Renal Tumors Flashcards
Describe the epidemiology of renal tumors
o About 40% of diagnosed die within 5 years
o Males > females (3:2)
o More common later in life (60+)
o Increasing incidence since the 1970’s for unknown reasons
o African-Americans affected 20% more than other ethnic groups
Two main acquired causes:
• Obesity (implicated in 40% of cancers)
• Smoking (implicated in 30%)
• HT = also a cause (may be from chronic inflammation)
• Other high risk situations: ESRD, familial/genetic RCC
Describe the detection of renal tumors
o Commonly as accidental finding on imaging
o Imaging criteria: enhancing mass on CT or MRI
• HU increased by 15 or more with contrast (because highly vascular)
o Symptoms = associated with advanced disease
List the subtypes of Renal Cell Carcinoma
Clear cell Papillary Type I Chromophobe Papillary Type II Collecting duct Renal medullary Uncategorized (1%)
Clear Cell Carcinoma
(85% = most common)
o Originates in proximal tubule
o Associated with mutation in Von Hippel Lindau gene (chromosome 3p)
o Sporadic (majority) or associated with VHL syndrome
o Gross: bright yellow
o Microscopic: chickenwire
Papillary Type I
(10%)
o Proximal tubule
o Associated with c-met oncogene activation on chromosome 7q
o Fairly good prognosis
Chromophobe
(2%) o Activation of folliculin gene o Collecting duct cells o Fairly good prognosis o Associated with Birt-Hogg-Dube syndrome
Papillary Type II
(rare)
o Associated with loss of Fumarate Hydratase form Krebs cycle → accumulation of fumarate → drives other oncogenic pathways
o Extremely aggressive
Collecting Duct
(rare)
o Very poor prognosis
Renal Medullary
(very rare)
o Collecting duct cells
o Associated with sickle cell carriers, commonly young
o High mortality
Transitional Cell Carcinoma (TCC)
- Effectively bladder cancer in renal collecting system
* Hallmark = Central tumors
Hereditary Types of RCC
Von Hippel-Lindau Disease
o Autosomal dominant (chromosome 3p)
• Mutation in VHL prevents Hypoxia Inducible Factor (HIF) inactivation
• HIF accumulates → stimulates VEGF and PDGF production
• Creates “pro-growth” environment
Clinical signs:
o Hemangioblastomas (especially cerebellar and spinal)
o Pheochromcytoma
o Angiomatosis (especially retinal)
o Other cysts: epididymis, broad ligament of uterus, endolymphatic sac, pancreas
o Clear cell RCC (often cystic)
Birt Hogg Dube Syndrome:
o Autosomal dominant of folliculin gene
• A tumor suppressor on chromosome 17p
• Found in skin, distal nephrons, and Type 1 pneumocytes
Clinical signs:
o Cysts: kidney and lung (leads to pneumothorax)
o Skin findings: Fibrofolliculomas (papules), trichodiscomas (benign, skin-colored tumor), achrochordons (skin tags)
Kidney cancer:
• Affects 15-30%
• Generally a chromophobe-oncocytoma hybrid tumor
• Relatively good prognosis
Describe appropriate radiographic and pathologic evaluation of renal masses
Bosniak classification of renal cysts:
o Types I and II: simple cysts
o IIF: more complex; need to follow
Grading: o Rated from 1-4 o Affected by: • Nuclear pleomorphism • Presence of nucleoli • Presence of mitoses
Tumor staging:
o T1a: < 4 cm
o T1b: 4-7 cm
o T2a: >7 m
o T2b: >10 cm
o T3a: invasion of peri-renal fat or renal vein clot
o T3b: tumor extends into vena cava below diaphragm
o T3c: tumor extends into vena cava clot above diaphragm or direct invasion of vein wall
o T4: direct extension beyond Gerota’s fascia or into adrenal gland
Nodes:
o N0: no nodal disease
o N1: nodal disease present
Metastasis
o M0: non present
o M1: metastatic disease present
Give examples of clinical syndromes associated with renal cell carcinoma.
Local effects: o Hematuria from tumor invasion o Flank pain o Palpable mass (rarely) o Abrupt varicocele development in men
Systemic effects: o Weight loss o Cough o Lymphadenopathy o Bone pain o Abdominal pain o Edema o Seizures
Paraneoplastic (in 20%)
o Hypercalcemia
o Hypertension
o Polycythemia
o Anemia
o Stauffer’s Syndrome
• Elevated liver function tests without hepatic invasion
• IL-6 and other cytokines implicated
• Generally resolves after resection of mass
• If not resolve: think about residual or metastatic tumor
Physical exam:
o Flank mass (but extremely difficult to palpate)
o Sudden development of L sided varicocele in men (swelling of testicular veins)
• Due to occlusion of left renal vein by tumor with occlusion of left gonadal vein
Discuss appropriate therapies, both surgical and medical, for small and large renal masses, with or without metastasis.
Surgical (primary treatment):
o Remove whole kidney
o Remove part (try to save nephrons) = Safe with smaller tumors when no metastasis
o Remove part of kidney through small holes (minimally invasive): Limited to tumors <5 cm and located away from center of kidney; Avoids flank incision = benefits patient
o Cytoreductive Nephrectomy: Remove primary tumor, follow with immunotherapy to augment immune system
• Improves survival
Newer, more targeted agents being evaluated:
• Interferon-alpha
• IL-2
• VHL pathway
• mTOR inhibitors
Surgical alternatives:
Destroy part of kidney through percutaneous approach
• Uses CT or US guidance
• Most effective on smaller masses (3-4 cm)
• Currently not as good, but appropriate for patient with high surgical risk or significantly elderly
Observation
• Due to slow growth rate of small masses and low likelihood of metastasis
• In patients with high surgical risk or infirm
• Not appropriate for younger or healthy patients with significant life expectancy
