Massive generalized crystal-storing histiocytosis associated with extracellular crystalline nephropathy: clinical, immunohistochemical, and ultrastructural studies of a unique disorder and review of the literature

Abstract

Crystal-storing histiocytosis (CSH) is a rare disorder characterized by the accumulation of nonneoplastic histiocytes containing intracytoplasmic crystallized immunoglobulins. In most cases, there is an associated underlying lymphoplasmacytic neoplasm expressing Ig kappa light chain. About 131 cases of CSH have been identified. There is a localized and a generalized form of CSH and it can involve several sites including bone marrow, lungs, lymph nodes, liver, spleen, gastrointestinal tract, and kidney. Generalized CSH is less frequent and involves multiple organs and tends to have a worst prognosis than localized CSH. Around 20 cases of renal involvement in CSH have been reported so far. Paraprotein-induced crystalline nephropathy can be divided into two categories based on whether the crystals in the kidney are intracellular (including light chain proximal tubulopathy with crystals and CSH) or extracellular (including the crystalline variant of myeloma cast nephropathy and crystalglobulin-induced nephropathy). The former tends to present with slowly worsening kidney dysfunction and generally has a good prognosis, whereas the latter usually presents with rapidly progressive renal failure and is associated with poor renal outcome. We present a case of generalized CSH associated with extracellular crystalline nephropathy with a fulminant and fatal clinical course. Kappa light-chain crystals were found exclusively extracellularly within the tubular lumen, not within the tubular epithelial cells nor the histiocytes, and the massive presence of those precipitates led to the acute renal failure. Consequently, we review the renal involvement in CSH in the literature and discuss the unique mechanism of renal injury in this case.

Keywords: Crystal-storing histiocytosis; Crystalline nephropathy; Histiocytes; Kappa light chains; Kidney.

Fig. 1

a Liver’s histiocytes showing intracytoplasmic crystalloid inclusions (black arrow) and extracellular crystals (white arrows) within periportal space (H–E staining × 10 000). Interstitial diffuse infiltration of histiocytes with intracytoplasmic crystalloid inclusions (arrows) in splenic parenchyma (b), BM (c) and lymph node (d) (b–d H–E staining × 4000). e Higher magnification of histiocytes in splenic parenchyma (H–E staining × 6000). Immunohistochemistry shows negative reactivity of the histiocytes (arrows) for kappa (f) and lambda (g) light chains (f, g × 4000). h Positive reactivity for CD68 in histiocytes of BM (× 4000). i Crystals (arrow) show negative birefringence under polarized light (× 2000). j Ultrastructural examination of the spleen shows intracytoplasmic electron dense hexagonal-like crystals, without periodic organization of the substructure (× 25,000)

Fig. 2

a Renal tissue shows intratubular large needle-shaped or rhomboid-like crystals (arrows) (H–E staining × 2000). b Intratubular crystals (arrow) show negative birefringence under polarized light (× 4000). c Crystal stain strongly yellow with the Masson’s trichrome stain. d Transmission electron microscopy microphotograph showing geometrically shaped crystals without periodic organization within the tubular lumen (× 25,000). Immunohistochemistry shows negative reactivity of crystals for kappa (e) and lambda (f) light chains (× 4000)

Fig. 3

Mass spectrometric proteomic analysis listing the proteins identified in the spleen and kidney tissue. Biops 1–2 represent peptides detected in the spleen. Biops 2–2 represent peptides detected in then kidney. Fragments of IgG heavy chain constant region and fragments of kappa light chain constant region were detected in both tissues