Pathology of Five Alström Patients

Rod Bronson and Jan D. Marshall
The Jackson Laboratory, Bar Harbor, Maine, USA

Autopsies were performed in local hospitals near the homes of 3 female and 2 male adult patients dying between the ages of 27 and 42 years. The pathology reports and some histological slides were later sent to the authors of this paper for examination. The slide sets from some patients represented only a few major tissues. Lesions were observed in in kidney, urinary bladder, liver, gonads, heart, lung, eyes and pancreas.

Kidney: The most consistent histopathologic finding was glomerular and interstitial renal fibrosis, observed in all patients. Affected glomeruli appeared as densely packed balls of collagen without recognizable glomerular structure. Such glomeruli were often present adjacent to normal glomeruli, but also clustered in areas of dense interstitial fibrosis. The percentage of affected glomeruli varied from patient to patient, ranging from 20% to 90%. The severity of interstitial fibrosis also varied from patient to patient.

Liver: Three patient had typical micronodular cirrhosis of liver, characterized by severe portal fibrosis and nodules of regenerative liver parenchyma. Many nodules exhibited fatty change. Two patients had mild portal fibrosis only.

Heart: Dilative cardiomyopathy (DCM) was present at some time in the lives of 4 of 5 patients. Of these, two females and one male had severe myocardial fibrosis. The female patient without a history of DCM had only mild myocardial fibrosis. Sections of heart from one male were not available.

Pancreas: The pancreas of 4 of 5 patients had interstitial fibrosis of pancreas. Only one islet was observed in one patient. It was hyalinized.

Testis: One male patient had testicular atrophy with obliterating fibrosis of seminiferous tubules, as described previously.

Urinary bladder: Sections of urinary bladder were available from one male and two female patient. There were thick facicles of collagen between bundles of smooth muscle and in the submucosa.

Lungs: The lung from one male patient was so severely fibrotic that nearly all normal tissue was destroyed. Large fasicles and nodules of fibroblasts and collagen obliterated much normal tissue. Relatively intact alveoli had very thickened walls and contained large macrophages, sometimes hemosiderin-laden. The lesions in part, were consistent with bronchiolitis obliterans obstructive pneumonia (BOOP). Slides of lungs from 2 patients with severe myocardial fibrosis had many hemosiderin-laden macrophages in alveoli, as expected in patients with heart failure. These lungs also exhibited mild interstitial fibrosis. One of these lungs had a focal area of suppurative bronchitis and bronchiectasis.

Eyes: Histological sections of eyes, available from 2 patients, showed severe retinal degeneration. All cell layers were severely reduced in the central retinas and nearly absent in peripheral retina. Deposits of melanin pigment were scattered in outer and inner nuclear layers. These lesions have been reported previously in AS patients.

Ovary: Ovaries from one patient were densely fibrotic with cystic changes, but no primary or secondary follicles and no corpora lutea. Another patient had a few follicles but no corpora lutea. A biopsy of ovary from a sixth living patient also showed severe fibrosis and cystic change.