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We describe the earliest evidence for neoplastic disease in the hominin lineage. This is reported from the type specimen of the extinct hominin Australopithecus sediba from Malapa, South Africa, dated to 1.98 million years ago. The affected individual was male and developmentally equivalent to a human child of 12 to 13 years of age. A penetrating lytic lesion affected the sixth thoracic vertebra. The lesion was macroscopically evaluated and internally imaged through phase-contrast X-ray synchrotron microtomography. A comprehensive differential diagnosis was undertaken based on gross- and micro-morphology of the lesion, leading to a probable diagnosis of osteoid osteoma. These neoplasms are solitary, benign, osteoid and bone-forming tumours, formed from well-vascularised connective tissue within which there is active production of osteoid and woven bone. Tumours of any kind are rare in archaeological populations, and are all but unknown in the hominin record, highlighting the importance of this discovery. The presence of this disease at Malapa predates the earliest evidence of malignant neoplasia in the hominin fossil record by perhaps 200 000 years.
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South African Journal of Science
http://www.sajs.co.za Volume 112 | Number 7/8
July/August 2016
Research Article Primary osteogenic tumour in Australopithecus sediba
Page 1 of 7
© 2016. The Author(s).
Published under a Creative
Commons Attribution Licence.
Osteogenic tumour in Australopithecus sediba:
Earliest hominin evidence for neoplastic disease
AUTHORS:
Patrick S. Randolph-Quinney1,2*
Scott A. Williams2,3
Maryna Steyn1
Marc R. Meyer4
Jacqueline S. Smilg2,5,6
Steven E. Churchill2,7
Edward J. Odes1,2
Tanya Augustine1
Paul Tafforeau8
Lee R. Berger2,9
AFFILIATIONS:
1School of Anatomical Sciences, University of
the Witwatersrand, Johannesburg, South Africa
2Evolutionary Studies Institute, School
of Geosciences, University of the
Witwatersrand, Johannesburg, South Africa
3Center for the Study of Human Origins,
Department of Anthropology, New York
University, New York, New York, USA
4Department of Anthropology, School of
Social & Behavioral Sciences, Chaffey
College, Rancho Cucamonga, California, USA
5School of Radiation Sciences, University of the
Witwatersrand, Johannesburg, South Africa
6Department of Radiology, Charlotte Maxeke
Academic Hospital, Johannesburg, South Africa
7Department of Evolutionary Anthropology,
Duke University, Durham, North Carolina, USA
8European Synchrotron Radiation Facility,
Grenoble, France
9DST/NRF South African Centre of Excellence
in Palaeosciences, University of the
Witwatersrand, Johannesburg, South Africa
*Current address: School of Forensic
and Applied Sciences, University of
Central Lancashire, Preston, Lancashire,
United Kingdom
CORRESPONDENCE TO:
Patrick Randolph-Quinney
EMAIL:
prandolph-quinney@uclan.ac.uk
POSTAL ADDRESS:
School of Forensic and Applied Sciences,
University of Central Lancashire, Preston,
Lancashire, PR1 2HE, UK
DATES:
Received: 11 Dec. 2015
Revised: 16 Mar. 2016
Accepted: 17 Mar. 2016
KEYWORDS:
Malapa; palaeopathology; neoplasia;
taphonomy; osteoma; malignant
HOW TO CITE:
Randolph-Quinney PS, Williams SA, Steyn M,
Meyer MR, Smilg JS, Churchill SE, et al.
Osteogenic tumour in Australopithecus sediba:
Earliest hominin evidence for neoplastic
disease. S Afr J Sci. 2016;112(7/8), Art.
#2015-0470, 7 pages. http://dx.doi.
org/10.17159/sajs.2016/20150470
We describe the earliest evidence for neoplastic disease in the hominin lineage. This is reported
from the type specimen of the extinct hominin Australopithecus sediba from Malapa, South Africa,
dated to 1.98 million years ago. The affected individual was male and developmentally equivalent
to a human child of 12 to 13 years of age. A penetrating lytic lesion affected the sixth thoracic
vertebra. The lesion was macroscopically evaluated and internally imaged through phase-contrast
X-ray synchrotron microtomography. A comprehensive differential diagnosis was undertaken
based on gross- and micro-morphology of the lesion, leading to a probable diagnosis of osteoid
osteoma. These neoplasms are solitary, benign, osteoid and bone-forming tumours, formed from
well-vascularised connective tissue within which there is active production of osteoid and woven
bone. Tumours of any kind are rare in archaeological populations, and are all but unknown in
the hominin record, highlighting the importance of this discovery. The presence of this disease
at Malapa predates the earliest evidence of malignant neoplasia in the hominin fossil record by
perhaps 200 000 years.
Introduction
A neoplasm (‘new-growth’ or tumour) is defined as a mass of localised tissue growth, the cellular
proliferation of which is no longer subject to the effects of normal growth-regulating mechanisms.1-3
A neoplasm may be benign or malignant. Malignant tumours are often referred to colloquially as cancer,
although the term ‘malignant neoplasia’ is more clinically appropriate.1 In the developed world, death from
malignancy is second only to cardiovascular disease and is often perceived as a disease of modernity.4
Neoplastic disease would have been prevalent in the past (e.g. Odes et al.5), but most likely occurred
at much lower levels of incidence than today, given the shorter life expectancy for victims1,6,7 and the
differing environmental context. Both these factors strongly influence the incidence and prognosis of any
cancer.3,8 The preserved signatures of neoplasms of any kind are rare in archaeological populations, and
are all but unknown in the hominin record. Here we present the earliest fossil evidence for neoplastic
disease in the human lineage, with a detailed description and diagnosis of a tumorous lesion affecting
the spine of a juvenile male Australopithecus sediba, Malapa Hominin 1 (MH1).9,10 This species has been
postulated as a possible ancestor of the genus Homo.9 The clinical and evolutionary implications of the
diagnosed condition are discussed.
The Malapa hominin site
The Malapa site is one of several hominin-bearing Plio-Pleistocene cave deposits located within the
Cradle of Humankind World Heritage Site to the northwest of Johannesburg, South Africa. The region
includes sites such as Sterkfontein11, Swartkrans12, Kromdraai13, Gladysvale14 and Rising Star15. The
fossil deposits in these caves were formed in roughly similar fashion as debris cone accumulations
deposited beneath vertical cave openings, which formed phreatically within the dolomites of the Malmani
Subgroup.15,16 At Malapa, the main hominin-bearing deposits have been dated using uranium-lead dating
of flowstones, combined with palaeomagnetic and stratigraphic analyses of flowstones and underlying
sediments, to 1.977 ± 0.002 million years ago (Ma).17 The cave deposits comprise five sedimentary
facies, termed A to E, from stratigraphically lowest to highest.
Facies A and B occur below a central flowstone sheet, and are overlain by an erosion remnant (facies C),
which in turn is overlain by the main hominin-bearing breccia, facies D. This has yielded well-preserved
macro- and micro-mammal fossils (such as carnivores, equids and bovids18), including the fossilised
remains of at least six hominins. Two of these, MH1 and MH2, have been reported in the literature as
representatives of a new hominin species, Australopithecus sediba9. Taphonomically the site has been
interpreted as a complex cave system with open deep vertical shaf ts that operated as death traps for animals
on the surface of the landscape. This death-trap scenario might have been the process by which the Malapa
hominins entered the cave system17,18, as evidenced by peri-mortem damage on the skeletons of MH1
and MH2, consistent with a fatal fall19. Furthermore, both skeletons present partial anatomical articulation
consistent with rapid incorporation into the cave sediments early in the decomposition process.18
Case study: Vertebra U.W. 88-37
A pathological lesion affects the spine of Malapa Hominin 1 (MH1), the type specimen of
Australopithecus sediba. This individual (Figure 1) was male, and at death he was at a developmental
stage equivalent to that of a human child aged 12 to 13 years9. The pathological specimen (U.W. 88-37)
is a complete vertebra originally assigned to T5-T710, now considered to represent the sixth thoracic
vertebra10. The dorsal surface of the right-side lamina exhibits a rounded penetrating defect (Figure 2),
measuring approximately 6.7 mm supero-inferiorly and 5.9 mm medio-laterally.
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Figure 2: Vertebra U.W. 88-37. Photographs of surface morphology of
U.W. 88-3 showing position of lesion on right side of vertebral
lamina: (a) right lateral aspect, (b) left lateral aspect, (c) inferior
aspect, (d) superior aspect, (e) posterior aspect, (f) anterior
aspect. Note that apertures seen on lateral aspects of the
vertebral body in images (a), (b) and (f) represent normal vascular
foramina infilled with residual breccia matrix. Images produced by
Peter Schmidt.
The defect presents as a lytic lesion that extends ventrally into the
lamina for much of its length, the most anterior portion of which remains
infilled with breccia matrix (Figure 3). On the surface, the lesion has
well-rounded edges with a somewhat sclerotic appearance. There is no
evidence of periosteal or reactive bone formation on the cortex of the
specimen. Viewing the right lamina from above, it appears thicker than
the left lamina and bulges laterally over the lesion, indicating a reactive
remodelling response to the presence of the defect.
Figure 3: Vertebra U.W. 88-37. Multi-focus (composite image stack)
micrograph of surface morphology of U.W. 88-37 showing
sub-angular penetrating defect on the right vertebral lamina.
The lesion has well-rounded edges with lateral bulging of
the cortex over the lesion, indicating a reactive remodelling
response to the presence of the defect. Note that anterior
portion of defect remains infilled with breccia matrix.
Micrograph taken with Olympus SZX Multi-focus microscope,
magnification 7x. Scale bar = 10 mm. Image courtesy of
Alexander Parkinson.
The lesion initially widens directly under the oval opening, but then
narrows as it progresses anteriorly. The base of the lesion appears
smooth and sclerotic under microscopic evaluation insofar as the
presence of residual breccia allows. The spinous process deviates
slightly to the right, but appears in keeping with slight asymmetry
noted elsewhere in the surviving thoracic vertebrae. This deviation falls
within normal variation; we do not consider it significant enough to
cause scoliosis or other vertebral misalignment, and it is unlikely that
this asymmetry was related to the pathology.
Figure 1: Surviving skeletal elements attributed to Malapa Hominin 1 (at time of writing).
Research Article Primary osteogenic tumour in Australopithecus sediba
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Because of the presence of breccia within the lesion, the internal
morphology of the specimen was assessed using phase-contrast
X-ray synchrotron microtomography (performed at the European
Synchrotron Radiation Facility, ESRF) and a specific acquisition
protocol applied for high-quality imaging of large fossils (see
Supplementary Appendix materials and methods). From the
microtomographic volume, the maximum long axis of the lesion in
the transverse plane measures 11.8 mm x 4.9 mm along the minor
axis, with a cross-sectional area of 45.6 mm, and in the sagittal
plane the lesion measures 14.7 mm x 7.9 mm, with a cross-sectional
area of 68.6 mm. The internal linear dimensions are consistently
less than 20 mm in diameter, which has important implications for
final diagnosis.
Figure 4: Vertebra U.W. 88-37. Sixth thoracic vertebra of juvenile
Australopithecus sediba (Malapa Hominin 1). Partially trans-
parent image volume with the segmented boundaries of
the lesion rendered solid pink. Volume data derived from
phase-contrast X-ray synchrotron microtomography. (a) left
lateral view, (b) superior view, (c) right lateral view. Images
produced by P.T.
Figure 4 shows the microtomographic imaging, with a semi-trans-
parent volume-rendered image row. The imaging indicates that the
lesion is highly penetrative and extends ventrally within the right-side
of the spinous process, penetrating the lamina before terminating
at the approximate level of the superior articular facet. The internal
morphology shows no involvement of the transverse process or
pedicle, and the lesion does not penetrate the vertebral canal. No
mineralised focal point or nidus was discerned. The edges of the first
two-thirds of the lesion (moving dorsal to ventral) display sclerotic
characteristics, with circumscribed margins of well-integrated
cortical bone, abutted and intersected by trabecular striae (Figure 5
and Supplementary Appendix). This pattern is indicative of a slow-
forming bony process, with remodelling and reorganisation of
posterior aspects of the lesion. The shape of a lesion is indicative of
its growth rate, with lesions that are long and oriented with the long
axis of a bone indicating a nonaggressive benign process. The ventral
third of the lesion, however, displays a geographic pattern of bone
destruction, showing a sharp non-sclerotic margin and evidence
of active osteolytic processes, with sharply-defined transection
of individual trabeculae, and active osteolytic penetration into the
anterior portion of the lamina. A volume-rendered negative surface
model of the lesion (Figure 6) demonstrates the clear distinction
between the dorsal sclerotic zone and the ventral lytic zone within the
body of the active lesion.
Key: S – quiescent sclerotic zone, O – active osteolytic zone, B – remaining breccia
matrix infill.
Figure 5: Transverse slices through vertebra U.W. 88-37 derived from
phase-contrast X-ray synchrotron microtomography. Relative
position and anatomical orientation of orthoslices (a), (b)
and (c) shown on the volume-rendered model. The posterior
portion of the lesion is sclerotic with circumscribed margins
of well-integrated cortical bone, abutted and intersected
by trabecular striae, with remodelling and reorganisation
of the cortex. The anterior portion of the lesion displays a
geographic pattern of bone destruction, showing a sharp non-
sclerotic margin and evidence of active osteolytic processes,
with sharply defined transection of individual trabeculae
and active osteolytic penetration into the anterior portion of
the lamina. Image produced by P.S.R.Q.
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Figure 6: Surface rendered image volume of the U.W. 88-37 lesion
derived from phase-contrast X-ray synchrotron microto-
mography. Images show isosurface derived from segmented
boundaries of the lesion (remaining breccia infill removed).
The arrow denotes the interface between the smoother dorsal
sclerotic zone and the disorganised ventral lytic zone within
the body of the lesion. (a) right lateral view, (b) medial view.
Images produced by P.T.
Differential diagnosis
Diagnosis was undertaken using palaeopathological and clinical
diagnostic criteria1,2,20-34. The accumulated evidence for osteolytic and
osteosclerotic processes indicates that the disease process was both
chronic and active at the time of death of MH1 (as mentioned, at a
developmentally equivalent stage to a modern human child of 12 to 13
years of age). The lesion was less than 15 mm at the largest diameter,
extending deep into the right side of the spinous process and involving
only the vertebral lamina. The presence of reorganised sclerotic bone
indicates a reactive ante-mortem process, and the lesion can therefore
not be attributed to taphonomic, diagenetic or pathology-mimicking
effects or processes1.
The morphology of the lesion externally and internally is inconsistent with
vertebral osteomyelitis. The absence of a proliferative cor tical inflammatory
response (such as periosteal and/or endosteal bone hypertrophy) or
secondary lytic lesions across both the U.W. 88-37 vertebra and the
surviving cranial and post-cranial elements of MH1 excludes a diagnosis
of specific or non-specific systemic infection, such as brucellosis, non-
specific osteitis, haematogenous osteomyelitis or treponemal osteitis.
There is no evidence of deformation or callus formation associated with
skeletal trauma such as a healed fracture, and the lesion does not present
morphology consistent with post-traumatic processes such as cortical
hypertrophy or the development of a cloaca. It is therefore most likely
that this condition represents a primary osteogenic or osseous tumour
of the spine. These are rare lesions with a much lower incidence than
metastases, multiple myeloma or lymphoma.1,2,20,21,23,27,32 Based on age
at death, sex, anatomical location of the lesion, and specific patterns of
expression and skeletal involvement, conditions such as osteosarcoma,
chondrosarcoma or Ewing’s sarcoma can be excluded; these neoplasms
are often more aggressive, with destruction of the cortex1,21,23.
Included in the differential diagnosis as the most likely cause of
the observed lesion are osteoid osteoma, osteoblastoma, giant
cell tumour and aneurysmal bone cyst. A number of secondary
diagnoses are possible, specifically enostosis (compact bone island),
fibrous cortical defect (fibroxanthoma), plasmacytoma, eosinophilic
granuloma, and hydatid cyst infection. The range of possible differential
diagnoses and primary diagnostic criteria are detailed in Table S1
(Supplementary Appendix).
Based on the observed pathological, morphological, and life-history
criteria, the two most likely diagnoses are osteoid osteoma and
osteoblastoma. Taking the demographic data for these two tumour
types into account, both options seem possible: both are primary bone-
forming tumours, osteoblastic in nature; benign; have a predilection for
males; and show the highest prevalence in juveniles and adolescents.
Osteoid osteoma resembles the observed lesion in terms of size, as
these tumours are usually less than 20 mm in diameter, with well-
circumscribed margins and being round or oval in form23.
McCall22 notes that computed tomography is the most valuable method
to investigate this type of lesion. Under CT imaging of osteoid osteoma
a small lucency is often recorded, which may have a central high
attenuation as a result of mineralisation, and surrounding sclerotic bone
is noted with some thickening of the lamina or pedicle. These are features
seen in MH1 (Figure 4). On plain radiographs, most osteoid osteomas
are osteosclerotic, with or without a visible nidus. By contrast, Kan and
Schmidt35 suggest that osteoblastomas are predominantly lucent or
lytic in roughly 50% of cases, sclerotic in 30% of cases, and mixed in
the remaining 20% of cases. On plain radiographs, osteoblastomas are
typically expansile with a scalloped or lobulated appearance, and their
margins are well-defined, with a sclerotic rim evident in approximately
30% of patients. A sclerotic rim is therefore much more common in
osteoid osteomas than in osteoblastomas. The smooth, sclerotic, well-
defined posterior margins of the lesion we studied are fully consistent
with a resolving osteoid osteoma. However, the skeletal distribution
of osteoid osteoma might argue against this being the most likely
diagnosis, as osteoid osteomas are most commonly found in the lower
extremities; occurrence in the spine is less likely than that exhibited
in osteoblastoma22.
To quantifiably assess the differential diagnosis, we applied Bayes
Theorem of conditional probability to the diagnosis of osteoid osteoma
and osteoblastoma. Using absolute clinical incidence data of osteoid
osteoma36-38 and osteoblastoma25,37-42 to calculate prior and conditional
probabilities of the disease expression in the vertebral column (as
opposed to elsewhere in the skeleton), a conditional probability of
0.214 was derived for the likelihood of osteoid osteoma, and 0.068
for osteoblastoma. These results indicate a 3.75-fold higher likelihood
that osteoid osteoma was represented in this case than osteoblastoma
(see supplementary online material Table S2 for discussion of Bayes
parameters and probability functions used). Given the morphological
and pathological similarities between the two tumour types, and the
age and nature of the specimen under analysis, the results suggest
osteoid osteoma firstly and osteoblastoma secondly as the most likely
diagnoses of what was clearly a benign entity of abnormal nature.
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Discussion
MH1 suffered from a primary osteogenic tumour, which affected the
right lamina of the sixth thoracic vertebra. The neoplastic lesion was
chronic and was still active at the time of his death. From modern
clinical studies36-38 it is likely that osteoid osteoma may have taken
months, rather than years, to develop. This neoplastic condition may
involve neurological deficits, although this is unlikely as the lesion did
not penetrate the neural canal, and no scoliosis was noted. However, the
position of the lesion may have affected normal musculoskeletal function
and movement of both the shoulder-blade and the upper right quadrant
of the back. The tumour may have invoked a number of physiological
responses including acute or chronic pain, muscular disturbance
and pain-provoked muscular spasm, as discussed in clinical case
studies.21,36-38,40 A close association exists between the affected region
and overlaying or closely inserting muscles such as trapezius, erector
spinae, and rhomboid major, and this might have led to limitations on
normal movement, given the likely arboreal component in the locomotor
repertoire of A. sediba.9,43
The presence of a primary bone-forming tumour of the spine presents
a number of considerations with regard to both the life-history of
Australopithecus sediba, and evidence for neoplasia elsewhere in the
deep past. Evidence for neoplastic disease is not unknown in the fossil,
archaeological and historical records1,8,44. However, preservational
factors limit the study of neoplasms to the skeleton (with the rare
exception of naturally and artificially mummified bodies that may
preserve pathological soft tissues) from which the confident diagnosis
of tumours has been problematical45. The earliest skeletal evidence for
neoplastic disease comes from pre-Cenozoic contexts, with purported
cases of neoplasm found in fossil fish from the Upper Devonian. The
earliest unequivocal case dates from 300 Ma, with evidence of benign
osteoma with focal hyperostosis affecting the skeleton of Phanerosteon
mirabile from the North American Lower Carboniferous3. Later terrestrial
cases include diagnoses of benign haemangioma and eosinophilic
granuloma in Jurassic dinosaurs; benign osteoma in mosasaurs;
and haemangioma, metastatic cancer, desmoplastic fibroma and
osteoblastoma in Cretaceous hadrosaurs.46,47 In the more recent past,
benign osteoid osteoma and osteoblastoma have been identified in
European mammoths dating from 24 000 to 23 000 years ago (ka).48
The presence of neoplastic disease in the hominin fossil record is highly
contentious. Until recently, the earliest purported evidence was suggested
to be from a mandible of archaic Homo from Kanam, Kenya. This fossil
is generally thought to derive from the Lower or Middle Pleistocene, and
expresses pathological growth in the symphysial region. The lesion has
been attributed to osteosarcoma, bone keloid, or Burkitt’s lymphoma,
although some researchers have diagnosed it as osteomyelitis resulting
from a facial fracture49-52. The first substantive evidence for malignant
neoplasia in hominins is derived from the SK7923 metatarsal fragment,
dated to 1.8 to 1.6 Ma, from the site of Swartkrans, South Africa; a bony
cortical exostosis together with osseous infilling of the medullary cavity
of the shaft of the bone has been attributed by Odes and colleagues to
osteosarcoma5.
The next significant evidence for near-human neoplastic disease is
suggested by Monge and colleagues, who present a case of fibrous
dysplasia in a rib of Homo neanderthalensis dated to 120 ka from the
European site of Krapina.53 The Middle Pleistocene site of Atapuerca
(Sima de los Huesos) evidenced small benign osteoid osteomata
affecting the orbital roof of crania AT-777 and the endocranial surface
of Cranium 4.54 Other evidence comes from the Vogelherd (Stetten) II
parietal bone, initially thought to represent a 35-ka-old Neanderthal,
but now known to be Neolithic in origin55; in this specimen new bone
formation has been linked to a possible meningioma although the
final diagnosis remains equivocal56. The most significant evidence for
neoplastic disease in antiquity derives from the bio-archaeological
record of the recent Holocene (and the last four millennia in particular)
and is detailed in a number of historical reviews and texts1-3,46 to which
the reader is directed.
As noted above, neoplastic disease in various forms, including osteoid
osteoma and osteoblastoma, is an ancient phenomenon. It first appeared
during the Palaeozoic and Mesozoic in extinct fish and members of the
Dinosauria respectively.3,46,47 However, the fact that reports of cancers
or neoplasms remain exceedingly rare in the fossil record of almost
any geological epoch1,3,8,46,47,53 may be due to a number of factors,
exacerbated by the relative disjunction between osseous tumours and
all other forms of neoplasms. Primary bone tumours are rare compared
with other neoplasms and account for around 7% of all soft and hard
tissue cancers.22 Neoplasms are historically reported to be rare in wild
living mammals, with only 1.8% of deaths in chimpanzee communities
reportedly resulting from cancer.3 A mere handful of neoplastic cases
have been recorded based on observational studies of camels, deer,
gibbons, tigers, kangaroos, pacaranas, fur seals, ferrets, killer whales,
harbour seals, sea lions and harp seals.3 However, recent reviews of
neoplasms in wild non-human primates57 have shown that neoplastic
disease might be far more widespread than previous studies suggest,
in both monkeys and great apes; however, the vast majority of such
cases involve benign soft tissue rather than malignant tumours. When
bone tumours have been noted, they have tended to present as small
benign growths such as button osteomata, which have been observed in
both gorilla subspecies but have not been seen in either chimpanzees or
orangutans57. An isolated case of benign osteochondroma was observed
in the Gombe chimpanzee ‘Old Female’.58 Whilst these rare cases of
neoplasia in non-human primates share morphological homology with
human disease expression, it is unclear whether they share a common
genetic basis or evolutionary history.
With regard to osteoid osteoma in humans, cytogenetic chromoso-
mal studies indicate some degree of a genetic basis. This includes
the involvement of chromosome 22, 22q monosomy and trisomy
aberrations59; aberrant expression of transcription factors Runx2 and
Osterix, both of which are master regulators of osteoblastic lineage
differentiation60; and duplications and deletions at 22q13.159, the
locus of which reflects genes that play a role directly in osteogenesis
(PDGF-B and ATF-4). The involvement of the latter suite of genes may
suggest a degree of evolutionary conservatism, which warrants further
investigation across primate taxa. As noted by Odes et al.5, whilst the
expression of neoplasia is rare in prehistory, the capacity for neoplastic
disease (as evidenced by both fossil evidence and oncogenes) was
present in deep-time.
It is no surprise that metastatic bone tumours are rare or absent in the
archaeological and fossil records, because of the limited life expectancies
of our ancestors6,7 and the low incidence generally of skeletally forming or
affecting neoplasms1,3,20,23,46. It is well known that primary bone tumours
mostly occur in younger individuals1,20,21,27,37,40, and it can therefore
be expected that such tumours would have been present and have a
similar prevalence to what is observed among modern individuals. It
seems likely that neoplastic disease was as prevalent in ancient hominin
populations as that expressed today in wild primate groups, but for
various reasons it left little fossil trace. One reason might be the sheer
paucity of individuals recovered from the hominin record, which would
represent an issue of epidemiological sampling6.
With regard to the earliest evidence for neoplastic disease in the hominin
fossil record reported here, the fact that primary bone neoplasms
are so rare makes this an important discovery. Whilst we consider it
unlikely that neoplastic disease would have played a major role in the
evolutionary forces operating on the Homininae, this case provides
a unique glimpse into the individual life experience of a single extinct
hominin. MH1 provides a window onto the expression and evolution
of neoplastic disease in the human lineage, and highlights the utility
of multidisciplinary clinical studies applied to the understanding of the
evolution and development of disease in the human lineage.
Acknowledgements
We would like to acknowledge the assistance and help of the
following people in the production of this research: Bonita de Klerk,
Wilma Lawrence and Jennifer Randolph-Quinney. S.A.W. would like
to acknowledge the help of Morgan Hill and Eric Mazelis from the
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Microscopy and Imaging Facility, and Neil Duncan and Eileen Westwig
of the Department of Mammalogy at the American Museum of Natural
History. Further support in scanning time was given by the European
Synchrotron Radiation Facility and by the Department of Radiology at
Charlotte Maxeke Academic Hospital in Johannesburg. The research
was funded by grants to L.R.B. from the National Geographic Society,
the National Research Foundation of South Africa and the DST/NRF
South African Centre of Excellence in Palaeosciences. Additional direct
support for E.J.O. was received from the National Research Foundation
of South Africa and the DST/NRF South African Centre of Excellence
in Palaeosciences. M.S. was supported by the National Research
Foundation of South Africa.
Authors’ contributions
P.S.R.Q. coordinated the research and wrote the original draft of the
manuscript, incorporating additional case notes and observational data
on U.W. 88-37 as provided by S.A.W., M.S., M.R.M., J.S.S., S.E.C.
and L.R.B. Detailed discussion of oncogenetics was provided by T.A,
and E.J.O. provided detailed discussion of the historical data on early
hominin palaeopathology. P.T. undertook the synchrotron scanning of
the specimen, and primary reconstruction, segmentation and imaging.
All authors contributed equally to data acquisition and analysis, and
to editing.
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Note: This article is accompanied by supplementary material.
Research Article Primary osteogenic tumour in Australopithecus sediba
Page 7 of 7
... A comprehensive review of the paleopathological literature has produced few cases of osteoid osteoma (Randolph-Quinney et al., 2016;Gawlikowska-Sroka et al., 2016;Varotto et al., 2019). The paleopathological literature is even more scant in terms of osteoblastoma, with only two recorded cases (Riccomi et al., 2018;Alrousan et al., 2022). ...
Article
Objective This project evaluates a cranial lesion from a Hellenistic-era individual excavated by the Muğla Archaeological Museum in Gülağzı, Turkey. Materials An osseous tumor measuring 3.02 × 3.54 × 2.98 cm originating from the occipital bone of a probable young adult male. Methods The tumor was examined using gross morphological inspection, plain radiography (x-ray), and computed tomography (CT) imaging to identify potential differential diagnoses for the osseous cranial tumor. Results The lesion in question displays features highly consistent with both osteoid osteoma and osteoblastoma. The tumor had a non-sclerotic, sharply demarcated border, a radiolucent nidus measuring less than 2 centimeters in diameter, and homogeneous sclerotic bone surrounding the nidus. Conclusions Differential diagnosis determined the osseous tumor to be a benign neoplasm, and in this case the features of the tumor are highly consistent with a diagnosis of either osteoblastoma or osteoid osteoma. Significance The identification of novel neoplastic cases in paleopathology represents an important contribution to ongoing discussions regarding the temporality and regional variability of neoplastic conditions in the past. Additionally, a rigorous diagnostic study augmented by x-ray, CT scans, and 3D modeling provides data that can be utilized in future paleopathological studies. Limitations Diagnostic interpretation would be aided by histological examination of the tumor, which was impossible in this case. Histological examination would provide a definitive diagnosis. Suggestions for further research Given the high incidence of benign tumors in the clinical literature but a paucity of reports in the paleopathological record, further research is indicated to better understand the implications of benign neoplasms in antiquity.
... The second case, an Australopithecus sediba boy (around 12 to 13 years old) from Malapa (MH1), dating to around 2 million years ago, showed evidence of a bony tumour of the spine (a primary osteogenic tumour, which affected the right lamina of the sixth thoracic vertebra). This tumour is likely to have limited movement of the shoulder and upper right part of the back, as well as causing chronic pain and muscle spasm (Randolph-Quinney et al. 2016). Given the continued arboreal component of mobility in Australopithecus sediba, this is likely to have limited mobility. ...
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... This communication is limited to human Osteo-Sarcoma. The oldest being dated to 1.7-2 million years before present [8] . In present times the ever present & essential; versatile transcription protein namely 'Signal Transducer and Activator of Transcription 3' (STAT3) is found in human osteosarcoma cell line samples. ...
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Osteosarcoma is adominanttype of bone cancer,associated withosteophytes (bone cells).Afflicts all age groups; generally manifesting in long bones of human physiology(also other parts; including fine joints). Chemotherapy, surgery and radiation are the current therapeutics – with uncertain results; often associated with high degree of failure; swift relapse; rebound aggression and above all with debilitating post treatment outcome conditions. In this investigation insilico drug designing procedures have been used to predict natural compounds from Kaempferiaparviflora (black ginger) as possible drug candidates for osteosarcoma. 8 of its phyto-compounds (PCs) are found to be non-toxic and also pass the Lipinski’s rule of 5 (@ 100%) vis-à-vis the over expressed Signal Transducer And Activator Of Transcription 3(STAT3) protein of the dreaded osteosarcoma. All the 8 PCs indicate better binding affinity (greater likeness) than the current best popular allopathic drug Zoledronic acid (Toxic). All the 8 offer good-excellent likeness. Alpha- Copaene (non Toxic) emerges as the Champion.
... This communication is limited to human Osteo-Sarcoma. The oldest being dated to 1.7-2 million years before present [8] . In present times the ever present & essential; versatile transcription protein namely 'Signal Transducer and Activator of Transcription 3' (STAT3) is found in human osteosarcoma cell line samples. ...
... This communication is limited to human Osteo-Sarcoma. The oldest being dated to 1.7-2 million years before present [8] . In present times the ever present & essential; versatile transcription protein namely 'Signal Transducer and Activator of Transcription 3' (STAT3) is found in human osteosarcoma cell line samples. ...
Article
Full-text available
Osteosarcoma is a dominant type of bone cancer, associated with osteophytes (bone cells). Afflicts all age groups; generally manifesting in long bones of human physiology(also other parts; including fine joints). Chemotherapy, surgery and radiation are the current therapeutics – with uncertain results; often associated with high degree of failure; swift relapse; rebound aggression and above all with debilitating post treatment out come conditions. In this investigation in silico drug designing procedures have been used to predict natural compounds from Kaempferia parviflora (black ginger) as possible drug candidates for osteosarcoma. 8 of its phyto-compounds (PCs) are found to be non-toxic and also pass the Lipinski’s rule of 5 (@ 100%) vis-à-vis the over expressed Signal Transducer And Activator Of Transcription 3(STAT3) protein of the dreaded osteosarcoma. All the 8 PCs indicate better binding affinity (greater likeness) than the current best popular allopathic drug Zoledronic acid (Toxic). All the 8 offer good-excellent likeness. Alpha- Copaene (non Toxic) emerges as the Champion.
... Ancient human civilization is based on orderly chaos and an ethos of heterogeneity. Solid tumors are heterogeneous in terms of their cellular composition and genetic integrity, and their existence dates back to early human civilization [1][2][3][4]. There are many similarities between the propagation of human civilization and human tumors. ...
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Chapter
Paleopathological and paleo-oncological research aims to unveil the long-time trajectory and the natural history of neoplasms, as well as how these conditions impacted human past societies. This area of research also scrutinizes how the interplay between environmental, biological, and sociocultural processes influenced the development of neoplasms across distinct spatial and geographic frames. In this chapter we explore the expression of cancer in our past, by examining the most direct sources of its evidence, the human skeletal remains and mummified bodies. An overview of the achievements, contributions, and limits of the paleo-oncological research is also presented. We argue that the study of the past has the potential to inform about the present and the future.
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Cancers in animals present a large, underutilized reservoir of biomedical information with critical implication for human oncology and medicine in general. Discussing two distinct areas of tumour biology in non-human hosts, we highlight the importance of these findings for our current understanding of cancer, before proposing a coordinated strategy to harvest biomedical information from non-human resources and translate it into a clinical setting. First, infectious cancers that can be transmitted as allografts between individual hosts, have been identified in four distinct, unrelated groups, dogs, Tasmanian devils, Syrian hamsters and, surprisingly, marine bivalves. These malignancies might hold the key to improving our understanding of the interaction between tumour cell and immune system and, thus, allow us to devise novel treatment strategies that enhance anti-cancer immunosurveillance, as well as suggesting more effective organ and stem cell transplantation strategies. The existence of these malignancies also highlights the need for increased scrutiny when considering the existence of infectious cancers in humans. Second, it has long been understood that no linear relationship exists between the number of cells within an organism and the cancer incidence rate. To resolve what is known as Peto's Paradox, additional anticancer strategies within different species have to be postulated. These naturally occurring idiosyncrasies to avoid carcinogenesis represent novel potential therapeutic strategies.
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The osteoma, among other forms of benign neoplastic disease, has received little palaeopathological or palaeoepidemiological interest largely because of its asymptomatic nature. This is problematic because these tumours are regarded as common occurrences in bioarchaeological contexts, despite there being scant data to support these claims. This investigation presents a palaeoepidemiological enquiry into osteomata. Five hundred ninety individuals from six skeletal assemblages from Poland, dating from the 9th to 17th century, were macroscopically surveyed for osteomata. This was followed by a palaeoepidemiological analysis, looking at sex‐ and age‐specific prevalence. Ninety‐three osteomata were observed in 67 individuals. The sex‐specific prevalence was 13.5% (95% confidence interval [CI]: 9.7–18.1) for males and 11.6% (95% CI 7.9–16.2) for females. The age‐specific prevalence for middle adults was 2.1% (95% CI: 0.6–5.2) and 5.3% (95% CI: 2.5–9.8) for mature adults. The results indicated the prevalence of benign tumours was similar between males and females and seemed to increase with age. This case study adds to a sparse area of palaeo‐oncological research and calls for further future investigation.
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The reported incidence of neoplasia in the extinct human lineage is rare, with only a few confirmed cases of Middle or Later Pleistocene dates reported. It has generally been assumed that premodern incidence of neoplastic disease of any kind is rare and limited to benign conditions, but new fossil evidence suggests otherwise. We here present the earliest identifiable case of malignant neoplastic disease from an early human ancestor dated to 1.8–1.6 million years old. The diagnosis has been made possible only by advances in 3D imaging methods as diagnostic aids. We present a case report based on re-analysis of a hominin metatarsal specimen (SK 7923) from the cave site of Swartkrans in the Cradle of Humankind, South Africa. The expression of malignant osteosarcoma in the Swartkrans specimen indicates that whilst the upsurge in malignancy incidence is correlated with modern lifestyles, there is no reason to suspect that primary bone tumours would have been any less frequent in ancient specimens. Such tumours are not related to lifestyle and often occur in younger individuals. As such, malignancy has a considerable antiquity in the fossil record, as evidenced by this specimen.
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Palaeontological and geological research at the Gladysvale Cave during the last decade has concentrated on de-roofed deposits located outside the Main Chamber. This area has been termed the Gladysvale External Deposit (GVED) and consists of fossil-rich calcified and decalcified sediments. Here we report on the recent analysis of both the faunal material and the geological context of this deposit. The faunal assemblage, excavated from the decalcified sediments contains 29 mammal species including taxa rare or absent in the Witwatersrand Plio-Pleistocene fossil record (e.g. Pelorovis and Kobus leche). Carnivores and porcupines are identified as accumulating agents of the bones. No new hominin findings can be reported from this deposit, and no cultural remains have been recovered. Geologically the calcified and decalcified breccias represent part of a large talus cone that is relatively unexposed. Uniquely for a cave fill in the Witwatersrand hominin-bearing sites, the sediments are horizontally stratified and form a number of flowstone bound sequences. The dating of the in situ cemented sediments is based on electron spin resonance (ESR) and palaeomagnetism. Recent results indicate that the deposits are of Middle-Pleistocene age.
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Osteoblastoma is a rare benign bone tumor. Although the histologic features in most cases are distinctive, there are various permutations that make the diagnosis challenging. It can mimic a variety of other benign bone tumors, but more importantly, distinguishing it from osteoblastoma-like osteosarcoma can be difficult. In this case report, I describe the clinicopathologic findings for a 13-year-old adolescent boy with T7 spinal osteoblastoma and review salient clinical, radiographic, and pathologic features of osteoblastoma, as well as the differential diagnoses.
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New excavations have been opened at the early hominid site of Kromdraai, which is the location of the type specimen of Australopithecus (Paranthropus) robustus. The history of excavation at the site is reviewed and preliminary results given of the latest activity. -Authors
Book
The third edition of Combined Scintigraphic and Radiographic Diagnosis of Bone and Joint Diseases has been comprehensively rewritten and rearranged. It now encompasses, in addition to the bone and joint diseases described in the two earlier editions, hitherto unpublished novel applications of pinhole scanning to the diagnosis of a broader spectrum of skeletal disorders than ever before, including those of the soft tissues. A large number of state-of-the-art scans and corroboratory images obtained using CT, MRI and/or sonography are presented side by side. The book has been considerably expanded to discuss five new themes: Normal Variants and Artifacts, Drug-Induced Osteoporosis, Soft-Tissue Tumors and Tumor-like Conditions, PET/CT in Bone and Joint Diseases and A Genetic Consideration of Skeletal Disorders. Topical chapters on rheumatic skeletal disorders, malignant tumors of bone, benign tumors of bone and traumatic diseases have also been thoroughly rewritten and are complemented by the addition of some 90 recently acquired cases.
Article
Objective: To analyze the clinical and imaging features of pulmonary metastasis of giant cell tumor of bone for clinical diagnosis and treatment. Methods: Five patients with histologically proven pulmonary metastasis from giant cell tumor of bone were reviewed, the imaging features and the progression of the pulmonary metastasis were evaluated. Results: The first operation of primary tumor was curettages and then local recurrence was seen in all 5 cases. The interval to metastasis ranged from 5 to 26 months. Pulmonary metastasis was diagnosed by chest radiographs in 4 cases and CT in all 5 cases. The imaging findings included solitary solid nodule (n=1), multiple solid nodules and mass (n=5), multiple ground-glass nodules (n=1) and complex form (n=2). The dynamic follow-up CT findings showed spontaneous regress nodules (n=1), metastasis occurring again 19 months after surgery of solitary nodule (n=1), some solid nodules unchangable for a long time in 3 patients with multiple nodules. Conclusions: The dynamic follow-up CT findings of pulmonary metastasis of giant cell tumor of bone are specific. The regular follow-up could play an essential role in early detection and prognosis of pulmonary metastasis within 2 years after primary tumor diagnosed.
Article
Demography in Archaeology, first published in 2006, is a review of current theory and method in the reconstruction of populations from archaeological data. Starting with a summary of demographic concepts and methods, the book examines historical and ethnographic sources of demographic evidence before addressing the methods by which reliable demographic estimates can be made from skeletal remains, settlement evidence and modern and ancient biomolecules. Recent debates in palaeodemography are evaluated, new statistical methods for palaeodemographic reconstruction are explained, and the notion that past demographic structures and processes were substantially different from those pertaining today is critiqued. The book covers a wide span of evidence, from the evolutionary background of human demography to the influence of natural and human-induced catastrophes on population growth and survival. This is essential reading for any archaeologist or anthropologist with an interest in relating the results of field and laboratory studies to broader questions of population structure and dynamics. © Andrew T. Chamberlain 2006 and Cambridge University Press, 2009.