RENAL CELL CARCINOMA IN CHILDREN AND ADOLESCENTS A RETROSPECTIVE - PowerPoint PPT Presentation

RENAL CELL CARCINOMA IN CHILDREN AND ADOLESCENTS A RETROSPECTIVE ANALYSIS OF A COOPERATIVE EUROPEAN COHORT Thomas Denize 3rd year resident @anotherpathres Pathology department, Pr Aurore Coulomb MD PhD APHP.6 Armand Trousseau Hospital, Paris, France T eam: Simona Massa, Christian Vokuhl, Alexander Valent, Adele T esti, Linda Dainese, Lucia Militti, Nathalie Rioux- Leclerq Estelle Thebaud, Rhoikos Furtwaengler, Kathy Pritchard-Jones, Norbert Graf, Filippo Spreafico, Arnauld Verschuur, Gordan Vujanic, Paola Collini

INTRODUCTION – RENAL CELL CARCINOMA 2016 WHO Classification: 16 subtypes + 6 emerging entities  2 – 6 % of renal malignancies in children  Variable prognosis depending on the subtype  Microphtalmia-associatedTranscription Factor translocated carcinoma  Renal cell carcinoma in children, adolescents and young adults: A national cancer database study. Akhavan A and al . Pediatric Urology 2015

MATERIEL AND METHODS 4 countries: France, Germany, Italy, United Kingdom  RTSG/SIOP pathologist panel  More than 40 centers  Centralized review of all cases  Reference: 2016 WHO classification  French/Italian cases: unified wide IHC panel  CK7, AMACR, CAIX, TFE3, Vimentin, CD117, CK19, HMWCK, P63,  INI1, HMB45, MelanA, ALK, SDHB, FH TFE3 FISH on all cases 

DEMOGRAPHICS TUMOR LOCALIZATION upper 2/3 162 children: 87 males, 75 females  4% Mediorenal Whole kidney 22% 17% 166 tumors  Median age: 11 years old (9m-18y)  Mean size: 6.4cm  Upper pole 23% Lower pole 34%

HISTOTYPE REPARTITION MiTF 41% Others 59%

TFE3 RCC N = 62  Girls > boys (SR 1.6)  Mean age 9.8y, median 11y  66% N+;  FO: late relapses, 4 known M+  Photo

MITF-TRANSLICATION RCC Photo  Photo  IHC 

CAIX AMACR 47% 94% HMB45 Vim 57% 18%

BEWARE OF TFEB N = 6  Can look like anything  Perform FISH whenever TFE3 is negative  No amplification in our series  MelanA

OTHER SUBTYPES Papillary chromophobe CCRCC, adult- type collecting duct carcinoma NON-MITF TUMORS SDHB deficient ALK translocated associated with neuroblastoma FH deficient Unclassified

FOCUS ON: HEREDITARY LEIOMYOMATOSIS AND RENAL CELL CANCER SYNDROME, OR FH-DEFICIENT RCC New entity 2016 WHO classification  Cutaneous and uterine leiomyomas + RCC → genetic counseling  Loss of FH IHC 

FH-DEFICIENT RCC Male, 14y  17cm left renal mass  N+  Death 17m after diagnosis → M+  (lung, bone)

FH DEFICIENT RCC

FH DEFICIENT RCC FH AMACR CK7 FH

CONCLUSION MiTF translocated RCC is the main subtype of pediatric RCC (41%)  Non MiTF translocated RCC: heterogenous (9 subtypes), similar to adult RCC  Accurate diagnosis requieres a large IHC panel including FH and SDHB  TFE3 FISH should be performed on all pediatric RCC  Ongoing molecular analysis for better characterization of the MiTF translocated RCC 