- UCLA Department of Neurosurgery, Semel Box 957039, Los Angeles, USA
- Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, USA
Celene B. Mulholland
UCLA Department of Neurosurgery, Semel Box 957039, Los Angeles, USA
DOI:10.4103/2152-7806.86835Copyright: © 2011 Mulholland CB. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Mulholland CB, Barkhoudarian G, Cornford ME, McBride DQ. Intraspinal primitive neuroectodermal tumor in a man with neurofibromatosis type 1: Case report and review of the literature. Surg Neurol Int 29-Oct-2011;2:155
How to cite this URL: Mulholland CB, Barkhoudarian G, Cornford ME, McBride DQ. Intraspinal primitive neuroectodermal tumor in a man with neurofibromatosis type 1: Case report and review of the literature. Surg Neurol Int 29-Oct-2011;2:155. Available from: http://sni.wpengine.com/surgicalint_articles/intraspinal-primitive-neuroectodermal-tumor-in-a-man-with-neurofibromatosis-type-1-case-report-and-review-of-the-literature/
Background:The occurrence of primitive neuroectodermal tumors (PNET) in patients with neurofibromatosis type 1 (NF1) has only been reported in two other cases in English-Language literature. Owing to the rarity of intraspinal PNET and the extremely high gene mutation variability in NF1, there is currently no conclusive evidence to suggest that PNET is associated with NF1. Here, we report a case of intradural PNET in a patient with NF1.
Case Description:A 27-year-old male underwent a C1-C3 laminectomy for resection of an intramedullary mass. Histopathology and immunohistopathology analysis was performed. Microscopic examination and immunohistochemical staining indicated the mass was a primitive neuroectodermal tumor. Within 1 month after tumor resection, the patient developed leptomeningeal carcinomatosis. The patient was not a candidate for radiation therapy but underwent palliative systemic chemotherapy. He subsequently developed neutropenia and died 3 months after tumor resection.
Conclusion:To our knowledge, this is the first reported intraspinal PNET associated with NF1. Genetic analysis of CNS PNETs suggests a possible correlation, but larger case series are needed to support this theory.
Keywords: Intramedullary primitive neuroectodermal tumors, neurofibromatosis type 1, primitive neuroectodermal tumor
Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder attributed to mutations in the tumor suppressor gene, NF1, located on chromosome 17q11.2.[
Although NF1 is the most common neurocutaneous disorder and is associated with numerous tumors - such as astrocytomas, optic nerve gliomas, and neurofibromas - the occurrence of a primitive neuroectodermal tumor in a patient with NF1 has only been described in two cases in the English language literature.[
Although there has been an increased number of reported cases of intraspinal PNET over the past decade, it remains a relatively rare entity.[
History and physical examination
A 27-year-old man with no significant past medical history was referred to our institution from an outside facility with mild myelopathy and gait instability. The patient reported a 2-month history of intermittent neck pain and 2 weeks of right upper extremity weakness and numbness accompanied by progressive gait instability. Physical exam revealed one café au lait spot on his front chest, axillary freckling, decreased vibratory sensation along right upper extremity, positive Romberg test, dysmetria on finger to nose with the right upper extremity only, and decreased right upper and lower extremity strength (4/5 biceps, triceps, hip flexion, and plantar flexion).
An MRI of the brain and neck revealed a cervical intramedullary mass extending from the medulla to the C4 level and detailed the presence of several other masses including: 1) a dumbbell-shaped enhancing mass expanding the left C5-C6 neural foramen 2) a right paraspinous soft tissue neck mass hyperintense on T2 with heterogenous enhancement 3) a dumbbell-shaped hetergeneously enhancing mass expanding the left T10-T11 neural foramen and 4) an ill-defined paraspinal paraortic enhancing soft tissue mass extending from T9-T11 [
MRI of the neck with gadolineum. a) Sagittal T1 image illustrating an intramedullary enhancing mass from the cervicomedullary junction to C4. Leptomeningeal enhancement is also present. b) Axial T1 image illustrating the intramedullary mass and leptomeningeal enhancement. c) Axial image of cervical spine illustrating a dumbbell mass extending through C5-C6 neural foramen and paraspinal mass. d) Coronal T1 image illustrating intramedullary mass
The presence of multiple parapsinal masses with characteristics of nerve sheath tumors and the presence of axillary freckling resulted in a clinical diagnosis of neurofibromatosis type 1. The patient indicated he had no known family history of NF1 and had not been previously diagnosed with NF1 or any prior malignancy.
The patient was recommended to undergo excisional biopsy of the intramedullary spine lesion as it was the likely symptomatic lesion. The peripheral nerve lesions – likely neurofibromas – were recommended to be observed. The patient agreed to the above, understanding the risks and benefits and subsequently underwent a wide C1 to C3 laminectomy microscopic resection of the intramedullary mass. Intraoperatively the mass was found to be a large, exophytic lesion extremely adherent to surrounding spinal cord tissue. Approximately 80% of the tumor was resected, with further resection halted when cardiovascular instability was encountered.
Microscopic examination of the tumor revealed a highly cellular, poorly differentiated neoplasm with focal areas of necrosis. The cells exhibited characteristic scanty cytoplasm, intense basophilic and pleomorphic nuclei, and atypical mitosis [
Postoperative course and treatment
During the immediate postoperative period, the patient's neurological exam remained at baseline. A postoperative MRI of the spine illustrated a small amount residual intramedullary tumor, largely localized in the superior region of the tumor. The patient was referred for radiation and chemotherapy. However, about 1 month post-operatively the patient developed a sudden loss of vision. An MRI of the orbits revealed abnormal enhancement of the optic nerve sheaths bilaterally, a nodular enhancement posterior to the optic chiasm, and diffuse basilar meningeal nodularity and enhancement consistent with leptomeningeal carcinomatosis. As such, the patient was not a candidate for radiation therapy. The patient underwent palliative chemotherapy, which was complicated by neutropenia. During that hospitalilzation, the patient experienced cardiopulmonary collapse, was unable to be resuscitated and subsequently expired. An autopsy was not performed.
Neurofibromatosis type 1 is the most common neurocutaneous disorder in the United States with prevalence estimates ranging from 1 per 2000 to 1 per 5000 people.[
Primary intraspinal PNET is a rare entity, with 82 cases reported in the literature to date. Interestingly, this tumor occurs more frequently in the cauda equina and rarely occurs as a primary intramedullary tumor.[
The two reported occurrences of PNET in NF1 include a 37-year-old male with a lumbar intraspinal pPNET and a 1-month-old male child with pPNET originating from within a plexiform neurofibroma.[
In the first case, the man presented with back pain and right lower extremity weakness. On imaging, an epidural lesion from L3-L5 that extended through the foramina into a paravertebral mass was noted. The mass was partially resected during an L3-L5 laminectomy and patient showed a slight clinical improvement postoperatively. Immunohistochemistry of the mass was positive for CD99, vimentin, enolase, neurofilaments, synaptophysin and was negative for GFAP, S100, EMA, LCA and chromograine. The patient was treated with lumbosacral radiation of 30 Gy (limited due to radiation side effects), was unable to receive chemotherapy, and died 6 months later.[
In the second case, an infant presented at birth with 3 café au lait spots and a large plexiform neurofibroma covering his anterior abdominal wall, lower back, buttock, and upper part of the thighs including the scrotum. In 2 month's time a new mass appeared over his left flank and right groin over the existing neurofibroma. The child underwent chemotherapy but the tumor metastasized and the child died at 12 months of age. Histological examination of the skin and tumor tissue demonstrated a mixed picture- with some areas having a characteristic appearance of plexiform neurofibroma and some areas consisting of small cells with a high nucleocytoplasmic ratio. Immunohistochemical staining was positive for S100 but negative for NSE. Cytogenetic studies revealed a hyportriploidy and structural abnormalities of chromosomes 13 and 14 but no abnormality of chromosome 17.[
Including the present case, most documented cases of intramedullary pPNET were in male patients with an age range of 17-38 years at time of diagnosis. The demographics of these cases resonate with a recent review that reiterated that the majority of intraspinal pPNET occurs in young adult males.[
As alluded to above, the genetic distinction between these two entities is relatively clear, with pPNET demonstrating the chromosomal translocation t(11;22)(q24;q12) and cPNET being associated with isochromosome 17q.[
The NF1 gene is expressed in various cells throughout the body including neurons, glial cells, and cells derived from the neural crest.[
Several studies have examined the presence of two specific splicing variants of the NF1 gene. Both Scheurlen et al., and Nishi et al., found a NF1-GRD splicing variant in primitive neuroectodermal tumors and suggest that this splicing variant might interfere with differentiation of neuroectodermal tissues- contributing to tumor formation.[
However, the studies examining the possible association between PNET and NF1 did not categorize PNET into cPNET and pPNET and did not conduct cytogentic analysis to determine if the chromosomal translocation t(11;22)(q24;q12) was present in the same tumors in which the NF1-GRD splicing variant was prevalent. The chromosomal translocation t(11;22)(q24;q12) present in pPNET produces a fusion protein that can act as a transcriptional activator, leading to aberrant cell growth.[
Patients with NF1 are at increased risk for developing many different malignancies, including those not traditionally associated with NF1. Although intraspinal PNET is a very rare condition and has not been reported in patients with NF1, based on several genetic studies, an association is still plausible. Further cytogenetic analysis of patients presenting with intraspinal PNET should be conducted to better understand the genetic makeup and pathophysiology of the neoplasm.
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