Here’s another unknown case in our small-but-growing collection (you can find other cases here, here, here and here).These cases are like the ones you see when you’re a medical student or pathology resident rotating through surgical pathology.

Usually, there’s a tray of these “unknowns” (maybe 10 or so) that’s put out ahead of time (a week if you’re lucky, a day if you’re unlucky). Then, there’s a conference, either around the multi-headed scope, or in a dark room with a screen (scarier), and you get called on to give your diagnoses and rationale. As much as I disliked these unknown conferences because of the inherent anxiety involved, they were a great way to learn. Maybe we can reproduce a bit of that learning here, minus the anxiety.

Take a look at the photo, and then the question below, to see if you can make a diagnosis before scrolling down to see the answer!

A 45-year-old male presents with pulmonary emphysema and repeated bouts of hepatitis. On liver biopsy, there are numerous eosinophilic, globular inclusions, such as the one at the center of the field. What do these inclusions contain?

A. Mallory hyalin
B. Alpha-1-antitrypsin
C. Lipofucsin
D. Hemosiderin
E. Fat

(scroll down for the answer)

This biopsy is from a patient with hereditary alpha-1-antitrypsin deficiency. Alpha-1-antitrypsin is normally present in serum, tissue fluids and macrophages. It’s a big-time inhibitor of proteases (which are destructive enzymes secreted by neutrophils during inflammation). Good thing to have around.

Patients who are deficient in alpha-1-antitrypsin, then, are less able to counter the effects of proteases, and the elastic tissue in the lung is eventually destroyed, producing emphysema (irreversible enlargement of the airspaces distal to the terminal bronchiole).

In addition to emphysema, patients with alpha-1-antitrypsin deficiency may develop hepatitis and even cirrhosis from accumulation of abnormally-folded alpha-1-antitrypsin within hepatocytes. These proteins are visible as brightly eosinophilic inclusions with regular hematoxylin and eosin staining. The disease varies in its presentation; some cases are severe at birth, and others are asymptomatic until later life. In patients with severe liver disease, liver transplantation is the treatment of choice.

Regarding the incorrect answers:

A. Mallory hyaline is a pinkish, globular, “ropy” material seen most often in conjunction with chronic alcoholism (but also seen in other liver diseases not related to alcohol, such as non-alcohol-related-cirrhosis, Wilson’s disease, liver tumors, and primary biliary cirrhosis).

C. Lipofuscin is a golden-brown pigment seen in many different tissues. It increases in amount with age.

D. Hemosiderin, an insoluble form of tissue storage iron, is seen if there is an excess of iron in the body, or if there has been a big bleed in some area. It has a globular, golden appearance.

E. Fat doesn’t stain with a regular H&E stain (it just looks like clear holes). You have to do a special stain (like an oil red O stain) to see fat.