Tumors of the Kidney & Urinary Tract PDF

Tumors of the Kidney & Urinary Tract September 11, 2023 9:30-10:15 am Tumors of the Kidney Tumors of Urinary Tract 1. Tumor-like lesions 1. Tumor-lik...

Tumors of the Kidney & Urinary Tract September 11, 2023 9:30-10:15 am Tumors of the Kidney Tumors of Urinary Tract 1. Tumor-like lesions 1. Tumor-like lesions 1a. xanthogranulomatous 1a. malakoplakia pyelonephritis 1b. metaplasia 1b. angiomyolipoma 2. Benign tumors 2. Benign tumors 2a. renal papillary adenoma 2a. urothelial papilloma 2b. oncocytoma 2b. inverted papilloma 3. Malignant tumors 3. Malignant tumors 3a. renal cell carcinoma 3a. urothelial carcinoma 3b. Wilms tumor Prof F. Lai [email protected] 3b. other carcinoma Dpt of Anatomical & Cellular Pathology  Tumors of the Kidney & Urinary Tract Tumors of the Kidney Terminology 1. Tumor-like lesions * usage: tumor = neoplasm 1a. xanthogranulomatous pyelonephritis * tumor: space occupying mass 1b. angiomyolipoma * neoplasm: new growth 2. Benign tumors variably regulated cells growth 2a. renal papillary adenoma 2b. oncocytoma * benign neoplasm 3. Malignant tumors * malignant neoplasm (cancer) 3a. renal cell carcinoma 3b. Wilms tumor * benign mass – tumor-like  Tumors of the Kidney 1. Tumor-like lesions 1a. xanthogranulomatous pyelonephritis chronic pyelonephritis, now uncommon bacterial infection, obstruction macroscopy: enlarged kidney with yellow nodules mimics malignant tumor microscopy: aggregates of foamy macrophages atrophy and loss of functional parenchyma nephrectomy for cure  Tumors of the Kidney 1. Tumor-like lesions 1b. angiomyolipoma malformation (hamartoma) or neoplasm macroscopy: single or multiple masses microscopy: vessels, smooth muscle, fat (PEComa - perivascular epithelioid cells) clinical: sporadic or tuberous sclerosis TSC1 9q34, TSC2 16p13.3 tumor suppressor genes > hamartin, tuberin mental retardation, skin lesions, benign tumors  Tumors of the Kidney 2. Benign neoplasms 2a. renal papillary adenoma often incidental findings macroscopy: single or multiple cortex, ≤ 1 cm microscopy: CK7 tubules and papilli benign cuboidal cells size & malignant potential Tumors of the Kidney 2. Benign neoplasms 2b. oncocytoma 5% of kidney tumors asymptomatic hematuria, palpable mass macroscopy: dark brown or mahogany mass, often central scar may be encapsulated microscopy: eosinophilic epithelial cells small round nuclei EM: abundant mitochondria (disrupted oxidative phosphorylation)  Tumors of the Kidney 3. Malignant neoplasms 3a. renal cell carcinoma (RCC) 85% of renal cancer, adults over 60 loin pain, mass, hematuria paraneoplasia (polycythemia, hypercalcemia…) risk factors: smoking, obesity, hypertension, CKD most are sporadic, 5% hereditary * von Hippel-Lindau’s (3p25-26) * Hereditary Leiomyomatosis & RCC (1q42.3-43) * Hereditary Papillary RCC (MET chr.7 mutation) * Birt-Hogg-Dubé’s (17p11.2)  Tumors of the Kidney 3. Malignant neoplasms 3a. renal cell carcinoma (RCC) macroscopy: yellowish, upper pole tumor extends to renal vein microscopy: (classification of RCC) a. clear cell RCC 75% b. papillary RCC 10%-15% c. chromophobe RCC 5% d. Xp11 translocation RCC < 2% b d e. collecting duct Ca < 1% f. others…  Tumors of the Kidney 3. Malignant neoplasms 3a. renal cell carcinoma (RCC) pathogenesis classification: a. clear cell RCC 75% von Hippel-Lindau (VHL) chr. 3p25 in sporadic and hereditary (5%) cases role of its product in Hypoxic Inducing Factors b b. papillary RCC 10%-15% MET gene chr. 7 mutation somatic in sporadic & germ line in familial cases c. chromophobe RCC 5% many chromosomal losses, undetermined loci reticular cytoplasm, perinuclear halo  Tumors of the Kidney diaphragm III 3. Malignant neoplasms capsule T3c 3a. renal cell carcinoma prognostic factors: IVC T3 grading by nuclear size – T1 a II (Fuhrman, WHO gradings) N1 I staging – TNM T3b III T2 >7cm metastasis to lungs, bone N2 treatment: surgery T4 IV interferon renal vein target therapy in Clear Cell RCC Gerota’s fascia 5-year survival: > 70% TNM staging I to IV  target therapy in Clear Cell Renal Carcinoma in both sporadic & hereditary tumors mutant VHLp (3p26-p25) VHLp β-domain α-domain Mα-domain HIF-α ubiquitin HIF1-α HIF2-α HIF1-α degradation (hypoxia inducible factor – TF) VEGF, IGF-1, GLUT1, PDGF.. tumorigenesis ( initiation, progression, metastasis ) target therapy : inhibitors of VEGF-r sorafenib, sunitinib, pazopanib, axitinib  Tumors of the Kidney 3. Malignant neoplasms 3b. Wilms Tumor commonest renal tumor in childhood abdominal mass, fever, hematuria familial 10%m sporadic 90% pathogenesis: WT-1 gene (11p13) WAGR: Wilms, aniridia, genital abn, retardation DDS: Denys-Drash syndrome BWS: Beckwith-Wiedermann’s (WT2 11p15.5) precursor: nephrogenic rests macroscopy: very large tumor, pale-grey, soft 10% bilateral or multicentric nephrogenic rests Tumors of the Kidney 3. Malignant neoplasms 3b. Wilms Tumor microscopy: triphasic: blastemal, stromal, epithelial * immature tubules, glomaruli * fibrotic cells, skeletal muscle, bone... prognostic factors: *anaplasia: large hyperchromatic nuclei, atypical mitosis * loss of material chr.11q, chr 16p * staging II N I II 1 treatment: I N surgery, chemotherapy and radiation 2 90% long-term survival V bilateral tumor  Tumors of the Kidney & Urinary Tract umbrella cell (uroplakin) Tumors of Urinary Tract (UT) urothelium 3-5 layers 1. Tumor-like lesions urothelial cells 1a. malakoplakia Terminology 1b. metaplasia * urothelium: 2. Benign tumors epithelium lining urinary tract 2a. urothelial papilloma 2b. inverted papilloma * old, traditional term: transitional cell epithelium 3. Malignant tumors * transitional cell carcinoma: TCC 3a. urothelial carcinoma 3b. other carcinoma urothelial carcinoma: Uca Tumors of the Urinary Tract (UT) 1. Tumor-like lesions 1a. malakoplakia soft plaque or mass, any UT site chronic recurrent cystitis (E.coli, gram-) xanthogranulomatous cystitis with Michaelis-Gutmannn bodies defective phagocytic macrophage Tumors of the Urinary Tract (UT) 1. Tumor-like lesions 1b. metaplasia normal urothelium * urothelium differentiated into another mature epithelium, reversible process * in chronic inflammation associated with stones or schistosomiasis (hematobium) squamous metaplasia squamous metaplasia may develop * may lead to squamous dysplasia and squamous carcinoma squamous cell carcinoma  Tumors of the Urinary Tract UT) 1. Tumor-like lesions 1b. metaplasia cystitis glandularis cystica * urothelium differentiated into another mature epithelium, reversible process * chronic inflammation, UT infection may lead to uretritis or cystitis glandularis glandular metaplasia or glandular or intestinal metaplasia * potentially or eventually to adenocarcinoma adenocarcinoma Tumors of the Urinary Tract (UT) 2. Benign Tumors of U.T. 2. urothelial papilloma inverted papilloma chronic inflammation exophytic, papillary endophytic, nodular single or multiple benign cellular features low malignant potential  Tumors of Urinary Tract (UT) 3. Malignant neoplasms 3b. Urothelial carcinoma (Transitional cell carcinoma, TCC) 90% renal cancers of Urinary Tract, 10% malignancies of Kidney over 50 year-old, men > women, hematuria, dysuria, UT infections  Tumors of Urinary Tract (UT) 3. Malignant Tumors of U.T. 3a. urothelial carcinoma (TCC) risk factors: smoking, industrial carcinogens (benzidine, aryl amines, other aromatic amines..) acquired gene mutations - p53 gene, Ras.. invasive papillary Ca flat Ca (CIS) flat invasive Ca  Tumors of Urinary Tract (UT) 3. Malignant Tumors of U.T. 3a. urothelial carcinoma (TCC) prognostic factors: grading – degree of cellular atypia papilloma papillary neoplasia, low malignant potential papillary urothelial carcinoma, low-grade papillary urothelial carcinoma, high-grade  Tumors of Urinary Tract (UT) 3. Malignant Tumors of U.T. 3a. urothelial carcinoma (TCC) prognostic factors: staging (AJCC/UICC) extent of tumor invasion Tis T1 T2 T3 T4 urothelium subepithelium muscle perivesical soft tissue Local LN distal LN Tumors of the Urinary Tract 3. Malignant Tumors of U.T. 3b. squamous cell carcinoma 5% bladder cancer squamous metaplasia schistosomiasis 3c. adenocarcinoma 3% cases, sometimes urachal intestinal metaplasia 3d. rhabdomyosarcoma rare, affects children large fleshy tumor (sarcoma botryoides) Tumors of the Kidney & Urinary Tract Robbins and Kumar BASIC PATHOLOGIC 11th edition 2023 Tumors of the Kidney p.112, 477, 763 Tumors of Urinary Tract p. 591