Understanding diseases that affected dinosaurs may shed additional light on their biology, daily living, and the environments in which they thrived. Despite the huge time gap between dinosaurs and humans, both were susceptible to diseases that shaped and greatly affected their evolutionary history. Thus, recognition of skeletal manifestations of specific diseases in humans may assist in identifying them in dinosaurs as well. For example, gout was recognized in tyrannosaurids1, osteoarthritis in Iguanodon2, and diffuse idiopathic skeletal hyperostosis (DISH) in Apatosaurus3. Neoplasms (cancer), albeit more difficult to diagnose (several misclassified cases were published in the past years), have also been identified in dinosaurs4,5. Disease occurrence in dinosaurs is very infrequent. When present, however, it can tell us about dinosaurs’ immune systems, metabolic disorders, growth and adaptation to a huge body mass, infections, environment, as well as shed light on their mating patterns and hunting techniques.

Herbivorous hadrosaurs, also referred to as “duck-billed” dinosaurs, have a near-global Late Cretaceous fossil record. They reached a length of over ten meters, weighed several tons, and appear to have lived in large herds. They are particularly well-known in southern Alberta, Canada where individual bones and teeth occur in abundance. In addition, several dozen hadrosaur-dominated bonebeds and hundreds of partial-to-complete skeletons have been discovered. In Dinosaur Provincial Park, examples of hadrosaur osteopathy are so common that more than half a dozen examples can be found daily by an experienced field worker. A number of hadrosaur taxa are known from the Park: the cranially uncrested Gryposaurus and Prosaurolophus as well as the crested Corythosaurus and Lambeosaurus are the most common. Trauma, in the form of healing caudal vertebrae (centrum and/or neural spinal crush fractures, related to intraspecific trampling), rib fractures, and osteochondrosis of the pedal phalanges, predominate. Fusions of dorsal and caudal vertebrae are also known to occur. A literature review of the entire Hadrosauridae family appears in Tanke and Rothschild6, with reviews and specific case studies of Albertan material appearing in Rothschild and Tanke7, Straight et al.8, Tanke and Rothschild7, and Tumarkin et al.9. Other Albertan hadrosaur-centric studies are currently underway.

Langerhans Cell Histiocytosis (LCH) is a benign osteolytic tumor-like bone lesion that is commonly manifested in the skeletal system in either a unifocal or multifocal form10,11; it is the most common of the non-infectious granulomatous bone disorders12,13. Histiocytosis is the clonal result of neoplastic mutation and proliferation of hematopoietic stem cell precursors of tissue-resident mononuclear phagocytes (histiocytes) or of precursor dendritic cells14,15,16,17. Mononuclear phagocytes can be divided into two groups: a monocyte-macrophage group (Erdheim-Chester disease), and a Langerhans (dendritic) cell group18,19,20. The latter group normally functions as antigen processors in the immune system. Since Erdheim-Chester disease produces osteosclerotic lesions21, in contrast to the lytic lesions of LCH, it will not be further discussed here.

The most common form of LCH, eosinophilic granuloma, is an isolated bone lesion, most commonly afflicting children and adolescents (between ages 5 and 10), with a slight bias toward males12,22,23. Two other syndromes, which are considered as the same disease, yet are less common (up to 20% of cases in children), are the Hand–Schuller–Christian and the Letterer–Siwe diseases. The first includes skull lesions, exophthalmos, and diabetes insipidus; the second includes disseminated lesions involving multiple visceral organs13,23.

Although LCH was first described in humans by Thomas Smith in 1865, its etiology and pathophysiology have been debated for many years12,13. Some consider it a disorder of the immune system (since myeloid cell line-derived and modulated immunological reactions exist), possibly of viral and other infectious causes (although no pathogen was isolated), or a neoplasia, after identifying clonal proliferation of cells and after its response to chemotherapeutic treatment24,25,26,27. Advancements in sequencing technology enabled the pathophysiology of LCH to be identified and revealed its association with a genetic mutation (mainly in BRAF or MAP2K1 genes), resulting in MAPK hyperactivation of myeloid precursor cells28 (and references therein).

LCH usually appears in the skull, followed by the femur, mandible, pelvis, spine, and ribs. Radiological features of the lesion vary between skeletal parts. For example, in the skull, it appears as a solitary or multiple punched-out lytic lesion without a sclerotic rim, whereas long bones exhibit endosteal scalloping and periosteal reaction. Spinal eosinophilic granuloma accounts for 6.5% to 25% of all skeletal LCH cases29,30. It usually appears as a solitary lesion involving the vertebral bodies of the thoracic vertebrae, followed by the lumbar and cervical regions of the spine22,31,32,33,34. LCH clinical manifestation varies: it can be asymptomatic and discovered as an incidental radiographic finding, or it can be symptomatic with pain, swelling, and tenderness around the lesion. The most common symptoms include neck or back pain, restricted motion of the spine, neurologic symptoms, and deformity11. Differential diagnosis includes Ewing sarcoma, osteomyelitis, metastases, round cell tumor, lymphoma, and leukemia23.

Recognition of disease in the fossil record is challenging. Although patterns of disease have proven diagnostic (at least when applied to skeletal populations)35, examination of isolated elements usually does not allow discrimination, and diagnosis of lytic lesions has been especially problematic36,37. Nevertheless, some diseases have reproducible differences in skeletal expression, e.g., metastatic cancer, tuberculosis, fungal disease, and as those documented in the current study, which enable distinguishing between them4,35,38. All forms of LCH in clinical cases are diagnosed through bone marrow aspirates or biopsies of lesions. The samples obtained are then tested for the presence of the Langerhans cell phenotype, using immune-histochemical staining or electron microscopy10,23. Unfortunately, loss of soft tissues through taphonomic processes in the dinosaurs and through defleshing processes in recent humans precluded applying such immunohistologic methodology at this time, since pertinent soft tissues (e.g., dendritic cells) are usually not preserved39.

Non-infectious granulomatous bone disorders have rarely been mentioned as a possibility in the anthropological literature27,40,41,42,43. The absence of previous reports of non-infectious granulomatous bone disorders in the fossil record may be related to difficulties in distinguishing these disorders from other bone tumors due to meager detailed macroscopic descriptions44 as the differences between the various lesions are below the resolution of routine radiological techniques, e.g., plain radiographs and CT35. Therefore, systematic surveys of skeletal collections for pathologies whose clinical records are available enables recognizing the apparent uniqueness of lesions and tumors such as granulomatous diseases, and creates a standard for their identification in the archaeological and paleontological records.

A search for pathologies in paleontological skeletal collections revealed unique lesions in a hadrosaur, which differed in character from what we had previously observed in individuals (both human and non-human) with cancer and bone tumors35,45. However, these lesions were indistinguishable from those noted in a human with clinically documented LCH.

The aim of the current study was to provide the most reasonable diagnosis for the lesions observed in the hadrosaur vertebrae, considering diagnostic criteria based on a systematic pathological survey of the Terry skeletal collection.