Something Old, Something New.

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1 Something Old, Something New. Michelle A. Fajardo, D.O. Loma Linda University Medical Center

2 Clinical Presentation 6 year old boy, presented with hematuria Renal mass demonstrated by ultrasound & CT scan Referred to Urology for work-up

3 3.7 cm cystic and solid mass of right kidney CT Scan

4 Localized Renal Cystic Lesions Simple renal cyst Cystic renal cell carcinoma Multilocular cyst / cystic nephroma Pediatric Wilms tumor (nephroblastoma) Cystic partially differentiated nephroblastoma (CPDN) Other occasionally cystic lesions

5 Partial Nephrectomy 3.5 cm cyst Ill-defined, spongy, 2 cm nodule in cyst wall

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12 Diagnosis: Cystic Renal Cell Carcinoma

13 Renal Cell Carcinoma Adults Children Common Rare (0.1%) 6 th & 7 th decade of life Median age: 9 10 years Clear cell (75%), Papillary (10-15%) Majority papillary RCC

14 Renal Epithelial Tumors in Children Papillary renal carcinoma Renal medullary carcinoma Translocation-associated renal carcinoma

15 Papillary RCC Most common subtype in children Pediatric counterpart to adult papillary RCC Similar morphologic, genetic, & immunohistochemical features

16 Renal Medullary Carcinoma Rare, aggressive tumor Associated with sickle cell trait, but not sickle cell disease Age range: years Clinical Gross hematuria, flank pain, weight loss Metastases may be first presentation (lymph nodes or brain)

17 Renal Medullary Carcinoma Solid nests or gland formation Sclerotic stroma Typically arises in renal medulla, rather than cortex

18 May occasionally see sickle cells in the specimen

19 Translocation-Associated RCC Typically Xp11.2 translocation breakpoint TFE3 gene on chromosome Xp11.2 fuses with gene (PRCC, PSF, ASPL ) on chromosome 1 Result: Increased expression of TFE gene Overexpression is detectable in nuclei of affected cells by IHC (anti- TFE3 antibody)

20 Cytogenetics, our case: Xp11.2 translocation with chromosome 1

21 RCC with Xp11.2 Translocation Variant t(x;1)(p11.2;q21) Frequency ~78% Fusion Product PRCC-TFE3 AFIP Atlas of Tumor Pathology, Series 4, p.86

22 RCC with Xp11.2 Translocation Variant t(x;1)(p11.2;q21) Frequency ~78% Fusion Product PRCC-TFE3 t(x;1)(p11.2;p34) ~20% PSF-TFE3 AFIP Atlas of Tumor Pathology, Series 4, p.86

23 RCC with Xp11.2 Translocation Variant t(x;1)(p11.2;q21) Frequency ~78% Fusion Product PRCC-TFE3 t(x;1)(p11.2;p34) ~20% PSF-TFE3 t(x;17)(p11.2;q25) rare ASPL-TFE3 AFIP Atlas of Tumor Pathology, Series 4, p.86

24 Translocation-Associated RCC Typically has mixed features: Papillary architecture Clear or granular cytoplasm

25 Prognosis Uncertain relatively few cases Study: 13 pediatric papillary RCC s Seven with Xp11.2 (TFE) Stage 1 patients with complete resection were relapse free at follow up 12 of 13 alive at 5 years Am J Clin Pathol Sep;126(3):332-4

26 Kidney Tumors in Infants & Children Nephroblastoma Mesoblastic nephroma Clear cell sarcoma Rhabdoid tumor Renal carcinoma Miscellaneous: Metanephric tumors Ossifying renal tumor of infancy Angiomyolipoma

27 Nephroblastoma (Wilms Tumor) Variety of histological patterns Typically triphasic Blastemal Differentiated stromal Tubular May be predominantly cystic

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31 Anaplasia Specific definition: Hyperchromasia 3 times nuclear enlargement Abnormal multipolar mitotic figures When so defined, associated with a worse prognosis in Wilms tumor

32 Nephroblastoma (Wilms Tumor) Most common GU cancer in children In last 50 years, survival has increased from 20% to 90% Sometimes associated with syndromes involving hemihypertrophy, aniridia, genital anomalies, etc. (Beckwith-Weidemann, Denys-Drash, WAGR)

33 Cystic Nephroma Rare, benign neoplasm of children Solitary, multilocular cystic lesion Cysts lined by cuboidal epithelial cells Fibrous septa lack blastema or other immature nephroblastic tissue

34 Cystic Partially Differentiated Nephroblastoma (CPDN) Clinically, radiographically & grossly resembles cystic nephroma Distinguishing feature: contains blastema or other immature elements in septa No expansile nodules of blastema

35 Cystic Partially Differentiated Nephroblastoma (CPDN) Caveat: If expansile nodules of nephroblastic tissue in septa, then best diagnosed as cystic Wilms tumor (metastatic potential) Prognosis: Excellent if complete resection, stage 1

36 Clear Cell Sarcoma Formerly known as bone metastasizing renal tumor of childhood Rare: 1/20 th as common as Wilms tumor Polygonal to spindled, often deceptively bland tumor cells, with clear cytoplasm

37 Clear Cell Sarcoma Characteristic vascular pattern ( chicken wire ) Can be predominantly cystic Worse prognosis than Wilms tumor

38 Mesoblastic Nephroma Rare tumor, generally of the first year of life May have prominent cystic component Microscopically resembles fibromatosis or fibrosarcoma Prognosis: good if completely resected

39 Rhabdoid Tumor Rare, aggressive tumor of infancy Histology: Monotonous sheets or nests of cells with large vesicular nuclei

40 Rhabdoid Tumor Typically focal eosinophilic rhabdoid inclusions in cytoplasm Nuclear features the most useful diagnostic clue Mutation or deletion of INI1 gene on chromosome 22q11 Dismal prognosis

41 Take Home Notes Renal cell carcinoma in childhood Rare Usually papillary architecture Translocation-associated: papillary and clear cell features May be cystic as in adults Differential diagnosis includes other pediatric renal tumors which can be cystic: Wilms tumor CPDN Rarely mesoblastic nephroma, clear cell sarcoma, etc.

42 Special Acknowledgements to Craig Zuppan, M.D. Anwar Raza, M.D.

95% of childhood kidney cancer cases are Wilms tumours. Childhood kidney cancer is extremely rare, with only 90 cases a year in

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