Influence of Microarchitecture on the Mechanical Fatigue Behaviour of Equine Subchondral Bone

Fractures of the equine metacarpophalangeal (MCP) joint are among the most common and fatal injuries experienced by racehorses. These bone injuries are a direct result of repetitive, high intensity loading of the skeleton during racing and training and there is consensus that they represent a mechanical fatigue phenomenon. Existing work has found the fatigue life of bone to be strongly determined by bone microarchitecture and the resulting stressed volume (i.e., the volume of bone stressed above yield). The purpose of this study was to quantify the influence of bone microarchitecture on the mechanical fatigue behaviour of equine subchondral bone from the MCP joint. Forty-eight subchondral bone samples were prepared from the third metacarpal (MC3) and proximal phalanx (P1) and subsequently imaged using high resolution micro-computed tomography (μCT) to quantify microarchitectural features of interest, including bone volume fraction, tissue mineral density, pore size, pore spacing, and pore number. Samples were cyclically loaded in compression to a stress of 70 MPa, and fatigue life was defined as the number of cycles until failure. Finite element models were created from the μCT images and used to quantify the stressed volume. Based on the expected log point-wise predictive density (ELPD), stressed volume was a strong predictor of fatigue life in both the MC3 and P1. Normalized stress (i.e., initial nominal strain) was also a strong predictor of fatigue life in samples from the MC3, but not for samples from the P1. This disparity can be attributed to differences in microstructure homogeneity. A regional analysis indicated fatigue life was more strongly associated with bone volume fraction in the superficial (r2 = 0.32, p < 0.001) and middle (r2 = 0.70, p < 0.001) regions of the subchondral bone, indicating that the cortical plate plays a more prominent role in the fatigue resistance of subchondral bone. By improving our understanding of the variance in fatigue life measurements, this research helps begin to clarify the underlying mechanisms of the mechanical fatigue process and provide a basic understanding of subchondral bone injuries in the equine fetlock joint

EWSR1::POU2AF3(COLCA2) Sarcoma: An Aggressive, Polyphenotypic Sarcoma With a Head and Neck Predilection

EWSR1::POU2AF3: (COLCA2) sarcomas are a recently identified group of undifferentiated round/spindle cell neoplasms with a predilection for the head and neck region. Herein we report our experience with 8 cases, occurring in 5 men and 3 women (age range: 37-74 years; median 60 years). Tumors involved the head/neck (4 cases), and one each the thigh, thoracic wall, fibula and lung. Seven patients received multimodal therapy, one patient was treated only with surgery. Clinical follow-up (8 patients; range 4-122 months; median: 32 months) showed 5 patients with metastases (often multifocal, with a latency ranging from 7-119 months), 3 of them along with local recurrence. The median local recurrence-free and metastasis-free survival rates were 24 months and 29 months, respectively. Of the 8 patients, 1 died of an unknown cause, 4 were alive with metastatic disease, 1 was alive with unresectable local disease and 2 were without disease. The tumors comprised of 2 morphologic subgroups: 1) relatively bland tumors consisting of spindled to stellate cells with varying cellularity and fibromyxoid stroma (2 cases) and 2) overtly malignant tumors comprised of nests of "neuroendocrine-appearing" round cells surrounded by spindled cells (6 cases). Individual cases in the 2 group showed glandular, osteogenic or rhabdomyoblastic differentiation. Immunohistochemical results included: CD56 (4/4 cases), GFAP (5/8) SATB2 (4/6), keratin (AE1/AE3) (5/8) and S100 protein (4/7). RNA sequencing identified EWSR1:: POU2AF3 gene fusion in all cases. EWSR1 gene rearrangement was confirmed by FISH in 5 cases. Our findings confirm the head/neck predilection and aggressive clinical behavior of EWSR1::POU2AF3 sarcomas, and widen the morphologic spectrum of these rare lesions to include relatively bland spindle cell tumors and tumors with divergent differentiation