Review Question - QID 108696

The most likely diagnosis in this patient is multiple myeloma, which is characterized by excess immunoglobulin production. The increased plasma protein concentration in multiple myeloma predisposes red blood cells (RBCs) to form linear stacks (rouleaux) which are visible on peripheral blood smear.

The differential diagnosis for chronic fatigue and bone pain in an elderly individual includes underlying malignancy, systemic rheumatologic disease, and endocrine disorders. These symptoms, in combination with laboratory findings notable for hypercalcemia and renal failure, should narrow the differential diagnosis to multiple myeloma. Multiple myeloma is a monoclonal plasma cell malignancy associated with excess immunoglobulin production. Symptoms of multiple myeloma are either caused by destruction of the bone and bone marrow by plasma cell proliferation or by deposition of immunoglobulins in various tissues. Anemia with a low reticulocyte count is a common laboratory finding in addition to hypercalcemia and signs of renal failure (elevated creatinine and elevated blood urea nitrogen). Urine analysis may show large eosinophilic casts composed free immunoglobulin light chains that deposit in the renal tubules (Bence-Jones proteins). Peripheral blood smear may show rouleaux because the increased plasma protein concentration facilitates the aggregation of RBCs.

Figure A demonstrates the classic appearance of the rouleaux formation of RBCs as seen on a peripheral smear. Note the abnormal linear stacking of RBCs.

Incorrect Answers:
Answer 1: Reticulocytes are immature RBCs. Increased numbers of reticulocytes are seen in various causes of anemia in order to replace lost RBCs. However, in the setting of multiple myeloma, the bone marrow is infiltrated by neoplastic plasma cells, thereby limiting the ability of the bone marrow to produce reticulocytes.

Answer 3: Schistocytes are fragmented, irregularly shaped RBCs that arise in microangiopathic diseases such as disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and macroangiopathic mechanisms such as artificial heart values or other intravascular implants.

Answer 4: Abundant granulocytes and cells of the myeloid lineage are seen in chronic myelogenous leukemia (CML). CML is often asymptomatic but can present with malaise, weight loss, fever, chills, and night sweats.

Answer 5: Smudge cells are characteristic of chronic lymphocytic leukemia (CLL). Like CML, CLL is often asymptomatic initially or presents with non-specific symptoms such as malaise, weight loss, fever, chills, and night sweats.

Bullet Summary:
Multiple myeloma is a neoplasm arising from malignant immunoglobulin-producing plasma cells. The resulting increase in plasma protein concentration predisposes RBCs to aggregate and form linear stacks called rouleaux which can be visualized on peripheral blood smear.