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A 68-year-old woman comes to the office due to increasing low back pain.  The pain is constant and worsens at night.  She has also had a 6.8-kg (15-lb) weight loss over the past 3 months.  Medical history is significant for osteoporosis and hypothyroidism.  Family history is significant for breast cancer in her mother.  She has smoked 1 pack of cigarettes daily for 30 years and drinks 1 or 2 glasses of wine every day.  The patient immigrated to the United States from China 30 years ago; she mainly eats food she cooks herself.  Vital signs are within normal limits.  Physical examination shows point tenderness over the L3 and L4 vertebrae.  MRI reveals lytic bone lesions in the corresponding vertebrae and also a right lower pole kidney mass.  Histologic examination of the mass is shown below:

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Which of the following risk factors most likely contributed to this patient's current condition?

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Renal cell carcinoma

Presentation

  • Hematuria, flank pain, palpable abdominal mass
  • Paraneoplastic syndrome (eg, polycythemia, hypercalcemia)

Risk factors

  • Smoking, hypertension, obesity
  • Toxin exposure (eg, heavy metal, petroleum by-products)

Gross examination

  • Spherical mass, often with invasion of the renal vein
  • Golden-yellow tissue (due to high lipid content)

Histology

(Clear cell)

  • Cuboidal or polygonal cells with abundant, clear cytoplasm
  • Branching, "chicken-wire" vasculature

This patient with back pain, osteolytic bone lesions, and histologic findings demonstrating rounded, polygonal clear cells has metastatic renal cell carcinoma (RCC).  RCC is often asymptomatic until the disease is advanced, and many patients have metastatic disease at the time of diagnosis.  Symptoms often include some combination of hematuria, abdominal mass, or flank pain; however, this classic triad occurs in <10% of cases.  Systemic symptoms (eg, fever, weight loss, fatigue) and symptoms related to metastases (eg, bone pain) are common.

Risk factors for RCC include smoking, toxin exposure (eg, trichloroethylene, asbestos, petroleum by-products), obesity, and hypertension.

(Choice A)  Alcohol use increases the risk of hepatocellular carcinoma and squamous cell carcinoma of the esophagus but is associated with a decreased risk of RCC.

(Choice B)  Diets high in cured meat and salt-preserved foods (which are prevalent in some Asian populations) are associated with an increased risk of gastric cancer but not RCC.

(Choice C)  Asian-American patients have a lower risk of RCC than other ethnicities.  Individuals of Asian heritage are at increased risk of developing IgA nephropathy.

(Choice D)  Patients with a strong family history of RCC (eg, first degree relative diagnosed before age 40) or those with certain hereditary cancer syndromes (eg, Von Hippel-Lindau disease) are at increased risk of RCC.  In contrast, a strong family history of breast cancer may be associated with BRCA gene positivity and places patients at higher risk for breast and ovarian cancers.

Educational objective:
Renal cell carcinoma may present with a combination of hematuria, abdominal mass, or flank pain; however, this triad occurs together in <10% of cases.  Pathology demonstrates rounded, polygonal cells with clear cytoplasm.  Risk factors include smoking, toxin exposure, and certain hereditary disorders (eg, von Hippel-Lindau syndrome).