Collecting Duct Carcinomas

Study Notes

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.