Clear Cell Carcinoma Clear cell carcinoma is a type of cancer characterized by the presence of cells with a clear, pale appearance when viewed under a microscope. This histological feature is due to the accumulation of substances like glycogen and lipids within the tumor cells, which are dissolved during tissue processing, leaving the cells with a "clear" cytoplasm. Clear cell carcinoma can occur in various organs, including the kidneys, ovaries, uterus, and, more rarely, in other tissues. Clear Cell Renal Cell Carcinoma (ccRCC) One of the most common and well-known forms of clear cell carcinoma is clear cell renal cell carcinoma (ccRCC), a subtype of renal cell carcinoma (RCC) that accounts for approximately 70-80% of all kidney cancers. ccRCC originates in the epithelial cells lining the proximal convoluted tubules in the kidney, which are involved in the filtration and reabsorption processes. Pathophysiology The majority of ccRCC cases are associated with mutations or alterations in the von Hippel-Lindau (VHL) gene, a tumor suppressor gene located on chromosome 3. The VHL gene plays a crucial role in regulating cell growth and oxygen sensing by targeting hypoxia-inducible factors (HIFs) for degradation under normal oxygen conditions. When VHL is mutated or inactivated, HIFs accumulate, leading to increased expression of angiogenic factors like vascular endothelial growth factor (VEGF) and promoting tumor growth and vascularization. Clinical Manifestations Patients with ccRCC may present with a variety of symptoms, though many cases are asymptomatic and detected incidentally during imaging studies for unrelated reasons. Common symptoms include:  Hematuria (blood in urine)  Flank pain or discomfort  A palpable abdominal mass  Unexplained weight loss  Fatigue Advanced cases may present with symptoms related to metastasis, as ccRCC has a tendency to spread to distant organs, particularly the lungs, bones, and liver.