Intradural calcifying fibroblastic proliferation associated with a nerve root: a reactive process mimicking a nerve sheath tumor.

STUDY DESIGN: Case Report. OBJECTIVE: To share our experience about the unique histological appearances of a calcified intradural, extramedullary lesion involving a nerve root. SUMMARY OF BACKGROUND DATA: A 53-year-old man presented with a long history of low back pain and a few months of occasional left groin pain with no neurological deficit. Imaging of the spine revealed a calcified intradural extramedullary lesion at L1, separate from vertebrae. Intraoperatively, the lesion was found to involve closely one of the roots and was heavily calcified but relatively easy to excise. The histology revealed calcifying fibroblastic proliferation associated with a nerve root. This is an unusual pathological entity, which appears distinct from the rare but occasionally reported reactive process known, as heterotopic bone formation in a nerve or "neuritis ossificans," and it is important to distinguish it from other calcified intradural neoplasms. METHODS: The histology of an excised calcified intradural extramedullary lesion was initially reviewed by our local neuropathologist. A second opinion was requested from Prof. Malcolm, who is a histopathologist and bone specialist. The unique histological features of the lesion were confirmed. The literature (no date limitations) was reviewed. RESULTS: A calcified intradural extramedullary lesion, closely related to nerve root was found to have unique histological features, not reported in the literature so far. CONCLUSION: The histological features of the calcified lesion that we report here have not been described before. It is highly likely they represent a reactive process. We think these features are useful to be added to the differential diagnosis of a calcified intradural extramedullary lesion involving a nerve root.

p53 is nuclear and functional in both undifferentiated and differentiated neuroblastoma.

Aberrant cytoplasmic sequestration has been reported as an alternative mechanism of p53 inactivation to mutation in neuroblastoma. We hypothesized that p53 localization and function in neuroblastoma is related to differentiation status. Eighty-two untreated and 24 paired pre and post-chemotherapy neuroblastomas were studied by immunocytochemistry for p53, p21(WAF1), BAX, Bcl2 and Ki67. Predominantly nuclear p53 was detected in undifferentiated neuroblastoma, and both nuclear and cytoplasmic p53 in differentiating neuroblastoma. The nuclear p53 labeling index (LI) correlated with the Ki67 LI (r = 0.51, p <0.001), and weakly with p21(WAF1) (r = 0.37), but not with BAX or Bcl2. There was a significant reduction in p53, p21(WAF1) and Ki67 LI after chemotherapy (p < 0.01), an increase in BAX (p <0.05), but no change in Bcl2. p53 localization and function were examined in two p53 wild-type undifferentiated and 9-cis retinoic acid differentiated neuroblastoma cell lines. Using immunocytochemistry, immunofluorescence and cell fractionation, p53 was found to be predominantly nuclear in both undifferentiated and differentiated cells. Following irradiation, there was upregulation of p53, p21(WAF1) and MDM2, but less induced PARP and caspase 3 cleavage in differentiated cells, suggesting intact p53 transcriptional function, but resistance to apoptosis. p53 function in undifferentiated and differentiated cells was confirmed by upregulation of p21(WAF1) and MDM2 following Nutlin-3 treatment. In conclusion, p53 is predominantly nuclear and functional in neuroblastoma regardless of differentiation status.