Brain Pathology Case of the Month - March 2004

DIAGNOSIS:    EXTRAVENTRICULAR NEUROCYTOMA

DISCUSSION:

The differential diagnosis of neurocytomas includes oligodendroglioma, ganglioglioma, and ependymoma. On radiological, surgical and histopathological examination, extraventricular neurocytomas most frequently resemble oligodendroglioma, but as in the present case, they are generally less infiltrative than glial tumors. The defining marker for the identification of neurocytomas has been synaptophysin, since neurocytic tumors show strong immunoreactivity, but glial tumors are mostly negative [10]. Extraventricular neurocytomas are histologically identical to the more common central neurocytomas, but are distinguished by their location outside the lateral ventricles. Neurocytomas have been reported in locations as diverse as the spinal cord, cerebellum, and cerebral cortex [1,2,4,5,7,8].

NeuN immunoreactivity has not been studied much in neurocytomas, central or extraventricular. In this case, we found that the mature neuron marker NeuN was expressed by some neurocytoma cells. NeuN was introduced in 1992 as an antibody that recognized the nuclei (and to a lesser extent the cytoplasm) of differentiated, postmitotic neurons [6]. As a marker of neurocytic differentiation in tumors, NeuN has been of questionable value, as NeuN immunoreactivity has sometimes been found in tumors that are considered to be glial, such as oligodendrogliomas [3,10]. On the other hand, it has also been suggested that traditional tumor classifications may need to be revised to reflect molecular expression data [5].

Since NeuN is normally found only in postmitotic neurons [6, 9], we hypothesized that even in tumors such as neurocytoma, NeuN might likewise be expressed only by cells that have exited the mitotic cycle. The double labeling results supported this hypothesis, since no neurocytoma cells expressed both NeuN and the proliferative cell marker Ki-67. This finding is consistent with the general idea that differentiation and proliferation tend to be alternative cellular states.

REFERENCES

  1. Brat DJ, Scheithauer BW, Eberhart CG, Burger PC (2001) Extraventricular neurocytomas: pathologic features and clinical outcome. Am J Surg Pathol 25:1252-1260
  2. Brown DM, Karlovits S, Lee LH, Kim K, Rothfus WE, Brown HG (2001) Management of neurocytomas: case report and review of the literature. Am J Clin Oncol 24:272-278
  3. Castellano-Sanchez AA, Perry A, Scheithauer BW, Burger PC, Brat DJ (2002) Distinguishing extraventricular neurocytoma from oligodendroglioma: Utility of NeuN immunohistochemistry and FISH analysis for 1p and 19q status. J Neuropathol Exp Neurol 61:452 Abstract
  4. Giangaspero F, Cenacchi G, Losi L, Cerasoli S, Bisceglia M, Burger PC (1997) Extraventricular neoplasms with neurocytoma features. A clinicopathological study of 11 cases. Am J Surg Pathol 21:206-212
  5. Miller DC, Lang FF, Epstein FJ (1993) Central nervous system gangliogliomas Part 1: Pathology. J Neurosurg 79(859-866)
  6. Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116: 201-211
  7. Nishio S, Takeshita I, Kaneko Y, Fukui M (1992) Cerebral neurocytoma: a new subset of benign neuronal tumors of the cerebrum. Cancer 70: 529-537
  8. Tortori-Donati P, Fondelli MP, Rossi A, Cama A, Brisigotti M, Pellicano G (1999) Extraventricular neurocytoma with ganglionic differentiation associated with complex partial seizures. AJNR Am J Neuroradiol 20: 724-727
  9. Wolf HK, Buslei R, Schmidt-Kastner R, Schmidt-Kastner PK, Pietsch T, Wiestler OD, Bluhmke I (1996) NeuN: a useful marker for diagnostic histopathology. J Histochem Cytochem 44: 1167-1171
  10. Wolf HK, Buslei R, Blumcke I, Wiestler OD, Pietsch T (1997) Neural antigens in oligodendrogliomas and dysembryoplastic neuroepithelial tumors. Acta Neuropathol 94:436-443

Contributed by Chris Englund, Daniel Silbergeld, Ellsworth C. Alvord, Jr., Randy Small, and Robert F. Hevner

International Society of Neuropathology