Clinical History:

A 60-year-old man presented to his physician because he was having increasing difficulty doing any kind of exercise. He also had swelling of his ankles. He said his heart beats seemed to be irregular at times. He was referred to a cardiologist. An echocardiogram revealed thickening of the left ventricle and septum. An EKG revealed arrhythmias. Cardiac catheterization revealed decreased cardiac output.

Image 4.1:

This is the light microscopic appearance of the myocardium by H&E stain. What is wrong? There are pale pink homogenous infitrates within the myocardium.

Image 4.2:

A Congo red stain of the myocardium is shown here. Describe what you see. The infiltrates stain positively (orange-red) with the Congo red stain.

Image 4.3:

The Congo red stained myocardium is shown here under polarized light microscopy. (This is about as exciting as light microscopy ever gets, so please be appropriately impressed). This is the world famous "apple-green birefringence".

Image 4.4:

This is the electron microscopic appearance of the myocardium. The abnormal deposits stained with Congo red appear as a feltwork of delicate fibrils.

Further History:

He has back pain. A radiograph reveals lytic bone lesions in the vertebrae. A bone marrow biopsy is performed. His serum calcium is 12.2 mg/dL (range 8.8 - 11.0). A urinalysis shows proteinuria, all Bence-Jones protein. He notes numbness and tingling involving the thumb and first two fingers of his hands. He develops a productive cough with yellowish sputum. A sputum culture is positive for Streptococcus pneumoniae and a chest radiograph reveals bilateral patchy infiltrates.

Image 4.5:

This is the light microscopic appearance of the bone marrow biopsy with H&E stain. The marrow has increased cellularity for his age.

Image 4.6:

This is the bone marrow smear. What cell type is seen in abundance?. The smear shows numerous plasma cells.

Image 4.7:

This is the pattern for the serum protein electrophoresis. Note the "spike" of immunoglobulin.

Questions:

1. What is the diagnosis?

Multiple myeloma. This is a neoplastic proliferation of plasma cells that occurs at multiple locations in bone (hence the lytic bone lesions).

2. How did this disease cause the cardiac findings?

There is a monoclonal proliferation of plasma cells secreting one heavy chain class and one form of light chain (e.g., IgG lambda), detected as the monoclonal immunoglobulin "spike" seen on serum (or urine) protein electrophoresis. Immunoelectrophoresis will identify the specific Ig class. The light chains are excreted in abundance (hence the Bence Jones proteinuria) and are broken down by proteases to form the AL substrate for amyloid fibrils that are deposited in a variety of tissues.

3. Explain the findings in the vertebral bone.

The lytic bone lesions are caused by the proliferations of plasma cells. Proliferation and survival of the neoplastic plasma cells is aided by the elaboration of IL-6, and IL-6 also activates osteoclasts to resorb bone. This accounts for his hypercalcemia.

4. Explain the pulmonary findings.

Decreased production of normal amounts of immunoglobulin leads to increasing risk for bacterial infections, particularly bronchopneumonia.

5. Explain the numbness and tingling in his hands.

The pattern is in the distribution of the median nerve, which passes beneath the flexor retinaculum (carpal tunnel) at the wrist. Entrapment and compression of the nerve at this point leads to carpal tunnel syndrome. In his case, it is the result of amyloid deposition in soft tissue.