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Understanding Borderline Ovarian Tumors: Disease Overview and Prognosis

Learn about Borderline Ovarian Tumors (BOT), including types, etiology, incidence, histology, spread, and prognosis. Explore factors influencing the development and progression of BOT. Discover the latest research on effective treatment strategies and outcomes.

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Understanding Borderline Ovarian Tumors: Disease Overview and Prognosis

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  1. Borderline Ovarian Tumors (BOT) Prof. Dr A. Ph. MAKAR Gynaecology/Oncology ZNA Middelheim University Hospital Gent

  2. Ovarian cancer (OC): Histologic subtypes Borderline or Invasive I. Epithelial tumours (90%): • Serous • Mucinous • Endometrioid • Brenner • Clear-cell • Mixed • Undifferentiated • Unclassified II. Germ cell tumours III. Sex cord tumours

  3. Differsfrominvasivecancers Borderline Tumors of the Ovary = separate entity • Etiology • Genteic profile • Epidemiology • Clinical & pathological presentation • CA 125 • Prognosis • Response to adjuvant chemotherapy • Overtreatment: surgically and pharmacologically

  4. Taylor (1929): semi malignant tumors • Epithelial tumors with histo-pathologic features and biologic behavior intermediate between clearly benign and frankly malignant • FIGO (1971): Cancer of low malignant potential • WHO (1973): Borderline tumors Borderline Tumors of the Ovary (BOT) • Hart and Norris (1973) & Scully (1979): • Epithelial cellulair proliferation: • Stratification multi-layering • mitotic activity & nuclear atypia • Without stromal invasion

  5. Etiology & Risk Factors • Increased serum gonadotrophin levels: • postmenopausal & fertility treatment ?? • Increasing parity & lactation reduces risk of BOT • Talc minerals in hygienic powders • Oral contraceptives decrease relative risk of IOC of 0.6 (Kumle 2004): • This protective effect was persistent and related to duration of use • Not in case of BOT • No correlation with positive family history • BRCA mutations don’t increase the risk of BOT

  6. Incidence • Incidence OC in western Europe 14-19/100.000 females per year: • OC in Belgium (1998): 813 patients • BOT represents (9-20%) of OC: • Norwegian Radium Hospital: 12% • Mean age: 45years vs (invasive >55y) • 27% are <40 years • Localized tumors (FIGO stadium I): 93% • Regional (stage II) or distant spread (stage III) : 7% vs 70% (invasive)

  7. Borderline tumors- Histologic TypeNorway 1970-1993

  8. Serous cystadenoma Cytogenetic of Serous BOT Mutation in BRAF or KRAS (76%) Serous Borderline tumor High grade serous carcinoma: BRCA / P53 Tubal IE carcinoma Low grade serous carcinoma

  9. I. Serous Borderline Tumors • >40% of borderline tumors • Bilaterality is frequent: (40%) • Stage I: 67% of cases: • Exophytic implants: • hidden peritoneal spread? • No impact on prognosis • Micro-invasion • Micropapillary pattern • Advanced stage: • Serosal implants • Invasive vs non invasive A. MAKAR

  10. Micro-papillairgroei • De aanwezigheid van een micro-papillaire groeipatroon van een minimum 5 mm diameter: • Gaat geassocieerd met aanwezigheid van invasieve peritoneale implanten • agressiever biologisch gedrag & slechte prognose • Bilateraliteit • Morfologische heterogeniteit van de sereuse BOT: • Uitgebreide pathologische sampling is vereist Micro-invasie • Twee patronen worden beschreven: • Voorkomen van losse cellen met eosinofiel cytoplasma in het stroma Of • De infiltratie door celgroepen, soms papillair, met inductie desmoplastisch stroma • De totale oppervlakte van micro-invasie mag <=10 mm2 en het individueel veld mag <= 3 mm doormeter hebben • Literatuuroverzicht: micro-invasie heeft geen negatief impact op overleving • 100% overleving in 94 patiënten met een wel gedocumenteerde micro-invasie na 6.7 jaren opvolging (Seidman et al)

  11. Extra Ovarian Spread of Serous BOT: Stage II-III • 35% peritoneal & omental implants • True implantation metastases ? • Multifocal in situ lesions of peritoneum ? • Non-invasive vs invasive implants • DD: Invasive implants vs endosalpingosis

  12. Extra Ovarian Spread of Serous BOT: stage II-III Serosal implants • Invasive implants: • - Worse prognosis • LN metastases • DD endosalpingosis • Non-invasive implants: • Spontaneous regression • Good prognosis • Fertility sparing surgery Desmoplastic type Epithelial type Endosalpingosis EpitheliaalMesotheel inclusies - Tubal type glandular structures

  13. Prognosis of Serous BOT 10y survival is related to FIGO stage • Stage I: 99% survival • Stage II - III: 60-80% survival, depending on type of extra –ovarian (serosal) implants: • Non-invasive implants: 93% survival • Regression after removal of primary tumor • Invasive implants: 60% survival • Progression to invasive cancer • Lymphatic metastases

  14. II. Mucinous Borderline Tumors • 50% of all borderline tumors • Intestinal subtype (90%): • Unilateral, multicystic, smooth capsule • Pseudomyxoma peritonei • Non intestinal subtype (10%): • Bilateral 20-30% • Exophytic paucilocular, implants (sero-mucinous) • FIGO stage I: 84% (67% serous tumors) • 10 years survival FIGO stage I: 97%

  15. Pseudomyxoma Peritonei • Only with mucinous tumors of intestinal type • Not related to pre or intraoperative rupture • Often with pseudomyxoma ovarii • Mucinous tumors of the appendix • Influence on survival is unclear • Primary surgical treatment: • Repeated surgery & peritoneal stripping • HIPEC

  16. Norwegian Cancer Registery (1970-1993): 2343 BOT • Age adjusted 5 years survival ( 93%) • Survival related to: • FIGO stage (localized vs EO spread) • Histologic type • Residual disease after primary surgery • Invasive peritoneal implants • Age (<44 vs older) • < 44 ys old: 5y survival of 99% • 75-89 ys old: 5y survival of 85% • 45-64 y: RR 4.7 (CI: 2.46 - 8.99) • 65-74 y: RR 11.09 (CI: 5.84 – 21.95) • 75-89 y: RR 34.16 (CI: 18.23-64.02) • DNA ploidy state

  17. Ploidy StateNorwegian Cancer Registery: (1970-1993): 2343 BOT • Kaern et al (1993): • 370 tumors >10y FU • 90% diploid • 10% aneuploid • Aneuploidy = 19X more risk of dying of disease

  18. CA 125 in Borderline tumors. Makar et al.(1992 & 1993) • Preoperative level lowerthanwithinvasiveovariancancer (IOC): • Borderline : 66 (5-272) U/ml vs • Invasivecancer: 327 (2-125000) U/ml • Grade 1: 68 U/ml • Grade II: 221 U/ml • Grade III: 490 U/ml • Serous BOT: 131 vs 391 U/ml for IOC • Mucinous BOT: 62 vs 49 U/ml for IOC • CA125 was elevated in only 15% BOT withdiseaserecurrencevs 82% with IOC

  19. BOT & Hormonal Receptor State • Almost 100% positive ER and/or PR • Invasive counterpart <10% positive hormonal receptors • What is the place of hormonal therapy?

  20. Patterns of Spread in BOTI. Transperitoneal

  21. II. Lymphatic spread ?? • Not in case of mucinous BOT (intestinal) • Serous BOT with: • Extra-ovarian spread of invasive implants • 19% (Camatte 2002) • Aneuploid tumors • True metastases? • In situ transformation ? • 2ry Mullerian epith in LN? • Endosalpingosis? • No impact on prognosis

  22. Borderline Tumors - Symptoms • Accidental: • Followingcystectomyforasymptomaticadnexalmass • Urinarysymptoms • Abdominalmass • Lessgasterointestinalsymptomscomparedwithinvasive tumors • Torsion

  23. Frozen section • DD: grade 1 vs BOT • DD: benign cystadenoma vs BOT • More difficult with mucinous than serous BOT A. MAKAR

  24. Frozen section dilemma Ovarian mass Frozen section • St. I • St II – III without invasive implants Borderline malignancy vs Gr 1 invasive cancer Young (<40 jaar) Family planning Older age Completed family planning Fertility sparing surgery even bilat cystectomy Long term follow-up Staging/debulking surgery Definitive surgery after family planning

  25. Conservative Surgery • Laparoscopic staging • More cyst rupture • Incomplete • No difference in OS • Inspection & palpation • Cytologic washing • Unilateral adnexectomy – cystectomy • Omentectomy (10% relapse risk with serous tumors) • Appendectomy (mucinous tumors) • Biopsy contralateral ovary (serous tumors) ? • Biopsy pelvic peritoneum • Curettage (endometrioid tumors)

  26. Conservative surgery & Contralateral Ovary • Serous tumors: bilateral in 40% of cases • Wedge resection ? • Microscopic disease was rarely found in grossly normal ovary • Tazelaar (1985): normal pathologic findings in wedge specimen did not exclude tumor • Adhesions and mechanical sterility

  27. Restaging Procedures • Snider (1991), Hoskins (1995), Boccara (2004), Morice (2011): • No upgrading in stage I mucinous tumors • Multifocal appendicular tumor • Upgrading in 12-20% of serous tumors • In case of cystectomy • Omentectomy ( serous tumors) • Per laparoscopy • Restaging had no impact on recurrence rate

  28. Cystectomy in case of bilateral tumorsCave mucinous tumors A. MAKAR

  29. A. MAKAR

  30. Conservative surgery -Cystectomy • Even cystectomy with bilateral tumors • Recurrence rate 15% in case of: positive resection margins or multifocality • Risk invasive cancer with mucinous tumors • Meticilous pathological examination of the resection margins • Careful follow-up: survival is not affected if patients are re-operated at recurrence

  31. Conservative surgeryClose Long Term Follow-up • Papadimitriou (1999): late recurrence in 70% of cases with stage I • Makar (1993): CA 125 was elevated in only 15% at recurrence • Vaginal sonography • Removal of the remaining ADNEX following completion of family planning ?

  32. Conservative Surgery in Stage II-III • Camatte (2002 BJOG): • Conservative surgery in 17 with stage II-III • 14/17 with non invasive implants • 6 spontaneous and 2 assisted pregnancies • No deaths • 2 recurrences (one with non invasive implant) • Morice et al (2011) in literature review: • Invasive implants is associated with >40% risk of recurrence, 2% death

  33. Pregnancy following Conservative Surgery • No difference in recurrence rate (5.4% & 6.9%) • Maintenance of menstrual cycle in patients who received cisplatinum as adjuvant treatment • Assisted fertility treatment: successful • Patients who wished to procreate succeeded • No higher incidence of miscarriages or dystocia • No increased risk of foetal malformations

  34. Adjuvant TherapyBorderline tumors are overtreated Without AdjuvantTherapy • Tropé (Gynecol Oncol 1993): • 253 BOT stage I-II in 4 randomized trials • No survival benefit of adjuvant therapy • Adjuvant therapy increased morbidity and mortality

  35. BOT in Randomized chemotherapy Trials: Tropé et al. 1993

  36. Outcome of stage II - IV AdjuvantTherapy Without AdjuvantTherapy

  37. Chemotherapy in Stage (II-III) ???? • Excellent survival without adjuvant therapy • Low response rate (<15%) • Increased morbidity • Non-invasive implants: • Good prognosis = no adjuvant therapy • Conservative surgery in young patients • Invasive implants: only progonostic factor is residual disease

  38. Conclusion-IBorderline Ovarian Tumors • Mostly as stage I with excellent long term prognosis • Women in reproductive age deserve conservative surgery • Surgeryis corner stone of treatment of advanced stages and in recurrence • No place for adjuvant CT = overtreatment = mobidity/mortality • Careful and long term follow-up • CA 125is of limited value in follow up

  39. Invasieve tumoren Borderline Conclusie: BOT hebben eigen entiteit • 55 j • 2/3 stadium III-IV • Chirurgie + 6 cycli Carbo/Taxol • Slechte overleving • Sereus: >80% • Horm receptor: negatief • Lymfadenectomie • Gevoelig voor chemo • Snelle recidieven • CA 125 follow-up: betrouwbaar • Verhoogd risico op erfelijkheid • 45 & >1/3< 40 jaar • 2/3 st. I = Fertiliteitssparende chirurgie • Chirurgie Zonder CT • Zeer goede overleving • Mucineus & sereus • Horm receptor: positief • Geen • Niet gevoelig voor CT • Recidieven na 10-15j • CA 125 follow-up: onbetrouwbaar • Geen verhoogd risico op erfelijkheid

  40. Stop georganiseerde moord op christenen in het Midden-Oosten

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