Abstract
Atypical teratoid rhabdoid tumours (ATRT) are rare, arising typically in childhood. ATRT arising as a secondary tumour in children treated for acute lymphoblastic leukaemia have not been reported so far. We report a case of ATRT in a 17-year-old boy, 11 years after he was treatment for acute lymphoblastic leukaemia with cranial radiation.
BACKGROUND
Secondary tumours arising in children treated for acute lymphoblastic leukaemia (ALL) with cranial radiation as part of the treatment is well documented. Most reported cases comprise of meningiomas and gliomas. We report a case of atypical teratoid rhabdoid tumour (ATRT) as a secondary tumour in a child who received cranial radiation as part of his therapy for ALL. To our knowledge ATRT following radiation treatment has not been reported so far; therefore, we thought our case is unique in that respect.
CASE PRESENTATION
A 17-year-old boy presented with severe headache. A computed tomography scan revealed a large well-defined enhancing space-occupying lesion measuring 5×5 cm with focal calcification and necrotic areas in the right frontoparietal lobe with perilesional oedema (fig 1). A right frontoparietal craniotomy with excision of the tumour was done. Previous history was significant. He was treated for ALL 11 years previously with standard ALL protocols along with cranial radiation as part of the treatment. He achieved complete remission and was in remission until the present complaint.
Figure 1.
Computed tomography of the right frontoparietal space-occupying lesion.
INVESTIGATIONS
Microscopy revealed a tumour composed of sheets of neoplastic cells with fairly uniform round to oval nuclei, coarse chromatin and scanty to moderate cytoplasm. Numerous mitotic figures and areas of necrosis were present. In places, features of a rhabdoid morphology of the tumour cells was evident with an eccentric nucleus, prominent nucleolus, distinct cell borders and homogeneous cytoplasm with an ill-defined, dense “pink” body (fig 2). On immunohistochemistry, the neoplastic cells were positive for epithelial membrane antigen, vimentin and neuron-specific enolase (fig 3). GFAP, LCA, TdT, myeloperoxidase, desmin, CD99 and cytokeratin were negative. Immunohistochemical staining with INI1 on the cerebral tumour was negative (fig 4).
Figure 2.
Neoplastic cells with a rhabdoid morphology. Haematoxylin and eosin, ×40.
Figure 3.
Neoplastic cells are positive for vimentin (A), EMA (B), neuron-specific enolase (C), and negative for desmin (D). Immunohistochemistry.
Figure 4.
Cerebral tumour cell nuclei are negative for INI1 on immunohistochemistry (positive endothelial cell nuclei act as an internal positive control).
A diagnosis of ATRT was arrived at.
TREATMENT
The patient underwent subsequent postoperative radiotherapy—external radiation with 6 MV photons on a linear accelerator to the whole brain and spinal axis: (1) dose 3600 cGy/30 frs followed by a boost to the right frontal region, and (2) dose 1800 cGy/10 frs at 180 cGy/frs over a period of 43 days. The patient had episodes of myelosuppression during spinal radiation that was corrected by granulocyte colony-stimulating factor administration.
OUTCOME AND FOLLOW-UP
Radiology revealed the presence of a residual tumour following surgery and postoperative radiotherapy. However, the patient is still alive and attending his regular studies 15 months after diagnosis.
DISCUSSION
Rhabdoid tumours of the brain was first described in 1987 arising typically in children under 2 years of age and were simply called a rhabdoid tumour.1 Rorke et al2 named these tumours as ATRT to bring attention to the combination of rhabdoid, primitive neuroepithelial, epithelial and mesenchymal elements. Subsequently, few reports of these tumours arising in adults have been published.3 These tumours contain rhabdoid cells with primitive neuroepithelial, peripheral epithelial and mesenchymal elements in varying proportions. Necrosis and brisk mitotic activity is present. Immunohistochemistry helps confirm the diagnosis. The cells almost always express EMA and vimentin, but do not consistently express SMA. They may express GFAP, NFP and keratin. Desmin and germ cell markers are always negative. The INI1 gene is ubiquitously expressed. Mutations involving this gene have been documented in ATRT with a negative immunohistochemical stain for INI1 protein as against other CNS tumours, which mostly stain positively for INI1 on immunohistochemistry.4 Nearly 200 of these cases have been reported to date, most of them occurring in childhood. Prognosis is poor, with no response to therapy and death is usually within a year.5 Our case is unusual in two aspects. First, the age is 17 years, which is higher than the usual age described. Second, its occurrence as a secondary tumour subsequent to cranial radiation that was part of his treatment for ALL 10 years previously.
The cumulative incidence of secondary CNS neoplasms after childhood ALL treated with cranial radiation has been well documented and studied.6–9 In their study of 1612 patients, Walter et al7 reported a cumulative incidence of brain tumours after radiation at 20 years to be 1.38%. In another large study of 14 361 survivors of childhood cancer who received cranial radiation, Neglia et al8 reported secondary CNS neoplasms in 116 patients—glioma occurred at a median of 9 years and meningioma at a median of 17 years from the original diagnosis. Exposure to radiation therapy remains the most important risk factor for the development of new CNS tumours in survivors of childhood cancer with a higher risk of subsequent glioma in children irradiated at less than 6 years of age, possibly due to the greater susceptibility of developing brain to radiation.7 The increased risk of brain tumours continues beyond 20 and 30 years after treatment. Most common CNS tumours reported so far are gliomas and meningioma. Ours is the first case of ATRT following radiation treatment.
To conclude, we report the first case of ATRT arising in a 17-year-old boy following treatment for ALL with cranial radiation.
Acknowledgments
I wish to thank Dr Ashok Parameswaran and Dr Ramesh K, Apollo Hospitals, Chennai, for reviewing the case and their opinion. I also wish to thank Dr Meenakshi Bhattacharjee, Baylor College of Medicine, USA, for her opinion and for performing the INI1 study on the case.
Footnotes
Competing interests: none.
Patient consent: Patient/guardian consent was obtained for publication.
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