Abstract
BackgroundWe examined the vascularity of mammary Paget disease histologically to confirm the increased blood flow observed previously by clinical imaging. The relationships among blood vessel density (BVD), histopathological parameters of blood flow in the nipple, and the expression of angiogenic factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) were examined.MethodsWe calculated the average CD34-positive BVD and podoplanin (D2–40)-positive lymphatic vessel density (LVD) and the proportion of proliferating of endothelial cells in 14 Paget disease, 3 dermatitis biopsy, and 14 age-matched control cases. As a parameter related to blood flow in the nipple, the total CD34-positive blood vessel lumen area relative to the entire nipple area was measured in each Paget disease and control case using an automated image analysis system. Immunohistochemical expression of bFGF and VEGFA in Paget cells was also examined.ResultsThe average BVD and LVD were significantly higher in the Paget disease cases than in the dermatitis (p = 0.003) and control (p < 0.001) cases. The proportion of proliferating endothelial cells was also increased in the Paget disease cases. The ratio of the CD34-positive blood vessel lumen area to nipple area was also significantly higher in the Paget disease than control cases (p = 0.003). The average BVD was correlated with the average LVD (r = 0.734, p < 0.001) and ratio of the blood vessel lumen area to nipple area (r = 0.692, p < 0.001). Immunohistochemical expression of bFGF was strong in all Paget disease cases, with a significantly higher expression score in the Paget disease than dermatitis (p = 0.003) and control (p < 0.001) cases. The bFGF, but not VEGFA, expression score, was strongly correlated with the average BVD (r = 0.818, p < 0.001) and ratio of the blood vessel lumen area to nipple area (r = 0.503, p = 0.006).ConclusionThese results provide direct histopathological evidence of a marked increase in nipple blood flow in Paget disease detected by clinical imaging. bFGF is considered to play a pivotal role in angiogenesis in mammary Paget disease.
Highlights
We examined the vascularity of mammary Paget disease histologically to confirm the increased blood flow observed previously by clinical imaging
Three biopsy specimens from nipple or areola dermatitis cases were collected during the same period (2004–2015); these biopsies had been performed to rule out mammary Paget disease, yielding a diagnosis of dermatitis
Comparisons of blood and lymphatic vessel densities and proportion of proliferating endothelial cells among the Paget disease, dermatitis, and control groups In the superficial area of the dermis, a few vessels were apparent in the control group (Fig. 2a, d, and g)
Summary
We examined the vascularity of mammary Paget disease histologically to confirm the increased blood flow observed previously by clinical imaging. The relationships among blood vessel density (BVD), histopathological parameters of blood flow in the nipple, and the expression of angiogenic factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) were examined. Contrastenhanced magnetic resonance imaging (MRI) is useful for detecting Paget lesions, because numerous vessels in the nipple/areola region provide a high contrast effect [4, 5]. Our group used Doppler sonography to reveal proliferation of blood vessels in the nipple in Paget disease, and found that the blood flow and capillary density were significantly higher in Paget disease lesions than in dermatitis [6]. The histological research on Paget disease vascularity is insufficient [6, 7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
