TREP Meeting Trieste April 12, 2012 Gonadal non-germ Cell Tumors C. Virgone G. Cecchetto TREP project (January 2000-March 2012)
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 -
23 girls (5-176 mo; median 110) Precocious puberty in 9/23 (8 JGCT) Ovarian torsion in 2, spontaneous tumor rupture in 1
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
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
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
Series update (March 31, 2012) Pts Age Endocrine Symptoms Side Surgery CT Stage and Outcome (FU) JGCT 19 70 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 6 128 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 4 125 mo (59-175) 0 2 left 2 right 2 ovariectomy 2 adnectomy 0 4 st. I 4 CR Sclerosing Stromal Tumor 2 172 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 1 144 mo 1 left adnectomy - St I CR (59 mo)
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
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
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
11 patients 5/11 < 1 year (median 23 mo; 1-171) 1/11 with hormonal signs, 9/11 testicular enlargement
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
Treatment 4 enucleations 1 scrotal approach (St. II)-> no CT 10/11 St I; 11/11 CR
New cases 2 new cases registered from 2010: 1 JGCT: 20 days, testicular enlargement, left orchifunicolectomy 1 Sertoli Cell tumor (only registration form)
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)
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
Remarks General compliance to guidelines LCT the most common histotype Clinical benign behaviour (early diagnosis?)
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)?
Epidemiological remarks
Epidemiological remarks
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
FOG-2 and GATA-4 15 ovarian SCSTs from TREP files
FOG-2 and GATA-4
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
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)