A 62-year-old man presents to the emergency department with increased fatigue and changes in his vision. For the past month, he has felt abnormally tired and today noticed his vision is blurry. The patient also endorses increased sweating at night and new-onset headaches. He currently feels dizzy. The patient has a medical history of diabetes and hypertension. His current medications include insulin, metformin, and lisinopril. His temperature is 99.5°F (37.5°C), blood pressure is 157/98 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. A cardiopulmonary exam is within normal limits. HEENT exam reveals non-tender posterior and anterior chain lymphadenopathy. Abdominal exam reveals splenomegaly and hepatomegaly. There are large, non-tender palpable lymph nodes in the patient's inguinal region. A neurological exam is notable for decreased sensation in the patient's hands and feet. He also complains of numbness and tingling pain in his extremities that has been persistent during this time. The dermatologic exam is notable for multiple bruises on his upper and lower extremities. Which of the following is most likely to be abnormal in this patient?
IgA and IgG
Calcium
T-cells
IgM
IgM
This patient is presenting with symptoms of hyperviscosity, fatigue, and organomegaly suggestive of a diagnosis of Waldenstrom macroglobulinemia (WM). WM is characterized by increased IgM production.

WM occurs secondary to a clonal B-cell that pathologically overproduces IgM. High levels of IgM can lead to symptoms of hyperviscosity including blurred vision, dizziness, headaches, and peripheral neuropathy. Organomegaly is a unique finding in WM and can present with hepatomegaly and splenomegaly. Other non-specific findings include fatigue, anemia, and lymphadenopathy. This disease can be diagnosed using protein electrophoresis, which would demonstrate a spike in the levels of IgM protein. Treatment can include plasmapheresis and rituximab.

Gertz et al. review the evidence regarding the diagnosis and treatment of patients with WM. They discuss how patients often present with organomegaly as well as symptoms of hyperviscosity. They recommend rituximab treatment in symptomatic patients.

Incorrect Answers:
Answers 1 & 2: Calcium and IgA/IgG can be elevated in multiple myeloma (MM). MM presents with fatigue, weight loss, bone pain (back pain in particular), and other non-specific findings. MM less commonly presents with symptoms of hyperviscosity and organomegaly and this phenomenon has been described primarily with the IgA subtype. This is a late phenomenon and would be unlikely without preceding symptoms of bone pain and weight loss as a substantial protein concentrations (>5 g/dL) are required for this phenomenon. Treatment is with systemic chemotherapeutic agents.

Answers 4 & 5: Natural killer cells and T-cells could be elevated in non-Hodgkin lymphoma which would present with fatigue, lymphadenopathy, and "B-symptoms" (e.g., night sweats and chills). It would not present with symptoms of hyperviscosity. Treatment is with multi-agent chemotherapy as well as possible local radiation therapy.

Bullet Summary:
Waldenstrom macroglobulinemia (hyper IgM syndrome) presents with symptoms of hyperviscosity, fatigue, and organomegaly.