Accounts of 3% of visceral cancers in USA and 85% of renal cancers in adults.
Age group is 6th & 7th decades with male predominance. Female to male ratio is 2:1
They are called hypernephromas because of their gross yellow colour & resemblance of tumor cells with clear cells of adrenal cortex.
Originate from tubular epithethial cells.
Epidemiology
Risk factors
Tobacco- cigarette smoke doubles the incidence of Renal cell carcinoma.
Obesity
Hypertension
Unopposed estrogen therapy
Exposure to asbestos, petroleum products & heavy metals.
Chronic renal failure
Acquired cystic disease
Renal cancers are usually sporadic
Autosomal dominant familial cancers develop in younger individuals and they account for 4% of renal cell carcinoma. There tumors are seen associated with
Von –Hippel Lindau (VHL) syndrome
1/2 to 2/3rd patients develop renal cysts and often bilateral & multiple renal cell carcinomas
VHL gene is implicated in the development of Renal cell carcinoma.
Hereditary familial clear cell carcinoma
Due to VHL gene abnormalities but do not show other manifestation of Von Hippel Lindau syndrome.
Hereditary papillary carcinoma:
Autosomal dominant form manifested by multiple bilateral tumors with papillary histology.
There tumors show mutations in the MET proto oncogene.
Herediatary leiomyomatosis and renal cell cancer syndrome
Autosomal dominant disease
Caused of FH gene mutation which expresses Fumarate hydratase
Characterised by uterine & cutaneous leiomyomata & an aggressive type papillary renal cell carcinoma.
It has increased propensiy for metastatic spread.
Birt –Hogg –Dube syndrome
Autosomal dominant inheritance pattern
Caused by BHD gene mutations which expresses folliculin
Syndrome is characterised by
Skin tumors
Pulmonary cysts
Renal tumors
Classification of Renal cell carcinoma depending upon the origin and cytogenetics
Clear cell carcinoma:
Common type (70 to 80% of RCC’s)
Origin – proximal tubular epithelial cells
95% are sporadic (few familial)
Assocaited with VHL syndrome
There is deletion of sequence on chromosome 3 which has VHL gene (3P25.3).Second non deleted allele of VHL gene shows somatic mutation or hypermethylation induced inactivation.This indicates that VHL gene is tumor suppressor gene.
VHL gene encodes for a protein that forms a part of ubiquitin ligase complex involved in the degradation of proteins. Important target protein is Hypoxia Inclucible Factor-1(HIF -1). By inactivation of VHL, HIF-1 levels are increased which causes inappropriate expression of certain genes like VEGF (gene that promote angiogenesis),Insulin like growth factor-1. HIF also collaborates with oncogenic factor MYC to “reprogram” cellular metabolism which factors growth
Excellent prognosis when compared to clear cell and papillary
XP11 translocation carcinoma
Genetically distinct subtype
Occurs in young patients
Cytogenetics- translocations of TFE3 gene located at Xp11.2 along with no of partner genes which results in increased expression of TFE3 transcript factor.
Collecting duct (Bellins duct) carcinoma-
1% or less of renal cell carcinomas
Origin – collecting duct cells in medulla
Cytogenetics –chromosomal losses & deletions without distinct pattern.
MORPHOLOGY
RCC affects mostly poles of the kidney
Clear cell RCC
Occurs as solitary unilateral circumscribed tumor which is bright yellow to gray white in colour.
Yellow colour is due to lipid accumulation in tumor cells.
Cut section – variegated with hemorrhagic & necrotic areas.
Microscopy-
Tumor cells are arranged in trabecular or tubular or solid or cystic pattern.
Tumor cells are polygonal or rounded having abundant clear or granular cytoplasm containing glycogen and lipids
Delicate vascular branching may be present
Tumor may invade pelvic calyces & may extend into ureter.
Characteristic feature in RCC is, it invades renal vein, interior vena cave and grows as solid cords of cells and may also extend into the right side of the heart
Papillary carcinoma
Can be multifocal and bilateral
Grossly they are large cystic & hemorrhagic
Microscopic:
Tumor cells are cuboidal to low columnar cells lining the papillae having fibrovascular core with foamy macrophages
Psammoma bodies may be present
Highly vascularised scant stroma is present.
Chromophobe RCC
Tumor cells have pale eosinophilic cytoplasm with perinuclear halo
Cells are arranged in solid sheets with perivascular arrangement of tumor cells
Collecting duct carcinoma
Tumor has irregular channels lined by highly atypical epithelium with hobnail pattern.
CLINICAL FEATURES
Clinical features in renal cell carcinoma are
Costovertebral pain
Palpable mass
Haematuria
Most common presentation is haematuria
Tumor is usually silent until it reaches 10cms or more in size
Other generalized symptoms are fever, weakness and weight loss
Renal cell carcinoma produces syndromes associated with hormone production. They are
Polycythemia
Hypercalcemia
Hypertension
Hepatic dysfunction
Feminization or masculinization
Cushing syndrome
Eosinophilia
Leukamoid reaction
Amyloidosis
Metastasis occurs widely before the local symptoms and signs. Most common organs for metastasis are Lungs (50%), bones (33%), followed by regional lymphnodes, liver, adrenal and brain
Prognosis depends upon grading, staging and presence or absence of distant metastasis.
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Reference
Charles E. Alpers. The Kidney. In: Vinay Kumar, Abul K. Abbas, Nelson Fausto, Jon C. Aster. Robbins And Cotran Pathologic Basis of Disease. Eighth edition, 2011;Chapter 20: 905-970
