Background: IgM myeloma is a rare subtype of multiple myeloma characterized by the proliferation of malignant plasma cells producing monoclonal IgM antibodies. Its presentation with acquired type I cryoglobulinemia and acquired von Willebrand disease (aVWD) leading to superior vena cava (SVC) syndrome is exceptionally uncommon. Case Presentation: A 30-year-old female presented with an 8-month history of intermittent fever and a 6-month history of headaches and quadriparesis. She developed facial puffiness and recurrent oral and nasal ulcerations with crusting and bleeding over the past 2 months. In the preceding week, her symptoms escalated to include blurred vision, intensified headaches, and multiple episodes of vomiting. Fundoscopic examination revealed grade 4 papilledema. Laboratory investigations showed anemia (hemoglobin: 6.7 g/dL), leukocytosis (10,800/μL), and positive cryoglobulins. Imaging studies demonstrated multiple filling defects in the SVC without mass lesions. Bone marrow biopsy revealed 15% plasma cells and plasmacytosis. Serum protein electrophoresis identified an M spike with significantly elevated IgM levels and positive lambda light chains, confirming IgM myeloma. Conclusion: This case underscores the complexity of diagnosing IgM myeloma presenting with rare complications such as acquired type I cryoglobulinemia and aVWD leading to SVC syndrome. Early recognition and comprehensive evaluation are crucial for optimal management of such atypical presentations.
IgM myeloma is an unusual and rare plasma cell dyscrasia, constituting less than 1% of all multiple myeloma cases [1,2]. It is characterized by the proliferation of malignant plasma cells producing monoclonal IgM immunoglobulins. Distinguishing IgM myeloma from Waldenström macroglobulinemia is essential due to differences in treatment approaches and prognostic implications [3,4]. While Waldenström macroglobulinemia involves lymphoplasmacytic cells, IgM myeloma is characterized by mature plasma cells infiltration in the bone marrow [5].
The clinical manifestations of IgM myeloma are diverse due to the physicochemical properties of IgM, including hyperviscosity, cryoglobulinemia, and interference with coagulation pathways [6]. Acquired type I cryoglobulinemia involves monoclonal immunoglobulins that precipitate at low temperatures, leading to vascular occlusion and symptoms ranging from purpura to Raynaud's phenomenon [7,8]. Acquired von Willebrand disease (aVWD) is a bleeding disorder resulting from the adsorption of von Willebrand factor (vWF) by monoclonal proteins, leading to impaired hemostasis [9,10].
Superior vena cava syndrome (SVCS) results from the obstruction of the SVC, leading to impaired venous return from the head, neck, and upper extremities. While malignancies are the most common cause, its occurrence due to intravascular paraprotein deposition is exceedingly rare [11]. We report a case of IgM myeloma presenting with acquired type I cryoglobulinemia and aVWD, culminating in SVCS—a constellation of findings that poses significant diagnostic and therapeutic challenges.
A 30-year-old female with no significant past medical history presented to our facility with complaints of intermittent low-grade fever for 8 months and persistent headaches for 6 months. She also reported progressive weakness in all four limbs over the same period. Two months prior to admission, she developed facial puffiness and recurrent ulcerations in the oral and nasal mucosa, which were associated with crusting and intermittent bleeding.
One week before hospitalization, the patient experienced worsening headaches, now severe and throbbing, accompanied by blurred vision and multiple episodes of non-bilious, non-bloody vomiting. There was no history of trauma, seizures, or loss of consciousness.
On examination, the patient was pale with noticeable facial edema. Vital signs were stable. Neurological examination revealed quadriparesis with muscle strength graded at 4/5 in all extremities. Fundoscopic examination showed bilateral grade 4 papilledema, indicating raised intracranial pressure. There were ulcerative lesions with crusting on the oral and nasal mucosa.
Laboratory investigations revealed:
Imaging studies included:
Given the suspicion of a hematological malignancy, a bone marrow aspiration and biopsy were performed, revealing 15% plasma cells and evidence of plasmacytosis. Immunophenotyping demonstrated the plasma cells to be positive for CD38 and CD138, and negative for CD19 and CD20.
Serum protein electrophoresis showed a prominent M spike. Immunofixation electrophoresis identified a monoclonal IgM lambda paraprotein. Serum IgM levels were significantly elevated. Coagulation studies indicated reduced levels of functional von Willebrand factor activity, consistent with aVWD.
Based on the clinical, laboratory, and imaging findings, the patient was diagnosed with IgM myeloma complicated by acquired type I cryoglobulinemia and aVWD, presenting as SVCS.
IgM myeloma is a rare entity that poses significant diagnostic challenges due to its overlapping features with other monoclonal gammopathies, particularly Waldenström macroglobulinemia [1,4]. The differentiation is crucial as it influences management strategies and prognostic outcomes. In IgM myeloma, the malignant cells are mature plasma cells with more than 10% infiltration in the bone marrow, whereas Waldenström macroglobulinemia is characterized by lymphoplasmacytic infiltration [3,5].
The presence of type I cryoglobulinemia in our patient contributed to vascular occlusions observed in the SVC, leading to SVCS. Type I cryoglobulinemia is associated with monoclonal immunoglobulins and can cause hyperviscosity and vascular occlusion due to cryoprecipitation [7,8]. Khwaja et al. reported that IgM paraprotein-associated type I cryoglobulinemia can lead to a spectrum of vascular complications due to the precipitation of monoclonal IgM at low temperatures [7].
Acquired von Willebrand disease in the context of plasma cell disorders is attributed to the adsorption of vWF onto the surface of malignant cells or binding to paraproteins, leading to its clearance from the circulation [9]. Mohri highlighted that aVWD associated with monoclonal gammopathies results in bleeding tendencies due to decreased vWF levels and activity [9]. Hopfting et al. described distinct mechanisms of IgM antibody-mediated aVWD and successful treatment approaches [10].
SVCS is rarely reported as a presenting feature of IgM myeloma. In this case, the absence of an external mass lesion suggests that intravascular factors, such as cryoglobulin-induced thrombosis and hyperviscosity, played a pivotal role. Yoshimura et al. reported a case of early-onset hyperviscosity syndrome caused by IgM myeloma, emphasizing the need for early diagnosis and intervention [6].
Management of such a complex case requires addressing the underlying plasma cell disorder and its complications. Therapeutic options include chemotherapy regimens used in multiple myeloma, plasmapheresis to reduce paraprotein levels, and supportive measures for complications like bleeding and thrombosis [2,11]. Mina et al. reported the successful use of daratumumab-based therapy in IgM myeloma with hyperviscosity syndrome, suggesting potential therapeutic avenues [11].
This case highlights the importance of considering rare hematological malignancies in patients presenting with multisystem involvement. IgM myeloma can present with unique complications such as acquired type I cryoglobulinemia and aVWD, leading to uncommon manifestations like SVCS. Early diagnosis and a multidisciplinary approach are crucial for effective management and improved patient outcomes.
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