An insight into cancer palaeobiology: does the Mesozoic neoplasm support tissue organization field theory of tumorigenesis?

BACKGROUND: Neoplasms are common across the animal kingdom and seem to be a feature plesiomorphic for metazoans, related with an increase in somatic complexity. The fossil record of cancer complements our knowledge of the origin of neoplasms and vulnerability of various vertebrate taxa. Here, we document the first undoubted record of primary malignant bone tumour in a Mesozoic non-amniote. The diagnosed osteosarcoma developed in the vertebral intercentrum of a temnospondyl amphibian, Metoposaurus krasiejowensis from the Krasiejów locality, southern Poland. RESULTS: A wide array of data collected from gross anatomy, histology, and microstructure of the affected intercentrum reveals the tumour growth dynamics and pathophysiological aspects of the neoplasm formation on the histological level. The pathological process almost exclusively pertains to the periosteal part of the bone composed from a highly vascularised tissue with lamellar matrix. The unorganised arrangement of osteocyte lacunae observed in the tissue is characteristic for bone tissue types connected with static osteogenesis, and not for lamellar bone. The neoplastic bone mimics on the structural level the fast growing fibrolamellar bone, but on the histological level develops through a novel ossification type. The physiological process of bone remodelling inside the endochondral domain continued uninterrupted across the pathology of the periosteal part. CONCLUSIONS: Based on the results, we discuss our case study's consistence with the Tissue Organization Field Theory of tumorigenesis, which locates the causes of neoplastic transformations in disorders of tissue architecture.

Demographics and significance of porotic hyperostosis as assessed by surface microscopy.

BACKGROUND: Examination of parietal surface anatomy has been limited because standard techniques have insufficient resolution to identify and characterize the structures of interest. Perspectives derived thereof have not clarified their nature. Surface microscopy is pursued as a nondestructive technique to assess the character and implications of porotic pores (referred to as porotic hyperostosis), which have been subject of much speculation. METHODS: The external surface of the skulls, selected on the basis of age and gender, from the Hamann-Todd human collection are examined by epi-illumination microscopy for surface pores and to assess correlation with age, ethnicity, gender, anemia, infection, cancer, hypertrophic bone disorders, renal disease, and fractures. RESULTS: Pore-like surface defects are present in 2.7%-5% of individuals in the third-fifth decades of life; 7%, in the sixth-eighth; and 25%, in the ninth-11th, but absent in the second decade of life. They are gender and birthdate independent, but slightly more common in African Americans. Fractures are more common among individuals with parietal pores, while tuberculosis, cancer, and hypertrophic bone diseases and anemia are less common. DISCUSSION: This is the first study to actually examine the prevalence of parietal pores as a function of known age, race, and sex and provides a baseline for comparison with populations in which those variables are not clearly identifiable. While some porotic pores may be related to marrow hyperplasia, transcortical circulation may explain the majority.

Cribra orbitalia is correlated with the meningo-orbital foramen and is vascular and developmental in nature.

Cribra orbitalia is a phenomenon with interdisciplinary interest. However, the etiology of cribra orbitalia remains unclear. Recently, the appearance of cribra orbitalia was identified as vascular in nature. This study assessed the relationship between anatomical variation of vasculature, as determined by the presence of meningo-orbital foramina, and the presence of cribra orbitalia in 178 orbits. Cribra orbitalia was identified in 27.5% (49:178) of orbits (22.7%, 35:154 adult orbits and 58.3%, 14:24 subadult orbits) and meningo-orbital foramina were identified in 65.8% (100:152) of orbits. Among the 150 total intact adult orbits (i.e., orbital roof and posterior orbits both intact), cribra orbitalia was found in 35 (23.3%). Of these 35 occurrences of cribra orbitalia, 32 (91.4%) had the concurrent finding of a meningo-orbital foramen. However, in the absence of the meningo-orbital foramen, cribra orbitalia was only found in three sides out of the total sample of intact orbits (3:150; 2.0%). Fisher's exact test revealed that the presence of cribra orbitalia and the meningo-orbital foramen were statistically dependent variables (p = .0002). Visual evidence corroborated statistical findings-vascular impressions joined cribra orbitalia to meningo-orbital foramina. This study identifies that individuals who possess a meningo-orbital foramen are anatomically predisposed to developing cribra orbitalia. Conversely, cribra orbitalia is unlikely to occur in an individual who does not possess a meningo-orbital foramen. Thus, the antecedent of cribra orbitalia is both vascular and developmental in nature. This report represents an important advancement in the understanding of cribra orbitalia-there is an anatomical predisposition to the development of cribra orbitalia.

Dinosaur senescence: a hadrosauroid with age-related diseases brings a new perspective of "old" dinosaurs.

Senile vertebrates are extremely rare in the fossil record, making their recognition difficult. Here we present the largest known representative of the Late Cretaceous hadrosauriform Gobihadros mongoliensis showing features of cessation of growth indicating attainment of the terminal size. Moreover, this is the first non-avian dinosaur with an age-related pathology recognized as primary calcium pyrophosphate deposition disease indicating its advanced age. Because senile dinosaurs are so rare and thus "senescence" in dinosaurs is unclear, we also propose a new unified definition of a senile dinosaur: an individual which achieved the terminal size as revealed by the presence of the external fundamental system and closed transcortical channels, has completely secondary remodeled weight-bearing bones and possesses non-traumatic, non-contagious bone pathologies correlated with advanced age.

Distinguishing between congenital phenomena and traumatic experiences: Osteochondrosis versus osteochondritis.

The current study is to distinguish between osteochondrosis and osteochondritis, utilizing surface microscopy of individuals with documented pathology. Osteochondrosis is associated with smooth borders and gradient from edge to defect base, while osteochondritis and subchondral impaction fractures are associated with subsidence of the affected area of articular surface with irregular edges. The base of osteochondrosis is penetrated by multiple channels, smoothly perforate its surface, indistinguishable from unfused epiphyses, confirming their vascular nature. This study provides a technique for distinguishing osteochondrosis and osteochondritis and further documents of the value of epi-illumination microscopy in expanding our understanding of bone and joint disease.

Cribra orbitalia is a vascular phenomenon unrelated to marrow hyperplasia or anemia: Paradigm shift for cribra orbitalia.

The orbital phenomenon, cribra orbitalia, has long been a source of controversy, especially with regard to its nature, derivation, and relationship to anemia. Therefore, the external surfaces of orbital roofs were systematically examined microscopically in human skulls from historical collections. Superior orbital surfaces of 278 individual crania within the Hamann-Todd collection were assessed at various magnifications using epi-illumination microscopy to identify the presence of cribra orbitalia and characterize its nature. Also, 12 additional individuals with diagnosed anemia in the Hamann-Todd collection were evaluated. Orbital roof alterations, present in one-third of examined crania, had two discrete appearances: Vascular grooves (45%) and application of new bone in a vascular branching pattern on the orbit surface (55%). Porosity of the orbit was not observed. Evaluation of the orbits of 12 individuals with diagnosed anemia revealed one with a single deep defect, suggesting a space-occupying phenomenon, but no evidence of bone accretion, vascular grooves, or porosity. Cribra orbitalia has often been lumped indiscriminately as an indicator of organismal stress, rather than identified as a indicating a specific etiology. Neither that perspective nor porosity are supported by high resolution examination of orbital roof changes. Recognition of the blood vessel imprint pattern falsifies previous speculations and provides a new paradigm. The actual character of cribra orbitalia is documented and new hypotheses generated. While population prevalence of cribra orbitalia seems excessive for explanation on the basis of these hypotheses, the imprints are clearly vascular in origin.

Anatomy of a dinosaur-Clarification of vertebrae in vertebrate anatomy.

The flat-end surfaces of dinosaur vertebral centra led to the presumption that intervertebral discs occupied the space between their vertebrae. A set of fused hadrosaur vertebrae allowed that hypothesis to be tested. The Tyrannosaurus rex responsible for this pathology did not escape unscathed. It left behind a tooth crown that had fractured. Fragments of that tooth were scattered through the intervertebral space, evidencing that there was no solid structure to impede its movement. That eliminates the possibility of an intervertebral disc and instead proves the presence of an articular space, similar to that in modern reptiles, but at variance to what is noted in birds. While avian cervical vertebral centra appear to be separated by diarthrodial joints, the preponderance of their thoracic vertebral centra is not separated by synovial joints.

Suggested Case of Langerhans Cell Histiocytosis in a Cretaceous dinosaur.

Susceptibility to diseases is common to humans and dinosaurs. Since much of the biological history of every living creature is shaped by its diseases, recognizing them in fossilized bone can furnish us with important information on dinosaurs' physiology and anatomy, as well as on their daily activities and surrounding environment. In the present study, we examined the vertebrae of two humans from skeletal collections with Langerhans Cell Histiocytosis (LCH), a benign osteolytic tumor-like disorder involving mainly the skeleton; they were diagnosed in life, along with two hadrosaur vertebrae with an apparent lesion. Macroscopic and microscopic analyses of the hadrosaur vertebrae were compared to human LCH and to other pathologies observed via an extensive pathological survey of a human skeletal collection, as well as a three-dimensional reconstruction of the lesion and its associated blood vessels from a µCT scan. The hadrosaur pathology findings were indistinguishable from those of humans with LCH, supporting that diagnosis. This report suggests that hadrosaurids had suffered from larger variety of pathologies than previously reported. Furthermore, it seems that LCH may be independent of phylogeny.

New tomographic contribution to characterizing mesosaurid congenital scoliosis.

The presence of a pathology in the vertebral column of the early Permian mesosaurid specimen ZPAL R VII/1, being one of the oldest amniotic occurrences of congenital scoliosis caused by a hemivertebra, was recently recognized. Here we provide CT data to further characterize the phenomenon. The affected hemivertebra is wedged (incarcerated) between the preceding and succeeding vertebrae. The neural canal is misshapen but continuous and the number of dorsal ribs on each side of the specimen corresponds with the number of the vertebrae, documenting its congenital (homeobox-related) derivation.

Arthritic lesions and congenital fusion in foot bones of Panochthus sp. (Xenarthra, Cingulata).

A set of lesions are re-described and new pathological findings in foot bones of Panochthus sp. (Xenarthra, Cingulata) are presented. The material reexamined in fact presents enthesiophytes instead of osteoartrithis, as previously interpreted. Furthermore, Calcium Pyrophosphate Deposition Disease (CPPD) was observed, a lesion absent in previous report. CPPD also was found in another set of foot bones and it was associated with a congenital fusion of two sesamoids. The material studied were collected in two natural tank deposits, one in Paraíba (material reexamined) and other in Rio Grande do Norte (new pathological findings) State.

Tuberculosis-like respiratory infection in 245-million-year-old marine reptile suggested by bone pathologies.

An absence of ancient archaeological and palaeontological evidence of pneumonia contrasts with its recognition in the more recent archaeological record. We document an apparent infection-mediated periosteal reaction affecting the dorsal ribs in a Middle Triassic eosauropterygian historically referred to as 'Proneusticosaurus' silesiacus. High-resolution X-ray microtomography and histological studies of the pathologically altered ribs revealed the presence of a continuous solid periosteal reaction with multiple superficial blebs (protrusions) on the visceral surfaces of several ribs. Increased vascularization and uneven lines of arrested growth document that the pathology was the result of a multi-seasonal disease. While visceral surface localization of this periosteal reaction represents the earliest identified evidence for pneumonia, the blebs may have an additional implication: they have only been previously recognized in humans with tuberculosis (TB). Along with this diagnosis is the presence of focal vertebral erosions, parsimoniously compared to vertebral manifestation of TB in humans.