Use of intra-operative frozen section in surgery for potential early stage

ovarian malignancy

September 2011Dr Paul Cross

Consultant Cellular PathologistQEH

Gateshead

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

Frozen SectionsAdvantages

RapidAccurate (usually)Liked by surgeonsAre far more widely used elsewhere in the worldOne anaesthetic

DisadvantagesTime consuming (?)Costly (?)Stressful/?disliked by PathologistsNot that widely used in UK pathologyInaccurate (occasionally)

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)

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)

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

Frozen section reporting

Frozen section Paraffin section

The iceberg principle…..

Table 1 Overall frozen section reporting profile n=1439

PS Benign PS Borderline PS Malignant

FS Benign769 39 19

FS Borderline

8 102 82

FS Malignant3 2 415

Table 2 Overall frozen section reporting, combining borderline and malignant categories n=1439

PS Benign PS Borderline/Malignant

FS Benign 769 58

FS Borderline/Malignant

11 601

Table 3 Primary ovarian epithelial tumours (serous, mucinous, endometrioid, clear cell, urothelial/Brenner) of the ovary at frozen section n=982

PS Benign PS Borderline PS Malignant

FS Benign 417 38 8

FS Borderline 8 97 74

FS Malignant 1 2 337

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

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

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

FS by categoriesNo %

• Epithelial 982 68.4– Serous 486 33.8– Mucinous 267 18.6– Endometrioid 151 10.5– Clear Cell 58 4– Brenner 20 1.4

• Sex-Cord stromal 138 9.6• Germ cell 78 5.4• Secondary 69 4.8• Benign non-neoplastic 169 11.8

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

Literature Comparison of PPV

No Ben% Bl% M% Defer%

Rose et al 383 92 65 99.1 -Yeo et al 316 98.2 - 100 -Cuello et al 842 98.2 - 96.7 -Twallfhoven et al 946 92 62 100 -Obiakor et al 311 95.3 - 100 2.6Lim et al 215 98.4 - 100 -Usubuton et al 360 92.1 - 93.1 3.3Pinto et al 243 93 61 93Gateshead 1439 92.9 53.1 98.8 0.4

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

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)