Recurring Problems in the Frozen Section of Adnexal Masses

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1 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

2 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.

3 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

4 Epithelial Ovarian Neoplasms Role of surgery Diagnosis No preop diagnosis Cytoreduction To improve survival with adjuvant chemo Staging Fertility preservation Ovarian function

5 Ovarian Carcinoma Histology Mean age diagnosis Overall % Stage I-II % Stage III- IV% Serous high grade Clear cell Endometrioid Mucinous Kobel, Behbakht 1998, Hoskins

6 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

7 Stage BOTs 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

8 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

9 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)

10 Gross Cut Surface

11 Four (4) blocks submitted for frozen section

12 FS Dx: Mucinous Tumor with Borderline Features

13 Final Dx: Mucinous Carcinoma, Well Differentiated pt1c NX Appendectomy: Neuroendocrine Tumor (G1, carcinoid )

14 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: White, VA; Trotter, MJ. Intraoperative Consultation/Final Diagnosis Correlation. Arch Pathol Lab Med. 2008; 132:29-36

15 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%

16 Most common mistakes Mucinous tumors undercall Met vs primary

17 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

18 Possible primaries for met mucinous tumors: Appendix Colon Pancreas Gall Bladder Uterine Cervix Small Bowel Stomach Lung

19 For a population of cases, Primaries are: Unilateral Cystic or glandular-papillary-cystic Whereas mets are Bilateral Solid or multinodular solid Show surface involvement

20 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

21 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?

22 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

23 Mucinous LMP are bilateral 40% of the time; may show seromucinous mixture; may be associated with endometriosis.

24 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)

25 FS Dx: Malignant ovarian neoplasm, favor stromal tumor

26 Two (2) blocks were submitted for frozen section

27 FS Dx: Malignant ovarian neoplasm, favor stromal tumor

29 Final Dx: Clear Cell Carcinoma

30 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: 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%

31 Ovarian Clear Cell Carcinoma Tubulocystic Papillary Solid Adenofibromatous Cystic pattern with flat lining

32 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.

33 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

34 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

35 ?

36 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 Schmeler 2010, Cho 2006, Lin, Feigenberg 2013 Benjamin 1999 Zapardiel Lee 2014, Fruscio 2013 HR for recurrence 4.2 with Grade 3, stage 1

37 References: EA Behbakht K, et al; Clinical characteristics of clear cell carcinoma of the ovary. Gynecol Oncol Aug;70(2): Benjamin I, et al; Occult bilateral involvement in stage I epithelial ovarian cancer. Gynecol Oncol Mar;72(3): Cho YH, et al; Is complete surgical staging necessary in patients with stage I mucinous epithelial ovarian tumors? Gynecol Oncol Dec;103(3): 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 May;49(8): Feigenberg T, et al; Is routine appendectomy at the time of primary surgery for mucinous ovarian neoplasms beneficial? Int J Gynecol Cancer Sep;23(7): Fruscio R, et al; Conservative management of early-stage epithelial ovarian cancer: results of a large retrospective series. Ann Oncol Jan;24(1):

38 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 May;29(3): Köbel M, et al; Tumor type and substage predict survival in stage I and II ovarian carcinoma: insights and implications. Gynecol Oncol Jan;116(1):50-6. Lee JY, et al; Safety of Fertility-Sparing Surgery in Primary Mucinous Carcinoma of the Ovary. Cancer Res Treat Aug 29. Lin JE, et al; The role of appendectomy for mucinous ovarian neoplasms. Am J Obstet Gynecol 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 Aug;20(6): Schmeler KM, et al; Prevalence of lymph node metastasis in primary mucinous carcinoma of the ovary. Obstet Gynecol Aug;116(2 Pt 1): Zapardiel I, et al; The role of restaging borderline ovarian tumors: single institution experience and review of the literature. Gynecol Oncol Nov;119(2): Epub 2010 Aug 24.

39 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: 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: Tornos, C, Intraoperative Diagnosis of Ovarian Lesions, USCAP short course, March White, VA; Trotter, MJ. Intraoperative Consultation/Final Diagnosis Correlation. Arch Pathol Lab Med. 2008; 132:29-36

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