Microvessel density, lymphovascular density, and lymphovascular invasion in primary cutaneous melanoma—correlation with histopathologic prognosticators and BRAF status

Phyu Phyu Aung, Dominick Leone, John Kyle Feller, Shi Yang, Marier Hernandez, Ron Yaar, Rajendra Singh, Thomas Helm, Meera Mahalingam

The relationship between microvessel density (MVD), lymphovascular density (LVD), and lymphovascular invasion (LVI) in primary cutaneous melanoma (PCM) remains unclear. Given this, a total of 102 PCMs were assessed for MVD (vascular endothelial growth factor receptor 2 and Endocan), LVD (D2-40), and LVI (immunostaining with D2-40/S-100 and hematoxylin and eosin); tumoral S-100A13, vascular endothelial growth factor receptor 2, and Endocan; and BRAF status. LVD was associated with MVD (P = .01). MVD was higher in PCMs with depth greater than or equal to 2 mm and ulceration (P = .04, .05), whereas LVD was higher in PCMs with depth greater than or equal to 2 mm and mitoses (P = .03, .02). After adjusting for MVD and LVD, only ulceration was associated with LVI (P < .02). A BRAF mutation was seen in 30.4% cases, and when present, both LVD and host response (P = .0008 and .04, respectively) were significantly associated with MVD. Immunostaining with S-100A13 was noted in 99% of cases and a significant association noted only with ulceration (P = .05). Immunostaining increased LVI positivity (46.5% versus 4.9% by hematoxylin and eosin, P < .0001). MVD and LVD are not associated with LVI, appear to be closely related with each other, and are associated with select markers of poor prognosticative value. The association between a host response and LVD and MVD in PCMs with a BRAF mutation suggests that they exhibit potential for strategizing immunotherapies.