Nephroblastoma and Renal Tumors Quiz

Renal Tumors: Overview

• Renal tumors are a diverse group of diseases
• The 2022 WHO classification of urinary and male genital tumors (5th edition) provides updated diagnostic criteria, molecular correlates, and nomenclature.

Kidney Tumors: WHO Classification (2022)

• Renal cell tumors:
  • Clear cell renal tumors
  • Papillary renal tumors
  • Oncocytic and chromophobe renal tumors
  • Collecting duct tumors
  • Other renal tumors
  • Molecularly defined renal carcinomas
• Metanephric tumors
• Mixed epithelial and stromal renal tumors
• Renal mesenchymal tumors
• Embryonal neoplasms of the kidney
• Miscellaneous renal tumors

Renal Oncocytoma: Classification and Features

• Classification: Oncocytic and chromophobe renal tumors,
• Oncocytoma: A subcategory of oncocytic and chromophobe renal tumors
• Clinical Features:
  • 5-9% of all renal tumors
  • Male to female ratio = 2:1
  • Often asymptomatic, though flank pain and hematuria can occur
  • CT or MRI may reveal a central scar

Renal Oncocytoma: Pathophysiology

• Originates from renal intercalated cells
• Filled with respiration-defective mitochondria
• Often associated with mitochondrial mutations
• These mutations can lead to metabolic checkpoint activation, autophagy impact, and mitochondrial buildup
• Some have hybrid morphologies
• Potential for multiple tumors
• Some connected to syndromic conditions
• Two main molecular variants:
  • Rearrangements of CCDN1 (11q13 translocations)
  • Aneuploidy (mainly involving chromosome Y and 1)
• Aneuploidy, combined with additional p53 mutations, may be associated with progression to eosinophilic chromophobe renal cell carcinoma.

Renal Oncocytoma: Gross Pathology

• Well-circumscribed, homogeneous cortical tumor
• Mahogany-brown cut surface
• Often displays a central, irregular fibrous scar
• Bilateral or multicentric in 2-3% of cases

Renal Oncocytoma: Microscopic Examination

• Well-circumscribed lesion
• Usually no pseudocapsule
• Composed of large eosinophilic cells (oncocytes) with dense granular cytoplasm
• Nuclei are round, regular, and have even chromatin with conspicuous nucleoli
• Cells are arranged in nests separated by edematous and hyalinized fibrous stroma

Renal Oncocytoma: Immunohistochemistry

• Positive stains: CD117/KIT, E-cadherin, S100A1, PAX8
  • Some subtypes of Low molecular weight keratin (CAM 5.2) and pancytokeratin
• Negative stains: CK7, AMACR, CAIX, Vimentin, HMB45, melanA, CK20, Hale colloidal iron

Renal Cell Carcinoma: Epidemiology

• Represents 1-3% of visceral cancers and 85% of renal malignancies in adults
• Most common in older adults (sixth and seventh decade)
• More prevalent in men (ratio of 2:1)
• Primarily sporadic; however, familial occurrences are possible.

Renal Cell Carcinoma: Risk Factors

• Cigarette smoking
• Obesity (especially in women)
• Hypertension
• Unopposed estrogen therapy
• Exposure to asbestos, petroleum products, and heavy metals
• Acquired polycystic kidney disease secondary to dialysis

Renal Cell Carcinoma: Clinical Presentation

• Often asymptomatic initially
• Possible silent presentation
• Common clinical presentation can be triad of Hematuria, Flank pain, Flank mass
• Hematuria is the most reliable sign but can be intermittent or microscopic, masking the tumor's presence until it's quite large.

Renal Cell Carcinoma: Paraneoplastic Syndromes

• Renal cell carcinoma can produce systemic symptoms unrelated to the kidney called paraneoplastic syndromes, arising from abnormal hormone production.
  • Polycythemia (elevated hematocrit - > 60%)
  • Hypercalcemia (elevated levels of parathyroid hormone-like hormone)
  • Hypertension
  • Hepatic dysfunction
  • Feminization or masculinization (due to elevated gonadotropins)
  • Cushing syndrome
  • Leukemoid reactions
  • Amyloidosis

Renal Cell Carcinoma: Metastasis

• Often metastasizes widely before causing local symptoms
• Radiologic evidence of metastases is present in about 25% of patients at the time of diagnosis
• Common metastatic sites include the lungs, bones, regional lymph nodes, liver, adrenals, and brain

Renal Cell Tumors: Clear Cell Renal Cell Carcinoma

• The most common type of renal cell carcinoma (70-80% of all renal cell carcinomas)
• Gross Pathology:
  • Solitary cortical mass
  • Bilaterality and multifocality are more common in familial cases.
  • Well-circumscribed, lobulated, golden-yellow cut surface
  • Cystic change, hemorrhage, necrosis, and calcification can be present

Clear Cell Renal Cell Carcinoma: Histopathology

• Nests of clear cells are dispersed by a delicate vascular network

Clear Cell Renal Cell Carcinoma: More Histology and Immunohistochemistry

• Positive stains in clear-cell RCC: Include PAX8, PAX2, CAIX (often diffuse or membranous), CD10, vimentin, epithelial markers (AE1/AE3, CAM5.2, EMA)
• Negative stains: CK20, Inhibin, melan-A/MART1, calretinin, TTF1, CEA.

Clear Cell Renal Cell Carcinoma: Metastasis

• Lung and bone are common sites of metastasis
• Bone metastases can lead to osteolytic lesions and pathological bone fractures.
• Increased alkaline phosphatase is a marker for bone metastases.

Nephroblastoma (Wilms Tumor): Overview

• A malignant embryonal tumor originating from nephrogenic blastema
• Resembling the histology of a developing kidney
• Primarily a childhood cancer.
• Named after the German surgeon Max Wilms.

Nephroblastoma: Epidemiology

• Most common in children aged 3 to 4 years
• Frequent in African children
• Relatively rare in East Asian children
• Congenital Wilms tumors are rare.
• Slightly more prevalent in females
• Majority of Wilms tumors are non-syndromic
• 10-15% have associated syndromes or congenital anomalies
• Familial cases are rare (1-2%)
• Relapse occurs in approx. 15% of children, most within 2 years of diagnosis.

Nephroblastoma: Etiology

• Thought to develop from persistent metanephric tissue or nephrogenic rests
• Related to genetic alterations during embryological development of the genitourinary tract
• WT1 gene at chromosome 11p13 is implicated; WT2 gene on chromosome 11p15 is another implicated gene

Nephroblastoma: Clinical Features

• Typically presents as an abdominal mass with no immediate symptoms.
• Less common presentations include Hematuria, abdominal pain, and hypertension.
• Anemia might also occur.
• Predisposition syndromes (with varying risk levels)

Nephroblastoma: Associated Syndromes

• WAGR syndrome (Aniridia, genital abnormality, mental retardation)
• Denys-Drash syndrome (Gonadal dysgenesis, renal abnormality)
• Beckwith-Wiedemann syndrome (Enlarged organs, including macro-glossia and hemi-hypertrophy).

Nephroblastoma: Morphology

• Gross: Lobulated, tan mass
• Microscopic: Tumor is composed of blastemal, epithelial, and stromal elements.
  • These three elements are in variable proportions
  • Can show differentiation variability (from poor differentiation to well differentiation).
• Excellent prognosis with 90% long-term survival.

Additional Information (general):

• Size: The sizes of tumors discussed are not specified for each tumor type
• Location: The location information of tumors is not always available to precisely discern and pinpoint any one tumor from the slides.
• Treatment: No treatment information is provided in the slides
• Survival: Survival is detailed for either specific types or classes of tumors