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Ovarian borderline tumors

Ovarian borderline tumors. Nadeem R. Abu-Rustum, MD Memorial Sloan-Kettering Cancer Center. Key Points. Serous LMP Mucinous LMP Favorable outcome Fertility consequences. Borderline tumors. Synonyms: Tumor of borderline malignancy Borderline tumor (BT)

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Ovarian borderline tumors

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  1. Ovarian borderline tumors Nadeem R. Abu-Rustum, MD Memorial Sloan-Kettering Cancer Center

  2. Key Points • Serous LMP • Mucinous LMP • Favorable outcome • Fertility consequences

  3. Borderline tumors • Synonyms: • Tumor of borderline malignancy • Borderline tumor (BT) • Tumor of low malignant potential (LMP) • Atypical proliferative tumor

  4. Borderline tumors • Borderline: Neither clinically benign nor malignant • Recurrence can occur, but death is uncommon

  5. Borderline tumors • Borderline: Neither clinically benign nor malignant • Recurrence is common, but death is uncommon • Borderline: Neither morphologically benign nor malignant • Architectural complexity without malignant cytologic features & NO invasion

  6. Borderline tumors • Serous BTs and seromucinous BTs are both pathologically “borderline” and clinically “borderline.”

  7. Borderline tumors • Serous BTs and seromucinous BTs are both histopathologically “borderline” and clinically “borderline.” • Gastrointestinal mucinous, endometrioid & transitional BTs are only pathologically “borderline” • They are clinically BENIGN.

  8. Serous LMP

  9. Serous LMP

  10. Serous LMP

  11. Serous LMP

  12. Serous Carcinoma: Pathogenesis Familial Sporadic Cystadenoma Fimbria? Dysplasia High Grade Serous Carcinoma Serous Epithelium Borderline tumor (BT) Micropapillary BT Low Grade Serous Carcinoma KRAS BRAF BRCA-1 mutation TP53 mutation TP53 mutation Courtesy: Rob Soslow, MSKCC

  13. Low grade serous carcinoma: pathogenesis

  14. Ovarian LMP Tumors • 10-15% of epithelial tumors • Median age in mid-40s • 50% of serous tumors & 90% of mucinous tumors are unilateral • 60% of serous tumors & 90% of mucinous tumors are stage I • Fertility-sparing surgery possible in majority of young patients • 10-yr. survival ~90% for both tumor types

  15. Risk factors for recurrence of ovarian serous borderline tumors • Age • Elevated preoperative CA-125 • Micropapillary histology • Invasive implants • Residual peritoneal disease Evaluation of peritoneum & omentum much more important than lymph nodes Shih KK, et al. (MSKCC) Gynecol Oncol 2011

  16. Serous BT 70% Stage I 30% > Stage I 90-95% Non-Inv 5-10% Inv 56% No Rec 44% Recur 83% Inv** 17% Non-Inv Serous Borderline Tumors:10-20 year Follow-up Silva EG, et al. Am J Surg Pathol 2006;30:1367-1371 **75% of patients died

  17. Serous Carcinoma: Pathogenesis Familial Sporadic Cystadenoma Fimbria? Dysplasia High Grade Serous Carcinoma Serous Epithelium Borderline tumor (BT) Micropapillary BT Low Grade Serous Carcinoma KRAS BRAF BRCA-1 mutation TP53 mutation TP53 mutation Courtesy: Rob Soslow, MSKCC

  18. Serous LMP

  19. Bilaterality common in Serous = Loss of Fertility

  20. Significance ofMicropapillary (MP) Architecture • Associated with invasive implants • More aggressive because of invasive implants • Recur more frequently • More bilateral (70% vs. 20%) • More involve surface (60% vs. 30%)

  21. Implant Terminology • Ovarian borderline tumor + peritoneal disease = borderline tumor with implants • Ovarian carcinoma + peritoneal disease = metastatic ovarian carcinoma

  22. Implant Terminology • Ovarian borderline tumor + noninvasive peritoneal disease = borderline tumor with noninvasive implants • Ovarian borderline tumor + invasive peritoneal disease = low grade serous carcinoma

  23. Significance of Implant Type Non-invasive implant 10 year survival: 95% Invasive implant 10 year survival: 33-50% Stage III low-grade serous ca 10 yr survival: 25-50%

  24. No invasion AND no diffuse high-grade cytologic atypia or micropapillary architecture: non-invasive epithelial implant

  25. Fat or muscle invasion: invasive implant

  26. Implant Assessment Yes No Yes No Yes No Courtesy of Rob Soslow, MSKCC

  27. Impact of ImplantsSerous LMP Evaluation of peritoneum & omentum much more important than lymph nodes

  28. Lymph Nodes • 30% of stage III SBTs have involved LNs • NO Prognostic implication • Differential diagnosis: • Carcinoma • Nodular aggregates > 1mm • Benign Mullerian inclusions (endosalpingiosis) • Mesothelial hyperplasia McKenney JK, Balzer BL, Longacre TA. Am J Surg Pathol , 2006

  29. Therapy of LMP & Low-Grade Serous Carcinoma Surgery is the main treatment • Hormonal therapy (90% or SBT are ER+) • Cytotoxic chemotherapy • 4% complete response to platinum and taxol* • Targeted therapy • MEK inhibitors for invasive implants/low grade serous carcinoma *Schmeler KM, et al. Gynecol Oncol. 2008

  30. Serous Carcinoma: Pathogenesis Familial Sporadic Cystadenoma Fimbria? Dysplasia High Grade Serous Carcinoma Serous Epithelium Borderline tumor (BT) Micropapillary BT Low Grade Serous Carcinoma KRAS BRAF BRCA-1 mutation TP53 mutation TP53 mutation Courtesy: Rob Soslow, MSKCC

  31. Behavior of Serous Borderline Tumors • Well staged Ovary-confined SBT (with or without MP) = Benign • Unstaged SBT+MP = uncertain malignant potential • SBT with non-invasive implants = slow malignant potential • SBT with invasive implants = carcinoma

  32. Mucinous Borderline Ovarian Tumors • Endocervical or seromucinous (15%) • Gastrointestinal (85%) • Metastasis from GI primary

  33. Mucinous Borderline: Pathogenesis Sporadic Cystadenoma Gastrointestinal Mucinous BT Endometriosis Endocervical Mucinous BT Seromucinous BT Rule out GI Primary Mucinous BT KRAS ARID1Amutation In 33%

  34. Seromucinous Borderline Tumors(15% of Mucinous LMP) • Synonyms • Endocervical-type mucinous borderline tumor • Mixed epithelial borderline tumor • “True” borderline tumor, like serous borderline tumor

  35. Seromucinous Borderline

  36. Seromucinous Borderline

  37. Seromucinous

  38. Seromucinous Borderline Tumors • Similarities with serous borderline tumor • Assessment of micropapillary architecture • Association with implants • Possibility of malignant behavior (very rare!) Shappell HW, et al. Am J Surg Pathol. 2002

  39. Seromucinous Borderline Tumors • Differences with serous borderline tumor • Association with “Precursor” Endometriosis • Malignant potential is lower

  40. Seromucinous BT: Evidence Supporting Relation to Endometrioid Neoplasia • Lack or paucity of WT1 staining • Presence of ARID1A mutation in approximately 1/3 of cases Vang R, et al. Int J Gynecol Pathol. 2006 Wu DH, et al. Int J Gynecol Pathol. 2012

  41. (Gastro)intestinal mucinous borderline tumor

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