Gliosarcoma in a Paediatric Patient: A Rare Entity and Review of Literature
Correspondence Address :
Dr. Sachin Kolte,
405, Main Building, VMMC and Safdarjung Hospital, Dehli, India.
E-mail: drsachinkolte@gmail.com
Primary Gliosarcoma is a rare malignant tumour of central nervous system in adults. It is usually a variant of Isocitrate Dehydrogenase (IDH) wild type glioblastoma. Its incidence is approximately 2% of glioblastomas and has a dismal prognosis. Most common age group is between 40-60 years of age is commonly seen in males. Paediatric gliosarcoma is even rarer than adults ones. Most common location is temporal and frontal lobes (cerebral hemisphere). Histologically, it shows biphasic pattern and is composed of both glial and mesenchymal components. Both these components has monoclonal proliferations. Here, a 20-month-old boy resident of Gorakhpur, presented with persistent crying for short duration in neurosurgery emergency. On magnetic resonance studies a frontotemporal lesion was found, for which he underwent tumour excision. The tumour proved to be a primary gliosarcoma. Due to malignant nature of tumour patient did not survive. Gliosacrcoma is rare adult tumour, but can rarely occur in children. A differential diagnosis of gliosarcoma should be kept in mind, while dealing with congenital tumours in children, due its aggressive nature with poor survival outcome.
Biphasic lesion, Central nervous system, Glioblastoma, Isocitrate dehydrogenase
A 20-month-old boy resident of Gorakhpur, presented with persistent crying of very short duration in neurosurgery emergency. Child was fully vaccinated till his age. No significant past history, family and medical history were unremarkable. On physical examination, patient was conscious, oriented, afebrile, no pallor, icterus, cynosis, oedema. On systemic examination cardiovascular system, respiratory system per abdomen examination were unremarkable. Central nervous system examination was also normal. His blood pressure and sugar was normal. The brain Magnetic Resonance Imaging (MRI) with contrast revealed a heterogenous appearing lesion in left frontotemporal region of brain measuring 6.10×5.26×3.10 cm. A provisional diagnosis of Primary Neuroectodermal Tumour (PNET) or meningioma, was made. Tumour was removed and sent for histopathological examination.
Gross examination-Received a single globular grey brown soft tissue piece measuring 6×4×2 cm (Table/Fig 1). On serial sectioning, grey white areas were identified. Microscopic examination showed biphasic pattern. Tumour was infiltrating in surrounding brain parenchyma. Tumour cells are arranged in sheets, fascicle and bundle, composed of spindle shape cells having mild to moderate eosinophilic cytoplasm, nuclei were elongated showing mild to moderate pleomorphism. Another component seen comprised of pleomorphic glial cells intermixed gemistocyte. These cells have moderate amount of amphiphilic cytoplasm, hyperchromatic nuclei irregular nuclear membrane and inconspicuous nucleoli.
Atypical mitosis 5-6/10 HPF were seen. Areas of necrosis and vascular proliferation was also identified. A differential diagnosis of glioblastoma, sarcoma primary or secondary was made (Table/Fig 2). Immunohistochemical (IHC) staining was performed and tumour cells were positive for vimentin (Table/Fig 3) and p53 (Table/Fig 4). Glial Fibrillary Acidic Protein (GFAP) was positive in glial component (Table/Fig 5) and mesenchymal component was positive for Desmin. Both the component were negative for IDH-1 (Isocitrate Dehydrogenase). On the basis of morphology and immunohistochemistry diagnosis of gliosarcoma {World Health Organisation (WHO) grade 4} was made. Baby expired three days after surgery because of aggressive nature of tumour.
Gliosarcoma is a rare malignant tumour of central nervous system. It is usually a variant of IDH wild type glioblastoma. Its incidence is approximately 2% of glioblastomas and has a dismal prognosis. Most common age group is between 40-60 years of age is commonly seen in male. Paediatric gliosarcoma is even rarer than adult ones (1),(2). Most common location is temporal and frontal lobes (cerebral hemisphere). Histologically, it shows biphasic pattern and composed of both glial and mesenchymal (sarcomatous) components. Both these components have monoclonal proliferations. The tumour usually appeared to be circumscribed and superficial located.
Microscopicaly, glioblastoma like differentiation was seen in glial component. This glial part showed astrocytic differentiation with less commonly oligodendroglial and ependymomal differentiation, was also reported. Mesenchymal (sarcomatous) component was composed of spindle cells arranged in fascicle with nuclear atypia along with atypical mitoses and necrosis. The mesenchymal component was reticulin rich (highlighted on reticulin stain) whereas the glial areas was reticulin poor. On IHC staining, glial fibrillary acidic protein was positive in glial areas while the mesenchymal areas were negative (1). Vimentin and p53 seen positive in both component. While IDH-1 was negative in both the tumour cells.
Paediatric gliosarcoma, is extermely rare and has worse prognosis, than glioblastoma. Clinical presentation and histological feature are same as that of adult gliosarcomas. On imaging studies, these tumours may mimic meningioma due its relative discreteness (3),(4). Similarly, on gross examination, it may mimic as a meningioma or metastases, as it appearance as firm, circumscribed mass with some attachment to dura (1). In the present case, a PNET was given as provisional radiological diagnosis. The diagnosis is made when the classic biphasic pattern is well developed and confirmed on immunohistochemistry. However, the sarcomatous areas in both paediatric and adult gliosarcoma can resemble fibrosarcoma. Mesenchymal differentiation can be other types such as striated muscle and smooth differentiation (resembling rhabdomyosarcoma and leiomyosarcoma), lipomatous differentiation (similar to liposarcoma) cartilage and bone formation (resembling chondro or osteosarcoma), and primitive neural differentiation. In paediatric gliosarcoma, if cartilage or bone, other mesenchymal differentiation are seen they can be mistaken for teratoma (5),(6),(7),(8),(9),(10). Another differential diagnosis was Desmoplastic Infantile Astrocytoma (DIA). It is rare slow-growing tumour, which commonally occurs in infants. However, DIA is WHO grade 1 tumour, unlike gliosarcoma which WHO grade 4 with poor prognosis. It appears as a large cystic mass in the supratentorial cerebral cortex, with some attachment to the dura. Histologically, as the name suggests, tumour is composed of a desmoplastic stroma, which is very prominent and streams of neoplastic astrocytes are lying in them. Mitotic activity is very low and necrosis is not seen. Ki-67 proliferating index is always <2% (1). At the molecular level, both adult and paediatric gliosarcomas exhibits Phosphatase and Tensin homologue (PTEN) and TP53 mutations and Cyclin-Dependent Kinase inhibitor 2A (CDKN2A) deletions.
In the present case, tumour was located in frontotemporal region, similar to reported by Din NU et al., (11), Okami N et al., (18). Granados AM et al., (14) reported a pineal gliosarcoma in a five-year-old girl, the first reported case in this unusual location. Mangement includes total resection of tumour, if possible. In this case, tumour was en-toto removed and chlid died in perioperative period similar to Rizk T et al., (19). When literature was reviewed authors found that only 14 case reports of paediatric gliosarcoma under five years of age have been reported till date (Table/Fig 6) (11),(12),(13),(14),(15),(16),(17),(18),(19),(20),(21),(22),(23). Howerver, paediatric gliosarcomas can be seen in other locations like thalamus (24). In the present case report, patient was less than two years of age. On histopathological examination, tumour proved to be a primary gliosarcoma. Due to malignant nature of tumour, patient did not survive.
Primary gliosarcomas are malignant tumours in young children. A differential diagnosis of gliosarcoma should be kept in mind while dealing with congenital tumours, due to its aggressive nature and poor survival outcome.
DOI: 10.7860/JCDR/2022/57154.17221
Date of Submission: Apr 26, 2022
Date of Peer Review: May 09, 2022
Date of Acceptance: Jun 22, 2022
Date of Publishing: Dec 01, 2022
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. NA
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