• Clinical science

Renal cell carcinoma (Hypernephroma…)


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.


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


Epidemiological data refers to the US, unless otherwise specified.


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!



  • Renal cell carcinomas are adenocarcinomas that usually arise from the epithelial cells of the proximal convoluted tubule.
  • Clear cell RCC is the most common histological variant (∼ 80% of all cases).
    • Due to a mutation of the VHL gene on chromosome 3p
    • Histology
      • Polygonal cells with a clear, glycogen and/or lipid-filled cytoplasm that are arranged as cords or tubules (clear cells)
      • Unifocal, unilateral growth
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
  • Large polygonal cells with a prominent cell membrane, eosinophilic cytoplasm, and a perinuclear halo
  • 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.


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 (> 40% of cases).
  • Anemia (common; ∼ 30–90% of cases): pallor, lethargy
  • Dragging/colicky flank pain (∼ 40% of cases)
  • Potentially palpable renal mass (∼ 25% of cases)
  • Constitutional symptoms: weight loss; (∼ 30% of cases), fatigue, night sweats; , fever (∼ 20% of cases)

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.



TNM classification (8th Edition, 2017)

TNM Expansion
  • Tumor is limited to the kidney
  • Tumor size is ≤ 7 cm in greatest dimension
  • Tumor is limited to the kidney
  • Tumor size is > 7 cm in greatest dimension

Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland or beyond the Gerota fasci

T4 Tumor extends beyond the Gerota fascia (including contiguous extension into the ipsilateral adrenal gland)
N0 No metastasis in regional lymph node(s)
N1 Metastasis in regional lymph node(s)
M0 No distant metastasis
M1 Distant metastasis

AJCC staging (8th Edition, 2017)

AJCC stage TNM
Stage I
  • T1; N0
Stage II
  • T2; N0
Stage III
  • T1 or T2; N1
  • T3; N0 or N1
Stage IV
  • T4; Any N2; M0
  • Any T; Any N; M1




  • 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 (∼ 30% of cases)
    • Renal ultrasound : renal lesion(s) with variable echogenicity
    • MRI
    • IVU and renal arteriography were performed in the past but have now been replaced by abdominal contrast CT scan and MR angiography respectively.
  • Evaluation of metastatic disease

Laboratory tests


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!



  • 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.



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.


The differential diagnoses listed here are not exhaustive.


  • Treatment of choice: surgical resection of the tumor via open, robotic, or laparoscopic surgery . Depending on the extent of the tumor (see RCC staging), the following surgical procedures are performed:
    • Stage I: cryoablation, thermal ablation, partial nephrectomy , or simple nephrectomy
    • Stage II–IV: radical nephrectomy
  • Patients who are unfit for surgery should be monitored for tumor growth and may be treated palliatively with:
    • Arterial embolization
    • External beam radiotherapy
  • Immunomodulatory and/or targeted therapy

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).


  • Patients who are not fit for surgery: abdominal CT/MRI within 6 months to determine if the tumor is growing, and thereafter annually
  • Patients who have been treated surgically
    • Stage I disease
      • Patients who have been treated with ablation: abdominal CT/MRI at 3 and 6 months, and thereafter annually for 5 years
      • Patients who have been treated with partial or simple nephrectomy: abdominal CT/MRI annually for 3 years
    • Stage II–IV: abdominal CT/MRI every 6 months after surgery for the first 3 years, and thereafter annually for the next 2 years



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.

  • Histopathology: Collecting duct carcinomas and RCC with a sarcomatoid appearance on histology are associated with a poor prognosis.
  • 5-year survival rates of RCC based on AJCC staging
    • Stage I: 81%
    • Stage II: 74%
    • Stage III: 53%
    • Stage IV: 8%
      • In < 5% of cases: spontaneous regression of metastasis after tumor resection
      • Motzer score is used to determine the prognosis of patients with stage IV disease. A point is assigned for each of the following criteria. Based on the resulting score, the prognosis of the metastatic RCC patient is estimated → high scores are associated with a poorer prognosis.
Motzer score
Karnovsky performance status (PS)

< 80%

Low hemoglobin level

< 12.0–15.5 g/dL

< 13.5–17.5 g/dL

Increased lactate dehydrogenase (LDH) > 420 U/L
Increased serum calcium > 10 mg/dL (> 2.5 mmol/L)
Time from diagnosis to systemic treatment < 1 year

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!