Keywords primary intracranial Ewing's sarcoma CD 99 Positive - spinal and pelvic metastasis
- excision of cranial and spinal lesions - primary spinal stabilization & mesh cranioplasty
- post-operative radiotherapy & chemotherapy - one year follow up without recurrence
Palavras-chave sarcoma de Ewing primário intracraniano - CD99 positivo - metástase - espinhal e pélvica
- excisão de lesões craniais e espinhais - estabilização primária da espinha - cranioplastia
com malha - radioterapia e químioterapia - pós-operatória - acompanhamento de um ano
Introduction
CNS Primitive Neuro Ectodermal Tumour (PNET) refers to a heterogeneous group of embryonal
tumors that occur predominantly in children and adolescents and show aggressive clinical
behavior. They may be phenotypically poorly differentiated, or show divergent differentiation
along neuronal, astrocytic, and ependymal lines. This group of peripheral primitive
neuro ectodermal tumors has been recently redefined on the basis of cytogenetic, molecular
genetics, and histopathologic characteristics.[1 ]
[2 ]
Most small round cell tumors previously classified as Ewing's sarcoma are now being
classified as peripheral PNET (pPNET). The cytogenetic abnormality in Ewing's sarcoma
and peripheral PNET have supported a common neuro ectodermal origin.
The term central-PNET (cPNET) has been used to describe tumors arising from the brain
and spinal cord, of which Medulloblastoma is the best example.
Small round blue cell non CNS tumors from the bone and soft tissue arising from the
germinal epithelium have been classified as pPNET/ Ewing's Sarcoma Family Tumours
(ESFTs), which includes Ewings sarcoma of bone, extra osseous Ewing's sarcoma, pPNET
(peripheral neuroepithelioma), and Askins tumor.[1 ]
[3 ]
Although traditionally known to arise from the soft tissue and bone, rare cases have
been occasionally reported in the cranial-spinal axis, which includes the brain, spine,
meninges, cranial, and spinal nerve roots. A literature review shows that less than
15 such cases have been reported so far. All of which fall into one of the two categories:
isolated dural-based lesion mimicking a meningioma or a diffuse involvement of cranial
and spinal leptomeninges meninges in the absence of a primary intracranial and meningeal
tumor.
Occurrence of the primary lesion at cranial site with metastasis at cervical spine
and pelvis has rarely been reported. Complete resolution of the multiple lesions after
treatment on one-year follow-up is another rare occurrence; hence, the importance
of this case report.
Clinical Presentation
We report on a 9-year-old girl who was hospitalised with features of progressive increase
in intracranial pressure with quadriparesis ([Fig. 1 ]).
Fig. 1 Nine-year-old girl with features of progressive increase in intracranial pressure
with quadriparesis.
Upon examination, the patient had 4/5 quadriparesis with bilateral papilledema.
MRI of the cervical spine revealed extensive paravertebral and paraspinal soft tissue
component, which was hypo intense in T1, hyper intense in T2, with homogenous contrast
enhancement ([Fig. 2 ]), and a completely collapsed fourth cervical vertebral body with marrow changes
and significant cord compression ([Fig. 3 ]). The rest of the thoracic and lumbar spine was normal.
Fig. 2 Paravertebral soft tissue.
Fig. 3 Collapse Dc4 vertebral body.
She underwent brain CT, which showed a large lobulated and irregular hyper dense contrast-enhancing
lesion in the right parietal region with bony expansion and lytic changes, dural infiltration,
and mass effect over the brain ([Fig. 4 ]). Multiple lytic lesions were also noted in the rest of the skull ([Fig. 5 ]).
Fig. 4 Hyperdense parietal lesion.
Fig. 5 Calvarial lytic lesions.
Brain MRI revealed well-defined hetero intense broad based lobulated lesion infiltrating
the dura with mass effect ([Fig. 6A, B ], and [7 ]).
Fig. 6 (A) Coronal MRI. (B) Axial MRI.
Fig. 7 Sagital MRI.
Metastatic work-up revealed a lesion in the left iliac bone ([Fig. 8A ]). Chest CT showed a small nodule in the left lung-lower lobe basal region ([Fig. 8B ]). Abdomen scans were normal. The rest of the long bones were also normal.
Fig. 8 (A) Lytic left illiac lesion. (B) Left lung basal secondary.
Child was worked up for surgery and, after careful consideration of the clinical condition
of the patient and the imaging studies, we decided to proceed with a single-stage
procedure for both the cranial and spinal lesions, along with stabilization of the
cervical spine and mesh cranioplasty for the skull.
We performed C4 corpectomy and titanium cage fixation by an anterior cervical approach.
The vertebral body was deformed and friable granulation tissue could be seen surrounding
the collapsed body, which was excised completely ([Fig. 9 ]).
Fig. 9 Titanium cage at corpectomy site.
Next, we surgically exposed the right side parietal cranial lesion. The tumor had
infiltrated the bone. Extensive soft tissue component was present. We encountered
a highly vascular lesion, greyish white with dural breach and an intradural lobulated
reddish mass involving the brain parenchyma, which we excised completely along with
the involved dura and bone and performed titanium mesh cranioplasty ([Fig. 10 ]).
Fig. 10 (A-F) Intra-op & post-op pictures; (G) a-post op X-ray with mesh and cervical cage.
The child tolerated the procedures well and there were no postoperative complications.
Her power recovered completely and there was no other neurological deficit.
Histopathology of the tumor was reported as peripheral PNET (Ppnet) belonging to the
Ewing's sarcoma family. We then noted fragments of bone and cartilage surrounded by
small round blue cells in a fibrocollagenous background with increased apoptosis ([Fig. 11 ]).
Fig. 11 (A) Small round blue cells. (B) Tumour with collagenous background.
Immunohistochemistry was positive for CD99 ([Fig. 12 ]) and negative for vimentin and CD45.
Fig. 12 IHC CD-99 positive.
Bone marrow biopsy was negative for metastatic deposits.
The child underwent focal Radiotherapy (300cGy), which was followed by twelve cycles
of chemotherapy (cisplatin, cyclophosphamide, and vincristine). Post-radiation and
chemotherapy, the child recovered fully and is doing well ([Fig. 13 ]). She has been undergoing periodic follow-up with no new lesions in one year follow-up
([Fig. 14 ]).
Fig. 13 Six months post-op.
Fig. 14 One year post-op.
She underwent full body radioisotope scintigraphy after one year ([Fig. 15 ]).
Fig. 15 Radioisotope full body scintigraphy after one year.
Discussion
Peripheral PNETs/ESFTs most commonly develop in the second decade of life and show
a slight male predominance. Signs and symptoms of pPNETs typically include a mass
and/or pain at the primary site.[1 ]
[2 ]
[3 ]
[4 ]
Bone pPNETs most often arise in the long bones of the extremities as metaphyseal or
diaphyseal lesions.
Soft tissue pPNETs, in turn, are found most commonly in the chest wall and paravertebral
extradural locations, although they are also found in the extremities, the retro peritoneum,
and occasionally in association with large peripheral nerves, such as the brachial
plexus or sciatic nerve. These tumors are highly aggressive and progress rapidly with
metastases most common to the lung, bone, and bone marrow.
Primary involvement of the craniospinal vault by ESFTs are rare occurrences. Isolated
CNS involvement of the ESFTs must be differentiated from metastasis of ESFTs to the
CNS. Most CNS ESFTs are extra-axial mass lesions involving the spinal or intracranial
dura matter. When presenting in the skull, these tumors can extend to the extradural
space and cause a mass effect on the underlying brain parenchyma, although dural invasion
and parenchymal involvement is rare. The masses are usually circumscribed with conspicuous
contrast enhancement, often mimicking meningiomas.[1 ]
[2 ]
Differentiating between pPNETs and cPNETs is of clinical importance, as correct pathologic
diagnoses are required for accurate prognostication. Appropriate treatment provides
a 5-year progression-free survival for approximately one half to two thirds of patients
with localized ESFTs. Examining CD99 expression and assaying for the presence of a
EWS/ETS gene fusion are reliable ways of distinguishing pPNETs from cPNETs.
Another defining characteristic of pPNETs/ESFTs is their expression of the MIC2 gene
product. The cell surface glycoprotein CD99, the product of the MIC2 gene, is detected
in most pPNET cases, and its expression is highly reliable as a positive marker for
this tumor group.
CD99 immunopositivity has been detected in other small round cell tumors, but staining
patterns in these cases are often cytoplasmic, rather than the distinct membranous
staining typical of pPNETs/ESFTs.
Optimal combined modality treatment, which includes surgical resection, chemotherapy,
and radiotherapy differs for pPNETs and cPNETs.
For Ewing's family tumors, the current chemotherapy regimens include the use of ifosfamide
and etoposide in addition to vincristine, doxorubicin, cyclophosphamide, and actinomycin
D.
For cPNETs, a combination of vincristine and cisplatin with lomustine or with cyclophosphamide
have proven to be effective.[3 ]
[4 ]
Conclusion
The patient had an unusual presentation, with primary in the cranial bone with cervical
spine and pelvic and suspicious lung secondaries, in contrast to the usual long bone
and soft tissue Ewing's tumors.
CD 99 positivity and characteristic histopathology confirmed the diagnosis of pPNET/ESFT.
Dural breach and brain parenchymal involvement was present in this patient, which
is rarely reported in these type of tumors.
We undertook a neurosurgically and aneasthesiologically challenging combined single-stage
surgical approach involving excision of skull and spine lesions with mesh cranioplasty
and titanium cage stabilization, which proved beneficial for the patient.
To conclude, ESFT/pPNETs of primary intracranial origin is a neoplasm primarily afflicting
children. It is most likely to present as circumscribed, extra-axial masses with or
without spinal and distant metastasis. Gross total excision of the tumor should be
the immediate goal of the treatment followed by chemotherapy and radiotherapy. A complete
screening including radioisotope uptake studies is necessary to rule out the recurrences
and prove complete remission of the lesions. Long term survival is better for ESFTs
compared with the cPNETs..[1 ]
[2 ]
We therefore advocate an aggressive approach for both the primary and secondaries,
in the form of radical excision followed by implant fixation, such as titanium mesh
cranioplasty and spinal cage fixation, done as a single stage procedure which may
augment the recovery and reduce post-operative mortality and morbidity.
