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Tumors in the Kidney (Pdf) Systemicist Pathology.. Lecture # 8 Title :Tumors In The Kidney Done by: Dema Mhmd Khdier A man may die, nations may rise and fall…….But an idea lives on Classification PRIMARY **Benign: 1)Papillary adenoma (in the cortex). 2)Oncocytoma 3)Medullary fibroma (interstitial cell T) **Malignant: 1)Renal cell carcinoma (most common): •Clear cell renal cell carcinoma. •Papillary renal cell carcinoma. •Chromophobe renal cell carcinoma. 2) Nephroblastoma (Wilms tumor). 3) Urothelial carcinoma of renal pelvis. SECONDARY **Benign renal tumors** _ Angiomyolipoma: Consists of vessels, smooth muscles & fat. Seen in 25-50% of patients with (Tuberous Sclerosis). **Malignant renal tumors** 1)Renal cell carcinoma (RCC) Tumors are derived from the renal tubular epithelium. • Most cases are sporadic. • 2-3% of all visceral cancers. ~85% of all renal cancer. • M:F = 2:1. Commonly 60-70 years. Risk factors 1) Smoking (most significant), obesity, HTN. 2)Unopposed estrogen Rx 3)Cadmium, petroleum products & heavy metals. 4)CRF & acquired cystic disease** (30 folds ) 5)Familial (4%) most are AD: _Von Hippel-Lindau (VHL) syndrome _Hereditary clear cell carcinoma _Hereditary papillary carcinoma Morphology of RCC Grossly: ▫ Mainly arise in cortex > polar & spherical. ▫ May extend into renal vein. ▫ Orange – yellow OR tan–brown, variegated tumor with hemorrhagic, necrotic & cystic areas. Classified according to the histological picture: 1)Clear cell carcinoma (70-80%). 2)Papillary carcinoma (10-15%). 3)Chromophobe renal carcinoma (5%). 4)Sarcomatoid carcinoma. A. Clear cell carcinoma • Most common RCC subtype. • Arise from proximal convoluted tubules. • Majority are sporadic & unilateral. • Familial forms, associated with germ-line mutation of the VHL tumor suppressor gene on 3p: *von Hippel-Lindau: rare tumor of adrenal gland tissue. _Hemangioblastomas of cerebellum & retina. _Pheochromocytoma. It results in the release of too much epinephrine and norepinephrine. _ Bilateral, multiple renal cysts clear cell carcinomas (40- 60%). *Familial clear cell carcinoma :Clear RCC confined to the kidney without manifestations of VHL. Microscopic: formed into or containing one or more vacuoles or small membrane-bound cavities within a cell -Vacuolated cells with clear or granular cytoplasm. -Highly vascularized )stroma solid tumor growth ) B. Papillary RCC • Arise from distal convoluted tubules. • Most are sporadic. Frequently multifocal &bilateral. • Familial forms are associated with activating mutation of MET protooncogene on 7q. •Microscopic: Papillae with fibrovascular cores (thin and delicate) C. Chromophobe renal cell carcinoma • Arise from cortical collecting ducts or their intercalated cells. **General good prognosis. • Multiple losses of entire chromosomes (as:1,2,6,10,13,17,21) extreme hypodiploidy •Microscopic: - Tumor cells have clear faint granular cytoplasm with prominent, distinct cell membranes - The nuclei are surrounded by halos of clear cytoplasm >> Raisen-like Tumor spread 1)Intra-renal > small satellite nodules . 2)To pelvicalyceal system & ureter. 3)Frequently the tumor invades the renal vein and grows in the IVC to RT side of the heart. 4)Direct invasion to perinephric fat, renal sinus fat, regional LNs, or adrenal gland. Clinical features of RCC • Hematuria is the most frequent symptom (50%). • Asymptomatic/incidental finding. • Triad of 3 symptoms (in 10%) characteristic: 1)Flank pain 2)palpable mass 3)hematuria. • Constitutional symptoms (Fever, weight loss) • Present with metastasis (esp. lungs and bones). • Paraneoplastic syndromes 1)Polycythemia 5-10%. 2) Hypercalcemia. 3)HTN. ▫ Cushing’s syndrome. 4)Feminization or masculinization. masculinization is the biological development of sex differences • Prognosis: 5 yr survival is around 70%. feminization is the development in an organism of physical characteristics that are usually unique to the female. 2) Nephroblastoma (Wilm’s tumor) • Uncommon renal tumor but one of the commonest childhood neoplasms (2-5 yrs). __Sporadic or familial associated with congenital malformations due to WT-1 or WT-2 genes mutaions on chr.11: 1)WAGR syndrome. 2)Denys-Drash syndrome (DDS). 3)Beckwith-Wiedemann syndrome. Morphology Gross: Large, well-circumscribed soft, tan-gray, homogenous tumor. Microscopic: Classic TRIPHASIC components: 1)Blastemal: sheets of undismal blue cells 2) Epithelial: abortive tubules or glomeruli. 3) Stromal. Clinical features: • Palpable abdominal mass, (may cross the midline) + hematuria, abdominal pain, or hypertension Prognosis: Generally good (currently 90% long term survival). Treatment: Combination of nephrectomy & chemotherapy 3. Urothelial Carcinoma of the Renal Pelvis • 5-10% of renal neoplasms •Often small & present early due to: 1)Painless hematuria 2) Pain or mass due to hydronephrosis. • Linked to Lynch syndrome & analgesic nephropathy. •In 50% of renal pelvic tumors there is a preexisting or concomitant bladder urothelial tumor (field effect). • Prognosis: Variable, depend on stage & grade. Despite removal by nephrectomy 50% 5 yrs. Diseases of Uterus & LUT Ureters • Sites of narrowing: ▫ Ureteropelvic junction. ▫ Ureterovesical junction. ▫ Crossing of iliac vessels. • In female pelvis, they lie close to uterine arteries and the cervix. Operations of the female genital tract and diseases of the cervix and uterus may affect ureters. “”Causes of Ureteral Obstruction Intrinsic 1)Calculi 2) Strictures 3)Tumors 4)Blood clots 5)Neurogenic Extrinsic1)Pregnancy 2) Retroperitoneal fibrosis 3) Endometriosis 4)Tumors Stricture: An abnormal narrowing esp, a tube or a canal . Retroperitoneal fibrosis :abnormal formation of fiber (fibrosis) occurs behind the membrane that lines the cavity. Endometriosis : tissue that forms the lining of your uterus grows outside of your uterine cavity Carcinoma of urinary bladder Epidemiology: 7% of cancers & 3% of cancer deaths. M>F. 50-80 yrs. Types: 1)Transitional (urothelial) cell carcinoma (>90% ). 2)Squamous cell carcinoma (5-7%). 3)Adenocarcinoma (~2%). Urothelial (transitional cell) neoplasms (commonly in bladder) _May involve any site of the urinary collecting system from renal pelvis to urethra. _Many are multifocal at presentation. Urothelial carcinoma – Etiology: Mostly are sporadic with unknown. Cause: Induction time~22yrs. • Possible causes: 1)Cigarette smoking (most important). 2) Dye and rubber industry _Aromatic amines 2 -naphthylamine _4-aminobiphenyl _ Benzidine. _ Azo dyes. 3) Cyclophosphamide 4) Phenacetin containing analgesics 5)S. Hematobium infestation (SCC+TCC). 6) Previous radiation. Classification of urothelial neoplasms Non-invasive (superficial ) Papillary: WHO/ISUP grade: 1)Urothelial papilloma 2)Papillary urothelial neoplasms of low malignant potential (PUNLMP) 3)Papillary urothelial carcinoma, low grade 4)Papillary urothelial carcinoma, high grade Flat : Carcinoma in-situ By definition high grade Invasive (can invade) 1)Papillary and invasive More in high grade 2)Flat and invasive **************************************************** 1)Morphologic patterns of bladder tumors 2) Exophytic tumor (Most arise from the lateral or posterior walls) 4) 3)Papilloma: Small papillary fronds lined by normal appearing urothelium -Some have endophytic growth (inverted papilloma) 4)PUNLMP: Resembles papilloma larger & is covered by thicker urothelium. 5)Low-grade papillary urothelial carcinoma Mild degree of atypia & mitosis with preserved polarity of cells 5) the cells are evenly spaced and cohesive 6)High-grade papillary urothelial carcinoma Increased a typica & mitosis with loss of polarity & dyscohesive cells Carcinoma in situ (CIS) or flat urothelial carcinoma Defined by the presence of any cytologically malignant cells within a flat urothelium (high grade by definition). Accounts for less than 1-3% of urothelial neoplasms seen in association with invasive carcinoma (45-65% ) Invasive urothelial cancer: May be flat or papillary,low or high grade: < 10% of low-grade cancers are invasive. 80% of high-grade carcinomas (including CIS)are invasive. • May be superficial (to lamina propria) or deeper (to muscularis propria). --The extent of the invasion is the most important prognostic factor Other bladder tumors • Squamous cell carcinoma (5%), linked to: 1)Schistosomiasis 2)Chronic bladder irritation. 3) Tobacco smoking • Adenocarcinoma (2%), linked to: 1)Urachal remnants. 2) Bladder exstrophy. 3)Cystitis glandularis. • Sarcomas. • Paraganglioma (micturition syncope). • Carcinoid. Painless hematuria is the dominant symptom. • Lesions that invade the ureteral or urethral orifices cause urinary tract obstruction. Prognosis: Overall 5-year survival is 57%. Depends on: _The depth of invasion of the lesion (stage). _Histologic grade. .
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