Pathological confirmation of cystic fibrosis in the fetus following prenatal diagnosis

Abstract

Prenatal diagnosis of cystic fibrosis is presently based on the determination of microvillar enzyme activities in the amniotic fluid. However, there seems to be no accurate means for confirming the diagnosis of the aborted fetus. During the past year we performed pathological and histopathological examinations on 7 fetuses diagnosed in the second trimester of pregnancy to be affected by cystic fibrosis and compared them with 4 control age-matched fetuses. Glycol-methacrylate-embedded 2-3-mu thick sections of the pancreas, lungs, bronchial tree, and GI tract were stained with toluidine blue, H&E, PAS, and AB-PAS, and examined microscopically. In the controls, PAS-positive granules were dispersed throughout the cytoplasm of most pancreatic acinar and tracheal submucosal glandular cells. In the affected fetuses 2 distinct groups were identified. In one group of 4 fetuses, the pancreatic and tracheal submucosal glands were dilated and contained a weak PAS-positive material. The glandular epithelial cells had very little PAS-positive granules. In this group, the tracheal epithelium was either atrophic or metaplastic and devoid of microvilli. In the second group of 3 fetuses there was less dilation of the glands, and both pancreatic acinar cells and tracheal submucosal glandular epithelial cells contained few PAS-positive granules, which were confined mainly to a perinuclear location. The tracheal epithelial cells contained few microvilli which, when present, appeared thicker and shorter as compared to controls. We feel that histochemical evaluation of pancreatic and bronchial tissue may be of help in the pathological confirmation of cystic fibrosis in human fetuses where the results of the biochemical studies are suggestive of the disease.

The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseases

“…Cells along the distal secreting ducts of the glands generate the H 2 O 2 -producing enzyme dual oxidase (Duox) (36). This is probably why the initial histological abnormality of CF fetuses occurs in submucosal glands (1,2), because in the absence of SCN Ϫ from the serous cells, unconsumed H 2 O 2 would be expected to irritate and harm the secreting glands, leading to inflammation and injuries. Duox activity indirectly stimulates mucin expression by epithelial cells (37); and mucin has a protective effect in that it scavenges ROS, including H 2 O 2 (38).…”

“…Lung injuries cause Ϸ90% of the morbidity and mortality of CF patients. The lungs of CF newborns exhibit no obvious anatomic abnormality, except the presence of somewhat thicker mucus secretion in submucosal glands and possible dilation of the gland ducts (1,2). Thick secretion may plug the ducts, predisposing them to infection.…”

Computed tomographic imaging of the airways: relationship to structure and function

“…Airway disease in CF is characterised by mucus plugging, chronic infection and an excessive inflammatory response, leading to peripheral airway changes in the first few months of life [101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119]. The characteristic airway abnormalities are bronchiectasis, thickening of the airway wall and mucus plugging [97,103,107,[120][121][122][123][124][125][126], as shown in figure 5.…”

Localization of cystic fibrosis transmembrane conductance regulator mRNA in human fetal lung tissue by in situ hybridization.

“…Recent studies have shown that CFTR can function as a Cl channel activated by protein kinase A phosphorylation and nucleoside triphosphates (9,10); mutations in CFTR cause cystic fibrosis (CF) (1 1, 12). Some complications of CF, including meconium ileus and pancreatic duct obstruction, occur before birth (13)(14)(15), suggesting the defective gene product is expressed in epithelia of these tissues prenatally. Therefore, the developmental regulation of CFTR gene expression in the human may bear directly on the timing of the disease onset.…”