A Diagnostic Challenge of AL Amyloidosis in a Patient with Positive Immunohistochemistry for AA Amyloidosis Later Confirmed to be AL Amyloidosis by Mass Spectrometry

Introduction: We present a case of a 64-year-old male with progressive orthostatic hypotension and multi-organ dysfunction ultimately diagnosed with AL amyloidosis following renal biopsy and mass spectrometry analysis. The case underscores the diagnostic challenge posed by atypical presentations of amyloidosis and highlights the importance of kidney biopsy in diabetic patients with proteinuria that does not fit the typical presentation. It also emphasizes the utility of mass spectrometry in indentifying the amyloid subtype. Case Description: This is a 64-year-old Hispanic male with a history of type 2 diabetes, hypertension, hyperlipidemia, and cerebrovascular accident who had a 3-year history of dizziness and orthostatic hypotension progressing to syncopal attacks, unintentional weight loss, paresthesia of the lower extremity and generalized weakness. Despite extensive evaluations, including neurologic and malignancy workups, the underlying cause remained elusive. Nephrology consultation was sought due to significant proteinuria with UPCR of 19 g/g. Renal biopsy revealed Congo red-positive amyloid deposits with positive immunohistochemistry for AA amyloidosis, but there was lambda restricted staining on IF with no kappa staining suggested a possible AL amyloidosis. Serum and urine electrophoresis along with serum IFE were negative for abnormal bands, urine IFE showed discrete monoclonal bands. Subsequent mass spectrometry analysis identified AL amyloidosis, and bone marrow biopsy with approximately 15% lambda light chain restricted plasma cells prompting initiation of CyborD chemotherapy. However, advanced multi-organ involvement, including cardiac and gastrointestinal manifestations, led to a palliative care approach. Discussion: This case highlights the importance of considering amyloidosis in the differential diagnosis of patients with orthostatic hypotension. Kidney biopsy is a valuable tool for establishing the diagnosis, with mass spectrometry emerging as a novel modality for accurate subtyping. Early recognition of AL amyloidosis is crucial for timely intervention and prevention of further amyloid deposition,as prognosis is poor in advanced disease stages with multi-organ involvement.