title: Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era.
abstract: Light chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were κ-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed λ-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients.
authors.affiliation: Departments of Pathology and mbs2101@cumc.columbia.edu.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Stokes
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York;
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Valeri
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, Ohio; and.
authors.forename: Leal
authors.initials: L
authors.lastname: Herlitz
authors.affiliation: Department of Medicine, Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Khan
authors.affiliation: Department of Medicine, Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: David S
authors.initials: DS
authors.lastname: Siegel
authors.affiliation: Departments of Pathology and.
authors.forename: Glen S
authors.initials: GS
authors.lastname: Markowitz
authors.affiliation: Departments of Pathology and.
authors.forename: Vivette D
authors.initials: VD
authors.lastname: D'Agati
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003460:Crystallization; D005198:Fanconi Syndrome / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
keywords: Renal pathology; multiple myeloma; renal proximal tubule cell