Ovarian Borderline Tumors - wesleyobgyn.com Bord… · of tumours of female reproductive organs....
Transcript of Ovarian Borderline Tumors - wesleyobgyn.com Bord… · of tumours of female reproductive organs....
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Ovarian Borderline
Tumors(What’s in a name?)
Diagnosis and Management
Jed Delmore, M.D.
Mark D. Laudenschlager, MD
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Conflict of Interest
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Objectives
• Definition/Natural History
• Diagnostic Criteria
• Surgical options
• Post-operative Therapy
• Surveillance
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Case #1
• 30 year old G0P0 with a tender, 7 cm.
bilobed cystic mass in the left adnexa. CA-
125 is 50 units. She wishes to attempt
pregnancy in the next year. Laparoscopic
left ovarian cystectomy with frozen section
shows serous borderline tumor.
Now What?
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Case #2
• 50 year old G2P2 with a tender, 8 cm.
cystic mass in the right adnexa. CA-125 is
normal. At the time of hysterectomy, BSO,
multiple 5-7 mm. pink nodules are
identified over the pelvic peritoneum.
• Final pathology shows serous BOT with
non-invasive peritoneal implants.
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Case #3
• 42 year old G2P2 with a bilateral adnexal
masses, 6 cm. CA-125 is 60 units.
Endometriosis is suspected. At the time of
hysterectomy, BSO, multiple 5-7 mm. pink
nodules are identified involving the
peritoneum and omentum.
• Final pathology shows low-grade serous
carcinoma.
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Case #4
• 61 year old G2P2 with a 15 cm., right
adnexal masses. CA-125 is normal. At the
time of hysterectomy, BSO, the right ovary
was drained of two liters of thick, viscous
fluid. The appendix is normal in
appearance.
• Final pathology shows mucinous borderline
ovarian tumor.
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Ovarian Borderline Tumors
History
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Ovarian Borderline TumorsNatural History
• 10-15% of all Ovarian Malignancies are
LMP Tumors
• 75% are Stage I at diagnosis
• Bilateral
– 30-60% in Serous Borderline Tumors
– <5% in Mucinous Borderline Tumors
• Primarily cystic
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Ovarian Borderline TumorsHistory
“proliferative ovarian tumors without
evidence of stromal invasion”
Malignant and Semimalignant Tumors of the Ovary
H.C. Taylor
Surg Gynecol Obstet 48:204-230, 1929
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Ovarian LMP TumorsHistory
“carcinoma of low malignant potential”
International Federation of Gynecology and
Obstetrics: Classification and staging of malignant
tumors in the female pelvis.
Acta Obstet Gynecol Scand 50:1-7, 1971
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Ovarian Borderline TumorsHistory
“borderline malignancies”
Serov SF, Scully RE, Solvin LH, eds.
International histologic classification of tumors no.9:
histologic typing of ovarian tumors.
World Health Organization, Geneva, 1973, pp 37-41.
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2014 WHO Classification of Tumours of the Female Genital
Organs
“borderline tumor” is interchangeable with
“atypical proliferative tumor”.
“tumor of low malignant potential” is no
longer recommended.
Kurman RJ, Carcangiu ML, Herrington CS, Young RHE (eds) (2014) WHO classification
of tumours of female reproductive organs. Lyon, IARC
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Serous Histology
• Serous borderline tumor (SBT) = Atypical
proliferative serous tumor (APST)
• SBT with micropapillary pattern = non-
invasive low grade serous carcinoma
(niLGSC)
• Non-invasive vs. Invasive implants
Kurman RJ, Carcangiu ML, Herrington CS, Young RHE (eds) (2014) WHO classification
of tumours of female reproductive organs. Lyon, IARC
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Borderline Ovarian TumorsSubtypes
• Serous
• Mucinous
• Endometrioid
• Clear Cell
• Seromucinous
• Brenner
95%
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Diagnostic Criteria
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Pathogenesis
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Serous Tumors• Benign, borderline, and malignant serous tumors account for
about 30% of all ovarian tumors.
• About 70% are benign or borderline, 30% are malignant.
• Benign and borderline tumors – younger patients 20-45 yrs
• Malignant tumors – later in life unless genetically susceptible (BRCA 1 and 2).
• Risk factors for malignant serous tumors:
– BRCA1/2 mutation – estimated risk 20-60% by the age of 70 years (these mutations are present in about 5% of women younger than 70 with ovarian cancer)
– Nulliparity/low parity
– Family history
• Reduced risk
– OCP use
– Tubal ligation
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Ovarian serous carcinomaLow-grade serous
carcinoma (LGSC)
• Arise in serous borderline tumors
• Mutation: KRAS, BRAF, ERBB2
• Wild type: TP53
High-grade serous
carcinoma (HGSC)
• Arise from STIC or inclusion cysts
• Mutation: TP53
• Amplification of oncogenes, deletions of tumor suppressor genes
• Present in BRCA1/2 • BRCA1/2 mutation
rare in sporadic HGSC
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Serous tumors• Biologic behavior depends on degree of differentiation and
peritoneal involvement (tumor present on ovarian surface vs
spread to peritoneum)
• SBT & LGSC – slow progression even with peritoneal
involvement, patient may survive for relatively long periods
• HGSC – often widely metastatic, rapid clinical deterioration
• Malignant tumors:
– 5 yr survival if confined to ovary – 70%
– 5 yr survival if involving peritoneum – 25%
• Borderline tumors:
– 5 yr survival if confined to ovary – 100% - but may recur
after many years
– 5 yr survival if involving peritoneum – 90%
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Atypical Proliferating Serous Tumor
Vang R, et el. Am J Surg Pathol. 2017 June;41(6) 725-737
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Non-invasive, Low Grade Serous Carcinoma
Vang R, et el. Am J Surg Pathol. 2017 June;41(6) 725-737
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Non-invasive Implants
Vang R, et el. Am J Surg Pathol. 2017 June;41(6) 725-737
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Invasive Implants
Vang R, et el. Am J Surg Pathol. 2017 June;41(6) 725-737
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• Gross examination: – May be cystic or solid
– Serous cystadenoma (benign)– smooth cyst wall filled with fluid• 20% are bilateral
– Serous borderline tumors – papillary projections on the cyst wall• 30% are bilateral
– Serous carcinoma – cystic/solid, +/- papillary areas, +/-hemorrhage and necrosis
• 66% are bilateral
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Serous Cystadenoma • Lined by a single layer of
columnar epithelium with
• No increased cytologicatypia, stratification, or architectural complexity
• Underneath the epithelial lining, the wall of the cyst is generally thick/fibrous
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SBT• Increased complexity of
the stromal papillae.
• Stratification of the
epithelium.
• Mild nuclear atypia, but
invasion of the stroma is
not seen.
• Micropapillary pattern –
papillae are long and
thin (“medusa head”)
Thought to be the
precursor to low-grade
serous
carcinoma.arcinoma
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Mucinous tumors• Mucinous tumors account for 20-25% of all ovarian
neoplasms
• Occur in middle adult life
• Majority are benign or borderline tumors, most are
unilateral
• KRAS proto-oncogene mutation found in benign,
borderline, & malignant mucinous tumors
• Pseudomyxoma peritonei:
– Characterized by extensive mucinous ascites, cystic
epithelial implants on peritoneal surfaces, adhesions,
and bilateral ovarian involvement
– Most cases are due to an appendiceal mucinous
neoplasm (not primary ovarian mucinous tumor),
which is involving the bilateral ovaries
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Mucinous cystadenoma
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Mucinous Borderline Tumor
• Demonstrate epithelial
stratification, tufting,
and/or papillary
intraglandular growth
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Diagnosis of Borderline
TumorsFrozen Section Evaluation
• Only rarely is a frozen section diagnosis of
Borderline tumor downgraded on permanent
section.
• 27% of frozen section diagnoses of borderline
tumor will be upgraded to invasive carcinoma on
permanent section.
Menzin AW, Rubin SC, Noumoff JS, et al. The accuracy of frozen section
diagnosis of borderline ovarian malignancy. Gynecol Oncol 1995;59:183-5.
Zaitia, N, et al. Asian Pac J Cancer 2017. 19(1), 213-218
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Stage of Borderline Tumors
0
10
20
30
40
50
60
70
80
90
Stage I Stage II Stage III Stage IV
Serous
Mucinous
%
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Diagnosis & Surgical Staging
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Surgery & Staging of
Borderline Tumors
• Based on FIGO specifications.
• Childbearing Completed:
– TAH, BSO, Staging, Tumor Reduction if
obvious metastatic tumor present.
• Childbearing Not Completed:
– Unilateral salpingo-oophorectomy and staging
– Ovarian cystectomy and staging
• If mucinous - perform an appendectomy.
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Surgery & Staging of
Borderline Tumors
• Sites of metastatic disease in decreasing
order.
– Peritoneum
– Uterine Serosa / Fallopian Tube Serosa
– Omentum
– Retroperitoneal nodes
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Surgery & Staging of
Borderline Tumors
With minimal evidence to support cytotoxic
chemotherapy or radiation therapy for
treatment of metastatic LMP tumor,
aggressive surgical cytoreducion of
metastatic disease is the mainstay of
therapy.
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Mucinous Borderline Tumors
• Almost always unilateral
• If mucinous borderline tumor is bilateral,
consider metastatic disease from GI tract.
• Advanced stage mucinous borderline with
psuedomyxoma peritonei is probably
appendiceal in origin.
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Conservative Surgery for
Borderline Tumors
• 108 patients treated conservatively for OBT
– 89 treated with oophorectomy
– 19 treated with ovarian cystectomy
• 3/89 (3.4%) treated with oophorectomy recurred.
• 3/19 (15.8%) treated with cystectomy recurred.
• 26/32 women attempting pregnancy conceived
and carried.
Lee SY, et al. Obstet Gynecol Sci. 2017; 60(3):289-295
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Conservative Surgery for
Borderline Tumors
• 38 patients with ovarian borderline tumors
treated conservatively.
• 8% recurrence in the contralateral ovary.
• 15 patients with 22 subsequent pregnancies.
Gotlieb WH, et al. Borderline tumors of the ovary:
fertility treatment, conservative management, and
pregnancy outcome. Cancer 82:141-46, 1998.
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Advanced Stage Tumors
• 5-10% of patients with advanced stage
borderline tumors will have invasive
implants.
• 90-95% of patients with advanced stage
borderline tumors will have noninvasive
implants.
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Ovarian Serous Borderline TumorsRisk of developing serous carcinoma
• 1978-2002: 1026 women in Danish Patient Registry
• All slides reviewed by Johns Hopkins Pathologists
• Risk of developing serous carcinoma at 5 & 20 years
– Atypical proliferative serous tumors: 0.9% & 3.7%
– Non-invasive LGSC: 5% & 13.9%
Hannibal CG, et al: Gynecol Oncol. 2017 January;144(1):174-180
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Ovarian Borderline TumorsPostoperative Therapy
• Stage I - None
• Stage II - IV with Noninvasive Implants-
None
• Stage II - IV with Invasive Implants-
Probably None
• Patients with residual or recurrent disease-
Chemotherapy
• Primum Non Nocere
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Postoperative Therapy
• Nothing
• Chemotherapy: For LGSC
• Antiestrogen therapy
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Post Treatment Surveillance
???