Gonadal non-germ Cell Tumors
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1 TREP Meeting Trieste April 12, 2012 Gonadal non-germ Cell Tumors C. Virgone G. Cecchetto TREP project (January 2000-March 2012)
2 Gonadal non-germ Cell Tumors Various and different histotypes including: Sex Cord-Stromal tumors (Ovary and Testis) 45 (13 t)» Juvenile Granulosa Cell tumors 24 (5 testic.)» Sertoli-Leydig Cell tumors 14 (8 testic.)» Others (fibrothecoma, GCT, ) 7 Epithelial tumors 15» Mucinous/Serous Cystadenoma (benign) 12» Mucinous/Serous Cystadenoma (border-line) 3» Mucinous/Serous Cystadenocarcinoma -
3 23 girls (5-176 mo; median 110) Precocious puberty in 9/23 (8 JGCT) Ovarian torsion in 2, spontaneous tumor rupture in 1
4 Ovarian SCST: staging and treatment STAGE FEATURES TREATMENT Stage I Stage II Stage III Stage IV Hidden disease Disease limited to the ovary (or both) and completely excised; negative peritoneal washing. No clinic, surgical or histologic evidence of disease extending beyond the ovary and tumoral markers' and/or hormons' levels in range after surgery. Microscopic residuals, spillage or nodes affected by disease (pathologist's measurement <2 cm); negative peritoneal washing. Tumoral markers positive or negative. Macroscopic residuals or initial biopsy only; local invasion (omentum, bowel, bladder); positve peritoneal washing; nodes affected (pathologist's measurement>2cm). Tumoral markers positive or negative Distant metastasis. Negative or positive markers Stage I but tumoral markers persistently out of normal range after a complete surgery. Surveillance PEB x 3 cycles PEB x 4 cycles, then surgery if possible PEB x 4 cycles, then surgery (metastasis included) if possible PEB x 4 cycles, then surgery (metastasis included) if possible
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8 Treatment 16/25 adnectomy, 8/25 ovarectomy; 1 enucleation 2 bilateral tumors» 1 SST: adnectomy and contralateral enucleation» 1 SLCT: bilateral adnectomy (metachronous) 19 St I, 3 St II and 1 St IV: CT in 4/23 (2 St I, 1 St II and St IV) 21 CR, 1 2 CR and 1 DOD
9 New cases 9 new patients registered from 2010» 7 JGCT» 1 GCT cistico, variante adulto» 1 Fibroma/Thecoma 7 St I, 1 St II e 1 St III PEB in 2 cases CR in 9/9 cases
10 Series update (March 31, 2012) Pts Age Endocrine Symptoms Side Surgery CT Stage and Outcome (FU) JGCT mo (4-172) 14 (prec. puberty) 11 left 8 right 6 ovariectomy 13 adnectomy 4 16 st. I 19 CR 2 st. II (29 mo; 3-86) 1 st. III SLCT mo (40-176) 0 4 left 1 bil 5 adnectomy 1 adnectomy 2 1 st. I 2nd CR 3 st. II 1 CR, 1 DOD* 1 st. IV CR* (14; 3-32) Thecoma mo (59-175) 0 2 left 2 right 2 ovariectomy 2 adnectomy 0 4 st. I 4 CR Sclerosing Stromal Tumor and 133 mo 0 1 right 1 bil 1 ovariectomy 1 adnectomy + contralateral enucleation 0 1 st. I 2 CR 1 st. II (12, unk.) GCT adult mo 1 left adnectomy - St I CR (59 mo)
11 Ovary: conclusive results (follow-up 24 months range 3-86) 32 cases: first CR 30 second CR 1 DOD 1 - JGCT: 19/19 first CR - SLCT: 4/6 first CR 1 second CR 1 DOD - Other: 7/7 first CR
12 Remarks General compliance to guidelines JGCT was the most frequent histotype: early stage at diagnosis and excellent prognosis SLCT affected older patients: major aggressiveness in tumors with heterologous elements and/or retiform pattern Fibroma/Thecoma tumors and sclerosing stromal tumors are uncommon in children and have a benign behaviour
13 Remarks Ovariectomy with sparing of adnexa when feasible Minimally invasive procedures only in small tumors Chemotherapy (as for MGCT) seems useful, but larger series are needed
14
15 11 patients 5/11 < 1 year (median 23 mo; 1-171) 1/11 with hormonal signs, 9/11 testicular enlargement
16 Testis SCST: staging and treatment STAGE FEATURES TREATMENT Stage I Stage II Stage III Disease limited to the testis and completely excised via inguinotomy. Tumoral markers' and/or hormons' levels in range after surgery. Negative histological examination after hemyscrotectomy (performed because of transscrotal approach at first surg.) Microscopic residuals, nodes affected by disease (pathologist's measurement <2 cm) or transcrotal orchiectomy with spillage. Tumoral markers positive or negative. Positive histological examination after hemyscrotectomy Nodes affected (pathologist's measurement>2cm). Tumoral markers positive or negative Surveillance PEB x 3 cycles PEB x 4 cycles, then surgery if possible Stage IV Hidden disease Distant metastasis. Negative or positive markers Stage I but tumoral markers persistently out of normal range after a complete surgery. PEB x 4 cycles, then surgery (metastasis included) if possible PEB x 4 cycles, then surgery (metastasis included) if possible
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20 Treatment 4 enucleations 1 scrotal approach (St. II)-> no CT 10/11 St I; 11/11 CR
21 New cases 2 new cases registered from 2010: 1 JGCT: 20 days, testicular enlargement, left orchifunicolectomy 1 Sertoli Cell tumor (only registration form)
22 Series update (March 31, 2012) Pts Mean age (range) Endocrine Symptoms Side Surgery Stage and Outcome (FU) JGCT 5 91 mo (1-139) 1 2 right 3 left 3 orchifunicolectomy 1 enucleation 3 st. I 5 CR 1 st. II (29; 12-52) LCT 4 8 mo (2-23) 0 3 right 1 left 1 orchifunicolectomy 3 enucleation 4 st. I 4 CR (47; 12-77) SCT 2 3 mo 0 1 left 1 ukn 1 orchifunicolectomy 1 unknown 1 st. I 1 CR 1 unknown (52) SCST incompl. diff. 2 1 mo; 171 mo 0 2 left 2 orchifunicolectomy 2 st. I 2 CR (92;6)
23 Testis: conclusive results (follow-up 44 months-range 12-92) 13 cases first CR 12 (1 case missing data) - JGCT: 6/6 first CR (3 enucl.) - LCT: 4/4 (1 enucl.) - SCT: 1/2 - other: 2/2
24 Remarks General compliance to guidelines LCT the most common histotype Clinical benign behaviour (early diagnosis?)
25 Remarks Enucleation accepted (if α-fp negative) Intraoperative frozen section to allow testis-sparing surgery Scrotal access doesn t need emiscrotectomy (if no micro residuals)?
26 Epidemiological remarks
27 Epidemiological remarks
28 Epidemiological remarks No children > 15 years in our testis SCST series» 2 patients > 10 ys No girls > 15 years in our ovarian SCST series» 11 patients > 10 ys Girls > 15 ys affected by epithelial tumors
29 FOG-2 and GATA-4 15 ovarian SCSTs from TREP files
30 FOG-2 and GATA-4
31
32 FOG-2 and GATA-4: FOG/GATA expression replicates embryonal gonadal phenotype:» JGCTs replicates primordial ovarian follicles» SLCTs embryonal testis In fibroma/thecoma group GATA-4 and FOG-2 indicate abnormal activation of GATA pathway and might be involved in the onset of these tumors
33 FOG-2 and GATA-4: No correlation between GATA-4 and prognosis and/or clinical behaviour both in JGCT and SLCT GATA-4 expression in JGCTs may be contrasted by strong FOG-2 expression (inhibiting role) FOG-2 expression in SLCTs may have a prognostic value? (lacking in advanced stage tumors)
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