Congenital intramedullary spinal cord tumours: a report of two cases

Wrodzone guzy śródrdzenioweL opis dwóch przypadków

Anna Sobieniecka1, Elżbieta Jurkiewicz1, Justyna Czech-Kowalska2, Monika Bekiesińska-Figatowska3, Wiesława Grajkowska4, Bożenna Dembowska-Bagińska5, Agnieszka Brożyna5, Anna Dobrzańska2, Danuta Perek5, Katarzyna Nowak1, Iwona Pakuła-Kościesza1, Katarzyna Malczyk1
1MRI Unit, Department of Diagnostic Imaging, The Children’s Memorial Health Institute, Warsaw Poland
Head of Department: prof. E. Jurkiewicz
2The Neonatal Intensive Care Unit, The Children’s Memorial Health Institute, Warsaw, Poland
Head of the Unit: prof. A. Dobrzańska
3Department of Diagnostic Imaging, Institute of Mother and Child, Warsaw, Poland
Head of Department: prof. M. Bekiesińska-Figatowska
4Department of Pathology, The Children’s Memorial Health Institute, Warsaw, Poland
Head of Department: prof. M. Pronicki
5Department of Oncology, The Children’s Memorial Health Institute, Warsaw, Poland
Head of Department: prof. D. Perek

We present two different cases of congenital intramedullary tumours, one of a patient in whom treatment was started without pathological confirmation of a malignant tumour and the other of a primitive neuroectodermal tumour. Magnetic resonance imaging is the most useful tool in the diagnosis of malignant intramedullary tumours and differentiation from other types of spinal cord lesions.

Key words: spinal cord, congenital tumour, intramedullary tumour, children, magnetic resonance imaging

Autorki przedstawiają dwa przypadki wrodzonych guzów śródrdzeniowych: jeden u dziecka, u którego wszczęto leczenie bez histopatologicznego potwierdzenia nowotworu złośliwego i drugi, potwierdzonego prymitywnego guza neuroektodermalnego. Rezonans magnetyczny jest najbardziej przydatną metodą rozpoznawania złośliwych guzów śródrdzeniowych i ich różnicowania z innymi zmianami patologicznymi rdzenia kręgowego.

Słowa kluczowe: rdzeń kręgowy, guz wrodzony, guz śródrdzeniowy, dzieci, rezonans magnetyczny

Paediatric intramedullary spinal cord tumours (IMSCTs) are rare neoplasms and different from those seen in adults. In children 35% of intraspinal tumours are intramedullary, more than 20% cited for adults. Also the pathology is somewhat different (1-5, 8). Glial neoplasms comprise the vast majority of such tumours in paediatric population. Astrocytomas predominate in younger children, but with age ependymomas become predominant. Lowgrade tumours are the most common in all age groups (1, 6, 8). Cervical spine is the region most often affected, followed by the thoracic spine, but both segments may become involved. Holocord tumours may also occur (2, 4). Malignant IMSCTs progress rapidly and diagnosis is usually made at an average of seven weeks from symptoms onset. Most common symptoms of these tumours are: pain, weakness, gait deterioration, torticollis, sensory disturbance and sphincter dysfunction (1, 9). Magnetic resonance imaging (MRI) is the most useful tool in the diagnosis of malignant intramedullary tumours and in differentiation from other types of spinal cord lesions like benign masses or vascular malformations (6, 7, 10). We present two different cases of congenital intramedullary tumours, one of a patient in whom treatment was started without pathological confirmation of a malignant tumour and the other of a primitive neuroectodermal tumour (PNET).

A male infant was born spontaneously at 39 weeks of gestation with a birth weight of 3710 g and Apgar score of 10 at 1 and 5 min. Physical examination after birth was unremarkable, without any signs of respiratory failure. On 2nd day of life the infant was admitted to the Department of Surgery due to anxiety, abdominal distention and lack of passage of meconium. Abdominal x-ray examination and ultrasound revealed imperforate anus. Colostomy was performed on the 4th day of life. Additionally, an ileal perforation was found and repaired. Early postsurgical period was uncomplicated. The infant’s respiratory function started to deteriorate rapidly from the 9th day of life leading to respiratory failure of unknown origin. At admission to the Neonatal Intensive Care Unit (NICU) severe respiratory distress with episodes of apnea, hypotonia and aphony was observed. The child was intubated and mechanical ventilation with sedation was started. Spontaneous breaths (15/minute) were noted at the beginning. On the following day, when sedation was discontinued, lack of spontaneous chest and upper extremities movements and very slight feet motions were observed. Only the face muscles were unaffected.
Because of prolonged mechanical ventilation the infant underwent tracheostomy. Chest X-ray and brain MRI were normal while spinal MR examination revealed intraspinal tumour extending from foramen magnum to Th3. Sagittal scans demonstrated large, expansile cystic intramedullary lesion with high signal intensity on T2-weighted images. Postcontrast T1-weighted images showed strong enhancement of the walls of the cystic tumour. Leptomeningeal metastatic dissemination was seen along the pial surface of the thoracic spinal cord and nerve roots within the thecal sac (fig. 1a, b, c). Because of the radiological evidence for intramedullary malignant neoplastic lesion with signs of massive intradural metastases neither total resection nor the biopsy of the tumour was indicated. The patient was excluded from any neurosurgical intervention. Despite the lack of pathological examination, due to ethical reasons the patient was treated with chemotherapy. The schedule used is a standard for WHO grade II, III and IV tumours in children younger than 3 years of age, accepted by the Polish Society of Paediatric Oncology and Haematology. Chemotherapy consisting of vincristine, etoposide, cyclophosphamide and cisplatin was started on the 32nd day of life. After two courses of chemotherapy spinal MRI showed total regression of the tumour with substantial thinning of the spinal cord from C2 to Th3. No pathological contrast enhancement within the spinal canal was noted (fig. 2a, b, c). Chemotherapy was complicated by fever of unknown origin and elevated liver enzymes: ALAT (up to 484U/l) and GGTP (up to 1031U/l). After 5th course of chemotherapy acute deterioration of pulmonary function was observed. Interstitial pneumonia of AH1N1 etiology was diagnosed by positive PCR reaction at bronchoalveolar lavage (BAL). Despite intensive ventilation and NO therapy the patient died of severe respiratory and heart failure at the age of 5 months. Autopsy confirmed pneumonia. Significant thinning of the cervical spinal cord was found. On light microscopy the cervical spinal cord was destroyed (fig. 3a). The grossly damaged regions of the cord were replaced by connective tissue, intense astrocytic-fibrous gliosis (fig. 3b), accumulation of macrophages (fig. 3c) and focally lymphocytes. No neoplastic cells were found.

A male neonate was born by caesarean section at 39 weeks of gestation with birth weight of 3500 g and Apgar score of 7 at the first minute of life. Physical examination following his delivery was normal and no neurological symptoms were observed. The infant’s development in the first 10 weeks of his life was unremarkable. At 11th week the baby was admitted to hospital because of uncontrollable attacks of crying and anxiety. Neurological examination revealed flaccid paresis and absence of tendon reflexes in the lower limbs, spasticity and exaggerated tendon reflexes in his upper limbs. Additionally, the patient presented with signs of otitis media. Brain and abdominal ultrasound did not show any abnormalities, while spinal MRI revealed an intramedullary tumour extending from Th11 to L4. The lesion was isointense on T1- and T2-weighted images with strong, homogenous enhancement after administration of gadolinium. The spinal canal was considerably expanded. At the age of 3 months the infant underwent a Th11 to L4 laminectomy and subtotal resection of the tumour. On histopathological examination the tumour showed features of primitive neuroectodermal tumour (PNET). Chemotherapy consisting of teniposide, cyclophosphamide, adriamycin and cisplatine was started in the 2nd week after laminectomy. During hospitalization the patient’s condition deteriorated considerably. CT showed intracranial metastasis and hydrocephalus. The baby died of disease progression at the age of 3,5 months.
Microscopically the tumour had undifferentiated areas composed of small cells with hyperchromatic nuclei and scant cytoplasm (fig. 4 a). Mitoses were abundant and foci of necrosis were found (fig. 4 b). The tumour revealed fibrous stroma. Immunohistochemistry showed expression of neuronal markers including synaptophysin and NSE in neoplastic cells (fig. 4 c). Focally tumour cells were positive for CD99. Immunohistochemistry for the Ki67 proliferation-associated nuclear antigen was observed in numerous neoplastic cells, with the value of about 40%. The diagnosis of PNET WHO grade IV was established.

Primitive neurectodermal tumours are malignant neoplasms of the central nervous system (CNS) that usually occur in the paediatric population. In 1973 Hart and Earle were the first to propose the term “primitive neuroectodermal tumours”. It is the term describing neoplasms which are composed of more than 90-95% highly undifferentiated neuroepithelial cells and do not fulfill the diagnostic criteria for other entities (2, 11, 12). PNETs are mainly located in the cerebellum (medulloblastoma), however, they can also arise in other sites of the CNS such as the cerebral hemispheres, pineal gland, brain stem and spinal cord (2, 11, 12). Primary intramedullary PNET is extremely rare. To our knowledge only eleven cases of purely intramedullary PNETs have been previously reported. Purely IPNETs present mainly in children and young adults. There is no evidence of gender differences (1, 2, 13). In this report, we describe one new IPNET case in a 2-month-old male infant. Primary IPNETs can locate in any region of the spinal cord, but they seem to have predilection for the thoracic region. Our patient had the tumour extending from Th11 to L4. The history of clinical presentation of IPNET is usually short (mean 3-4 weeks) (6, 8, 12, 13) and the course of the disease is characterized by recurrence, progression and intracranial dissemination. In our patient symptoms evolved in one week. Over the course of the disease increased intracranial pressure developed caused by intracranial metastases, resulting in hydrocephalus which required a ventriculoperitoneal shunt. Other authors describe that 37% of patients with IPNETs show intracranial dissemination (2). Surgery followed by craniospinal radiotherapy and chemotherapy is the best possible treatment for patients with PNETs, including those localized in the spinal cord. Our patient underwent subtotal resection of the tumour. Due to his age radiotherapy was contraindicated and chemotherapy alone was recommended. Rapid progression of the disease was observed and our patient died one month after surgery. Outcome of patients with IPNET is generally poor. Most patients die within two years in spite of surgical resection followed by radiotherapy and chemotherapy. The survival rate of infants and very young children with brain tumours is significantly worse than that of older children. In our case subtotal removal of the tumour was the effect of the surgery. The baby was under 3 years of age, so radiotherapy was impossible (4) and chemotherapy was recommended. In the treatment of IPNETs surgery and radiotherapy are essential and chemotherapy is adjuvant (13). Neurosurgeons have to try to resect as much of the tumour as possible (9). After surgery, radiation of the whole craniospinal axis is recommended. Many clinicians think chemotherapy has only an adjuvant role in the management of IPNETs. For patients under 3 years of age chemotherapy may have an essential role (4-9, 13). In the presented case the infant was alive only one month after surgery. In conclusion, the prognosis in congenital intramedullary spinal cord tumours is very poor.

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Corresponding author’s address:
Elżbieta Jurkiewicz
Department of Diagnostic Imaging
The Children’s Memorial Health Institute
Al. Dzieci Polskich 20, 04-730 Warszawa