Renal cancer Flashcards
Renal papillary adenomas mostly occur in the (1)
- renal cortex
Angiomyolipoma of the kidney is a tumor composed of an admixture of ?
smooth muscle, blood vessels and fatty tissue
Angiomyolipoma of the kidney originate from ?
perivascular epithelioid cells
Angiomyolipoma of the kidney frequently seen (up to 50%) in cases of (1), loss of function mutation of TSC1 or the TSC2 tumor suppressor gene
tuberous sclerosis
While they are histologically benign, angiomyolipomas of the kidney are important because of their propensity for (1) due to their increased vasculature
- spontaneous hemorrhage
Renal oncocytoma, is thought to arise from the (1); it accounts for up to 15% of all renal neoplasms.
- collecting ducts
The Renal oncocytoma tumors are (1) in appearance and frequently show (2). The tumor cells are strongly (3) and their cytoplasm demonstrates numerous (4) when viewed with the electron microscope
- tan
- a central scarred area
- eosinophilic
- mitochondria
The common benign renal neoplasms are ?
renal papillary adenoma, angiomyolipoma and renal oncyctoma
(1) is the biggest risk factor for renal cancer
- Tobacco smoking
Risk factors for renal cancer besides tobacco smoking
Hypertension, exposure to heavy metals, asbestosis exposure and chronic kidney disease are additional risk factors along with a history of long term dialysis(acquired cystic disease).
(1) accounts for 80% of renal cancers.
- Clear cell renal cell carcinoma
Both familial and sporadic types of clear cell renal cell carcinoma are associated with (1) of function of the (2) gene on chromosome (3)
- loss
- VHL tumor suppressor
- 3
(1) gene encodes for proteins involved in the ubiquitin ligase complex which is involved in protein degradation. One protein regulated by this complex is (2) This is a factor promoting cell growth and angiogenesis.
- VHL
- HIF-1 (hypoxia inducible factor).
refers to clear cell renal cell carcinoma
When (1) is inactivated the activity of (2) goes unregulated thus increasing cell growth and proliferation and tumor development
- VHL
- HIF-1 (hypoxia inducible factor).
refers to clear cell renal cell carcinoma
Papillary renal cell carcinoma sporadic cases show (1) and loss of (2).
- trisomy 7 and trisomy 17
2. Y chromosome in males
Familial forms of papillary renal cell carcinoma feature (3)
- trisomy chromosome 7.
Both familial and sporadic forms of papillary renal cell carcinoma in addition feature (1) mutations.
- activating MET
Clinical features of renal cell carcinoma are (1). Constitutional symptoms of (2) are often also present.
- costovertebral angle pain, presence of a palpable mass and often hematuria (intermittent)
- fever, malaise and weight loss
Renal cell carcinomas can produce a diverse number of symptoms from abnormal hormone production such as (1) which may confuse the diagnosis.
- polycythemia, HTN, hypercalcemia and Cushing’s syndrome
Frequent metastatic sites of renal cell carcinomas are ?
lungs and bone
Tumor extension to involve perirenal or the presence of tumor within (1) are signs of poor prognosis
- renal veins (renal vein invasion)
(1) are the mainstays of treatment along with (2) drugs
- Radical or partial nephrectomy (for smaller tumors) and chemotherapy
- VEGF and tyrosine kinase inhibitor
Urothelial carcinoma originates from the (1). (2) is a frequent presenting symptom. Larger tumors may produce (3)
- urothelial lining cells of the renal pelvis
- Hematuria
- hydro nephrosis
Urothelial carcinoma may frequently be present in other portions of the (1)
renal pelvis, ureters or bladder
(1) is the most common primary kidney tumor in children (1 in 10,000 children) and the fourth most common pediatric malignancy. Tumors are bilateral in up to 10% of cases.
- Wilms tumor or nephroblastoma
Wager syndrome patients (1) have a >30% lifetime risk of developing a Wilms tumor
- aniridia, genital abnormalities, mental retardation
Wager syndrome features germline deletions of (1) and studies of these patients led to the identification of the (2).
- 11p13
2. Wilms tumor associated gene (WT1)
(1) is crucial to the proper development of the kidneys and gonadal development.
- The WT1 gene
Denys-Drash syndrome patients (1) have a 90% lifetime risk of developing a Wilms tumor. These patients have a (2) mutation of the (3) ( this interferes with the proper function of the remaining wild type allele).
- gonadal dysgenesis, early onset nephropathy with renal failure
- dominant negative inactivating
- WT1 gene
Beskwith-Wiedmann syndrome patients (1) also have an increased incidence of Wilms tumors.
- enlargement of individual body parts or body segments
Beskwith-Wiedmann syndrome is an example of a disorder of (2) whereby certain genes are inactivated during gametogenesis.
- genomic imprinting
The area of interest is an area of at least 10 genes distal to the WT1 locus and although the exact gene has not been identified the area is now called the (3). (4) is one of the genes in this area and it normally is only expressed by the paternal allele and the maternal gene is “imprinted” (inactivated normally”).
- “WT2 gene”.
- IGF-2
refers to Beskwith-Wiedmann syndrome
Loss of imprinting of the (1) gene is believed to occur allowing for overexpression of (2) thus promoting organ enlargement or tumor development in (3)
- maternal
- IGF-2
- Beskwith-Wiedmann syndrome
often come to light due to presence of an easily palpated very large abdominal mass that may even extend into the pelvic area
Wilms tumors
Wilms tumors may produce what s/s?
intestinal obstruction, hematuria, fever and weight loss.
Three groupings of congenital malformations feature an increased risk for the development of Wilms tumor
Wager syndrome patients (aniridia, genital abnormalities, mental retardation)
Denys-Drash syndrome patients (gonadal dysgenesis, early onset nephropathy with renal failure)
Beskwith-Wiedmann syndrome patients (enlargement of individual body parts or body segments)
Angiomyolipoma
Lesion with 1) Origin is from 2) 25‐50% of 3) patients have them Loss of suppressor function in TSC1 or TSC2 genes Significant because risk of 4)
1) fat, smooth muscle and blood vessels
2) perivascular epithelioid cells
3) Tuberous Sclerosis
4) spontaneous hemorrhage
Renal ocnocytoma–> gross hallmark
central scarring
Clear cell carcinoma
VHL encodes protein for _____ promoting degradation of ______ which promotes cell growth and ____
ubiquitin ligase complex
HIF‐1 (hypoxia inducible factor )
angiogenesis
halo around nucleus
Chromophobe type renal cell carcinoma
Diverse symptoms from hormone production (systemic symptoms unrelated to the kidney itself) Polycythemia HTN Hypercalcemia Cushing’s syndrome
Renal cell carcinoma clinical features
Treatment options for renal neoplasms:
3 things
Radical nephrectomy Partial nephrectomy ( smaller tumors) VEGF and tyrosine kinase inhibitors if metastatic disease present
aniridia, genital abnormalities, mental retardation‐33% lifetime risk
Wager syndrome
Germline deletions of 11p13 (WT1 gene);
Two hit hypothesis
Wager syndrome
Dominant negative inactivating mutation of WT1 gene
Denys‐Drash syndrome
gonadal dysgenesis, renal abnormalities‐90% lifetime risk
Denys‐Drash syndrome
Denys‐Drash syndrome
1) mutation of WT1 gene
Interferes with function of the remaining wild type allele
Bi‐allelic WT1 inactivation leads to tumor development
1) Dominant negative inactivating
Triphasic combination of elements in WILMS tumor
1, 2, 3
blastemal
stroma;
epithelial cell types(abortive tubules or glomeruli)
