Immunohistochemical Analysis of Endothelial Cells in Vascular Transformation of Lymph Node Sinuses: Vascular or Lymphatic Differentiation?

INTRODUCTION: Vascular transformation of sinuses (VTS) is an uncommon and benign lesion, defined by conversion of lymph node sinuses into complex, anatomizing and endothelial-lined channels. Despite the name of VTS, which implies a change in differentiation from lymphatic to vascular endothelium, very few studies have systematically examined VTS with modern immunohistochemical markers commonly used in clinical laboratories. It is unclear whether endothelial cells in VTS display pure vascular or lymphatic differentiation, or both.

DESIGN: A total of 11 cases with a diagnosis of VTS (identified in the tissue archives of the Cleveland Clinic between 1992 and 2015) were reviewed and confirmed. Twenty cases of benign lymph nodes without specific diagnoses were used as control tissues. Immunohistochemical stains were performed on formalin-fixed, paraffin-embedded lymph node tissue using an automated immunohistochemistry platform with antibodies against CD31, CD34, D2-40, and ERG. Positivity in the VTS lesions was defined as distinct expression in the appropriate cell compartment in ≥20% of cells. In control cases, staining was evaluated in both vascular and lymphatic channels-vascular structures were identified by presence of red cells or well-formed vascular walls and lymphatics by anatomic location and absence of vascular features.

RESULTS: In the VTS lesions, D2-40 expression was absent in the lesional endothelial cells of 5/11 (45%) cases. In the cases lacking D240 expression, uninvolved lymphatic endothelium maintained expression. CD34 expression was also seen in 6/11 (54%), CD31 was seen in 10/11 (90%), and ERG expression was seen in all cases. In all the control cases, D240 expression was exclusively seen in lymphatic endothelial cells and not seen in vascular endothelial cells (eg, vascular channels in the hilum). CD34 was weakly positive in the lymphatic endothelium of only 7/20 (35%) control cases, but expressed in 20/20 (100%) control cases in the vascular endothelium. 20/20 (100%) of control cases showed expression of CD31 and ERG in both vascular and lymphatic endothelium.

CONCLUSION: VTS lesional endothelial cells demonstrate patterns of vascular markers that show mixed blood vascular and lymphatic features. There appears to be a degree of alignment toward endothelial differentiation with decreased expression of D2-40 in some cases.