Urinary Tract Pathology Lab

1. Urinary Tract Pathology Lab

2. CASE 1 History: • This was a 27 week gestational age stillborn. Severe oligohydramnios was present. Fetal ultrasound was difficult because of the lack of amniotic fluid, but enlarged, cystic kidneys were thought to be present. At autopsy, the kidneys were symmetrically enlarged and on sectioning displayed numerous 0.1 to 0.2 cm cysts. Other findings included: pulmonary hypoplasia, flattened nose, and varus deformities of the feet.

3. Slide 1.1The gross appearance of the markedly enlarged kidneys expanding the abdomen are seen here. Note that the kidneys are symmetrical.

4. Slide 1.2At low power, the cysts appear radially arranged.

5. Slide 1.3At high power, the cysts comprise most of the parenchyma, and there are rare residual glomeruli.

6. Slide 1.4The gross appearance of dominant polycystic kidney disease is seen here. Note the large size of the cysts in this 3 kilogram kidney.

7. Slide 1.5The gross appearance of multicystic renal dysplasia is seen here. Note the asymmetry of the kidneys

8. Slide 1.6The gross appearance of multicystic renal dysplasia is seen here. Note the variably sized cysts.

9. Slide 1.7The microscopic appearance of multicystic renal dysplasia is seen here. Note the variably sized cysts and the cartilage.

10. Slide 1.8The normal gross appearance of fetal kidney is seen here. Note fetal lobulations.

11. Slide 1.9The normal gross appearance of the cut surface of fetal kidney is seen here. Note the paler cortex.

12. Case 1: Questions: • What is the diagnosis? • What are the consequences of this disease? • How would you counsel the family regarding the recurrence risk for this disease? • How does this case differ from the other forms of cystic disease of the kidney?

13. CASE 1: Recessive Polycystic Kidney Disease (RPKD) • What is the diagnosis? This is recessive polycystic kidney disease (RPKD), also known as infantile polycystic kidney disease. • What are the consequences of this disease? Renal failure develops. Those infants who survive for a while may develop congenital hepatic fibrosis along with cysts in the liver. The disease is essentially uniformly fatal. • How would you counsel the family regarding the recurrence risk for this disease? Since it is recessive, there is a 25% recurrence risk. • How does this case differ from the other forms of cystic disease of the kidney? Dominant polycystic kidney disease has an autosomal dominant pattern of inheritance, compared to autosomal recessive for the infantile form. The disease is usually manifested in adults in middle or old age. The kidneys are massively enlarged with huge cysts, seen in slide 1.4. • Multicystic dysplastic kidneys are seen in fetuses and infants sporadically with no specific pattern of inheritance. The cysts are variably sized, and the kidneys are typically asymmetric (slides 1.5 and 1.6). The term "dysplasia" here means that the development is disordered, with few glomeruli and tubules and with an irregular primitive stroma, sometimes containing cartilage (slide 1.7). This form of cystic renal disease is much more common than either RPKD or DPKD. (Compare with normal kidney, slides 1.8 and 1.9).

14. CASE 2 History: • This was a 45 year old female who underwent autologous bone marrow transplantation for metastatic carcinoma of the breast. She was doing well in the first two weeks following the transplantation, but then she developed decreased urine output with fever to 102 F. A urinalysis showed increased WBC's with WBC casts.

15. Slide 2.1Multiple small yellowish foci are seen in the renal parenchyma.

16. Slide 2.2Leukocytes infiltrate the intersititum and tubules at low power.

17. Slide 2.3Leukocytes infiltrate the intersititum and tubules at medium power.

18. Slide 2.4With PAS stain, budding cells with pseudohyphae are seen at high power.

19. Case 2: Questions: • What is the diagnosis? • How does an infectious agent reach the kidney? • How do you explain the findings present on urinalysis? • What is the organism responsible for this infection (look closely)?

20. CASE 2: Acute pyelonephritis • What is the diagnosis? This is acute pyelonephritis. • How does an infectious agent reach the kidney? Most urinary tract infections are ascending infections, but hematogenous spread can also occur. Urinary tract stasis from obstruction is a common antecedent. Women are more prone to infections because of a shorter urethra. • How do you explain the findings present on urinalysis? With acute inflammation of the lower urinary tract, increased numbers of white cells would be present. White cell casts would indicate acute pyelonephritis of the kidney. • What is the organism responsible for this infection (look closely)? Budding cells with pseudohyphae characteristic of Candida infection are present.

21. CASE 3 History: • A 52 year old female had a long history of hypertension which was poorly controlled despite therapy with multiple anti-hypertensive regimens. On the day of admission to hospital, she had suffered a seizure. Prior to this, she had severe headaches for several days. Physical examination revealed a blood pressure of 230/140. The skin of her fingers appeared taut. A urinalysis revealed both proteinuria and hematuria. Laboratory data revealed BUN of 81 and creatinine of 4.8.

22. Slide 3.1Multiple small petechiae are seen over the cortex.

23. Slide 3.2There are changes in the medium to small arteries consisting of intimal proliferation as well as very prominent fibrinoid necrosis.

24. Slide 3.3The renal parenchyma shows many microinfarcts. The glomeruli are relatively normal.

25. Slide 3.4There is fibrinoid necrosis of the small artery with surrounding hemorrhage.

26. Case 3: Questions: • What is the diagnosis? • What additional laboratory findings would you suspect? • What other organs may be affected by this disease? • What is the course of this disease?

27. CASE 3: Scleroderma Kidney with Malignant Hypertension • What is the diagnosis? She has scleroderma with renal involvement and malignant hypertension. • What additional laboratory findings would you suspect? Her antinuclear antibody test will probably be positive (with an anti-nucleolar pattern). The most specific autoantibody for her disease is anti-DNA topoisomerase I. The ANA with an anti-centromeric pattern would be more typical for CREST syndrome in which severe renal disease is less likely. • What other organs may be affected by this disease? The skin shows sclerodactyly. Fibrosis in the gastrointestinal tract with dysmotility and/or malaborption is common. Pulmonary fibrosis may also occur. • What is the course of this disease? Patients with diffuse scleroderma (diffuse systemic sclerosis) and malignant hypertension may die from renal failure. Those without severe hypertension may die from restrictive lung disease and cor pulmonale. The course of CREST syndrome is more benign.

28. CASE 4 History: • The mother of a five year old child noted that the child's abdomen seemed to be getting larger. She took the child to a pediatrician who found a large, firm abdominal mass on physical examination. Urinalysis was normal. An abdominal CT scan revealed a 10 cm solid mass involving the right kidney. The right kidney was removed at surgery.

29. Slide 4.1Most of the kidney is replaced by a white, lobulated firm tumor mass.

30. Slide 4.2At low power microscopically, most of the neoplasm is composed of small round blue cells (this is one of the small round blue cell tumors of childhood).

31. Slide 4.3At medium power microscopically in some areas, the tumor is attempting to form primitive tubules and glomeruli.

32. Slide 4.4The neoplasm tends to resemble the primitive nephrogenic zone of the fetal kidney seen at low power here microscopically beneath the capsule at the right.

33. Case 4: Questions: • What is the diagnosis? • What is the peak age incidence of this tumor? • What is the survival of patients with this tumor today?

34. CASE 4: Wilm's tumor • What is the diagnosis? This is a Wilm's tumor of the kidney. • What is the peak age incidence of this tumor? Wilm's tumor is seen most often between ages 2 and 4. • What is the survival of patients with this tumor today? With surgery, radiation, and chemotherapy, survival is now in excess of 90%.

35. CASE 5 History: • A 54 year old psychiatrist noted dull left flank pain that was becoming more constant over the past few weeks. A urinalysis showed 50-75 RBC's/hpf. A CT scan of the abdomen revealed a large left renal mass that was solid. A left radical nephrectomy was performed.

36. Slide 5.1A large mass involves the lower pole of the kidney and is variegated, with yellow, tan, and hemorrhagic necrotic areas. The tumor in this case did not involve the renal vein.

37. Slide 5.2The tumor cells are fairly uniform and aggregate in small nests surrounded by capillaries. The cells have abundant clear cytoplasm dut to large amounts of glycogen. The nuclei are small and bland. Mitoses are rare.

38. Slide 5.3At low power, the adjacent kidney shows chronic inflammation microscopically.

39. Slide 5.4At high power, the adjacent kidney shows chronic inflammation with lymphocytes and plasma cells.

40. Case 5: Questions: • What the diagnosis of the neoplasm? What additional diagnosis can you make in the kidney adjacent to the neoplasm? • Name some paraneoplastic syndromes associated with this lesion. • What is the natural history of this lesion? What does the size of the tumor tell you? • What is the lesion in the adjacent kidney and what caused it?

41. CASE 5: Renal cell carcinoma; Chronic pyelonephritis • What is the diagnosis of the neoplasm? What additional diagnosis can you make in the kidney adjacent to the neoplasm? This is a renal cell carcinoma. Adjacent renal parenchyma shows infiltrates of lymphocytes and plasma cells consistent with chronic pyelonephritis, probably consequent to obstruction by the tumor. • Name some paraneoplastic syndromes associated with this lesion. Paraneoplastic syndromes associated with renal cell carcinomas include: polycythemia, hypercalcemia, hypertension, femininization, masculinization, Cushing's syndrome, amyloidosis, leukemoid reactions (very high white cell count). • What is the natural history of this lesion? What does the size of the tumor tell you? Renal cell carcinomas may metastasize just about anywhere. Sometimes they can have solitary metastases which, if resected, result in a cure. Metastases may be so slow growing that they appear 1 to 2 decades after the primary is discovered. • What is the lesion in the adjacent kidney and what caused it? The adjacent kidney shows chronic pyelonephritis, probably as a result of obstruction by the tumor.

42. CASE 6 History: • A 64 year old male with a 50 pack/year history of smoking and who worked for many years in a printing shop noted that for the past week there was blood in his urine when he first urinated in the morning. He went to a urologist who did cystoscopy but did not see a lesion in the bladder. Biopsies and urine cytology specimens were sent to the laboratory. The biopsies showed benign transitional epithelium, but the cytology specimens showed atypical cells present. The urologist then did another cystoscopy and took separate urine cytology samples from each ureter. The atypical cells were present on the left. An intravenous pyelogram showed a filling defect of the left renal pelvis. A left nephrectomy was performed.

43. Slide 6.1The kidney has been bivalved to show the collecting system. A soft pink papillary mass is attached to the urothelium and fills part of the collecting system.

44. Slide 6.2At low power microscopically, the neoplasm has a papillary configuration with the epithelium covering frond-like papillae.

45. Slide 6.3The urothelium looks very similar to normal, except it is more than seven layers thick and has occasional mitoses. The tumor is limited to the urothelium and has not invaded through the renal pelvis.

46. Case 6: Questions: • What is the diagnosis? • Where do these tumors occur? • Are there any risk factors or environmental causes of this tumor? • What must be remembered about the origin of these tumors?

47. CASE 6: Transitional cell carcinoma of renal pelvis • What is the diagnosis? This is a transitional cell carcinoma of the renal pelvis. • Where do these tumors occur? Transitional cell carcinomas occur anywhere in the urinary tract, but they are most common in the bladder. • Are there any risk factors or environmental causes of this tumor? Smoking, exposure to analine or azo dyes, and napthylamine exposure are the best known associations with urothelial cancers. • What must be remembered about the origin of these tumors? Urothelial tumors often have a multicentric origin. These patients need careful followup.

48. CASE 7 History: • A 71 year old male had increasing hesitancy and frequency of urination over several years' time. He noted difficulty in starting the stream of urine. His physician found that the prostate appeared enlarged to twice normal size and was firm with palpable nodules on physical examination. A urinalysis showed no RBC's but did show 10-15 WBC's/hpf, and the urine was nitrite positive. He was referred to a urologist who performed a biopsy. This was followed by prostatectomy (usually this is a transurethral resection).

49. Slide 7.1The prostate weighed 75 grams (three times normal size) and is nodular.

50. Slide 7.2At low power, the prostate has several ill-defined nodules.