Tumors of the Kidney and Urinary bladder Dr. Raid Jastania

Objectives By the end of this session the student should be able to: List the common benign and malignant tumors of the kidney List the types of renal cell carcinoma Know the clinical presentation of Wilms tumor Understand the basis of the classification of urothelial carcinoma

Case Presentation

A 63-year-old man was found to have microscopic hematuria on urinalysis done as part of a pre-employment physical examination. The remainder of the urinalysis was normal, as was the physical exam. The patient did not complain of any fever, weight loss, pain, malaise, weakness, or urinary tract symptoms.

Hct: 57% Hb: 19 g/dL BUN: 12 mg/dL Creatinine: 0.7 mg/dL WBC: 7,450/mm3 with a normal differential Urine cytology: negative

Work-up for the hematuria was begun with noninvasive imaging studies, which included a renal ultrasound examination and an intravenous pyelogram. A mass was seen in the left kidney with both imaging studies. The patient underwent nephrectomy.

Renal Cell Carcinoma

Renal Tumors Benign: Malignant: Oncocytoma Renal cell adenoma Renal cell carcinoma Wilms tumor Urothelial carcinoma

Tumors of the Kidney Renal cell carcinoma Arise from tubular epithelium 85% of primary malignant tumors of the kidney 2-3% of cancer in adults 6th-7th decade of life, Men 2x> women Increased risk in smokers, occupational exposure to cadmium, in dialysis-associated cysts

Clinical: Hematuria 50% Pain Mass Paraneoplastic syndrome: Fever, polycythemia 5-10% (erythropoietin) Hypercalcemia, hypertension, cushing syndrome Metastases to lung, bone

Renal cell carcinoma: types 1. Conventional RCC (clear cell) 2. Papillary RCC 3. Chromophobe RCC

Renal cell carcinoma: types 1. Conventional RCC (clear cell RCC) 70-80% of RCC Familial and sporadic Associated with von Hippel-Lindau syndrome VHL is autosomal dominant Multiple tumors: hemantioblastoma of cerebellum and retina, renal cysts, renal cell carcinoma Germline mutation in VHL gene (3p25) Loss of second allele by somatic mutation Seen in sporadic RCC as well

Renal cell carcinoma: types 2. Papillary RCC 10-15% arise from proximal tubular epithelium Multifocal, bilateral Familial and sporadic MET proto oncogene (7q31) Trisomy 7, Mutation of chromosome 7 In sporadic cases: trisomy 7, 16, 17

Renal cell carcinoma: types 3. Chromophobe RCC: 5% arise from collecting ducts Loss of Ch 1,2,6,10,13,17,21 Hypodiploidy Good prognosis

Morphology: Clear cell Papillary Chromophobe Solitary, large, cortical, well defined Yellow-orange, gray-white, cysts, hemorrhage, necrosis May extend to pelvis, ureters May invade renal vein and inferior vena cava Papillary Bilateral, multiple Chromophobe Brown-tan

Micro: Clear cell RCC Papillary Chromophobe: Lipid, glycogen Clear cells Round nuclei Vascular Papillary Chromophobe: Perinuclear halo, macrovesicles Well defined cell membrane

Thick cell membrane, perinuclear halo Coventional RCC Papillary Chromophobe Clear cell papillary Thick cell membrane, perinuclear halo VHL gene 3p MET oncogene 7q Loss of chromosomes Cortical, yellow orange with hemorrhage, necrosis Papillary, might be multifocal, bilateral Cortical, Brown

Oncocytoma

Renal Cell Adenoma

Case Presentation

Our patient is a 5 year-old, Caucasian female who presented to the primary pediatric clinic in early spring with chief complaints of cough, fever by touch, and decreased activity for six days. Our patient's illness began with rhinorrhea and progressed to appetite loss and fever that her parents felt was unresponsive to acetaminophen.

On physical exam our patient appeared worrisomely “sick” On physical exam our patient appeared worrisomely “sick”. She was fatigued. The outstanding physical findings consisted of a slightly erythematous throat. On abdominal exam a mass of 9 cm width by 4 cm length with regularly shaped margins was palpated with light depth and verified with percussion in the left upper quadrant. The mass was smooth, slightly firm, oval, nonmobile, and did not cross the midline. The child denied pain during the exam, but was uncomfortable during palpation.

Our patient was then admitted to the children's hospital after her fever and upper respiratory symptoms subsided for biopsy. Biopsy confirmed diagnosis of Wilms' tumor. The tumor was shrunk with chemotherapy for five months and then removed from the left kidney via complete nephrectomy and partial right nephrectomy.

Wilms Tumor

Wilms Tumor (Nephroblastoma) Most common primary kidney tumor in children Occur commonly between 2-5 years WT1 gene, WT2 gene Risk with congenital malformation: WAGR syndrome Denys-Drash syndrome Beckwith-Weidmann syndorme

Wilms Tumor (Nephroblastoma) Risk with congenital malformation: WAGR syndrome Loss of ch 11p13 (WT1) Aniridia, genetal abnormalities, mental retardation Denys-Drash syndrome Gonadal dysgenesis Renal abnormalities Beckwith-Weidmann syndrome Enlarged body organs (tongue, kideny, liver), adrenal enlargement, hemihypertrophy (body segment enlargement) Ch 11p15.5 (WT2)

Wilms Tumor (Nephroblastoma) Clinical: Mass Cross the midline Hematuria Intestinal obstruction Prognosis: good 2 year-survival: 90%

Wilms Tumor (Nephroblastoma) Morphology: Large well-circumscribed 10% bilateral, multiple Soft homogeneous, tan-gray Hemorrhage, cysts, necrosis Triphasic: Epithelial: tubules Stroma: fibrous, myxoid Blastema: small blue cells Foci of anaplasia Nephtogenic rests: precursor lesions

Case Presentation

A 73-year-old man presented with painless hematuria and urinary frequency

Radical prostatocystectomy specimen revealed urothelial carcinoma with invasion of the muscularis, circumferentially involving the bladder base. Carcinoma in situ was seen at the right ureteral margin. There was also invasion of the prostate, local lymph nodes and vascular structures

Tumors of the Urinary Bladder

Tumors of Urinary Bladder and collecting system Classification, ISUP (international society of urologic pathology). Benign Urothelial papilloma Malignant Papillary Papillary urothelial neoplasm of low malignant potential Papillary urothelial carcinoma – low grade Papillary urothelial carcinoma – high grade Flat Urothelial carcinoma in-situ Invasive urothelial carcinoma Squamous cell carcinoma

Tumors of Urinary Bladder and collecting system Clinical: Painless hematuria 50-70 year, men 3x>women Risk factors Smoking Industrial solvent, hydrocarbons, dyes Cystitis Schistosomiasis cyclophosphamide

Tumors of Urinary Bladder and collecting system Clinical: High recurrence rate Fatal by ureteric obstruction Overall survival 5y: 57% Ureteric carcinoma 5y survival: 10%

Squamous cell carcinoma

Objectives By the end of this session the student should be able to: List the common benign and malignant tumors of the kidney List the types of renal cell carcinoma Know the clinical presentation of Wilms tumor Understand the basis of the classification of urothelial carcinoma

Pictures