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. 2019 Feb 7;5(3):425–426. doi: 10.1001/jamaoncol.2018.6766

Triassic Cancer—Osteosarcoma in a 240-Million-Year-Old Stem-Turtle

Yara Haridy 1,, Florian Witzmann 1, Patrick Asbach 2, Rainer R Schoch 3, Nadia Fröbisch 1, Bruce M Rothschild 4
PMCID: PMC6439844  PMID: 30730547

Abstract

This case study documents osteosarcoma in 240-million-year-old stem-turtle, which suggests that cancer is not a modern physiological defect.


Paleopathology, the study of ancient disease, is a vital way by which we understand the evolution of pathogens, immune systems, healing physiology, and ultimately the environment. Cancer research has focused on its prevalence in various organisms and has found that although some animals have a high propensity for cancer,1 others seem to be resistant.2 The prevalence of cancer in the tree of life is certainly interesting, but its antiquity should be regarded with equal interest considering the increase in human cancer, which has been related to environmental and genetic changes, and the extreme rarity of cancer in the fossil record.3 This study documents bone cancer in a 240-million-year-old reptilian amniote from the Triassic period, which adds an important data point to the history of cancer in tetrapod evolution. Herein, we present a case study of an osteosarcoma, a highly malignant bone tumor, on the femur of the shell-less stem-turtle Pappochelys rosinae4 (Figure 1) from the middle Triassic period of present-day Germany. The appearance of the tumor on this specimen conforms with present-day periosteal osteosarcoma in humans.

Figure 1. Morphology of Osteosarcoma on Fossil Stem-Turtle Femur.

Figure 1.

A micro-computed tomography scan shows the undisturbed cortical bone and the extent of the periosteal mass (circled area). CB indicates cortical bone; OS, osteosarcoma; SP, spicular outgrowth. The black scale bar represents 1 cm.

Methods

The specimen described herein consists of an isolated, left femur collected in 2013 in southwestern Germany and is curated at the Staatliches Museum für Naturkunde, Stuttgart, Germany, under inventory number SMNS 91680. This specimen was macroscopically investigated at the Museum für Naturkunde Berlin using a Wild M3C stereo binocular microscope, and a micro-computed tomography (CT) scan was performed using a GE Phoenix nanotom scanner. The resulting 3-dimensional volumes were analyzed using the visualization software Volume Graphics Studio MAX 2.2. Institutional review board approval was waived because no live animals were used.

Results

The virtual sections produced by the micro-CT scans allow the delineation of the compact cortex and the interior cancellous bone and facilitate a detailed analysis of the mass in the femur (Figure 2). The most affected region of the femur is the dorsal side of its proximal half. In the transverse section, the original dense cortical bone is easily distinguishable from the overlying mass (Figure 2B and C). The original compact bone is not resorbed or disturbed, the medullary cavity is not penetrated at any point along the shaft, and there are no penetrating lesions, canals, or foramina present.

Figure 2. Micro-computed Tomography (CT) Virtual Thin Sections of Osteosarcoma on Triassic Stem-Turtle Femur.

Figure 2.

A, The red lines represent the locations of the thin sections shown in panels B and C. The white scale bars on panels B and C represent 1 mm. CB indicates cortical bone; MC, medullary cavity; OS, osteosarcoma.

Discussion

Owing to the fossilized nature of the specimen, the mass on the femur is diagnosed as a periosteal osteosarcoma based on the following radiomorphological observations5: (1) broad-based attachment of the mass to the entirely contiguous cortical bone (ruling out exostosis6); (2) spicular outgrowths from the cortex to the exterior of the mass (ruling out osteoma and ossifying fibroma); (3) lack of medullary involvement; (4) absence of large lytic lesions or effect on the native cortex; and (5) the rugose, pocked external texture of the mass. Osteosarcoma types are dependent on degree of differentiation, location within the bone, and histological features.5 Although a parostotic osteosarcoma has been reported in an Early Triassic amphibian,6 the periosteal osteosarcoma in a Middle Triassic stem-turtle described herein is, to our knowledge, the oldest instance of bone cancer in an amniote. As is common in paleopathology, this study is limited by the lack of histopathological confirmation because soft tissues are not preserved; therefore, tumor-specific staining is impossible. Thus, the fossil record is biased toward hard tissues, which is the only way to understand the occurrence of disease in deep time.

This study provides evidence that unregulated neoplastic cell growth occurred as early as the Triassic period and that cancer is not a modern physiological defect but rather a vulnerability that is rooted deep in vertebrate evolutionary history.

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