Early detection of newly emerging diseases, lesion severity assessment, differentiation of medical conditions and automated screening are examples for the wide applicability and importance of anomaly detection (AD) and unsupervised segmentation in medicine. Normal fine-grained tissue variability such as present in pulmonary anatomy is a major challenge for existing generative AD methods. Here, we propose a novel generative AD approach addressing this issue. It consists of an image-to-image translation for anomaly-free reconstruction and a subsequent patch similarity scoring between observed and generated image-pairs for precise anomaly localization. We validate the new method on chest computed tomography (CT) scans for the detection and segmentation of infectious disease lesions. To assess generalizability, we evaluate the method on an ischemic stroke lesion segmentation task in T1-weighted brain MRI. Results show improved pixel-level anomaly segmentation in both chest CTs and brain MRIs, with relative DICE score improvements of +1.9% and +4.4%, respectively, compared to other state-of-the-art reconstruction-based methods.