Kidney tumor
General
Nonneoplastic kidney
Authors: Yong Jia, M.D., Deepak K. Pruthi, M.D., M.Sci.-T.S., Miao (Vivian) Lu, M.D., Ian W. Gibson, M.B.Ch.B., M.D.
Editorial Board Member: Debra L. Zynger, M.D.
Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.
Last author update: 12 August 2021
Last staff update: 12 August 2021
Copyright: 2021, PathologyOutlines.com, Inc.
PubMed Search: Nonneoplastic kidney [TIAB]
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Immunofluorescence description | Immunofluorescence images | Electron microscopy description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Jia Y, Pruthi DK, Lu M, Gibson IW. Nonneoplastic kidney. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumornonneoplastic.html. Accessed January 3rd, 2025.
Definition / general
- Nonneoplastic kidney (NNK) in tumor nephrectomies
- Medical kidney disease
Essential features
- Evaluation for medical renal disease should be performed in every tumor nephrectomy and included in the synoptic report (as per College of American Pathologists [CAP] kidney cancer dataset and in the American Urological Association [AUA] renal mass guidelines)
- Medical kidney disease is common and often unrecognized in tumor nephrectomy specimens (Am J Surg Pathol 2007;31:1703, Arch Pathol Lab Med 2009;133:1012, Arch Pathol Lab Med 2009133:189, Adv Anat Pathol 2010;17:235, Ann Diagn Pathol 2013;17:176)
- Medical conditions that commonly affect the kidney, such as diabetes and hypertension, are risk factors for renal neoplasia
- Nephrectomy is a risk factor for subsequent chronic kidney disease (CKD) (Am J Surg Pathol 2006;30:575, Adv Chronic Kidney Dis 2014;21:91)
- Severity of chronic renal parenchymal damage is prognostically important for postoperative risk of progressive renal insufficiency (Mayo Clin Proc 2000;75:1236, Arch Pathol Lab Med 2013;137:531, Am J Clin Pathol 2019;151:108, Semin Nephrol 2020;40:69)
ICD coding
Epidemiology
- Medical kidney disease is common and often unrecognized in adult tumor nephrectomy specimens
- Chronic kidney disease stage 3 or above involves up to 26% of renal cell carcinoma (RCC) patients even before nephrectomy (Lancet Oncol 2006;7:735)
- Depending on baseline medical comorbidity, up to 36% of total nephrectomy and 26% of partial nephrectomy patients develop chronic kidney disease (≥ 3) (Mayo Clin Proc 2000;75:1236, J Urol 2004;171:120, Lancet Oncol 2006;7:735, World J Urol 2013;31:1531, World J Urol 2013;31:835, J Urol 2020;203:475)
- Mortality is more strongly associated with estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m² (J Urol 2020;203:475)
Pathophysiology
- Renal function decline due to nephron loss and consequent hyperfiltration injury in remaining nephrons after nephrectomy (J Am Soc Nephrol 2020;31:1107, Nat Rev Nephrol 2014;10:135)
- Progressive diabetic glomerular disease and hypertensive vascular disease (J Am Soc Nephrol 2020;31:1107, Nat Rev Nephrol 2014;10:135)
Etiology
- Risk factors:
- Diabetes
- Hypertension
- Smoking
- Aging
Clinical features
- Often asymptomatic
- Can have normal creatinine or estimated glomerular filtration rate
- May have chronic kidney disease
- Can have concomitant microhematuria or proteinuria
Diagnosis
- Suggested features to routinely include in kidney cancer synoptic report (College of American Pathologists: Protocol for the Examination of Resection Specimens from Patients with Invasive Carcinoma of Renal Tubular Origin [Accessed 14 April 2021])
- Glomerular:
- Estimate percentage of global glomerulosclerosis
- Specific changes, such as nodular glomerulosclerosis and focal segmental glomerulosclerosis
- Presence of Tamm-Horsfall protein in glomerular Bowman spaces suggests obstructive nephropathy
- Tubulointerstitial:
- Estimate percentage of cortical interstitial fibrosis and tubular atrophy and associated interstitial inflammation
- Presence of tubular Tamm-Horsfall protein casts and neutrophilic casts
- Vascular:
- Severity of arteriosclerosis of intrarenal arteries
- Severity of arteriolar nodular hyalinosis
- Glomerular:
- When features suggestive of diabetic nephropathy or hypertensive vascular disease are identified, clinicopathological correlation is indicated
- There may be insufficient tissue to fully evaluate nonneoplastic kidney in partial nephrectomies with minimal surrounding renal parenchyma, due to glomerular and tubulointerstital scarring from adjacent tumor compression; nodular diabetic glomerulosclerosis lesions can still be identified in the compressed scarred nonneoplastic renal parenchyma immediately surrounding the renal neoplasm and chronic vascular disease can still be assessed (World J Urol 2013;31:1531, World J Urol 2013;31:835)
- If significant chronic renal parenchymal damage is present, recommend careful follow up of postoperative renal function and suggest nephrology consultation
Radiology description
- Renal scintigraphy (rare usage outside transplant evaluation)
Prognostic factors
- Progressive medical kidney disease in nonneoplastic kidney is a major determinant for the longterm survival of patients with renal tumors, especially those with early stage tumors
Treatment
- Early detection of a nonneoplastic kidney disease provides better opportunities for early medical intervention
Gross description
- Sample at least 1 block of nonneoplastic renal cortex and medulla from as far distant from the tumor as possible to avoid nonspecific peritumoral compression related chronic changes (College of American Pathologists: Protocol for the Examination of Resection Specimens from Patients with Invasive Carcinoma of Renal Tubular Origin [Accessed 14 April 2021])
- For partial nephrectomy specimens, CAP protocol recommends 5 mm as minimum sufficient nonneoplastic renal parenchyma in order to evaluate nonneoplastic kidney
- If patient has known history of chronic renal insufficiency or significant proteinuria at time of surgery, consider sampling renal cortex for immunofluorescence (fresh frozen tissue) and electron microscopy studies
Microscopic (histologic) description
- Periodic acid-Schiff (PAS) and Masson trichrome stains are recommended as routine for evaluation of the nonneoplastic kidney
- Some histologic findings might be subtle and easily missed by H&E stain alone; special stains become extremely important to help identify the presence and severity of pathological changes
- PAS is very helpful for examining the glomerular mesangium and the basement membranes of the glomerular capillaries and tubules as well as for identifying nodular hyaline arteriolosclerosis
- Trichrome stains show the severity of interstitial fibrosis and vascular intimal fibrosis
- In selected cases, Jones methanamine silver (PAMS) and Congo red amyloid stains may also be helpful
- Consultation with specialist nephropathologist is recommended
- Specific medical renal pathological findings in nonneoplastic kidney
- Among the medical renal diseases, diabetic nephropathy and arterionephrosclerosis / hypertensive nephropathy are 2 of the most common findings, which may be missed when only an H&E stain is reviewed by a pathologist not familiar with medical renal pathology
- Note: listed below are the summarized microscopic findings of common medical renal diseases in nonneoplastic kidney; for detailed histologic descriptions of each disease entity, refer to kidney nontumor chapter, Fogo: Diagnostic Atlas of Renal Pathology, 3rd Edition, 2016 and Jennette: Heptinstall's Pathology of the Kidney, 7th Edition, 2014
- Diabetic nephropathy
- Diffuse and nodular mesangial matrix expansion, large Kimmelstiel-Wilson PAS positive mesangial nodules, glomerular capillary hyaline insudation and glomerular basement membrane (GBM) thickening
- Hyaline capsular drops on Bowman capsules
- Afferent and efferent arteriolar nodular hyaline arteriolosclerosis
- Arterionephrosclerosis / hypertensive nephropathy
- Arterial intimal fibrosis, with reduplications of internal elastic lamina
- Afferent arteriolar nodular hyaline arteriolosclerosis
- Focal segmental glomerulosclerosis
- Segmental mesangial matrix expansion with obliteration of capillary loops, tuft to capsule adhesions and hyalinosis lesions
- Secondary hilar focal segmental glomerulosclerosis most common
- Collapsing glomerulopathy features with prominence of glomerular epithelial cells suggests APOL1 G1 / G2 risk alleles
- Atheroembolic disease
- Intrarenal arteries with luminal cholesterol clefts, macrophage and multinucleated giant cell reaction or embedded within intimal fibrosis
- Obstructive nephropathy and pyelonephritis
- Abundant PAS positive Tamm-Horsfall protein casts in tubules and Tamm-Horsfall protein within glomerular Bowman spaces
- Tubular neutrophilic casts indicate active pyelonephritis
- Periglomerular fibrosis and chronic tubulointerstitial scarring
- Common with obstructing urothelial carcinoma of renal pelvis / ureter
- Glomerulonephritis
- Membranous nephropathy, primary or secondary to neoplasm, with diffuse glomerular capillary wall thickening, epimembranous spikes on PAMS stain
- Proliferative glomerulonephritis with focal or diffuse mesangial or endocapillary proliferation, focal necrotizing or crescentic glomerular injury
- Suspicion of membranous nephropathy or proliferative IgA nephropathy can be further investigated by immunofluorescence and electron microscopy studies
- Thrombotic microangiopathy (TMA)
- Acute TMA with glomerular capillary and arteriolar fibrin thrombi, arterial endothelial swelling, intimal edema and fibrinoid injury
- Chronic TMA with glomerular capillary glomerular basement membrane reduplications and arterial "onion skin" proliferative change
- Possible TMA changes secondary to chemotherapy for neoplasm
- Renal amyloidosis
- Glomerular mesangial and capillary wall, tubulointerstitial and vascular extracellular eosinophilic and congophilic amyloid deposition
- If positive for amyloid, typing of the amyloid requires further immunohistochemical or mass spectroscopy studies
- Lymphoma infiltrates
- Monotonous, dense, small lymphocytic atypical interstitial infiltration may warrant immunophenotyping for possible involvement by small lymphocytic lymphoma / chronic lymphocytic leukemia
- Diabetic nephropathy
Microscopic (histologic) images
Contributed by Ian W. Gibson, M.B.Ch.B., M.D.
Kimmelstiel-Wilson nodules, hyaline arteriolosclerosis
Nodular hyaline arteriolosclerosis
Organized atheromatous embolism
Tubular neutrophilic casts
Monotonous dense small lymphocytes
Immunofluorescence description
- Immunofluorescence staining of paraffin sections with pronase digestion for immunoglobulins and complement components may be helpful for investigation of possible glomerulonephritis (e.g. IgA nephropathy, membranous nephropathy, including PLA2R staining)
Immunofluorescence images
Contributed by Ian W. Gibson, M.B.Ch.B., M.D.
PAS, PAMS and
immunofluorescence
stains
Electron microscopy description
- Electron microscopy of reprocessed paraffin block material may be helpful for further investigation of possible glomerular disease
Sample pathology report
- Left kidney, nonneoplastic kidney (block #):
- Glomerular: approximately 10% global glomerulosclerosis; nonsclerotic glomeruli show nodular glomerulosclerosis with nodular mesangial matrix expansion and scattered focal segmental glomerulosclerosis (see comment)
- Tubulointerstitial: patchy chronic tubulointerstitial damage affecting approximately 20% of cortex
- Vascular: moderate arteriosclerosis of intrarenal arteries; widespread severe nodular and focally circumferential hyaline arteriolosclerosis (see comment)
- Comment: The nodular glomerulosclerosis and severe hyaline arteriolosclerosis suggest diabetic related nephropathy, if clinically appropriate. Clinicopathological correlation and close follow up of postoperative renal function is recommended. Nephrology consultation should be considered.
Differential diagnosis
- Please refer to kidney nontumor chapter for differential diagnosis of each entity
Board review style question #1
A 75 year old man underwent radical nephrectomy for renal pelvic urothelial carcinoma. Nonneoplastic kidney tissue shows the above changes. Which of the following medical renal diseases should be considered?
- Arteriosclerosis
- Diabetic nodular glomerulosclerosis
- Focal segmental glomerulosclerosis
- Membranous nephropathy
Board review style answer #1
Board review style question #2
In order to evaluate nonneoplastic kidney in partial nephrectomy specimen, what is the minimal size of sufficient nonneoplastic renal parenchyma according to CAP protocol?
- 1 mm
- 3 mm
- 5 mm
- 1 cm
- 2 cm
Board review style answer #2
