Co-occurrence of malignant neoplasm and Hyperostosis Frontalis Interna in an Iron Age individual from Münsingen-Rain (Switzerland): A multi-diagnostic study

Objective: To re-analyze one of the oldest cases of malignant bone neoplasm with different analytical techniques. Material: The available skeletal remains of grave 138 (G138) from the Iron Age necropolis of Münsingen-Rain (Switzerland, 420–240 BC). Methods: The bones are analyzed by means of morphological, radiographic, histological, and biogeochemical methods. Results: The individual, a male aged between 35–50 years old, presents morphologically and radiographically a previously described coral-like bone neoformation on the proximal left humerus. The new analyses highlight previously undocumented coarse bone proliferation on the left scapula and lobular apposition on the endocranial surface of the frontal bone. The histological analysis of the humerus shows a ‘lace-like’ pattern of osteoid deposition without lamellation. Conclusions: Our data support a diagnosis of osteoblastic malignant neoplasm, probably an osteosarcoma or, more likely, a dedifferentiated chondrosarcoma for the humerus and scapula, and of hyperostosis frontalis interna on the frontal. The co-presence of a malignant neoplasm and hyperostosis frontalis interna may be related to a hormonal imbalance, a possibility also suggested by atypical funerary treatment. Significance: This study confirms G138 as one of the oldest cases of malignant bone neoplasm, adds new paleopathological data on this individual, and demonstrates the advantages of a multidisciplinary approach. Limitations: The discussion of the pathological changes is limited by the representation and preservation of the skeletal elements. Suggestion for Future Research: Biomolecular and protein biomarkers analyses may help to refine the diagnostic conclusions.