This article presents an overview of spinal neurocytomas. A rare manifestation of an uncommon tumor, extraventricular neurocytomas (EVNs) should be included in the differential for spinal intradural and intramedullary tumors. Spinal EVNs are generally benign with an indolent pathologic course but may display a variety of acute or chronic clinical behaviors, depending on their anatomic location. Only a handful of spinal EVNs have been described in the literature, often in the form of individual case reports or small case series. Discussion includes a review of the literature and an overview of the clinical, pathologic, and radiologic features of this rare tumor type, as well as the differential diagnosis, treatment options, and general prognosis.
Key points
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A rare form of an uncommon tumor, extraventricular neurocytomas (EVN), should be included in the differential for spinal intradural and intramedullary tumors.
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Like the more common intraventricular neurocytoma, EVNs exhibit a wide range of immunohistopathologic and radiologic features that may resemble other common tumor types.
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Spinal EVNs are generally benign with an indolent pathologic course but may display a variety of acute or chronic clinical behaviors depending on their anatomic location.
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Gross total resection is the gold standard treatment of spinal neurocytoma; residual or recurrent tumors may be amenable to repeat resection, radiation, or chemotherapy.
Introduction: Nature of the problem
Central neurocytomas were first recognized by the World Health Organization as a distinct class of central nervous system (CNS) tumors in 1982 after being described in a novel case report by neuropathologists Hassoun and colleagues. This report described 2 distinct cases of benign, intraventricular tumors that demonstrated topographic and morphologic features consistent with pure neuronal differentiation. Since then, the central neurocytoma has been defined as a typically benign, often supratentorial mass located within or around the lateral ventricles that is amenable to resection and postoperative radiotherapy. Histologically, they are described as bland tumors, characterized by small, uniform hyperchromatic cells, perinuclear halos, and small nuclei, with infrequent mitoses and pleiomorphic cells.
In contrast to central neurocytomas, a term specific for lateral and third ventricle tumors, extraventricular neurocytomas (EVN) encompass histologically equivalent tumors that develop in other locations, such as the cerebrum, thalamus, hypothalamus, cerebellum, brainstem, retina, spinal cord, cauda equine, and pelvic cavity. Like the central forms, spinal neurocytomas are benign, intramedullary tumors with comparable morphology and favorable prognosis. Only a handful of spinal EVNs have been described in the literature, often in the form of individual case reports or small case series. This article describes the epidemiologic, pathologic, and radiologic characteristics of these rare tumors and discusses common treatment options and overall prognosis for this generally benign tumor.
Epidemiology
Spinal EVNs are rare manifestations of an uncommon tumor. Central neurocytomas in general comprise an estimated 0.1% to 0.5% of all brain neoplasms. In contrast, only 20 individual cases of spinal neurocytomas have been reported in the literature at this time ( Table 1 ). Spinal EVN occurs predominantly in male patients, with a male-to-female ratio of 1.86:1 (65% male), and a wide range of ages at the time of diagnosis (range 6–67 years old; mean 35.05 years; median 41.5 years). In general, spinal EVNs follow a benign course (both histologically and clinically) and correspond to a relatively low morbidity and mortality, as defined by progression-free or recurrence-free survival. Of the 20 reported cases, 3 patients (cases 2, 9, and 13) experienced postresection recurrence at 30, 10, and 15 months, respectively. No deaths directly attributable to disease have been reported for spinal EVN, and most patients were observed to experience long-term, recurrence-free survival.
| No. | Authors, Year | Age | Sex | Levels | MRI: Location, Enhancement | Ki-67 (%) | Treatment | Recurrence (at Time After Initial Surgery) |
|---|---|---|---|---|---|---|---|---|
| 1 | Louis et al, 1990 | 67 | M | C2-C6 | Biopsy + RT | −rec, 10 y | ||
| 2 | Tatter et al, 1994 | 49 | M | C3-C4 | Intramed, homo | (1) STR + RT (2) GTR | +rec, 30 mo −rec, 5 y | |
| 3 | Coca et al, 1994 | 65 | M | T10-T11 | Intramed | GTR | −rec, 30 mo | |
| 4 | Stapleton et al, 1997 | 12 | M | C4-T1 | Intramed, hetero | GTR | −rec, 24 mo | |
| 5 | Stephan et al, 1999 | 46 | F | T12-L1 | Intramed | 1.2 | GTR | −rec, 12 mo |
| 6 | Ashkan et al, 2000 | 12 | M | C6-T1 | Intramed, homo | 11.2 | STR | −rec, 33 mo |
| 7 | Martin et al, 2002 | 50 | M | T2-T5 | STR, then GTR by cord resection | −rec, 24 mo | ||
| 8 | Baehring et al, 2005 | 13 | M | T5-T7 | Intramed, hetero | <1 | — | — |
| 9 | Sharma et al, 2005 | 24 | M | C5-T1 | Intramed, hetero | 9 | (1) GTR (2) STR | +rec, 10 mo +Dissemination, 14 mo |
| 10 | Singh et al, 2007 | 8 | M | T2-T8 | Intramed, hetero | 13 | STR | −rec, 3 mo |
| 11 | Gokhan et al, 2008 | 49 | F | C3-C5 | Intramed, homo | 1 | STR | |
| 12 | Marucci et al, 2009 | 51 | M | T10-T11 | Intramed, hetero | 1 | GTR | −rec, 12 mo |
| 13 | Polli et al, 2009 | 37 | F | T12-L1 | Intramed, hetero | 5 | (1) STR (2) STR + RT | +rec, 15 mo −rec, 12 mo |
| 14 | Polli et al, 2009 | 15 | M | C1-T11 | Intramed, hetero | <1 | STR | −24 mo, died (postop pulmonary embolism) |
| 15 | Polli et al, 2009 | 6 | M | C1-C7 | Intramed, hetero | <1 | STR | −rec, 23 y |
| 16 | Furtado et al, 2010 | 54 | F | T1-T5 | Intramed, hetero | 16 | STR + RT | −rec, 16 mo |
| 17 | Tsai et al, 2011 | 54 | F | T3-T5 | 1 | GTR | −rec, 6 mo | |
| 18 | Gepp Rde et al, 2012 | 15 | F | C-spine | STR | |||
| 19 | Wu et al, 2014 | 48 | F | Medulla-T1 | STR | −rec, 18 mo | ||
| 20 | Wu et al, 2014 | 26 | M | Medulla-T4 | STR | −rec, 2 y |
Presentation
In contrast to intracerebral or intraventricular neurocytomas (IVN) that tend to present with headaches, seizures, and/or hemiparesis, spinal EVN patients are more likely to present with sensory and motor deficits of the upper or lower extremities ( Box 1 ). Myelopathy, weakness, numbness, and paresthesias have been commonly described, and bowel and bladder sphincter dysfunction may occur with involvement of the conus medullaris. Disorientation has also been described in a patient whose T1-T5 tumor disrupted cerebrospinal fluid flow, resulting in MRI-confirmed hydrocephalus. Intracranial hypertension and altered mental status may also be present, even without any noticeable abnormalities on head CT imaging. Because neurocytomas tend to grow slowly, patients tend to experience slow symptom progression and evolution; however, rapid deterioration is possible, most likely the result of spontaneous intratumoral hemorrhage or venous thrombosis.
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Weakness
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Hypoesthesia
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Paresthesias
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Abnormal reflexes
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Bowel/bladder dysfunction
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Altered mental status
Histology
Central neurocytomas and EVNs share the same histopathologic findings, namely, monomorphic cells with round nuclei. The cytoplasm is often described as being clear or finely granular and faintly eosinophilic and may exhibit clear perinuclear haloes reminiscent of an oligodendroglioma. EVN neurocytes are rarely infiltrative and more often form discrete borders. The tumor may also have regions of variable density. In areas of lower cellularity, cell clusters are surrounded by a neuropil-like fibrillary matrix; in high-density regions, cells may be arranged in sheet, cluster, ribbon, rosette, or island configurations, with the solid sheetlike architecture being most common. More than one pattern is often seen in a single tumor. EVNs with several rosettes, pseudorosettes, or neuropil islands may resemble other CNS tumors, such as ependymoma or neuroblastoma. Box 2 lists some pathologic features that have been reported in the literature.
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Low cellularity
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Sheetlike growth
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Round nuclei, clear cytoplasm, ± perinuclear haloes
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Cell clusters in neuropil-like fibrillary matrix
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Perivascular pseudorosettes or Homer-Wright rosettes
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Hyalinized vessels
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Rosenthal fibers
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Granular bodies
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Usually less than 2 mitoses/10 HPF (Furtado)
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No focal necrosis
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Synaptophysin, S-100: strong/diffuse
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GFAP/EMA/p-53/chromogranin positivity: none or focal (rare)
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Mitoses: none or very rarely
Immunohistochemical stains may be used to distinguish neurocytomas from other types of tumors. Glial fibrillary acidic protein (GFAP), an intermediate filament protein normally expressed by several CNS cell types such as astrocytes and ependymal cells, is rarely or focally detected in EVN neurocytes. EVNs commonly demonstrate strong synaptophysin and S-100 immunopositivity, and epithelial membrane antigen (EMA), p53 protein, and chromogranin stain immunonegativity. Mitotic index—as measured by cancer antigen MIB-1 Ki-67 present in actively dividing cells—is generally low (see corresponding column in Table 1 ).
“Atypical” EVNs have been reported in the literature and are characterized by histologic atypia or anaplastic features, hemorrhage, and necrosis. These findings have been presumed to correlate with theoretic “malignant potential” in these generally benign tumors; however, prognostic assessment studies suggest that these findings may better reflect vascular fragility and do not correlate with malignant transformation or patient morbidity and mortality.
Radiographic Features
In general, EVNs are complex, solitary, variably enhancing, and well-demarcated lesions that often contain cystic components and/or calcifications. Evidence of hemorrhage may or may not be present depending on the clinical course and timing of image acquisition. Spinal EVNs are more commonly intramedullary masses that are iso-intense on T1-weighted MRI and hyperintense on T2-weighted imaging ( Box 3 ). Lesions have been shown to enhance heterogeneously or homogeneously with gadolinium administration. MR imaging may also detect intramedullary fluid cavities and can be useful to track resolution or progression of syringomyelic cysts or pseudocysts postoperatively.
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Solid or cystic/nodular appearance
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Intramedullary >extramedullary
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± Contrast enhancement (vs universal enhancement in central neurocytomas)
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Enhancement may be heterogeneous or homogeneous
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± Infiltration of nearby structures
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± Calcifications
Radiologically, IVNs or intracranial EVNs can resemble gangliogliomas, oligodendrogliomas, or pilocytic astrocytomas. The radiologic findings of spinal EVNs are often misleading, due to their variable nature and localization. Biopsy and pathologic examination are often required to differentiate the mass from other common spinal cord tumors, such as ependymomas, astrocytomas, and oligodendrogliomas. An unusual case of an exophytic thoracic spine growth with cord compression strongly mimicking a mengingioma has also been reported.
Differential Diagnosis
The differential diagnosis for spinal EVN varies with respect to its appearance on radiologic and histopathologic examination (refer to the above sections on Histologic and Radiologic features of spinal EVNs). Table 2 describes distinguishing features that help distinguish neurocytomas from other common CNS tumors. The list of common alternative diagnoses that should be considered includes the following:
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Ependymoma
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Astrocytoma
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Oligodendroglioma
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Mixed glioma
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Meningioma
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Neuroblastoma
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Metastasis
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