Gestione dei tumori borderline iniziali e avanzati nelle donne in età fertile

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Gestione dei tumori borderline iniziali e avanzati nelle donne in età fertile Pierandrea De Iaco pierandrea.deiaco@aosp.bo.it SSD ONCOLOGIA GINECOLOGICA AOU SANT ORSOLA-MALPIGHI BOLOGNA

Borderline ovarian tumors: rare entities? 10-15% of epithelial tumors 2,5-5/100.000 women/year mean age: 45 years 35% < 40 years recruitment in our Centre : 25 patients/year

New ovarian tumor classification Early stage treatment Relapse treatment Advanced stage treatment Borderline in pregnancy Pregnancy after ovarian borderline

Why a cathegory BORDERLINE * Intermediate morphologic features benign-malign * Intermediate biologic features benign-malign * Impossibility to predict outcome 1962

Progressione Type I Pathway Cistoadenoma Borderline Intraepithelial Microinvasive Invasive

Type I ovarian carcinoma Type II ovarian carcinoma Clinical behaviour - Slow growth, no aggressive,frequently stage I histology - LG (micropapillary) serous - Endometrioid - Mucinous - Clear cell - Transitional (Brenner) Morphology and pathogenesis - heterogeneos - From precursor: borderline tumors and endometriosis Clinical behaviour - Fast growth, aggressive, frequently advanced stages histology - HG serous - MMMT (carcinosarcoma) - Indifferentiated Morphology and pathogenesis - Homogeneous - de novo development

BORDERLINE CLASSIFICATION WHO pre-2014 Serous tumors Mucinous tumors (intestinalendocervical like) Endometrioid tumors Clear cell tumors Transitional cell tumors WHO 2014 Serous tumors Serous micropapillary variant Mucinous intestinal tumors Sero-mucinous tumors Endometrioid tumors Clear cell tumors Transitional cell tumors

BORDERLINE: Specific histologic features Micropapillary Peritoneal implants Carcinoma in situ Microinvasive carcinoma

cellular shedding from the tumor same features on all mullerian tissues

New ovarian tumor classification Early stage treatment Relapse treatment Advanced stage treatment Borderline in pregnancy Pregnancy after ovarian borderline

Surgical treatment of early stage borderline tumors Radical - bilateral salpingo-oophorectomy Conservative - monolateral salpingo-oophorectomy Ultraconservative - cystectomy (mono or bilateral) Laparoscopic - smaller tumors (<10 cm?) Laparotomic - larger tumors - associated pathologies (sistemic)

Borderline ovarian tumor Young patient wishing to preserve fertility Unilateral tumor (unconfirmed/absence frozen section) Unilateral tumor (confirmed at frozen section) Bilateral tumor (at frozen section) Cistectomy if feasible Unilateral salpingooophorectomy if not Cistectomy if feasible Unilateral salpingooophorectomy if not (and for mucinous) Peritoneal staging Bilateral cistectomy if feasible Peritoneal staging Restaging procedures should be suggested for high-risk patients and for residual disease From Darai et al., 2013 modified

De Iaco, et al. 2009 For large tumors: Possibility to reduce volume by intraperitoneal puncture Removal by endobag Enlargement of the cutaneous incision (no tumor fragmentation for correct pathology)

For supeficial tumors: Oophorectomy

Staging procedures: washing for cytology peritoneal biopsies (at least 6) omental biopsy biopsy of all suspected lesions (verify suspected endometriosis foci)

New ovarian tumor classification Early stage treatment Relapse treatment Advanced stage treatment Borderline in pregnancy Pregnancy after ovarian borderline

Post-treatment relapses After conservative surgery: total 0-25% After cystectomy: 10-42% After monolateral oophorectomy: 5-10% After bilateral oophorectomy: 0-5% Stage: Stage I 13% Stage II-III 38% Cancerization: 2-3% Mucinous at higher risk 5 year survival 95% Stage I 98%

Treatment of relapses Sonographic diagnosis in 100% of cases 68% still treated with conservative surgery laparoscopic surgery 12 pregnancies after surgery for relapse late relapses (> 10 years)

Risk factors Micropapillary Relapses: 39% Peritoneal implants No invasive mortality 4% Invasive mortality 34% Microinvasion Relapses: 15% (possibility of invasive relapse) Mucinous Borderline Risk of invasive relapse: 13%

New ovarian tumor classification Early stage treatment Relapse treatment Advanced stage treatment Borderline in pregnancy Pregnancy after ovarian borderline

Conservative surgery for advanced stages: High incidence of relapses (55%) In case of relapses: possibility of conservative surgery 20% invasive carcinoma at third relapse in case of third relapse: 75%mortality Complete surgical debulking: bilateral oophorectomy omentectomy large peritonectomy possible intestinal resection

New ovarian tumor classification Early stage treatment Relapse treatment Advanced stage treatment Borderline in pregnancy Pregnancy after ovarian borderline

Borderline tumor during pregnancy 40 patients: borderline tumor during pregnancy Mean age: 30 years Diagnosis: pain 16% sonography 68% clinical evaluation 16% First trimester diagnosis: 68% Surgery: oophorectomy: 24 cystectomy: 11

New ovarian tumor classification Early stage treatment Relapse treatment Advanced stage treatment Borderline in pregnancy Pregnancy after ovarian borderline

Pregnancy after borderline tumor Pregnancy rate: 54% Risk factors: treatment conservative/radical laparoscopic/laparotomic age>40 histotype higher frequency of mucinous serous frequently associated to infertility (bilateral tumors) Darai et al., 2013