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FISHing for tricky naevi

FISHing for tricky naevi. Dr Hardeep Singh Manchester BAOP 2011. Over diagnosis of MM. Inappropriate therapy Psychological burdens Life assurance issues. Under-diagnosis of MM. Inadequate treatment of a deadly cancer. FISH for skin melanocytic lesions.

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FISHing for tricky naevi

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  1. FISHing for tricky naevi Dr Hardeep Singh Manchester BAOP 2011

  2. Over diagnosis of MM • Inappropriate therapy • Psychological burdens • Life assurance issues

  3. Under-diagnosis of MM • Inadequate treatment of a deadly cancer

  4. FISH for skin melanocytic lesions • Now a well established tool in the analysis of challenging, controversial, or ambiguous melanocytic lesions • Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma. Gerami P, et al Am J Surg Pathol. 2009 Aug;33(8):1146-56.

  5. Approach • Utilizing commercially available probes (Vysis) that assess copy numbers of: • RREB1 (6p25) • MYB (6q23) • CCND1 (11q13) • In relation to a centromeric reference point Cep6.

  6. Methodology • Assessment of 3 areas of 10 adjacent cells each….30 cells in total. • A positive FISH result is if any of the following criteria are met: • Gain in RREB1 relative to CEP6 >55% • Gain in RREB1>29% • Loss of MYB relative to CEP6 >40% • Gain in CCND1 >38%

  7. ‘…….. 86.7% sensitivity and 95.4% specificity in the validation cohort. The test also correctly identified as melanoma all 6 of 6 cases with ambiguous pathology that later metastasized. ……………………………………. this assay can have significant clinical impact and improve classification of melanocytic neoplasms with conflicting morphologic criteria’.

  8. Conjunctival naevi • When does junctional activity burn out…?? • What is significance of junctional activity over banal, maturing stromal component?

  9. Service evaluation validation of FISH in conjunctiva • 5 naevi • 5 melanosis without ‘atypia’ • 10 cases of atypical melanosis / C-MIN / in-situ MM with invasive MM in same eye

  10. Outcome • 5 Naevi….FISH negative • 5 melanosis without ‘atypia’..FISH negative • 10 cases of atypical melanosis /C-MIN/In-situMM and invasive MM….all FISH positive. • Correlated with results of a previous paper: Distinction of conjunctival melanocytic nevi from melanomas by FISH Busam et al. J. Cut. Pathol. 2010. Only looked at 2 ‘equivocal cases’…1 case was clearly in-situ on morphology…other was clearly invasive….fragmentation and tangential cutting were the inclusion criteria for ‘equivocal classification’. • Technique works in our hands

  11. Study of tricky naevi 7 patients 4 male ; 3 females. Males: 23, 31, 33, 46, Females: 46, 59, 70 All with naevus-like lesions clinically. Some change in colour / size noted. Excised.

  12. Histology • H &E showed some junctional activity over banal stromal naevus component. • In some cases, junctional activity beyond stromal naevus component. • FISH’ed because of ‘atypical’ junctional component.

  13. Normal FISH pattern in a benign naevus with 2 copies of each signal.

  14. Junctional component of ‘naevus’ Invasive MM after re-excising residual area

  15. Outcomes • 5 out of 7 ‘atypical’ junctional components were FISH ‘positive’: Classed as in-situ melanoma on morphological, architectural and FISH criteria, developing over naevus. The stromal naevus component in the 5 cases was FISH negative. • 2 out of 7 were FISH ‘negative’: Designated as ‘atypical naevi’ with careful follow up.

  16. Post-excision outcomes • 3 cases of in-situ melanoma showed residual intraepithelial FISH positive cells after excision or original ‘naevus’.

  17. Further service evaluation. • Assessment of the post MMC bx after treatment of in-situ MM /C-MIN / atypical melanosis. • Finding that FISH can pick out abnormal copy number in post MMC individual melanocytes in epithelium, along basal layer….helping in interpretation of bx.

  18. FISHing expedition… • Great for small volume tissue • Result is visual. • Correlate histology and molecular phenotype. • Very useful -not miraculous. • Morphology is still important. • If the histology is atypical, a positive FISH result is highly supportive, but a negative FISH result should not be taken as dismissal. • Expensive….therefore should really use on ‘equivocal / ambiguous’ cases only.

  19. Thanks

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