SURGICAL PATHOLOGY

1. SURGICAL PATHOLOGY ROBERTO D. PADUA JR., MD, DPSP DEPARTMENT OF PATHOLOGY FATIMA COLLEGE OF MEDICINE RENAL DISEASES

2. Glomerular lesions associated with the nephrotic syndrome

3. Glomerular lesions associated with the nephrotic syndrome

4. WHO Classification of Lupus nephritis and clinicopathologic classification

5. WHO classification of Lupus nephritis with clinicopathologic classification

6. Dysplastic lesions of the renal artery

7. Cystic diseases of the kidney • Multicystic renal dysplasia • Anomalous differentiation of the mesonephros • Most common form of cystic disease in children • Most common cause of abdominal masses in newborns • Dysplasia is usually unilateral

8. Cystic diseases of the kidney Multicystic renal dysplasia Dysplastic kidney of an infant.

9. Cystic diseases of the kidneyMulticystic renal dysplasia Section of kidney showing embryonic-like connective tissue and tubules

10. Cystic diseases of the kidney • Autosomal dominant (adult) polycystic kidney disease • Hereditary condition char by expanding cysts that progressively destroy the renal parenchyma of both kidneys  renal failure • 1 or 2 per 1000 live births • 10% of cases requires dialysis or renal transplantation • Transmitted as autosomal dominant with complete penetrance

11. Cystic diseases of the kidneyAdult polycystic kidney diseases • Mutation in PKD1 (16p13.3) – 85 to 90% • Mutation in PKD2 (4q13-23) • PKD3 – seen in ADPKD not linked to PKD1 & 2 • Male=Females • Symptomatic in 4th-5th decade of life with gradual onset of renal failure • Clinical manifestations – flank pain, flank mass, hematuria, HPN, renal failure • 20% develop nephrolithiasis

12. Cystic diseases of the kidneyAdult polycystic kidney diseases • Diagnosis – UTZ, CT-scan • Bilateral involvement of kidneys • Markedly enlarged kidneys with bosselated outer cortical surface • Cysts develop in all segments of the renal tubule and glomerular capsule • Light microscopy – cysts are lined by cuboidal, flattened epithelium, and hyperplastic polypoid foci also seen

13. Cystic diseases of the kidneyAdult polycystic kidney diseases External and cut surface of a nephrectomy specimen from a patient with ADPKD.

14. Cystic diseases of the kidney • Autosomal recessive (infantile) polycystic kidney disease • Rare disorder – 1 per 20,000 live births • Genetic defect localized in the short arm of chromosome 6 • Liver and both kidneys are affected • Neonatal period – renal symptoms • Later in life – hepatic disease

15. Cystic diseases of the kidneyInfantile polycystic kidney disease • Present with large abdominal masses at birth • “Potter” phenotype – char facies due to oligohydramios, joint deformities, pulmonary hypoplasia • Death is due to respiratory failure • Beyond perinatal period – renal failure, HPN, and portal HPN • Estimated perinatal mortality is 30-50% • 5-year survival rate after first month of life is 80-95%

16. Cystic diseases of the kidneyInfantile polycystic kidney disease • Kidneys markedly enlarge bilaterally but retain their reniform configuration • Cysts tend to be linear and radiate from the medulla to the outer cortex • Microscopcally, cysts appear as dilated tubular structures lined by cuboidal or flattened epithelium, intervenning tissue may contain uninvolved nephron

17. Cystic diseases of the kidney • Medullary sponge kidney • Char by dilated medullary and papillary collecting ducts which give the medulla a sponge-like appearance • True incidence is unknown (1 per 5000 pop) • Asymptomatic unless complicated by nephrolithiasis, hematuria, or infections • Symptoms start in the 4th-5th decades of life • Male=Female • 25% of cases have associated hemihypertrophy of the body

18. Cystic diseases of the kidney • Nephronophthisis-medullary cystic kidney disease complex • 2 major groups • Nephrolithiasis – autosomal recessive mode of inheritance • 3 forms • Juvenile (NPH1) = 13 years  ESRD • Infantile (NPH2 = 1-3 years • Adolescent (NPH3) = 19 years • MCKD – autosomal dominant trait • 2 variants • MCKD1 = 62 years • MCKD2 = 32 years

19. Cystic diseases of the kidneyNephronophthisis-MCKD complex • Juvenile NPH • Most common genetic cause of ESRD in children • Both sexes are equally affected • Clinical presentation = polydipsia, polyuria, anuresis, dec. in urinary concentration, severe anemia, growth retardation • 12% of cases assoc with retinitis pigmentosa (Senior-Loken syndrome) • Other assoc conditions = hepatic fibrosis, skeletal malformations, defects in the CNS • NPHP1 identified on chromosome 2q13 nephrocystin

20. Cystic diseases of the kidneyNephronophthisis-MCKD complex • MCKD • Symptoms occur in the 3rd and 4th decades of life • Similar to NPH1 minus the growth retardation and severe anemia + extrarenal disorders • Associated with huperuricemia and gout • MCKD1 = 1q21; MCKD2 = 16p13

21. Cystic diseases of the kidneyNephronophthisis-MCKD complex • Kidneys are normal or slightly reduced in size with a granular surface • Renal involvement is always bilateral • Cut section – cortex and medulla both thinned • Cysts arise from the loop of Henle, DCT, and CD • Tubulointerstitial fibrosis with lymphocytic inflammatory infiltrate, tubular atrophy and cysts formation seen histologically

22. Cystic diseases of the kidney • Acquired renal cystic disease • 7-22% of patients with renal failure who are not on dialysis • 40% of patients on dialysis for 3 years • 80-90% of patients on dialysis for 10 years • Theory – cysts results from obstruction of the renal tubules, by local fibrosis, oxalate deposition, or epithelial hyperplasia • Usually asymptomatic but the cysts may bleed, rupture or become infected • Most serious complication is development of renal adenocarcinoma (50X in patients on dialysis)

23. Cystic diseases of the kidney • Simple cysts • Most common cystic abnormality seen in the kidneys • Incidence increases with age • Usually asymptomatic and found incidentally on autopsy • May cause pain as a result of hemorrhage or infection • Occur more commonly in the renal cortex derived from pre-existing tubules • Usually unilocular less than 5cm in diameter

24. Pediatric tumors and tumor-like conditions • Wilm’s tumor • Also known as nephroblastoma, embryoma, carcinosarcoma, adenosarcoma, adenomyosarcoma • Primarily seen in infants – 50% occurring before 3 y/o; 90% before the age of 6 years • Both kidneys are equally affected • Incidence of synchronous or metachronous bilateral involvement is 5-10% • Extrarenal sites have been reported

25. Pediatric tumors and tumor-like conditions • Wilm’s tumor • Expression of WT1 gene • Conditions associated with definite increased risk : WAGR syndrome, omphalocoele-macroglossia (Beckwith-Wiedemann syndrome), hemihypertrophy, Denys-Drash syndrome • Conditions associated with possible increased risk : renal and genital malformations, cutaneous nevi and angiomas, trisomy 18, Klippel-Trenaunay syndrome, neurofibromatosis, Bloom syndrome, and cerebral gigantism

26. Pediatric tumors and tumor-like conditions • Wilm’s tumor • Clinical presentation – abdominal mass, HPN, proteinuria • Diagnosis • IVP – shows intrarenal mass that displaces and distorts the pelvis • UTZ • CT-scan • MRI • Potential tumor markers – inc hyaluronic acid, acquired Von Willebrand’s factor, inactive renin, inc eryhtropoietin

27. Pediatric tumors and tumor-like conditions • Wilm’s tumor • Gross • Solitary, well-circumscribed, rounded, and soft • Cut section is solid, pale gray or tan often exhibits areas of cystic change, necrosis, and hemorrhage • A lobular pattern results from fibrous septation

28. Wilm’s tumor - Gross Tumors show a variegated appearance

29. Tumor is homogenous and nodular Tumor has extensive areas of infarct-like necrosis

30. Wilm’s tumor • Microscopic = has 3 major components • Undifferentiated blastema – cellular, composed of small round-to-oval primitive cells • Mesenchymal (stromal) tissue – spindle cell fibroblast-like configuration; exhibit differentiation toward various cell types particularly smooth muscle and skeletal muscle • Epithelial tissue – characterized by the formation of embryonic tubular (sometimes glomerular) structures that closely recapitulate the appearance of normal developing metanephric tubules (and glomeruli)

31. Wilm’s tumor • Histochemical and Immunohistochemical features • Blastematous elements – (+) for vimentin, keratin, EMA • Mesenchymal – (+) for myogenin and desmin, NSE, S-100, glial fibrillary acidic protein • Type I insulin-growth factor receptors – responsible for increased proliferation and inhibition of differentiation • Electron microscopic features • Closely resembles developing metanephros

32. Wilm’s tumor • Spread and metastasis • Local spread in perirenal soft tissues  adrenal glands, bowel, liver, vertebrae, paraspinal region • Renal vein invasion is common • 15% of cases involves regional LN • Distant metastasis – lungs, liver, and peritoneum • Therapy • Stage I and II – nephrectomy and 2 agent chemo

33. Wilm’s tumor • Prognosis • Overall cure rate for unilateral Wilm’s tumor is 80-90% • Age – less than 2y/o – good • Stage – most important prognostic determinator; increased rate of relapse: presence of inflammatory pseudocapsule, invasion of the renal sinus, extensive infiltration of the renal capsule, and tumor infiltration of intrarenal vessels • Size – bigger tumor – poor • Anaplasia - poor

34. Wilm’s tumor • Prognosis • Extensive tubular differentiation – good prognosis • Skeletal muscle differentiation – good prognosis • Mucin production – poor prognosis • P53 mutation – poor prognosis

35. Pediatric tumors andtumor-like lesions • Mesoblastic nephroma • Also known as fetal, mesenchymal, or leiomyomatous hamartoma • A congenital renal neoplasm that is usually discovered before the patient reaches 6 months of age • Gross • Solid, yellowish gray to tan, with a whorledconfiguration • Most are centered near the hilus of the kidney • Well-circumscribed but may infiltrate the renal parenchyma and perirenal fat • Areas of necrosis and hemorrhage are usually absent

36. Gross appearance. The tumor is well-circumscribed with a fibrous cut surface.

37. Mesoblastic nephroma • Microscopic • Cellular growth of spindle cells • Proliferating cells have features of fibroblast, myofibroblasts, and smooth muscle cells • Tubules and glomeruli may be seen surrounded by spindle cells with some exhibiting hyperplastic and metaplastic changes • Small islands of hyaline cartilage and foci of extramedullary hematopoiesis may be present • There is no capsule separating the tumor from rhe uninvolved parenchyma • Areas of necrosis and hemorrhage may be seen

38. Microscopic appearance showing a monotonous proliferation of spindle cells with bland nuclei and abundant fibrillary acidophilic cytoplasm.

39. Mesoblastic nephroma • Contain the t(12;15)(p13;q25) translocation, which results to gene fusion • Definitive treatment is nephrectomy

40. Pediatric tumorsand tumor-like lesions • Multicystic nephroma • Also called multilocular cystic nephroma; multilocular cyst • Arises in early infancy but may present clinically at any age • Clinical presentations result from the presence of a mass or ureteral obstruction by one of the daughter locules

41. Multicystic nephroma • Gross • Lesion is usually solitary, unilateral and sharply delineated from the uninvolved renal parenchyma • Cut surface shows a multilocular appearance, individual cyst measures 1 mm to 3 cm or more • The cysts do not communicate with each other or with the pelvis • Extension of the lesion beyond the renal capsule may occur

42. Gross appearance of muticystic nephroma involving most of the kidney.

43. Multicystic nephroma • Microscopic • Cysts are lined by tubular epithelium ranges in height from columnar to flat resembling endothelium and simulating the appearance of lymphangioma • A “hobnail” pattern is common

44. LPO. Shows multiple cysts lined by flattened epithelium and separated by a cellular spindle cell stroma.

45. The epithelial lining of the cyst shows a “hobnail” pattern. The cyst lining is flat, simulating endothelium.

46. Pediatric tumorsand tumor-like lesions • Nephroblastomatosis and nephrogenic rests • Congenital dysontogenetic rather than neoplastic disorders • Can be associated with Wilm’s tumor • They share the same mutation of WT1 • Single or multifocal, unilateral or bilateral subcapsular aggregates of primitive metanephric tissue • Microscopic in size – called nephrogenic rests • Massive – called nephroblastomatosis

47. Pediatric tumorsand tumor-like lesions • Clear cell sarcoma • Also known as bone-metastasizing renal tumor • Comprises 4% of childhood renal tumors, peaks in the 2nd year of life • Gross • Large, sharply outlined and centered in the medullary or central region of the kidney • Homogenous cut surface of light brownish gray color and myxoid appearance • Consistency is hard and cystic formations are common

48. The tumor is well circumscribed and whitish, and it bulges on the cut surface.

49. Clear cell sarcoma • Microscopic • Diffuse growth of relatively small cells with round normochromatic nuclei, inconspicous nucleoli, vacuolated cytoplasm, and indistinct cell margins • Nuclear grooves are common, mitosis infrequent

50. Trabecular pattern of growth.