Neoplasms Of The Urinary Tract Flashcards
What is the most common renal neoplasm of childhood?
Wilms tumor
What three syndromes are associated with an increased risk for wilms tumors
Denys-Drash (DDS)
- associated with inactivation of WT1 gene on 11p13
Beckwith-Wiedemann
- associated with WT2 inactivation on band p15.5 of chromosome 11
- presents with hypermegaly of all organs in the body
WAGR syndrome
- associated with inactivation of WT1 gene on 11p13
only need one mutated copy of WT1 gene
Renal papillary adenoma
Small/discrete (<0.5cm) tumors arising from the renal tubular epithelium
- commonly found at autopsy (7-22%)
Are usually pale-yellow in appearance
- share similar IHC and cytogenic features with papillary cancers
- includes trisomy 7 and 17*
the prognostic factor is SIZE >3cm = going to die
Angiomyolipoma
Benign neoplasm consisting of smooth muscle and fat droplets
Clinical importance of angiomyolipoma is due largely to spontaneous hemorrhages.
- *Are present in 25-50% of patients with tuberous sclerosis**
- caused by a loss of function mutations in TSC1/2 tumor suppressor genes
- characterized by lesions of the cerebral cortex and skin abnormalities such as unusually benign tumors
Oncocytoma
An epithelial neoplasm composed of large eosinophilic cells with having small rounded normal nuclei appearance
- accounts for roughly 5-15% of renal neoplasms
Tumors are tan/brown and homogeneous with a generalized central scar (33%)
- the scar is fibrotic more than necrosis
Renal cell carcinoma (RCC)
Represent 3% of all cancers in US
- makes up 85% of renal cancers as well
- 5% in males, 3% in females (2:1)
- usually occurs in 60-70s
Risk factors
- smokers
- hypertension
- obese patients
- cadmium exposure
- acquired polycystic disease with dialysis (30x increase)
3 common types
- clear cell
- papillary cell
- chromophobe renal
Common metastasis sites = lungs and bones
Clear cell carcinoma
Is the most common type of RCC overall
- accounts for 65% of total RCC’s
- in 40-60% of clear cell patients, they present with hundreds of bilateral renal cysts
Make of cells with very clear cytoplasm
- most common arise in the proximal tubular epithelium and appear bright yellow-gray-white with foci of hemorrhagic discoloration
- most are sporadic in nature, but those that aren’t are tied to familial forms of Von hippel-Lindau disease*
- VHL = also shows hemangioblastomas of the cerebellum and retina
- VHL pathogenesis = VHL gene mutations in 3p25 band on chromosome 3 in both copies
very commonly invades the renal vein and grows as a solid column of cells before metastizing
How does VHL mutations cause clear cell carcinomas?
Normal VHL protein action = degrades hypoxia-induced factors (HIF’s)
In VHL disease = HIFs stay around and are transcription factors for vascular endothelial growth factor (VEGF)
Clinical features of renal cell carcinoma
Triad of
- painless hematuria (most common 50%)
- Palpable abdominal mass
- dull flank pain
- *may not show all of these three, but these are the most common**
Often shows paraneoplastic effects also
- polycythemia
- fever
- hypercalcemia
- HTN
- Cushing syndrome
Papillary renal cell carcinoma
Account for 10-15% of all renal cancers and are frequently multi focal and bilateral
Look like early-stage tumors and have a unique papillary growth pattern
- have clear and pinkish cytoplasm
Can be familial and sporadic forms
- familial = MET proto-oncogene mutations on chromosome 7q
- sporadic = can be above, but also can be idiopathic
Chromophobe renal carcinoma
5% of all renal cell carcinomas
Composed of cells with prominent cell membranes and pale eosinophilic cytoplasm
- have a “halo” like appearance around the nucleus
Have multiple chromosome losses and extreme hypodiploidy genetically
- are thought to grow from intercalated cells of collecting ducts and have excellent prognosis
- also difficult sometimes to distinguish from oncocytomas
Urothelial cell carcinomas (transition cell carcinoma)
5-10% of primary tumors arise from the urothelial of the renal pelvis
- are also the majority of tumors found in the ureter
- most occur in 60-70s
Have a wide variety of ranges (can be grade 1 benign to aggressive stage 4 metastatic)
- regardless they all have poor prognosis since they have a very high tendency to infiltrate the walls of the renal pelvis and calyces
Produce hematuria and are always small when discovered (since hematuria starts very early
- in late stages = hydronephrosis
Wilms tumor
Nephroblastoma
Most common in children 2-5 yrs of age
Are typically large solitary well-circumscribed masses with tan-gray colors
Can present with “nephrogenic rests” which are precursor lesions of wilms tumors in the renal parenchyma adjacent to the tumor
- if present, increases risk for development of wilms tumors in the contralateral kidney
Clincial features
- fever
- sometimes hematuria
- palpable mass that extends pass midline (most common)
Prognosis is very good and only requires surgical resection and mild chemo unless diffuse anaplasia is present
If a wilms tumor has foci of anaplasia on histology, what gene is additionally mutated?
TP53
- also signals resistance to chemotherapy
foci of anaplasia = deep purple and segmented nuceli
Urinary bladder cancers
More common in white males than females and other races(2x) and more common in the industrialized world
- most common patients aged 50-80s
95% are epithelial cell origin with most being urothelial or transitional tumors
Risk factors
- cigarette smoking
- occupational carcinogens
- family history
- excessive cyclophosphamide use or radiation use
- **schistosoma infections
Symptoms:
- painless hematuria
- flank pain and sometimes hydronephrosis if chronic
