Pediatric Renal Tumors

Pediatric Renal Tumor , WILMS TUMOUR , NEPHROBLASTOMA , MESENCHYMAL TUMOUR , CLEAR CELL SARCOMA , RHABDOID TUMOUR , PATHOLOGY , HISTOPATHOLOGY , CANCER ,WHO CLASSIFICATION
#PediatricRenalTumor #Renal #Tumor #WilmsTumor
#Pathology #Pediatrics

1. Pediatric Renal Tumors Presenter – Dr Utsab Das Dept of Pathology ,Calcutta National Medical College Moderator – Dr Piyali Ghosh Demonstrator ,Dept of Pathology ,Calcutta National Medical College

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3. Peditaric Renal Tumors -- Broadly classified into 2 categories (WHO) --- ( A ) Nephroblastic and cystic tumours (B ) Mesenchymal tumours

4. (A) Nephroblastic and cystic tumours occurring mainly in children 1) Nephrogenic Rest 2) Nephroblastoma / Wilm’s Tumour 3) Cystic partially differentiated nephroblastoma 4) Paediatric cystic nephroma

5. 1) Nephrogenic Rest Defn – P ersistent foci of embryonal cells (> 36 wk POG) Epidemiology— 40% cases of Wilms Tumor Histopathology- P erilobar and I ntralobar type- Each type subclassified into- Dormant/incipient R egressing / sclerosing H yperplastic

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7. P erilobar N ephrogenic R est- .

8. Intralobar Nephrogenic Rests .

9. 2) Nephroblastoma / Wilm’s Tumour Defn - Malignant embryonal neoplasm derived from nephrogenic bla stemal cells ,m imics developing kidney &shows divergent patterns of differentiation Epidemiology- 1 in 8000 90% cases <6yrs age Signs and symptoms- A bdominal mass Pain , haematuria, proteinuria Hypertension S econdary to traumatic rupture

10. Conditions associated with highest risk of Wilms tumor - WAGR syndrome Beckwith– Wiedemann syndrome H emihypertrophy Denys–Drash syndrome Familial nephroblastoma Other conditions - C utaneous nevi and angiomas T risomy 18 Klippel – Trénaunay syndrome Neurofibromatosis Bloom syndrome Frasier syndrome Perlman syndrome C erebral gigantism ( Sotos syndrome). -

11. - Macroscopy - Gross- Solitary , well circumscribed, soft cut section - P ale gray ,cystic change, necrosis , hemorrhage .

12. - 1 Variegated appearance. 2 More homogeneous and nodular . 3 Extensive areas of infarct-like necrosis.

13. Histopathology- Triphasic pattern - 1) Undifferentiated blastema 2) M esenchymal (stromal) tissue 3) Epithelial tissue . Blastemal - H ighly cellular, overlapping nuclei . Diffuse, nodular ,serpentine, basaloid growth Mesenchymal - Spindle cells with smooth muscle features Epithelial- Small round tubular structures resembling rosettes

14. - 1 combination of blastema , stroma,epithelial tubular formations,immature glomeruli 2 blastema , stroma , and immature tubular formations.

15. - Diffuse blastemal Pattern Serpentine blastemal pattern

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17. Molecular Genetics WT1 -- 11p13 WT2 -- 11p15.5 WTX gene Inactivation (6-30%) Activation of β-catenin CTNNB1 ( 14–20%) Mutation/overexpression of TP53 ( 5%) MYCN amplification SIX/2 assoc with Blastemal WT Abnormalities in chromosomes—1p, 7q,8,12,16q

18. IHC Markers- Epithelial – KERATIN ,EMA Mesenchymal – Desmin , Myogenin Neural elements – NSE , GFAP , S-100 Additional Markers – Nuclear WT1 (80%) Nuclear PAX8 CD 56 (96%) TTF-1 (17%)

19. Metastasis - 1) Local spread – Perirenal soft tissues 2) Regional LN Spread (15%) 3) Distant Mets – Lungs >> Liver, Peritoneum Treatment Regimes – *SIOP – pre-operative chemo followed by surgery *COG - I nitial resection with subsequent therapy post tumor histology and stage

20. Prognosis - 1. Age 2. Stage 3. Anaplasia *** ( 4% of the cases ) ***criteria for anaplasia - (A) marked enlargement of nuclei (B) obvious hyperchromasia (C) multipolar mitotic figures

21. - Prognosis – (contd..) 4. Size 5 . Extensive tubular differentiation*** 6. Skeletal muscle differentiation*** 7. Post-chemotherapy morphology 8. TP53 mutation 9. Loss Of Heterozygosity at 1p and 16q

22. - Anaplastic (“Unfavorable Histology”) Wilms Tumor . Marked pleomorphism with giant hyperchromatic nuclei and atypical mitoses .

23. - Anaplastic (“Unfavorable Histology”) Wilms Tumor. Strong nuclear immunoreactivity for p53.

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26. 3)Cystic Partially Differentiated Nephroblastoma Multilocular , exclusively cystic neoplasm containing nephroblastomatous tissue Large size ,mean diameter 10 cm Well circumscribed and consist cysts of variable size. Thin septa .

27. Histopathology- C ysts separated by septa F lattened , cuboidal or hobnail epithelium Primitive nephroblastic elements focally within septa

28. 4) Paediatric cystic nephroma M ultilocular , cystic S epta - fibrous tissue & differentiated tubules Histopathology- C ysts separated by septa D/D- Cystic partially differentiated nephroblastoma Genetic profile- DICER 1 mutations.

29. - Gross appearance of pediatric cystic nephroma involving most of the kidney

30. - . Low-power microscopic appearance - M ultiple cysts lined by flattened epithelium separated by cellular spindle cell stroma

31. - The epithelial lining of the cyst has a hobnail quality stroma is loose and hypocellular

32. - Pediatric Cystic Nephroma -- stroma shows subtle cellularity adjacent to the epithelium, which is more atrophic.

33. Type- B) Mesenchymal tumours occurring mainly in children Clear Cell Sarcoma Rhabdoid Tumor 3) Congenital mesoblastic nephroma 4) Ossifying renal tumour of infancy

34. 1) Clear Cell Sarcoma Synonym – Bone-metastasizing renal tumour F eatures- 4 % of malignant renal tumours in childhood Male:female 2: 1 Genetics- S omatic internal tandem duplication in BCOR sequence (85%) YWHAE-NUTM2 fusion (10 %).

35. - Gross Appearance – W ell circumscribed and whitish , bulges on the cut surface

36. - Histology- N ests or cords of cells separated by regularly spaced , arborizing fibrovascular septa Histologic Patterns- 1)Classical 2)Trabecular 3) Myxoid 4) Sclerosing 5) Acinar 6)Palisading 7)Cellular 8) Storiform 9)Anaplastic

37. - Clear cell sarcoma of kidney, prototypical appearance- branching capillary Vasculature and open chromatin of epithelioid cord cells

38. - Clear cell sarcoma of kidney, trabecular pattern of growth

39. - Myxoid pattern

40. - Sclerosing pattern -- resembling osteoid

41. - Acinar pattern Resembling nephroblastoma Palisading pattern Resembling schwannoma

42. - Cellular pattern Resembling blastemal nephroblastoma Storiform pattern Resembling Fibrohistiocytic Neoplasia

43. - Metastasis- S keletal metastases, particularly skull R egional lymph nodes, brain, lung, liver * Prognosis- T reatment with doxorubicin Stage A ge at diagnosis T umor necrosis -- all are independent prognostic factors

44. 2) Rhabdoid Tumor Highly Aggressive P art of SMACRB1-associated neoplasms Epidemiology- 2 % of renal neoplasms in children Clinical features- Haematuria , abdominal mass CNS counterpart : A typical Teratoid / Rhabdoid tumour (posterior fossa) (15%)

45. - Gross- Solid ,soft ,well circumscribed Microscopy- Large eosinophilic hyaline globule displace nucleus laterally ( Plasmacytoid )

46. - Cytological triad of – Vesicular chromatin Prominent cherry-red nucleoli Hyaline pink cytoplasmic inclusion

47. - Rhabdoid Tumor of Kidney. The nuclear grade is high. An eosinophilic amorphous (“hyaline”) material fills the scanty cytoplasm and pushes the nucleus aside

48. - Diffuse growth of neoplastic cells Sheet like Diffuse pattern Of monomorphic Neoplastic cells Overrunning a Native glomeruli

49. - Syncytial sheets of highly atypical cells , with admixed inflammation.

50. - Molecular Genetics- hSNF5/INI-1 (chr22q11.2) deletion/mutation SMARCB1 retaining – SMARCA4 /BRG1 Markers- V imentin or cytokeratin Loss of SMARCB1 (hSNF5) Prognosis- * High tumor stage and male sex -unfavorable

51. 3)Congenital mesoblastic nephroma *Low-grade fibroblastic neoplasm * M ost common renal tumor of newborns(2-4%) Clinical features * 90 % <1 yr age Abdominal mass

52. - Macroscopy - S olid Y ellow-gray W ell-circumscribed and its fibrous cut surface well illustrated

53. - Classic CMN- monotonous proliferation of spindle cells with bland nuclei, resembling “Infantile F ibromatosis ”

54. - Cellular CMN- Accompanied by Mitotic Activity. Resembles “Infantile Fibrosarcoma ”

55. - Genetic profile Polysomy of chromosomes 8, 11, 17,20 * Cellular CMN – t(12;15) (p13;q25) results in ETV6–NTRK3 gene fusion Treatment & Prognosis- *Nephrectomy *7 % recurrence with local invasion * A ge at diagnosis & adequacy of excision - more important than morphology

56. 4)Ossifying renal tumour of infancy I ntracalyceal mass composed o f - 1) Osteoid trabeculae 2) Osteoblast-like cells 3) Spindle cell component * Arise from and attached to M edullary P yramid . Clinical features- M ale predominance, Age < 2 years G ross haematuria **

57. - Macroscopy - W ell circumscribed , 1 -6 cm diameter Histopathology O steoid core O steoblastic cells within and periphery B land spindle cells Genetic profile Relation with other paediatric renal neoplasms uncertain A small number of cases shown trisomy 4

58. - Ossifying renal tumour of infancy

59. My references- 1) WHO Classification of Tumours of Urogenital system -2016 2) ROSAI AND ACKERMAN’S Surgical Pathology 11 th Ed 3) Sternberg's Diagnostic Surgical Pathology 6th Ed

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