Elsevier

Human Pathology

Volume 44, Issue 5, May 2013, Pages 927-933
Human Pathology

Case study
Complete remission of monoclonal gammopathy with ocular and periorbital crystal storing histiocytosis and Fanconi syndrome

https://doi.org/10.1016/j.humpath.2012.10.012Get rights and content

Summary

A 62-year-old woman presented with crystalline keratopathy, crystal-storing histiocytosis, Fanconi syndrome, and a serum monoclonal IgG-κ and urinary κ light chain. Histology and electron microscopy studies revealed the presence of crystals within macrophages in multiple eye sites, in the kidney and in the bone marrow. The variable domain of the pathogenic κ light chain related to the Vk1-39 gene that was also involved in most previously reported cases of Fanconi syndrome. Owing to the severity of the damage to the eye and a potentially poor kidney prognosis, the patient underwent autologous stem cell transplantation. After 18 months follow-up, she is in complete hematological, ophthalmological, and renal remission.

Introduction

Monoclonal immunoglobulin light chains (LCs) may be responsible for a variety of diseases featuring deposition of amorphous, fibrillar, or crystalline material in multiple tissues, leading to clinical complications that may require strong treatments of the LC-secreting tumor [1]. In relatively rare cases, the variable regions of monoclonal κ LCs resist normal degradation by proteases and accumulate inside kidney proximal epithelial cells, causing Fanconi syndrome (FS) [2]. In crystal-storing histiocytosis (CSH), Gaucher-like macrophages containing numerous immunoglobulin crystals accumulate in the bone marrow. Crystal deposition may, however, also occur in extramedullary sites such as the kidney and the cornea. Deposition in renal proximal tubular epithelium causes FS, a slowly progressive disorder featuring glycosuria, aminoaciduria, and hypophosphatemia. Immunoglobulin (Ig) LC deposition usually contributes to progressive organ damage, including renal failure.

We report a case of monoclonal gammopathy of undetermined significance (MGUS) with crystal formation and storage histiocytosis involving the kidney and eye. Early diagnosis and intensive treatment with autologous stem cell transplantation led to complete remission.

Section snippets

Clinical presentation

A 62-year-old woman was admitted to the ophthalmology department in October 2008 after a decrease in visual acuity over 3 years. She had no significant medical history except a mild hypertension. Visual acuity was 3/10 in both eyes. Slit-lamp examination detected a diffuse and punctiform infiltrate in both the anterior and posterior corneal stroma but no epithelial or endothelial abnormalities (Fig. 1A). The rest of the eye examination was normal. Confocal microscopy images revealed the

Discussion

Our patient presented with 2 distinct complications of a κ LC–secreting MGUS involving the eye and the kidney, both of which featured intracellular crystal deposition. Although FS due to monoclonal Ig LC usually displays progressive interstitial fibrosis and chronic renal failure, in the present case, early hematologic treatment allowed preserving the renal function.

References (15)

There are more references available in the full text version of this article.

Cited by (21)

  • An update to the pathogenesis for monoclonal gammopathy of renal significance

    2020, Critical Reviews in Oncology/Hematology
    Citation Excerpt :

    The abnormal κLC cannot be degraded by the lysosomes, thereby leading to the accumulation of the crystal formation in the histiocytes. CSH occurs in patients with proximal renal tubular dysfunction, also supporting the hypothesis that CSH may be attributed to the decreased excretion of Ig El Hamel et al., 2010; Duquesne et al., 2013. Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits was proposed as a novel disease entity, characterized by confined and non-organized glomerular deposition Nasr et al., 2009.

  • Gastric Crystal Storing Histiocytosis: Clinicopathologic Findings and Morphologic Mimics

    2018, Human Pathology: Case Reports
    Citation Excerpt :

    Systemic CSH is most likely seen in lymphoplasmacytic lymphoma or multiple myeloma. Localized CSH involving lung, bone marrow [1], kidney [2–4], skin [5,6], ocular and periorbital areas [7,8] has been reported. In majority of the cases, localized CSH is related directly to the presence of an underlying lymphoproliferative disorder.

  • Two Cases of Paraproteinemic Keratopathy

    2023, Journal of Korean Ophthalmological Society
View all citing articles on Scopus
1

Contributed equally to the study.

View full text