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
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
Incidence Carcinoma 22,000 yearly (2013) Borderline Ovarian Tumor (BOT) 3000/yr
Ave age 53yo carcinoma 44yo BOT
BOT 2/3 serous, 1/3 mucinous
Siegel 2013
Epithelial Ovarian Neoplasms
Role of surgery Diagnosis
No preop diagnosis
Cytoreduction To improve survival with adjuvant chemo
Staging Fertility preservation Ovarian function
Ovarian Carcinoma
Histology Mean age diagnosis
Overall % Stage I-II
% Stage III-
IV%
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 87% 10yr 21 Endometrioid 95% 10yr 50.9 Mucinous 95% 10yr 14.6
Mackay 2010 , Kobel 2010
BOTs
Stage I: 82.3 II: 7.6 III: 10.1 Stage II-III Serous: 24.1% Mucinous: 3.8%
Recurrence Overall recurrence: 8%, deaths 4.5% MV risk factors for recurrence
Stage 2.8 Fertility preservation 3.5 Incomplete staging 2.2 Tumor residual 3.4 Organ preservation 2.3
DuBois 2013
Surgical dilemma in apparent stage I ovarian neoplasm
Diagnosis may not be clear Need to stage
30% upstage avoid unnecessary procedures
Wish to preserve fertility Wish to preserve ovarian function
Case 1
• 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
pT1c NX
Appendectomy: Neuroendocrine Tumor (G1, “carcinoid”)
Context -‘Benchmark’
Frozen section – Permanent discrepancy rate between 1.1 and 3.3% 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
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
• 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:
Appendix Colon Pancreas Gall Bladder
Uterine Cervix Small Bowel Stomach Lung
For a population of cases, Primaries are:
Unilateral Cystic or glandular-papillary-cystic Whereas mets are Bilateral Solid or multinodular solid Show surface involvement
For the individual case
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
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?”
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
Mucinous LMP are bilateral 40% of the time;
may show seromucinous mixture; may be associated with endometriosis.
Case 2
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)
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
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
Tubulocystic Papillary Solid Adenofibromatous Cystic pattern with flat lining
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
CONSENT Learn your patient’s priorities Discuss and document plan for benign,
borderline and carcinoma
OK to return to OR if final path changes Minimally invasive can be easier for patient Discuss before first surgery Educate about limitations of frozen section
?
Early Stage Mucinous Neoplasm
Lymph node dissection Omit in apparent stage 1 BOT or mCA
Appendectomy Omit if normal appearing
Ovarian wedge resection Consider: 2.5% occult positive
Restaging – not necessary Fertility preservation
HR for recurrence 4.2 with Grade 3, stage 1
Schmeler 2010, Cho 2006, Lin, Feigenberg 2013
Benjamin 1999 Zapardiel
Lee 2014, Fruscio 2013
References: EA
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):138-44.
References: EA 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
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