Chromogranin A Tubulopathy: Differing Histopathologic Patterns of Acute Tubular Injury in the Setting of Neuroendocrine Neoplasms

Abstract

Introduction Neoplasms of neuroendocrine derivation or differentiation may express specific peptides, some of which are capable of producing clinical symptomatology and others used as biomarkers: one such peptide being chromogranin A (CGA). Herein, we describe histopathologic changes present in kidney specimens from patients with such neoplasms, and illustrate 2 patterns of acute tubular injury (ATI) attributable to CGA. Methods Eleven patients with a history of a neoplasm of neuroendocrine derivation or differentiation and having histopathologic sampling of the kidney were retrospectively identified, 3 of whom had ATI with either engorgement of the proximal tubular epithelium by resorbed material or tubular cast formation. Results Two patterns of ATI were observed. One characterized by acutely injured proximal tubular cells engorged with resorption granules that expressed CGA via immunoperoxidase staining. Another pattern was characterized by intraluminal tubular cast material associated with ATI that did not exhibit restriction of immunoglobulin light chains (LCs), but immunoperoxidase staining for CGA revealed that the cast material was composed of the neuroendocrine-associated peptide. The level of serum CGA does not appear to necessarily equate to developing either of these 2 patterns of ATI. Conclusions Patients with a neoplasm of neuroendocrine derivation or differentiation may develop ATI, and in certain cases may be secondary to CGA renal tubular deposition.