Systemic amyloidosis is a condition where amyloid proteins accumulate in organs and tissues, causing multisystem dysfunction. Its presentation often overlaps with other conditions like lymphoproliferative disorders and multiple myeloma (MM). Lymphadenopathy is rare in amyloidosis but can complicate the clinical picture, mimicking more common hematological diseases. We present a case of systemic amyloidosis in a patient initially suspected of having lymphoma, complicated by underlying multiple myeloma and probable cardiac amyloidosis.

A 63-year-old male with a history of heart failure and chronic kidney disease presented with frequent hospital admissions due to dyspnea. Axillary lymphadenopathy prompted referral to hematology. PET-CT revealed widespread FDG-avid lymphadenopathy, suggesting lymphoma. Biopsy showed plasma cell infiltration (10-11%) with kappa light chain monotypic plasma cells and amyloid deposits, indicating systemic amyloidosis. Concurrent imaging revealed pleural effusions, calcified lymphadenopathies, and findings consistent with granulomatous disease. Further hematological evaluation suggested underlying plasma cell dyscrasia, likely multiple myeloma. The patient's history of heart failure raised the suspicion of cardiac amyloidosis, a common complication in systemic amyloidosis, warranting cardiology evaluation and planned cardiac MRI.

This case underscores the diagnostic challenge posed by systemic amyloidosis, especially when lymphadenopathy is present, leading to initial misdiagnosis as lymphoma. Amyloidosis-related lymphadenopathy is uncommon but should be considered, especially when plasma cell dyscrasias like multiple myeloma are involved. The concurrent diagnosis of multiple myeloma further complicates the clinical course, necessitating a tailored therapeutic approach.

Cardiac amyloidosis is a serious complication often seen in patients with systemic amyloidosis, especially AL-type, where amyloid deposits infiltrate the myocardium, leading to restrictive cardiomyopathy. In this case, the patient's long-standing heart failure and arrhythmia raised the likelihood of cardiac involvement. Early detection is crucial, as cardiac amyloidosis is associated with a poor prognosis. The integration of advanced cardiac imaging, such as MRI, is essential in confirming the diagnosis and guiding treatment.

This case illustrates the importance of considering systemic amyloidosis in patients with unexplained lymphadenopathy and highlights the need for multidisciplinary management, particularly when cardiac involvement is suspected.