British Journal of Radiology (2003) 76, 62-65
© 2003 British Institute of Radiology
doi: 10.1259/bjr/47707206
Primitive neuroectodermal tumour in a 60-year-old man: a case report and literature review
M J Balafouta, MD1,
J R Kouvaris, MD1,
A C Miliadou, MD1,
X N Papacharalampous, MD1,
D V Kolokouris, MD2,
V E Kouloulias, MD1,
A D Mariolis, MD3 and
L J Vlahos, MD1
1 Department of Radiology-Radiotherapy, Aretaieion Hospital, University of Athens, 76 Vas Sophias Av, Athens 115 28, 2 Departement of Neurology Aiginiteion Hospital, University of Athens, Athens 3 Department of Internal Medicine, Hippokration Hospital, Athens, Greece
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Abstract
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Primitive neuroectodermal tumour (PNET) is very rare, especially in adults. We report a 60-year-old man presented with a PNET. The symptoms at the time of diagnosis were intense headache, Broca's aphasia and right hemiparesis. Only an open biopsy was performed. Irradiation of the primary tumour was the main treatment (total tumour dose 59.8 Gy) because of serious haematological side effects due to chemotherapy. The patient tolerated radiation therapy extremely well and his neurological symptoms were improved. 1 month after completion of radiotherapy, MRI showed no regression of the tumour. Clinical deterioration was observed 10 months after the initial diagnosis and the patient died 2 months later. In cases of PNET, initial therapy is surgical bulk reduction whenever possible. Irradiation of the cerebrospinal axis is justified as a routine treatment but, owing to the radioresistance of the tumour, the addition of multiregimen chemotherapy appears to improve survival, according to the literature.
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Introduction
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In 1973, Hart and Earle [1] coined the term primitive neuroectodermal tumour (PNET), which draws attention to the primitive nature of the tumour rather than to histogenesis. This entity is primarily a disease of childhood, with a median age at diagnosis of 9 years [2]. According to Gaffney et al [3], PNETs represent 2.8% of all primary cerebral tumours of childhood and adolescence. In adults, because of the relative infrequency of disease, its clinical characteristics are less well defined and it can be expressed by a variety of symptoms [4].
PNETs are highly malignant, undifferentiated, supratentorial neoplasms arising from germinal matrix cells of the primitive neural tube. They may be multicentric at the time of diagnosis and frequently seed within the central nervous system (CNS) [5, 6]. Autopsy studies suggest that the incidence of spinal seeding may be greater than that suspected clinically [7].
In children, the mean survival from time of diagnosis is approximately 8 months [1, 7, 8]. Optimal multimodal therapy consists of surgical resection (total, subtotal or partial), neuraxis radiotherapy (RT) and multiagent adjuvant chemotherapy.
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Case report
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A 60-year-old man presented with a 2-month history of intense headache, Broca's aphasia and right hemiparesis. CT scans showed a large heterogeneous hemispheric mass with heterogeneous post-contrast enhancement in the left fronto-parietal area. MRI demonstrated a well circumscribed tumour (Figure 1
). The pre-operative differential diagnosis was glioblastoma multiforme, malignant lymphoma or metastatic tumour. A right craniotomy was performed, the tumour found to be unresectable and only a biopsy was performed. After the operation the patient developed severe dysarthria.
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Figure 1. (a) Non-enhanced computed tomography (NECT) scan shows a heterogeneously hyperdense frontoparietal mass. (b) T1 weighted, post-contrast MR image with inhomogeneous enhancement.
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Histological examination revealed a PNET with glial and cartilaginous differentiation. The MIC-2 (CD99) was strongly positive. It was classified according to Rorke's classification as Category 5 (8). Spinal MRI and cerebrospinal fluid (CSF) examination were negative. The patient underwent neuraxis irradiation and CCNU (110 mg m-2 at day 1 of the cycle, on the first day of neuraxis irradiation). Due to severe myelotoxicity (platelet count=50000 µl-1, white blood cell count=400 µl-1, hemoglobulin (Hb)=9.3g dl-1), chemotherapy and spinal RT were discontinued after 12.6 Gy in seven fractions. Improvement of motor activity was clearly observed after 12 Gy of neuraxis RT. The patient received whole brain and focal (tumour site) irradiation (37.8 Gy in 21 fractions and 22 Gy in 11 fractions, respectively). The total tumour dose was 59.8 Gy in the brain (31 fractions in 50 days) and 12 Gy in the spine. 1 month after completion of therapy, MRI revealed a slight progression of the lesion. The patient was followed up with brain MRI (with Gd-DTPA contrast) and routine laboratory studies every 3 months. Clinical deterioration and recurrence on imaging was observed 10 months after initial diagnosis. 1 month later the patient was bedridden with urinary and faecal incontinence. His level of consciousness was decreased (Glasgow comma scale 6/14). The patient died 12 months after initial diagnosis.
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Discussion
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According to the new World Health Organization classification of brain tumours [9], PNET is included as a generic term for cerebellar medulloblastomas and neoplasms that are histologically indistinguishable from medulloblastoma but are located in sites other than the cerebellum. Although these tumours show some similarities to posterior fossa medulloblastomas, they exhibit important differences in natural history and treatment response [5]. Until more is known about the pathogenesis and biology of PNET, it is convenient to consider it as a neoplasm of undifferentiated, multipotential stem cells with the ability to differentiate into more mature elements (glial, ependymal, neuronal) [6]. Primary PNETs are very rare in the spinal cord. As far as we know only two cases have been reported, one in a child [10] and one in an adult [3]. PNETs have no sex predilection in childhood [3].
The approach to PNET in an adult should not differ significantly from that to PNET in a child. Initial staging should include neuraxis MRI and CSF examination, which are also required for planning craniospinal RT or intrathecal chemotherapy [5]. Extraneural metastasis at the time of presentation is so unusual that routine systemic evaluation of asymptomatic patients is of very low yield and probably unwarranted (4).
The optimal treatment regimen is not yet established. Complete tumour resection whenever feasible, adjuvant craniospinal RT and multiregimen chemotherapy are the standard therapeutic modalities because of the tendency of the tumour to spread throughout the subarachnoid space [4]. Prados et al [11] concluded that hyperfractionated craniospinal radiation therapy (total dose 72 Gy to the primary tumour and 30 Gy to the rest of the craniospinal axis) offers no survival advantage over that seen with conventional fractionated radiation. Gaffney et al [3] advised that maximum irradiation dose to the primary site should be 50–55 Gy given in an overall time of 7–8.5 weeks. The minimum prophylactic dose to the spinal cord and uninvolved parts of the brain should be 30–35 Gy, given in an overall time of 5 weeks. The role of radiosurgery in the management of PNET needs further clarification [12]. Although radiation therapy appears to improve survival time, outcome is generally poor and most patients develop local or regional recurrences and disseminated CNS metastases. Gaffney et al [3] reported on a patient that developed skeletal metastases.
Adjuvant chemotherapy, with agents such as Vincristine, CCNU and cis-platin, may be of value as this tumour appears to be more radioresistant than medulloblastomas, and eradication of the primary tumour is difficult [3, 13].
Since 1987 only 23 cases of primitive neuroectodermal tumours in adults have been reported in the literature [3–5, 11, 12, 14, 15], 21 supratendorial cases, 1 case localized in the spinal cord and 1 case in the posterior fossa (Table 1). These included 11 men and 8 women. In the remaining four cases, gender is not known. Age ranged from 19 years to 57 years (mean 29.7 years, median 29 years). Our patient is the oldest reported. CT and/or MRI were the diagnostic studies used for all patients. At the time of diagnosis, four lesions were limited in the temporoparietal lobe, three in the parietal lobe, three in the frontal lobe, three in the temporal lobe, one in the septum pellucidum and one in the left cerebellopontine angle. In three cases the exact location of the tumour in the cerebrum is not available, and in four cases there was widespread CNS involvement. In one case the primary tumour was localized in the spinal cord. The majority of tumours (21 of 23) were resected. 14 patients underwent subtotal, 5 patients partial and 2 patients total resection. 1 of the 23 patients underwent radiosurgery and 1 patient biopsy. In our patient, the tumour was located in the left frontoparietal lobe, was unresectable and only biopsy was performed. 22 of the 23 patients described in the literature underwent irradiation. The reported total tumour dose of radiotherapy is not consistent (range 19–72 Gy). From 23 reported cases of adult PNET, 10 received chemotherapy. Our patient received only one cycle of chemotherapy and, because of severe myelosuppression, chemotherapy and spinal cord irradiation were discontinued.
Overall survival varies from 3 months to 66 months (mean 25.17 months, median 22 months). Gaffney et al [3] reported a patient alive at 9 years follow-up. In one patient, data on survival is not available. Survival in adult patients with PNET seems to be longer than overall survival in children. Reviewing the literature, a disparity in outcome data among investigators was noticed, probably reflecting the heterogeneity of malignancies classified under the term PNET [16]. Patients treated with chemotherapy had a better prognosis for survival. Detailed information concerning the literature review is shown in Table 1. Duffner et al [17] reported three children with PNET who survived an average of 24 months after complete treatment. Of the 23 patients previously described, 18 died due to local recurrence of disease. One patient died because of surgical complications. Our patient died 12 months after diagnosis; less than the mean survival time for adult patients. We suppose that this is owing to incomplete treatment; neither surgery nor chemotherapy was completed.
Received for publication November 28, 2001.
Revision received August 12, 2002.
Accepted for publication August 14, 2002.
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References
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Abstract
Introduction
