Yonago Acta medica 2004;47:91–96

Myeloma-Associated Fanconi Syndrome Due to λ-Light
Chain Crystal Deposition
Keitaro Noguchi, Chishio Munemura, Satoko Maeda, Satoru Yamamoto, Yoshikazu
Murawaki, Toshiyuki Kaidoh* and Shinichi Morino†
Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, *Division of Morphological Analysis, Department of Functional, Morphological andRegulation Science, School of Medicine and †Laboratory of Electron Microscopy, Tottori
University Faculty of Medicine, Yonago 683-8503 Japan
Multiple myeloma is uncommonly complicated with Fanconi syndrome, due to the deposition of light chains in renal tubular epithelial cells. A 76-year-old man with λ-BenceJones type multiple myeloma had adult Fanconi syndrome. Electron microscopy showedthat rhomboid, high-density substances of various sizes, were accumulated in the proximal tubular epithelial cells on renal biopsy. Immunoelectron microscopy demonstrated
that these crystals were λ-light chains. The deposition of κ-light chain in patients withmyeloma-associated Fanconi syndrome has been known. This is the 1st report showing
the deposition of λ-light chain in renal proximal tubular epithelial cells.
Key words: Fanconi syndrome; immunoelectron microscopy; multiple myeloma

Multiple myeloma is complicated with various renal disorders, and their onset closely involves thepresence of immunoglobulin light chains. Fanconi
syndrome, a renal disorder, is characterized by generalized aminoaciduria, hypophosphatemia, renal
diabetes and metabolic acidosis, due to impaired
reabsorption of various substances in the proximal
renal tubules, which is thought to result from proximal renal tubular damage by light chain immunoglobulins (Orfila et al., 1991; Lajoie et al., 2000; Guet al., 2003). There have been several reports onmorphological changes in these proximal renal tubules, including electron-microscopic observationsof crystalline structures in the cytoplasm (Costanzaand Smoller, 1963; Maldonado et al., 1975; Thorneret al., 1983; Chan et al., 1987; Truong et al., 1989;
Uchida et al., 1990; Yonemura et al., 1997; Marlowitz et al., 2000; Minemura et al., 2001). We recently

encountered a patient with Fanconi syndrome associated with λ-Bence Jones type multiple myeloma,and could demonstrate the deposition of λ-lightchains in the proximal renal tubules by immunoelectron microscopy.
Patient Report
A 76-year-old man sustained a fracture of the left
femoral neck in March 1999. Admitted to a local
hospital, he was diagnosed as having osteomalacia.
Proteinuria was revealed on admission, and the reaction level gradually increased thereafter. In June
2002, the patient was referred and admitted to our
University Hospital for further examination. He
had a history of partial gastrectomy for stomach
ulcer at 39 years of age.

Abbreviations: FBS, fasting blood sugar; OGTT, oral glucose tolerance test91

K. Noguchi et al.

Fig. 1. Proximal tubular epithelial cells
are swollen, containing numerous finegranules (periodic acid-Schiff stain)(original magnification, × 1000).

tubular phosphate reabsorption was 28.5%, rateof bicarbonate excretion was 15.8% and fractional
excretion of uric acid was 70.7%.
Bone marrow examination showed 22%
plasma cells including markedly atypical, binucleate or vacuolated forms. These findings led us
to a diagnosis of Fanconi syndrome associated with
λ-Bence Jones type multiple myeloma.
Light microscopy showed no pathologicalchanges in 35 renal glomeruli. Interstitial fibrosis
and cell infiltration were noted in some areas, andproximal renal tubular cells were swollen, containing numerous fine granules (Fig. 1). No abnormalities were observed in the distal renal tubules. No
amyloid deposition was found by Congo-red staining.
Immunofluorescence staining showed no deposits of immunoglobulins or complements. Immunoperoxidase staining demonstrated the presence of λ-light chains in the cytoplasm of proximal
tubular epithelial cells (Fig. 2). No κ-light chainswere present. There was no deposition of λ- orκ-light chains in the distal tubules.
Transmission electron microscopy showed thatrhomboid, high-density substances of various sizes,
partially enveloped in endoplasmic reticulum-likestructures, were accumulated in the proximal tubular epithelial cells. The remaining organelles weredecreased, for example mitochondria (Figs. 3a andb).

His blood pressure on admission was 140/84
mmHg, and his pulse rate was 52/min and regular.
There were no abnormalities in the chest, abdomenand nervous system. In addition to pain in the backduring movement, mild edema of the lower extremities was noted.
Laboratory findings were as follows: whiteblood cell count, 4,100/mm3; Hb, 9.3 g/dL; hematocrit, 27.6%; platelet, 14.8 × 10 3 /mm 3; Na, 147
mEq/L; K, 3.2 mEq/L; Cl, 122 mEq/L; Ca, 8.3mg/dL; P, 2.2 mg/dL; blood urea nitrogen, 14mg/dL; Cr, 1.66 mg/dL; uric acid, 1.6 mg/dL; total
protein, 5.0 g/dL; albumin, 3.2 g/dL; alkali phosphatase, 1,413 IU/L; fasting blood sugar (FBS), 80
mg/dL; immunoglobulin G, 514 mg/dL; immunoglobulin A, 64 mg/dL; immunoglobulin M, 46 mg/dL; λ-Bence Jones protein, + (by protein fractionation and serum and urine immunoelectrophoresis);creatinine clearance, 30.2 mL/min and 75-g oral
glucose tolerance test (OGTT), normal. Blood gas
analysis revealed metabolic acidosis: partial pressure of O2, 102.8 mmHg; partial pressure of CO2,38.1 mmHg; pH, 7.265; bicarbonate, 16.7 mmol/Land base excess, –9.1 mmol/L.
Urinalysis showed 1+ for protein, negative foroccult blood and 4+ for glucose. Taken together
with the FBS and 75-g OGTT results, these findings suggested renal diabetes. Daily urinary protein excretion was 2.3 g, about 70% of which was
Bence Jones protein. Urinary amino acid analysis
showed generalized aminoaciduria. Calculated

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Fanconi syndrome

Fig. 2. Immunoperoxidase staining for
λ-light chain shows positivity in thecytoplasm of proximal tubular epithelial
cells (peroxidase-antiperoxidase stain)(hematoxylin counterstain, × 1000).

2 µm

1 µm

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Fig. 3. Low- (a) and high-power (b)electron photomicrographs of proximal
tubular epithelial cells. These cells contain a large number of crystals, severalof which seem to be within membranebound structures interpreted as phagolysosome.