S6021 Diagnostic Yield of Duodenal Biopsy in Unexplained Chronic Diarrhea: A Case of Duodenal AL Amyloidosis

Introduction: Duodenal AL (light chain) amyloidosis is a rare but critical cause of chronic diarrhea, often overlooked due to nonspecific symptoms and normal endoscopic findings. Duodenal biopsy with Congo red staining is essential for diagnosis. Case Description/Methods: A 78-year-old woman with a 6-year history of smoldering multiple myeloma presented with 2 years of progressive, non-bloody watery diarrhea (8–12 episodes/day), 40-pound weight loss, and signs of malabsorption. Extensive GI and infectious workup was unremarkable. Fecal pancreatic elastase was severely reduced (<10 µg/g). Upper endoscopy revealed mild duodenal mucosal changes. Duodenal biopsies demonstrated focal lymphangiectasia and thickened submucosal vessels with amorphous eosinophilic deposits on hematoxylin and eosin staining. Congo red stain revealed salmon-pink amyloid deposits, and polarized light microscopy confirmed apple-green birefringence, diagnostic of amyloidosis. Serum free light chain assay revealed elevated lambda chains (72.9 mg/L) with a skewed kappa/lambda ratio. SPEP showed a monoclonal IgG spike (10.9 g/L). Bone marrow biopsy revealed 10–15% clonal plasma cells with vascular Congo red–positive deposits. Cytogenetics showed monosomy 17, consistent with high-risk plasma cell dyscrasia. She was diagnosed with systemic AL amyloidosis involving the duodenum and pancreas, in the setting of progression to active multiple myeloma. The patient was initiated on Dara-CyBorD (daratumumab, cyclophosphamide, bortezomib, dexamethasone) and responded rapidly, with lambda chains decreasing to 18.6 mg/L after 1 cycle. She was also started on pancreatic enzyme replacement therapy, which improved stool consistency and frequency. Discussion: This case highlights the important role of duodenal biopsy in diagnosing chronic diarrhea of unknown cause, particularly in patients with plasma cell disorders. Even when endoscopic findings appear normal, targeted biopsies using Congo red staining can lead to a diagnosis of gastrointestinal AL amyloidosis. Histological confirmation should be sought in patients experiencing ongoing symptoms, malabsorption, or those with known plasma cell dyscrasias.