Review Question - QID 217075

This patient with a right-sided varicocele (large, soft, supratesticular scrotal mass), history of hypertension and cigarette smoking, pain to palpation of the right flank, anemia, and biopsy showing cells with ample clear cytoplasm arranged in irregular nests most likely has renal cell carcinoma (RCC).

RCC accounts for over 90% of malignant neoplasms arising from the kidney. RCCs are twice as common in men as women and are associated with hypertension, obesity, and cigarette smoking. About 70% of RCC cases show clear cell histology, in which neoplastic cells have clear cytoplasm, low nucleus/cytoplasm ratio, and are arranged in nests with intervening blood vessels. The classic signs and symptoms of RCC are hematuria, flank or abdominal pain, and a palpable flank or abdominal mass; however, this triad is found in less than 10% of patients with RCC. Other signs and symptoms of RCC include anemia, fever, weight loss, varicocele, arterially enhancing mass on imaging, and paraneoplastic syndromes (erythrocytosis, hypercalcemia, dysfibrinogenemia, or non-metastatic hepatic dysfunction [Stauffer syndrome]). A right-sided varicocele is particularly suggestive of RCC invasion of the renal vasculature, as the right renal vein inserts obliquely into the inferior vena cava (IVC) after a relatively short course compared to the left renal vein. Survival for renal cell carcinoma has markedly improved with both earlier detection and a variety of new treatment options including tyrosine kinase inhibitors, anti-VEGF antibodies, mTOR inhibitors, and PD-1 inhibitors.

Hsieh et al. review the epidemiology, genetics, pathogenesis, clinical presentation, diagnostic investigation, staging, prognosis, and treatments for RCC.

Figure/Illustration A shows the histologic appearance of clear cell RCC. The neoplastic cells are arranged in nests with intervening blood vessels (yellow outline) and have a clear cytoplasm (red arrow).

Incorrect Answers:
Answer 1: Angiomyolipomas are benign neoplasms that may cause a renal mass. They comprise approximately 1% of resected renal masses, may occur sporadically in older adults, and are associated with tuberous sclerosis in younger patients. Histologically, angiomyolipomas consist of an admixture of dysmorphic blood vessels, smooth muscle, and adipose tissue.

Answer 2: Lymphomas may metastasize to the kidney and cause a similar presentation to RCC, with flank pain, weight loss, palpable abdominal mass, and hematuria. Lymphomas can be distinguished from clear cell RCC on imaging, with lymphomatous masses being hypovascular with minimal contrast enhancement; as opposed to RCCs showing more avid arterial enhancement. Histologically, lymphomas will show numerous lymphocytes as opposed to the nests of clear cells seen in this patient. Of note, metastatic lymphomas are also the most common testicular cancer in older men.

Answer 4: Seminomas are the most common germ cell testicular cancer in older men. However, seminomas generally present as a painless, homogeneously enlarged testicle that does not transilluminate, not a supratesticular mass that suggests a varicocele. The histological appearance of seminomas shows large cells in lobules with watery cytoplasm and a “fried egg” appearance.

Answer 5: Transitional cell carcinomas are a malignancy of urothelial cells that may involve the renal pelvis or renal calyces. Although the morphologic appearance of transitional cell carcinoma can be heterogeneous, histology generally shows neoplastic cells with a high nucleus/cytoplasm ratio, hyperchromasia, and nuclear pleomorphism arranged in irregular nests invading the lamina propria. This patient’s histology shows cells with clear cytoplasm and has invasion of the renal vasculature, making RCC more likely than transitional cell carcinoma.

Bullet Summary:
Clear cell RCC is associated with smoking and hypertension and can present with hematuria, flank pain, flank mass, anemia, and a right-sided varicocele with a histologic appearance of nests of neoplastic cells with clear cytoplasm.