Skip to main content
SpringerLink
Log in

Correlation of histological and ex-vivo confocal tumor thickness in malignant melanoma

  • Original Article
  • Published:
Lasers in Medical Science Aims and scope Submit manuscript

Abstract

The ex-vivo confocal laser scanning microscopy (ex-vivo CLSM) is a novel diagnostic method for fresh tissue examination, which has already shown promising results in the evaluation of healthy skin and different skin tumors. In malignant melanoma, the histological tumor thickness plays an essential role for further treatment strategies. The immediate perioperative measurement of tumor thickness by means of ex-vivo CLSM might accelerate the decision for further operating procedures in malignant melanoma. Ten histologically confirmed malignant melanomas from various donor sites were blindly examined by two investigators via ex-vivo CLSM and conventional light microscopy. The histopathological tumor thickness (HTT) and confocal tumor thickness (CTT) were measured independently and evaluated using correlation curves, Spearman’s correlation coefficient, and Bland-Altman plots. Bland-Altman plots for HTT and reflectance-mode CTT, as well as for fluorescence-mode CTT, showed high correlations. Spearman’s correlation coefficient of HTT and CTT was 1.00 in FM and RM. The mean difference of RM-CTT and FM-CTT versus HTT was 0.09 ± 0.30 mm and 0.19 ± 0.35 mm. In one case, the HTT was identical to the CTT in both modes. This pilot study shows high conformity of CTT and HTT measured in malignant melanoma underlining the potential of ex-vivo CLSM for perioperative decisions on safety margin excisions of malignant melanoma in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Gartmann N, Brühwiler D (2009) Kontrolle und Visualisierung der Verteilung funktioneller Gruppen auf mesoporösem Siliciumdioxid. Angew Chem 121:6472–6475

    Article  Google Scholar 

  2. Scharnagl N, Schossig M (2005) Charakterisierung von Membranen. Chem Ing Tech 77:517–526

    Article  CAS  Google Scholar 

  3. Ulrich M, Lange-Asschenfeldt S (2013) In vivo confocal microscopy in dermatology: from research to clinical application. J Biomed Opt 18:61212. doi:10.1117/1.JBO.18.6.061212

    Article  Google Scholar 

  4. Lange-Asschenfeldt S, Bob A, Terhorst D, Ulrich M, Fluhr J, Mendez G, Roewert-Huber H, Stockfleth E, Lange-Asschenfeldt B (2012) Applicability of confocal laser scanning microscopy for evaluation and monitoring of cutaneous wound healing. J Biomed Opt 17:076016. doi:10.1117/1.JBO.17.7.076016

    PubMed  Google Scholar 

  5. von Braunmühl T, Welzel J (2015) Noninvasive diagnostic imaging in dermatology. Hautarzt 66:492. doi:10.1007/s00105-015-3645-6

    Article  Google Scholar 

  6. Sattler EC, Maier T, Hoffmann VS, Hegyi J, Ruzicka T, Berking C (2012) Noninvasive in vivo detection and quantification of Demodex mites by confocal laser scanning microscopy. Br J Dermatol 167:1042–1047

    Article  CAS  PubMed  Google Scholar 

  7. Guitera P, Menzies SW, Longo C, Cesinaro AM, Scolyer RA, Pellacani G (2012) In vivo confocal microscopy for diagnosis of melanoma and basal cell carcinoma using a two-step method: analysis of 710 consecutive clinically equivocal cases. J Investig Dermatol 132:2386–2394

    Article  CAS  PubMed  Google Scholar 

  8. Maier T, Sattler EC, Braun-Falco M, Korting HC, Ruzicka T, Berking C (2013) Reflectance confocal microscopy in the diagnosis of partially and completely amelanotic melanoma: report on seven cases. J Eur Acad Dermatol Venereol 27:e42–52

    Article  CAS  PubMed  Google Scholar 

  9. Hartmann D, Ruini C, Mathemeier L, Dietrich A, Ruzicka T, von Braunmühl T (2015) Identification of ex-vivo confocal scanning microscopic features and their histological correlates in human skin. J Biophotonics. doi:10.1002/jbio.201500124

    PubMed  Google Scholar 

  10. Longo C, Rajadhyaksha M, Ragazzi M, Nehal K, Gardini S, Moscarella E, Lallas A, Zalaudek I, Piana S, Argenziano G, Pellacani G (2014) Evaluating ex vivo fluorescence confocal microscopy images of basal cell carcinomas in Mohs excised tissue. Br J Dermatol 171:561–570

    Article  CAS  PubMed  Google Scholar 

  11. Karen JK, Gareau DS, Dusza SW, Tudisco M, Rajadhyaksha M, Nehal KS (2009) Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy. Br J Dermatol 160:1242–1250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gareau DS, Karen JK, Dusza SW, Tudisco M, Nehal KS, Rajadhyaksha M (2009) Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy. J Biomed Opt 14:34012

    Article  Google Scholar 

  13. Longo C, Ragazzi M, Gardini S, Piana S, Moscarella E, Lallas A, Raucci M, Argenziano G, Pellacani G (2015) Ex vivo fluorescence confocal microscopy in conjunction with Mohs micrographic surgery for cutaneous squamous cell carcinoma. J Am Acad Dermatol 73:321–322

    Article  PubMed  Google Scholar 

  14. Bennàssar A, Vilata A, Puig S, Malvehy J (2014) Ex vivo fluorescence confocal microscopy for fast evaluation of tumour margins during Mohs surgery. J Br Dermatol 170:360–365

    Article  Google Scholar 

  15. Longo C, Ragazzi M, Castagnetti F, Gardini S, Palmieri T, Lallas A, Moscarella E, Piana S, Pellacani G, Zalaudek I, Argenziano G (2013) Inserting ex vivo fluorescence confocal microscopy perioperatively in Mohs micrographic surgery expedites bedside assessment of excision margins in recurrent basal cell carcinoma. Dermatology 227:89–92

    Article  PubMed  Google Scholar 

  16. Hartmann D, Ruini C, Mathemeier L, Bachmann MR, Dietrich A, Ruzicka T, von Braunmühl T (2015) Identification of ex-vivo confocal laser scanning microscopic features of melanocytic lesions and their histological correlates. Submitted

  17. Engelhardt J, Knebel W (1993) Konfokale Laserscanning-Mikroskopie. Physik Unserer Zeit 24:70–78

    Article  CAS  Google Scholar 

  18. Breslow A (1970) Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172:902–908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fitzpatrick TB (1975) Soleil et peau [Sun and skin]. J Med Esth Chir Dermatol 2:33–34

  20. Fitzpatrick TB (1986) Ultraviolet-induced pigmentary changes: benefits and hazards. Curr Probl in Dermatol 15:25–38

  21. Longo C, Ragazzi M, Gardini S, Moscarella E, Argenziano G (2015) Ex vivo fluorescence confocal microscopy of eccrine syringomatous carcinoma: a report of 2 cases. JAMA Dermatol 151:1034–1036

    Article  PubMed  Google Scholar 

  22. Debarbieux S, Gaspar R, Depaepe L, Dalle S, Balme B, Thomas L (2015) Intraoperative diagnosis of nonpigmented nail tumours with ex vivo fluorescence confocal microscopy: 10 cases. Br J Dermatol 172:1037–1044

    Article  CAS  PubMed  Google Scholar 

  23. Pflugfelder A, Kochs C, Blum A, Capellaro M, Czeschik C, Dettenborn T, Dill D, Dippel E, Eigentler T, Feyer P, Follmann M, Frerich B, Ganten M, Gärtner J, Gutzmer R, Hassel J, Hauschild A, Hohenberger P, Hübner J, Kaatz M, Kleeberg UR, Kölbl O, Kortmann R, Krause-Bergmann A, Kurschat P, Leiter U, Link H, Loquai C, Löser C, Mackensen A, Meier F, Mohr P, Möhrle M, Nashan D, Reske S, Rose C, Sander C, Satzger I, Schiller M, Schlemmer H, Strittmatter G, Sunderkötter C, Swoboda L, Trefzer U, Voltz R, Vordermark D, Weichenthal M, Werner A, Wesselmann S, Weyergraf AJ, Wick W, Garbe C, Schadendorf D (2013) Malignant melanoma S3-guideline “Diagnosis, therapy and follow-up of melanoma”. J Dtsch Dermatol Ges 11:1–116

    PubMed  Google Scholar 

  24. Clark WHJR, From L, Bernardino EA, Mihm MC (1969) The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 29:705–727

    PubMed  Google Scholar 

  25. Andres C, Schneider JJ, Sander C, Braun-Falco M, Haraida S, Hein R, Ihrler S, Flaig MJ (2011) Histopathologie und molekulare pathologie (Zytogenetik). In: Berking C (ed) Maligne melanome, 6th edn. Zuckschwerdt Verlag, München, pp 42–46

    Google Scholar 

  26. Buttner P, Garbe C, Bertz J, Burg G, d’Hoedt B, Drepper H, Guggenmoos-Holzmann I, Lechner W, Lippold A, Orfanos CE (1995) Primary cutaneous melanoma. Optimized cutoff points of tumor thickness and importance of Clark’s level for prognostic classification. Cancer 75:2499–2506

    Article  CAS  PubMed  Google Scholar 

  27. Garbe C, Peris K, Hauschild A, Saiag P, Middleton M, Spatz A, Grob J, Malvehy J, Newton-Bishop J, Stratigos A, Pehamberger H, Eggermont A (2012) Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline—update 2012. Eur J Cancer 46:270–283

    Article  Google Scholar 

Download references

Acknowledgments

We would like to thank Mr. Sebastian Harraßer for his expert support and experimental assistance.

Author information

Author notes

    Authors and Affiliations

    1. Department of Dermatology and Allergology, Ludwig-Maximilian University, Frauenlobstr. 9-11, 80337, Munich, Germany

      Daniela Hartmann, Sebastian Krammer, Cristel Ruini, Thomas Ruzicka & Tanja von Braunmühl

    2. Department of Dermatology, Municipal Hospital of Munich, Thalkirchner Str. 48, 80337, Munich, Germany

      Daniela Hartmann, Cristel Ruini, Thomas Ruzicka & Tanja von Braunmühl

    Authors
    1. Daniela Hartmann
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Sebastian Krammer
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Cristel Ruini
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Thomas Ruzicka
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Tanja von Braunmühl
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Daniela Hartmann.

    Ethics declarations

    The trial was conducted following the principles of Helsinki.

    Conflict of interest

    The Vivascope® device was provided by Mavig GmbH for the time of the study from August to October 2015. The authors declare that they have no conflict of interest.

    Statement of all funding sources that supported the work

    There are no funding sources.

    Informed consent

    Informed consent was obtained from all individual participants included in the study.

    Additional information

    Daniela Hartmann and Sebastian Krammer contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Hartmann, D., Krammer, S., Ruini, C. et al. Correlation of histological and ex-vivo confocal tumor thickness in malignant melanoma. Lasers Med Sci 31, 921–927 (2016). https://doi.org/10.1007/s10103-016-1936-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10103-016-1936-5

    Keywords

    Search

    Navigation