1. Use of intra-operative frozen section in surgery for potential early stage ovarian malignancy September 2011 Dr Paul Cross Consultant Cellular Pathologist QEH Gateshead

2. Ovarian “cancer” - Clinical Problem Want to try and diagnose as early as possible to allow definitive surgical treatment (if this was applicable) Need tissue diagnosis to do so Clinical discussion about possible use of frozen section to help diagnose intra- operatively to prevent second procedure if possible Can diagnose and help stage in early stage disease

3. Frozen Sections Advantages Rapid Accurate (usually) Liked by surgeons Are far more widely used elsewhere in the world One anaesthetic Disadvantages Time consuming (?) Costly (?) Stressful/?disliked by Pathologists Not that widely used in UK pathology Inaccurate (occasionally)

4. Why Gateshead? Northern Gynaecological Oncology Centre based at Gateshead Act as the Cancer Centre for women with Gynaecological malignancy for a population of approx 2,000,000 about 400 ovarian cancers/year High referral of cases of suspected ovarian malignancy (use of RMI >200)

5. Use of Ovarian Frozen Section Reporting Used in ovarian surgery to help decide if lesion is malignant or potentially malignant (borderline) or benign at the time of surgery If malignant or borderline then requires more tissue sampling to allow FIGO staging to assess possible extent of tumour involvement of other tissues If benign then requires no more surgery QEH is, as far as is known, one of a few centres in UK to routinely operate this ovarian FS service Ovarian FS makes about 86% of all the FS we do in our lab (n=195 for 2010)

6. Frozen Section Protocol All cases are discussed prior to surgery in MDT Those with possible stage 1 or 2 ovarian malignancy are put on theatre list for possible FS Laboratory are informed 24 hours in advance with details and approximate time Duty Pathologist (1 of 5) covers for FS Porter brings directly to lab when available FS processed (routinely 2 blocks) and report phoned back to theatre

16. Frozen section reporting Frozen section Paraffin section

17. The iceberg principle…..

18. Table 1 Overall frozen section reporting profile n=1439 PS BenignPS BorderlinePS Malignant FS Benign 7693919 FS Borderline 810282 FS Malignant 32415

19. Table 2 Overall frozen section reporting, combining borderline and malignant categories n=1439 PS BenignPS Borderline/ Malignant FS Benign 76958 FS Borderline/ Malignant 11601

20. Table 3 Primary ovarian epithelial tumours (serous, mucinous, endometrioid, clear cell, urothelial/Brenner) of the ovary at frozen section n=982 PS BenignPS BorderlinePS Malignant FS Benign417388 FS Borderline89774 FS Malignant12337

21. Summary - 1 Median time for reporting 20 minutes (range 10-45, mean 18.5 minutes) Overall specificity 98.6% Overall sensitivity 91.2% Lymphadenectomy rate 97.4% in malignant epithelial cases Overall metastasis to ovary from elsewhere 4.8%, of which 77% were raised at the time of the FS

22. Summary - 2 Of the 1439 frozen sections reported here (representing 1342 women), 94.5% of the women had the correct operative procedure at the initial surgical operation (that is staging or no-staging depending on the frozen section report). 4.3% of the women were under-staged at this first surgery, and required potentially a second procedure 1.2% of the women were over-staged based on the frozen section report

23. Summary - 3 19 false negatives(benign->malignant) –7 interpretational errors – 12 sampling errors 3 false positive (malignant -> benign) –All interpretational errors Educational feedback always given after interpretational errors Sampling errors hard to fully eliminate

24. FS by categories No % Epithelial 98268.4 –Serous 486 33.8 –Mucinous 26718.6 –Endometrioid 15110.5 –Clear Cell 584 –Brenner 201.4 Sex-Cord stromal 1389.6 Germ cell 785.4 Secondary 694.8 Benign non-neoplastic 16911.8

25. Summary - 4 Overall sampling errors depend on size/weight and type of ovarian lesion False negative rate for serous lesions is 0.7% and is for mucinous tumours 3.8% These two epithelial types accounted for 52.4% of FS overall Surgeons understand higher inherent error rate with mucinous lesions

26. Literature Comparison of PPV NoBen%Bl%M% Defer% Rose et al383926599.1- Yeo et al31698.2-100- Cuello et al84298.2-96.7- Twallfhoven et al9469262100- Obiakor et al31195.3-1002.6 Lim et al21598.4-100- Usubuton et al36092.1-93.13.3 Pinto et al243936193 Gateshead143992.953.198.80.4

27. Pathology FS Cost Require cryostat (which most/all labs have) Require –availability of lab staff (about 25 mins per FS case) –availability of Pathologist (about 10 mins per FS case) Availability can depend on geography of lab/offices and rotas Not a difficult skill to acquire to interpret Consumables – slides/blades/cryofreeze/stains - pence

28. Conclusion Ovarian frozen section service does work clinically but needs regular material, good team work and communication Good outcomes and can confidently be used to help manage the clinical situation Trusted by clinicians, pathologists and patients – the vast majority of women are correctly treated at first procedure (94.5% overall, 98.2% in the BL/malignant group)