1. Santa Monica 2006 IGCS - Interactive Session
21/04/2017
Interactive Session Ovarian Cancer II
Serous Borderline Tumors of the Ovary: Pathology, Biology, and Management
Jaime Prat, M.D.
Nathalie Sieben, M.D.
David Gershenson, M.D.
Santa Monica, CA
October 16, 2006

2. Surface epithelial ovarian tumors

3. Ovarian Epithelial Tumors ___________________________________________________________________________________________
Benign
60%
Serous
Mucinous
Endometrioid
Clear cell
Transitional cell
Undifferentiated Ca
30% BL
10%

4. Serous Tumors of the Ovary
Benign %
Borderline %
Carcinomas %

5. Borderline Ovarian Tumors
(Low Malignant Potential)
Epithelial hyperplasia
Nuclear atypia
Mitotic activity
NO “destructive” stromal invasion
WHO

6. Serous Borderline Tumors
Frequency % of Non-Bg
Age yrs
Bilaterality 30%
Stage I 70%

7. SBT

8. SBT

9. Serous carcinoma

10. Serous Borderline Tumor
Serous Carcinoma

11. Serous Borderline Tumor
Diagnostic Features
1. Branching papillae
2. Variable nuclear atypia
3. No stromal invasion

12. SBT - Micropapillary pattern

14. SBT - Micropapillary pattern

15. Serous Borderline Tumors
Typical Micropapillary
n=102 (%) n=18 a (%)
Mean age
Bilateral /96 (23) (67)
Exophytic growth /92 (29) /16 (44)
Stage
I (76) (28)
II (24) (72)
(p = )
Noninvasive implants (83) (92)
Invasive implants (17) (8)
(a) Microinvasive + micropapillary (3 cases)
Prat J, de Nictolis M
Am J Surg Pathol 2002

16. (More invasive implants?)
SBT - Micropapillary
(More invasive implants?)
1999 Eichhorn et al Possible
2002 Slomovitz et al No
2002 Deavers et al Yes (17% vs 6%)
2002 Prat & De Nictolis No
2003 Gilks et al No
2005 Longacre et al Yes
Overall survival similar to typical SBT

17. Carcinoma (> 3 mm) in SBT-MP

18. SBT with Microinvasion < 10 mm2
Cumulative literature: Excellent prognosis
Stanford data: Risk factor for disease progression

19. Serous Borderline Tumors
(Risk of progression)
Stage
Florid epithelial proliferation
(MP-cribriform pattern)
Microinvasion (?)
Type of peritoneal implants
Other factors yet unidentified
TA Longacre et al
Am J Surg Pathol 2005

20. Serous Borderline Tumors
Peritoneal Implants (30%)

22. Peritoneal Implants (SBT) Non-invasive - Epithelial - Desmoplastic
Bell DA, et al
Cancer 1988; 62:2212

23. Noninvasive epithelial implant

24. Noninvasive (desmoplastic) implant

25. Invasive implant

26. Invasive implant

27. Invasive implant

28. Serous Borderline Tumors
(Death from tumor )
Non-invasive implants Invasive implants
McCaughey et al 2/13 4/5
Bell DA et al 3/ /6
De Nictolis et al 0/10 4/9
Kennedy and Hart 1/25 0/1
Seidman and Kurman 1/ /3
Gershenson et al 6/ /39
Eichhorn et al 0/ /3
Bell KA et al 2/ /31
Prat and de Nictolis 0/34 3/6
Longacre et al 2/75 5/14
20/390 (5%) /117 (32%)

29. Serous Borderline Tumors
Two hypotheses

30. Serous Borderline Tumors
(Genome-wide allelotyping and B-RAF/K-RAS)
26 specimens from 10 patients
23 microsatellite markers
Peritoneal implants (6 invasive, 4 noninvasive); lymph nodes (3)
Concordance in 22 tumors of 8 informative patients
Sieben NLG et al
J Pathol (in press) 2006

31. Santa Monica 2006 IGCS - Interactive Session
21/04/2017
Sieben N et al.
J Pathol (in press) 2006

32. Serous Tumors (10 yr Survival) Bord Stage Ca 95% 1 54% 91% 1-4 23%
95% %
91% %
71% %

33. SBT in Lymph Nodes: 30% LN: Mullerian cysts (endosalpingiosis)

34. Serous Borderline Tumor
Carcinoma

35. SBT
6th recurrence
TCC

36. Epithelial Ovarian Cancer
(Pathogenesis)
Serous Borderline - B-RAF, K-RAS
Serous Ca - p53, LOH 17q21 (BRCA1),
13q12-q14 (BRCA2, RB1)
Mucinous tumors - K-RAS
Endometrioid Ca - Beta-catenin, PTEN, PIK3CA,
Microsatellite instability

37. Expression Profiling of Serous Low Malignant Potential, Low-Grade, and High-Grade Tumors of the Ovary.
Bonome T, et al. Cancer Res 2005; 65:10602
Overexpressed in SBT and Low-Grade Carcinoma
p53
p21
Cyclin D1
CIRP
c-FOS
Overexpressed in High-Grade Carcinoma
Cyclin E
CD20
STAT-1
Apoliprotein E
Rsf-1

38. Sieben N et al,
J Clin Oncol 2005

39. Santa Monica 2006 IGCS - Interactive Session
21/04/2017
Sieben N et al
J Clin Oncol 2005

40. High Grade
SBT
L G
Ovarian Serous Tumors

41. Santa Monica 2006 IGCS - Interactive Session
21/04/2017
SBT + MPSCa

42. Santa Monica 2006 IGCS - Interactive Session
MPSCa
SBT + MPSCa
Santa Monica 2006 IGCS - Interactive Session
21/04/2017

43. (Pathogenesis - Dualistic model)
Serous Tumors
(Pathogenesis - Dualistic model) Bg
SBT
SBT-MP
MP Ca (Inv)
G1-2
KRAS and BRAF mutations (70%)
Serous Ca G3
p53 mutations, LOH 17q (80%)
HER-2/neu amplification/overexpression
Singer et al
Am J Pathol 2002

44. SBTs and Serous Carcinomas
SBT-MP pattern is a risk factor within the SBT category rather than a separate category. Poor prognosis only with invasive implants.
Non-invasive implants, common and benign
Invasive implants, rare (12%) and fatal (clonal)
Serous dualistic model (working guide)
Low grade serous carcinomas are rare (B-Raf, K-ras)
High grade serous carcinomas are common (p53, LOH, chromosomal instability)

45. Santa Monica 2006 IGCS - Interactive Session
21/04/2017