Portal de Periódicos da CAPES

Antiquity of cancer

2004; Wiley; Volume: 113; Issue: 1 Linguagem: Inglês

10.1002/ijc.20610

1097-0215

Luigi Capasso,

Paleopathology and ancient diseases

Cancer's relationship with the genetic characteristics of the hosts and environmental conditions has been demonstrated convincingly in modern populations. Environmental conditions and the genetic characteristics of human populations have changed markedly over our long history, and these changes have inevitably caused changes in the epidemiology of cancer. From a genetic standpoint the changes are so important as to seem banal. The first representatives of our genus, for example Homo habilis, which lived in East Africa roughly 2 million years ago, were phenotypically characterized by small body size (maximum stature = 1.20 m), relatively low cranial capacity (about 400 cc), perfectly erect posture and bipedal gait. They likely used some sort of primordial articulate, symbolic language, and were surely able to produce artefacts, such as stone and wood utensils, which represent the first technology on Earth. Beginning at this time technology assumed an important role in human evolution, with humans furthering their evolution not just through slow biological modifications but also through rapid technological advances. This is a unique development in the history of life on Earth. These primordial humans differed considerably from modern humans in terms of biology, cultural capabilities and social organization, and it is quite obvious that these differences must have produced variations in their ability to contract, develop and spread diseases, including the types and prevalences of neoplasms. In conclusion, it would seem likely that genetic changes in humans caused biological variations, including susceptibility to cancer over time, and socio-cultural changes also changed the patterns of human cancer. The role of paleopathology is to detect these variations, extending the research to pre-humans, and obviously non-human animals, observing the presence and prevalence of neoplasms in fossil animals, comparing ancient and modern evidence and creating a comparative pathology not limited to differing extant species, but that also extends to individual species during their evolution. The environment also changed markedly over time, as did the relationship between humans and the ecosystem, which itself changed during our evolution, in part because of our changing lifestyles. The first humans were nomadic, obtaining the food they needed by hunting and by gathering spontaneous vegetables. Only about 12,000 years ago did humans introduce farming and herding, developing sedentary habits, and then and gathering into densely populated communities. Environmental and ecological changes can also be linked to human activities, especially those that have occurred recently in the more developed countries. All these environmental changes and the tremendous changes in human habits may have modified human cancer in terms of both the types of neoplasms and their prevalence. Paleopathology must also determine the history of the relationships between human cancer and environmental, cultural and socio-economic changes. Only through the paleopathologic analysis of both pre-human remains (including the non-human fossil record) and ancient human remains we can reconstruct (i) the existence of cancer in antiquity, for example the evidence for cancer in the fossil record (also before the relatively recent origin and rise of our species), (ii) the type and prevalence of cancer in both pre-human and ancient human populations, (iii) the relationship between cancer prevalence and the demographic structure of human populations and its variations over time, (iv) the variations in type and prevalence of cancer as related to the genetic or environmental changes that occurred during biological, social, cultural and economic human evolution and (v) the general biological significance of cancer with respect to life on the Earth over a very long interval of observation (i.e., millions of years). These analyses can only be made if one considers cancer as a phenomenon strictly linked to life, studying the pathologic events comparatively and (vi) considering the types and prevalences of cancer with respect to the systematic relationships of the animals that this disease affects today. According to Brothwell,1 the interpretation of neoplasms is one of the more interesting and difficult aspects of paleopathology. The most important difficulties are linked to the particular materials available to paleopathologists. In fact, with the rare, but very important exception of mummified tissues, paleopathological materials consist of osseous remains; the digenetic processes that affect the skeletons can produce post-mortem alterations that either simulate or overshadow cancer-linked lesions that occurred during life. Chemical factors (such as soil acidity), physical agents (such as mechanical erosion and micro-fractures) and biological factors (such as fungi, bacteria and viruses) can produce focal erosions, including multiple, confluent erosions that can mimic the osteolytic lesions characteristic of primary and metastatic bone lesions. In addition, the digenetic phenomena can superimpose alterations (both erosions and incrustations) that can hide the lesions produced during life or change their original appearance. These difficulties are more serious in the case of the differential diagnosis of possible multiple lesions linked to possible bone metastasis of carcinoma, or to multiple myeloma. Finally, one must keep in mind that the lesions due to cancer may have changed over time, with the result that our diagnostic techniques and criteria may be inappropriate for detecting and diagnosing cancers on ancient and fossil remains. The difficulties inherent in paleopathological analysis involve not just the diagnosis of the single case at the individual level, but also epidemiological aspects. Indeed, the materials examined represent samples selected from the original populations, and the criteria of selection are largely unknown. In addition, the size of the samples that survived to be examined can be not representative of the original population. Both these factors may be important sources of error in estimating cancer prevalence among ancient populations, be they human or pre-human. No clear evidence of cancer has been demonstrated on living plants, and cancer seems to be absent in modern invertebrates, excluding some experimental conditions (i.e., tumour-like conditions induced in Drosophyla sp.). Even though Harshberger2 has suggested the possibility of neoplasms in invertebrate animals, and Kaiser3 has demonstrated some sorts of "growths" in plants and inferior animals, we have no clear evidence of true neoplastic diseases other than in the vertebrate animals. At present true neoplastic diseases, including cancer, seem to be restricted to vertebrate animals, and only one observation of a true cancer has been described in one of the more simple living vertebrates, specifically hepatomas in a jawless hagfish.2 This is a very important case for the comparative pathology of cancer, because lampreys are among the simplest living vertebrates. The presence of neoplastic diseases beginning with the lesser vertebrates seems to be consistent with the hypothesis that cancer is a pathology characteristic of vertebrate animals. Cancer has been reported throughout the entire spectrum of vertebrates. In the elasmobranch fish a case of chondroma in a lumbar vertebra has been described in the species Squalus mitsukurii (dogfish),4 and a case of fibrosarcoma has been described in Raja macrorhyncha (skate).4 Rising along the biological scale, in the bony fish (osteichthyians) neoplasms seem to be more frequent, and we have some descriptions of both benign tumours (i.e., osteoma, chondroma, osteocondroma) and malignancies (i.e., fibrosarcoma in a dorsal fin of a carp, the fin of a skate ray and in the mandible of a codfish).4 In addition, osteosarcoma has been clearly identified in a bone of the anal fin of Esox lucius (a pike) and in the pectoral fins and opercular bones of some codfish.4 Carcinoma without skeletal involvement has been reported in trout,5 climbing perch6 and perch.5, 6 Lymphoma2 and lymphosarcoma have also been observed in a northern pike.2 Hyperostosis is relatively frequent in many living species of bony fish and seems to be a form of so-called osteomata.7 The focal neoformation of compact bone is one of the more frequent benign neoplasms in all living fish, and researchers invariably discuss the nomenclature linked to these forms. We prefer to follow the older nomenclature (i.e., focal hyperostosis, osteoma, ivory osteoma) that were introduced in comparative pathology by Gervais8 at the end of the 19th Century. I have demonstrated the phylogenetic relationship between focal hyperostosis in living fish and the osteoma in modern humans.7 Osteoma is one of the more common neoplasms. We have been aware of its presence and its high prevalence in fish 2 centuries.8 Osteoma has been documented in butterfly fish, file fish, red tai, angelfish, codfish, pike, flounder, croaker, flatfishes, scabbard fish, coal fish, rock fish, speckled trout, carp.4 No cases of neoplasms have been found among the amphibians. The only case4 reported in literature may simply be a callus subsequent to a fracture.9 In modern reptiles there have been occasional cases of parathyroid adenoma in turtles.10 Researchers have also observed chondroma4 and osteochondroma11, 12 in the representatives of the genus Varanus. A clear case of osteosarcoma has been observed in the spine of a rufous-beaked snake.13 In addition, chondrosarcoma has been reported in corn snakes2, 14 and osteochondrosarcoma has been described in the vertebral column of an individual attributable to Natrix melanoleuca.15 Neurofibrosarcoma has been reported in a Korean viper,16 and presumed melanoma has been observed in a snake from the Everglades.15 Lymphatic tumours seem to be relatively frequent in modern wild reptiles. Lymphatic leukemia has been described in boa constrictors17 and in Python.18 Lymphoma has been reported in rhinoceros vipers, death adders, Indian rock pythons, and hog nose snakes.16 In addition, lymphosarcoma has been reported in rhinoceros vipers and spitting cobras.16 Leukaemia has been observed in Acanthophis antarctica, Bitis arietans and Bitis nasicornis.16 Neoplasms in birds are relatively common but are strictly limited to captive animals. In wild bird populations neoplasms seem to be extremely rare if present. No cases of neoplasms have been described in wild birds. In 25–33% of captive budgerigars tumours are the cause of death and in psittaci formes at least 3.5% of deaths are caused by malignancies.19 Pituitary tumours are particularly common although osteosarcoma has also been reported with particular frequency in domestic budgerigars and canaries.19 According to Jubb and Kennedy,20 wild living mammals neoplasms are rare. In domestic dogs there is a greater prevalence of neoplasms, which is concentrated in the 6–8-year age span, a fact that is of particular interest considering that these animals have a life expectancy of 10–14 years.20 In wild mammal populations neoplasms are surely more rare. Epidemiological data exists only for chimpanzees and we know that 1.8% of the deaths in chimpanzee communities are due to cancer. Single observations of chondrosarcoma have been reported in the femur of a kangaroo,18, 21 and in the caudal vertebra of a ferret.22 A single case of fibrosarcoma was observed in a Northern fur seal.23 Neoplasms of the lymphatic cells seem to be slightly more common in many mammals. A case of possible myeloma of the lumbar vertebra associated with plasma cells dyscrasia has been reported in a ferret.22 Hodgkin's lymphoma, without skeletal involvement, has been reported in Orcinus orca.24 Lymphosarcoma has been noted in many marine and terrestrial mammals including harbor seals, sea lions, Northern fur seals, harp seals23 and deer.18 Leukaemia has been documented in pacaranas18 and in gibbons.25 The focal hyperostosis known as osteoma, which produces compact bone buttons on the cranial vault and more subordinate buttons on the surfaces of the long bones (commonly called ivory osteoma),7 merit special consideration. This type of benign bone neoplasm has been induced in mice by the RFB osteoma virus.26 Osteoma is frequent particularly in many mammals, as well as in bony fish,7 and has been documented in wild species (i.e., ferrets and Platecarpus).9, 27 Diffuse hyperostosis is also relatively frequent in bony fish and mammals. It is characteristic of 3 orders of mammals and present in all subjects: Proboscidea (i.e., sirenia), Hyracoidea (i.e., trichecus) and Tubulidentata (i.e., dugongo). In all these animals, the axial skeleton is replaced completely by medullary bones,28 a congenital condition called pachyostosis. Focal hyperostosis in the form of mandibular swelling, however, has also been documented in dogs.29 Multiple hereditary osteochondromata is relatively common in some other modern mammals: domestic horses, cats and dogs.30, 31, 32, 33, 34 In the family Canidae only domestic dogs are affected.35, 36, 37, 38 Malignant degeneration into osteosarcoma or chondrosarcoma has been demonstrated in about 18% of the cases.32 Multiple hereditary osteochondromata have also been observed in Nothocyon, Tomarctus, Daphoenus and Cynodictis.39, 40 The prevalence of neoplasms in the modern human population as cause of death is particularly high. This datum is an exception within the general framework of the comparative pathology of neoplasms. The very high prevalence of neoplasms in modern humans seems similar to the high prevalence of neoplasms in the population of domestic dogs or in populations of captive birds. In conclusion, the comparative pathology of extant neoplasms shows the following remarkable points: (i) neoplasms are a pathology typical of all the extant vertebrates, starting from jawless fish; (ii) neoplasms in extant wild vertebrate populations seem to be extremely rare in amphibians and birds, and slightly more frequent in fish, reptiles and mammals; (iii) one of the more frequent forms of extant neoplasm in both bony fish and mammals seems to be the focal (osteoma) and the regional (pachyostosis) benign bone tumour; and (iv) in captivity the prevalence of neoplasms, including cancer, seem to be considerably higher, perhaps independently from the systematic position of involved populations (i.e., both in birds and in mammals). There are only a few dozen cases of neoplasms in the fossil record, most of which have doubtful diagnoses. The earliest known possible case of neoplasm is in a Dinichthys, an armored fish from Cleveland, Ohio that dates to the Upper Devonian (about 350 million years BP).41 The case consists of a dip pit on the internal surface of the lower jawbone. The authors47 interpret this lesion as the result of bone reabsorption due to a tumour, suggesting the presence of a Stafne' defect. As an alternative diagnosis, it is also possible that the lesion, which certainly occurred during the life of the fish, was caused by trauma. Some researchers have shown that the armored fish living in fresh waters were aggressive animals, and indeed some individuals present lesions that are obviously traumatic in origin and can be linked to intra-specific aggression.42 If a tumour of the soft tissues of the mouth floor produced the lesion, however, it is worth noting that the armored fish were one of the first groups of vertebrates to appear on the Earth. It would follow that neoplasms appeared on our planet with the first vertebrates, confirming the supposed biological link between vertebrates and neoplasms. The earliest known unequivocal neoplastic case was noted on the partial skeleton of a North American lower carboniferous (about 300 million years BP) fossil fish, Phanerosteon mirabile.43 The pathology presents as the classic fish osteoma including a bone focal hyperostosis of the sort also observed in living representatives of bony fish. This indicates that this type of neoplasm was among the first of the neoplastic diseases to appear on Earth. The 2 examples from the Paleozoic fossil record show that neoplasms occurred occasionally in all the prevalently aquatic vertebrates living during the Paleozoic Era. There are also many well-documented, unequivocally diagnosed cases of neoplasms among the animals, especially the terrestrial animals, that lived during the Jurassic, and, to a greater degree, the Cretaceous, from about 200–70 million years BP. Indeed, the analysis of millions of fossil bones from extinct Jurassic and Cretaceous reptiles has showed the presence of a bone osteoma in a vertebra of a mosasaurus (a large marine reptile). This is the earliest known case of a bone tumour in a terrestrial fossil.44, 45, 46 An additional case of osteoma has been observed in a Platecarpus sp.,9 and a possible additional case of osteoma has been observed on the left scapula of a Pachyrhinosaurus from Alberta, Canada, although scientific documentation is required to confirm the diagnosis.47 Focal bone hyperostosis was also observed in a caudal vertebra of a Cretaceous hadrosaur from Alberta, Canada, and likely represents an additional case of osteoma in dinosaurs.48 Other possibly benign neoplasms have been noted in dinosaur bones.49 For example, an intraosseous cyst interpreted as a neoplasm was observed on the cranial crest of a Stenonychosaurus inegualis from the Cretaceous of Alberta, Canada,50 and a possible hemangioma was described by Moodie46 in a tail vertebra of a Cretaceous herbivorous dinosaur from North America.46 Exostosis of the right scapula was observed in a Triceratops from the Mesozoic of North America. The attribution of the lesion to a neoplasm remains doubtful51 because exostoses can also be linked to ossification of soft tissue after traumatic events. We have noted this in the dinosaur bones of the collection of the museum at the University of Chieti (Italy). There is also a case of fused caudal vertebrae with new bone formation in a Jurassic sauropod from Wyoming (USA) that Moodie52 interpreted as possibly neoplastic. A more recent evaluation and comparison with similar cases has shown that these vertebral ankyloses are due to a rheumatic condition, for example diffuse hydropathic skeletal hyperostosis (DISH).53 In the paleopathological collections of the Biomedical Museum of the State University of Chieti (Italy), we have one of the earliest known cases of neoplasm in a dinosaur. The specimen (Fig. 1) is a fragment of a right rib of a giant Apatosaurus sp., found in Jurassic sediments in Wyoming (USA). This specimen presents a sub-rounded mass with multilobulated surface implanted on the external surface of the rib (Fig. 1a). The radiograph shows that the mass consists of high density bone tissue and the normal cortical bone appears to be eroded under the area of insertion of the neoformed mass (Fig. 1b). We think that the gross morphology and the radiographic picture are consistent with a possible osteochondroma (this is the first time this case has been mentioned). Fragment of a right rib of a large dinosaur, Apatosaurus sp. (a), which presents a sub-rounded mass with multilobulated surface (c), and high radiographic density (b) (Jurassic, Wyoming, USA; sample 323 of the University Museum, Chieti). The earliest known case of hemangioma, observed in a possible vertebral centra from a large sized terrestrial dinosaur from the Morrison Formation (Utah),54 dates to the Jurassic. The first clear, well-documented case of malignancy also dates to the Jurassic, as does the first unequivocal case of metastasis. In the humerus of a theropod dinosaur (Allosaurus fragilis) from the late Jurassic Morrison formation in Utah (USA), Stadtman observed a large mass of new-formed bone (surely due to neoplastic disease invading the surrounding normal bone) and interpreted it as a probable chondrosarcoma.55 The evidence for metastatic cancer consists of multiple lytic lesions with cortical bone invasion that were observed histologically and radiographically in a fossil bone fragment from a large-sized terrestrial dinosaur from the Jurassic Morrison formation in Colorado (USA).56 A possible multiple myeloma affecting the squamosal bone of a latest Cretaceous horned dinosaur, Torosaurus latus, has been suggested by Norman57 and a similar interpretation has been proposed for a case involving extra openings in the cranial bone of an ornithischian dinosaur.58 As these considerations show, all our knowledge of neoplasms during Jurassic and Cretaceous periods, including our first consistent information on the antiquity of cancer, are linked to the study of dinosaur bones. The very impressive sizes reached by many representatives of this group during the last part of the Mesozoic Era may have been related to endocrine disturbances. Some researchers suggest that the huge size typical of some dinosaurs was a form of gigantism, perhaps due to acromegalia linked to an increase in the endocrine function of the hypophysis.59, 60 Although a vast number of fossil dinosaur bones have been excavated perfectly and examined by specialists, no more than a dozen possible neoplasms have been observed, some of which are not confirmed. This number is minute. At the end of the Mesozoic Era (the passage from the Cretaceous to the Tertiary, also known as the K-T boundary) a massive extinction affected life on Earth, with the disappearance of millions of animal species (including all the dinosaurs) and the rise of mammals began. Despite the major changes that affected many animal groups and despite the dramatic changes in the relative importance of the various animal populations present on Earth during the Tertiary and Quaternary Eras, the prevalence of neoplasms remained constant: they did not disappear, but remained quite rare. We have several dozen reports of neoplasms in fossils from several countries and dating to the various periods of the Tertiary and Quaternary Eras. Benign neoplasms include osteoma that was reported in fossil elephants from Poland,61 as well as solitary bony cysts and bone defects in Tertiary Bovidae.62, 63 Other possibly benign neoplasms in Tertiary and Quaternary mammals have been observed in Nototerium sp.,64 Canidae65, 66 and Ursusus spelaeus.67 Many cases of fish osteoma have been observed in the fossil record of the Tertiary and Quaternary Eras. These types of focal and regional hyperostoses were so frequent in both fossils and extant species of fossil fish that Konnerth68 named the hyperostotic fish bones "Tilly Bone," in honor of the vertebrate paleontologist Tilly Edinger from Harvard University, who spent part of her life studying these neoplastic items. Because of their swollen and thickened nature, fish bones affected by focal hyperostoses are more durable and should better resist mechanical erosion and chemical dissolution and thus be preserved frequently. Indeed, Tilly bones are often found in Tertiary and Quaternary soils in both North America and Europe (Fig. 2).69 although some researchers consider hyperostoses to be part of a normal aging process,70 others have shown that they can be considered true neoplastic lesions.7, 69 Some species developed focal hyperostoses often, for example Platax artriticus and the Miocene Aphanius crassicaudatus.70, 71 Recent observations suggest that the affected fossil and extant species develop focal and regional hyperostoses because their habitats are highly saline.72 We have shown recently that all the Tertiary ancestors of extant sirenidae show pachyostosis,72 for example regional hyperostosis. Two fish vertebrae with focal bone hyperostosis (fish-osteoma or Tilly-bones), compared to a normal vertebra of the same species of fish and from the same locality (right) (Glades Country, Florida, USA, Pleistocene (sample 439-1,2,3 of the University Museum, Chieti, Italy). Focal hyperostosis in fish and pachyostosis in sirenidae could be phenotypic adaptations on the part of these aquatic animals to increase their body weight and thus facilitate swimming (the fish) or browsing shallow sea bottoms (the sirenidae) in hypersaline waters.72 Multiple hereditary osteochondroma have been observed in Oligocene Canidae Hesperocyon sp.73 Neoplasms derived from dental tissues are also well demonstrated in the Tertiary and Quaternary fossil record. It would seem that this type of neoplasm had a fairly high prevalence during this time, although one must keep in mind that teeth, which are the hardest animal tissue, are one of the more common elements of the fossil record. Odontoma has been reported in Tertiary ungulates from Argentina,74 in fossil horses,75 in European mammoths76 and in some Japanese fossil elephants.77 In our Museum we have a well-documented, unpublished case of odontoma in a Holocene fossil walrus from Alaska. There are also some examples of malignancy in the Tertiary and Quaternary fossil record, including osteosarcoma in a Pleistocene buffalo78 and a Holocene Capra79 and chondrosarcoma in some species of fossil Canidae.32, 80 Two final aspects regarding neoplasms in Tertiary and Quaternary Time must be considered. The first aspect is the rarity of neoplasms, especially in light of the vast number of fossil bones of reptiles, birds, and especially mammals that have been recovered. For example, Rancho La Brea, in California (a Pleistocene freshwater lake associated with a tar seep where a great many animals were trapped and died more than 2 million years ago) has yielded millions of fossil bones that have all been examined by paleontologists. No bone neoplasms have been found and the situation is similar in all other Tertiary and Quaternary fossil locations. It is also worth noting that most of the Tertiary and Quaternary neoplasms observed affected mammals, which were the most common class of vertebrate at the time, much the way that in Mesozoic Time the majority of neoplasms observed involved reptiles. The observed rarity of cancer may be explainable by the fact that the affected animals were presumably more vulnerable to predation, and in eating them the predators would have destroyed the traces of the pathologies they suffered from. In summary, the pre-human fossil record leads to some interesting conclusions (Fig. 3) : (i) neoplasms have existed since the Paleozoic Era and the first cases involved aquatic vertebrates such as primitive fish; (ii) during the Paleozoic Era neoplastic diseases were extremely rare; (iii) only during the Mesozoic Era did the incidence of neoplastic disease increase (although remaining rare), and the increase was concurrent primarily with the rise of terrestrial vertebrates such as the reptiles; (iv) the K-T boundary marks one of the most significant mass extinctions to strike life on Earth, with new Tertiary species replacing those of the Cretaceous; even so, the prevalence of neoplasms remained very low; (v) during the Tertiary and Quaternary Eras neoplastic diseases remained rare, although they now primarily affected mammals; (iv) focal hyperostosis of fish and pachyostosis of sirenidae seem to be forms of neoplasms adopted by these kinds of aquatic animals over millions of years as mechanisms by which to increase their body weights and thus facilitate bottom browsing at shallow depths or swimming in hypersaline waters; and (vii) the rarity of cancer in the fossil record must have been influenced by predatory activity, because sick animals were more vulnerable and therefore less likely to be fossilized. Incidence of neoplasms (including cancer) over the evolution of the vertebrates. The incidence is calculated on the basis of the ratio between the number of pathological specimens and the total number of fossils studied. Paleopathologists have spent decades discussing the "Kanam mandible," a fragment of mandibular ramous attributable to a Homo erectus from Kanam, Kenya, which presents a bizarre pathological growth in its symphysial region. This lesion was attributed initially to a possible Burkitt's lymphoma81 or an ossifying sarcoma,82 although some researchers have suggested recently it might be an overabundant bone callus associated with a healed fracture.83 If this case, with dates to about 1.5 million years ago, is a true neoplasm, it is the earliest known example of these diseases in man.84 Anthropologists have recovered and studied thousands of fossil bones pertaining to Neanderthal men in Europe, finding only one lesion possibly related to a neoplasm. It is the Stetten II parietal bone (from Germany, dating to about 35,000 years BP). The lesion consists of new bone formation theoretically linked to a possible meningioma although the evidence is neither clear nor convincing.85 Possible cases of neoplasms remained rare in prehistoric and ancient historic human populations and increased significantly only relatively recently in medieval and modern populations. As a general rule, the number of cases of possible neoplasms increases with the physical number of human remains available for analysis and also increases with decreasing antiquity. Almost all types of modern human neoplastic diseases have also been documented in ancient human remains and for a complete discussion of all the references made in the literature we suggest consulting one of the major analyses (i.e., Aufderide and Rodriguez-Martin, Capasso and Mariani-Costantini, Ortner).84, 86, 87 We summarize these reports to provide a general discussion on the topic of cancer in human antiquity. Cartilaginous exostoses have been demonstrated from early on, with one of the earliest known cases dating to the 12th Dynasty in Egypt.87 They were also present in ancient Europe.84 Hereditary multiple exostoses have also been demonstrated in ancient remains. The earliest known case dates to about 2,000 years ago and is from Poland.88 The earliest known case