Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.
Cystic fibrosis (CF) is the most common life-shortening disorder and involves many systems. The disease, which is inherited in an autosomal-recessive pattern, is due to dysfunction of the chloride channels of exocrine glands, which is a consequence of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) protein. The lungs and pancreas are the most frequently affected organs; however, the upper airways, intestine, liver, and reproductive organs can also be affected. Whereas the life expectancy of someone with CF was barely a few months in the 1950s, the median life expectancy of affected individuals is now 40 years. Advances in diagnosis and symptomatic treatment have improved the health and survival of people with this condition.1
Histological Findings in Cystic Fibrosis
Chronic bronchitis, abnormal pulmonary function tests, bronchiectasis, atypical asthma, allergic bronchopulmonary aspergillosis (ABPA), and infection with Pseudomonas aeruginosa are all lung manifestations of CF.2 Nasal polyps are common in CF and affect people of all ages. Histological examination of the polyps reveals mucus cysts and hyperplastic mucus glands. The polyps may cause nasal obstruction with widening of the nasal bridge.3
Tissues affected by bronchitis and bronchiolitis show a mixed infiltrate of acute and chronic inflammatory cells, such as neutrophils, lymphocytes, plasma cells, and histiocytes. All bacterial lesions appear similar on histologic examination. Marked follicular hyperplasia is common.3
ABPA in CF manifests as asthma, impacted mucus, bronchiectasis, bronchocentric granulomatosis, and eosinophilic pneumonia. Histologic examination reveals bronchial wall infiltration by eosinophils, desquamated epithelium, thickening of the basement membrane, and mucus plugging with significant numbers of eosinophils and Charcot-Leyden crystals.3
Pathological changes in the pancreas were among the first features of CF to be noticed, and the condition was previously called “cystic fibrosis of the pancreas.” An accumulation of secretions dense in eosinophils with ductule dilatation can be seen as early as at 20 weeks of gestation. Tissue damage in the postnatal exocrine pancreas is due to acinar release of lytic enzymes, along with loss of acini, fibrosis, and fatty replacement. Four histological grades are mentioned. Grade I is characterized by an accumulation of secretions, grade II by exocrine atrophy, and grade III by atrophy with lipomatosis; grade IV fibrosis shows complete obliteration of the exocrine glands and ducts with scattered islets of Langerhans.4 The pancreatic ducts are dilated and filled with numerous lamellated concretions, which are related to fibrosis. Fibrocystic alterations with normal islets, significant nesidioblastosis, and persistence of focal exocrine tissue are seen in patients without diabetes. Total loss of the exocrine pancreas occurs in young adult patients who are diabetic, with fat replacement, an absence of nesidioblastosis, and diminished islets.4
Meconium ileus in the small bowel can be one of the first signs of CF. The “meconium plug syndrome,” in which a hard plug of meconium in the colon is associated with abdominal distension, affects some newborns. After passing the plug, the infant recovers and normal bowel function resumes. Intussusception can develop in up to 1% of cases of CF. If oral fluid intake is inadequate or pancreatic enzyme preparations are not prescribed, “meconium ileus equivalent” or “distal intestinal obstruction syndrome” may develop in older patients with CF.3
Histological findings include plugging of the mucosal crypts with mucoid secretions, distended goblet cells, and a thick layer of mucus admixed with fecal material, which adheres to the mucosal surface.5
Biliary and Hepatic Systems
Histologic examination of liver biopsy specimens from patients with CF-associated liver disease reveals a wide range of pathological findings: pan-acinar steatosis, cholestasis, bile duct proliferation, fibrosis of variable severity, portal inflammation, and nodular regenerative hyperplasia. An infiltrate predominantly of neutrophils is also noted.6
CFTR protein dysfunction disrupts epithelial cell activity and causes a change in the composition of bile, which results in poor secretion and an accumulation of thick, viscous bile with a low level of alkalinity, along with chronically damaged biliary epithelium.7 In cases of obstructive biliary disease, inspissated secretions can be noted in the bile ducts before birth, in addition to bile duct proliferation, foci of chronic inflammatory infiltrate, and areas of fibrosis. Clinical obstruction can occur due to accumulation of mucus leading to intrahepatic and extrahepatic biliary stones. Clinical obstruction can occur due to accumulation of mucus leading to intrahepatic and extrahepatic biliary stones.3
- Naehrig S, Chao CM, Naehrlich L. Cystic fibrosis. Dtsch Arztebl Int. 2017;114(33-34):564-574. doi:10.3238/arztebl.2017.0564
- Yu E, Sharma S. Cystic fibrosis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; August 11, 2021.
- Sheppard MN, Nicholson AG. The pathology of cystic fibrosis. Curr Diagn Pathol. 2002;8(1):50-59. doi:10.1054/cdip.2001.0088
- Jain D. Cystic fibrosis. PathologyOutlines.com. Accessed January 29, 2022.
- Jeffrey I, Durrans D, Wells M, Fox H. The pathology of meconium ileus equivalent. J Clin Pathol. 1983;36(11):1292-1297. doi:10.1136/jcp.36.11.1292
- Betapudi B, Aleem A, Kothadia JP. Cystic fibrosis and liver disease. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; August 11, 2021.
- Pairojtanachai P. The pathological features of cystic fibrosis and the diagnostic techniques and treatments involved. Int J Med Sci Public Health. 2020;9(8):452-458.
Reviewed by Debjyoti Talukdar, MD, on 1/30/2022.