Testicular thrombotic microangiopathy: An unrecognized complication

Abstract

Thrombotic microangiopathy (TMA) causes global endothelial damage and multiorgan injury. No study has described reproductive organ involvement in TMA. Our study aimed to characterize testicular involvement in TMA. We reviewed autopsies from four patients who underwent hematopoietic cell transplant (HCT) complicated by TMA. Three patients had striking histologic evidence of TMA, while the fourth had normal testicular histology. This suggests that TMA injures the testicles and may adversely affect fertility. There is now an urgent need for a larger analysis of reproductive organ involvement in TMA.

Keywords: fertility; hematopoietic cell transplant; thrombotic microangiopathy; vascular biology.

Figure 1:. Vascular Injury in Testicular Tissue Associated with TMA after HCT.

Blue arrows in Panel A show capillaries and small to medium sized vessels with evidence of chronic vascular changes associated with TMA. These rigid-appearing vessels have abnormally increased wall to lumen ratios, best seen at higher magnification (24x and 38.5x). Blood vessel basement membranes are thickened and lamellated, with occasional splintering. The collagenous stroma surrounding vessels shows hyalinizing fibrosis, suggesting chronic injury (blue asterisks), with an expansion evident even at low power (3x). Panel B shows overall normal vessels (black arrows), with no evidence of TMA-related vascular injury as shown in Panel A. The stroma is delicate and light, with normal cellularity and no fibrous expansion (black asterisks). Independently, the basement membrane of atrophic seminiferous tubules is thickened (green arc). Panel C shows normal testicular vasculature (black arrows) and stroma (black asterisks). The high power inset images highlight representative vessels present in each respective field. Images were obtained using a Leica’s Aperio AT2 whole slide scanner, and Leica’s eSlide Manager software platform. Images were captured at 40x magnification in eSlide Manager’s Web Viewer. Image Resolution (microns/pixel): 0.2517.