• Clinical science

Renal cell carcinoma (Hypernephroma…)

Summary

Renal cell carcinoma (RCC), which arises from renal tubular epithelium, is the most common cause of renal malignancy in adults. While a fraction of cases of RCC occur in association with hereditary disorders, most cases are sporadic. Important risk factors for RCC include smoking, acquired cystic disease of the kidney, nephrolithiasis, and chronic acetaminophen use. Clinical features of RCC include hematuria, flank pain, a flank mass, anemia, and weight loss. Patients may also present with paraneoplastic manifestations such as hypercalcemia and hypertension. The most important initial test is a contrast CT of the abdomen. The treatment of choice is surgical resection. RCC is notoriously resistant to classical chemotherapeutic agents. Early stage RCC with tumor growth limited to the kidney has a very good prognosis.

Epidemiology

  • Most common malignancy of the renal parenchyma (85% of renal cancers in adults are RCC)
  • Sex: > (∼ 2:1)
  • Age of onset: 60–80 years

References:[1][2][3][4][5]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Most renal cell carcinomas occur sporadically. However, approx. 4% of renal cell carcinomas are associated with hereditary factors. In both forms, sporadic and hereditary RCCs, structural alterations of the short arm of chromosome 3 (3p) and subsequent alterations of the VHL gene are commonly found.

Risk factors for sporadic renal cell carcinoma

Hereditary renal cell carcinomas

Hereditary renal cell carcinomas are autosomal dominant and tend to affect patients at a younger age than sporadic renal cell carcinomas!

References:[6][1][7][8][2][3][4][5][9]

Pathophysiology

Type of RCC Relative frequency Cell of origin Cytogenetics Histology Prognosis
Clear cell RCC ∼ 80% Proximal convoluted tubule Mutation of the VHL gene on chromosome 3p
  • Polygonal cells with a clear, glycogen and/or lipid-filled cytoplasm that are arranged as cords or tubules (non-papillary growth)
  • Unifocal, unilateral growth
  • Measured prognosis
Papillary (chromophilic) RCC ∼ 10% Trisomy 7, trisomy 17, and loss of Y chromosome
  • Cuboidal, low columnar cells that grow in papillary formations
  • Bilateral, multifocal growth may occur.
  • Type 1 papillary RCC: measured prognosis
  • Type 2 papillary RCC: aggressive tumor with a poor prognosis
Chromophobic RCC ∼ 5% Intercalated cells of the cortical collecting duct Hypodiploidy
  • Excellent prognosis
Oncocytic RCC ∼ 5% Unknown
  • Originate from oncocytomas
  • Similar to chromophobic RCC except that there is no perinuclear halo and the cells occur as tumor nests
  • Excellent prognosis
Collecting duct carcinoma (Bellini duct carcinoma) ∼ 1% Medullary collecting duct Unknown
  • Aggressive tumor with a poor prognosis

A sarcomatoid pattern (containing foci of high-grade spindle cells), which can occur in any type of RCC, is associated with a poor prognosis.

References:[1][10][3][11][4][12][13][14][15]

Clinical features

Renal cell carcinomas are asymptomatic in the early stages. Patients become symptomatic when the tumor has reached a large size (usually > 10 cm) and/or if metastases are present.

  • Hematuria is the most common presenting symptom.
  • Anemia (common): pallor, lethargy
  • Dragging/colicky flank pain
  • Potentially palpable renal mass
  • Constitutional symptoms: weight loss; , fatigue, night sweats; , fever

The classical triad of renal cell carcinoma consists of hematuria, flank pain, and a palpable flank mass. However, only 5–10% of patients present with all three components of the triad and > 25% present with one or more atypical symptoms related to paraneoplastic syndromes and/or disseminated disease.

References:[6][1][7][8][2][16][17][3][11][18][19][20]

Diagnostics

Imaging

  • Evaluation of RCC
    • Best initial test: abdominal CT scan with contrast
      • Distorted renal outline and stretched renal calyces
      • Renal lesion(s) with thickened irregular walls, variable enhancement, and calcification
    • Renal ultrasound : renal lesion(s) with variable echogenicity
  • Evaluation of metastatic disease

Laboratory tests

References:[8][2][16][17][3][11][21]

Differential diagnoses

Differential diagnoses for renal masses in adults

The most common renal tumor in children is a nephroblastoma (Wilm's tumor)!

Common differential diagnoses for renal masses in adults include:

Renal cell carcinoma is the most common cause of a small renal mass (< 4 cm) in adults. If the mass is less than 1 cm in size and asymptomatic, a watch and wait approach is recommended. All renal masses > 1 cm in size are presumed to be renal cell carcinoma and treated as such!

References:[17][22][4]

Angiomyolipoma

  • Definition: benign renal tumors that arise from perivascular epithelioid cells and consist of blood vessels, smooth muscle, and mature fat cells
  • Epidemiology
    • Mean age of onset: 43 years
    • Sex: > (4:1)
  • Etiology
    • Sporadic
    • May be associated with the following syndromes:
  • Pathology
  • Clinical features
  • Diagnostics
    • Imaging usually provided the diagnosis
      • Abdominal ultrasound: round, well-circumscribed, highly echogenic (similar echogenicity to renal pelvis) renal tumor often located near the renal capsule
      • Abdominal CT: tumor with macroscopic fat deposits , no calcification
    • Percutaneous biopsy may be required if imaging is inconclusive
  • Treatment: Surgical resection; of the tumor is indicated for angiomyolipomas that measure more than 4 cm in diameter.

References:[1][22][23]

Oncocytoma

Oncocytoma is a benign epithelial tumor. Histologically, an oncocytoma consists of large, acidophilic, mitochondria-rich tumor cells (so-called oncocytes) without perinuclear clearing (vs. chromophobic RCC); . An oncocytoma is not confined to the kidneys and may develop in the thyroid gland, pancreas, or the pituitary gland.

  • Definition: benign tumor arising from the intercalated tubular cells
  • Pathology
  • Therapy
    • Surveillance
    • If tumor increases in size → suspicious for malignant transformation in RCC → nephrectomy
    • Often resected in order to exclude RCC
  • Prognosis: Oncocytomas are not invasive, but they may transform into a malignant oncocytic RCC.

References:[7]

The differential diagnoses listed here are not exhaustive.

Treatment

Chemotherapy is not used to treat RCC because RCC is highly resistant to chemotherapeutic agents, with a response rate of only 15–30%! This occurs because tumor cells express MDR-1 (multidrug resistance protein-1).
References:[6][7][8][16][11][24][25][22]

Prognosis

The overall prognosis is determined by the anatomic extent of the disease (stage of cancer at diagnosis) and the histopathology of the tumor. Early stage RCC with tumor growth limited to the kidney generally has a good prognosis.

Increased awareness and screening (e.g., ultrasound) of high-risk patients in recent years has led to earlier tumor detection and improved the prognosis of RCC!
References:[3][14][26]