Collagen type III glomerulopathy in a tumour nephrectomy specimen: beware of a coincidental medical kidney disease

Abstract

Coincidental medical kidney disease in tumour nephrectomy specimens is not uncommon and may have a significant impact on patient outcomes.1Henriksen K.J. Meehan S.M. Chang A. Nonneoplastic kidney diseases in adult tumor nephrectomy and nephroureterectomy specimens: common, harmful, yet underappreciated.Arch Pathol Lab Med. 2009; 133: 1012-1025Crossref PubMed Google Scholar,2Henriksen K.J. Meehan S.M. 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: 1703-1708Crossref PubMed Scopus (65) Google Scholar However, these specimens are usually not processed in a way optimal for evaluation of medical kidney disease which may lead to misdiagnosis or underdiagnosis.1Henriksen K.J. Meehan S.M. Chang A. Nonneoplastic kidney diseases in adult tumor nephrectomy and nephroureterectomy specimens: common, harmful, yet underappreciated.Arch Pathol Lab Med. 2009; 133: 1012-1025Crossref PubMed Google Scholar,2Henriksen K.J. Meehan S.M. 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: 1703-1708Crossref PubMed Scopus (65) Google Scholar We report a case of type III collagen glomerulopathy in a nephrectomy specimen and discuss a practical approach to evaluate these specimens for medical kidney disease. An 82-year-old female presented for left nephrectomy. She had kidney failure requiring dialysis in the year prior and a recent diagnosis of squamous cell carcinoma of the left renal pelvis. The kidney failure was presumed to be secondary to hypertension. Other comorbidities included heart failure, cerebrovascular accident, rheumatoid arthritis, and polymyalgia rheumatica. Serological evaluation was non-contributory. A left radical nephrectomy was performed. Gross examination revealed a 6.3 cm mass in the renal pelvis, consistent with an invasive urothelial carcinoma with extensive squamous differentiation, without involvement of the kidney parenchyma. The uninvolved portion of the kidney revealed severe global glomerulosclerosis. Non-sclerotic glomeruli demonstrated moderate mesangial expansion by eosinophilic material, without mesangial or endocapillary hypercellularity. This material stained pale on periodic acid-Schiff (PAS) and Jones methenamine silver (JMS) and blue on trichrome stains (Fig. 1A–C). The glomerular basement membranes demonstrated segmental duplication with interposition of the PAS and JMS pale material. A few glomeruli demonstrated segmental sclerosis. Severe tubulointerstitial scarring, severe arterio- and arteriolosclerosis were also present. Several ancillary studies were performed. Mesangial material was negative for Congo red stain, negative for DnaJ heat shock protein family member B9, a marker of fibrillary glomerulonephritis, by immunostain, and also negative for IgG, IgM, IgA, κ, and λ by immunofluorescence performed on formalin-fixed paraffin-embedded (FFPE) tissue after pronase digestion. However, electron microscopy performed on deparaffinised FFPE tissue demonstrated mesangial curvilinear fibrils without involvement of the glomerular basement membranes (Fig. 1D). These fibrils were bundled together focally with frayed ends (Fig. 1D, inset). Taken together, these findings were diagnostic of type III collagen (collagenofibrotic) glomerulopathy (T3CG). We report the first case of T3CG in a tumour nephrectomy specimen. T3CG, first described by Arakawa et al. in 1979, is characterised by accumulation of type III collagen in the mesangium and subendothelial areas.3Kurien A.A. Larsen C.P. Cossey L.N. Collagenofibrotic glomerulopathy.Clin Kidney J. 2015; 8: 543-547Crossref PubMed Scopus (6) Google Scholar,4Wilson A.V. Costigliolo F. Farris A.B. et al.Collagen type III glomerulopathy.Kidney Int Rep. 2021; 6: 1738-1742Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Patients with T3CG typically present with chronic kidney disease, with variable proteinuria and haematuria.3Kurien A.A. Larsen C.P. Cossey L.N. Collagenofibrotic glomerulopathy.Clin Kidney J. 2015; 8: 543-547Crossref PubMed Scopus (6) Google Scholar Their biopsies demonstrate mesangial expansion by PAS and JMS-pale material, unlike diabetic nephropathy in which the mesangium stains strongly positive for PAS and JMS. Histological differential is broad and includes other entities with PAS and JMS pale mesangial expansion, such as amyloidosis, fibrillary glomerulonephritis, light chain deposition disease, thrombotic microangiopathy, and other rare entities.3Kurien A.A. Larsen C.P. Cossey L.N. Collagenofibrotic glomerulopathy.Clin Kidney J. 2015; 8: 543-547Crossref PubMed Scopus (6) Google Scholar,4Wilson A.V. Costigliolo F. Farris A.B. et al.Collagen type III glomerulopathy.Kidney Int Rep. 2021; 6: 1738-1742Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Diagnosis of T3CG is confirmed by the negative routine immunofluorescence and demonstration of mesangial collagen bundles on electron microscopy, unlike Nail-Patella syndrome (NPS) in which collagen fibrils involve the glomerular basement membranes. In addition, those with NPS typically present in childhood with extrarenal findings, such as patellar aplasia, exostoses of the iliac crests, or poorly developed nails, unlike our patient. At some centres, an immunostain for type III collagen may also be available to confirm the diagnosis.4Wilson A.V. Costigliolo F. Farris A.B. et al.Collagen type III glomerulopathy.Kidney Int Rep. 2021; 6: 1738-1742Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Pathogenesis and optimal treatment for T3CG remain unknown. While T3CG is rare, this report highlights the importance of assessing for coincidental medical kidney disease in tumour nephrectomy specimens and offers several practical lessons. First, surgical pathologists should review the medical history of patients undergoing tumour nephrectomy for unexplained chronic kidney disease (as in our patient) or systemic diseases associated with kidney disease, such as diabetes, monoclonal gammopathy, and hepatitis C virus. In such cases, more thorough evaluation for medical kidney disease, possibly including PAS and JMS stains,2Henriksen K.J. Meehan S.M. 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: 1703-1708Crossref PubMed Scopus (65) Google Scholar should be performed. Second, surgical pathologists should be familiar with the morphology of diabetic nephropathy, the most common coincidental finding in tumour nephrectomy specimens.2Henriksen K.J. Meehan S.M. 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: 1703-1708Crossref PubMed Scopus (65) Google Scholar Lastly, surgical pathologists should have a low threshold to obtain medical renal consultation in cases that are not classic for diabetic nephropathy (i.e., cases without a history of diabetes or cases with PAS and JMS pale mesangial expansion or hypercellular glomeruli, etc), since such cases may require additional work-up, including immunofluorescence and electron microscopy, both of which can be performed on FFPE tissue at some centres. In summary, we present a case of T3CG in a tumour nephrectomy specimen. Evaluation of the tumour is important, but so is the uninvolved kidney.