#PathPointer: Heavy Chain Deposition Disease – The Forgotten MIDD

PathPointers highlight important everyday teaching points when reviewing kidney histology. These brief and easy-to-read blog posts include real clinical images to demonstrate various biopsy findings.

When it comes to plasma cell dyscrasias, nephrologists love discussing the various manifestations of this disease in the kidney. Cast nephropathy, light chain deposition disease, amyloid, proximal tubule dysfunction, and Fanconi’s syndrome, and even acquired C3 glomerulopathy (remember NephMadness 2019, anyone?) all usually spring to mind. We even coined a phrase (MGRS) specifically for when monoclonal gammopathy affects our organ!

But what about heavy chain disease? After all, it’s an important component of immunoglobulins, yet it hardly draws breath when monoclonal immunoglobulin deposition disease (MIDD) is mentioned. Turns out, heavy chain deposition disease (HCDD) is incredibly rare, with only about 70 cases reported since 1992. Clinical manifestations are similar to other MIDDs and include proteinuria (oftentimes nephrotic range), hematuria, hypertension, and reduced GFR. Histologic manifestations are variable on light microscopy, and include mesangial expansion, nodular sclerosis, or an MPGN-pattern. Congo red staining will be negative.

The key finding distinguishing HCDD from LCDD is on immunofluorescence, where heavy chain deposits (most frequently with γ heavy chain) are found to be monoclonal by monotypic staining of an IgG subclass. Light chain staining for kappa and lambda are negative. Electron microscopy shows punctate or amorphous deposits often described as “pepper-like” or “powdery” along the glomerular and/or tubular basement membranes.

Punctate mesangial deposits in monoclonal immunoglobulin deposition disease

A recent AJKD article by Zhang et al looks at a group of 25 patients in a Chinese biopsy database who met the criteria above. Their characteristics are described below, along with the classic HCDD findings that were seen in this cohort:

Table 1 from Zhang et al, AJKD © National Kidney Foundation

Heavy chain disposition disease with typical nodular glomerulosclerosis and ultrastructural features. (A) Increased mesangial matrix in the glomerulus, nodule formation (periodic acid–Schiff [PAS]; original magnification, ×200). (B) Partial mesangial dissolution (PAS; original magnification, ×400). (C) Nodules were poorly argyrophilic and containing capillary microaneurysms (periodic acid-silver metheramine; original magnification, ×200). (D) Immunofluorescence identified linear deposits of immunoglobulin G along the glomerular (GBMs) and tubular basement membranes (TBMs) (original magnification, ×200). (E, F) Finely granular or “powdery” electron-dense deposits were detected along the (E) inner aspect of GBMs (electron microscopy; original magnification, ×10,000) and (F) outer aspect of the TBMs (electron microscopy; original magnification, ×23,000). Figure 1 from Zhang et al, AJKD © National Kidney Foundation

When it came to describing treatment, some form of chemotherapy was administered in 13 of the 20 patients that had clinical follow-up available. Of the 7 patients that did not receive any treatment, 5 patients progressed to kidney failure, whereas 12 of the 13 patients that received chemotherapy had improved kidney function.

Table 5 from Zhang et al, AJKD © National Kidney Foundation

Although care needs to be taken to draw conclusions from such a small group, it is also clear that we are never going to see randomized controlled trials in such a rare disease. Additionally, treatment strategies for plasma cell dyscrasias have improved dramatically over the past 10 years that it seems reasonable to treat these patients similar to those prompt chemotherapy. As we have learned from cast nephropathy trials like MYRE and EuLITE, the reduction in circulating paraproteins (in the case of HCDD, the heavy rather than light chains) is paramount to achieve improvement in kidney function.

For more information on this rare disease, be sure to check out this installment of the AJKD Atlas of Renal Pathology (freely available).

– Post prepared by Timothy Yau, AJKD Social Media Editor. Follow him @Maximal_Change.

 

To view Zhang et al (subscription required), please visit AJKD.org.

Title: Heavy Chain Deposition Disease: Clinicopathologic Characteristics of a Chinese Case Series
Author: Y. Zhang, X. Li, D. Liang, F. Xu, S. Liang, X. Zhu, N. Zheng, X. Huang, Z. Liu, and C. Zeng
DOI: 10.1053/j.ajkd.2019.08.013

 

 

 

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