A case of primary spinal atypical teratoid/rhabdoid tumor in a 5-year-old child.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare central nervous system neoplasm affecting children, and isolated primary spinal involvement is extremely rare. Authors describe a case of spinal AT/RT in a 5-year-old male child presenting with rapidly progressing quadriparesis diagnosed and managed surgically and medically. Biopsy revealed large, rhabdoid cells with prominent nucleoli in nest and immunohistochemistry further showed loss of integrase integrator 1 expression considered to be gold standard for diagnosis. AT/RT has extremely poor prognosis with median survival being 6 months.

Introduction

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare tumor of the central nervous system (CNS) which usually affects children under 3 years of age.[12345] These tumors are termed AT/RT as they contain sheets of RT cells, primitive neuroectodermal tumor (PNET) cells, and mesenchymal spindle-shaped tumor cells.[6789] The most common site of involvement is the posterior fossa, and primary isolated extracranial primary spinal involvement is an extremely rare presentation.[371011] AT/RT is a highly malignant, aggressive tumor with median survival being 6 months even with optimum surgical and medical treatment.[4512] Authors report a case of primary spinal AT/RT in a 5-year-old male child and discuss the pathological characteristics, treatment options, prognosis, and a comprehensive review of literature of this very rare tumor.

Case Report

A 5-year-old previously healthy male child presented to pediatric emergency with symptoms of rapidly progressing ascending quadriparesis since last 1 week with severe respiratory distress. The patient was intubated and required ventilator support. Power in left upper limb was 2/5 while in other limbs was 0/5. He had complete sensory loss below the level of nipples. Features of myelopathy were present.

Neuroimaging

Magnetic resonance imaging (MRI) of the spine revealed an oblong inferiorly tapering T1 and T2 heterogeneous signal intensity intradural extramedullary lesion in the dorsal spinal canal extending from D5 to D10 level with mass effect on the cord. T2-weighted images showed hypointense rim suggestive of hemosiderin deposit. On contrast administration, mild peripheral enhancement of the lesion was noticed. T2 hyperintensity was seen in the spinal cord extending from pontomedullary junction up to D8 level suggestive of associated syrinx. Cranial MRI revealed no abnormality. Detailed metastatic work up was done and chest and abdomen imaging did not reveal any lesion. Considering the rapidly progressing quadriparesis and age of the patient, a working diagnosis of AT/RT or spinal PNET was made [Figures 1 and F2].

Figure 1

Magnetic resonance imaging spine showing ill-defined intradural heterogeneous intensity lesion extending from D5 to D10 level. T1-weighted (a), T2-weighted image with associated syrinx (b) and heterogeneous peripheral contrast enhancement (c)

Figure 2

Axial contrast-enhanced magnetic resonance imaging spine (a) showing heterogeneous enhancing lesion (arrow) severely compressing cord. Axial magnetic resonance imaging of brain (b and c) showing no lesion

Surgical intervention

The patient was taken for emergency surgery under general anesthesia. A D4–D10 laminoplasty with tumor decompression was performed. Intraoperatively, after opening the dura, an ill-defined yellowish, friable intradural dorsal exophytic tumor tissue with areas of hemorrhage indistinguishable from underlying necrotic cord was identified Figure 3. Tumor was highly vascular and had areas of necrosis. Tumor was infiltrating the normal cord and no plane of cleavage was present; therefore, only subtotal decompression could be achieved. Frozen section and operative findings were suggestive of highly malignant spine tumor, and differentials of spinal PNET and AT/RT were considered. He was discharged after being weaned off from the ventilator. After the surgery, motor power improved from 0/5 to 2/5 in the lower limbs. The child is receiving adjuvant chemotherapy 1 month after surgery at last follow-up visit.

Figure 3

Intraoperative showing image showing tumor (arrow) with underlying necrotic cord

Neuropathology

Histopathological examination showed a tumor composed of sheets of rhabdoid cells along with large areas of necrosis. Tumor cells had moderate to abundant cytoplasm with eccentrically placed nucleus, vesicular chromatin, and prominent nucleolus, which were immunopositive diffusely for vimentin and focally for cytokeratin and epithelial membrane antigen, while negative for glial fibrillary acid protein, desmin, myogenin, and smooth muscle actin. Immunohistochemistry further revealed loss of integrase integrator 1 (INI1) immunoexpression. Brisk mitotic activity was noted with an MIB labeling index of 30%. A final diagnosis of AT/RT was rendered Figure 4.

Figure 4

Photomicrographs showing sheets of rhabdoid cells with eccentric nucleus and prominent nucleolus (a and b; H and E), exhibiting immunopositivity for cytokeratin (c; IHC) and epithelial membrane antigen (d; IHC). Tumor cells are immunonegative for desmin (e; IHC), smooth muscle actin (f; IHC) and glial fibrillary acid protein (g; IHC). INI1 expression is lost in tumor cells while retained in few interspersed lymphocytes (h; IHC). MIB1 labeling index is high (i; IHC); (×400)

Discussion

AT/RT was first described by Rorke et al. and now classified as World Health Organization grade (IV) tumors.[8] These are rare tumors of infancy and usually affect children under 3 years of age.[41113141516] Mean age at presentation is usually 2 years of life according to Hilden et al.[13] The most common site of CNS AT/RT is the posterior fossa, and primary isolated spinal involvement is extremely rare and till date, only 14 pediatric cases have been reported in world literature [Table 1].

Table 1

Literature review for pediatric primary spinal atypical teratoid rhabdoid tumor

These are rare cases and can be misdiagnosed as spinal PNET.[7914] Differentiation between PNET and AT/RT is important as PNET has a better prognosis.[271718] It is almost impossible to differentiate PNET from AT/RT radiologically.[9101119] AT/RT histologically shows large, rhabdoid cells with prominent nucleoli in nest whereas PNET shows small, blue cells.[914] The presence of necrosis, fibrovascular septae, dystrophic calcification, and epithelial differentiation is usually seen in AT/RT.[914]

Differentials on basis of radiology are spinal tuberculosis with arachnoiditis, PNET, Infection and high-grade glioma. Neuroradiological findings are not specific, and diagnosis of AT/RT requires biopsy and immunohistochemistry.[141720] Mutation of hSNF5/INI1 gene also known as SMARCB1 located on chromosome 22q11 is considered to be hallmark of AT/RT.[1718] INI1, a tumor suppressor gene located on 22q11.2, is responsible for the pathogenesis of both cranial and spinal AT/RT. Loss of INI1 expression as observed in our case is now considered the gold standard for establishing the diagnosis of AT/RT.[171820]

Overall prognosis of both cranial and spinal AT/RT is extremely poor and only 15% patients survive beyond 2 years.[356712] According to Biegel et al., absence of INI1 immune expression as seen in our case is associated with even poorer prognosis.[1720]

The main aim of the surgery is to decrease tumor burden, remove spinal compression, and provide pathological diagnosis. According to previously published reports, response to treatment is poor even with adjuvant chemotherapy and radiotherapy.[135712]

Conclusion

The diagnosis of spinal AT/RT should always be considered in pediatric patient with rapidly worsening symptoms and atypical radiological findings. Authors recommend early surgery and institution of adjuvant chemotherapy for this aggressive spinal tumor.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.