Introduction: Systemic mastocytosis (SM) is a clonal disorder characterized by abnormal accumulation of mast cells in various tissues and is categorized into distinct subtypes per the World Health Organization (WHO) 2022 classification. When SM is associated with another hematologic neoplasm, typically of myeloid lineage, it is classified as systemic mastocytosis with an associated hematologic neoplasm (SM-AHN). Coexistence with plasma cell dyscrasias is rare, with fewer than 15 published cases involving either smoldering multiple myeloma (SMM) or multiple myeloma (MM). ALECT-2 amyloidosis, a non-immunoglobulin-derived amyloid subtype, is typically isolated to the kidneys and has not been previously reported in context of SM-AHN. Case Presentation: We describe the first documented case of concurrent SMM, SM-AHN, and ALECT-2 amyloidosis in a 67-year-old male of Egyptian descent with stage 3B chronic kidney disease and proteinuria. Diagnostic workup revealed lambda-restricted plasma cell infiltration, KIT D816V-positive multifocal mast cell aggregates, and renal-limited ALECT-2 deposits confirmed by mass spectrometry. Serum immunofixation electrophoresis showed a monoclonal lambda free light-chain band without a corresponding intact heavy-chain M-protein, and serum protein electrophoresis showed no M-spike. The patient was managed with active surveillance, and the available records document approximately 24 months of follow-up. Conclusion: This case highlights the diagnostic and clinical implications of overlapping hematologic and renal disorders, underscores the role of proteomic amyloid typing in avoiding misdiagnosis, and explores potential pathogenic interplay between mast cells, plasma cells, and the marrow microenvironment. This case also underscores the importance for clinicians remaining vigilant and consider the possibility of non-AL amyloidosis, even when a plasma cell disorder diagnosis has been documented.
Soliman et al. (Mon,) studied this question.