Atlas of Renal Pathology II

Agnes B. Fogo, MD, Editor

AJKD Atlas of Renal Pathology: Heavy Chain Deposition Disease

Agnes B. Fogo, MD,1 Mark A. Lusco, MD,1 Behzad Najafian, MD,2 and Charles E. Alpers, MD 2

Clinical and Pathologic Features interposition results in double-contour appearance of

Heavy chain deposition disease (HCDD) is the the glomerular basement membranes.
rarest of the monoclonal immunoglobulin deposition Etiology/Pathogenesis
diseases (MIDD), and is diagnosed by immunofluo-
rescence or immunohistochemistry. The reported age HCDD is due to deposition of monoclonal heavy
range of HCDD is from 35-79 years with men and chain in mesangial areas and along glomerular,
women equally affected, and one-third of patients tubular, and/or arterial basement membranes. The
demonstrating hypocomplementemia. Patients present monoclonal protein is due to an underlying plasma
with proteinuria, often in the nephrotic range, hema- cell dyscrasia. In some cases, it has been shown that
turia, hypertension, and reduced glomerular filtration the heavy chain deposits represent a truncated heavy
rate. The prognosis is dependent on the underlying chain with deletion of CH1, preventing binding of the
dysproteinemic disorder. Most patients have pro- heavy chain to heavy chain–binding protein in the
gressive glomerular filtration rate loss. Recurrence of endoplasmic reticulum and impairing assembly with
MIDD has been reported in the transplant. light chains. The truncated abnormal heavy chains
Light microscopy: HCDD typically shows nodular have a predisposition for tissue deposition, and are
sclerosis, with variable crescents in some cases. therefore usually not found in the urine. Monoclonal
Nearly all cases demonstrate glomerular deposits, protein is most often detected in the serum, without
with most cases also showing deposits along tubular detectable isolated monoclonal heavy chain in the
and arterial wall basement membranes. Glomerular urine.
basement membrane double contours may occur. Differential Diagnosis
Tubulointerstitial fibrosis and atrophy are pro-
portional to glomerular injury. Congo Red stain is HCDD may be distinguished from other causes of
negative. nodular sclerosis and mesangial expansion by spe-
Immunofluorescence microscopy: The key finding cific heavy chain staining in glomerular and tubular
is monoclonal heavy chain staining, most frequently basement membranes, negative Congo Red stain,
with g heavy chain, in a pseudolinear or occasional and characteristic punctate, amorphous, or ground
granular fashion along glomerular, and often tubular, pepper–like appearance of deposits on electron mi-
and occasional arterial wall basement membranes. A croscopy. Fibrillary glomerulonephritis is Congo
minority of cases also show concomitant complement Red negative, and usually manifests as deposits of
C3 deposits. polyclonal immunoglobulin G; diabetic nephropa-
Electron microscopy: Deposits are present along thy shows no deposits, and other types of MIDD
glomerular, tubular, and arterial wall basement mem- show staining restricted either to one light chain
branes, corresponding to deposits seen on immuno- subclass only or to one heavy and light chain sub-
fluorescence. These may be finely granular, punctate, class only. Other causes of a membranoproliferative
powdery, or ground pepper–like, with occasional sub- glomerulonephritis pattern show disease-specific
structure observed in some cases. Occasional cellular immunofluorescence and electron microscopic
appearances.
Key Diagnostic Features

From the 1Department of Pathology, Microbiology and Immu-

 Variable mesangial expansion, membranoprolifer-
nology, Vanderbilt University, Nashville, TN; and 2Department of ative appearance, or nodular sclerosis
Pathology, University of Washington, Seattle, WA.  Monoclonal heavy chain staining in mesangium
Support: None. and along glomerular and tubular basement mem-
Financial Disclosure: The authors declare that they have no branes with linear appearance, most often immu-
relevant financial interests.
Address correspondence to [email protected]
noglobulin G
Am J Kidney Dis. 67(3):e11-e12.  Punctate, amorphous, or ground pepper–like de-
Ó 2016 by the National Kidney Foundation, Inc. posits on electron microscopy
0272-6386
http://dx.doi.org/10.1053/j.ajkd.2016.01.004

Am J Kidney Dis. 2016;67(3):e11-e12 e11

 Atlas of Renal Pathology II

Figure 1. Heavy chain deposition disease with nodular scle-

rosis and glomerular basement membrane double contours
(Jones stain). Case shared by Dr Paisit Paueksakon, Vanderbilt
University. Figure 3. Heavy chain deposition disease with powdery
to ground pepper–like deposits along glomerular base-
ment membranes (electron microscopy). Case shared by
Dr Paisit Paueksakon, Vanderbilt University.

Figure 2. Heavy chain deposition disease with immunoglob-

ulin G3 pseudolinear staining along glomerular and tubular base-
ment membranes (immunofluorescence, IgG3). Case shared by
Dr Paisit Paueksakon, Vanderbilt University.

Figure 4. Heavy chain deposition disease with powdery

to ground pepper–like deposits along tubular basement
membranes (electron microscopy). Case shared by Dr Paisit
Paueksakon, Vanderbilt University.
-

e12 Am J Kidney Dis. 2016;67(3):e11-e12