canal stenosis along with pre and para vertebral involvement
[[Figure 5]]a,[[Figure 5]]b,[[Figure 5]]c. Positron emission tomography (PET) computed tomography revealed increased fluorodeoxyglucose
uptake in the L4 body and in the prevertebral, paravertebral regions and in the spinal
canal [[Figure 6]]. He was taken up for revision decompression considering his progressive lower limbs
weakness. Intra operatively, we found extensive friable tissue engulfing and surrounding
the dura at L4 vertebral level for which extensive debulking was carried out [[Figure 7]]. The debulked tissue was sent for histopathological and microbiological analysis.
Microbiological reports were inconclusive as no organism was isolated. PET scan showed
features in favor of infective etiology and no similar lesions elsewhere. According
to the histopathology report the biopsy tissue had features in favor of Epitheloid
Sarcoma. Microscopic appearance showed neoplastic tissue with infiltration by tumor
cells which are round to oval shape with nuclear pleomorphism, irregular nuclear membrane,
and moderate cytoplasm. Many cells showed prominent cells with the epithelioid appearance
and eosinophilic nuclei with adjacent lymphoid cells [[Figure 8]]. Subsequently, the tissue was also subjected to IHC in which the tumor cells were
positive for Vimentin and Epithelioid Membrane Antigen (EMA), thereby reconfirming
the diagnosis of Epithelioid Sarcoma [[Figure 9]]. Fever was managed with antipyretics and rehabilitative physiotherapy was initiated.
Wound healing was good. There was no improvement in the neurological status. Radiotherapy
and Chemotherapy were planned but the patient died 4 weeks postoperative due to multiorgan
dysfunction.
Figure 1: Preoperative X-ray showing sclerosis of L4 vertebral body
Figure 2: (a and b) Sagittal T1 and T2 weighted magnetic resonance imaging respectively showing
heterogenous signal intensity and mild collapse of L4 vertebral body with extradural
collection compressing the dura, (c) Sagittal STIR sequence showing hyperintense lesion
involving L4 body with extension into the epidural space, (d) Axial T2 weighted magnetic
resonance imaging showing near complete occlusion of the spinal canal
Figure 3: (a-c) Contrast magnetic resonance imaging showing homogenous enhancement of the lesion
in L4 body with extension into the spinal canal, pre vertebral and paravertebral region
Figure 4: Postoperative X-ray at 1 month follow up showing the implants in situ without further collapse of L4
Figure 5: (a-c) Sagittal T2, Sagittal T1 and axial T2 weighted magnetic resonance imaging respectively
at the end of one month following initial surgery showing increase in the lesion and
wide involvement of the L4 body and extension of the lesion into the spinal canal
Figure 6: Intraoperative image showing friable tissue engulfing the dural sac during revision
procedure
Figure 7: Positron emission tomography computed tomography showing increased fluorodeoxyglucose
uptake in the L4 body and in the pre, para vertebral regions and in the spinal canal
Figure 8: HPE showing epitheloid cells with deeply stained eosinophilic cytoplasm and intercellular
deposition of hyalinised collagen
Figure 9: Immunohistochemistry showing cells positive for Epitheloid Membrane Antigen
Discussion
Epitheloid sarcoma is rare tumors which is common in the extremities[[10]] but it is extremely rare in the spine. It commonly strikes young adults, yet no
age group is immune. The male:female ratio is 2:1. It can metastasize to regional
lymph nodes, lung, brain, bone, and other locations, including the scalp.[[1]] Epitheloid sarcoma known for its aggressive behavior, has higher rates of relapse
after initial treatment and tends to recur locally.[[7]] Studies have cited the inactivation of SMARCB1 gene[[15]],[[16]] to be a major contributor for disease activation. SMARCB1 gene has been shown to
be a potent tumor suppressor gene[[17]],[[18]] and its inactivation is responsible for the unregulated cellular growth and the
formation of cancer tumors.[[12]] Epitheloid sarcoma is known to simulate a benign process by showcasing protracted
growth and usually a painless scenario[[1]],[[2]],[[9]] like our patient who had diffuse backache for only 15 days without any other symptoms.
Radiologically MR signal intensity of the epithelioid sarcoma is isointense to muscle
on T1-weighted image and hyperintense on T2-weighted image with strong enhancement.
Large soft-tissue mass with necrosis or hemorrhage is characteristic of epithelioid
sarcoma.[[6]],[[19]],[[20]],[[21]] Histologically, epitheloid Sarcoma is commonly characterized by multiple granulomatous
nodules. In the center of the nodules, necrosis, hemorrhage and cystic changes commonly
appear. In addition, infiltration of chronic inflammatory cells like lympthocytes
can also be found. The nodules are surrounded by large epithelioid cells, which are
polygonal, round, or ovoid. The neoplastic nuclei tend to be circular or ovoid, and
the atypia is relatively mild. Apart from that, small nucleoli can be noted.[[22]] This lymphocytic infiltration and central necrosis give a pseudo granulomatous
picture which can masquerade as a granulomatous infection and thereby misguide us
in planning the treatment. For the immunohistochemical features, Epithelioid Sarcoma
demonstrates positive stain for cytokeratin and EMA in >90% of the cases. Vimentin
also is usually positive in most cases. The differential diagnosis can be granuloma,
epithelioid angiosarcoma, malignant melanoma, synovial sarcoma, malignant extrarenal
rhabdomyoid tumor.[[19]]
The prognosis of epithelioid sarcoma is poor and the recurrence rate can be as much
as 19%–56% within 1year.[[12]],[[23]],[[24]],[[25]],[[26]] The truncal location of the tumor, tumor size >5 cm, infiltration into the surrounding
structures, lymph node involvement, pulmonary metastases, rhabdoid cytomorphology
with necrosis, and local recurrence are considered poor prognostic factors and can
result in multi-organ dysfunction.[[12]],[[23]] The primary line of treatment of Epitheloid sarcoma is the radical excision of
the tumor mass with tumor-free margins. In the spine, total eradication of the tumor
by radical or en-bloc excision is difficult due to the presence of neural structures.
Thus, the intralesional resection is the left out option.[[8]],[[9]] Histologically, tumor-free surgical margin is the basis for higher disease-free
survival and even the microscopically left out tumor cells are potent enough to cause
a recurrence.[[13]] Though the chances to prevent the local recurrence were uncertain. Radiotherapy
is to be resorted in patients in whom complete resection of tumor cannot be accomplished
and tumor-free margin cannot be obtained.[[24]] In case of recurrence, repeat radical resection has to be performed and spinal
implants contaminated with the tumor cells have to be exchanged.
In our case, though the radiological findings, including the PET scan, were guiding
us to the provisional diagnosis of an infection, the high power histopathological
morphology and immunohistochemical pattern supported the diagnosis of epithelioid
sarcoma. Except metastasis, our patients had all the other poor prognostic factors.
The scope of misdiagnosing the disease is quite high due to its uncertain radiology
and low power histological appearance simulating an infection or a chronic inflammatory
change masking the underlying lesion. This is the clinical scenario where the suspicion
of the treating surgeon and communication with the investigating pathologist comes
into play.
Spinal epithelioid sarcoma is an extremely rare neoplasm and challenging to diagnose
as it masquerades an infection. It is a highly aggressive tumor with poor prognosis,
lymphovascular metastasis, and high reccurence rate. It is always advisable to consider
intraoperative tissue analysis to attain tumor-free margins by involving the pathologist
right from the time of surgical planning and proceed with special immunohistochemical
studies to determine the possibility of epithelioid sarcoma in patients with spinal
lesions having paraspinal involvement and mass invading the extradural space, thereby
diagnosis of such aggressive neoplasms cannot be missed.
Declaration of patient consent
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In the form the patient(s) has/have given his/her/their consent for his/her/their
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understand that their names and initials will not be published and due efforts will
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