We report about the rare case of a patient who developed large soft-tissue mass formations related with revision total knee arthroplasty which was implanted 4 years prior. Owing to suspected periprosthetic joint infection, the prosthesis was removed and the lesions were resected, resulting in severe soft-tissue loss and temporary arthrodesis using a poly(methyl methacrylate) spacer. Histological analysis revealed a type VI periprosthetic membrane. The situation was further complicated by wound infection requiring multiple revision surgeries. After discussion and evaluation of the available treatment options, the decision for an above-the-knee amputation was made. The tissue reaction resulting in these soft-tissue lesions is referred to as an “adverse local tissue reaction.” Wear-induced lesions after total knee arthroplasty, especially of this magnitude, are very rare and difficult to treat.