You schedule a follow-up visit for your patient to review the findings and decide on your next steps.
You describe your concerns for a cold agglutinin-mediated process. Mr. C. is happy to hear you might have an explanation for his symptoms – though he has seen many doctors over the past year, his acrocyanosis remained a mystery.
He asks you why this might be happening to him at this age, and if there is any further testing you recommend.
How would you answer his question? Do you think there is an underlying cause of his cold agglutinin disease? If so, what is the most probable cause – and if not, why not?
You explain your suspicions to your patient – tearfully, he tells you his father died of mesothelioma, and he hopes to avoid the suffering his father experienced. You recommend a bone marrow biopsy to the patient; Mr. C. and his wife are agreeable. (we should discuss indications for biopsy)
You perform a core bone marrow biopsy in your office, and send the sample for pathology, immunophenotyping, and lymphoid sequencing.
In several days, you receive a report with the following results:
Core pathology: Hypercellular bone marrow with erythroid-predominant maturing trilineage hematopoiesis. Evidence of involvement by a B-cell lymphoproliferative disorder.
Aspirate pathology: Erythroid precursors are increased in number and exhibit left-shifted maturation. A 500-cell differential shows 5% plasma cells.
Immunophenotyping/flow cytometry: A minute population of kappa-restricted B-cells lacking expression of CD5 and CD10. Correlation with pathology and cytogenetics is recommended.
Lymphoid sequencing: KMT2D R5282* mutation detected. In lymphomas, KMT2D is believed to function as a tumor suppressor.