• transitional epithelium aka urothelium
  • renal calyces, ureters: 3-4 layers
  • bladder: 5-7 layers (varies according to bladder distension)
• superficial zone
  • single layer of large, flattened cells called umbrella cells (indicates normal urothelium)
• cell layer thickness of intermediate zones vary based on stretch of bladder
  • 4-5 layers in stretched
  • 6-8 layers in fully contracted
• basal zone (single layer) is cuboidal when contracted bladder and flat when stretched bladder

• von Brunn's nests- compact group of epithelial cells in the lamina propria of the bladder adjacent to or in direct contiguity with epithelium
• cystitis cystica-von Brunn's nests present a central lumen and accumulation of colloid material
• cystitis glandularis- further enlargement of central lumen of von Brun;s nests and a columnar, mucus secreting cell lining

• reactive atypia
• dysplasia
• atypia of uncertain clinical significance
• carcinoma in situ
  • flat non invasive carcinoma
  • occur alone or in association with invasive carcinoma (more common to be association)

• epidemiology
  • very common in endemic countries (Egypt)
  • much less common in US
• causative agent: Schistosoma hematobium

• leiomyosarcoma (most common bladder sarcoma in adults)
• rhabdomyosarcoma (most common bladder sarcoma in children)
  • embryonal type with botryoid features

• benign
• malignant

Uncommon

• direct extension from carcinomas of cervix, prostate, and rectum is most common
• hematogenous spread (less common)

• composition
  • delicate fibrovascular cores covered by normal appearing urothelium
• characteristics
  • small
  • do not recure

• growth pattern: papillary vs. solid/flat
• histologic grade
  • based on cellular atypia
  • correlates with patient survival
• pathologic stage
  • invasive vs. noninvasive
  • if invasive, depth of invasion
  • lamina propria invasion vs. muscle invasion

• papillary
• flat, non-papillary growth
• noninvasive
• invasive/infiltrating

• exophytic polypoid lesion attached to mucosa by stalk with tumor grwoing into lumen of bladder
  • penetration of BM, infiltration of wall may or may not be present

• tumor confined to surface
• tend to be higher grade than papillary lesions

• thickening of mucosa by proliferation of carcinoma cells without penetrating BM

• penetrating the mucosal BM
• growing into the lamina propria and wall of bladder

• tumor cells well differentiated, closely resemble normal transitional cell epithelium
• may show some atypia
• number of cell layers may be slightly increased and there may be some loss of polarity

• tumor still readily recognizable as originating from transitional cell epithelium
• number of cell layers increased
• greater loss of polarity of cells
• mitoses readily found
• cells with great variability in cell size, shape, arrangement of nuclear chromatin

• tumor difficult to recognize from transitional epithelial origin
• all changes of grade II worse, esp. disarray of cells
• prominent mitoses

• all transitional cell carcinomas have a tendency to recur following excision, and usually the recurrence may exhibit greater anaplasia

• renal papillary adenoma
• renal oncocytoma
• angiomyolipoma
• renal fibroma (hamartoma, interstitial cell tumor)

• gross composition
  • small (<1 cm)
  • gray to yellow circumscribed masses within renal parenchyma
• microscopic composition
  • branching papillary fronds with thin fibrovascular cores frequently projecting into cystic space
  • tubular, glandular, sheet like growth patterns may also be seen
  • cells bland with round nuclei
    • inconspicuous nucleoli
    • abundant clear to eosinophilic cytoplasm
    • thought to oritinate from tubular epithelium

• microscopic appearance
  • epithelial neoplasma of cells with abundant eosinophilic cytoplasm and small round nuclei
  • cytoplasm with abundant mitochondria
• gross appearance
  • well circumscribed
  • homogeneous and brown
  • frequently with central scar
• tx- excision (partial or complete)
• clinical app- can look like granular renal cell carcinoma or chromophobe renal cell carcinoma

• composition
  • vary between different tumors and between different areas of same tumor
  • irregular and admixed proliferations of bv's, smooth muscle, and fat
• main clinical significance- resemble renal cell carcinoma and found within 25% of patients with tuberous sclerosis
• tx- complete excision

• gross appearance
  • small
  • present in renal medulla
  • gray white firm nodules
• microscopic appearance- proliferations of bland fibroblasts, collagen
• prognosis- clinically benign lesions that have no malignant potential

• male predominance
• more common in 6th and 7th decade of life
• major risk factors
  • tobacco
  • obesity
  • HTN
  • unopposed estrogen therapy
  • some enviornmental exposures
  • chronic renal insufficiency
  • acquired cystic disease
• most case are sporadic

• von Hippel-Lindau syndrome
• hereditary clear cell carcinoma
• hereditary papillary carcinoma

• costovertebral pain
• palpable mass
• hematuria (may lead to anemia as well)

frequently asymptomatic until large

• polycythemia
• hypercalcemia
• HTN
• hepatic dysfunction
• feminization
• masculinization
• Cushing's syndrome
• eosinophilia
• leukemoid reactions
• amyloidosis

• lungs
• bones
• regional LN
• liver
• adrenal glands
• brain

• tx- nephrectomy
• prognosis- half 5 yr survival

• clear cell carcinoma (MOSTCOMMON)
• papillary carcinoma
• chromophobe renal cell carcinoma
• collecting duct carcinoma

• gross appearance
  • nodular and variegated masses within renal parenchyma
  • extend beyond capsule and have propensity for venous invasion
  • cut surface generally bright yellow (high lipid content of cells) with prominent areas of hemorrhage and necrosis
• microscopic appearance
  • prominent capillary vasculature
  • cells arranged in sheets, trabeculae, tubules
  • cells with clear cytoplasm (due to abundant lipids and glycogen)
  • nuclie vary from small and uniform with inapparent nucleoli to large, pleomorphic with prominent macronucleoli
• some have sarcamatoid differentiation (bad prognostic sign)

• gross appearance
  • papillary architecture may be evident
  • focal cystic spaces and frond like projection
• microscopic appearance
  • papillary architecture pronounced
  • cells cuboidal to low columnar with eosinophilic cytoplasm
  • interstitial foam cells in papilolary cores
  • psammoma bodies may be present

• pale eosinophilic cells
• distinct cell borders and perinuclear clearin

mimic oncocytoma

• associated with sickle cell trait (termed medullary carcinoma which is uniformly and rapidly fatal in clinical course)
• high grade variant
• lined by highly atypical epithelium with hobnail pattern

• sporadic and inherited
• associated with deletion/unbalanced translocation resulting in loss of portion of chromosome 3p
  • contains VHL gene, which explain high incidence of association with renal cell carcinoma
  • this is a tumor suppressor gene that inhibits elongin, a transcription elongation complex

• trisomy 7 (familial and sporadic)- MET proto-oncogene
  • a TK receptor for hepatocyte GF 
• trisomy 16
• trisomy 17
• loss of Y chromosome
• chromosome 1: PRCC (associated with sporadic tumors in children)

• unique symptoms
  • renal colic
  • hydronephrosis
  • hematuria when fragment (they sit right in the collecting system)
• unlike renal cell carcinomas, they tend to become apparent earlier in disease course
• similar clinical, gross, microscopic features to tumors of the rest of the UT

• increased incidence of additional synchronous and metachronous urothelial carcinomas
• infiltration of pelvic and calyceal walls is common
  • prognosis is worse than urothelial carcinomas
  • low grade lesions: 5 yr survival 50-70%
  • high grade lesions: 5 yr survival 10%

• most common neoplasm of childhood
• fifth most common malignant neoplasm of childhood
• mostly occur btw ages 2-4 (90% of cases before age 6)
• no geneder predominance
• incidence stable worldwide
• no known environmental causative factors

• most common presenting symptoms of palpable abdominal mass with concomitant:
  • hematuria
  • abdominal pain
  • GI obstruction
  • HTN
  • retroperitoneal hemorrhage
• genetics- generally sporadic associated with certain congenital syndromes
  • WT1 and WT2 (tumor suppressor genes) located on chromosome 11p

• gross appearance
  • circumscribed masses usually greater than 5 cm
  • cut surface fleshy, friable, grey-white to tan, and may have areas of hemorrhage and/or necrosis

• blastema

  • undifferentiated small cells w/ hyperchromatic nuclei, scant cytoplasm
  • frequent mitotic figures arranged in serpinginous, trabecular, diffuse, nodular patterns

  epithelial

  • primative tubules, glomerular structures, and rare rosettes
  • foci of mucinous or squamous metaplasia may be seen as well as neural or endocrine differentiation
• stromal
  • fibroblastic and/or myxoid spindle cell background
  • may have heterologous elements (muscle, bone, fat, cartilage, glia)

varying proportions of all three elements, although biphasic and monophasic tumors can occur 

• grading- presence, distribution, quantity of nuclear anaplasia
• staging- based on:
  • completeness of resection
  • confinement of the tumor to the kidney
  • prior open or needle core biopsy
  • hematogenous metastases

• regional LN's
• lungs
• liver

• age greater than 2 yrs old
• high stage at presentation
• diffuser anaplasia

• overall prognosis is good
• most cases have no anaplasia and present at stage 1 and 2
• tx is always curative
  • surgery in select cases
    • usually include double agent chemo
  • if tumor has poor prognosis, you can use more toxic chemo and radiation