What are the types of kidney tumors?

Types of Kidney Tumors

Kidney tumors are classified into malignant renal cell carcinomas (RCCs), benign tumors, and rare entities, with the 2024 WHO classification now incorporating molecular-defined subtypes alongside traditional histologic categories. 1

Major Malignant Renal Cell Carcinomas

Clear Cell RCC (ccRCC)

• Represents approximately 80% of all malignant renal tumors in adults 1
• Characterized by cells with clear cytoplasm due to glycogen and lipid accumulation, arranged in tubular and solid patterns with prominent capillary stroma 2
• Associated with VHL gene mutations (>80% of sporadic cases), along with mutations in chromatin remodeling genes (PBRM1: 41%, BAP1: 8-10%, SETD2: 11.5%) 1

Papillary RCC (pRCC)

• Accounts for 7-15% of RCCs and is the most common non-clear cell subtype 2
• Divided into two biologically distinct subtypes: Type 1 (associated with MET pathway alterations) and Type 2 (associated with NRF2-ARE pathway activation, CDKN2A loss) 1
• Type 2 papillary RCC generally carries worse prognosis, particularly when associated with hereditary leiomyomatosis and FH mutations 1

Chromophobe RCC

• Comprises 5-10% of RCCs 2
• Features polygonal cells with pale reticulated cytoplasm and clear cytoplasmic membrane delimitation 2
• Shows diffuse CK7 positivity (distinguishing it from oncocytoma) and frequent chromosome losses with TP53 as the most commonly mutated gene (32%) 1
• Associated with Birt-Hogg-Dubé syndrome 2

Molecular-Defined RCC Entities (2024 WHO Classification)

The most recent WHO classification introduces six new molecular-defined RCC subtypes that require molecular testing for definitive diagnosis 1:

Eosinophilic Solid and Cystic RCC

• Characterized by TSC mutations and mTOR pathway activation 1
• Typically clinically indolent with reported responses to mTOR inhibitors 1

ELOC-Mutated RCC

• Features ELOC (TCEB1) mutations with clear cells containing abundant cytoplasm and fibromuscular bands 1
• Based on limited data, appears to behave indolently with good prognosis 1

ALK-Rearranged RCC

• Defined by ALK rearrangements with morphologically heterogeneous appearance 1
• Responses to ALK inhibitors have been documented 1

SMARCB1-Deficient Medullary RCC

• Highly aggressive subtype characterized by SMARCB1 loss 1
• Frequently occurs in young patients with sickle cell trait (though not required for diagnosis) 1

TFEB-Altered RCC

• Includes both TFEB-translocated (typically indolent) and TFEB-amplified (highly aggressive) variants 1
• TFEB-amplified RCC tends to occur in older patients with poor prognosis 1
• Must be ruled out in young patients (<40 years) presenting with papillary architecture or complex architecture with clear/epithelioid cells 1

FH-Deficient RCC

• Characterized by FH loss or mutation, may be associated with hereditary leiomyomatosis and RCC syndrome 1

Aggressive Rare Subtypes

Collecting Duct Carcinoma (Bellini Duct)

• Highly aggressive RCC arising from renal collecting tubules, representing <1% of kidney cancers 1
• Characterized by unique gene expression signature and immune profile with average 22% tumor-infiltrating lymphocytes 1

Renal Medullary Carcinoma

• Variant of collecting duct carcinoma initially described in sickle cell trait-positive patients 1

Sarcomatoid and Rhabdoid Differentiation

• Not distinct RCC types but rather patterns of dedifferentiation that can arise in any RCC subtype 1
• Both are graded as WHO/ISUP grade 4 and associated with poor prognosis, high stage, and increased risk of death independent of other factors 1

Benign Renal Tumors

Oncocytoma

• Distinguished from chromophobe RCC by negative or focal CK7 positivity (versus diffuse positivity in chromophobe) 1

Multilocular Cystic Renal Neoplasm of Low Malignant Potential

• Previously termed multilocular cystic ccRCC, renamed due to indolent behavior 1

Papillary Adenoma

• Benign lesion included in WHO classification 1

Pediatric Renal Tumors

While the question appears focused on adult tumors, pediatric renal tumors represent a distinct spectrum 3, 4:

• Wilms tumor (nephroblastoma): 80% of pediatric renal cancers 4
• Clear cell sarcoma of kidney 4
• Malignant rhabdoid tumor 4
• Congenital mesoblastic nephroma (more common in first year of life) 3

Clinical Implications

The shift to molecular-defined classification highlights the need for genome sequencing to identify actionable mutations for personalized treatment 1. Testing for germline mutations is recommended for younger patients, those with multiple/bilateral lesions, those with family history, and those with related disorders or who have exhausted standard therapies 1.

Important diagnostic pitfall: Renal neoplasia occurring post-chemotherapy/radiation in pediatric patients represents a heterogeneous group without sufficient data to support a unique subtype, though clear cell RCC is most common in this setting 1.