Cancer nowadays is the second most common cause of death in high-income countries. However, only five cases of malignant-soft-tissue tumours are present in the palaeopathological literature.1 The rarity of cancer in antiquity is a highly debated problem and the main reasons are apparently the short lifespan of past populations, the scarcity of mummified remains, and the technical difficulties of detecting neoplastic lesions in mummified tissues.2
Three ancient malignant tumours were identified in the mummified remains of members of the Aragonese court—from the 15th and 16th centuries—that are preserved in the basilica of Saint Domenico Maggiore in Naples, Italy.
The autopsy of the natural mummy of King Ferrante I of Aragon (1424–94) revealed a well preserved rectum. Histology showed crowded epithelial tumour cells in cords and glands, typical of a moderately differentiated mucinous adenocarcinoma (figure A). Strong immunoreactivity for pan-cytokeratin was shown and DNA analysis of KRAS exons 1–2 showed the presence of a mutation that is characteristic of sporadic colorectal cancer and associated with exposure to natural carcinogens that would have been present in the diet of the time.3
The histological study of the natural mummy of Prince Luigi Carafa of Stigliano (1511–76) revealed an extraordinarily well preserved colon mucosa with an evident villous adenoma and strong immune positivity for keratins and p53 (TP53).1 In some sections of the tumour, clear invasion of the polyp stalk or soma pill was evident (figure B). This histological picture is that of a well differentiated adenocarcinoma at stage T1.1
The natural mummy of Duke Ferdinando Orsini of Gravina (circa 1490–1549), showed a wide, destructive lesion on the right orbit and nose. Bone histology revealed large lacunae where the normal lamellar bone had been destroyed. These cavities contained clusters of cells with solid epithelial-like aspects and a darker margin at the cellular rim (figure C), with strong positivity for pan-cytokeratin, which is typical of a destructive basal-cell carcinoma.4
The finding that, of a small group of mummies from Naples (eleven adults, ten men and one woman), three (aged 55–71 years) had cancer is very important. Despite the small number of specimens, the cancer prevalence of 27% that was found is close to the 31% found in modern countries.5 We can hypothesise that cancer must have been frequent after age 50–60 years, at least in the Renaissance elite classes with specific alimentary and lifestyle habits, as was found in this group of Aragonese nobles.
In conclusion, the assumptions that cancer was an extremely rare event in past populations should be revised. Future accurate autopsy studies of mummies will be essential to not only diagnose new palaeopathological cases, but also to clarify the mechanisms of ancient neoplastic progression.
Figure Caption
(A) Colorectal adenocarcinoma from Ferrante I of Aragon infiltrating the fibrous stroma (haematoxylin and eosin stain, magnification 100×). (B) Colon adenocarcinoma from Luigi Carafa, with invasion of the polyp stalk indicated by the arrow (anti-Pan Keratin, Ventana Medical Systems Inc., Tucson, AZ, USA, magnification 250×). (C) Basal-cell carcinoma from Ferdinando Orsini, with the solid tumour that destroyed the lamellar bone and the typical cellular rim indicated by the arrow (Van Gieson’s stain, magnification 120×).
References
- Fornaciari, G. Histology of ancient soft tissue tumors: a review. (published online March 21.)Int J Paleopathol. 2017
- David, AR and Zimmerman, MR. Cancer: an old disease, a new disease or something in between?.Nat Rev Cancer. 2010; 10: 728–733
- Ottini, L, Falchetti, M, Marinozzi, S, Angeletti, LR, and Fornaciari, G. Gene-environment interactions in the pre-Industrial Era: the cancer of King Ferrante I of Aragon (1431–1494). Human Pathol. 2011;42: 332–339
- Gaeta, R, Ventura, L, and Fornaciari, G. The cutaneous cancer of Ferdinando Orsini 5th Duke of Gravina. ((in press).)JAMA Dermat. 2017;
- Torre, LA, Bray, F, Siegel, RL, Ferlay, J, Lortet-Tieulent, J, and Jemal, A. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65: 87–108
