Recurring Problems in the
Frozen Section of Adnexal
Masses
John Bishop, M.D. & Edwin Alvarez M.D.
UC Davis Pathology and Laboratory
Medicine Symposium
24 October, 2014
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We have no financial interests to declare.
Objectives:
Apply sampling and interpretive criteria to reduce
frozen section discrepancy rates in ovarian
masses.
Discuss the surgical and clinical consequences of
such discrepancies.
Epithelial Ovarian Neoplasms
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Incidence
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Ave age
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Carcinoma 22,000 yearly (2013)
Borderline Ovarian Tumor (BOT) 3000/yr
53yo carcinoma
44yo BOT
BOT
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2/3 serous, 1/3 mucinous
Siegel 2013
Epithelial Ovarian Neoplasms
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Role of surgery
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Diagnosis
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Cytoreduction
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No preop diagnosis
To improve survival with adjuvant chemo
Staging
Fertility preservation
 Ovarian function
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Ovarian Carcinoma
Histology
Stage I-II Stage IIIMean age
Overall %
%
IV%
diagnosis
Serous
high grade
57
68
17
83
Clear cell
53
12.2
71- 97
2.5-39
Endometrioid
57
11.3
50
50
Mucinous
52
3.4
97
3.0
Kobel, Behbakht 1998, Hoskins
EOC - Survival
Histology
Early stage
Advanced stage
survival (months)
Serous - high grade
57% 10yr
40.8
Clear cell
Endometrioid
Mucinous
87% 10yr
95% 10yr
95% 10yr
21
50.9
14.6
Mackay 2010 , Kobel 2010
BOTs
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Stage
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I: 82.3 II: 7.6 III: 10.1
Stage II-III Serous: 24.1% Mucinous: 3.8%
Recurrence
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Overall recurrence: 8%, deaths 4.5%
MV risk factors for recurrence
Stage
 Fertility preservation
 Incomplete staging
 Tumor residual
 Organ preservation
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2.8
3.5
2.2
3.4
2.3
DuBois 2013
Surgical dilemma in apparent
stage I ovarian neoplasm
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Diagnosis may not be clear
Need to stage
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30% upstage
avoid unnecessary procedures
Wish to preserve fertility
Wish to preserve ovarian function
Case 1
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•
•
•
63 year old woman presents with an
adnexal mass, NOS (duration 35 years??)
The right tube and ovary weigh 4,850 gm
greatest dimension of 26.4 cm
Characterized as solid-cystic (70% solid)
(The left ovary was unremarkable)
Gross Cut Surface
Four (4) blocks submitted for
frozen section
FS Dx: Mucinous Tumor with
Borderline Features
Final Dx: Mucinous Carcinoma,
Well Differentiated
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pT1c NX
Appendectomy:
Neuroendocrine
Tumor (G1,
“carcinoid”)
Context -‘Benchmark’
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Frozen section – Permanent discrepancy
rate between 1.1 and 3.3%


Raab, SS; Tworek, JA; Souers, R; Zarbo, RJ.
The Value of Monitoring Frozen SectionPermanent Section Correlation Data Over
Time. Arch Pathol Lab Med. 2006; 130:337342
White, VA; Trotter, MJ. Intraoperative
Consultation/Final Diagnosis Correlation.
Arch Pathol Lab Med. 2008; 132:29-36
Context - Ovarian
•
Brun J-L, Cortez A, Rouzier R, et al. Factors
influencing the use and accuracy of frozen section
diagnosis of epithelial ovarian tumors. Am J Obstet
Gynecol 2008;199:244.e1-244.e7
414 Patients
Benign
LMP
Malignant
FS Sensitivity
97%
62%
88%
FS Specificity
81%
96%
99%
Most common mistakes
•
•
Mucinous tumors – undercall
Met vs primary
Predictive Factors in Misdiagnosis
of LMP tumors
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•
•
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Histologic type (mucinous)
Tumor size (less than 10 cm)
The borderline component (less than
10%)
Pathologist’s experience
Tendency to undercall borderlines
Possible primaries for met
mucinous tumors:
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Appendix
Colon
Pancreas
Gall Bladder
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Uterine Cervix
Small Bowel
Stomach
Lung
For a population of cases,
Primaries are:
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Unilateral
Cystic or glandular-papillary-cystic
Whereas mets are
Bilateral
Solid or multinodular solid
Show surface involvement
For the individual case
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this does not hold well enough
because:
Many mets are unilateral
Most solid tumors are in fact primary
Many mets are cystic
Keys to intraoperative exam
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Gross exam including careful inspection of
the surface
Clean cystic lesions well looking for
nodules, papillary areas, hemorrhagic
areas
Select samples
Freeze multiple samples on any complex
mucoid lesion
See or ask: “what does the other ovary
look like?”
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Malignant mucinous tumors can exhibit loss
of most of their mucin
When mucinous tumors are bilateral, that
favors metastasis
When a unilateral tumor is <13 cm, that
favors metastasis (about 87% of the time)
 BUT Mets from colon and appy can be
quite large
Other signs of mucinous mets incl
involvement of surface or of hilum;
infiltrative growth, either with nodular or
desmoplastic pattern; lots of signet rings
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Mucinous LMP are bilateral 40% of the
time;
may show seromucinous mixture;
may be associated with endometriosis.
Case 2
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A 60 year old woman presents with a
pelvic mass.
The right adnexa consist of a 180 gm
mass 16 cm in greatest dimension.
Grossly characterized as a soft tan
lobulated tumor with some cystic change
and hemorrhage.
(The left ovary was unremarkable)
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FS Dx: Malignant ovarian neoplasm,
favor stromal tumor
Two (2) blocks were submitted
for frozen section
FS Dx: Malignant ovarian
neoplasm, favor stromal tumor
Final Dx: Clear Cell Carcinoma

Azadeh Rakhshan · Hanieh Zham · Mehdi
Kazempour. Accuracy of frozen section diagnosis
in ovarian masses: experience at a tertiary
oncology center. Arch Gynecol Obstet (2009) 280:223–
228
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Overall accuracy 95.7%
Clear cell carcinoma may be a particularly difficult
problem on FS.
282 Patients
Benign
LMP
Malignant
FS Sensitivity
99%
60%
92%
Ovarian Clear Cell Carcinoma
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Tubulocystic
Papillary
Solid
Adenofibromatous
Cystic pattern with flat lining
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Recall that many of features by which
we name the tumor ‘clear cell’ are
formalin induced/ enhanced, including
papillary pattern and clear cytoplasm.
FS may subdue these features.
When in doubt on an ovarian
frozen:
 Re-check
the gross
 Take more samples
 Check for history in EMR
 Ask about the other ovary and
the abdomen generally
Surgeon’s conclusions
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CONSENT
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Learn your patient’s priorities
Discuss and document plan for benign,
borderline and carcinoma
OK to return to OR if final path changes
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Minimally invasive can be easier for patient
Discuss before first surgery
Educate about limitations of frozen section
?
Early Stage Mucinous Neoplasm
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Lymph node dissection
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Appendectomy
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Omit if normal appearing
Ovarian wedge resection
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Omit in apparent stage 1 BOT or mCA
Consider: 2.5% occult positive
Restaging – not necessary
Fertility preservation
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Schmeler 2010, Cho 2006,
Lin, Feigenberg 2013
Benjamin 1999
Zapardiel
Lee 2014, Fruscio 2013
HR for recurrence 4.2 with Grade 3, stage 1
References: EA
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Behbakht K, et al; Clinical characteristics of clear cell carcinoma of the ovary.
Gynecol Oncol. 1998 Aug;70(2):255-8.
Benjamin I, et al; Occult bilateral involvement in stage I epithelial ovarian
cancer. Gynecol Oncol. 1999 Mar;72(3):288-91.
Cho YH, et al; Is complete surgical staging necessary in patients with stage I
mucinous epithelial ovarian tumors? Gynecol Oncol. 2006 Dec;103(3):878-82.
du Bois A, et al; Arbeitsgmeinschaft Gynäkologische Onkologie (AGO) Study
Group. Borderline tumours of the ovary: A cohort study of the
Arbeitsgmeinschaft Gynäkologische Onkologie (AGO) Study Group. Eur J
Cancer. 2013 May;49(8):1905-14.
Feigenberg T, et al; Is routine appendectomy at the time of primary surgery
for mucinous ovarian neoplasms beneficial? Int J Gynecol Cancer. 2013
Sep;23(7):1205-9.
Fruscio R, et al; Conservative management of early-stage epithelial ovarian
cancer: results of a large retrospective series. Ann Oncol. 2013 Jan;24(1):13844.
References: EA
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Köbel M, et al; Cheryl Brown Ovarian Cancer Outcomes Unit of the British
Columbia Cancer Agency, Vancouver BC. Differences in tumor type in low-stage
versus high-stage ovarian carcinomas. Int J Gynecol Pathol. 2010
May;29(3):203-11.
Köbel M, et al; Tumor type and substage predict survival in stage I and II
ovarian carcinoma: insights and implications. Gynecol Oncol. 2010
Jan;116(1):50-6.
Lee JY, et al; Safety of Fertility-Sparing Surgery in Primary Mucinous Carcinoma
of the Ovary. Cancer Res Treat. 2014 Aug 29.
Lin JE, et al; The role of appendectomy for mucinous ovarian neoplasms. Am J
Obstet Gynecol. 2013 Jan;208(1):46.e1-4.
Mackay HJ, et al; Gynecologic Cancer InterGroup. Prognostic relevance of
uncommon ovarian histology in women with stage III/IV epithelial ovarian
cancer. Int J Gynecol Cancer. 2010 Aug;20(6):945-52.
Schmeler KM, et al; Prevalence of lymph node metastasis in primary mucinous
carcinoma of the ovary. Obstet Gynecol. 2010 Aug;116(2 Pt 1):269-73.
Zapardiel I, et al; The role of restaging borderline ovarian tumors: single
institution experience and review of the literature. Gynecol Oncol. 2010
Nov;119(2):274-7. Epub 2010 Aug 24.
References: JWB

Azadeh Rakhshan · Hanieh Zham · Mehdi Kazempour.
Accuracy of frozen section diagnosis in ovarian masses:
experience at a tertiary oncology center. Arch Gynecol Obstet
(2009) 280:223–228




Brun J-L, Cortez A, Rouzier R, et al. Factors influencing the
use and accuracy of frozen section diagnosis of epithelial
ovarian tumors. Am J Obstet Gynecol 2008;199:244.e1-244.e7
Raab, SS; Tworek, JA; Souers, R; Zarbo, RJ. The Value of
Monitoring Frozen Section-Permanent Section Correlation Data Over
Time. Arch Pathol Lab Med. 2006; 130:337-342
Tornos, C, Intraoperative Diagnosis of Ovarian Lesions, USCAP
short course, March 2011.
White, VA; Trotter, MJ. Intraoperative Consultation/Final Diagnosis
Correlation. Arch Pathol Lab Med. 2008; 132:29-36