Atypical rhabdoid tumor of lateral ventricle: Report of an unusual tumor.

Supratentorial atypical teratoid rhabdoid tumors (AT/RTs) of infancy and childhood are rare, highly malignant neoplasms, most common in the first 2 years of life. In spite of multiple treatment regimens consisting of surgical resection, radiation therapy, and multi-agent chemotherapy, the prognosis is very poor. The majority of these tumors are located in the cerebellum, cerebellopontine angle, pineal gland, spinal cord, and the suprasellar region; supratentorial location is relatively uncommon, and the intraventricular location is extremely rare. We report a rare case of AT/RT arising in the lateral ventricle in a 4-year-old patient.

Introduction

Supratentorial atypical teratoid rhabdoid tumors (AT/RTs) of infancy and childhood are rare, highly malignant neoplasms, most common in the first 2 years of life.[1] They are characterized by a unique histological entity with an aggressive natural history. In spite of multiple treatment regimens consisting of surgical resection, radiation therapy, and multi-agent chemotherapy, the prognosis is very poor. Historically, AT/RTs were frequently misdiagnosed as PNETs because of their similar histologic features. With more widespread use of immunohistochemistry (IHC) and chromosomal mutation analysis this tumor is being recognized as a separate entity; although it may prove difficult sometimes even in hands of expert.[12] The majority of these tumors are located in cerebellum, cerebellopontine angle, pineal gland, spinal cord, and suprasellar region; Supratentorial location is uncommon in children and the intraventricular location is extremely rare.[123]

Case Report

A 4-year-old girl presented to us with headache and vomiting. She also has a single episode of generalized tonic-clonic convulsion. On neurological examination, she was conscious, oriented. Her motor examination revealed left hemiparesis (Medical Research Council grade 4 in both upper and lower limb); rest of the examination was normal. Her computed tomography (CT) scan showed a well-defined contrast enhancing lesion in right temporal lobe extending into the temporal horn with significant perilesional edema and mass effect. Magnetic resonance imaging (MRI) brain with gadolinium contrast was done which revealed contrast enhancing bright lesion in right temporal lobe with intraventricular extension, with significant edema and mass effect [Figures 1–3]. The patient underwent right frontotemporal craniotomy with gross total tumor resection through transcortical approach. Intraoperatively tumor was located in the temporal horn of right lateral ventricle with no definite tumor - brain interface; it was grayish pink, vascular and suckable with cavitron ultrasonic aspirator. Gross total resection was achieved. The postoperatively patient recovered well and her power improved in both left upper and lower limbs. Postoperative CT brain showed gross total resection with postoperative changes [Figure 4]. Histopathology revealed large and pleomorphic rhabdoid cells with abundant eosinophilic cytoplasm, with filamentous cytoplasmic inclusions and vacuoles; along with eccentric round nuclei and prominent nucleolus. IHC revealed tumor cells to be positive for vimentin, epithelial membrane antigen (EMA), smooth muscle antigen (SMA), with patchy positivity for glial fibrillary acidic protein and synaptophysin, thus confirming the diagnosis of AT/RT. The patient was referred further planned for chemotherapy and radiotherapy at a specialist center [Figure 5].

Figure 1

Preoperative computed tomography brain with contrast showing the lesion

Figure 3

Preoperative magnetic resonance imaging brain T2-weighted images

Figure 4

(a and b) Postoperative computed tomography brain with contrast showing complete exision of lesion

Figure 5

(a) Rhabdoid cells with vesicular nuclei, prominent nucleoli, and spherical cytoplasmic filamentous inclusions (H and E, ×200). (b) Small hyperchromatic cells similar to PNET showing dense nuclei, dispersed chromatin, small to inconspicuous nucleoli, with scant cytoplasm and indistinct cell borders, arranged in a solid pattern (H and E)

Preoperative magnetic resonance imaging brain T1-weighted images with contrast showing the lesion

Discussion

Brain tumors in infancy and childhood are often highly malignant and difficult to classify due to overlapping morphologic and IHC findings. Malignant rhabdoid tumors (MRT) are biologically aggressive neoplasms that occur most frequently in the kidneys of infants and children. Similar tumors occur in other locations, including the central nervous system (CNS). In the brain, they may be composed purely of rhabdoid cells or have a mixture of rhabdoid cells, neuroepithelial, epithelial and mesenchymal elements. These tumors are histologically different from more familiar teratomas and are negative for routine germ-cell markers.[12] AT/RT is a tumor of infancy and childhood and very rare in adults. AT/RT contributes to 6–7% of all CNS neoplasms in patients under the age of 7. The mean age of the patients is 2 years with 1.9:1 male predominance.[12] AT/RT was included for the 1st time in the World Health Organization classification of tumors of the CNS in 2000, although it had been recognized during the early 1980s as a rhabdoid tumor of the CNS with an unfavorable prognosis.[12]

These tumors can arise at any location in the CNS, with approximately half of all tumors arising in the posterior fossa.[1] Clinical presentation depends on the age of onset and the location as well as extension of the tumor. Clinical features depend on the location of the tumor though features of raised intracranial pressure are common. Lethargy, ataxia, vomiting, headache, squint, seizures, and irritability are common presenting features.[3] MRT has a marked tendency for subarachnoid dissemination which may be due its spread along Virchow–Robin spaces and one-third of tumors already have CNS dissemination at presentation.[3] The radiologic features of AT/RT are nonspecific. There is increased density on nonenhanced CT scan and heterogeneous contrast enhancement. On MRI, there is decreased signal intensity on T1-weighted images, iso or decreased density on T2-weighted images (due to hypercellularity) and heterogeneous enhancement postgadolinium. Therefore, the radiological differential diagnosis before histochemistry analysis includes PNET, medulloblastoma, teratoma, astrocytoma, choroid plexus papilloma, and ependymoma.[123] AT/RTs usually occur off the midline, a useful imaging feature to differentiate them from primitive neuro-ectodermal tumors.[3] Light microscopic examination of AT/RT reveals a diffuse growth pattern of predominantly polygonal cells arranged in a focally trabecular or alveolar fashion, cells with vesicular nuclei and prominent nucleoli, and scattered cells with globular hyaline cytoplasmic inclusions in the vicinity of the nuclei. Electron microscopy shows whorls of filaments in the cytoplasm, which can be classified as intermediate filaments and represent vimentin. Results of the IHC studies are positive for three antibodies whose epitopes are almost always expressed: EMA, vimentin and SMA.[12] The early age of onset, larger size, and polymorphic appearance help in differentiating MRT with PNETs.

AT/RT is tumor of infancy and childhood, most commonly seen in <7 years of age. Only 30 cases of AT/RT are reported in adults until date. In contrast to childhood these tumors are found in supratentorial location in adults. The tumor is more aggressive in children compared to childhood with mean survival being 7 months and 26 months, respectively. Leptomeningeal dissemination is early in children as compared to adults.[4]

AT/RT is the only nervous system tumor for which a pathognomonic alteration of a tumor suppressor gene has been identified. Molecular studies have revealed that AT/RTs show alteration of the INI1/hSNF5 gene on chromosome 22. This is a component of the SWItch/Sucrose Non-Fermentable chromatin remodeling complex and functions as a tumor suppressor by positively regulating transcription of a particular set of eukaryotic genes, possibly including the c-Myc target genes involved with differentiation and apoptosis. The loss of expression of INI1 is considered to be diagnostic for AT/RT. Multiples studies have demonstrated that a loss of INI1 protein expression caused by homozygous deletions or truncating mutations of INI1 are associated with rhabdoid tumors. Consequently, IHC staining for INI1 is now used for the diagnosis of AT/RT.[5]

Treatment is highly variable but multi-modal comprising of surgery, radiation, and chemotherapy. The degree of surgical resection appears to be one of the most important factors in predicting prognosis.[1] Another important variable in the prognosis of the patients is the age and the inability to use full dose craniospinal irradiation, although rapid disease recurrence and progression typically occurs even in those patients who do receive full dose craniospinal irradiation. Overall prognosis is poor and median survival is 6 months.[1]

Conclusion

Supratentorial AT/RT is uncommon in children and intraventricular location in the lateral ventricle is seldom described in the literature. The overall prognosis of AT/RT is dismal. Differentiation of this tumor from medulloblastoma and CNS-PNET is important due to the apparent poorer prognosis. Unusual location and nonspecific imaging features mimicking other childhood tumors make this case interesting. Early age of onset, large size at presentation, varying density pattern and inhomogeneous enhancement should alert the concerned surgeon to consider AT/RT in the list of differential diagnosis, and prompt to use IHC for confirming the pathological diagnosis as the outcome of this tumor is very poor when compared to other pathological.

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Conflicts of interest

There are no conflicts of interest.