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.

Clinicopathologic Spectrum of Lysozyme-Associated Nephropathy

“…Ultrastructurally, these droplets correspond to intracytoplasmic, membrane-bound vacuoles containing homogenous and/or granular electron dense material, sometimes with admixed cellular debris. LyN must be distinguished from other proximal tubulopathies characterized by accumulation of excess intracytoplasmic noncrystalline proteins, including chromogranin tubulopathy 30 and noncrystalline form light chain proximal tubulopathy. 31 , 32 Immunohistochemical staining for chromogranin and immunofluorescence staining for kappa and lambda light chains (including with pronase digestion) are useful in excluding these entities.…”

Low Efficacy of Chromogranin A Elimination by Therapeutic Plasma Exchange for Treatment of Chromogranin A Tubulopathy

“… 2 , 3 , 4 Because CgA tubulopathy is a rare but important complication directly attributed to tubular CgA precipitates, eliminating serum CgA could provide a therapeutic approach. 1 Although PEX might remove serum CgA, its low efficacy in this case suggests that the combination of a large volume of distribution and high CgA synthetic rate exceeds its clearance capacity by PEX.

Figure 1 Kidney biopsy result confirming CgA tubulopathy and efficacy of CgA elimination by using PEX.

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“…Previous seminal work has shown that chromogranin A (CgA) can mediate tubular injury, either by intraluminal precipitation with cast formation or excessive tubular CgA uptake. 1 We report an additional case of kidney injury in the context of CgA tubulopathy and explored the efficacy of CgA elimination by therapeutic plasma exchange (PEX). A 69-year-old Caucasian male with a past medical history of pancreatic neuroendocrine neoplasm presented to our department with progressive worsening of kidney function for two years and proteinuria (741.6 mg/g creatinine).…”