Pathology & Oncology Research

, Volume 20, Issue 4, pp 981–985 | Cite as

Ectopic lymphoid structures in primary cutaneous melanoma

  • Andrea LadányiEmail author
  • Tímea Sebestyén
  • Anita Mohos
  • Gabriella Liszkay
  • Beáta Somlai
  • Erika Tóth
  • József Tímár


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.


Ectopic lymphoid structures Primary melanoma B cells T cells Follicular dendritic cells High endothelial venules 



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.


  1. 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 10:1417–1425CrossRefGoogle Scholar
  2. 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 179:4929–4938PubMedCrossRefGoogle Scholar
  3. 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 72:3997–4007PubMedCrossRefGoogle Scholar
  4. 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 179:37–45PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Coronella-Wood JA, Hersh EM (2003) Naturally occurring B-cell responses to breast cancer. Cancer Immunol Immunother 52:715–738PubMedCrossRefGoogle Scholar
  6. 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 71:6391–6399PubMedCrossRefGoogle Scholar
  7. 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 26:4410–4417PubMedCrossRefGoogle Scholar
  8. 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 104:92–97PubMedCrossRefGoogle Scholar
  9. 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 118:2476–2485PubMedCrossRefGoogle Scholar
  10. 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 61:8794–8802PubMedGoogle Scholar
  11. 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 60:1729–1738PubMedCrossRefGoogle Scholar
  12. 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 56:1459–1469PubMedCrossRefGoogle Scholar
  13. 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 1:829–839Google Scholar
  14. 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 2:765PubMedCrossRefPubMedCentralGoogle Scholar
  15. 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 35:1392–1396PubMedCrossRefGoogle Scholar
  16. 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 107:2470–2473PubMedCrossRefGoogle Scholar
  17. 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 63:3275–3280PubMedGoogle Scholar
  18. 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 50:523–532PubMedCrossRefGoogle Scholar
  19. 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 102:18538–18543PubMedCrossRefPubMedCentralGoogle Scholar
  20. 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 196:37–43PubMedCrossRefGoogle Scholar
  21. 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 207:1791–1804PubMedCrossRefPubMedCentralGoogle Scholar
  22. 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 14:369–375PubMedGoogle Scholar
  23. 23.
    van Baren N, Baurain JF, Coulie PG (2013) Lymphoid neogenesis in melanoma. What does it tell us? OncoImmunology 2:e22505Google Scholar

Copyright information

© Arányi Lajos Foundation 2014

Authors and Affiliations

  • Andrea Ladányi
    • 1
    Email author
  • Tímea Sebestyén
    • 3
  • Anita Mohos
    • 5
  • Gabriella Liszkay
    • 2
  • Beáta Somlai
    • 4
  • Erika Tóth
    • 1
  • József Tímár
    • 6
  1. 1.Department of Surgical and Molecular PathologyNational Institute of OncologyBudapestHungary
  2. 2.Department DermatologyNational Institute of OncologyBudapestHungary
  3. 3.Department of PathologySt. John’s HospitalBudapestHungary
  4. 4.Department of Dermato-VenerologySemmelweis UniversityBudapestHungary
  5. 5.1st Institute of Pathology and Experimental Cancer ResearchSemmelweis UniversityBudapestHungary
  6. 6.2nd Institute of PathologySemmelweis UniversityBudapestHungary

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