Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 1890
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

CASE REPORT Table of Contents  
Ahead of print publication
Heavy chain deposition disease in a case of clear cell renal cell carcinoma- A jack in the box


1 Department of Nephrology, IPGME and R and SSKM Hospital, Kolkata, West Bengal, India
2 Department of Pathology, IPGME and R and SSKM Hospital, Kolkata, West Bengal, India
3 Consultant, Renopath, Chennai, Tamil Nadu, India

Click here for correspondence address and email

Date of Submission22-Apr-2021
Date of Decision22-May-2021
Date of Acceptance03-Jun-2021
Date of Web Publication07-Jun-2022
 

   Abstract 


Renal cell carcinoma (RCC) is the most common subtype of adult renal tumors, and its detection rate in the early stages has been increased in the dawn of advanced imaging modalities. Nephrectomy is the mainstay of treatment; determination of tumor category and staging is the primary concern of oncopathologists. Non-neoplastic renal parenchyma is overlooked majority of times and thus misses the opportunity to detect concomitant medical renal diseases which also predict the renal outcome in the postoperative era. Although any kind of glomerular or extraglomerular pathology may be encountered, vascular changes in the form of arterionephrosclerosis are the commonest one. Here, we take the opportunity to report an unusual association of heavy chain deposition disease (HCDD) with clear cell subtypes of renal cell carcinoma in a 48-year-old male of Indian ethnicity.

Keywords: Heavy chain deposition disease, medical renal disease, renal cell carcinoma


How to cite this URL:
Kumar A, Roychowdhury A, Sengupta M, Basu K, Abraham A, Chatterjee U, Mukherjee S. Heavy chain deposition disease in a case of clear cell renal cell carcinoma- A jack in the box. Indian J Pathol Microbiol [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=346842





   Introduction Top


Primary renal tumors account for 2%–3% of all human malignancy, and the major subtype is renal cell carcinoma (RCC).[1] The advent of newer imaging modalities contributes to early detection and prompts removal of the tumor either as partial or total nephrectomy. During the evaluation of resected specimens, oncopathologists check all the pathological parameters enlisted in the standard protocol for reporting such as histological subtypes, grade, stage, etc.[2] The majority of the times peritumoral and distant renal parenchyma is overlooked and the opportunity to identify concurrent familiar or unfamiliar medical renal diseases is missed. Bijol et al.[3] stated that more than 60% of nephrectomy specimens had pathology in non-neoplastic renal parenchyma which is responsible for the deterioration of renal function disproportionate to nephron loss in the postoperative era. Vascular pathology related to hypertension was most commonly encountered followed by diabetic kidney disease.[4]

To the best of our knowledge, this is one of the first reports demonstrating concurrent heavy chain deposition disease (HCDD) with clear cell subtypes of renal cell carcinoma in a 48- year-old male of Indian ethnicity.


   Case Report Top


The present case was a 48-year-old nondiabetic, nonhypertensive male of Indian ethnicity. The patient was a chronic smoker and alcoholic. He was referred to us with anuria, anorexia, and recurrent vomiting for the last 2 days from a peripheral health center where he was treated for gradually progressive body swelling and a decrease in urine output for the last 3 months. Anasarca was not associated with orthopnea, fever, rash, mucosal ulcer, or arthralgia. No neurological symptoms such as headache, visual disturbances, psychosis, or seizures had been reported. General physical examination showed pallor and anasarca with pitting edema. His pulse rate was 94 beats per min, and his blood pressure was 130/90 mm of Hg. The respiratory rate was documented as 18 breaths per min. Systemic examination revealed pleural effusion, ascites, and mild pericardial effusion. Pleural fluid analysis revealed a transudative nature with protein of 1.6 mg/dL and sugar of 116 mg/dL. Adenosine deaminase levels (7 U/L) were within the normal range. Laboratory workup revealed abnormal renal function with the rapid rise of creatinine from 1.04 mg/dL to 14.5 mg/dL within 3 days. Urine examination revealed nephrotic-range proteinuria and 30–35 (mostly dysmorphic) red blood cells/high power field magnification. Bence Jones proteins were absent. Twenty-four-hour urine proteins were 7.2 g. His serum protein was 5.0 g/dL with serum albumin of 2.2 g/dL. Fasting and postprandial blood sugars were within normal limits. Liver function tests were within normal limits, and coagulation workup revealed a prothrombin index of 100%. The lipid profile showed a serum total cholesterol of 334 mg/dL. Hemogram showed hemoglobin of 8.2 g/dL, a total leukocyte count of 10 × 109/L with a normal differential count, and platelets of 1.51 × 109/L. Serum complement levels were normal, and his ANA hep 2, C ANCA, P ANCA, MPO, and PR3 titers were negative. Serum electrophoresis did not show any “M-band.” Human immunodeficiency virus, hepatitis B surface antigen, and antihepatitis C virus antibodies were negative. Ultrasound examination revealed normal-sized kidneys (right kidney 10.5 cm and left kidney 9.5 cm) with mildly raised cortical echo texture but maintained cortico-medullary differentiation. However, there was a 5 × 4.6 cm heterogenous hypoechoic space-occupying lesion (SOL) in the upper pole of the left kidney with increased vascularity. Contrast-enhanced computer tomography (CECT) of the kidney and urinary bladder showed a well-defined SOLs of size about 53 mm × 53 mm having heterogeneous enhancement in the upper pole of the left kidney.

Under ultrasound guidance, renal biopsy was performed. Two tissue cores were obtained and delivered into two separate containers (buffered formalin and cold normal saline) for both light microscopic and immunofluorescence examination. For light microscopic evaluation, two trained neuropathologists examined four separately stained sections according to the standard protocol [Hematoxylin and eosin (H and E), periodic acid-Schiff (PAS), silver methanamine (SM), and Masson Trichrome (MT) stains.] Frozen sections were performed for immunofluorescence examination. Total twenty-nine glomeruli were identified among which none were globally sclerosed. There was nodular mesangial expansion in all glomeruli. The nodules were PAS-positive, equivocal on the silver stain, and blue on the trichrome stain. Congo red–stained section was noncontributory. A mild increase in mesangial cellularity was also noted in all glomeruli. There were no spikes or double contouring of the glomerular basement membrane. Epithelial proliferation was identified in two glomeruli. No significant inflammatory infiltrate or fibrosis was seen in the interstitium. There was tubular epithelial cell injury. The vascular compartment was unremarkable. On immunofluorescence examination, a total of nine glomeruli were examined and revealed negative expression for IgA, IgM, C3c, C1q, kappa, and lambda. Glomerular and tubular basement membranes showed intense (3+) linear positivity for IgG only [Figure 1] and [Figure 2]. Final impression was nodular glomerulosclerosis with IgG restriction consisting with heavy chain deposition disease (HCDD).
Figure 1: Kidney biopsy finding. (a) Light microscopy- renal cortex showed two glomeruli with nodular mesangial expansion. (H and E; 100×). (b) Mesangial nodules were PAS-positive (Periodic acid-Schiff stain; 200×). (c) Mesangial nodules were less argyrophilic (Silver methanamine stain; original magnification 400×). (d) Mesangial nodules were blue. (Masson Trichrome stain, 200×)

Click here to view
Figure 2: (a) Immunofluorescence microscopy (fluorescein isothiocyanate–conjugate antisera to gamma-heavy chain, original magnification, 200×). Linear deposits in the mesangial, along the glomerular basement membrane. (b and c) No significant staining was observed with kappa and lambda light chains. (d) Tubular basement membranes showed linear positivity. (fluorescein isothiocyanate–conjugate antisera to gamma-heavy chain, original magnification, 200×)

Click here to view


In view of SOL in the left kidney with features in CECT suggestive of malignancy, the patient underwent radical nephrectomy of the left kidney. Specimens of the left kidney measured 12 × 8 × 5 cm3 with one well-circumscribed mass measuring 5 cm across. Histopathological examination of the growth revealed histological features consisting with clear cell renal cell carcinoma. The nuclear grade was grade II, and tumor stage was T2N0MX. Surrounding non-neoplastic renal parenchyma showed light microscopic features similar to native renal biopsy from the right kidney. Nodular glomerulosclerosis with fibrocellular crescents was the pattern of injury [Figure 3]. Paraffin immunofluorescence after proteinase digestion revealed only heavy chain (IgG) deposition along the glomerular and tubular basement membrane. All findings were re-evaluated by another experienced nephropathologist.
Figure 3: (a) Histopathological examination revealed clear cell renal cell carcinoma separated from non-neoplastic parenchyma by compressed renal capsule. (H and E; 100×) Inset showed hypoechoic space-occupying lesion on ultrasonography examination. (b-d) showed surrounding non-neoplastic renal parenchyma revealing nodular glomerulosclerosis with fibrocellular crescents. (Periodic acid-Schiff and Silver methanamine stain; 200×)

Click here to view


The detailed postoperative radiological evaluation did not reveal any lytic bony lesions or lymphadenopathy. Bone marrow examination revealed 05% plasma cells only. The patient remained dialysis-dependent and had expired 1 month after admission due to sepsis.


   Discussion Top


Evaluation of nontumor renal parenchyma plays a crucial role in prognostication of nephrectomized patients. It is essential to examine all four compartments of the kidney including glomerulus, tubules, interstitium, and vessel similar to medical renal biopsy assessment which demands additional stains and tests such as paraffin and immunofluorescence. Previously, several authors have attempted to establish the need for the incorporation of non-neoplastic kidney disease as a checklist in the standard reporting protocol.[1],[2],[3],[4]

Histopathological findings are subdivided into three broad categories by Truong et al.[5] Subtype I includes chronic tubulointerstitial changes characterized by interstitial fibrosis and tubular atrophy accompanied by glomerulosclerosis in peritumoral parenchyma. These changes are attributed to the compression effect of expanding tumor mass. A comparative analysis of histological parameters of peritumoral and distant parenchyma showed similar observations.[6] Subtype II comprises renal parenchymal injury due to obstruction of pyelocaliceal system along with superimposed bacterial infection. The degree of renal parenchymal changes varies from mild scarring to reflux nephropathy. These two spectrums of changes are predominantly restricted to a tubulointerstitial compartment with milder involvement of glomerular and vascular alcove. Subtype III shows uniform pathology in distant as well as in the vicinity. Critical appraisal of non-neoplastic renal parenchyma helps to identify the medical renal diseases. Moreover, it is also a tool for assessment of the status of the remaining nephron of the solitary preserved kidney which predicts the long-term prognosis of the patient.

A wide range of glomerular and extraglomerular pathologies has been documented along with renal cell carcinoma. The existence of some medical renal diseases can be explained by certain age of occurrence, but the majority are co-incidental. Being the established contributing factors, diabetic nephropathy is most commonly encountered followed by hypertensive vascular changes. Even the presence of mild host-related changes negatively impact the clinical outcome of the patient with one kidney and demand proper management.

Both nonimmune (minimal change disease, focal segmental glomerulosclerosis, thrombotic microangiopathy) and immune complex–mediated (membranous nephropathy, membranoproliferative glomerulonephritis, and IgA nephropathy) glomerular injuries are detected incidentally.[3] In a large series, non-neoplastic renal pathology was encountered in one in every ten tumor nephrectomy specimens.[7] In our report, identification of an unfamiliar renal disease also supports this concern. During this period, there were 5536 native and allograft kidney biopsies performed in our tertiary care center, among which 19 cases were reported as light-chain deposition disease (LCDD) in comparison to one case of heavy chain deposition disease (HCDD) which was concurrently identified in a patient with renal cell carcinoma. We have made an attempt to report this entity due to its rareness in our population. From our country, Rane et al.[8] reported one case from their archival that showed a similar presentation but no association with renal malignancy. Heavy chain deposition disease is the least frequent member of non- amyloidotropic monoclonal immunoglobulin deposition disease. The largest series with 15 cases was reported by Bridoux et al.[9] who describe the comprehensive analysis of clinical, histopathological, and molecular details of this rare entity. Although nodular glomerulosclerosis is the characteristic pattern of glomerular injury, a variable percentage of extra capillary proliferation is exclusively documented in α3 heavy chain deposition.[9] We found similar glomerular changes in IgG heavy chain deposition.

In conclusion, fatal consequence in this patient was attributed to medical renal disease as the tumor was well-differentiated and in early stage. Thus, this case highlighted the importance of the incorporation of non-neoplastic parenchymal pathology in the standard reporting protocol of renal malignancy. Heavy chain deposition disease is a rare form of monoclonal immunoglobulin deposition disease. Co-occurrences with clear cell subtype of renal cell carcinoma demand future research on cancer cell–derived immunoglobulin production.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Noroozinia F, Makhdoomi K, Behnamfard H, Mohammadi S, Dindarian S, Bagheri M, et al. The pathological evaluation of nonneoplastic kidney disorder in tumor nephrectomy specimens. Saudi J Kidney Dis Transpl 2018;29:586-90.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Henriksen KJ, Meehan SM, Chang A. Nonneoplastic kidney diseases in adult tumor nephrectomy and nephroureterectomy specimens: Common, harmful, yet underappreciated. Arch Pathol Lab Med 2009;133:1012-25.  Back to cited text no. 2
    
3.
Bijol V, Mendez GP, Hurwitz S, Rennke HG, Nosé V. Evaluation of the nonneoplastic pathology in tumor nephrectomy specimens: Predicting the risk of progressive renal failure. Am J Surg Pathol 2006;30:575-84.  Back to cited text no. 3
    
4.
Wee JW, Kang HR, Kwon SH, Jeon JS, Han DC, Jin SY, et al. Clinical value of pathologic examination of non-neoplastic kidney in patients with upper urinary tract malignancies. Korean J Intern Med 2016;31:739-49.  Back to cited text no. 4
    
5.
Truong LD, Shen SS, Park MH, Krishnan B. Diagnosing nonneoplastic lesions in nephrectomy specimens. Arch Pathol Lab Med 2009;133:189-200.  Back to cited text no. 5
    
6.
Wang X, Liu Q, Kong W, Huang J, Chen Y, Huang Y, et al. Pathologic analysis of non-neoplastic parenchyma in renal cell carcinoma: A comprehensive observation in radical nephrectomy specimens. BMC Cancer 2017;17:900.  Back to cited text no. 6
    
7.
Henriksen KJ, Meehan SM, Chang A. Non-neoplastic renal diseases are often unrecognized in adult tumor nephrectomy specimens: A review of 246 cases. Am J Surg Pathol 2007;31:1703-8.  Back to cited text no. 7
    
8.
Rane S, Rana S, Mudrabettu C, Jha V, Joshi K. Heavy-chain deposition disease: A morphological, immunofluorescence and ultrastructural assessment. Clin Kidney J 2012;5:383-9.  Back to cited text no. 8
    
9.
Bridoux F, Javaugue V, Bender S, Leroy F, Aucouturier P, Debiasis-Delpech C, et al. Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management. Kidney Int 2017;91:423-34.  Back to cited text no. 9
    

Top
Correspondence Address:
Moumita Sengupta,
244 AJC Bose Road, Kolkata - 700 020, West Bengal
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_397_21



    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

Top
 
  Search
 
  
  
 Article in PDF
     Search Pubmed for
 
    -  Kumar A
    -  Roychowdhury A
    -  Sengupta M
    -  Basu K
    -  Abraham A
    -  Chatterjee U
    -  Mukherjee S


    Abstract
   Introduction
   Case Report
   Discussion
    References
    Article Figures

 Article Access Statistics
    Viewed268    
    PDF Downloaded16    

Recommend this journal