Furthur In Vestigation Of Etiology And Pathology Of The Congenital Pseudarthrosis Of The Tibia

Congenital pseudarthrosis of the tibia (CPT) is a rare disease with its incidence as one in 250,000 newborns. Yet its etiology and pathology have not been universally understood. Its occurrence was considered to be associated with the presence of neurofibromatosis. However, little evidence was described about the lesion pathology in the literature. The author carried out the pathological and immunohistochemical studies and investigation chromosomal karyotype of CPT on a larger number of CPT specimens. Objective: To investigate the pathological changes , origin and possible etiology of congenital pseudarthrosis of tibia (CPT). Method: We investigate the ultrastructure ,the change of type I or III collagen, the expression of BMP,IL-1,IL-6,TNF- , b-FGF, -SM a c tin,Vimentin and Desmin and the variation of chromosomal karyotype of 25 specimens taken from 24 CPT patients by eletron microscopy,histochemistry,immunohistochemistry and cell culture .The control specimens were taken from normal periosteum(lOcases) , fibromatiosis (lOcases) and traumatic pseudarthrosis(20cases). Result: (1) The soft tissue interposed between the CPT bone ends had the same pathological change as CPT periosteum. Both of them were proliferated dense connective tissues in whichthere were a large number of cellular components and collagen fibers, including plenty of fibroblast and myofibroblast and some indifferential cells. The pathological change of the periosteum between the normal periosteum and CPT periosteum was similar to the CPT periosteum .(2) High positive expression of type I collagen was noted in the normal periosteum. High positive expression of type III Collagen was noted in fibromatosis and the periosteum of CPT (P<0.05) . The expression level of type I or III collagen in the traumatic pseudarthrosis is high.(3)All specimens were positive for Vimentin and negative for Desmin. 20specimens of CPT and 8 specimens of fibromatiosis were positive for -SM a ctin ,there was not significant difference of expression level of -S M actin between the periosteum of CPT and fibromatosis(P>0.05). The specimens of normal periosteum and traumatic pseudarthrosis were negative for -S M actin, The expression of -SM a ctin in fibromatosis and the periosteum of CPT was higher than that in normal periosteum and traumatic pseudarthrosis (PO.01) . All specimens of normal periosteum were positive for BMP and negative for IL-1,IL-6,TNF-, b-FGF .8 specimens of traumatic pseudarthrosis were positive for BMP ,but all specimens of traumatic pseudarthrosis were negative for IL-1,IL-6,TNF-, b -FGF . Some specimens of CPT and fibromatiosis were positive for IL-1,IL-6,TNF- and b-FGF ,but all specimens of CPT and fibromatiosis were negative for BMP. There was not significant difference of expression level of IL-1,IL-6,TNF- , b-FGF between the periosteum of CPT and fibromatosis(P>0.05). The expression of IL-1,IL-6,TNF-, b-FGF in fibromatosis and the periosteum of CPT was higher than that in normal periosteum and traumatic pseudarthrosis (P<0.05 ) Conclusion: (l)CPT is a non-neuro origin.Neurofibromatosis is not etiology of CPT.(2) CPT is periosteum original fibromatosis which had a strong activity of cellular proliferation and corrosion (3) Abnormal expression of cytokines and high expression of type III collagen playan important role in the pathogenesis of congenital pseudarthrosis of tibia. (4) CPTpathological characteristic is the contractile circinate coarctation that is formed bypachyntic periosteum including plenty of fibroblast, myofibroblastand andabnormal cytokine.The contractile circinate coarctation invades and compresses tibiathen leades to CPT. ( 5 ) Chromosomal karyotype of CPT isnormal.