11/16/2010 Case 4: Neuronal gigantism after radiation

Presented by: Dr. Roy Rhodes - Robert Wood Johnson University Hospital


Clinical History:

An 85-year-old man with a meningioma was treated several times for recurrences. Outside tissue diagnosis:  Meningioma, Grade 1. There were three craniotomies and three radiotherapy treatments since 2006, followed by cyberknife therapy. The patient was sent to RWJ University Hospital for laser thermal ablation. The laser was inserted. The usual short (around a minute) laser pulse was given. The patient was coughing during surgery which may have affected the final laser position.  The laser was not attached to the patient's skull.  After the laser was applied, there was copious blood in the hemisphere and it was thought that an artery had been thermally ablated.  The patient was sent, per protocol, to an imaging room for examination.

Sections showed a meningioma with both transitional and chordoid patterns.  The cortex, which was obtained at the time of craniotomy to remove the blood, showed back to back neurons, achromatic neurons and clustering of neurons, with vascular sclerosis.  The large neurons were NeuN positive.  The specimen represents neuronal gigantism after radiation. 

Diagnostic Notes:


Little information exists on the pathogenesis of neuronal changes after radiation.  These neuronal findings are similar to those previously called focal neuronal gigantism by Caccamo and Rubinstein, who found them after radiation (see Reference).  Case 2009-5 from the AANP slide session also showed radiation-induced cortical dysplasia, but those neurons did not stain with NeuN.  Lampert and Davis reported large neurons in the molecular layer in 1964.  This finding has been studied using rodent models.  Fetal irradiation causes neuronal loss, especially of the GABAergic subsets, neuronal apoptosis, neuronal dispersion, disorganization and clustering. 

References:        

  • Lampert PW, Davis RL. Delayed effects of radiation on the human central nervous system.  “Early” and “late” delayed reactions.  Neurology 1964;14:912-917.
  • Marín-Padilla M, Tsai RJ, King MA, Roper SN.  Altered corticogenesis and neuronal morphology in irradiation-induced cortical dysplasia:  a Golgi-Cox study.  JNEN 2003;62:1129-1143.
  • Deukmedjian AJ, King MA, Cuda C, Roper SN.  The GABAergic system of the developing neocortex has a reduced capacity to recover from in utero injury in experimental cortical dysplasia.  JNEN 2004;63:1265-1273.
  • Kellinghaus C, et al.  Severity of histopathologic abnormalities and in vivo epileptogenicity in the in utero radiation model of rats is dose dependent.  Epilepsia 2004;45:583-591.
  • Fujimori A, et al.  Ionizing radiation down regulates ASPM, a gene responsible for microcephaly in humans.  Biochem Biophys Res Commun 2008;369:953-957.
  • Shull ERP, et al.  Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBS.  Genes Dev 2009;23:171-180.
  • Caccamo D, Herman MM, Urich H, Rubinstein LJ.  Focal neuronal gigantism and cerebral cortical thickening after therapeutic irradiation of the central nervous system.  Arch Pathol Lab Med 1989;113:880-885.
  • Gaughen JR, et al.  Focal neuronal gigantism:  a rare complication of therapeutic radiation.  AJNR 2009;30:1933-1935.
  • 3. Rosenblum MK, two personal cases.