There have been less than a dozen reported cases of intracranial extraskeletalmyxoid chondrosarcoma in the literature.  We present the youngest case to date with review of the literature.  A 16-year-old boy initially presented with headaches and vomiting.  At outlying hospital, the patient was found a large tumor in the pineal location with hydrocephalus. He was referred to our center after an intracranial biopsy following an endoscopic third ventriculostomywas not conclusive for pathology.  He underwent resection at our institution and the pathology confirmed an extraskeletalmyxoid chondrosarcoma.  The patient underwent adjuvant treatment, but ultimately required shunting for diffuse leptomeningeal disease.  The shunt failed due to viscous CSF due to excessive presence ofmyxoid material. His disease progressed significantly and developed carcinomatous ascites and expired 16 months after diagnosis.

Case Report

A 16-year-old male with no past medical history in otherwise normal health developed progressive headache over 2 months in the right frontal region. These were worse in the morning, but progressed to headache throughout the day. Additionally, he developed a few episode of emesis for 4-6 weeks. These symptoms prompted a CT and MRI of the brain at an outside institution. CT brain revealed a hypodense mass with patchy hyperdense lesion within it in the right thalamus to pineal region with obstructive hydrocephalus (Figure 1). MRI of the brain showed heterogeneous enhancing lesion extending to the quadrigeminal cistern and lateral ventricle from the right thalamus (Figure 2). He had no neurological deficits upon initial presentation.

The patient underwent endoscopic third ventriculostomy (ETV) and craniotomy at the outside hospital. The sample had a mucinous mucoid appearance. The pathology was inconclusive as the craniotomy was aborted due to brain swelling and only biopsy was obtained. His initial post-operative course was complicated by severe brain edema managed with induced coma. He made a substantial recovery, but was left with an upper quadrant hemianopia on the left side and short term memory dysfunction.

Over the next month, the tumor continued to rapidly increase in size and cross the midline. There was cerebral herniation of the occipital lobe out the craniotomy site as well. MR showed contrast enhancing large tumor in the pineal location extending to the lateral ventricle involving the thalamus of the right side (Figure 3). His examination showed a left-side homonymous hemianopia and Parinaud signs. Four months after the initial craniotomy, he was transferred to our institution for a second opinion and elected for a repeat craniotomy for further tumor resection. At the time of surgery an external ventricular drain (EVD) was placed for brain relaxation. He underwent an occipital transtentorial approach for sub-total resection of the tumor (Figure 4). Tumor resection was stopped after extensive debulking due to the involvement of the vein of Galen and internal cerebral veins. Post-operatively he underwent a ventriculo-peritoneal (VP) shunt placement 1 week after resection due to inability to wean off the EVD .The CSF profiles at that time showed protein 50 mg/dL, glucose61mg/dL, 24rbc /cu.mm and 1 wbc/cu.mm without tumor cells. His Parinaud syndrome eventually resolved.

The pathology revealed individual neoplastic cells floating in an abundant amount of myxoid material. Some of these individual cells formed small groups or cord-like structures, and a majority of the cells had a bubbly to vacuolated cytoplasm (Figure 5A, 5B). The tumor stained strongly for Vimentin (Figure 5C). It had occasional cells positive for EMA, SMA, S-100, and Calponin. D2-40, GFAP, C-Kit, Keratin AE1/AE3, and P63 were negative. There was loss of normal nuclear expression of INI-1 (Figure 5D). The differential diagnosis included an unusual Atypical Teratoid Rhaboid Tumor, Myoepithelial Carcinoma, and an Extraskeletal Myxoid Chondrosarcoma. Occasional interspersed fragments of dense, disordered hyaline cartilage with atypical appearing chondrocyte-like cells and calcification were seen. In conjunction with the above immunohistochemical stains, the morphology favored an Extraskeletal Myxoid Chondrosarcoma.

He underwent adjuvant treatment with proton radiation therapy and pazopanib. He received craniospinal irradiation with boost to the original tumor area due to positive cerebrospinal fluid (CSF) cytology. He had boost of 30.67 cobalt grey equivalent (CGE) to the primary site and 36.30 CGE to the craniospinal axis at 2 months postoperatively. However, over the next 6 months he developed multiple cranial nerve abnormality. By 12 months postoperatively, he had decreased vision bilaterally, bilateral hearing loss, facial paralysis, and uvula deviation. His MRI brain revealed stable lateral ventricle and thalamic disease with subtle leptomeningeal enhancement .

One month later, he underwent VP shunt exploration after his lateral ventricles became large and he became poorly responsive (Figure 6). The endoscopic observation showed open ETV but whitish clumps of tumor floating between the ventricle and prepontinesubarachnoid space, and the ventricular CSF was extremely viscous (Video 1). The CSF was extremely viscous. The CSF profiles indicate protein 126 mg/dL, glucose 50 mg/dL, 71 red blood cell /cu.mm and 7 white blood cell/cu.mm with tumor cells. His abdomen was not absorbing the fluid causing extensive ascites. The CSF profile 10 days later showed protein 275 mg.dL, glucose 68 mg/dL, 275 rbc/cu.mm and 52 wbc/cu.mm. Both CSF and ascites cytology revealed extensive malignancy. He ultimately received an external pigtail catheter placement into the peritoneum for the ascites and was discharged. He expired 16 months after the diagnosis.

DISCUSSION

Intracranial extraskeletalmyxoid chondrosarcoma is extremely rare. Extraskeletalmyxoid chondrosarcoma has been described in many organ systems [1,16,17]. Our case appears to have originated from the choroid plexus, thalamus, or the pineal region. A similar case of thalamic location as ours was reported by Park et al. [18], which was considered to have originated from the choroid plexus. However, the extensive tumor invasion makes the origin hard to determine. Our case did not have significant calcification as others have described [16]. The S-100 was focally present as previously described [16,17]. The INI-1 loss is still unclear for the diagnostic utility [19]. However, INI1 negativeextraskeletalmyxoid chondrosarcoma was reported [20].

Importance of total resection was emphasized for tumor control. However, complete resection is often not possiblefor those occurring in the cerebellopontine angles, pineal and sellar location. In our case a gross total resection was not attainable with the extensive invasiveness. Park et al. reviewed the 8 cases reported in the literature [18]. Six of theseeight were able to have a complete resection. It appears the aggressive nature of the tumor warrants an aggressive, but safe surgical plan. Radiation therapy seems appropriate for such a highly malignant tumor [2,3,5,7,10]. However, it is unclear about a survival advantage with adjuvant chemotherapy.

At the terminal stage, the patient showed widespread metastasis in the ventricle and subarachnoid space together with peritoneal cavity through the shunt.The viscous nature of the ventricular CSF is due to not only theelevated CSF protein and numerous malignant cells in the CSF but also to the presence of mucin secreted by myxoidchondrosarcoma.

CONCLUSION

Our case is the youngest reported of an intracranial extraskeletalmyxoid chondrosarcoma. There is a paucity of available data in the literature for these rare tumors. We advocate aggressive maximal safe resection with upfront adjuvant therapy. One should be aware extremely viscous CSF due to presence of myxoid material once the tumor disseminates in the cerebral ventricle.