A 72-year-old man presents to the clinic with a 2-month history of worsening fatigue, blurry vision, and recurrent nosebleeds. He also mentions a pins and needles sensation in his feet. Past medical history is significant for hypothyroidism and hypertension. He takes levothyroxine and chlorthalidone. Vital signs are within normal limits. On physical examination, he has moderate hepatosplenomegaly and several small, palpable axillary lymph nodes. Funduscopic examination reveals dilated, tortuous retinal veins with scattered flame-shaped hemorrhages.
Laboratory studies show the following:
Hemoglobin: 9.8 g/dL
Platelet count: 142,000/μL
Total protein: 9.2 g/dL
Serum protein electrophoresis (SPEP): Large M-spike in the gamma globulin region
Serum immunofixation: Monoclonal IgM spike
Serum viscosity: 4.5 centipoise (Normal: 1.4–1.8)
Which of the following bone marrow findings is most consistent with this patient’s diagnosis?
The correct answer is:
B) Infiltration by pleomorphic cells with both lymphocytic and plasmacytic features
This patient is presenting with Waldenström macroglobulinemia (WM), a low-grade B-cell lymphoma characterized by the proliferation of lymphoplasmacytic cells. These cells are intermediate in appearance between a B-lymphocyte and a plasma cell. The hallmark of WM is the production of a monoclonal IgM antibody. Because IgM is a large pentamer, high levels significantly increase serum viscosity. This leads to the classic clinical triad of hyperviscosity syndrome:
Visual disturbances: "Sausage-link" retinal veins and hemorrhages.
Neurological symptoms: Headache, dizziness, or peripheral neuropathy.
Bleeding: Mucosal bleeding (epistaxis, gums) due to interference with clotting factors and platelet function.
Unlike multiple myeloma, Waldenström macroglobulinemia typically presents with lymphadenopathy and hepatosplenomegaly, and it notably lacks lytic bone lesions and hypercalcemia.
Answer choice A: >10% clonal plasma cells with "clock-face" nuclei, is incorrect. This is the diagnostic criterion for multiple myeloma (MM). While MM also features an M-spike, it is typically IgG or IgA. IgM myeloma is extremely rare and usually presents with bone lesions, which are absent in WM.
Answer choice C: Large B-cells in a diffuse pattern with prominent nucleoli, is incorrect. This describes diffuse large B-cell lymphoma (DLBCL), an aggressive high-grade lymphoma. WM is a more indolent, low-grade process.
Answer choice D: Presence of Auer rods in immature myeloid blasts, is incorrect. These are found in acute myelogenous leukemia (AML), specifically the myeloid lineage, not the lymphoid/plasma cell lineage involved in WM.
Answer choice E: Small, mature lymphocytes with smudge cells, is incorrect. This is the classic finding for chronic lymphocytic leukemia (CLL). While CLL can sometimes produce a small M-spike, it would not cause the profound hyperviscosity seen in this case.
Key Learning Point
Waldenström macroglobulinemia is a lymphoplasmacytic lymphoma associated with a monoclonal IgM M-spike. The primary clinical complications are driven by hyperviscosity, such as blurry vision, headaches, and mucosal bleeding. Management of acute hyperviscosity involves emergence plasmapheresis to rapidly remove the large IgM pentamers from the circulation.
