Path: Tumors of the Kidney and Urinary Tract

uriniferous tubule

functional unit of the kidney

papillary adenoma

• small, discrete adenomas arising from the renal tubular epithelium

• found commonly at autopsy

• <1.5 cm in diameter

• well demarcated and low-grade nuclei

• appear grossly as pale yellow-gray discrete, well-circumscribed nodules

papillary adenoma

angiomyolipoma

benign vessels + smooth muscle + fat tumor

angiomyolipoma

• originate from perivascular epithelioid cells

• 25-50% of patients with tuberous sclerosis (TS) - TSC1 and TSC2

angiomyolipoma

buzzword: retinal hamartomas and cardiac rhabdomyomas

angiomyolipoma

oncocytoma

arises from intercalated cells of CD

oncocytoma

numerous mitochondria = granular eosinophilic cytoplasm

oncocytoma

mahogany brown with central scar

xanthogranulomatous pyelonephritis

• proteus (>50%), E coli, pseudomonas, klebsiella

• urine cultures negative!!

• palpable mass that can mimic tumor

• UT obstruction, staghorn, DM

xanthogranulomatous pyelonephritis

pus, scarring, stones

xanthogranulomatous pyelonephritis

sheets of foamy, lipid-laden macrophages

• cigs

• long term dialysis or hypertension

• ESRD, chronic kidney disease

• trichloroethylene (metal degreaser and chemical additive)

RF for renal cancer

RCC

von hippel-lindau syndrome (VHL)

• AD

• chromosome 3p mutation

• renal cysts and bilateral, multiple

von hippel-lindau syndrome (VHL)

• retinal and CNS hemangioblastomas

• pheos

• pancreatic serous cystadenoma

• cafe au lait

hereditary papillary carcinoma

• AD

• MET proto-oncogene mutations

• multiple bilateral

hereditary leiomyomatosis and RCC syndrome

• AD

• mutations of FH gene (fumarate hydratase)

• cutaneous and uterine leiomyomas

• aggressive with increased propensity for mets

birt-hogg-dube syndrome

• AD

• folliculin mutation

• skin, pulmonary (cysts or blebs), renal tumors (oncocytic and chromophobe)

clear cell RCC

• most common RCC

• arise from proximal tubular epithelium

• tendency to invade renal vein

von hippel-lindau syndrome (VHL)

buzzword: high HIF-1, increase VEGF and IGF-1

clear cell RCC

clear cell RCC

glycogen and lipid cytoplasm with rich vascular network

papillary RCC

• arise from distal convoluted tubules

  • multifocal and bilateral

MET

proto-oncogene that encodes the tyrosine kinase receptor for hepatocyte growth factor

papillary RCC

papillary vs. clear cell: multifocal

clear cell RCC

papillary vs. clear cell: arise in proximal tubular epithelium

papillary RCC

papillary vs. clear cell: arise in distal tubular epithelium

papillary RCC

papillary RCC

chromophobe RCC

arise from intercalated disc of collecting ducts; multiple chromosome loss and extreme hypodiploidy

chromophobe RCC

RCC with best prognosis

intercalated cells

chromophobe RCC and oncocytomas both arise from?

chromophobe RCC

raisinoid nuclei

CD (bellini duct) RCC

• very rare

• several chromosomal losses and deletions

• arise in collecting duct cells in medulla

CD (bellini duct) RCC

medullary carcinoma

buzzword: younger patients with sickle cell trait

Xp11 translocation carcinoma

• genetically distinct subtype of RCC

• young patients

• TFE3 translocation

• clear cytoplasm with papillary architecture

clear cell RCC

RCC type: -3p VHL

papillary RCC

RCC type: +7 (met), +17, -Y

hematuria

most reliable cue for RCC

1. costovertebral

2. palpable mass

3. hematuria

clinical triad for RCC

lung, bone (LN, liver, adrenal glands, brain)

most common RCC mets to?

UCC of renal pelvis

patients with Lynch syndrome have significantly increased incidence of

UCC

which usually diagnosed earlier, UCC or RCC?

UCC of renal pelvis

ureteropelvic junction obstruction (UPJ) of infants and children

• most common cause of hydronephrosis

• present early

• males

• bilateral

ureteropelvic junction obstruction (UPJ) of adults

• women

• unilateral

• abnormal organization of smooth muscle bundles or excess stromal deposition of collagen between smooth muscle bundles

fibroepithelial polyp

• tumor-like lesion of the ureter in children

• loose, vascularized CT overlaid by urothelium

proximal

unilateral obstructive lesions of the ureter due to stones or neoplasms are usually proximal or distal?

distal

bilateral obstructive lesions of the ureter such as BPH are usually proximal or distal?

vesicoureteral reflux (VUR)

• most common and serious congenital anomaly of the bladder

• abnormal movement of urine from the bladder into ureters and kidneys

• predisposes to ascending pyelonephritis and loss of renal function

• abnormal connections between the bladder and vagina, rectum, or uterus may create fistulae

primary

vesicoureteral reflux due to incomplete closure of the UVJ or failure of anti-reflux mechanism is due to shortening of the intravesical ureter

secondary

VUR due to abnormally high pressure in the bladder causing failure of the closure of the UVJ during bladder contraction

obstruction → hydroureter → hydronephrosis → pyelonephritis

effect of intrinsic or extrinsic ureteral obstruction?

renal stones

most common cause of intrinsic urinary tract obstruction

BPH

most common cause of acquired bladder diverticulum

focal failure of development of detrusor muscle or urinary tract obstruction during fetal development

most common cause of congenital bladder diverticulum

exstrophy of the bladder

• developmental failure in the anterior wall of the abdomen and the bladder

• communicates directly with the abdominal surface

• chronic infection

• increased risk of adenocarcinoma

urachal canal

• connects the fetal bladder with the allantois and is normally obliterated at birth

• failure to close can result in a fistulous urinary tract connection between the bladder and umbilicus

• increased risk for adenocarcinoma

urachal cyst

central region of patent urachus persists

cystitis

inflammation of the bladder, more common in women

e coli (proteus, klebsiella, enterobacter)

most common cause of infectious cystitis

iatrogenic

non-infectious cystitis in patients receiving systemic chemotherapy or pelvic irradiation

hemorrhagic

non-infectious cystitis due to cytotoxic agents such as cyclophosphamide

interstitial (chronic pelvic pain syndrome)

• cystitis with unknown etiology

• mucosal fissures and punctate hemorrhages (glomerulations)

• rule out CIS

• symptoms > 6 weeks

malakoplakia

• distinctive chronic inflammatory reaction that appears to stem from acquired defects in phagocyte function

• chronic E coli or proteus infection

• renal transplant recipients! (immuno comp)

malakoplakia

sheets of large foamy macrophages with granular cytoplasm = von hansemann cells

malakoplakia

michaelis-gutmann bodies = laminated mineralized concretions resulting from deposition of calcium in enlarged lysosomes

polypoid cystitis

• inflammatory lesion resulting from irritation of the bladder mucosa

• result of instrumentation (catheters)

• mistaken for papillary UCC (clinically and histologically)

cystitis glandularis

metaplasia of von Brunn nests and take on a cuboidal or columnar appearance

cystitis cystica

metaplasia of von Brunn nests and take on a cuboidal or columnar appearance that being very dilated spaces

keratinizing

which type of squamous metaplasia of the bladder can be a precursor lesion to dysplastic lesions and often seen with schistosomiasis

nephrogenic adenoma

• unusual lesion of the bladder that may not be a form of true metaplasia

• same sex chromosome status with allograft kidneys in transplanted patients

• overlying urothelium is focally replaced by cuboidal

urothelial (transitional)

most common neoplasm of the bladder

1. papillary

2. flat (CIS)

two types of noninvasive urothelial cell lesions that can become invasive

false (noninvasive papillary can be low or high grade, but flat are ALWAYS high grade)

T/F: noninvasive flat urothelial carcinoma (CIS) can be low or high grade

cigarette smoking

most important risk factor for UCC of the bladder

polypoid urothelial carcinoma of the bladder

papillary urothelial neoplasms of low malignant potential (PUNLMP)

• thicker urothelium with greater density of cells

• larger than papillomas

• indistinguishable from cancers

• can recur but progression rare

invasive UCC

• painless hematuria, frequency, urgency, dysuria

• occasional ureteral orifice obstruction may lead to pyelonephritis or hydronephrosis

depth of invasion into bladder wall

most important prognostic factor for invasive UCC and determine treatment modality

painless hematuria

most common symptom of bladder cancer

BCG (bacillus calmette-guerin)

intravesical instillation of an attenuated strain of mycobacterium to treat bladder cancer

schistosomiasis

most common risk factor for SCC of the bladder

false (rare)

T/F: metastatic spread of the bladder is very common