Abstract
Melanoma has a propensity for lymph node metastasis. However, the incidence of lymphatic invasion detected by histology alone in primary melanoma is disproportionately low in comparison to the incidence of positive sentinel lymph nodes (SLN). With the discovery of lymphatic endothelial cell markers, such as podoplanin and LYVE-1, lymphatic vessels can be reliably detected in formalin-fixed paraffin-embedded (FFPE) tissues. There is a now consensus that lymphatic invasion detected by immunohistochemical stains in primary melanoma is much more common than previously reported by histological examination alone. Immunohistochemical stains show that lymphangiogenesis and lymphatic invasion in primary melanoma may occur intratumorally or peritumorally, and lymphatic invasion is common across the range of tumor thicknesses in primary vertical growth phase (VGP) melanomas. A number of studies have shown that lymphatic invasion in primary melanoma is associated with a positive sentinel lymph node biopsy and a worse clinical outcome. Although not currently a part of the standard of care for staging of melanoma, the detection of lymphatic invasion in primary melanoma using immunohistochemical markers may be helpful in planning of therapy in some cases and may find a routine role in primary melanoma microscopic attributes in future.
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References
Balch CM, Cascinelli N (2006) Sentinel-node biopsy in melanoma. N Engl J Med 355:1370–1371
Balch CM, Soong SJ, Gershenwald JE et al (2001) Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on cancer melanoma staging system. J Clin Oncol 19:3622–3634
Alitalo K, Tammela T, Petrova TV (2005) Lymphangiogenesis in development and human disease. Nature 438:946–953
Dadras SS, Paul T, Bertoncini J et al (2003) Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival. Am J Pathol 162:1951–1960
Giorgadze TA, Zhang PJ, Pasha T et al (2004) Lymphatic vessel density is significantly increased in melanoma. J Cutan Pathol 31:672–677
Al-Rawi MA, Mansel RE, Jiang WG (2005) Molecular and cellular mechanisms of lymphangiogenesis. Eur J Surg Oncol 31:117–121
Banerji S, Ni J, Wang SX et al (1999) LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol 144:789–801
Adams RH, Alitalo K (2007) Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 8:464–478
Rinderknecht M, Detmar M (2008) Tumor lymphangiogenesis and melanoma metastasis. J Cell Physiol 216:347–354
Alitalo A, Detmar M (2011) Interaction of tumor cells and lymphatic vessels in cancer progression. Oncogene. doi:10.1038/onc.2011.602
Gordon EJ, Rao S, Pollard JW et al (2010) Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation. Development 137:3899–3910
Yun SJ, Gimotty PA, Hwang WT et al (2011) High lymphatic vessel density and lymphatic invasion underlie the adverse prognostic effect of radial growth phase regression in melanoma. Am J Surg Pathol 35:235
Xu X, Gimotty PA, Guerry DP et al (2008) Lymphatic invasion revealed by multispectral imaging is common in primary melanomas and associates with prognosis. Hum Pathol 39:901–909
Valencak J, Heere-Ress E, Kopp T et al (2004) Selective immunohistochemical staining shows significant prognostic influence of lymphatic and blood vessels in patients with malignant melanoma. Eur J Cancer 40:358–364
Dadras SS, Lange-Asschenfeldt B, Muzikansky A et al (2005) Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes. J Cutan Pathol 32:84–84
Sahni D, Robson A, Orchard G et al (2005) The use of LYVE-1 antibody for detecting lymphatic involvement in patients with malignant melanoma of known sentinel node status. J Clin Pathol 58:715–721
Egger ME, Gilbert JE, Burton AL et al (2011) Lymphovascular invasion as a prognostic factor in melanoma. Am Surg 77:992–997
Morton DL, Thompson JF, Cochran AJ et al (2006) Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 355:1307–1317
Thompson JF, Shaw HM (2007) Sentinel node mapping for melanoma: results of trials and current applications. Surg Oncol Clin N Am 16:35–54
Schuchter L, Schultz DJ, Synnestvedt M et al (1996) A prognostic model for predicting 10-year survival in patients with primary melanoma. Ann Intern Med 125:369–375
Niakosari F, Kahn HJ, McCready D et al (2008) Lymphatic invasion identified by monoclonal antibody D2-40, younger age, and ulceration: predictors of sentinel lymph node involvement in primary cutaneous melanoma. Arch Dermatol 144:462
Doeden K, Ma Z, Narasimhan B et al (2009) Lymphatic invasion in cutaneous melanoma is associated with sentinel lymph node metastasis. J Cutan Pathol 36:772–780
Petersson F, Diwan AH, Ivan D et al (2009) Immunohistochemical detection of lymphovascular invasion with D2‐40 in melanoma correlates with sentinel lymph node status, metastasis and survival. J Cutan Pathol 36:1157–1163
Petitt M, Allison A, Shimoni T et al (2009) Lymphatic invasion detected by D2-40/S-100 dual immunohistochemistry does not predict sentinel lymph node status in melanoma. J Am Acad Dermatol 61:819–828
Rose AE, Christos PJ, Lackaye D et al (2011) Clinical relevance of detection of lymphovascular invasion in primary melanoma using endothelial markers D2-40 and CD34. Am J Surg Pathol 35:1441
Storr SJ, Safuan S, Mitra A et al (2012) Objective assessment of blood and lymphatic vessel invasion and association with macrophage infiltration in cutaneous melanoma. Mod Pathol 25:493–504
Fohn LE, Rodriguez A, Kelley MC et al (2011) D2–40 lymphatic marker for detecting lymphatic invasion in thin to intermediate thickness melanomas: association with sentinel lymph node status and prognostic value – a retrospective case study. J Am Acad Dermatol 64:336–345
Xu X, Chen L, Guerry DP et al (2012) Lymphatic invasion is independently prognostic of metastasis in primary cutaneous melanoma. Clin Cancer Res 18:229–237
Acknowledgments
We would like to thank Jie Dai for technical assistance. This work was supported by NIH grant CA-093372.
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Xu, X., Gimotty, P.A., Guerry, D., Karakousis, G., Elder, D.E. (2014). Lymphatic Invasion as a Prognostic Biomarker in Primary Cutaneous Melanoma. In: Thurin, M., Marincola, F. (eds) Molecular Diagnostics for Melanoma. Methods in Molecular Biology, vol 1102. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-727-3_15
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DOI: https://doi.org/10.1007/978-1-62703-727-3_15
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