Naina Goel

Real-time PCR assay based on the differential expression of microRNAs and protein-coding genes for molecular classification of formalin-fixed paraffin embedded medulloblastomas

BACKGROUND Medulloblastoma has recently been found to consist of 4 molecularly and clinically distinct subgroups: WNT, Sonce hedgehog (SHH), Group 3, and Group 4. Deregulated microRNA expression is known to contribute to pathogenesis and has been shown to have diagnostic and prognostic potential in the classification of various cancers. METHODS Molecular subgrouping and microRNA expression analysis of 44 frozen and 59 formalin-fixed paraffin embedded medulloblastomas from an Indian cohort were carried out by real-time RT-PCR assay. RESULTS The differential expression of 9 microRNAs in the 4 molecular subgroups was validated in a set of 101 medulloblastomas. The tumors in the WNT subgroup showed significant (P < .0001) overexpression of miR-193a-3p, miR-224, miR-148a, miR-23b, and miR-365. Reliable classification of medulloblastomas into the 4 molecular subgroups was obtained using a set of 12 protein-coding genes and 9 microRNAs as markers in a real-time RT-PCR assay with an accuracy of 97% as judged by the Prediction Analysis of Microarrays. Age at diagnosis, histology, gender-related incidence, and the relative survival rates of the 4 molecular subgroups in the present Indian cohort were found to be similar to those reported for medulloblastomas from the American and European subcontinent. Non-WNT, non-SHH medulloblastomas underexpressing miR-592 or overexpressing miR-182 were found to have significantly inferior survival rates, indicating utility of these miRNAs as markers for risk stratification. CONCLUSIONS The microRNA based real-time PCR assay is rapid, simple, inexpensive, and useful for molecular classification and risk stratification of medulloblastomas, in particular formalin-fixed paraffin embedded tissues, wherein the expression profile of protein-coding genes is often less reliable due to RNA fragmentation.

Primary paraganglioma of the spine: A clinicopathological study of eight cases

Context: Spinal paragangliomas are rare neuroendocrine tumors of the extra-adrenal paraganglionic system. Aims: This study describes the clinicopathological features of eight cases of spinal paraganglioma and highlights the significance of important morphological features and immunohistochemistry in the diagnosis of paraganglioma at this unusual site. Material and Methods: All the cases of primary spinal paragangliomas diagnosed during the last six years (2008-2013) in the Department of Pathology at our hospital were reviewed. Results: There were six males and two females. The mean age at diagnosis was 50.4 years. All patients presented with low back pain. All tumors were located in the cauda equina or conus medullaris region. Magnetic Resonance Imaging and intraoperative appearance were that of a vascular, well-circumscribed intradural, extramedullary tumor suggestive of either schwannoma or ependymoma. All the patients underwent gross total resection of the tumor. Histopathology in five of the cases showed ‘ependymoma-like histology’ while only three cases had a predominant classic ‘zellballen’ pattern. Two cases had prominent ‘gangliocytic differentiation’. In the five cases with ‘ependymoma-like histology’, the diagnosis was confirmed on Immunohistochemistry (IHC). Conclusions: Even though relatively rare, paraganglioma should be considered in the differential diagnosis of spinal tumors and due to their clinical, radiological and histopathological similarity to schwannoma and ependymoma, the diagnosis should be based on close examination of the clinical, radiological and pathological findings.

MiR-206, a Cerebellum Enriched miRNA Is Downregulated in All Medulloblastoma Subgroups and Its Overexpression Is Necessary for Growth Inhibition of Medulloblastoma Cells

Medulloblastoma is the most common and a highly malignant pediatric brain tumor located in the cerebellar region of the brain. Medulloblastomas have recently been shown to consist of four distinct molecular subgroups, viz., WNT, SHH, group 3, and group 4. MiR-206, a miRNA first identified as a myomiR due to its enriched expression in skeletal muscle was found to be expressed specifically in the cerebellum, the site of medulloblastoma occurrence. MiR-206 expression was found to be downregulated in medulloblastomas belonging to all the four molecular subgroups as well as in established medulloblastoma cell lines. Further, the expression of murine homolog of miR-206 was also found to be downregulated in SHH subgroup medulloblastomas from the Smo+/+ transgenic mice and the Ptch1+/− knockout mice. MiR-206 downregulation in all the four medulloblastoma subgroups suggests tumor-suppressive role for miR-206 in medulloblastoma pathogenesis. The effect of miR-206 expression was analyzed in three established medulloblastoma cell lines, viz., Daoy, D425, and D283 belonging to distinct molecular subgroups. Restoration of miR-206 expression to the levels comparable to those in the normal cerebellum, however, was found to be insufficient to inhibit the growth of established medulloblastoma cell lines. OTX2, an oncogenic miR-206 target, overexpressed in all non-SHH medulloblastomas, is known to inhibit myogenic differentiation of medulloblastoma cells. Overexpression of miR-206 was necessary to downregulate OTX2 expression and inhibit growth of medulloblastoma cell lines.

A case of cerebellopontine angle epidermoid tumor and brainstem squamous cell carcinoma presenting as collision tumor

Dear Editor, ‘Collision’ brain tumors are described as a clinical situation when two tumors of diverse histological nature are in close proximity to each other, giving an impression that the two are in direct contact or in collision with each other [4, 5]. We report a ‘collision’ tumor where an epidermoid tumor was in collision with an intra-axial brainstem tumor that was diagnosed to be a squamous cell carcinoma. The squamous cell carcinoma probably arose from the epithelial lining of the epidermoid tumor.

Hemangiopericytoma of the cervical spine.

A 28-year-old male presented with neck pain and dysesthesias in the right upper limb. On examination, he had a firm, well-defined midline posterior cervical mass discernible on palpation at the mid-cervical level. He had no neurological deficit. Neuroradiology revealed a variegated enhancing cervical mass is arising from C3 lamina. The mass extended into the right extradural space eroding the C3 lamina and posteriorly into the intermuscular plane. The tumor was excised totally. Histopathology of the tumor showed features of hemangiopericytoma (HPC). The patient underwent postoperative radiotherapy. Primary osseous spinal HPC are rare malignant extra-axial tumors that tend to recur and metastasize. Only two cases of primary osseous HPC have been reported earlier to involve the cervical spine. The clinical presentation and management of the present case with a review of the literature is presented.

Malignant peripheral nerve sheath tumour of scalp with extradural extension: case report.

Malignant peripheral nerve sheath tumours are uncommon aggressive soft tissue sarcomas that originate from peripheral nerves or cells associated with the nerve sheath. Scalp malignant peripheral nerve sheath tumours are extremely rare and the role of multimodality management is unclear. We report a 43-year-old female with scalp swelling and rapid growth. Imaging demonstrated an aggressive lesion with extradural extension. A wide excision with negative margins was achieved and he defect reconstructed by rotational flap. The patient was given adjuvant radiation. A follow-up scan done one year post radiation did not show any recurrence. Malignant peripheral nerve sheath tumours of the scalp are extremely rare and such an extradural extension has not been described earlier.

Circumferential craniocervical extradural tuberculous granulations

A 49-year-old female presented with a 7-month history of progressive quadriparesis. Investigations revealed a circumferential lesion involving the cervicomedullary junction and the upper cervical cord. The firm extradural granulomatous lesion was partially resected. Histological examination revealed that the lesion comprised tuberculous granulation tissue, which resolved on anti-tuberculous drug treatment. We were unable to find a similar report of extradural tuberculous granuloma in our literature search.

Hydatid disease of the spine: A rare case

Hydatid disease or hydatidosis is the most widespread zoonosis caused by Echinococcus granulosus. Liver and lungs are the most common sites. Bone involvement is rare and reported in 0.5%–4% with spinal involvement reported in 50% of these cases. We present a case of spinal hydatidosis in a 35-year-old male presenting with lower extremity weakness and numbness. Magnetic resonance imaging (MRI) of the spine showed multiple cystic lesions at the T9–T11 level with involvement of the paraspinal muscles. The lesion was seen intraspinal, intradural, intramedullary, and epidural. Radiological impression was aneurysmal bone cyst. The patient underwent laminectomy, and the excised cysts showed characteristic features of hydatid cyst (HC) on histopathology. The patient was started on antihelminthic therapy postoperatively. MRI is a diagnostic modality for HC, but the unusual location and absence of characteristic features can cause diagnostic difficulty. A high index of suspicion should be kept in patients residing in endemic areas and presenting with unusual cystic lesion of spine.

Intramedullary conus metastasis from carcinoma lung

A 46-year-old male presented with progressive paraparesis and sensory impairment in both lower limbs since 2 months. He had urinary and bowel incontinence. On examination he had flaccid paraplegia with a sensory level at 11th dorsal vertebral level. Magnetic resonance imaging (MRI) scans of the lumbosacral spine showed an enhancing intramedullary lesion in the conus. The patient underwent excision of the conus mass. Histopathology confirmed the tumor to represent a poorly differentiated metastatic carcinoma from an unknown primary. A positron emission tomography-computed tomography (PET-CT) scan of the whole body revealed hypermetabolic activity in the hilum of the right lung confirmed to be a lung carcinoma on a CT-guided biopsy. The patient was undergoing chemoradiation at 1 month follow-up. The authors literature search has yielded only four other case reports of conus metastasis of which only one is in English literature. The present case report and review of literature are presented.

Fulminant fatal meningitis following partial resection of an endodermal cyst

Sir, We wish to report in this presentation a patient that developed fulminant fatal meningitis following partial evacuation of endodermal cyst contents and analyse the management implications. A 21-year-old lady presented with complaints of moderate headache and imbalance on walking for 2 months. The symptoms were progressive. She had papilledema and truncal gait ataxia. Magnetic resonance imaging (MRI) revealed a large lesion anterior to the brainstem that extended on both sides of the midline. The lesion was hyperintense on T1weighted images and hypointense on T2-weighted images. (Fig. 1) The patient underwent a retrosigmoid craniectomy on the side with larger extension of the lesion. The thin cyst wall was exposed between the laterally displaced cranial nerves. An incision was taken in the wall, and yellowish white liquid resembling thin pus was evacuated. As soon as the fluid was drained, the cyst collapsed, and direct operative examination of the extension of the cyst on the contralateral side was not possible. The wall of the cyst was thin and transparent resembling arachnoid membrane. A partial resection of the cyst wall was done. The cyst wall could not be identified in its entirety, and safe complete resection of the wall between the cranial nerves was not possible. The patient improved in her symptoms immediately after surgery and was discharged. Histological examination of the wall showed a cyst lined by stratified columnar epithelium. (Fig. 1) Two weeks following surgery, the patient was readmitted with clinical features suggestive of fulminant meningitis. Examination of cerebrospinal fluid did not reveal any bacterial or fungal growth. Repeat MRI showed presence of residual cyst content (Fig. 1). Despite the high grade fever and ill-health of the patient, she was re-explored. During operation, it was observed that the cyst fluid flowed freely and merged with the adjoining cerebrospinal fluid. There were inflammatory adhesions of the cerebellum with the dura. A radical evacuation of the cyst material was carried out, and the region was thoroughly irrigated and cleaned with saline. No attempt was made even at this stage to resect the cyst capsule. However, the patient continued to worsen and succumbed to meningitis in 48 h.