Skip to main content

Advertisement

SpringerLink
Log in

Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

Acral lentiginous melanoma (ALM) is a poor prognosis subtype and is the most prevalent in non-Caucasian populations. The presence of tumor infiltrating lymphocytes (TILs) has been associated with poor prognosis in melanoma. A large cohort of ALM cases was studied to determine status of TIL and its association with outcome.

Methods

All patients with cutaneous melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Peru were retrospectively identified. Clinicopathological information was obtained from the medical charts. A prospective evaluation of TIL was performed. Analysis of association between ALM and clinicopathological features including TIL as well as survival analysis compared the outcome of ALM to whole group and extremity NALM was performed.

Results

537 ALM from a total of 824 cutaneous melanoma cases were studied. Older age (p = 0.022), higher Breslow (p = 0.008) and ulceration (p < 0.001) were found to be more frequent in ALM. Acral had worse overall survival (OS) compared with the whole group (p = 0.04). Clinical stage (CS) I–II patients had a median OS of 5.3 (95% CI 4.3–6.2) for ALM and 9.2 (95% CI 5.0–7.0) for extremity NALM (p = 0.016). Grade 0 (absence of TIL), I, II and III were found in 7.5, 34.5, 32.1, and 25.9%, respectively. Lower TIL grade was associated with larger tumor size (p = 0.003), higher Breslow (p = 0.001), higher Clark level (p = 0.007), higher CS (p = 0.002), extremity location (p = 0.048), histological subtype ALM (p = 0.024) and better OS (p = 0.001).

Conclusions

ALM is highly prevalent in Peru and carries poor outcome. Lower TIL levels were associated with poor outcome and ALM.

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. Piliang MP. Acral lentiginous melanoma. Clin Lab Med. 2011;31(2):281–8.

    Article  PubMed  Google Scholar 

  2. Bradford PT, Goldstein AM, McMaster ML, Tucker MA. Acral lentiginous melanoma: incidence and survival patterns in the United States, 1986–2005. Arch Dermatol. 2009;145(4):427–34.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wu XC, Eide MJ, King J, Saraiya M, Huang Y, Wiggins C, et al. Racial and ethnic variations in incidence and survival of cutaneous melanoma in the United States, 1999–2006. J Am Acad Dermatol. 2011;65:S26–37.

    Article  PubMed  Google Scholar 

  4. Lino-Silva LS, Dominguez-Rodriguez JA, Aguilar-Romero JM, Martinez-Said H, Salcedo-Hernandez RA, Garcia-Perez L, et al. Melanoma in Mexico: clinicopathologic features in a population with predominance of acral lentiginous subtype. Ann Surg Oncol. 2016;23(13):4189–94.

    Article  PubMed  Google Scholar 

  5. Vazquez Vde L, Silva TB, Vieira Mde A, de Oliveira AT, Lisboa MV, de Andrade DA, et al. Melanoma characteristics in Brazil: demographics, treatment, and survival analysis. BMC Res Notes. 2015;8:4.

    Article  PubMed  Google Scholar 

  6. Pozzobon F, Fierro E, Acosta Á, Carreñoc A. Características del melanoma cutáneo primario en el Instituto Nacional de Cancerología 2006–2010. Revista Colombiana de Cancerología. 2013;17(3):111–8.

    Article  Google Scholar 

  7. Zemelman V, Roa J, Tagle SR, Valenzuela CY. Malignant melanoma in Chile: an unusual distribution of primary sites in men from low socioeconomic strata. Clin Exp Dermatol. 2006;31(3):335–8.

    Article  CAS  PubMed  Google Scholar 

  8. Phan A, Touzet S, Dalle S, Ronger-Savle S, Balme B, Thomas L. Acral lentiginous melanoma: a clinicoprognostic study of 126 cases. Br J Dermatol. 2006;155(3):561–9.

    Article  CAS  PubMed  Google Scholar 

  9. O’Leary JA, Berend KR, Johnson JL, Levin LS, Seigler HF. Subungual melanoma. A review of 93 cases with identification of prognostic variables. Clin Orthop Relat Res. 2000;378:206–12.

    Article  Google Scholar 

  10. Green A, McCredie M, MacKie R, Giles G, Young P, Morton C, et al. A case-control study of melanomas of the soles and palms (Australia and Scotland). Cancer Causes Control. 1999;10:21–5.

    Article  CAS  PubMed  Google Scholar 

  11. Egger ME, McMasters KM, Callender GG, Quillo AR, Martin RC 2nd, Stromberg AJ, et al. Unique prognostic factors in acral lentiginous melanoma. Am J Surg. 2012;204(6):874–9 (discussion 9–80).

    Article  PubMed  Google Scholar 

  12. Pollack LA, Li J, Berkowitz Z, Weir HK, Wu XC, Ajani UA, et al. Melanoma survival in the United States, 1992 to 2005. J Am Acad Dermatol. 2011;65(5 Suppl 1):S78–86.

    PubMed  PubMed Central  Google Scholar 

  13. Kuchelmeister C, Schaumburg-Lever G, Garbe C. Acral cutaneous melanoma in caucasians: clinical features, histopathology and prognosis in 112 patients. Br J Dermatol. 2000;143(2):275–80.

    Article  CAS  PubMed  Google Scholar 

  14. Slingluff CL Jr, Vollmer R, Seigler HF. Acral melanoma: a review of 185 patients with identification of prognostic variables. J Surg Oncol. 1990;45(2):91–8.

    Article  PubMed  Google Scholar 

  15. Tan KB, Moncrieff M, Thompson JF, McCarthy SW, Shaw HM, Quinn MJ, et al. Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting. Am J Surg Pathol. 2007;31(12):1902–12.

    Article  PubMed  Google Scholar 

  16. Bello DM, Chou JF, Panageas KS, Brady MS, Coit DG, Carvajal RD, et al. Prognosis of acral melanoma: a series of 281 patients. Ann Surg Oncol. 2013;20(11):3618–25.

    Article  PubMed  Google Scholar 

  17. Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet. 2012;44(9):1006–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135–47.

    Article  CAS  PubMed  Google Scholar 

  19. Furney SJ, Turajlic S, Fenwick K, Lambros MB, MacKay A, Ricken G, et al. Genomic characterisation of acral melanoma cell lines. Pigment Cell Melanoma Res. 2012;25(4):488–92.

    Article  CAS  PubMed  Google Scholar 

  20. Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24(26):4340–6.

    Article  CAS  PubMed  Google Scholar 

  21. Turajlic S, Furney SJ, Lambros MB, Mitsopoulos C, Kozarewa I, Geyer FC, et al. Whole genome sequencing of matched primary and metastatic acral melanomas. Genome Res. 2012;22(2):196–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. McGovern VJ, Shaw HM, Milton GW. Prognosis in patients with thin malignant melanoma: influence of regression. Histopathology. 1983;7(5):673–80.

    Article  CAS  PubMed  Google Scholar 

  23. Clemente CG, Mihm MC Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer. 1996;77(7):1303–10.

    Article  CAS  PubMed  Google Scholar 

  24. Tuthill RJ, Unger JM, Liu PY, Flaherty LE, Sondak VK, Southwest Oncology G. Risk assessment in localized primary cutaneous melanoma: a Southwest Oncology Group study evaluating nine factors and a test of the Clark logistic regression prediction model. Am J Clin Pathol. 2002;118(4):504–11.

    Article  PubMed  Google Scholar 

  25. van Houdt IS, Sluijter BJ, Moesbergen LM, Vos WM, de Gruijl TD, Molenkamp BG, et al. Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumor infiltrating T-lymphocytes and preserved MHC class I antigen expression. Int J Cancer. 2008;123(3):609–15.

    Article  PubMed  Google Scholar 

  26. Mihm MC Jr, Clemente CG, Cascinelli N. Tumor infiltrating lymphocytes in lymph node melanoma metastases: a histopathologic prognostic indicator and an expression of local immune response. Lab Invest. 1996;74(1):43–7.

    PubMed  Google Scholar 

  27. Hillen F, Baeten CI, van de Winkel A, Creytens D, van der Schaft DW, Winnepenninckx V, et al. Leukocyte infiltration and tumor cell plasticity are parameters of aggressiveness in primary cutaneous melanoma. Cancer Immunol Immunother. 2008;57(1):97–106.

    Article  PubMed  Google Scholar 

  28. Mandala M, Imberti GL, Piazzalunga D, Belfiglio M, Labianca R, Barberis M, et al. Clinical and histopathological risk factors to predict sentinel lymph node positivity, disease-free and overall survival in clinical stages I–II AJCC skin melanoma: outcome analysis from a single-institution prospectively collected database. Eur J Cancer. 2009;45(14):2537–45.

    Article  CAS  PubMed  Google Scholar 

  29. Bogunovic D, O’Neill DW, Belitskaya-Levy I, Vacic V, Yu YL, Adams S, et al. Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival. Proc Natl Acad Sci USA. 2009;106(48):20429–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Burton AL, Roach BA, Mays MP, Chen AF, Ginter BA, Vierling AM, et al. Prognostic significance of tumor infiltrating lymphocytes in melanoma. Am Surg. 2011;77(2):188–92.

    PubMed  Google Scholar 

  31. Azimi F, Scolyer RA, Rumcheva P, Moncrieff M, Murali R, McCarthy SW, et al. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol. 2012;30(21):2678–83.

    Article  PubMed  Google Scholar 

  32. Taylor RC, Patel A, Panageas KS, Busam KJ, Brady MS. Tumor-infiltrating lymphocytes predict sentinel lymph node positivity in patients with cutaneous melanoma. J Clin Oncol. 2007;25(7):869–75.

    Article  PubMed  Google Scholar 

  33. Gimotty PA, Van Belle P, Elder DE, Murry T, Montone KT, Xu X, et al. Biologic and prognostic significance of dermal Ki67 expression, mitoses, and tumorigenicity in thin invasive cutaneous melanoma. J Clin Oncol. 2005;23(31):8048–56.

    Article  PubMed  Google Scholar 

  34. Barnhill RL, Fine JA, Roush GC, Berwick M. Predicting five-year outcome for patients with cutaneous melanoma in a population-based study. Cancer. 1996;78(3):427–32.

    Article  CAS  PubMed  Google Scholar 

  35. Wong SL, Kattan MW, McMasters KM, Coit DG. A nomogram that predicts the presence of sentinel node metastasis in melanoma with better discrimination than the American Joint Committee on Cancer staging system. Ann Surg Oncol. 2005;12(4):282–8.

    Article  PubMed  Google Scholar 

  36. Pasquali S, Mocellin S, Campana L, Vecchiato A, Bonandini E, Montesco M, et al. Maximizing the clinical usefulness of a nomogram to select patients candidate to sentinel node biopsy for cutaneous melanoma. Eur J Surg Oncol. 2011;37(8):675–80.

    Article  CAS  PubMed  Google Scholar 

  37. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Cockburn MG, Zadnick J, Deapen D. Developing epidemic of melanoma in the Hispanic population of California. Cancer. 2006;106(5):1162–8.

    Article  PubMed  Google Scholar 

  39. Lv J, Dai B, Kong Y, Shen X, Kong J. Acral melanoma in Chinese: a clinicopathological and prognostic study of 142 cases. Sci Rep. 2016;6:31432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gershenwald JE, Mansfield PF, Lee JE, Ross MI. Role for lymphatic mapping and sentinel lymph node biopsy in patients with thick (≥4 mm) primary melanoma. Ann Surg Oncol. 2000;7(2):160–5.

    Article  CAS  PubMed  Google Scholar 

  41. Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355(13):1307–17.

    Article  CAS  PubMed  Google Scholar 

  42. Yee VS, Thompson JF, McKinnon JG, Scolyer RA, Li LX, McCarthy WH, et al. Outcome in 846 cutaneous melanoma patients from a single center after a negative sentinel node biopsy. Ann Surg Oncol. 2005;12(6):429–39.

    Article  PubMed  Google Scholar 

  43. Scolyer RA, Thompson JF, Stretch JR, Sharma R, McCarthy SW. Pathology of melanocytic lesions: new, controversial, and clinically important issues. J Surg Oncol. 2004;86(4):200–11.

    Article  PubMed  Google Scholar 

  44. Rex J, Paradelo C, Mangas C, Hilari JM, Fernandez-Figueras MT, Ferrandiz C. Management of primary cutaneous melanoma of the hands and feet: a clinicoprognostic study. Dermatol Surg. 2009;35(10):1505–13.

    Article  CAS  PubMed  Google Scholar 

  45. Moehrle M, Metzger S, Schippert W, Garbe C, Rassner G, Breuninger H. “Functional” surgery in subungual melanoma. Dermatol Surg. 2003;29(4):366–74.

    PubMed  Google Scholar 

  46. Barnes BC, Seigler HF, Saxby TS, Kocher MS, Harrelson JM. Melanoma of the foot. J Bone Joint Surg Am. 1994;76(6):892–8.

    Article  CAS  PubMed  Google Scholar 

  47. Durbec F, Martin L, Derancourt C, Grange F. Melanoma of the hand and foot: epidemiological, prognostic and genetic features. A systematic review. Br J Dermatol. 2012;166(4):727–39.

    Article  CAS  PubMed  Google Scholar 

  48. Heaton KM, Naggar A, Ensign LG, Ross MI, Balch CM. Surgical management and prognostic factors in patients with subungual melanoma. Ann Surg. 1994;219(2):197–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Torres-Cabala CA, Wang WL, Trent J, Yang D, Chen S, Galbincea J, et al. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type. Mod Pathol. 2009;22(11):1446–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Paolino G, Bekkenk M, Didona D, Eibenschutz L, Richetta A, Cantisani C, et al. Is the prognosis and course of acral melanoma related to site-specific clinicopathological features? Age. 2016;61(129):62.

    Google Scholar 

  51. Paolino G, Panetta C, Cota C, Didona D, Moliterni E, Di Mattia C, et al. Vitamin D receptor immunohistochemistry variability in sun-exposed and non-sun-exposed melanomas. Melanoma Res. 2017;27(1):17–23.

    Article  CAS  PubMed  Google Scholar 

  52. Johnson DB, Peng C, Abramson RG, Wolchok JD, Sosman JA, Carvajal RD, Ariyan CE. Ipilimumab in acral melanoma: A retrospective review. ASCO Annual Meeting Abstracts. J Clin Oncol 2014;32(15_suppl) (May 20 Supplement), Abstract 9056.

  53. Larkin J, Hodi FS, Wolchok JD. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(13):1270–1.

    Article  PubMed  Google Scholar 

  54. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.

    Article  CAS  PubMed  Google Scholar 

  55. Day CL Jr, Sober AJ, Kopf AW, Lew RA, Mihm MC Jr, Golomb FM, et al. A prognostic model for clinical stage I melanoma of the trunk. Location near the midline is not an independent risk factor for recurrent disease. Am J Surg. 1981;142(2):247–51.

    Article  PubMed  Google Scholar 

  56. Clark WH Jr, Elder DE, Dt Guerry, Braitman LE, Trock BJ, Schultz D, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst. 1989;81(24):1893–904.

    Article  PubMed  Google Scholar 

  57. Daud AI, Wolchok JD, Robert C, Hwu WJ, Weber JS, Ribas A, et al. Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma. J Clin Oncol. 2016;34(34):4102–9.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Carbognin L, Pilotto S, Milella M, Vaccaro V, Brunelli M, Calio A, et al. Differential activity of nivolumab, pembrolizumab and MPDL3280A according to the tumor expression of programmed death-ligand-1 (PD-L1): sensitivity analysis of trials in melanoma, lung and genitourinary cancers. PLoS ONE. 2015;10(6):e0130142.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Oncology Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru

    C. A. Castaneda & H. L. Gomez

  2. Research Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru

    C. A. Castaneda, M. Castillo, V. Villegas, L. Cano, J. Sanchez & R. Galvez

  3. Departments of Pathology and Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    C. Torres-Cabala

  4. Pathology Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru

    S. Casavilca

  5. Breast Cancer Surgery Department, Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos Este 2520, Surquillo, 15038, Lima, Peru

    J. Dunstan, G. Calderon, M. De La Cruz, J. M. Cotrina & J. Abugattas

Authors
  1. C. A. Castaneda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Torres-Cabala
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Castillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. Villegas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Casavilca
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. Cano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Sanchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Dunstan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G. Calderon
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. De La Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J. M. Cotrina
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. H. L. Gomez
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. R. Galvez
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. J. Abugattas
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CAC, SC and CTC contributed to the conception and design of the study and performed data analysis and interpretation; CAC, SC and MC performed data acquisition, as well as providing administrative, technical, and material support; all authors drafted the article and made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.

Corresponding author

Correspondence to C. A. Castaneda.

Ethics declarations

Conflict of interests

The authors declare that they have no conflict of interests.

Ethics approval and consent to participate

The Institutional Review Board of INEN approved the conduct of this survey (#047-2015-CRP-DI-DICON/INEN), and all written informed consent was obtained from patients.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Castaneda, C.A., Torres-Cabala, C., Castillo, M. et al. Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America. Clin Transl Oncol 19, 1478–1488 (2017). https://doi.org/10.1007/s12094-017-1685-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-017-1685-3

Keywords

Search

Navigation