Solitary osteochondromas in paleo-oncology: A case report from 4th-century BCE Pontecagnano (southern Italy).

OBJECTIVE: This study presents a new case of solitary osteochondroma (SOC) identified on the proximal tibia of a 4th-century BCE individual from Pontecagnano (Salerno, Italy) with an aim to contribute to differential diagnosis of bone tumors in archeological contexts. MATERIALS: Paleopathological assessment of a male individual with an estimated age-at death of 45.9-62.9 years brought to light during the archaeological excavations in the funerary sector of 'Sica de Concillis' within the necropolis of Pontecagnano. METHODS: Macroscopic and radiographic analyses were performed for diagnostic purposes. RESULTS: The proximal portion of the right tibia exhibited a large exophytic bone formation extending from the anteromedial to the posteromedial portion of the diaphysis. The x-ray confirmed the lesion being characterized by regular trabecular bone tissue with cortico-medullary continuity. CONCLUSIONS: The lesion observed is diagnostic of sessile SOC, a neoplasm that must have had aesthetic and, possibly, neurovascular complications due to its large size. SIGNIFICANCE: By offering a detailed description of a case of tibial osteochondroma and discussing the possible complications the individual might have experienced during life, this study highlights the role and importance of benign bone tumors in paleo-oncology. LIMITATIONS: Histological analysis was not carried out in order to preserve the integrity of the affected tibia. SUGGESTIONS FOR FURTHER RESEARCH: More attention should be devoted to benign tumors in paleopathology as their occurrence and manifestations in the past will lead to a better understanding of their impacts on the quality of life of affected individuals and to greater knowledge of their natural history.

Francesco Maria Fiorentini (1603-1673): An Italian physician in 'The Iron Century'.

The aim of this paper is to shed light on the figure of Francesco Maria Fiorentini, a 17th-century physician from Lucca (Tuscany, Italy) and member of the Iatromechanical School, who distinguished himself for his role during the plague and the typhus epidemics that spread throughout Italy in the first half of that century. His work must be contextualized in a precise historical moment, which marked the gradual transition of Western medicine from the archaism of Galenic doctrine to that of the Iatromechanical School, when the foundations started to be laid for an experimental type of medicine that based its assumptions on the direct observation of phenomena concerning the human body. In this work, we mainly focus on the medical biography of Fiorentini and on the reasons why he enjoyed great social prestige among the most prominent figures of his time. However, Fiorentini should also be remembered as a multifaceted scholar, as evidenced by his numerous writings, which underline his erudition in disparate fields of knowledge.

Paleopathology of Endocranial Lesions: A Possible Case of a Middle Meningeal Artery Aneurysm in an Etruscan Child from Pontecagnano (Southern Italy).

A middle meningeal artery (MMA) aneurysm is a type of intracranial aneurysm that has been rarely documented and is not completely understood in clinical medicine and especially in pediatrics, because juvenile cases have been extremely uncommon. Vascular conditions have occasionally been diagnosed in osteoarchaeological remains, providing evidence of their occurrence in previous eras. In the present report, we have described a lesion that was highly consistent with a case of an MMA aneurysm observed in an Etruscan child, whose remains had been exhumed during archaeological excavations in the necropolis of Pontecagnano (Salerno, southern Italy). The remains date back to the seventh to sixth century BC. Macroscopic and radiological examinations revealed an oval depression in the endocranial area corresponding to the parietal branch of the right MMA. The localized thinning of the bone and the absence of a bone reaction were compatible with a long-lasting compression of vascular origin highly consistent with an MMA aneurysm. Primary malignant bone tumors, bone metastasis, benign neoplastic conditions, and other non-neoplastic conditions, including calvarial venous malformations, eosinophilic granuloma, and sarcoidosis, could be excluded from the differential diagnosis, although the occurrence of other pathologies, such as dural arteriovenous fistulas, could not be rejected. Although it was not possible to definitely establish whether the MMA aneurysm was symptomatic, it could not be ruled out that rupture and subsequent extradural hemorrhage and/or intracranial hemorrhage could have caused the death of the child. From a paleopathological viewpoint, the case illustrated provides an interesting historical perspective on a rare neurovascular disorder that continues to be debated in modern clinical research.

A 13th-century cystic echinococcosis from the cemetery of the monastery of Badia Pozzeveri (Lucca, Italy).

OBJECTIVE: To differentially diagnose a calcified formation recovered from a 13th century AD grave from the Tuscan monastery of Badia Pozzeveri, Lucca, Italy. MATERIALS: A calcified formation from the thoraco-abdominal region of a skeleton buried in the monastery cemetery. METHODS: Cone Beam Computed Tomography, Scanning Electron Microscope and Energy Dispersive X-Ray Spectroscopy. RESULTS: A hollow, calcified ovoid formation was identified as typical of a hydatid cyst, permitting the diagnosis of cystic echinococcosis in a 35-45year-old female. CONCLUSIONS: The study reveals the circulation of the parasite Echinococcus granulosus in the region of Lucca in late medieval Tuscany. SIGNIFICANCE: This finding is the fourth case of cystic echinococcosis from an archaeological context in Italy and provides insight into environmental conditions that appear to have affected members of a community, irrespective of social status. LIMITATIONS: Caution and the application of multiple analyses must be exercised in the differential diagnosis to discriminate among calcified formations. SUGGESTIONS FOR FURTHER RESEARCH: Analysis of stable isotopes of the calcified formation, such as 15N and 13C, in order to compare them with isotopic values of the host individual and to further confirm the parasitic origin of the find.

A human MMTV-like betaretrovirus linked to breast cancer has been present in humans at least since the copper age.

The betaretrovirus Mouse Mammary Tumor Virus (MMTV) is the well characterized etiological agent of mammary tumors in mice. In contrast, the etiology of sporadic human breast cancer (BC) is unknown, but accumulating data indicate a possible viral origin also for these malignancies. The presence of MMTVenv-like sequences (MMTVels) in the human salivary glands and saliva supports the latter as possible route of inter-human dissemination. In the absence of the demonstration of a mouse-man transmission of MMTV, we considered the possibility that a cross-species transmission could have occurred in ancient times. Therefore, we investigated MMTVels in the ancient dental calculus, which originates from saliva and is an excellent material for paleovirology. The calculus was collected from 36 ancient human skulls, excluding any possible mouse contamination. MMTV-like sequences were identified in the calculus of 6 individuals dated from the Copper Age to the 17th century. The MMTV-like sequences were compared with known human endogenous betaretroviruses and with animal exogenous betaretroviruses, confirming their exogenous origin and relation to MMTV. These data reveal that a human exogenous betaretrovirus similar to MMTV has existed at least since 4,500 years ago and indirectly support the hypothesis that it could play a role in human breast cancer.

Multiple osteomata from medieval Tuscany, Italy (ca. 10th-12th AD).

OBJECTIVE: To explore the possible etiology of multiple osteomata on a skull and long bones from an individual from a medieval site in Tuscany, Italy. MATERIALS: Human skeletal remains dating to the 10th-12th century AD from the parish church of S. Pietro in Pava, in the province of Siena (Tuscany, Central Italy). METHODS: Macroscopic and imaging analyses (Cone Beam Computed Tomography). RESULTS: Nine round-shaped new bone formations are observed on a female individual aged 40-50 years. The lesions have a smooth surface and range from 2.2-6 mm in diameter. CONCLUSIONS: Cone Beam Computed Tomography confirmed that the lesions were composed of compact bone. Macroscopic and radiological features suggest the presence of nonsyndromic multiple osteomata. SIGNIFICANCE: Single cranial osteomata are commonly observed in osteoarchaeological remains, but multiple osteomata are rare and might assist in our understanding of neoplastic conditions in the past. LIMITATIONS: The lack of soft tissues prevents the diagnosis of complex disorders, such as the Gardner syndrome, which is characterised by multiple osteomata and polyposis of the colon. SUGGESTIONS FOR FURTHER RESEARCH: Careful investigation and reporting of all neoplastic lesions in ancient human remains in order to increase our knowledge about the etiology in past human populations.

Multiple myeloma in paleopathology: A critical review.

This paper provides a critical literature review concerning paleopathological evidence of multiple myeloma discovered both in the Old and in the New World. A critical assessment of the bioarchaeological and paleopathological documentary sources permitted to identify a total of 25 ascertained cases of multiple myeloma from different geographical areas in the world ranging from Prehistoric times up to the Contemporary age. The distribution of multiple myeloma findings in past times shows that the majority of cases have been discovered in the Old World (n = 18) and extend back to the Middle Ages, while the evidences in the New World (n = 7) seems to date back to the pre-Columbian era. The demographic profile suggests a sex ratio of 1.3:1, while 91.7% of affected individuals (n = 24) are adults. This critical review also discusses the diagnostic criteria and methodological issues commonly attempted in paleo-oncological research, with particular regard to the differential diagnosis of multiple myeloma. As such, the main focus of this work is to present a comprehensive and exhaustive scrutiny of the skeletal manifestations identified as multiple myeloma in order to improve the accuracy of diagnoses within the field of paleopathology.

Metastatic Prostate Carcinoma from Imperial Rome (1st to 2nd Centuries AD).

OBJECTIVE: This study describes and discusses a rare case of metastatic carcinoma that affected the skeleton of an adult male recovered in the necropolis of Casal Bertone in Rome (Italy). The necropolis, which dates back to the Imperial Age (1st to 2nd century AD), is located near some residential structures and a large place identified as a fullery (fullonica). METHODS: Anthropological and paleopathological studies of the skeletal remains were performed via careful macroscopic, microscopic, radiological (X-ray and CT scan), and histological investigation. RESULTS: The skeleton displayed mixed osteoclastic and osteoblastic lesions that mainly involved the axial bones, in particular the sternum, the ribs, the spine, and the scapular and pelvic girdles. The anatomical distribution and the destructive and proliferative nature of the lesions suggested diffuse metastases arising from a soft-tissue primary cancer. The age and sex of the individual, as well as radiographic and histological pictures, allowed diagnosis of an advanced prostate cancer with extensively diffused bone metastases. CONCLUSION: At present, this is the only case of prostate cancer from the Imperial Age recovered in Rome.

Paleopathological evidence of paranasal lesions: Two cases of frontal sinus osteomata from Imperial Rome.

The archaeological excavations carried out in 1999 in the Collatina necropolis of the Roman Imperial Age (1st-3rd centuries AD) (Rome, Italy) discovered the skeletal remains of two adult males with evidence of paranasal lesions. Both individuals showed postmortem damage in the frontal bone, through which it was possible to macroscopically detect an oblong new bone formation. In both specimens, radiological examination of the defects' morphology showed new pediculated-based bone formations. Radiology also confirmed the presence of benign osseous masses arising from the right frontal sinus and interpreted as osteomata. Their dimensions did not exceed 10 mm, so that mechanical complications and compression of the adjacent structures could be ruled out. The osteomata of paranasal sinuses are rarely reported in paleopathology, since they can be discovered only incidental to bone breakage or radiography. Hence, the evaluation of their occurrence in past populations represents an important challenge. The two cases presented here show direct and rare evidence of frontal sinus osteomata dating back to the Roman Imperial Age.

On the history of gout: paleopathological evidence from the Medici family of Florence.

OBJECTIVES: Throughout history, gout has been referred to as the "disease of the kings", and has been clearly associated with the lifestyle of the aristocratic social classes. According to the written sources, several members of the famous Medici family of Florence suffered from an arthritic disease that contemporary physicians called "gout". A paleopathological study carried out on the skeletal remains of some members of the family, exhumed from their tombs in the Church of San Lorenzo in Florence, offered a unique opportunity to directly investigate the evidence of the arthritic diseases affecting this elite group. METHODS: The skeletal remains of several members of the family were examined macroscopically and submitted to x-ray investigation. RESULTS: The results of the study allowed us to ascertain that the so-called "gout of the Medici" should be considered the clinical manifestation of three different joint conditions: diffuse idiopathic skeletal hyperostosis, rheumatoid arthritis and uratic gout. In particular, uric acid gout was diagnosed in the Grand Duke Ferdinand I (1549-1609). Recently, a new case of this disease was diagnosed in Anton Francesco Maria (1618-1659), a probable illegitimate member of the family. CONCLUSIONS: With this new case, uratic gout was observed in 2 out of 9 adult males, leading to suppose that the disease should have been a common health problem within the family. The aetiology of the disease has to be searched in environmental factors, since both historical and paleonutritional studies demonstrated that the diet of this aristocratic court was rich in meat and wine.

Trichuris trichiura in a post-Colonial Brazilian mummy

Trichuris trichiura is a soil-transmitted helminth which is prevalent in warm, moist, tropical and subtropical regions of the world with poor sanitation. Heavy whipworm can result either in Trichuris dysenteric syndrome - especially in children - or in a chronic colitis. In heavy infections, worms can spread proximally and may cause ileitis. Here we provide first microscopic evidence for a T. trichiura adult worm embedded in the rectum of a post-Colonial Brazilian adult mummy. During Colonial and post-Colonial times, many European chroniclers described a parasitic disease named Maculo whose symptomatology coincides with heavy helminthiasis. Based on our findings and on comparison of ancient textual evidence with modern description of heavy whipworm, we feel confident in considering that the two syndromes are expressions of the same pathological condition.

Pulverized human skull in pharmacological preparations: possible evidence from the "martyrs of Otranto" (southern Italy, 1480).

ETHNOPHARMACOLOGICAL RELEVANCE: Ever since the Late Medieval Ages historico-medical literature has attested the use of cranium humanun as an ingredient in pharmacological preparations for the treatment of epilepsy. Some authors suggest the use of pulverized bone obtained from individuals who died a violent death and were not buried. MATERIALS AND METHODS: The skeletal remains of hundreds of male inhabitants from Otranto, killed by the Ottomans in a mass execution on 14 August, 1480, are preserved in the Chapel of Martyrs in Otranto Cathedral (Apulia, southern Italy). The so-called "martyrs of Otranto" were beatified in 1771 and canonized by Pope Francis on 12 May, 2013. A cranial vault with 16 holes of different sizes, with regular rounded shape, was noticed among the skeletal remains, symmetrically arranged behind five large rectangular windows. Eight of the 16 holes, which exposed the diploe without reaching the endocranial surface, are incomplete perforations, while 8 holes are complete perforations; no evidence of bone reaction is visible. RESULTS: The lesions are the result of a multiple trepanation performed by using an instrument equipped with a large rounded tip. This tool could not produce bone discs, but only bone powder. It is impossible to establish with certainty the reasons for these multiple trepanations, but several hypotheses can be advanced, ranging from experimental surgery to a procedure designed to obtain relics. However, saint bones are very likely to have been regarded as having medicinal properties. As a matter of fact the martyrs of Otranto died a violent death and were not buried, and the pulverized bone obtained from their skulls might have been considered a particularly powerful ingredient for pharmacological preparations, as attested in the historico-medical literature. CONCLUSIONS: The skull of Otranto might represent a unique evidence of multiple trepanations carried out to obtain bone powder as ingredient for therapeutic preparations.

A possible case of Garre's sclerosing osteomyelitis from Medieval Tuscany (11th-12th centuries).

Archaeological excavations carried out at the castle of Monte di Croce near Florence brought to light a small cemetery complex belonging to the castle church, dated back to the 11th-12th centuries. An elite stone tomb contained the skeletal remains of a male aged 35-45 years with obvious pathology of the right tibia. The proximal metaphysis and the upper half of the diaphysis appear massively enlarged as a result of severe chronic periostitis. A transverse section illustrates complete obliteration of the medullary cavity by new spongy bone, with some large cavitations. The primary, but completely remodeled tibial shaft is still recognizable. This finding and the strong sclerotic reaction with some central cavitations rule out any form of bone tumor and indicate a chronic inflammatory disease. The morphological and radiological picture and the tibial localization suggest a diagnosis of chronic sclerosing osteomyelitis of Garré, a rare form of chronic osteomyelitis characterized by an intense periosteal reaction with little or no suppuration.

The "gout of the Medici": making the modern diagnosis using paleopathology.

Documentary sources show that painful joint disease afflicted several members of the Medici family, which dominated Renaissance Florence in Italy. The term frequently reported in contemporary archives to indicate these morbid episodes is "gout." Paleopathology allows us to verify the nosological information obtained from the written documents and to clarify the nature of the rheumatological condition that afflicted the Medici. A paleopathological study carried out on the skeletal remains of several members of the Medici family buried in the basilica of S. Lorenzo in Florence demonstrated that the "gout" of the Medici was truly a uric acid gout only in Ferdinand I (1549-1609), whose left foot showed peculiar lesions. Genetic and environmental factors, with particular regard to diet, may have been involved in the etiology of this disease, which in Ferdinand was associated with diffuse idiopatic skeletal hyperostosis (DISH). DISH was observed also in the column of Cosimo the Elder (1389-1464) and Cosimo I (1519-1574); a link between the incidence of DISH and high social status, especially in terms of lifestyle and nutritional patterns, has been suggested and the present study seems to further confirm this association. Finally, rheumatoid arthritis (RA) was diagnosed in Cosimo the Elder, Piero "the Gouty" (1416-1469) and Cardinal Carlo (1596-1666); as for Carlo, macroscopic and radiological findings were supported by molecular results which revealed that he was bearing the specificity HLA-DR4 predisposing to RA. The coexistence of DISH and RA attested in Cosimo the Elder can be interpreted as coincidental. In conclusion, the term "gout" as used in Renaissance texts has to be regarded as the clinical manifestation of a number of different joint diseases. In the case of the Medici family in Florence, these included DISH, rheumatoid arthritis and uric acid gout.