Histologic, histochemical, and ultrastructural analysis of soft tissues from cleft and normal lips

The cause of cleft lip remains speculative. The nature and extent of pathophysiologic changes in cleft lip muscle are controversial. This study was undertaken to better understand the developmental processes at work. There were two groups of patients. In group 1, 40 fresh tissue specimens were taken from 22 patients who were 2 to 5 months old-their age at the time of their primary cleft lip repair. In group 2, eight control specimens were collected from six children who were seen in the emergency department with lip lacerations. Fresh specimens fixed in neutral buffered formalin were evaluated by the use of hematoxylin and eosin with Luxol fast blue, Bielschowsky, and Masson trichrome stains. Fresh frozen tissue was histochemically assessed by the use of hematoxylin and eosin, modified Gomori trichrome, and adenosine triphosphatase. Ultrastructural analysis was performed on fine sections of glutaraldehyde-fixed tissue. Histologic examination revealed increased endomysial and perimysial collagen in cleft specimens with evidence of muscle-bundle size variation and nonneurogenic atrophy. Insignificant differences were observed between cleft-side and noncleft-side specimens when the means of 200 counts of neural-tissue bundles in the subdermis were compared (p = 0.093). Histochemical examination revealed no typical checkerboard pattern, but a preponderance of type 2 fiber was seen. By means of electron microscopy, increased numbers of subsarcolemmal mitochondria were found in cleft, noncleft, and control specimens. Increased absolute numbers of mitochondria and variations in size, shape, and crystal arrangement were identified. In conclusion, there is no evidence of deficient neural supply in the cleft lip. There is also no evidence of neurogenic muscle atrophy or a metabolic abnormality. There are characteristic myopathic changes. These, in concert with the observed interstitial fibrosis, may have far-reaching implications for growth and function.