Collecting Duct Carcinomas

Small Collecting Duct Carcinomas

• Can arise in a medullary pyramid, but most are large, infiltrative masses, and extension into the cortex is common.
• Consist of an admixture of dilated tubules and papillary structures typically lined by a single layer of cuboidal cells, often creating a cobblestone appearance.
• Usually have high grade, advanced stage, and are unresponsive to conventional therapies.

Clinical Presentations

• Many renal masses remain asymptomatic and nonpalpable until they are locally advanced.
• More than 60% of RCCs are now detected incidentally.
• Symptoms associated with RCC can be due to local tumor growth, hemorrhage, paraneoplastic syndromes, or metastatic disease.
• Classic triad of flank pain, gross hematuria, and palpable abdominal mass is now rarely seen.

Clinical Presentations

• Flank pain is usually due to hemorrhage and clot obstruction, or locally advanced or invasive disease.
• Other symptoms: Hematuria, Abdominal mass, Perinephric hematoma.
• Obstruction of the inferior vena cava can cause bilateral lower extremity edema or right-sided varicocele.

Paraneoplastic Syndromes

• Found in 10% to 20% of patients with RCC.
• More common in metastatic disease and less common in patients with small, incidental renal masses.
• The most common syndrome is elevated erythrocyte sedimentation rate, which accounts for more than 50%.
• Other syndromes: producing 1,25-dihydroxycholecalciferol, renin, erythropoietin, prostaglandins, parathyroid hormone–like peptides, lupus-type anticoagulant, human chorionic gonadotropin, insulin, and various cytokines and inflammatory mediators.

Etiology

• The majority of cases of RCC are sporadic; only 4% to 6% are believed to be familial.
• Smoking: well-established risk factor, with relative risks ranging from 1.4 to 2.5 compared with controls.
• Obesity: increased relative risk of 1.07 for each additional unit of body mass index.
• Hypertension: the third major causative factor for RCC.

Pathology

• Most RCCs are round to ovoid and circumscribed by a pseudocapsule of compressed parenchyma and fibrous tissue.
• No reliable histologic or ultrastructural criteria to differentiate benign from malignant renal epithelial tumors, except for oncocytomas and some small (≤5 mm) low-grade papillary adenomas.

Modified 2016 World Health Organization Classification of Renal Neoplasms

• Focus on adult neoplasms.

RCC Grading

• Grading based primarily on nuclear size and shape and the presence or absence of prominent nucleoli.

RCC Pathology

• All RCCs are, by definition, adenocarcinomas, derived from renal tubular epithelial cells.
• Most RCCs share ultrastructural features with normal proximal tubular cells and are believed to be derived from this region of the nephron.
• Chromophobe RCC, renal medullary carcinoma, and collecting duct carcinoma appear to be derived from more distal elements of the nephron.

Clear Cell Renal Cell Carcinoma

• The most common subtype, accounting for 70% to 80% of all RCCs.
• Typically yellow and highly vascular.
• Clear cells are typically round or polygonal with abundant cytoplasm containing glycogen, cholesterol, cholesterol esters, and phospholipids.
• Clear cell RCC has a worse prognosis compared with papillary type 1 or chromophobe RCC, but is more likely to respond to VEGF-targeted therapy, checkpoint inhibitors, or high dose IL-2.

Papillary Renal Cell Carcinoma

• The second most common histologic subtype, accounting for 10%–15% of all RCCs.
• Gross features: beige to white color, spherical boundary, and frequent hemorrhage, which may mimic cystic components radiologically.
• One unique feature: tendency toward multicentricity, which approaches 40%.
• More commonly occurs in patients with end-stage renal disease and acquired renal cystic disease.

Papillary Renal Cell Carcinoma

• Type 1 papillary RCC: consists of basophilic cells with scant cytoplasm.
• Type 2 papillary RCC: includes potentially more aggressive variants with eosinophilic cells and abundant granular cytoplasm.
• Type 1 papillary RCC carries a better prognosis than clear cell RCC, whereas type 2 papillary RCC is similar or worse than clear cell RCC.

Chromophobe Renal Cell Carcinoma

• Represents 3% to 5% of all RCCs and appears to be derived from the distal convoluted tubules.
• Commonly seen in the BHD syndrome, but most cases are sporadic.
• Localized chromophobe RCC has a better prognosis than clear cell RCC, but has a poor outcome in patients with sarcomatoid features or metastatic disease.
• Has the tendency of growing to large sizes, thus presenting at an earlier T stage.

Collecting Duct Carcinoma

• Carcinoma of the collecting ducts of Bellini is a relatively rare subtype of RCC, with a predictably poor prognosis.