Illuminating Renal Pathology

Though we’re all born with two kidneys, German surgeon Gustav Simon discovered that humans can live a perfectly normal life with just one, performing the first successful nephrectomy in a human in the 18th century (though only after success with animal experimentation). And thus, removal of the entire kidney became the main option for renal cancer treatment over the next century.

In recent years, a paradigm shift towards more conservative nephron-sparing procedures, such as ablation techniques or partial nephrectomy, has occurred for two main reasons. First, not all kidney tumors are bad; some are benign, low-stage or low-grade. Second, and more importantly, there is a greater survival benefit in preserving kidney function. Currently, urologists and oncologists are gaining the upper hand against kidney cancer. For example, in the USA, there are more than 65,000 new diagnoses every year, and earlier detection has resulted in substantial stage migration. Nowadays, over 60 percent of kidney cancers are stage one, with a five-year survival that exceeds 95 percent. Even though the oncologic outcomes are similar, nephron-sparing surgery results in improved outcomes compared with radical nephrectomy because of its superior preservation of renal function.

The classification of renal tumors has also evolved during the last three decades. One major advancement is the emergence of several benign and low-grade neoplastic entities. In 2010, the International Society of Urological Pathology conducted a consensus conference in Vancouver, Canada, to update the 2004 World Health Organization (WHO) renal tumor classification guidelines. This schema became the basis for the new 2016 WHO classification of renal tumors. The nosologic innovations are important for pathologists because some newer entities, which under the old system would have been considered renal cancers, are now excluded due to their favorable outcomes. Some examples include clear cell papillary renal cell carcinoma, multicystic clear cell neoplasm of low malignant potential, and hybrid oncocytic chromophobe tumor. The traditionally known benign kidney tumors, such as renal oncocytoma, metanephric adenoma, and the now unified cystic nephroma-mixed epithelial stromal tumor, remain important for pathologists involved in renal cancer diagnosis.

There is a known association between chronic kidney disease, especially end-stage renal disease, and renal cell carcinoma. Given that hypertension, diabetes, obesity and smoking are all independent risk factors for this cancer, their respective non-neoplastic renal injuries are commonplace in kidney cancer patients. Of the 14 pathologic parameters required by the College of American Pathologists in all synoptic reports for kidney cancer, we can now reasonably argue that the status of the non-neoplastic kidney parenchyma is the most important in T1 tumors – something that is definitely true for patients with benign tumors, which comprise approximately 25 percent of small renal masses.

For example, we recently encountered a pauci-immune crescentic glomerulonephritis in a 60-year-old female with diabetes who underwent radical nephrectomy for a 3.5 cm tumor – a T1a clear cell renal cell carcinoma. Under current American Urological Association guidelines for the management of small renal masses, nephron-sparing surgery is the preferred option. Renal function preservation is especially important for this patient, as most studies of T1a renal cell carcinomas demonstrate a five-year survival rate that approaches 100 percent. The patient is cured of her cancer, but the non-neoplastic kidney disease will result in end-stage kidney disease that will be fatal. This outcome would be the same even if only diabetic nephropathy was present, which occurs in approximately one out of every 12 kidney resection specimens in the US.

In addition, several studies have discovered that non-neoplastic kidney diseases can be observed in at least 15 percent of tumor nephrectomy specimens, and that 60 to 88 percent of these diagnoses are overlooked by practicing surgical pathologists. In fact, at least 65 percent of US pathology residency training programs did not offer formal exposure to renal pathology until the Accreditation Council of the Graduate Medical Education added it as a requirement. Just as in cancer, early detection of non-neoplastic renal diseases is essential for optimal clinical management – and that demands an accurate evaluation from pathologists.