A 65-year-old man comes to the office for evaluation of blood in the urine. The patient has no abdominal pain, urinary frequency, or urgency. He has hypertension, type 2 diabetes mellitus, and stage II chronic kidney disease. He quit smoking 10 years ago and had smoked a pack of cigarettes daily for 30 years. On examination, vital signs are within normal limits. The patient's BMI is 33 kg/m². After appropriate work-up, the patient undergoes a renal biopsy; histopathologic findings are shown below. Which of the following processes most likely accounts for the abnormal appearance of these cells?

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11ec160b_3a4c_dd51_9249_b5d069f61b0c_MD0001_00 Gross painless hematuria in an older adult should be considered a sign of urinary tract cancer (urothelial or renal cell carcinoma) until proven otherwise. This patient's renal biopsy shows rounded/polygonal cells with abundant clear cytoplasm, which is characteristic of clear cell carcinoma, the most common form of renal cell carcinoma. Clear cell carcinoma originates from proximal tubular epithelial cells and contains copious amounts of intracellular glycogen and lipids. Standard tissue fixation and staining techniques typically dissolve glycogen and lipids from pathologic specimens, leaving clear spaces. (Choice B) Karyorrhexis is fragmentation of pyknotic (condensed) nuclei during apoptotic cell death. The cells in the above image have intact nuclei. (Choice C) Plasma membrane damage caused by lipid peroxidation can be visualized using immunofluorescent microscopy. Lipid peroxidation is a form of free radical damage and is associated with inflammation, atherosclerosis, and tumorigenesis. (Choice D) Mitochondrial swelling usually occurs during cell injury and would not be expected to render the cell cytoplasm completely clear on routine hematoxylin and eosin stain. (Choice E) Melanin and hemosiderin are pigments commonly seen in histologic specimens. Hemosiderin is an iron oxide pigment that stains tissues at sites of bleeding. Educational objective: The most common renal malignancy is clear cell carcinoma, which arises from renal proximal tubular cells. Rounded or polygonal cells with abundant clear cytoplasm are seen on light microscopy. The cells contain large amounts of glycogen and lipids that dissolve during routine tissue preparation, leaving clear spaces within the cytoplasm.

A 65-Year-Old Man Comes to the Office for Evaluation of Blood