Cryofibrinogen-associated glomerulonephritis accompanied by advanced gastric cancer

Abstract

We had a 72-year-old man with advanced gastric cancer, poorly differentiated adenocarcinoma, receiving chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) plus oxaliplatin. Ascites developed despite remission of gastric cancer and metastasis. Given no malignant cells in ascites, leg edema, renal impairment, hypoalbuminemia, and massive proteinuria, we diagnosed as nephrotic syndrome with microscopic hematuria. Renal biopsy showed membranoproliferative glomerulonephritis with no deposition of immunoglobulins and complements. Of note, electronic microscopy found organized deposits with microtubular structures in the glomerular capillary lumens and subendothelial spaces. The liquid chromatography-tandem mass spectrometry method detected fibrinogen alpha chain, beta chain, gamma chain, and fibronectin, and we eventually diagnosed cryofibrinogen-associated glomerulonephritis. Cryofibrinogen was not detected in plasma. He was expired at 5 months following renal biopsy due to the progression of refractory nephrotic syndrome. In addition to the detailed assessment of specifically organized deposits, the analysis using liquid chromatography-tandem mass spectrometry method is useful to diagnose cryofibrinogen-associated glomerulonephritis. We should consider cryofibrinogen-associated glomerulonephritis as a differential diagnosis when the patients with malignancy showed abnormal urinalysis and renal impairment, though it is a rare disease.

Keywords: LC–MS/MS; Mass spectrometry; Membranoproliferative glomerulonephritis; Nephrotic syndrome; Organized deposit.

Fig. 1

Imaging findings at the time of gastric cancer diagnosis. a Endoscopic findings of the stomach. A deeply ulcerated tumor with ulcer mounds on the upper gastric body. b Abdominal contrast-enhanced computed tomography findings. The yellow arrow indicates primary tumor of gastric cancer. The red arrow indicates abdominal lymph node metastasis. The blue arrows indicate liver metastasis. c Chest contrast-enhanced computed tomography findings. The yellow arrowhead indicates the thrombosis in his left subclavian and brachiocephalic vein

Fig. 2

Clinical course. SOX S-1 (tegafur, gimeracil, and oteracil potassium) plus oxaliplatin, PTX paclitaxel, U-P urine protein, S-Alb serum albumin, S-Cr serum creatinine

Fig. 3

Computed tomography findings at the time of kidney biopsy (horizontal view [left] and coronal view [right]). Bilateral kidneys were not atrophied. Massive ascites was observed

Fig. 4

Light microscopic findings in the glomerulus. a Nodular lesions in glomeruli at low magnification. Mild infiltration of inflammatory cells in the renal interstitium and tubular atrophy. (Periodic acid-Schiff stain, original magnification ×40). b Lobular accentuation of the glomerular capillary tufts with marked mesangial expansion and capsular adhesion. Infiltration of foam cells in glomerular capillaries. (Periodic acid-Schiff stain, original magnification ×200). c Expansion of subendothelial spaces and double contours in the glomerular capillary walls. (Periodic acid-methenamin-silver stain, original magnification ×200). d CD68 positive infiltrating cells in the glomerular capillaries. (Immunoenzyme stain, original magnification ×200)

Fig. 5

Immunofluorescence findings of the glomerulus. a Immunoglobulin G negative (direct immunofluorescence, original magnification ×200). b Immunoglobulin A negative (direct immunofluorescence, original magnification ×200). c Complement 3 negative (direct immunofluorescence, original magnification ×200). d Segmental deposition of fibrinogen in the glomerular capillaries (direct immunofluorescence, original magnification ×200)

Fig. 6

Electron microscopic findings in the glomerulus. a Large amounts of organized deposits in the subendothelial spaces (original magnification ×3000). b Higher magnified image of these deposits. Randomly arranged microtubular structures with 40–50 nm diameter. (original magnification ×20,000). c Similar microtubular structures in another subendothelial space. (Original magnification ×20,000)

Fig. 7

Liquid chromatography-tandem mass spectrometry (LC–MS/MS) findings. LC–MS/MS using the Scaffold database identified fibrinogen alpha chain, beta chain and gamma chain (red arrows) in addition to fibronectin

Fig. 8

Serial sections of Masson’s trichrome stain and immunostaining for fibrinogen. Serial sections of Masson’s trichrome stain and immunostaining for fibrinogen showed that red color of deposition in glomeruli in Masson staining was identified by positive for fibrinogen, indicating fibrinogen deposition in subendothelial areas in glomeruli