Lecture 21: Kidney Tumors & Lower Urinary Tract

Renal Papillary Adenoma

Renal Papillary Adenoma

benign: < 0.5 cm & Papillary architecture

Oncocytoma

Oncocytoma

dense pink cytoplasm (eosinophilic) cell nests with bland nuclei; little mitotic activity in a paucicellular hyalinized stroma

Oncocytoma

Benign

Gross: well circumscribed but unencapsulated, brown to yellow, often with central scar

Micro: dense pink cytoplasm (eosinophilic) cell nests with bland nuclei; little mitotic activity in a paucicellular hyalinized stroma

Angiomyolipoma

Angiomyolipoma

Angiomyolipoma

Benign, but if large may fatally hemorrhage

Neoplasm composed of: Vessels + Smooth muscle + Fat

Genetic AML: In Tuberous Sclerosis LOF mutations of Tuberous Sclerosis Complex Tumor Suppressor genes TSC1 (Hamartin) or TSC2 (Tuberin) normally inhibit mTOR (mTOR upregulates MYC → cell cycle progression).

Cutaneous Stigmata: Facial Angiofibromas, Periungual Fibromas, “Ash leaf” spots (hypomelanotic macules) or Shagreen patches (plaque-like skin lesions usually on nape of neck or lower back); nearly all have CNS involvement (intractable epilepsy, cognitive impairment); some develop Heart Rhabdomyoma or Pulmonary Lymphangioleiomyomatosis (proliferation in lung of smooth muscle-like cells)

Renal Cell Carcinoma

Top risk factor: Tobacco

Clear Cell (Conventional) type: most common, VHL mutations

Yellow color due to lipids in the clear cells; marked vascularity with hemorrhages (↑VEGF); multiple foci of cystic necrosis

Clear cytoplasm due to Glycogen & Lipids

Early metastasis and renal vein invasion

Papillary: GOF Germline MET Oncogene

papillae & foamy macrophages within stalks

Clinical features of Renal Cell Carcinoma

Costovertebral pain, palpable mass, hematuria

Tumor may be asymptomatic until it reaches a large size → fever, malaise, cachexia

Paraneoplastic Syndromes: Hypercalcemia (PTHrP & other cytokines), Hypertension (↑ Renin), anemia of Chronic Disease (↑ Hepcidin), Polycythemia (↑ Erythropoietin), Cushing’s disease (↑ ACTH), liver dysfunction, eosinophilia, leukemoid reactions, AA amyloidosis

Most common cause of Hydronephrosis in infants & children

Ureteropelvic Junction (UPJ) Obstruction- congenital

Most common congenital bladder abnormality

Vesicoureteral Reflux (VUR)

Reflux Nephropathy (repeated Acute or Chronic Pyelonephritis; loss of urine concentrating ability; hypertension; renal failure; high back pressure generated by bladder during micturition → hydronephrosis)

Pyelonephritic scarring

Exstrophy of the bladder

Exstrophy of the bladder

Exstrophy of the bladder

Exstrophy of the bladder

Urachus

Urachus (median umbilical ligament) is a fibrous remnant of embryonic Allantois that runs that from bladder dome to umbilicus

Urachal Fistula: urine passed via belly button

Bacterial Cystitis

Predisposing factors: obstruction, women, long-term catheterization

Complication: Pyelonephritis → leukocyte casts in urine

Hemorrhagic cystitis

cytotoxic chemotherapy (Cyclophosphamide) or Adenovirus infection

Interstitial Cystitis (Chronic Pelvic Pain Syndrome)

fissures, punctate hemorrhages, ulceration (Hunner Ulcers)

middle-aged women

may ultimately progress to a scarred contracted bladder

path → minimal changes, few Mast cells in mucosa

Polypoid Cystitis

due to marked submucosal edema from irritation

most often seen with indwelling catheters

Malakoplakia

usually in context of chronic bacterial infection or immunosuppressed transplant patients

Path → sheets of macrophages with abundant granular cytoplasm (Phagolysosomes with bacterial fragments) & mineralized inclusions (Michaelis-Gutmann bodies)

Malakoplakia

Soft, yellowish plaques

Malakoplakia

concentrically layered Michaelis-Guttman bodies

Malakoplakia

Macrophages with abundant eosinophilic granular cytoplasm

Michaelis-Gutmann body

Malakoplakia

Michaelis-Gutmann bodies containing Iron & Calcium

Cystitis Cystica et Glandularis

Chronic Cystitis or mucosal irritation

Extensive intestinal type metaplasia is a risk factor for adenocarcinoma

Squamous Metaplasia

in response to chronic injury, urinary tract infections, irritation or inflammation

Risk factor for squamous cell carcinoma

Nephrogenic metaplasia/adenoma

Chronic Cystitis or mucosal irritation

No malignant potential

Bladder Cancer

Urothelial derived Transitional Cell Carcinoma (TCC)

Risk factors:

Cigarettes

male & Older age

industrial exposure to Aromatic amines (Aniline dyes)

Schistosoma haematobium infection → squamous carcinoma

Therapeutic irradiation or cyclophosphamide

Phenacetin

Bladder Cancer Clinical and Diagnosis

usually presents with PAINLESS HEMATURIA

may present with symptoms from obstruction (hydronephrosis) or pyelonephritis

Diagnosis: Cystoscopy

BIG PICTURE for Urothelial tumors

Low grade, Noninvasive tumors with papillary growth are not going to kill you

High grade, Noninvasive, papillary or flat (Carcinoma in situ) might very well kill you

Urothelial cancer is often Multifocal and often recurs at a different site

Precursor lesions to invasive Urothelial cancer

Low Grade: Papillary urothelial carcinoma, Low Grade, Noninvasive

High Grade:

Papillary urothelial carcinoma, High Grade, noninvasive

Flat noninvasive urothelial carcinoma (Carcinoma in situ)- most invasive cancers arise from CIS

Squamous Cell Carcinoma of Bladder

Schistosomiasis (aka Bilharzia)

Arises from squamous metaplasia

Treatment of Bladder Cancer

Transurethral resection for localized, noninvasive, low-grade tumors

BCG (Bacillus Calmette-Guerin) intravesical instillation of attenuated M. bovis for high risk of progression lesions

Radical Cystectomy for tumors invading detrusor muscle, for CIS refractory to treatment or extending into prostatic Urethra or urethral ducts

Most common cause of bladder outlet obstruction

Men: Benign Prostatic Hyperplasia

Women: Cystocele (Bladder Prolapse)

May cause:

Urinary incontinence

Bladder neck obstruction

Angiomyolipoma