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Multiple osteomata from medieval Tuscany, Italy (ca. 10th–12th AD)
International Journal of Paleopathology 25 (2019) 56–61
Contents lists available at ScienceDirect
International Journal of Paleopathology journal homepage: www.elsevier.com/locate/ijpp
Multiple osteomata from medieval Tuscany, Italy (ca. 10th–12th AD) a,⁎
a
a
T
b
Valentina Giuffra , Simona Minozzi , Giulia Riccomi , Antonio Giuseppe Naccarato , Maura Castagnab, Riccardo Lencionic, Silvio Chericonid, Valeria Mongellia, Cristina Felicie a
Division of Paleopathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 57, 56126 Pisa, Italy Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 57, 56126 Pisa, Italy Division of Diagnostic Radiology 1, Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy d Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, via Roma 55, 56126 Pisa, Italy e Department of History and Cultural Heritage, Via Roma 56, 53100 Siena, Italy b c
A R T I C LE I N FO
A B S T R A C T
Keywords: Button lesions Gardner syndrome Nonsyndromic osteomata Cone beam computed tomography
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.
1. Introduction Osteomata are the most common primary benign bone tumors of the skull. They are relatively-circular raised areas of dense bone, characterized by slow growth and are usually asymptomatic (Yudoyono et al., 2018). In the paleopathological literature, these lesions are often detected on the ectocranium, especially on the parietal and frontal bones, followed by the temporal bone, and more rarely on the endocranial surface (Aufderheide and Rodringuez-Martin, 1998:375; Marques, 2019:668). Morphologically, ectocranial osteomata appear as small circumscribed ivory-like lumps with smooth surfaces, and are defined as “button osteomas” (Aufderheide and Rodringuez-Martin, 1998:375). Radiographically (X-ray and CT scan), button osteomata appear as radiopaque bone lesions (Chae et al., 2015). Osteomata are classified as central, if they arise from the endosteum, and as peripheral, if they arise from the periosteum (Sayan et al., 2002). The pathogenesis of peripheral osteoma is still debated
⁎
(Yudoyono et al., 2018). The embryologic etiology of osteomata is linked to developmental anomalies of the fronto-ethmoid region; however, this does not explain the large number of osteomata occurring in other locations. Osteomata could also be a reactive condition triggered by trauma, but does not explain the large number of patients with no prior history of trauma. Finally, osteomata might originate from infection such as tuberculosis, syphilis and sinus drainage dysfunction with subsequent inflammation. However, none of these theories have been confirmed. Several classifications of these benign lesions have been proposed. Rokade and Sama (2012) histologically distinguished three types of osteomata on the basis of the proportions between dense and cancellous bone: 1) ivory or eburnated osteoma, typical of the skull vault, is composed of dense, mature lamellar bone without Haversian systems; 2) mature osteoma, or osteoma spongiosum, is composed of trabecular, mature lamellar bone with Haversian systems; 3) mixed osteoma consists of the ivory and mature types. Eshed et al. (2002), based on
Corresponding author. E-mail address: valentina.giuff[email protected] (V. Giuffra).
https://doi.org/10.1016/j.ijpp.2019.04.003 Received 13 February 2019; Received in revised form 15 April 2019; Accepted 29 April 2019 Available online 06 May 2019 1879-9817/ © 2019 Elsevier Inc. All rights reserved.
International Journal of Paleopathology 25 (2019) 56–61
V. Giuffra, et al.
4. Discussion
research using the Hamann-Todd collection, proposed a classification based on location and histological features, distinguishing “sinus osteomata,” localized on the paranasal sinuses composed by ivory, spongy or mixed bone tissue, “button lesions,” bone formations of dense compact bone, and “ballooned osteomata,” composed of a dense bony shell with a core of trabecular bone. Cranial osteomata are largely underrepresented in modern clinical studies, as they are generally asymptomatic and only incidentally detected. Their prevalence in modern populations, therefore, has not been ascertained. Alternatively, osteomata are commonly observed in human skeletal remains. Hence, this apparently trivial clinical lesion presents several aspects of remarkable scientific interest (Capasso, 1997).
The morphological and radiological characteristics of the lesions observed in the skeleton (SU 8065) can be diagnosed as osteomata since in clinical practice, CT scan and X-ray are considered sufficient to complete the diagnosis (Shanavas et al., 2013). Although Eshed et al. (2002) differentiated “button lesions,” “sinus osteoma,” and “ballooned osteoma” based on histological features, the lesions macroscopically and radiologically observed in the skeleton from Pava can be defined as button lesions. Osteomata are relatively frequent lesions located on the cranial vault. Eshed et al. (2002) found osteomata in 37.6% of the 585 individuals from the Hamann-Todd osteological collection, with 24.1% displaying a single lesion, 7.6% displaying two lesions and 5.8% with multiple lesions. The frequency of lesions increased with age. Conversely, multiple osteomata are less common and can be associated with Gardner syndrome, which is an autosomal disorder characterized by intestinal polyposis, multiple epidermoid cysts, osteomata, dental anomalies, and congenital hypertrophy of the retinal pigment epithelium (Koh et al., 2016). Dental abnormalities include osteomatous lesions (well-defined radiopacity not surrounded by a radiolucent zone), impacted and ectopic teeth, supernumerary teeth, and compound odontoma (Wolf et al., 1986; Carl and Sullivan, 1989; Seehra et al., 2016). Gardner syndrome is a variant of familial adenomatous polyposis, linked to the chromosome band 5q21 in the APC gene (adenomatous polyposis coli locus), in which osteoma formation precedes intestinal polyposis (Bilkay et al., 2004). The prevalence of Gardner syndrome is one per one million people in the United States, with annual incidence of one in 8000 individuals (Charifa and Zhang, 2018). Intestinal polyposis has 100% risk of progressing to malignancy, as the mutations in APC are strongly correlated with the onset of carcinoma and colorectal adenoma (Gu et al., 2008). In modern clinical studies, the progression to malignant transformation occurs between 30 and 50 years of age and the average age of malignancy diagnosis is 39.2 years (Bilkay et al., 2004). Although detection of APC gene mutation is feasible in preserved mummified tissues (Feldman et al., 2016), it has not been attempted in dry bones. Clinical studies report that 68–82% of patients with Gardner syndrome have osteomata, 50% of whom present three or more osteomata in the maxilla or in other locations (Chimenos- Küstner et al., 2005). Radiologically, osteomata are described as radiopaque masses attached to the surface of the cortex with a well-defined periphery (Koh et al., 2016; Yu et al., 2018). Although most common location of osteomata is the mandible, the skull and long bones can be affected (Bilkay et al., 2004). Some authors report that Gardner syndrome can be considered a possible diagnosis if more than three osteomata of the maxillo-facial complex are present (Ida et al., 1981). Skeleton SU 8065 displayed nine osteomata, six on the external cranial surface and three on postcranial bones. Due to poor preservation and ante mortem tooth loss, a detailed evaluation of dental abnormalities was not possible, and no pathological changes typical of Gardner syndrome were observed. In conclusion, since the clinically recognized presence of intestinal polyposis is the marker for Gardner syndrome (Herrmann et al., 2003), and osteomata of the maxillo-facial complex and dental anomalies are absent or unobservable in SU 8065, the diagnosis of Gardner syndrome remains possible but doubtful. Clinically, cases of multiple osteomata have been reported that are unrelated to Gardner or other syndromes (Shanavas et al., 2013). Single cranial osteomata are commonly observed in osteoarchaeological remains, but multiple osteomata appears to be a rare paleopathological condition. Two cases appear in the literature. The first is in a female aged 30–50 years recovered in Switzerland and dated to the Iron Age, where the diagnosis of Gardner syndrome was posited, but not confirmed (Moghaddam et al., 2013). The second case is in a female aged 40–50 years from the medieval cemetery of Caravate (Varese,
2. Materials and methods Archaeological excavations were carried out by the University of Siena in the Medieval site of Pieve di Pava, located in the Asso Valley of the province of Siena (Tuscany, Central Italy) from 2004 to 2013 (Felici, 2016). Pieve di Pava is a medieval church with a large cemetery that was continuously used from the Late Antiquity to the Middle Ages. Archaeological stratigraphy reveals that the church of Pava, entitled to Saint Pietro, was built in the second half of the 5th century on the remains of a Roman villa. A large funerary area was arranged around the religious building starting from the Early Middle Ages, with some privileged burials located at the entrance and inside the church. The largest part of the cemetery was located externally, all around the building; it was largely used between the 10th and 12th centuries AD and continued to be active until the 13th century AD, when Saint Pietro’s church had already been abandoned. Approximately 900 burials were excavated, representing one of the largest and best-preserved medieval cemeteries in Italy. A skeleton (SU 8065), dated to the 10th-12th centuries AD, displayed abnormalities of the ectocranium. The skeletal remains were well-preserved with class 4 Anatomical Preserved Index (API) and class 4 Qualitative Bone Index (QBI) (Bello et al., 2006). In particular, the cranium and the mandible were well-preserved, but the maxilla was not (Fig. 1). Sex determination was performed on the basis of the morphological features of the cranium and the pelvis (Ferembach et al., 1980; Buikstra and Ubelaker, 1994). Age at death was determined according to the morphological changes of the auricular surface of the ilium (Lovejoy et al., 1985), dental wear (Lovejoy, 1985), and sternal rib end modifications (İşcan et al., 1984a, 1984b, 1985). Pathological evidence was evaluated by means of a low magnification (5X). Macroscopic observation was followed by Cone Beam Computed Tomography (CBCT) using a PlanMeca Promax Classic with the following parameters: 5.6–12 mAS with 86 keV, and 2D acquisition with the following parameters: 10–10.5 mAS with 64 keV. Histological analysis of the pathological lesions was not performed in order to avoid destruction of the specimens. 3. Results Skeleton (SU 8065) belongs to a female aged 40–50 years. All mandibular posterior dentition (except LM3 and R and LP1) were lost ante mortem. In the maxilla, more than half of the teeth were lost ante mortem. Marked occlusal dental wear, caries, abscesses, and severe alveolar resorption were present in both the maxilla and the mandible. Six osteoblastic lesions were observed on the cranial vault, appearing relatively round with smooth surfaces and well-defined margins, and of different sizes (Table 1). Three similar lesions were observed on post-cranial bones (Table 1 and Figs. 2 and 3). CBCT confirmed that all the lesions are composed by compact bone (Fig. 4). No bone nor dental alterations of the mandible were evident (Fig. 5). While the maxilla was in poor condition, the frontal sinuses and the left maxillary sinus were macroscopically visible through post-mortal breakages, showing no abnormalities. 57
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Fig. 1. Preserved bones and the location of the osteomata (white stars) recorded for individual SU 8065.
Table 1 Size and location of osteoblastic lesions observed on the cranial vault and long bones of individual SU 8065. Location
Shape
Dimensions in mm
Posterior portion of the left parietal bone (Fig. 2a) Central portion of the right parietal bone (Fig. 2a) Centro-posterior portion of the right parietal bone (Fig. 2a) Central portion of the frontal bone (Fig. 2b) Close to bregma on the left parietal bone (Fig. 2c) Adjacent to the left coronal suture, close to bregma, on the frontal bone (Fig. 2c) Posterior surface mid-shaft of the left ulna (Fig. 3a) Dorsal distal portion of a second hand phalanx (Fig. 3b) Lateral portion of the proximal diaphysis of the left third metacarpal (Fig. 3c)
circular circular circular circular circular circular oval circular elongated
27.0 6.0 3.0 2.6 3.0 2.0 3.8 × 2.7 2.0 12.0 × 3.0
Abbreviations: SU Stratigraphic Unit. 58
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Fig. 2. Osteomata on the cranial vault: (a) osteomata on the right and left parietal bones (from right to left measuring 27 mm. 6 mm. and 3 mm); (b) osteoma in the central portion of the frontal bone (2.6 mm); (c) two osteomata near bregma, one on the left parietal (3 mm), and one on the frontal bone (2.2 mm).
in the paleopathological record potentially provides important information towards our understanding of benign and malignant diseases in the past. It is crucial to pay close attention to all neoplastic lesions in ancient human remains in order to increase recognition of the existence and impact among ancient populations and to advance in the field of paleo-oncology.
Northern Italy). Once again, a possible diagnosis of Gardner syndrome was proposed (Licata et al., 2016a, 2016b), but the absence of pertinent disease markers made the diagnosis speculative. There is controversy whether osteomata represent true neoplasm or whether they reflect the presence of trauma, inflammation, or the end stage of hamartomatous conditions such as fibrous dysplasia (Gundewar et al., 2013). For this reason, each instance of these lesions
Fig. 3. Osteomata on post-cranial bones: (a) oval osteoma of on the left ulna (3.8 × 2.7 mm); (b) osteoma on a hand phalanx (2 mm); (c) elongated osteoma on the left third metacarpal (12 × 3 mm). 59
International Journal of Paleopathology 25 (2019) 56–61
V. Giuffra, et al.
Fig. 4. Cone Beam Computed Tomography of the cranial osteomata: (a) the lesion on the left parietal bone (27 mm); (b) the lesion on the right parietal bone (6 mm); (c) the lesion on the right parietal bone (3 mm). osteoma: a review of ten cases. Ann. Dermatol. 27, 394–397. Charifa, A., Zang, X., 2018. Gardner Syndrome. StatPearls [internet]. StatPearls Publishing LLC. Chimenos-Küstner, E., Pascual, M., Blanco, I., Finestres, F., 2005. Hereditary familial polyposis and Gardner’s syndrome: contribution of the odonto-stomatology examination in its diagnosis and a case description. Med. Oral Patol. Oral Cir. Bucal 10, 402–409. Eshed, V., Latimer, B., Greenwald, C.M., Jellema, L.M., Wish-Baratz, S., Hershkovitz, I., 2002. Button osteoma: its etiology and Pathophysiology. Am. J. Phys. Anthropol. 118, 217–230. Feldman, M., Hershkovitz, I., Sklan, E.H., Kahila, Bar-Gal, G, Pap, Szikossy, I., RosinArbesfeld, R., 2016. Detection of a tumor suppressor gene predisposing to colorectal cancer variant in an 18th century Hungarian mummy. PLoS One 11 (2), E0147217. https://doi.org/10.1371/journal.pone.0147217. Felici, C., 2016. La lunga diacronia di un sito archeologico toscano: il complesso di Pava (Siena) dal II al XIII sec. d.C. FOLD&R 365, 1–20. Ferembach, D., Schwidetzky, I., Stloukal, M., 1980. Recommendations for age and sex diagnoses of skeletons. J. Hum. Evol. 9, 17–549. Gu, G.L., Wang, S.L., Wei, X.M., Bai, L., 2008. Diagnosis and treatment of Gardner syndrome with gastric polyposis: a case report and review of the literature. World J. Gastroenterol. 14, 2121–2123. Gundewar, S., Kothari, D.S., Mokal, N.J., Ghalme, A., 2013. Osteomas of the craniofacial region: a case series and review of the literature. Indian J. Plast. Surg. 46, 479–485. Herrmann, S.M., Adler, Y.D., Schmidt-Petersen, K., Nicaud, V., Morrison, C., Paul, M., Zouboulis, Ch.C., 2003. The concomitant occurrence of multiple epidermal cysts, osteomas and thyroid gland nodules is not diagnostic for Gardner syndrome in the absence of intestinal polyposis: a clinical and genetic report. Br. J. Dermatol. 149, 877–883. Ida, M., Nakamura, T., Utsunomiya, J., 1981. Osteomatous changes and tooth abnormalities found in the jaw of patients with adenomatosis coli. Oral Surg. Oral Med. Oral Pathol. 52, 2–11. İşcan, M.Y., Loth, S.R., Wright, R.K., 1984a. Metamorphosis at the sternal rib: a new method to estimate age at death in males. Am. J. Phys. Anthropol. 65, 147–156. İşcan, M.Y., Loth, S.R., Wright, R.K., 1984b. Age estimation from the rib by phase analysis: white males. J. Forensic Sci. 29, 1094–1104. İşcan, M.Y., Loth, S.R., Wright, R.K., 1985. Age estimation from the rib by phase analysis: white females. J. Forensic Sci. 30, 853–863. Koh, K.-J., Park, H.-N., Kim, K., 2016. Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cyst. Imaging Sci. Dent. 46, 267–272. Licata, M., Borgo, M., Armocida, G., Nicosia, L., Ferioli, E., 2016a. Diagnosis of multiple osteomas in an ancient skeleton discovered in the necropolis of Caravate – Northern Italy. Eur. J. Oncol. 21, 238–242. Licata, M., Borgo, M., Armocida, G., Nicosia, L., Ferioli, E., 2016b. New paleoradiological investigations of ancient human remains from North West Lombardy archaeological excavations. Skeletal Radiol. 45, 323–331. Lovejoy, C.O., 1985. Dental wear in Libbean population: its functional pattern and role in
Fig. 5. Cone Beam Computed Tomography of the mandible.
Financial support This research was funded by the project PRA_2018_40 project (Progetti di Ricerca di Ateneo, University of Pisa) entitled “On the antiquity of cancer: the contribution of paleopathology to the study of ancient tumours”. Declarations of interest None. References Aufderheide, A.C., Rodriguez-Martin, C., 1998. The Cambridge Encyclopedia of Human Paleopathology. Cambridge University Press, Cambridge. Bello, S.M., Thomann, A., Signoli, M., Dutour, O., Andrews, P., 2006. Age and sex bias in the reconstruction of past population structures. Am. J. Phys. Anthropol. 129, 24–38. Bilkay, U., Erdem, O., Ozek, C., Helvaci, E., Kilic, K., Ertan, Y., Gurler, T., 2004. Benign osteoma with Gardner syndrome: review of the literature and report of a case. J. Craniofac. Surg. 15, 506–509. Buikstra, J.E., Ubelaker, D.H., 1994. Standards for Data Collection From Human Skeletal Remains. Arkansas Archaeological Survey, Fayetteville. Capasso, L., 1997. Osteoma: palaeopathology and phylogeny. Int. J. Osteoarchaeol. 7, 615–620. Carl, W., Sullivan, M.A., 1989. Dental abnormalities and bone lesions associated with familial adenomatous polyposis: report of cases. J. Am. Dent. Assoc. 119, 137–139. Chae, S.Y., Sim, H.B., Kim, M.J., Jang, Y.H., Lee, S.-J., Kim, D.W., Lee, W.J., 2015. Button
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maxillofacial region: a study of 35 new cases. J. Oral Maxillofac. Surg. 60, 1299–1301. Seehra, J., Patel, S., Bryant, C., 2016. Gardner’s Syndrome revisited: a clinical case and overview of the literature. J. Orthod. 43, 59–64. Shanavas, M., Chatra, L., Shenai, P., Veena, K.M., Rao, P.K., Prabhu, R.V., 2013. Multiple osteomas of forehead: report of a rare case. Ann. Med. Health Sci. Res. 3, 105–107. Wolf, J., Jarvinen, H.J., Hietanen, J., 1986. Gardner’s dento-maxillary stigmas in patients with familial adenomatosis coli. Br. J. Oral Maxillofac. Surg. 24, 410–416. Yu, D., Ng Cw, B., Zhu, H., Liu, J., Lin, Y., 2018. Bone and dental abnormalities as first signs of familial Gardner’s syndrome in a Chinese family: a literature review and a case report. Med. Sci. (Paris) 34, 20–25. Yudoyono, F., Sidabutar, R., Dahlan, R.H., Gill, A.S., Ompusunggu, S.E., Arifin, M.Z., 2018. Surgical management of giant skull osteomas. Asian J. Neurosurg. 12, 408–411.
the determination of adult skeletal age at the death. Am. J. Phys. Anthropol. 68, 47–56. Lovejoy, C.O., Meindl, R.S., Pryzbeck, T.R., Mensforth, R.P., 1985. Chronological metamorphosis of the auricolar surface of the ilium: a new method for the determination of adult skeletal age at death. Am. J. Phys. Anthropol. 68, 15–28. Marques, C., 2019. Tumors of bone. In: Buikstra, J. (Ed.), Ortner’s Identification of Pathological Conditions in Human Skeletal Remains, 3rd edition. Academic Press, London, pp. 639–718. Moghaddam, N., Langer, R., Ross, S., Nielsen, E., Lösch, S., 2013. Multiple osteosclerotic lesions in an Iron age skull from Switzerland (320-250 BC) – an unusual case. Swiss Med. 143, w13819. Rokade, A., Sama, A., 2012. Update on management of frontal sinus osteoma. Curr. Opin. Otolaryngol. Head Neck Surg. 20, 40–44. Sayan, N.B., Ucok, C., Karasu, H.A., Gunhan, O., 2002. Peripheral osteoma of the oral and
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Contents lists available at ScienceDirect
International Journal of Paleopathology journal homepage: www.elsevier.com/locate/ijpp
Multiple osteomata from medieval Tuscany, Italy (ca. 10th–12th AD) a,⁎
a
a
T
b
Valentina Giuffra , Simona Minozzi , Giulia Riccomi , Antonio Giuseppe Naccarato , Maura Castagnab, Riccardo Lencionic, Silvio Chericonid, Valeria Mongellia, Cristina Felicie a
Division of Paleopathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 57, 56126 Pisa, Italy Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 57, 56126 Pisa, Italy Division of Diagnostic Radiology 1, Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy d Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, via Roma 55, 56126 Pisa, Italy e Department of History and Cultural Heritage, Via Roma 56, 53100 Siena, Italy b c
A R T I C LE I N FO
A B S T R A C T
Keywords: Button lesions Gardner syndrome Nonsyndromic osteomata Cone beam computed tomography
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.
1. Introduction Osteomata are the most common primary benign bone tumors of the skull. They are relatively-circular raised areas of dense bone, characterized by slow growth and are usually asymptomatic (Yudoyono et al., 2018). In the paleopathological literature, these lesions are often detected on the ectocranium, especially on the parietal and frontal bones, followed by the temporal bone, and more rarely on the endocranial surface (Aufderheide and Rodringuez-Martin, 1998:375; Marques, 2019:668). Morphologically, ectocranial osteomata appear as small circumscribed ivory-like lumps with smooth surfaces, and are defined as “button osteomas” (Aufderheide and Rodringuez-Martin, 1998:375). Radiographically (X-ray and CT scan), button osteomata appear as radiopaque bone lesions (Chae et al., 2015). Osteomata are classified as central, if they arise from the endosteum, and as peripheral, if they arise from the periosteum (Sayan et al., 2002). The pathogenesis of peripheral osteoma is still debated
⁎
(Yudoyono et al., 2018). The embryologic etiology of osteomata is linked to developmental anomalies of the fronto-ethmoid region; however, this does not explain the large number of osteomata occurring in other locations. Osteomata could also be a reactive condition triggered by trauma, but does not explain the large number of patients with no prior history of trauma. Finally, osteomata might originate from infection such as tuberculosis, syphilis and sinus drainage dysfunction with subsequent inflammation. However, none of these theories have been confirmed. Several classifications of these benign lesions have been proposed. Rokade and Sama (2012) histologically distinguished three types of osteomata on the basis of the proportions between dense and cancellous bone: 1) ivory or eburnated osteoma, typical of the skull vault, is composed of dense, mature lamellar bone without Haversian systems; 2) mature osteoma, or osteoma spongiosum, is composed of trabecular, mature lamellar bone with Haversian systems; 3) mixed osteoma consists of the ivory and mature types. Eshed et al. (2002), based on
Corresponding author. E-mail address: valentina.giuff[email protected] (V. Giuffra).
https://doi.org/10.1016/j.ijpp.2019.04.003 Received 13 February 2019; Received in revised form 15 April 2019; Accepted 29 April 2019 Available online 06 May 2019 1879-9817/ © 2019 Elsevier Inc. All rights reserved.
International Journal of Paleopathology 25 (2019) 56–61
V. Giuffra, et al.
4. Discussion
research using the Hamann-Todd collection, proposed a classification based on location and histological features, distinguishing “sinus osteomata,” localized on the paranasal sinuses composed by ivory, spongy or mixed bone tissue, “button lesions,” bone formations of dense compact bone, and “ballooned osteomata,” composed of a dense bony shell with a core of trabecular bone. Cranial osteomata are largely underrepresented in modern clinical studies, as they are generally asymptomatic and only incidentally detected. Their prevalence in modern populations, therefore, has not been ascertained. Alternatively, osteomata are commonly observed in human skeletal remains. Hence, this apparently trivial clinical lesion presents several aspects of remarkable scientific interest (Capasso, 1997).
The morphological and radiological characteristics of the lesions observed in the skeleton (SU 8065) can be diagnosed as osteomata since in clinical practice, CT scan and X-ray are considered sufficient to complete the diagnosis (Shanavas et al., 2013). Although Eshed et al. (2002) differentiated “button lesions,” “sinus osteoma,” and “ballooned osteoma” based on histological features, the lesions macroscopically and radiologically observed in the skeleton from Pava can be defined as button lesions. Osteomata are relatively frequent lesions located on the cranial vault. Eshed et al. (2002) found osteomata in 37.6% of the 585 individuals from the Hamann-Todd osteological collection, with 24.1% displaying a single lesion, 7.6% displaying two lesions and 5.8% with multiple lesions. The frequency of lesions increased with age. Conversely, multiple osteomata are less common and can be associated with Gardner syndrome, which is an autosomal disorder characterized by intestinal polyposis, multiple epidermoid cysts, osteomata, dental anomalies, and congenital hypertrophy of the retinal pigment epithelium (Koh et al., 2016). Dental abnormalities include osteomatous lesions (well-defined radiopacity not surrounded by a radiolucent zone), impacted and ectopic teeth, supernumerary teeth, and compound odontoma (Wolf et al., 1986; Carl and Sullivan, 1989; Seehra et al., 2016). Gardner syndrome is a variant of familial adenomatous polyposis, linked to the chromosome band 5q21 in the APC gene (adenomatous polyposis coli locus), in which osteoma formation precedes intestinal polyposis (Bilkay et al., 2004). The prevalence of Gardner syndrome is one per one million people in the United States, with annual incidence of one in 8000 individuals (Charifa and Zhang, 2018). Intestinal polyposis has 100% risk of progressing to malignancy, as the mutations in APC are strongly correlated with the onset of carcinoma and colorectal adenoma (Gu et al., 2008). In modern clinical studies, the progression to malignant transformation occurs between 30 and 50 years of age and the average age of malignancy diagnosis is 39.2 years (Bilkay et al., 2004). Although detection of APC gene mutation is feasible in preserved mummified tissues (Feldman et al., 2016), it has not been attempted in dry bones. Clinical studies report that 68–82% of patients with Gardner syndrome have osteomata, 50% of whom present three or more osteomata in the maxilla or in other locations (Chimenos- Küstner et al., 2005). Radiologically, osteomata are described as radiopaque masses attached to the surface of the cortex with a well-defined periphery (Koh et al., 2016; Yu et al., 2018). Although most common location of osteomata is the mandible, the skull and long bones can be affected (Bilkay et al., 2004). Some authors report that Gardner syndrome can be considered a possible diagnosis if more than three osteomata of the maxillo-facial complex are present (Ida et al., 1981). Skeleton SU 8065 displayed nine osteomata, six on the external cranial surface and three on postcranial bones. Due to poor preservation and ante mortem tooth loss, a detailed evaluation of dental abnormalities was not possible, and no pathological changes typical of Gardner syndrome were observed. In conclusion, since the clinically recognized presence of intestinal polyposis is the marker for Gardner syndrome (Herrmann et al., 2003), and osteomata of the maxillo-facial complex and dental anomalies are absent or unobservable in SU 8065, the diagnosis of Gardner syndrome remains possible but doubtful. Clinically, cases of multiple osteomata have been reported that are unrelated to Gardner or other syndromes (Shanavas et al., 2013). Single cranial osteomata are commonly observed in osteoarchaeological remains, but multiple osteomata appears to be a rare paleopathological condition. Two cases appear in the literature. The first is in a female aged 30–50 years recovered in Switzerland and dated to the Iron Age, where the diagnosis of Gardner syndrome was posited, but not confirmed (Moghaddam et al., 2013). The second case is in a female aged 40–50 years from the medieval cemetery of Caravate (Varese,
2. Materials and methods Archaeological excavations were carried out by the University of Siena in the Medieval site of Pieve di Pava, located in the Asso Valley of the province of Siena (Tuscany, Central Italy) from 2004 to 2013 (Felici, 2016). Pieve di Pava is a medieval church with a large cemetery that was continuously used from the Late Antiquity to the Middle Ages. Archaeological stratigraphy reveals that the church of Pava, entitled to Saint Pietro, was built in the second half of the 5th century on the remains of a Roman villa. A large funerary area was arranged around the religious building starting from the Early Middle Ages, with some privileged burials located at the entrance and inside the church. The largest part of the cemetery was located externally, all around the building; it was largely used between the 10th and 12th centuries AD and continued to be active until the 13th century AD, when Saint Pietro’s church had already been abandoned. Approximately 900 burials were excavated, representing one of the largest and best-preserved medieval cemeteries in Italy. A skeleton (SU 8065), dated to the 10th-12th centuries AD, displayed abnormalities of the ectocranium. The skeletal remains were well-preserved with class 4 Anatomical Preserved Index (API) and class 4 Qualitative Bone Index (QBI) (Bello et al., 2006). In particular, the cranium and the mandible were well-preserved, but the maxilla was not (Fig. 1). Sex determination was performed on the basis of the morphological features of the cranium and the pelvis (Ferembach et al., 1980; Buikstra and Ubelaker, 1994). Age at death was determined according to the morphological changes of the auricular surface of the ilium (Lovejoy et al., 1985), dental wear (Lovejoy, 1985), and sternal rib end modifications (İşcan et al., 1984a, 1984b, 1985). Pathological evidence was evaluated by means of a low magnification (5X). Macroscopic observation was followed by Cone Beam Computed Tomography (CBCT) using a PlanMeca Promax Classic with the following parameters: 5.6–12 mAS with 86 keV, and 2D acquisition with the following parameters: 10–10.5 mAS with 64 keV. Histological analysis of the pathological lesions was not performed in order to avoid destruction of the specimens. 3. Results Skeleton (SU 8065) belongs to a female aged 40–50 years. All mandibular posterior dentition (except LM3 and R and LP1) were lost ante mortem. In the maxilla, more than half of the teeth were lost ante mortem. Marked occlusal dental wear, caries, abscesses, and severe alveolar resorption were present in both the maxilla and the mandible. Six osteoblastic lesions were observed on the cranial vault, appearing relatively round with smooth surfaces and well-defined margins, and of different sizes (Table 1). Three similar lesions were observed on post-cranial bones (Table 1 and Figs. 2 and 3). CBCT confirmed that all the lesions are composed by compact bone (Fig. 4). No bone nor dental alterations of the mandible were evident (Fig. 5). While the maxilla was in poor condition, the frontal sinuses and the left maxillary sinus were macroscopically visible through post-mortal breakages, showing no abnormalities. 57
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Fig. 1. Preserved bones and the location of the osteomata (white stars) recorded for individual SU 8065.
Table 1 Size and location of osteoblastic lesions observed on the cranial vault and long bones of individual SU 8065. Location
Shape
Dimensions in mm
Posterior portion of the left parietal bone (Fig. 2a) Central portion of the right parietal bone (Fig. 2a) Centro-posterior portion of the right parietal bone (Fig. 2a) Central portion of the frontal bone (Fig. 2b) Close to bregma on the left parietal bone (Fig. 2c) Adjacent to the left coronal suture, close to bregma, on the frontal bone (Fig. 2c) Posterior surface mid-shaft of the left ulna (Fig. 3a) Dorsal distal portion of a second hand phalanx (Fig. 3b) Lateral portion of the proximal diaphysis of the left third metacarpal (Fig. 3c)
circular circular circular circular circular circular oval circular elongated
27.0 6.0 3.0 2.6 3.0 2.0 3.8 × 2.7 2.0 12.0 × 3.0
Abbreviations: SU Stratigraphic Unit. 58
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Fig. 2. Osteomata on the cranial vault: (a) osteomata on the right and left parietal bones (from right to left measuring 27 mm. 6 mm. and 3 mm); (b) osteoma in the central portion of the frontal bone (2.6 mm); (c) two osteomata near bregma, one on the left parietal (3 mm), and one on the frontal bone (2.2 mm).
in the paleopathological record potentially provides important information towards our understanding of benign and malignant diseases in the past. It is crucial to pay close attention to all neoplastic lesions in ancient human remains in order to increase recognition of the existence and impact among ancient populations and to advance in the field of paleo-oncology.
Northern Italy). Once again, a possible diagnosis of Gardner syndrome was proposed (Licata et al., 2016a, 2016b), but the absence of pertinent disease markers made the diagnosis speculative. There is controversy whether osteomata represent true neoplasm or whether they reflect the presence of trauma, inflammation, or the end stage of hamartomatous conditions such as fibrous dysplasia (Gundewar et al., 2013). For this reason, each instance of these lesions
Fig. 3. Osteomata on post-cranial bones: (a) oval osteoma of on the left ulna (3.8 × 2.7 mm); (b) osteoma on a hand phalanx (2 mm); (c) elongated osteoma on the left third metacarpal (12 × 3 mm). 59
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Fig. 4. Cone Beam Computed Tomography of the cranial osteomata: (a) the lesion on the left parietal bone (27 mm); (b) the lesion on the right parietal bone (6 mm); (c) the lesion on the right parietal bone (3 mm). osteoma: a review of ten cases. Ann. Dermatol. 27, 394–397. Charifa, A., Zang, X., 2018. Gardner Syndrome. StatPearls [internet]. StatPearls Publishing LLC. Chimenos-Küstner, E., Pascual, M., Blanco, I., Finestres, F., 2005. Hereditary familial polyposis and Gardner’s syndrome: contribution of the odonto-stomatology examination in its diagnosis and a case description. Med. Oral Patol. Oral Cir. Bucal 10, 402–409. Eshed, V., Latimer, B., Greenwald, C.M., Jellema, L.M., Wish-Baratz, S., Hershkovitz, I., 2002. Button osteoma: its etiology and Pathophysiology. Am. J. Phys. Anthropol. 118, 217–230. Feldman, M., Hershkovitz, I., Sklan, E.H., Kahila, Bar-Gal, G, Pap, Szikossy, I., RosinArbesfeld, R., 2016. Detection of a tumor suppressor gene predisposing to colorectal cancer variant in an 18th century Hungarian mummy. PLoS One 11 (2), E0147217. https://doi.org/10.1371/journal.pone.0147217. Felici, C., 2016. La lunga diacronia di un sito archeologico toscano: il complesso di Pava (Siena) dal II al XIII sec. d.C. FOLD&R 365, 1–20. Ferembach, D., Schwidetzky, I., Stloukal, M., 1980. Recommendations for age and sex diagnoses of skeletons. J. Hum. Evol. 9, 17–549. Gu, G.L., Wang, S.L., Wei, X.M., Bai, L., 2008. Diagnosis and treatment of Gardner syndrome with gastric polyposis: a case report and review of the literature. World J. Gastroenterol. 14, 2121–2123. Gundewar, S., Kothari, D.S., Mokal, N.J., Ghalme, A., 2013. Osteomas of the craniofacial region: a case series and review of the literature. Indian J. Plast. Surg. 46, 479–485. Herrmann, S.M., Adler, Y.D., Schmidt-Petersen, K., Nicaud, V., Morrison, C., Paul, M., Zouboulis, Ch.C., 2003. The concomitant occurrence of multiple epidermal cysts, osteomas and thyroid gland nodules is not diagnostic for Gardner syndrome in the absence of intestinal polyposis: a clinical and genetic report. Br. J. Dermatol. 149, 877–883. Ida, M., Nakamura, T., Utsunomiya, J., 1981. Osteomatous changes and tooth abnormalities found in the jaw of patients with adenomatosis coli. Oral Surg. Oral Med. Oral Pathol. 52, 2–11. İşcan, M.Y., Loth, S.R., Wright, R.K., 1984a. Metamorphosis at the sternal rib: a new method to estimate age at death in males. Am. J. Phys. Anthropol. 65, 147–156. İşcan, M.Y., Loth, S.R., Wright, R.K., 1984b. Age estimation from the rib by phase analysis: white males. J. Forensic Sci. 29, 1094–1104. İşcan, M.Y., Loth, S.R., Wright, R.K., 1985. Age estimation from the rib by phase analysis: white females. J. Forensic Sci. 30, 853–863. Koh, K.-J., Park, H.-N., Kim, K., 2016. Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cyst. Imaging Sci. Dent. 46, 267–272. Licata, M., Borgo, M., Armocida, G., Nicosia, L., Ferioli, E., 2016a. Diagnosis of multiple osteomas in an ancient skeleton discovered in the necropolis of Caravate – Northern Italy. Eur. J. Oncol. 21, 238–242. Licata, M., Borgo, M., Armocida, G., Nicosia, L., Ferioli, E., 2016b. New paleoradiological investigations of ancient human remains from North West Lombardy archaeological excavations. Skeletal Radiol. 45, 323–331. Lovejoy, C.O., 1985. Dental wear in Libbean population: its functional pattern and role in
Fig. 5. Cone Beam Computed Tomography of the mandible.
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