Robert A. Soslow, MD soslowr@mskcc
Transcript of Robert A. Soslow, MD soslowr@mskcc
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Outline
• Orientation
• Ovarian tumor overview
• Non serous borderline tumors
• Serous borderline tumors
– Clinical summary
– Morphologic description
– Prognostic indices
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Borderline tumors
• Synonyms:
– Tumor of borderline malignancy
– Borderline tumor (BT)
– Tumor of low malignant potential (LMP)
– Atypical proliferative tumor
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Borderline tumors
• Borderline: Neither clinically benign nor
malignant
– Recurrence is common, but death is uncommon
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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 or invasion
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“Borderline” tumors
Serous
Intestinalmucinous
Sero-mucinous
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Borderline tumors
• Serous BTs and seromucinous BTs are both
histopathologically “borderline” and clinically
“borderline.”
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Borderline tumors
• Serous BTs and seromucinous BTs are both
histopathologically “borderline” and clinically
“borderline.”
• Intestinal mucinous, endometrioid and transitional
BTs are only histopathologically “borderline”; they
are not clinically borderline. They are instead
clinically benign.
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Serous carcinoma: pathogenesis
Fimbria?
Dysplasia
High grade carcinoma
BRCA-1mutation
TP53 mutation
Familial Sporadic
TP53 mutation
Surface Epithelium
Borderline tumor (BT)
Micropapillary BT
Low grade carcinoma
BRAFKRAS
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Low grade serous carcinoma: pathogenesis
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Clinical
• Fifth decade
• Pelvic discomfort
• +/- elevated CA125
• 70% stage I (30% of total are bilateral)
• 30% have extraovarian, peritoneal disease
• 95% 5-year survival
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Serous borderline tumor:
5/10 yr follow up
SBT
70% Stage I 30% >Stage I
90-95% Non-Inv 5-10% Inv
70% No Rec
30% Recur
70% Inv**
30% Non-Inv
** ~50% of patients diedGershenson DM, Silva EG. Cancer 1990;65:578-85
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Serous borderline tumors:
10/20 yr follow up
SBT
70% Stage I 30% >Stage I
90-95% Non-Inv 5-10% Inv
56% No Rec
44% Recur
83% Inv**
17% Non-Inv
**75% of patients diedSilva EG, et al. Am J Surg Pathol 2006;30:1367-1371
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Prognosis
– Confirmed
• Stage
– Success of debulking
– Implant invasion
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Prognosis
– Confirmed
• Stage
– Success of debulking
– Implant invasion
– Probable
• Architecture i.e. micropapillarity
• Microinvasion
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Prognosis
– Confirmed
• Stage
– Success of debulking
– Implant invasion
– Probable
• Architecture i.e. micropapillarity
• Microinvasion
– Not
• Lymph node involvement
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Implant terminology
• Ovarian borderline tumor + peritoneal disease
= borderline tumor with implant
• Ovarian carcinoma + peritoneal disease =
metastatic ovarian carcinoma
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Significance of implant type
Non-invasive implant survival (10 yr): ~95%Invasive implant survival (10-20 yr): 33-50%
Stage III low grade serous carcinoma survival (10-20 yr): 25-50%
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Implant morphology• No invasion WITHOUT diffuse high grade cytologic atypia or
micropapillary architecture: non-invasive
• Tumor stroma prominent WITHOUT fat or muscle invasion, diffuse high grade cytologic atypia or micropapillary architecture: non-invasive
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Implant morphology• No invasion WITHOUT diffuse high grade cytologic atypia or
micropapillary architecture: non-invasive
• Tumor stroma prominent WITHOUT fat or muscle invasion, diffuse high grade cytologic atypia or micropapillary architecture: non-invasive
• Fat or muscle invasion: invasive
• Diffuse high grade cytologic atypia: carcinoma
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Implant morphology• No invasion WITHOUT diffuse high grade cytologic atypia or
micropapillary architecture: non-invasive
• Tumor stroma prominent WITHOUT fat or muscle invasion, diffuse high grade cytologic atypia or micropapillary architecture: non-invasive
• Fat or muscle invasion: invasive
• Diffuse high grade cytologic atypia: carcinoma
• Endophytic micropapillary architecture WITHOUT fat or muscle invasion or diffuse high grade cytologic atypia: indefinite for invasion/probably invasive/may progress and then invade
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No invasion AND no diffuse high grade cytologic atypia or micropapillary architecture:
non-invasive epithelial implant
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Exophytic micropapillary architecture WITHOUT fat or muscle invasion or diffuse high grade cytologic atypia:
controversial entity
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Tumor stroma prominent AND no fat or muscle invasion, diffuse high grade cytologic atypia or
micropapillary architecture:non-invasive “desmoplastic” implant
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Tumor stroma prominent AND no fat or muscle invasion, diffuse high grade cytologic atypia or
micropapillary architecture:non-invasive “desmoplastic”
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Fat or muscle invasion: invasive implant
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Endophytic micropapillary architecture WITHOUT fat or muscle invasion or diffuse high grade cytologic atypia:
indeterminate/probably invasive/may progress and then invade
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Diffuse high grade cytologic atypia: high grade serous carcinoma
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Fat invasion
Invasive Cytologic atypia
Carcinoma Micropapillary
?Invasive Non-invasive
Yes
Yes No
No
Yes No
Implant assessment
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Significance of micropapillary (MP)
architecture in a non-invasive ovarian
tumor
• Established:
– MP tumors are more frequently associated with
invasive implants
– MP tumors are more frequently bilateral (70% vs
20%)
– MP tumors more frequently involve the ovarian
surface (60% vs 30%)
– MP tumors are more aggressive because of their
association with invasive implants
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Significance of micropapillary (MP)
architecture in a non-invasive ovarian
tumor
• Established:
– MP tumors are more frequently associated with invasive implants
– MP tumors are more frequently bilateral (70% vs 20%)
– MP tumors more frequently involve the ovarian surface (60% vs 30%)
– MP tumors are more aggressive because of their association with invasive implants
• Probable:
– MP tumors present at higher stage
– MP tumor recur more frequently
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Significance of micropapillary (MP)
architecture in a non-invasive ovarian
tumor
• Does this justify classification as “carcinoma?”
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Significance of MP architecture in an
ovarian tumor
Analogy: MP tumors are akin to low grade carcinomas in situ
1) If they’re non-invasive, they behave like other low grade,
non-invasive tumors.
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Significance of MP architecture in an
ovarian tumor
Analogy: MP tumors are akin to low grade carcinomas in situ.
1) If they’re non-invasive, they behave like other low grade,
non-invasive tumors.
2) If they’re invasive (anywhere), they behave like low grade
carcinoma.
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Significance of MP architecture in an
ovarian tumor
Analogy: MP tumors are akin to low grade carcinomas in situ.
1) If they’re non-invasive, they behave like other low grade,
non-invasive tumors.
2) If they’re invasive (anywhere), they behave like carcinoma.
3) If they’re incompletely excised, they can progress to
carcinoma.
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Significance of MP architecture in an
ovarian tumor
Analogy: MP tumors are akin to low grade carcinomas in situ.
1) If they’re non-invasive, they behave like other low grade,
non-invasive tumors.
2) If they’re invasive (anywhere), they behave like carcinoma.
3) If they’re incompletely excised, they can progress to
carcinoma.
4) If you don’t know whether they’re invasive, you must
investigate further.
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Significance of MP architecture in an
ovarian tumorAnalogy: MP tumors are akin to low grade carcinomas in situ.
1) If they’re non-invasive, they behave like other low grade, non-invasive tumors.
2) If they’re invasive (anywhere), they behave like carcinoma.
3) If they’re incompletely excised, they can progress to carcinoma.
4) If you don’t know whether they’re invasive, you must investigate further.
5) Avoid unequivocal diagnosis of borderline tumor at FS when MP architecture is present
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Microinvasion• Definition
– One or more foci
– <5mm in any one dimension or <10mm2
• Description
– Pink cells in spaces
– Micropapillary or cribriform nests
• Associations: pregnancy
• Significance (not pregnancy-associated)
– Over-represented in high stage cases
– Adverse outcome (Longacre)
McKenney JK, Balzer BL, Longacre TA. Am J Surg Pathol 30:1209-21, 2006
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Lymph nodes
• ~30% of stage III SBTs have involved LNs
• Prognostic implication: none
• Differential diagnosis:
– Carcinoma
• Nodular aggregates > 1mm
– Benign Mullerian inclusions (endosalpingiosis)
– Mesothelial hyperplasia
McKenney JK, Balzer BL, Longacre TA. Am J Surg Pathol 30:614-24, 2006
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Therapy
• Surgical disease
• Hormonal therapy
• 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 Mar;108(3):510-4.
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Serous carcinoma: pathogenesis
Fimbria?
Dysplasia
High grade carcinoma
BRCA-1mutation
TP53 mutation
Familial Sporadic
TP53 mutation
Surface Epithelium
Borderline tumor (BT)
Micropapillary BT
Low grade carcinoma
BRAFKRAS
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MEK inhibitors
Nature.com
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Managerial classification of SBT
• BENIGN:
– Ovary-confined SBT (with or without MP)
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Managerial classification of SBT
• BENIGN:
– Ovary-confined SBT (with or without MP)
• UNCERTAIN MALIGNANT POTENTIAL:
– Unstaged SBT-MP
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Managerial classification of SBT
• BENIGN:
– Ovary-confined SBT (with or without MP)
• UNCERTAIN MALIGNANT POTENTIAL:
– Unstaged SBT-MP
• (S)LOW MALIGNANT POTENTIAL:
– SBT (with or without MP) with noninvasive implants
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Managerial classification of SBT
• BENIGN:
– Ovary-confined SBT (with or without MP)
• UNCERTAIN MALIGNANT POTENTIAL:
– Unstaged SBT-MP
• (S)LOW MALIGNANT POTENTIAL:
– SBT (with or without MP) with noninvasive implants
• MALIGNANT
– SBT (with or without MP) with invasive implants
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Seromucinous borderline tumor
• Synonyms
– Mullerian mucinous borderline tumor
– Endocervical-type mucinous borderline tumor
– Mixed epithelial borderline tumor
• “True” borderline tumor, akin to serous
borderline tumor
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Seromucinous borderline tumor
• Similarities with serous borderline tumor
– Growth pattern
• Assessment of micropapillary architecture
– Association with implants
• Assessment for invasion
– Possibility of malignant behavior (very rare!)
Shappell HW, et al. Am J Surg Pathol. 2002 Dec;26(12):1529-41.
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Seromucinous borderline tumor
• Similarities with serous borderline tumor
– Growth pattern
– Association with implants
– Possibility of malignant behavior (very rare!)
• Differences with serous borderline tumor
– Association with endometriosis
– Morphologic similarities to endometrial cancers with mucinous metaplasia
– Malignant potential is lower
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Summary
• Serous and seromucinous BTs as a group are neither benign nor overtly malignant
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Summary
• Serous BTs as a group are neither benign nor overtly malignant
• Prognosis depends on stage, debulking, implant type, microinvasion and, possibly, micropapillary architecture
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Summary
• Serous BTs as a group are neither benign nor overtly malignant
• Prognosis depends on stage, debulking, implant type, microinvasion and, possibly, micropapillary architecture
• Tumors with invasive implants are morphologically and clinical similar to low grade serous carcinoma
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Summary
• Serous BTs as a group are neither benign nor overtly malignant
• Prognosis depends on stage, debulking, implant type, microinvasion and, possibly, micropapillary architecture
• Tumors with invasive implants are similar to low grade serous carcinoma
• Tumors with non-invasive implants may recur as invasive implants/low grade serous carcinoma
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