Diagnosing vascular (venous) invasion in colorectal carcinomas

Transcription

1 Diagnosing vascular (venous) invasion in colorectal carcinomas Improving reproducibility and potential pitfalls Gábor Cserni Bács-Kiskun County Teaching Hospital, Kecskemét & University of Szeged Hungary

2 Venous invasion (VI) whether portal or (porto-)caval is an independent prognostic factor for haematogenous metastasis and survival in CRC

3 Incidence with HE in previous reports: 9-28% Stewart CJR et al. Histopathology 2007;51:372-8.

4 VI in previous HE series HE 365/703 RC (52%) Talbot I et al. Histopathology 1981;5: HE 12/82 (22%) of previously reported as V0 CC Stewart CJR et al. Histopathology 2007;51:372-8.

5 Clues Orphan artery Protruding tongue Circumferential muscular wall Circumferential elastic layer

6 Orphan artery Circumferential muscular wall Circumferential elastic layer Protruding tongue

7 Orphan artery Circumferential muscular wall Circumferential elastic layer Protruding tongue

8 Intramural vs extramural Both impact on prognosis. Petersen VC et al. Gut 2002; 51: Sternberg A et al. J Clin Pathol 2002; 55:17-21.

9 Reproducibility HE slides of pt3/pt4 CCs, 4 GI pathologists, St James Hospital, Leeds, UK Kappa 0.29 to 0.59 (poor to moderate agreement) elastic stain or standardized criteria Littleford SE et al. Histopathology 2009; 55:

10 Incidence with special stains in previous reports: 27-52% Stewart CJR et al. Histopathology 2007;51:372-8.

11 HE vs elastic stains EMVI: 18/75 (24%) 32/75 (43%) IMVI: 8/75 (11%) 30/75 (40%) Vass DG et al. J Clin Pathol 2004;57: /92 (18%) 57/92 (62%) Howlett CJ et al. J Clin Pathol 2009;62: (36%) vs 208 (46%) In Dukes stages A+B: 36/167 (22%) vs 37/113 (32%) p < Abdulkader M et al. Histopathology 2006;49: /121 (23%) (2002) vs 81/121 (67%) (2007) Bogner B et al. Magyar Onkol 2009;53:

12 Venous invasion HE detected VI in 18% Orcein (elastica stain) detected VI in 71% 11/89 CRCs had synchronous metastasis (M1) 9 N+ (pn1 or pn2) all VI+ i.e. V1 Median follow-up of 17 months 9 further cases were diagnosed with metachronous distant metastasis 6 N+ and all VI+ Sejben I et al. JCP 2010;63(7):575-8.

13 Venous invasion Specificity and sensitivity for predicting distant metastasis: LN metastasis: 0.56 and 0.75, respectively Orcein detected VI: 0.39 and 1, respectively Elastic stains enable the detection of clinically relevant VI in greater frequency than HE stained histological slides. If nodal involvement is an indication for systemic chemotherapy, our data suggest that VI detected by the orcein stain should also be an indication for that. Sejben I et al. JCP 2010;63(7):575-8.

14 HE x40 x100 x100 x400

15 Orcein x40 x100 x100 x400

16 Orcein staining Orcein electively stains elastic fibres in an acidic-alcohol milieu. Deparaffination Staining with orcein solution overnight orcein D 0,1 g 70% alcohol (ethanol) 100 ml concentrated HCl 2 ml Differentiation with 70% alcohol Dehydratation, clearing, mounting

17 Suspected VI in muscularis pr NOT VI! Unsuspected VI in submucosa VI!

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19 Reproducibility 2 40 HE slides, then 6w later 40 corresponding Movat-stained slides of CRCs (22 with unequivocal VI), 6 GI & 6 nongi pathologists, CANADA HE (kappa) Movat (kappa) GI 30% 58% NonGI 9% 35% All 20% (0.32) 46% (0.43) Kirsch R et al. AJSP 2013; 37:

20 Poststudy survey 9. Do you think that routine elastin staining of all blocks containing tumor should be introduced to facilitate the identification of venous invasion? 4/6 GI yes & 5/6 ngi yes 11. Would it be FEASIBLE to adopt routine elastin staining in your department? 4-5/6 GI yes & 4/6 ngi yes 12. What would be the reasons for you NOT routinely using an elastin stain to assess venous invasion? Cost, workforce constraints, both 1/6 GI & 4/6 ngi; other 1/6 GI & 4/6 ngi Kirsch R et al. AJSP 2013; 37:

21 Regarding costs and workload net benefits gained from the introduction of these special stains outweighed the small extra cost and effort and, in addition, saved time for the reporting pathologists. Abdulkader M et al. Histopathology 2006;49: About HUF for a staining solution used for about 3 months, processing about 200 slides, about 66 HUF/slide (320 HUF = 1 Euro), about 20 cents/slide, i.e. 1 Euro/case

22 Reproducibility 3 Incidence & practice assessment in 8 hospitals (1450 CRCs), different cohorts of 20 (10) cases w/wo special stains, w/wo guidance, w/wo area selection, Delphi method - development of new set of criteria; VI and LVI together or separately, JAPAN Kappa for VI: not different 0.52 (HE) to 0.50 (elastica stain), 0.55 with criteria; but 0.62 with the new criteria Kojima M et al. J Clin Pathol 2013; 66:551-8.

23 Criterion Scanning at X4 to identify suspected lesions, then further assessment at higher power. Elastica: thick arteries surrounded by tumor cluster; if elastica-stained internal elastic membrane covering more than half of circumference (basis for diagnosis) is present VI even in the absence of accompanying artery, vascular structure or space. Kojima M et al. J Clin Pathol 2013; 66:551-8.

24 Potential pitfalls Pseudo-venous invasion Cserni G et al. J Clin Pathol 2013; 66:

25 Capillary (A), venous (B,C) & arterial (D) invasion in CRC CD34 Orcein EVG Cserni G et al. J Clin Pathol 2013; 66:543-7.

26 Arterial (A, B) and venous (C, D) wall invasion Orcein Cserni G et al. J Clin Pathol 2013; 66:543-7.

27 Subserosal elastic lamina

28 Subserosal elastic lamina

29 Occasional submucosal elastic layer

30 Occasional submucosal elastic layer Diverticular mucosal protrusion

31 Periganglionic elastic fibres

32 Periganglionic elastic fibres

33 Periganglionic elastic fibres

34 Periganglionic elastic fibres

35 Postirradiation (noxious) changes Periglandular elastosis

36 Postirradiation (noxious) changes Periglandular elastosis

37 Postirradiation (noxious) changes Periglandular elastosis

38 Postirradiation (noxious) changes Periglandular elastosis

39 Postirradiation (noxious) changes Perimuscular elastosis

40 Postirradiation (noxious) changes Perimuscular elastosis (EVG)

41 Postirradiation (noxious) changes Perineural elastic fibres

42 Postirradiation (noxious) changes Perineural elastic fibres

43 Postirradiation (noxious) changes Perineural elastic fibres

44 Very rare perilymphoglandular elastic fibres

45 Very rare perilymphoglandular elastic fibres

46 Perifollicular elastic fibres (rectal ca)

47 Perifollicular elastic fibres (rectal ca)

48 Erythrocytes

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50 Conclusions Routine elastic stains are valuable in identifying an important prognosticator of CRC. They double or triple the rate of VI. (This is often neglected) ODx This may improve reproducibility, but consensus based diagnostic criteria also help. Pseudo-VI should be distinguished from VI.

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