## 1 Introduction  
Paleopathological studies reconstruct past health patterns and identify diseases, such as [PERSON]'s disease (leprosy), tuberculosis, and syphilis, by analyzing human osteological remains [1; 2]. However, this discipline has limitations since it relies mainly on the macroscopic observation of bones and teeth. Moreover, identifying a disease based on bone changes alone is not without interpretative error [3; 4]. For this reason, paleopathology has embraced a multidisciplinary approach when exploring diseases in the past in later years. Unfortunately, this multidisciplinary approach is often dependent on institutional resources and, for this reason, palaeopathological studies continue to rely heavily on osteological remains (e.g., bone) macroscopic analysis. In recent years, advanced paleopathological research has been complemented with ancient DNA (aDNA) analysis, alongside other biochemical and biomolecular techniques, furthering our understanding of disease at a microscopic and evolutionary level, allowing the identification of disease-related pathogens. Pathological cases with a conditioned diagnosis can be reassessed, and a positive diagnosis reached. The integration of molecular analysis in palaeopathological studies has already yielded exciting data, for example, on _Mycobacterium tuberculosis_, leprosy, plague, and syphilis [5; 6; 7; 8; 9]. Within paleopathology, syphilis is one of the few infectious diseases inferred by analyzing skeletonized human remains with a certain degree of certainty. Other diseases include [PERSON]'s disease (leprosy) and tuberculosis. These diseases may leave bone changes easily observable, identified as disease-related, and tagged as pathognonic of specific diseases, be it syphilis, leprosy, or tuberculosis. For example, destruction of the maxillary alveolar bone and atrophy of the anterior spine may be viewed as pathognomic of leprosy. Furthermore, cranial typical crater-like lesions with stellate radiating lines are pathognomic of skeletal tropenomatosis (as detailed below) [1; 10; 11]. However, these need to be interpreted with care, and their presence does not exclude the need for a differential diagnosis when assessing bone changes and addressing their probable etiology. Bone reaction to disease tends to be monotonous because bone tissue reactions are essentially destructive or reactive, with variations in degree and form. This diversification, allied to its distribution in the various bone elements of a skeleton and/or within a bone itself, is the basis for building a paleopathological diagnosis. Hence, a disease's pathognomic trait is a significant asset in the paleopathological interpretation and diagnosis of diseases in human remains. However, it must be contextualized. In syphilis, the skeleton is affected only in its tertiary stage, and bone lesions may take between 2 and 10 years to develop after the infection [10]. Although any bone from the skeleton may exhibit changes, these tend to be bilateral, with a preference towards the tibias, the nasal cavity bones, and the cranial vault, followed by other long bones of the extremities, and cancellous bone, such as the ribs and sternum, rich in hematopoietic marrow [10]. The bone-change pattern results from chronic non-granulomatous inflammation and/or a granulomatous (gummatous) processes involving bones' outer surfaces, cortex, and, sometimes, the medullary cavity. Syphilis bone lesions are primarily characterized as gummatous destruction, with period osteoclast reactions involving both the periosteum and underlying bone [10; 11]. The diagnostic feature (pathognomic feature) is observable in the skull and named \"caries sicca\", corresponding to healed superficial gummatous osteeitis of the calvaria, described as \"...nodules coming together to form star-shaped depressions, which may be deep, or wide and flat...\", i.e., cranial crater-like lesions with stellate radiating lines, forming a consistent pattern of changes [11].