Primary central nervous system primitive neuroectodermal tumors (CNS-PNETs) of the spinal cord in children: four cases from the German HIT database with a critical review of the literature

Abstract

Approximately 30-50% of patients with intracranial primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) develop spinal metastases. In contrast, primary spinal CNS-PNETs are extremely uncommon. The database and study records of the German/Austrian brain tumor trials HIT 91, HIT SKK 92, and HIT 2000 were retrospectively reviewed to describe clinical features, treatment modalities, and outcome of children with primary CNS-PNETs of the spinal cord who were registered as observational patients. Out of 1,248 patients with medulloblastomas or CNS-PNETs registered in the HIT database four patients (female, n = 3) with primary CNS-PNETs of the spinal cord were identified. Age at diagnosis was 10, 16, 23, and 174 months. Location of primary tumors was medulla oblongata-T3, C2-T1, T10-L2, T7-T10. Two patients had metastatic disease at diagnosis. Complete and incomplete resection was performed in one patient each, whereas two patients underwent a biopsy only. Two patients received chemotherapy only, in accordance with the HIT 91 trial (sandwich chemotherapy arm). They developed disease progression and died six months after diagnosis. One patient was given chemotherapy in accordance with the HIT 2000 trial followed by craniospinal radiotherapy and four courses of maintenance chemotherapy. The patient is in complete remission almost four years after diagnosis. The fourth patient developed disease progression while receiving induction chemotherapy. Hence, chemotherapy was switched to a modified Head Start protocol. After three cycles he underwent double autologous stem cell transplantation and craniospinal irradiation. Forty months after diagnosis the patient is alive and well, but surveillance MRIs still show nodular enhancing lesions in the area of the primary tumor and intracranial meningeal enhancement. Primary CNS-PNETs of the spinal cord probably require multimodal treatment including radiotherapy to achieve sustained tumor control.

Ewing's Sarcoma Family Tumors in the Jaws: Case Report, Immunohistochemical Analysis and Literature Review

“…To determine the exact number of children/young adults with primary ES or ES/pPNET of the jaws in the medical literature is very difficult, and in fact, the data reported are confusing. Firstly, in older reports, imaging methods must be regarded as insufficient to exclude metastases from primary central PNETs or medulloblastomas (37). Secondly, and most importantly, ES/pPNETs were often not separated from ES of the jaw and were reported together in case series and literature reviews (37,38).…”

“…Firstly, in older reports, imaging methods must be regarded as insufficient to exclude metastases from primary central PNETs or medulloblastomas (37). Secondly, and most importantly, ES/pPNETs were often not separated from ES of the jaw and were reported together in case series and literature reviews (37,38). Thirdly, immunohistochemical and molecular genetic data that enable separation of central PNETs from peripheral PNETs were not reported in most cases, particularly those published before 2000 (37,39).…”

“…Secondly, and most importantly, ES/pPNETs were often not separated from ES of the jaw and were reported together in case series and literature reviews (37,38). Thirdly, immunohistochemical and molecular genetic data that enable separation of central PNETs from peripheral PNETs were not reported in most cases, particularly those published before 2000 (37,39). Pooling of patient data would, however, enable such a comparison to be made, thereby identifying possible differences between ES and ES/pPNETs.…”

Primitive neuroectodermal tumors of the brainstem in children treated according to the HIT trials: clinical findings of a rare disease

“…We excluded 4 patients with insufficient tumor material for exact histological diagnosis on central review, and 3 patients having a large supratentorial tumor proportion or a large extension to the cervical spinal cord outside the brainstem, as previously reported. 6 Eight cases of CNS-PNET diagnosed between September 1992 and November 2011 from 8 different centers in Germany were further analyzed. All institutions participating in the HIT trials had received approval from their institutional review boards, and informed consent was obtained from all patients or their legal guardians.…”

“…6 They are a rare tumor entity accounting for only 4.8% of childhood brain tumors. 19 CNS-PNETs are highly malignant embryonal tumors capable of disseminating throughout the CNS.…”