Renal Tumors Overview and Classification

Renal Tumors Overview

• Renal tumors encompass a diverse range of conditions, both benign and malignant.
• WHO (World Health Organization) 2022 classification of urinary and male genital tumors (5th edition) provides a detailed framework for diagnosis.
• Diagnostic criteria, molecular correlates, and nomenclature have been updated.
• Selected tumor types are detailed.

Renal Cell Tumors

• Renal cell tumors are a significant group within kidney tumors.
• Sub-categories within RCC include clear cell renal tumors, papillary renal tumors, oncocytic and chromophobe renal tumors, and collecting duct tumors.
• Additional subtypes encompass other renal tumors and molecularly defined renal carcinomas.
• Mixed epithelial and stromal renal tumors, renal mesenchymal tumors, and embryonal neoplasms are also types of renal cell tumors.
• Miscellaneous renal tumors are a catchall category.

Oncocytoma

• Oncocytoma is a type of benign renal tumor.
• It accounts for 5-9% of renal tumors, with a male-to-female ratio of 2:1.
• Most cases are asymptomatic.
• Flank pain or hematuria are possible presenting symptoms.
• Patients have characteristically an identifiable central scar on CT or MRI imaging.
• Oncocytomas arise from renal intercalated cells, and usually contain respiration-defective mitochondria.
• Mitochondrial mutations may contribute to pathophysiology.
• Two molecular variants associated with oncocytomas are CCDN1 rearrangements and aneuploidy, often involving chromosome Y and 1.
• In some cases, aneuploidy, p53 mutations and progression to eosinophilic chromophobe renal cell carcinoma is possible.
• Grossly, oncocytoma appears as a well-circumscribed, homogeneous cortical tumor, with a mahogany-brown cut surface and a central fibrous scar. Bilateral or multicentric forms are seen in a small percentage.
• Microscopically, the tumor shows a well-circumscribed lesion, typically without a pseudocapsule. It is comprised of large eosinophilic cells (oncocytes) with granular cytoplasm, rounded/regular nuclei and prominent nucleoli. The cells arrange in nests separated by edematous and hyalinized fibrous stroma.
• Oncocytoma cells stain positively for CD117/KIT, E-cadherin, S100A1, PAX8, low molecular weight keratin (CAM 5.2), and pancytokeratin.
• Oncocytoma cells stain negatively for CK7, AMACR, CAIX, Vimentin, HMB45, melanA, CK20, and Hale colloidal iron

Renal Cell Carcinoma

• Renal cell carcinoma (RCC) is the most common malignant kidney tumor in adults.
• Epidemiology: A prevalent type of visceral cancer (1%–3% of all visceral cancers), accounting for 85% of renal malignancies in adults. It most commonly presents in the 6th and 7th decades of life and shows a male predominance (2:1).
• Risk factors include: smoking, obesity (particularly in women), hypertension, unopposed estrogen therapy, exposure to asbestos, petroleum products and heavy metals. Past history of acquired polycystic kidney disease secondary to dialysis may also be a risk factor.
• Clinical presentation: Often ‘silent’ in early stages (only 10% present with the classical triad of hematuria, flank pain, and flank lump).
• Paraneoplastic syndromes: RCC frequently causes systemic symptoms unrelated to the kidney, resulting from abnormal hormone production.
• Possible paraneoplastic syndromes include polycythemia (erythropoietin increase), hypercalcemia (PTH-like hormone), and hypertension.
• Other paraneoplastic effects include hepatic dysfunction, feminization/masculinization, Cushing syndrome, leukemoid reactions, and amyloidosis.
• Metastasis occurs often and commonly involves the lungs (over 50%), bones (33%), regional lymph nodes, liver, adrenals, and brain.

Clear Cell Renal Cell Carcinoma

• Clear cell renal cell carcinoma (ccRCC) represents a significant proportion of renal cell cancers (70-80%).
• Gross appearance: Solitary, renal cortical mass. Bilaterality and multifocality are more frequent in familial cases. The mass is well-circumscribed with a lobular, golden-yellow cut surface. Cystic change, hemorrhage, necrosis, and calcifications are frequently present.
• Histopathology: Nests of clear cells interspersed by a delicate vascular network, demonstrating distinct cellular morphology. Additional characteristics include intracellular glycogen, positivity for PAS stain.
• Positive markers include PAX8, PAX2, CAIX (diffuse, membranous in 75-100% of cases), CD10, RCC, vimentin, and epithelial markers (AE1/AE3, CAM 5.2, EMA).
• Negative markers include CK20, inhibin, Melan-A/MART1, calretinin, TTF1 and CEA.
• Metastasis involves lungs and bones, commonly presenting with osteolytic lesions and pathological fractures. Increased alkaline phosphatase can indicate bone metastasis.

Nephroblastoma (Wilms Tumor)

• Nephroblastoma is a malignant embryonal tumor arising from nephrogenic blastema, mimicking the developing kidney's histology.
• Epidemiology: Relatively common neoplasm in children, most frequently appearing between 3 and 4 years of age, showing a slight female predominance in children.
• Etiology may result from persistent metanephric tissue or nephrogenic rests, with genetic alterations in embryonic development of the genitourinary tract as a potential cause. WT1 gene on chromosome 11p13 and WT2 on chromosome 11p15 are implicated in tumorigenesis.
• Clinical presentation: Commonly presents as an abdominal mass with no other immediate symptoms though in 20-30% also includes hematuria, abdominal pain, hypertension and/or anemia.
• Associated syndromes: Wilms tumor may be associated with specific predisposition syndromes (WAGR, Denys-Drash, and Beckwith-Weidemann syndrome).
• Pathology: Grossly, the tumor forms a lobulated mass. Histologically, the tumor exhibits a triphasic appearance with blastemal, epithelial, and stromal elements and variable differentiation (from poor to well-differentiated).
• Excellent long-term survival (approximately 90%).