title: Significantly high lymphatic vessel density in cutaneous metastasizing melanoma.
abstract: BACKGROUND
  Cutaneous melanoma has the propensity to early metastatic spread via the lymphatic vessels. Recent studies have found a positive correlation between an increased number of tumor-associated lymphatics and lymph node metastasis. The aim of this study was to determine whether there was a difference in the lymphatic vessel density (LVD) when cutaneous metastasizing melanomas were compared with nonmetastasizing melanomas and nevi.
  
  
  METHODS
  Ninety-five melanoma specimens (45 with lymph node metastasis, 50 nonmetastasizing) and 22 nevi specimens (7 compound, 5 intradermal, 4 blue, and 6 dysplastic) were investigated by immunostaining for the lymphatic endothelial marker D2-40. The quantification of lymphatics was conducted by computer-assisted morphometric analysis. Metastasizing and nonmetastasizing melanoma specimens were matched according to their thickness into three classes ≤2.0 mm, 2.01 - 4.0 mm, >4.0 mm.
  
  
  RESULTS
  Metastasizing melanomas thick 2.01-4.0 mm and thicker than 4.0 mm, showed a significantly higher intratumoral and peritumoral LVD compared with nonmetastasizing melanomas (2.01-4.0 mm, p =0.006 and p =0.032, respectively; >4.0 mm, p =0.045 and p =0.026, respectively). No significant difference in intratumoral and peritumoral LVD was found between metastasizing and nonmetastasizing melanomas of thickness ≤2.0 mm. Metastasizing melanomas showed a significantly higher intratumoral LVD compared with compound, intradermal, blue and dysplastic nevi p <0.001, p =0.002, p =0.002 and p <0.001, respectively), and significantly higher peritumoral LVD compared with compound nevi (p=0.039). Total average LVD was significantly higher in metastasizing melanomas than in nonmetastasizing melanomas (p <0.001), compound, intradermal, blue and dysplastic nevi (p <0.001, p <0.001, p =0.001 and p <0.001, respectively).
  
  
  CONCLUSIONS
  This study shows higher LVD in metastasizing melanomas compared with nonmetastasizing melanomas and nevi. In melanomas with intermediate thickness and in thick melanomas, higher intratumoral and peritumoral LVD are significantly associated with lymph node metastasis. This finding suggests that LVD can be a useful marker for identifying melanomas which are at a higher risk for the metastasis development. Hippokratia 2015; 19 (3): 210-215.
authors.affiliation: Department of Nuclear Medicine and Thyroid Diseases, Clinical Centre Banja Luka, Republic of Srpska, Bosnia and Herzegovina.
authors.forename: Z
authors.initials: Z
authors.lastname: Špirić
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Erić
authors.affiliation: Department of Pathology, Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Ž
authors.initials: Ž
authors.lastname: Eri
authors.affiliation: Department of Nuclear Medicine, Faculty of Medicine, University of Banja Luka, Banja Luka, Republic of Srpska, Bosnia and Herzegovina.
authors.forename: M
authors.initials: M
authors.lastname: Skrobić
keywords: D2-40; Melanoma; lymphatic vessel density; metastasis; nevi