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Renal Cell Carcinoma SubtypesEdit

Renal cell carcinoma (RCC) is the predominant form of kidney cancer in adults and is a biologically diverse group of tumors that arise from the renal cortex and adjacent structures. The disease is characterized by a spectrum of histologies, genetic alterations, and clinical behaviors that influence diagnosis, prognosis, and treatment choices. A practical understanding of the major subtypes—along with their molecular drivers—helps clinicians tailor surgical strategies and systemic therapies, and guides discussions about hereditary risk and surveillance for affected families. The major subtypes include clear cell RCC, papillary RCC, and chromophobe RCC, with several rarer forms that each carry unique implications for pathology and patient management. For context, RCC can be discussed in relation to broader kidney cancer topics and hereditary cancer syndromes, which shape screening and prevention strategies in at-risk populations.

Renal cell carcinoma subtypes

Clear cell renal cell carcinoma (ccRCC)

  • Most common subtype by far, with distinctive clear cytoplasm on light microscopy and a rich vascular network.
  • Key genetic features include inactivation of the VHL gene on chromosome 3p, often accompanied by losses of other chromosome segments and mutations in genes such as PBRM1, SETD2, and BAP1.
  • Immunohistochemistry and molecular profiling support diagnosis and can reveal concurrent alterations that may influence prognosis.
  • Clinical implications: ccRCC tends to respond to vascular-targeted therapies and to immunotherapies in advanced disease, and treatment decisions frequently incorporate tests for molecular characteristics in addition to traditional staging.
  • See also: Renal cell carcinoma, VHL gene, Papillary renal cell carcinoma, MiT family translocation RCC.

Papillary renal cell carcinoma (PRCC)

  • Distinct papillary architecture with foamy macrophages often present in the tumor stroma.
  • Two main molecular patterns are recognized: type 1 (often driven by MET alterations, generally better prognosis) and type 2 (more heterogeneous, can be associated with worse outcomes and, in some cases, FH alterations).
  • Clinically, PRCC may present with different patterns of growth and metastatic spread compared with ccRCC, influencing surveillance and management after nephrectomy.
  • See also: Papillary renal cell carcinoma, MET proto-oncogene, Fumarate hydratase-deficient renal cell carcinoma.

Chromophobe renal cell carcinoma (ChRCC)

  • Composed of pale to eosinophilic cells with pale cytoplasm and prominent perinuclear halos; often arises from intercalated cells of the collecting ducts.
  • Generally associated with a more favorable prognosis than ccRCC and PRCC, particularly in localized disease.
  • Can be distinguished by characteristic immunohistochemical patterns and by specific cytogenetic alterations.
  • See also: Chromophobe renal cell carcinoma.

Collecting duct carcinoma (CDC)

  • A rare and aggressive form that originates from the collecting ducts in the renal medulla.
  • Tends to present at a higher stage and has a poorer prognosis relative to the major RCC subtypes.
  • Management typically involves combination systemic therapies, and prognosis remains a clinical challenge.
  • See also: Collecting duct carcinoma.

Renal medullary carcinoma (RMC)

  • Extremely rare and typically occurs in younger patients, often with sickle cell trait or disease.
  • Characterized by a highly aggressive course and distinct histology; diagnosis relies on pathology and correlation with clinical context.
  • See also: Renal medullary carcinoma.

MiT family translocation RCC

  • Encompasses tumors with transcription factor translocations involving TFE3 or TFEB, leading to characteristic morphological features across a broad age range.
  • These subtypes have diverse presentations and can share overlapping histology with other RCCs, so molecular confirmation is important.
  • See also: TFE3 translocation RCC; TFEB translocation RCC.

FH-deficient RCC

Sarcomatoid differentiation

  • Not a separate lineage but a histologic pattern that can accompany any RCC subtype.
  • Presence of sarcomatoid features is associated with a more aggressive course and poorer response to some therapies, influencing treatment planning.

Diagnosis, prognosis, and genetics

  • Diagnosis relies on imaging and histopathology, with immunohistochemistry and, increasingly, molecular profiling helping to define subtypes.
  • Prognosis varies by subtype and stage at diagnosis. While localized disease can be managed surgically with nephron-sparing approaches when feasible, advanced or metastatic disease requires systemic therapy tailored to histology and molecular features.
  • Genetic testing and counseling are particularly important for subtypes linked to hereditary syndromes (for example, FH-deficient RCC and HLRCC; MiT translocation RCCs can occur sporadically or in familial contexts). See adjacent sections for links to hereditary topics such as VHL disease and Birt-Hogg-Dubé syndrome.

Treatment considerations by subtype

  • Surgical management: Partial nephrectomy or radical nephrectomy decisions depend on tumor size, location, patient comorbidity, and kidney function, with a growing emphasis on organ preservation when oncologically safe.
  • Systemic therapy for advanced disease: A range of targeted therapies (including VEGF inhibitors) and immune checkpoint inhibitors are used, with the choice and sequence guided by histology, molecular features, patient performance status, and risk stratification models such as the International Metastatic RCC Database Consortium (IMDC) criteria.
  • Subtype-specific nuances: ccRCC often responds to immune-based regimens and VEGF-targeted therapies; PRCC may derive benefit from certain targeted approaches in addition to immunotherapy; ChRCC generally has a different sensitivity profile, which can influence systemic therapy decisions in advanced cases.
  • See also: Sunitinib, Pazopanib, Nivolumab, Pembrolizumab, Axitinib, Temsirolimus.

Hereditary and familial considerations

See also