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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)