Skip to main content

Advertisement

SpringerLink
Log in

Ectopic lymphoid structures in primary cutaneous melanoma

  • Research
  • Published:
Pathology & Oncology Research

Abstract

Ectopic lymphoid structures have been described in several tumor types including metastatic lesions, but not primary tumors, of patients with melanoma. Here we present evidence of B-cell follicles in primary cutaneous melanomas, being present in 39 of 147 cases (27 %). B-cell clusters were associated with T lymphocytes, most of which belonging to CD45RO+ memory T cells. A network of CD21+ follicular dendritic cells was demonstrated in 8 of 22 cases studied (36 %). MECA-79+ HEV-like venules were observed in the neighborhood of the follicles in the majority of cases, however, their presence was not confined to tumors hosting ectopic lymphoid structures. The appearance of B-cell aggregates did not show association with the outcome of the disease, although a trend for their higher prevalence was observed in thicker tumors. Our results show that neogenesis of lymphoid structures does occur in primary melanomas, albeit with lower frequency compared to that reported in metastases.

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

Similar content being viewed by others

References

  1. Bell D, Chomarat P, Broyles D, Netto G, Moumneh Harb G, Lebecque S, Valladeau J, Davoust J, Palucka KA, Banchereau J (1999) In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med 10:1417–1425

    Article  Google Scholar 

  2. Bombardieri M, Barone F, Humby F, Kelly S, McGurk M, Morgan P, Challacombe S, De Vita S, Valesini G, Spencer J, Pitzalis C (2007) Activation-induced cytidine deaminase expression in follicular dendritic cell networks and interfollicular large B cells supports functionality of ectopic lymphoid neogenesis in autoimmune sialoadenitis and MALT lymphoma in Sjögren’s syndrome. J Immunol 179:4929–4938

    Article  PubMed  CAS  Google Scholar 

  3. Cipponi A, Mercier M, Seremet T, Baurain JF, Théate I, van den Oord J, Stas M, Boon T, Coulie PG, van Baren N (2012) Neogenesis of lymphoid structures and antibody responses occur in human melanoma metastases. Cancer Res 72:3997–4007

    Article  PubMed  CAS  Google Scholar 

  4. Coppola D, Nebozhyn M, Khalil F, Dai H, Yeatman T, Loboda A, Mulé JJ (2011) Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling. Am J Pathol 179:37–45

    Article  PubMed  PubMed Central  Google Scholar 

  5. Coronella-Wood JA, Hersh EM (2003) Naturally occurring B-cell responses to breast cancer. Cancer Immunol Immunother 52:715–738

    Article  PubMed  Google Scholar 

  6. de Chaisemartin L, Goc J, Damotte D, Validire P, Magdeleinat P, Alifano M, Cremer I, Fridman WH, Sautès-Fridman C, Dieu-Nosjean MC (2011) Characterization of chemokines and adhesion molecules associated with T cell presence in tertiary lymphoid structures in human lung cancer. Cancer Res 71:6391–6399

    Article  PubMed  Google Scholar 

  7. Dieu-Nosjean MC, Antoine M, Danel C, Heudes D, Wislez M, Poulot V, Rabbe N, Laurans L, Tartour E, de Chaisemartin L, Lebecque S, Fridman WH, Cadranel J (2008) Long-term survival for patients with non–small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol 26:4410–4417

    Article  PubMed  CAS  Google Scholar 

  8. Iwamoto M, Shinohara H, Miyamoto A, Okuzawa M, Mabuchi H, Nohara T, Gon G, Toyoda M, Tanigawa N (2003) Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas. Int J Cancer 104:92–97

    Article  PubMed  CAS  Google Scholar 

  9. Jensen TO, Schmidt H, Møller HJ, Donskov F, Høyer M, Sjoegren P, Christensen IJ, Steiniche T (2012) Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma. Cancer 118:2476–2485

    Article  PubMed  CAS  Google Scholar 

  10. Kirk CJ, Hartigan-O’Connor D, Mulé JJ (2001) The dynamics of the T-cell antitumor response: Chemokine-secreting dendritic cells can prime tumor-reactive T cells extranodally. Cancer Res 61:8794–8802

    PubMed  CAS  Google Scholar 

  11. Ladányi A, Kiss J, Mohos A, Somlai B, Liszkay G, Gilde K, Fejős Z, Gaudi I, Dobos J, Tímár J (2011) Prognostic impact of B-cell density in cutaneous melanoma. Cancer Immunol Immunother 60:1729–1738

    Article  PubMed  Google Scholar 

  12. Ladányi A, Kiss J, Somlai B, Gilde K, Fejős Z, Mohos A, Gaudi I, Tímár J (2007) Density of DC-LAMP+ mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor. Cancer Immunol Immunother 56:1459–1469

    Article  PubMed  Google Scholar 

  13. Martinet L, Le Guellec S, Filleron T, Lamant L, Meyer N, Rochaix P, Garrido I, Girard JP (2012) High endothelial venules (HEVs) in human melanoma lesions. Major gateways for tumor-infiltrating lymphocytes. OncoImmunology 1:829–839

  14. Messina JL, Fenstermacher DA, Eschrich S, Qu X, Berglund AE, Lloyd MC, Schell MJ, Sondak VK, Weber JS, Mulé JJ (2012) 12-chemokine gene signature identifies lymph node-like structures in melanoma: Potential for patient selection for immunotherapy? Sci Rep 2:765

    Article  PubMed  PubMed Central  Google Scholar 

  15. Miyagawa S, Soeda J, Takagi S, Miwa S, Ichikawa E, Noike T (2004) Prognostic significance of mature dendritic cells and factors associated with their accumulation in metastatic liver tumors from colorectal cancer. Hum Pathol 35:1392–1396

    Article  PubMed  Google Scholar 

  16. Moldenhauer G, Popov SW, Wotschke B, Brüderlein S, Riedl P, Fissolo N, Schirmbeck R, Ritz O, Möller P, Leithäuser F (2006) AID expression identifies interfollicular large B cells as putative precursors of mature B-cell malignancies. Blood 107:2470–2473

    Article  PubMed  CAS  Google Scholar 

  17. Nzula S, Going JJ, Stott DI (2003) Antigen-driven clonal proliferation, somatic hypermutation, and selection of B lymphocytes infiltrating human ductal breast carcinomas. Cancer Res 63:3275–3280

    PubMed  CAS  Google Scholar 

  18. O’Brien PM, Tsirimonaki E, Coomber DW, Millan DW, Davis JA, Campo MS (2001) Immunoglobulin genes expressed by B-lymphocytes infiltrating cervical carcinoma show evidence of antigen-driven selection. Cancer Immunol Immunother 50:523–532

    Article  PubMed  Google Scholar 

  19. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen Y-T, Ohtani H, Old LJ, Odunsi K (2005) Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 102:18538–18543

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Suzuki A, Masuda A, Nagata H, Kameoka S, Kikawada Y, Yamakawa M, Kasajima T (2002) Mature dendritic cells make clusters with T cells in the invasive margin of colorectal carcinoma. J Pathol 196:37–43

    Article  PubMed  Google Scholar 

  21. Thompson ED, Enriquez HL, Fu YX, Engelhard VH (2010) Tumor masses support naïve T cell infiltration, activation, and differentiation into effectors. J Exp Med 207:1791–1804

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Tsukayama S, Omura K, Yoshida K, Tanaka Y, Watanabe G (2005) Prognostic value of CD83-positive mature dendritic cells and their relation to vascular endothelial growth factor in advanced human gastric cancer. Oncol Rep 14:369–375

    PubMed  CAS  Google Scholar 

  23. van Baren N, Baurain JF, Coulie PG (2013) Lymphoid neogenesis in melanoma. What does it tell us? OncoImmunology 2:e22505

Download references

Acknowledgments

The authors thank K. Derecskei and M. Kónya (National Institute of Oncology, Budapest) for technical assistance. The study was supported by the National Scientific Research Fund OTKA 72836 and 105132.

Author information

Authors and Affiliations

  1. Department of Surgical and Molecular Pathology, National Institute of Oncology, 7-9. Ráth György u., Budapest, H-1122, Hungary

    Andrea Ladányi & Erika Tóth

  2. Department Dermatology, National Institute of Oncology, 7-9. Ráth Gy. u., Budapest, H-1122, Hungary

    Gabriella Liszkay

  3. Department of Pathology, St. John’s Hospital, 1-3. Diós árok, Budapest, H-1125, Hungary

    Tímea Sebestyén

  4. Department of Dermato-Venerology, Semmelweis University, 41. Mária u., Budapest, H-1085, Hungary

    Beáta Somlai

  5. 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, 26. Üllői út, Budapest, H-1085, Hungary

    Anita Mohos

  6. 2nd Institute of Pathology, Semmelweis University, 93. Üllői út, Budapest, H-1091, Hungary

    József Tímár

Authors
  1. Andrea Ladányi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tímea Sebestyén
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anita Mohos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriella Liszkay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Beáta Somlai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Erika Tóth
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. József Tímár
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Ladányi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ladányi, A., Sebestyén, T., Mohos, A. et al. Ectopic lymphoid structures in primary cutaneous melanoma. Pathol. Oncol. Res. 20, 981–985 (2014). https://doi.org/10.1007/s12253-014-9784-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-014-9784-8

Keywords

Search

Navigation