Case Report: Borderline type I/II cryoglobulinemia associated with marginal zone lymphoma: a diagnostic challenge

Cryoglobulinemia comprises heterogeneous disorders caused by immunoglobulins that precipitate at low temperatures, leading to vascular occlusion and immune-mediated tissue injury. Type I disease is typically linked to monoclonal gammopathies, whereas mixed forms (Type II or III) are characterized by immune complex-mediated vasculitis, rheumatoid factor activity, and renal involvement. The immune complexes are generally composed of IgM rheumatoid factor and IgG. We describe a 67-year-old woman with marginal zone lymphoma who developed an unusual cryoglobulinemia phenotype combining monoclonal IgM-κ cryoglobulins with clinical features characteristic of mixed disease, including purpura, transient rheumatoid factor positivity, and renal impairment. Diagnosis was delayed due to initial false-negative cryoglobulin testing and atypical presentation. Despite rituximab therapy, subsequent R-CVP, and intensive plasmapheresis, the patient's condition progressed, ultimately requiring bendamustine-rituximab, after which she deteriorated and died shortly after discharge. The exceptional nature of this case lies the concomitant clinical manifestation of Type I and Type II cryoglobulinemia, which complicated the diagnostic process and therapeutic management. This case underscores a significant diagnostic challenge in hematology.