Multidisciplinary Exploration of Computed-Tomographic and Ancient-DNA Data of an Iron Age Skull From Latvia With Multiple Lytic Bone Lesions: Differential Diagnosis Between Metastatic Carcinoma, Multiple Myeloma and Skeletal Tuberculosis.

Multiple lytic lesions of the cranial vault are among the most diagnostically ambiguous findings in paleopathology, since at least three pathological processes (metastatic carcinoma, multiple myeloma and disseminated tuberculosis) can produce morphologically convergent "punched-out" foci, while diagenetic erosion can mimic all three. Differential diagnosis based on macroscopic observation alone is therefore frequently inconclusive. The recent debate about whether multiple myeloma should be regarded as an ancient disease at all further reinforces the need for adjunct diagnostic streams. We hypothesised that, in a single archaeological individual presenting with multiple lytic cranial lesions, the integration of high-resolution computed tomography (CT, including assessment of the postcranial skeleton) with shotgun ancient DNA (aDNA) analysis can constrain the differential diagnosis between metastatic carcinoma, multiple myeloma and tuberculosis even when overall aDNA preservation is limited. We analysed the cranium and the first cervical vertebra (atlas, C1) of a 40-50-year-old female from a disturbed grave at the Čunkāni-Dreņģeri cemetery, Latvia, dated to the 10th CEntury CE, by subjecting it to direct visual paleopathological examination, computed tomographic and aDNA analysis. CT and aDNA streams support different leading diagnoses: CT favours metastatic carcinoma based on irregular margins and lesion-size variability, whereas aDNA provides a weak signal compatible with tuberculosis. Hyperdiploid multiple myeloma is effectively excluded. The combined cranial-plus-cervical pattern is consistent with hematogenously disseminated systemic disease, and the partial diagenetic component requires histological and X-ray fluorescence spectrometry authentication of lesion margins. The discordance between CT and aDNA streams demonstrates that single-stream paleopathological assessment can be misleading, and that targeted M. tuberculosis in-solution capture should be the next step.