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Pathology of Renal Cell Carcinoma

• Renal cell carcinoma (1/8): Definition and Epidemiology
• Renal cell carcinoma (2/8): Etiology
• Renal cell carcinoma (3/8): Pathology
• Renal cell carcinoma (4/8): Signs and symptoms
• Renal cell carcinoma (5/8): Diagnostic work-up
• Renal cell carcinoma (6/8): Treatment with radical nephrectomy
• Renal cell carcinoma (7/8): Treatment with partial nephrectomy
• Renal cell carcinoma (8/8): Targeted therapy of advanced disease

TNM Tumor Stages [UICC 2010]

T1:

• T1a: Tumor size ≤4 cm
• T1b: Tumor size 4–7 cm

T2:

• T2a: Tumor size 7–10 cm.
• T2b: Tumor size >10 cm

T3:

Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond the renal fascia.

• T3a: Tumor extension into major renal veins or infiltration of perirenal adipose tissue
• T3b: Tumor extension into the vena cava below the diaphragm
• T3c: Tumor extension into vena cava above the diaphragm or invasion of the wall of the vena cava

T4:

Tumor invades beyond the renal fascia or shows contiguous extension into the ipsilateral adrenal gland

N:

• N0: No regional lymph node metastases
• N1: Metastasis in regional lymph nodes

M:

• M0: No distant metastasis
• M1: Distant metastasis are present

G:

• G1: well differentiated
• G2: moderately differentiated
• G3: poorly differentiated
• G4: undifferentiated

Stage Grouping [UICC]

• Stage I: T1 N0 M0
• Stage II: T2 N0 M0
• Stage III: T3 N0 M0 or T1–T3 N1 M0
• Stage IV: T4 N0–1 M0 or T1–4 N0–1 M1

Surgical specimen of a clear cell renal cell carcinoma: typical yellow-brown cut surface and distinct separation from the normal kidney tissue. Public domain image of Dr. Edwin P. Ewing, Public Health Image Library, Centers for Disease Control and Prevention, USA, www.cdc.gov.

Macroscopic Pathology of Renal Cell Carcinoma

The classic clear cell renal cell carcinoma has a yellow-brown cut surface and is inhomogeneous due to hemorrhage and necrosis [fig. surgical specimen kidney with renal cell carcinoma]. Macroscopically, it is relatively well separated from the normal renal tissue, but there may be a risk to form microscopic tumor satellites. Only sarcomatoid tumors always present with an infiltrative growth. Other macroscopic manifestations include cystic growth pattern or calcifications (10–20%). Invasion of the renal veins occurs in 10%, and by continuous tumor growth a thrombus develops which may extend via the vena cava inferior into the right atrium [fig. large tumor thrombus in the vena cava inferior].

CT: large tumor thrombus of a right-sided renal cell carcinoma (right horizontal plane and left frontal plane). (=>) marks the thrombus (right) and the cranial extension (left). With kind permission, Prof. Dr. K. Bohndorf, Augsburg.

Microscopic Pathology of Renal Cell Carcinoma

The current classification of renal cell carcinoma takes into consideration morphological, genetic and prognostic differences (Moch et al, 2016). Since different subtypes have a different molecular carcinogenesis, differences in the therapeutic response to inhibitors of signal transduction are likely (Algaba et al, 2011).

Clear cell renal cell carcinoma (70–80%):

Clear cell renal cell carcinoma macroscopically has a yellow-brown cut surface. The cells are derived from the proximal convoluted tubule. The rich content of glycogen and fat in the cytoplasm of the cells produce a clear appearance in conventional staining [fig. histology of renal cell carcinoma]. But there are also eosinophilic, sarcomatoid (1-5 %) and mixed patterns of differentiation. 75% of clear cell RCC, mutations of the VHL gene are detectable.

Histology of clear cell renal cell carcinoma: rich glycogen and fat content in the cytoplasm of the cells produce a clear appearance with conventional staining methods. Picture from Dr. Edwin P. Ewing, Jr. Public Health Image Library, Centers for Disease Control and Prevention, USA, www.cdc.gov.

Papillary renal cell carcinoma (10%):

Papillary renal cell carcinoma present with basophilic (type 1) or eosinophilic (type 2) cells that form papillary or tubular patterns. The cells are derived from the proximal convoluted tubule. In contrast to clear cell renal cell carcinoma, papillary RCC is not well vascularized. The prognosis is better if localized, but worse if metastasized in comparison to clear cell renal cell carcinoma (Steffens et al, 2012).

Chromophobe renal cell carcinoma (5%):

Chromophobe renal cell carcinoma is derived from the cortical portion of the collecting duct. The lack of staining of the cytoplasm in the tumor cells was eponymous. Numerous microvesicles containing a mucopolysaccharide are visible with electron microscope. Chromophobe renal cell carcinoma is the malignant variant of Onkozytoma. The prognosis is better than clear cell RCC.

Collecting duct carcinoma or Bellini duct cancer (1%):

Collecting duct carcinoma shows a mixed image of dilated tubules and papillary structures. The prognosis is very bad.

Renal medullary carcinoma (less than 1%):

Renal medullary carcinoma occurs almost only in sickle cell disease and arises from the epithelium of the calyces. Histology and prognosis is similar to the collecting duct carcinoma, some authors consider it to be a subtype of the collecting duct carcinoma.

Mucinous tubular and spindle cell carcinoma (less than 1%):

Mucinous tubular and spindle cell carcinoma is considered as a low-grade entity and occurs mainly in women under 60 years. Some authors consider it to be a subtype of papillary renal cell carcinoma.

MiT Family translocation renal cell carcinoma:

Translocation renal cell carcinoma is defined by various translocations with activation of the MiT family. Known translocation affect chromosome Xp11.2 or t(6;11). Mainly children and adolescents are affected, this tumor type is usually detected at an advanced stage.

Succinate Dehydrogenase–Deficient Renal Cell Carcinoma:

SDH-deficient RCC are characterized by al loss of expression of SDHB, which is a marker of mitochondrial dysfunction. The tumors are solid with a brown cut surface and cytoplasmic vacuoles. It affects mainly young adults, most patients have a germline mutation. The prognosis is favourable.

Not classifiable renal cell carcinomas:

4–7% renal cell carcinomas are large and undifferentiated and cannot be clearly classified. The prognosis is poor (median survival 4–5 months).

Oncocytoma (5%):

Please see section oncocytoma.

Metastasis of Renal Cell Carcinoma

RCC most commonly metastasizes into lung, soft tissues (lymph nodes, muscles), bone, liver, CNS and skin (in descending order of frequency).

References

  Deutsche Version: Nierenzellkarzinom