1. Tumors of the Kidney and Urinary bladder
Dr. Raid Jastania

2. 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

3. Case Presentation

4. 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.

5. 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

6. 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.

10. Renal Cell Carcinoma

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

12. 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

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

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

19. 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

20. 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

25. 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

28. 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

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

30. 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

31. Oncocytoma

32. Renal Cell Adenoma

33. Case Presentation

34. 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.

35. 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.

37. 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.

38. Wilms Tumor

39. 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

40. 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)

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

49. 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

50. Case Presentation

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

54. 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

55. Tumors of the Urinary Bladder

56. 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

57. 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

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

71. Squamous cell carcinoma

72. 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

73. Pictures