Renal · Urologic Oncology
The facts most likely to be tested
The classic clinical triad of flank pain, palpable abdominal mass, and hematuria is present in fewer than 10% of patients at the time of diagnosis.
Clear cell carcinoma is the most common histological subtype, originating from the proximal convoluted tubule epithelium.
Smoking is the most significant modifiable risk factor, while von Hippel-Lindau (VHL) syndrome is the most common hereditary association.
Renal cell carcinoma frequently presents with paraneoplastic syndromes, most notably erythrocytosis due to ectopic erythropoietin production.
Left-sided varicocele that fails to decompress when the patient is supine suggests tumor thrombus obstruction of the left renal vein.
Abdominal CT scan with contrast is the diagnostic imaging modality of choice for characterizing a suspected renal mass.
Surgical resection (partial or radical nephrectomy) is the definitive treatment for localized disease, as these tumors are generally radioresistant and chemoresistant.
Vignette unlocked
A 62-year-old male presents to the clinic with a 3-month history of intermittent gross hematuria and a 10-pound unintentional weight loss. Physical examination reveals a non-tender, firm mass in the left flank and a left-sided varicocele that does not empty when the patient is in the supine position. Laboratory studies are significant for a hemoglobin of 18.2 g/dL. The patient has a 40-pack-year smoking history.
What is the most likely diagnosis and the underlying mechanism for the patient's elevated hemoglobin?
Renal cell carcinoma; ectopic erythropoietin production.
The patient presents with the classic signs of RCC, including hematuria and a left-sided varicocele caused by renal vein obstruction; the elevated hemoglobin is a paraneoplastic manifestation due to ectopic EPO secretion.
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Etiology / Epidemiology
Most common renal malignancy in adults; smoking and obesity are the primary modifiable risk factors.
Clinical Manifestations
Classic triad of hematuria, flank pain, and palpable mass is rare; paraneoplastic syndromes are common.
Diagnosis
CT abdomen/pelvis with contrast is the gold standard for staging and diagnosis.
Treatment
Radical nephrectomy is the definitive treatment for localized disease; RCC is notoriously resistant to chemotherapy.
Prognosis
Prognosis is stage-dependent; 5-year survival for localized disease is ~90%, but drops significantly with metastasis.
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Epidemiology & Etiology
RCC accounts for 90% of primary renal neoplasms, typically occurring in patients aged 50–70. Smoking doubles the risk, while hypertension and obesity are significant independent contributors. Genetic predisposition includes von Hippel-Lindau (VHL) syndrome, which is associated with clear cell carcinoma.
Pertinent Anatomy
Tumors most commonly arise from the proximal renal tubular epithelium. The right renal vein is shorter than the left, increasing the risk of tumor thrombus extension into the inferior vena cava.
Pathophysiology
Loss of the VHL tumor suppressor gene leads to constitutive activation of hypoxia-inducible factor (HIF). This triggers overexpression of VEGF and PDGF, promoting intense angiogenesis and tumor growth. The tumor is highly vascular, explaining its propensity for hematogenous spread.
Clinical Manifestations
The classic triad of hematuria, flank pain, and palpable mass is present in <10% of patients. Red flags include unexplained weight loss, night sweats, and varicocele (left-sided) due to venous obstruction. Paraneoplastic syndromes like erythrocytosis (via EPO production) or hypercalcemia (via PTHrP) may be the presenting sign.
Diagnosis
Initial evaluation is via ultrasound to distinguish solid from cystic masses. CT abdomen/pelvis with contrast is the gold standard for definitive diagnosis and staging. Avoid biopsy if the mass is highly suspicious for RCC, as it carries a risk of tumor seeding.
Treatment
Localized disease is managed with radical nephrectomy (or partial nephrectomy for small tumors). Metastatic disease is treated with immunotherapy (e.g., nivolumab) or tyrosine kinase inhibitors (e.g., sunitinib). Radiation and chemotherapy are generally ineffective for RCC.
Prognosis
The Fuhrman nuclear grade is the most important histologic prognostic factor. Patients require lifelong surveillance for recurrence, typically via serial CT imaging of the chest and abdomen.
Differential Diagnosis
Angiomyolipoma: contains macroscopic fat on CT
Renal oncocytoma: central stellate scar on imaging
Transitional cell carcinoma: associated with bladder cancer/hematuria
Renal abscess: presents with fever and leukocytosis
Polycystic kidney disease: bilateral, multiple cysts