Combined crystal-storing histiocytosis, light chain proximal tubulopathy, and light chain crystalline podocytopathy in a patient with multiple myeloma: a case report and literature review

Figures & data

Figure 1. A large number of purple granular inclusions and needle-shaped crystals could be seen in the cytoplasm of bone marrow plasma cells (Wright Giemsa stain, 1000 × original magnification).

Figure 2. Crystalline inclusions in podocytes (a: HE; b: PAS), proximal tubular epithelial cells (c, d: PAS) and histiocytes (e: PAS; f: HE) (original magnification all ×1000).

Figure 3. Periodic acid–Schiff (PAS)-positive, heterogeneous, and granular casts could be seen in the tubular lumens (a: PAS, original magnification × 100; b: PAS, original magnification × 200; c: PAS, original magnification × 400).

Figure 4. On immunohistochemistry, kappa light chain-restricted expression (a: κ, 200 × original magnification) while lambda was negative (b: λ, 200 × original magnification) in proximal tubular epithelial cells (c: κ, 400 × original magnification), histiocytes (d: κ, 400 × original magnification), and podocytes (e: κ, 400 × original magnification).

Figure 5. Immunohistochemical stains for immunoglobulins confirm the nature of the crystalline inclusions within the histiocytes. Immunoreactivity for kappa light chain is strong within the histiocytes as well as in the plasma cells, which demonstrates kappa light chain restriction. Immunohistochemistry showed that there were histiocytosis in renal interstitium (a: CD68, 100 × original magnification; b: κ, 100 × original magnification; c: CD68, 400 × original magnification).

Figure 6. Immunofluorescence with pronase digestion on formalin-fixed paraffin-embedded tissue shows bright staining for kappa (400 × original magnification).

Figure 7. Electron microscopy showed crystalline inclusions in the podocytes (a, b), mesangial cells (c, d), proximal tubular epithelial cells (e, f), and histiocytes (g, h) (uranyl acetate and lead citrate staining, original magnification: a, f, g: ×4, 200, bar = 2 μm; b: ×6, 000, bar = 2 μm; c: ×9, 900, bar = 1 μm; d: ×20, 500, bar = 500 nm; e: ×11, 500, bar = 1 μm; h: ×6, 000, bar = 2 μm).

Figure 8. Immunoelectron microscopy showed that kappa light chain was strongly positive (a, b, c) in the crystalline inclusions and lysosomes of proximal tubular epithelial cells and podocytes, while lambda light chain was negative (d) (original magnification: a, b: κ × 26, 500, bar = 200 nm; c: κ × 11, 500, bar = 1 μm; d: λ × 20, 500, bar = 500 nm).

Table 1. Overview of CSH with renal involvement.

	Author [Ref]	Age/Sex	Scr (mg/dL)	Urine protein	Renal clinical manifestations	Monoclonal protein	Hematologic disease	Distribution of crystals			Cast nephropathy	Extrarenal involvement	Outcome
								Glomerulus	TE	Histiocyte
1	Gupta et al. [4]	71/M	1.18	3.6	CKD	IgMκ	LPL	G-Cl	Yes	Yes	No	None	N/A
2	Gupta et al. [4]	67/M	2.7	Yes	AKI	IgGκ	MGRS	G-Cl	No	Yes	No	None	Died of MODS
3	Gupta et al. [4]	74/M	3.5	2	AKI	κ	MM	G-Cl	No	Yes	No	None	N/A
4	Galeano-Valle et al. [5]	65/M	7.6	N/A	AKI	κ	MGRS	No	lumen	No	No	BM, liver, spleen, LN	Died of GI hemorrhage
5	Wu et al. [6]	48/M	12.6	N/A	CKD	κ	MM	No	Yes	Yes	No	None	Stable, CTX, HD
6	El et al. [7]	52/M	2.9	0.29	CRF + FS	IgMκ	MGRS	N/A	N/A	N/A	No	BM	Died of sepsis, 25 years
7	El et al. [7]	70/M	2.4	0.8	CRF + FS	IgMκ	DLBCL	N/A	N/A	N/A	No	None	Died of sepsis, 14 months, Scr 3.2 mg/dL
8	El et al. [7]	65/M	6.3	2.5	CRF + FS	IgGκ	MGRS	N/A	N/A	N/A	No	None	Stable, 19 months, HD
9	Duquesne et al. [8]	62/F	normal	3.2	FS	IgGκ	MGRS	No	Yes	Yes	No	BM, eye	Stable, CTX, 18 months, CR
10	Ungari et al. [9]	66/F	1.6	1.95	CKD	κ	MM	No	Yes	Yes	No	BM	Stable, CTX, 6 months
11	Sethi et al. [10]	58/M	3.3	0.51	AKI	IgMλ	MZL	mes	No	Yes	No	None	Stable, CTX
12	Pitman et al. [11]	70/F	2.8	NA	AKI	κ	MGRS	No	No	Yes	No	None	Died of stroke, 6 months
13	Farooq et al. [12]	66/M	2.5	NA	AKI	IgGκ	MM	No	Yes	Yes	No	BM	Stable, CTX-ASCT, 6 months
14	Aline-Fardin et al. [13]	69/M	1.0	0.69	No FS	κ	MGRS	No	Yes	Yes	No	BM, LN	Stable, CTX, 12 months, CR
15	Keane et al. [14]	65/M	abnormal	NA	CKD	κ	MGRS	Yes	Yes	Yes	No	BM	N/A
16	Stokes et al. [15]	41/M	4.2	20.2	CKD + FS	IgDκ	MM	No	Yes	Yes	Yes	None	Stable, CTX-ASCT, 6 months, CR, Scr 2.2 mg/dL
17	Weichman et al. [16]	45/M	eGFR 64	0.7	None	IgGκ	MM	No	Yes	Yes	No	None	Stable, CTX-ASCT, CR
18	Tholouli et al. [17]	62/F	N/A	N/A	AKI	IgGκ	MM	No	Yes	Yes	No	None	Stable, CTX, 6 months, CR
19	Takahashi et al. [18]	60/M	N/A	N/A	CKD	IgAκ	MM	No	No	Yes	No	BM, liver, spleen	Died of electrolyte imbalance, 3.75 years
20	Kapadia et al. [19]	78/F	N/A	N/A	AKI	IgMκ	LPL	N/A	N/A	N/A	No	head and neck, LN	Died of AKI, CTX, 5 months
21	Garc-ia et al. [20]	44/M	N/A	N/A	N/A	IgGκ	LPL	No	No	Yes	No	BM, GI-Tract, Liver, heart, lung, spleen, head and neck, LN, pancreas, pleura and mesentery	Died of MODS, CTX, more than 1 year
22	Dogan et al. [21]	60/M	7	6.02	CKD	IgGκ	MM	VEC, mes	Yes	Yes	No	BM, eye	Stable, CTX, HD
23	Reeders et al. [22]	57/M	2.0	NA	CKD	IgGκ	LPL	VEC, endo, mes	Yes	Yes	No	Retroperitoneal area	N/A
24	Matthai et al. [23]	48/F	6.42	4.6	AKI + NS	κ	MM	VEC	Yes	Yes	Yes	None	N/A
25	Papla et al. [24]	51/M	abnormal	NA	CKD	κ	MM	VEC, endo, mes	Yes	Yes	No	BM, liver, lung	Died of MODS, 1 year
26	Nakamura et al. [25]	66/F	4.72	2.2	AKI	κ+ B-J	MGRS	VEC	Yes	Yes	Yes	None	N/A
27	Yamamoto et al. [26]	75/M	7.13	N/A	N/A	IgGκ	MM	VEC	Yes	Yes	No	BM, eye	Died of septic, CTX, 5 year
28	Ito et al. [27]	65/F	1.94	2.0g/gCr	AKI	IgGκ	MGRS	endo	Yes	Yes	No	None	Stable, CTX, 9 courses
29	Present	69/F	11.1	2.66	AKI on CKD	IgGκ + κ	MM	VEC, mes	Yes	Yes	No	BM	Stable, CTX, 3 years

Abbreviations: AKI: Acute kidney injury; ASCT: Autologous stem cell transplant; BM: Bone marrow; CKD: Chronic kidney disease; CTX: Chemotherapy; DLBCL: Diffuse large B-cell lymphoma; endo: Glomerular endothelial cell; F: Female; FS: Fanconi syndrome; G-Cl: Glomerular capillary loops; GI: Gastrointestinal; HD: Hemodialysis; LN: Lymph node; LPL: Lymphoplasmacytic lymphoma; M: Male; mes: Mesangial cell; MGRS: Monoclonal gammopathy of renal significance; MM: Multiple myeloma; MODS: Multiple organ dysfunction syndrome; MZL: Marginal zone lymphoma; N/A: Not available; Scr: Serum creatinine; TE: tubular epithelial cell; VEC: Visceral epithelial cell.

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Data availability statement

All data generated or analyzed during this study are included in this published article.