Multilobular tumor of bone arising from the palatomaxillary suture line in the skull of a dog.

A 6-year-old neutered male bloodhound dog was presented for surgical evaluation of an intraoral hard palate mass noted during a routine dental cleaning performed by the primary veterinarian. Computed tomography (CT) of the skull revealed a well-defined, multilobular, mineralized mass with a coarse, granular appearance, centered along the palatomaxillary suture extending into both the nasal and oral cavities. Bilateral caudal maxillectomy was performed for curative-intent resection of the tumor. The histopathology of the mass was consistent with a completely excised palatomaxillary multilobular tumor of bone (MLTB). This is apparently the 1st successful report of surgical excision of an MLTB associated with the palatomaxillary suture line. Key clinical message: Our findings emphasized that MLTB should be considered as a differential diagnosis for masses arising in the location of cranial sutures, and a definitive diagnosis can be made postoperatively with histopathology of the mass.

Tumeur osseuse multi-lobulaire résultant de la ligne de suture palato-maxillaire dans le crâne d'un chien. Un chien Saint-Hubert mâle castré de 6 ans a été présenté pour évaluation chirurgicale d'une masse intrabuccale du palais dur notée lors d'un nettoyage dentaire de routine effectué par le vétérinaire initial. La tomodensitométrie (CT) du crâne a révélé une masse minéralisée multi-lobulaire bien définie avec un aspect grossier et granuleux, centrée le long de la suture palato-maxillaire s'étendant dans les cavités nasale et buccale. Une maxillectomie caudale bilatérale a été réalisée pour une résection à visée curative de la tumeur. L'histopathologie de la masse était compatible avec une tumeur osseuse multi-lobulaire palato-maxillaire complètement excisée (MLTB). Il s'agit apparemment du premier rapport réussi d'excision chirurgicale d'une MLTB associé à la ligne de suture palato-maxillaire.Message clinique clé :Nos résultats ont souligné que la MLTB doit être considérée comme un diagnostic différentiel pour les masses apparaissant à l'emplacement des sutures crâniennes, et un diagnostic définitif peut être posé en postopératoire avec l'histopathologie de la masse.(Traduit par Dr Serge Messier).

Proliferative tenosynovitis in Brazilian Mangalarga Marchador horses.

Proliferative tenosynovitis (PT) is an inflammatory and proliferative disorder of the synovial membrane of the tendon sheath that is rare in animals. The histological alterations are characterized by multinodular neovascularization, with infiltration of histiocytic and multinucleated giant cells and haemosiderin deposition. We reviewed necropsy and biopsy records of horses submitted to the Setor de Anatomia Patológica of the Universidade Federal Rural do Rio de Janeiro from January 2017 to December 2020 to select cases of PT. We identified PT in three adult Brazilian Mangalarga Marchador horses with nodular lesions on the metacarpophalangeal, metatarsophalangeal or carpal joints. The three horses were under 6 years of age and presented with lameness and pain on palpation. There were recurrences in two horses after surgical removal. Radiographic and ultrasound examinations detected masses in the flexor or extensor tendons and subtendinous bursa. Histological study of synovial membrane and tendon sheath revealed an increased number of vessels, fibroplasia, osseous metaplasia and infiltration of lymphocytes, plasma cells and siderophages. This is the first description of PT in horses, which should be included as an orthopaedic differential diagnosis, especially in Mangalarga Marchador horses with lameness.

Canine Idiopathic Arteriopathy, Appendicular Bone Infarcts, and Neoplastic Transformation of Bone Infarcts in 108 Dogs (Canis lupus familiaris).

Osteosarcoma (OSA) is the most common primary bone tumor in both dogs and humans. The dog is an important research model for OSA, yet dogs have much higher prevalence of bone tumors than do humans, a disparity that has yet to be explained. Neoplastic transformation of cells within or adjacent to bone infarcts into primary bone tumors has been described in humans but only sparsely characterized in the veterinary literature. In this study, 653 cases of canine bone infarcts were received through a referral veterinary osteopathology service over a 14-y period. We identified an idiopathic disorder affecting the nutrient artery, termed canine idiopathic arteriopathy (CIA), which to our knowledge has no direct counterpart in human medicine. This disorder was documented alongside ischemic necrosis of the medullary cavity in 114 bone infarcts in 108 dogs. We hypothesize that CIA precipitated an ischemic environment, resulting in development of a bone infarct down- stream of the abnormal artery. In 52% (59 of 114) of cases, bone infarcts demonstrated evidence of repair (termed reparative bone infarcts [RBI]), while in 48% (55 of 114) of infarcts, a bone tumor was also present, including pleomorphic sarcoma, OSA, fibrosarcoma, and chondrosarcoma. In some cases, a spectrum of tumors was present. We hypothesize that the ischemic infarct environment provoked bone marrow mesenchymal stem cells (MSCs) to attempt repair of the stroma, and in approximately half of cases, MSCs underwent neoplastic transformation (BINT) to produce tumors. The most common sites of bone infarcts were the distal femur, distal radius, proximal humerus, and distal tibia, coinciding with common sites of canine OSA. The authors propose that CIA leading to bone infarcts and infarct-derived tumors, in combination with possible underdiagnosis of canine bone infarcts and misdiagnosis of some RBI as neoplasia, may contribute to the higher reported proportion of bone tumors in dogs compared with humans.

Invasive Tendon Sheath Fibrosarcoma Causing Radial Osteolysis in a Golden Retriever.

This case report details a previously undescribed malignancy of the tendon sheath in a golden retriever. This dog originally presented with lameness of the left forelimb, at which point radiographs revealed a monostotic, lytic lesion of the distal radius with overlying soft-tissue swelling. A fine-needle aspirate was performed, and cytology was compatible with a sarcoma, with the primary differential being an osteosarcoma. After amputation, the leg was submitted for histopathology, which revealed inconsistencies with a typical osteosarcoma lesion, including lack of osteoid deposition. Second opinion histopathology showed a fibrosarcoma that appeared to have originated in the tendon sheath of an extensor tendon and then secondarily invaded the radius. At the time of publication, ∼17 mo after amputation, the dog continues to do well without any evidence of recurrent or metastatic disease.

Case Report: Metastatic Parosteal Osteosarcoma in a Dog.

This case report describes a rare form of malignant bone tumor in an 8-year-old Labrador retriever. This dog initially presented for evaluation of a right distal humeral mass. Radiographs of the right elbow and thorax were performed, revealing a smooth mineralized mass adjacent to the lateral aspect of the distal humerus and a 5mm pulmonary nodule. Computed tomography (CT) of the humerus and thorax showed a smooth mineralized lesion adjacent to the lateral humeral epicondyle, and a right cranial lung lobe nodule with a thin mineral rim. Surgical biopsies of both lesions were diagnostic for parosteal osteosarcoma (POSA). The dog was then treated with stereotactic body radiation therapy (SBRT) which controlled the dog's discomfort for 14 months until he became progressively painful and subsequently had his right forelimb amputated. This case report is the first to document the CT imaging characteristics of a metastatic appendicular POSA in a dog and the first dog described with POSA treated with SBRT. The dog lived for 623 days after histopathologic diagnosis and 849 days after initial presentation with pulmonary metastatic disease.

A complex histopathological challenge: suspicion of an osteoblastoma-like osteosarcoma arising from the second thoracic vertebra in a cat.

BACKGROUND: Reports of osteoblastic tumours are limited to a few case reports in veterinary medicine. Osteoblastoma-like osteosarcoma has been accepted by the World Health Organization as an intermediate form between an osteosarcoma and osteoblastoma. This type of tumour indicates an osteosarcoma, that may resemble osteoblastoma clinically, histologically, and radiologically and have the capability for metastasis. Osteoblastoma-like osteosarcoma has not been described in veterinary medicine so far. CASE PRESENTATION: An eight-year old cat was presented due to progressive ataxia and paraparesis of the pelvic limbs. Imaging confirmed a well-defined, extradural mass originating from the spinous process of the second thoracic vertebra (T2) leading to severe compression of the spinal cord. Decompressive cytoreduction was achieved by removal of the mass after dorsal laminectomy of T1. After recovering from an acute worsening 3.5 weeks after surgery, the cat had an improved neurological status and the dorsal compression was resolved at follow-up 8 months later. A focal contrast enhancing lesion was still evident at the base of T2 spinous process and lung metastasis was additionally suspected. Based on histopathological, radiographic, and clinical features, an "osteoblastoma-like osteosarcoma" was suspected. CONCLUSIONS: To the best of our knowledge, this is the first description of this tumour in veterinary medicine. In addition, this case report highlights the difficulty in the diagnosis and definition of osseous neoplasia in cats and provides a literature review.

Idiopathic arteriopathy-induced focal osteonecrosis of the femoral head in a young dog.

CASE DESCRIPTION: A 15-month-old 6.5-kg (14.3-lb) castrated male mixed-breed dog was evaluated because of a 4-month history of progressive intermittent non-weight-bearing lameness of the left pelvic limb. CLINICAL FINDINGS: Orthogonal radiography of the hip joints revealed a 4-mm atypical radiolucent lesion on the distal caudomedial aspect of the left femoral head and a disproportionately large-diameter femoral medullary canal with a low canal flare index. Prolonged unresponsiveness to medical management and progressive enlargement of the lesion prompted the recommendation for total hip replacement (THR). TREATMENT AND OUTCOME: THR was performed to restore pain-free function of the left pelvic limb and normal activity. A circular osteochondral flap was grossly evident on the femoral head. Histopathologic findings for this portion of the bone indicated an arteriopathy-induced focal subchondral osteonecrosis that had resulted in articular surface collapse. The noted idiopathic arteriopathy had disrupted the normal blood supply to the affected area. On reexamination and radiographic evaluation 13 months after THR, the dog appeared to have pain-free function of the affected limb and had returned to normal activity with no reported complications or problems. CLINICAL RELEVANCE: To the authors' knowledge, this report represented the first description of arteriopathy-induced focal osteonecrosis of the caudomedial aspect of the femoral head and its successful treatment in a young dog. This type of lesion may more commonly be the cause of hip joint osteoarthritis in young dogs than previously recognized because establishing a definitive diagnosis requires early recognition and histologic evaluation before advanced degenerative changes develop that obscure the underlying etiology.

Radiographic features of histologically benign bone infarcts and bone infarcts associated with neoplasia in dogs.

OBJECTIVE: To describe the radiographic appearance of benign bone infarcts and bone infarcts associated with neoplasia in dogs and determine the utility of radiography in differentiating benign and malignancy-associated bone infarcts. SAMPLE: 49 dogs with benign (n = 33) or malignancy-associated (16) infarcts involving the appendicular skeleton. PROCEDURES: A retrospective cohort study was performed by searching a referral osteopathology database for cases involving dogs with a histologic diagnosis of bone infarction. Case radiographs were anonymized and reviewed by 2 board-certified veterinary radiologists blinded to the histologic classification. Radiographic features commonly used to differentiate aggressive from nonaggressive osseous lesions were recorded, and reviewers classified each case as likely benign infarct, likely malignancy-associated infarct, or undistinguishable. RESULTS: Only 16 (48%) of the benign infarcts and 6 (38%) of the malignancy-associated infarcts were correctly classified by both reviewers. Medullary lysis pattern and periosteal proliferation pattern were significantly associated with histologic classification. Although all 16 (100%) malignancy-associated lesions had aggressive medullary lysis, 23 of the 33 (70%) benign lesions also did. Eight of the 16 (50%) malignancy-associated infarcts had aggressive periosteal proliferation, compared with 7 of the 33 (21%) benign infarcts. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that radiography was not particularly helpful in distinguishing benign from malignancy-associated bone infarcts in dogs.

Mandibular Ossifying Fibroma and Multiple Oral Papillomas in a Roe Deer (Capreolus capreolus).

An emaciated, adult, free-ranging roe deer (Capreolus capreolus) presenting a large mandibular mass, was shot by a game warden in Sissach, Switzerland. The head of the roe deer was submitted to the Center for Fish and Wildlife Health for examination. Grossly, the mass consisted of a 6 × 7 × 4 cm mandibular exophytic growth, associated with loss of incisors teeth. On cut section, a hard, light-tan core was rimmed by a thick layer of soft tissue. Computed tomography examination confirmed the mandibular origin of the mass. Histologically, the mass consisted of an unencapsulated fibro-osseous neoplasm. The bony portion was composed of multiple haphazardly arranged spicules rimmed by osteoblasts with no associated periosteal layer. Embedding the bony spicules were short anastomosing and branching streams and bundles of spindled cells. The overlaying partially ulcerated mucosa, showed prominent rete ridges deepening into the submucosa. In addition to the mandibular mass, multiple soft cauliflower-like proliferations were expanding from the gingival surface. Histologically, these masses were arranged in papillary elements composed of pluristratified squamous epithelium with long rete ridges extending into a rich underlying fibrovascular supportive stroma. Neither papillomaviral DNA nor antigen could be identified in association with the oral masses. The gross, histological and radiological features of the mandibular mass are consistent with an ossifying fibroma, while the cauliflower oral masses were diagnosed as papillomas.

Multimodal Imaging to Identify and Characterize a P3 Cystic Lesion and Pathologic Fracture.

Lameness remains a common cause of retirement in the equine athlete and among hobby enthusiasts. The distal limb is one of the most frequently imaged areas, and recent advances in diagnostic imaging capabilities help practicing veterinarians differentiate normal variants from informative pathology. Although acute, non-weight-bearing lameness is commonly associated with etiologies, such as fractures, abscesses, and laminitis, other uncommon differentials such as cystic lesions and neoplasia might also be considered. This report describes the characterization of a large, cystic lesion in the third phalanx (P3), which resulted in an acute, pathologic fracture. The lesion was fully characterized with the use of postmortem magnetic resonance imaging, gross pathology, and histopathology.

Characterization of five newly derived canine osteosarcoma cell lines.

BACKGROUND: Canine and human osteosarcomas (OS) are notably similar and have a high rate of metastasis. There is a poor understanding of the tumor development process, predisposing causes, and varying levels of aggression among different cell lines. By characterizing newly developed canine osteosarcoma cell lines, treatments for people and pets can be developed. Of the seven subtypes of OS, three are represented in this group: osteoblastic (the most common), fibroblastic, and giant cell variant. To our knowledge, there are no other giant cell variant canine OS cell lines in the published literature and only one canine fibroblastic osteosarcoma cell line. Understanding the differences between the histologic subtypes in dogs will help to guide comparative research. RESULTS: Alkaline phosphatase expression was ubiquitous in all cell lines tested and invasiveness was variable between the cell lines tested. Invasiveness and oxidative damage were not correlated with in vivo growth rates, where TOT grew the fastest and had the higher percentage of mice with metastatic lesions. TOL was determined to be the most chemo-resistant during cisplatin chemotherapy while TOM was the most chemo-sensitive. CONCLUSIONS: Further comparisons and studies using these cell lines may identify a variety of characteristics valuable for understanding the disease process and developing treatments for osteosarcoma in both species. Some of this data was presented as a poster by KMF at the August 5th, 2017 National Veterinary Scholars Program in Bethesda, MA. Characterization of 5 newly generated canine osteosarcoma cell lines. Kelli Franks, Tasha Miller, Heather Wilson-Robles.

Characterization of bony changes localized to the cervical articular processes in a mixed population of horses.

The objectives of this observational, cross-sectional study were to characterize and establish the prevalence of osseous proliferation of articular surfaces, joint margins and adjacent soft tissue attachments (i.e., joint capsule and deep spinal muscles) in a mixed population of horses of variable ages, sizes, and breeds to better capture the full spectrum of disease affecting the cervical articular processes. Cranial and caudal articular processes of the cervical and first three thoracic vertebrae (C2-T3) from 55 horses without a primary complaint of neck pain were evaluated for the presence and severity of abnormal bony changes. Data were analyzed to compare alterations in joint margin quadrants, paired articular surfaces within a synovial articulation, left-right laterality, and vertebral level distributions and to determine associations with age, wither height and sex. Seventy-two percent of articular processes had bony changes that were considered abnormal. Osteophyte formation was the most common bony change noted. Overall grades of severity included: normal (28%), mild (45%), moderate (22%), and severe (5%). The highest prevalence of mild changes was localized to the C3-C6 vertebral levels; moderate changes to C6-T2; and severe changes to C2-C3 and C6-T2. Most paired articular surfaces and left-right grades of severity were not significantly different. The grade of osseous pathology was positively associated with both age and wither height. A high prevalence and wide variety of abnormal bony changes of varying severity were found in articular processes across all vertebral levels. The clinical significance of the described lesions is unknown, but the findings are expected to enhance the reporting of articular process and periarticular changes noted on advanced diagnostic imaging of the equine cervical and cranial thoracic vertebral regions.

Zygomatic Arch Parosteal Osteosarcoma in Dogs and a Cat.

Parosteal osteosarcoma is a rare, slow-growing tumor most commonly arising from the surface of long bones. Tissue or histological sections from 5 dogs and 1 cat with zygomatic arch masses were examined. Clinical presentations varied from chronic sneezing to facial swelling. Imaging consistently demonstrated osseous proliferation in the area of the zygomatic arch. Histologically, the masses were characterized by well-differentiated fibro-osseous and chondroid components that radiated outward from the periosteum of the zygomatic bone. Cellular atypia and mitotic figures were uncommon. Parosteal osteosarcomas have previously been reported in the skulls of dogs and cats, but only 1 has been reported on the zygomatic arch. Initially, these tumors are of low histologic low grade, but with time, they can show more aggressive behavior and invade the underlying bone.

Sheep embryonic stem-like cells engrafted into sheep femoral condyle osteochondral defects: 4-year follow-up.

BACKGROUND: Articular cartilage lacks a regenerative response. Embryonic stem cells (ESCs) are a source of pluripotent cells for cartilage regeneration. Their use, however, is associated with a risk of teratoma development, which depends on multiple factors including the number of engrafted cells and their degree of histocompatibility with recipients, the immunosuppression of the host and the site of transplantation. Colonies of sheep embryonic stem-like (ES-like) cells from in vitro-produced embryos, positive for stage-specific embryonic antigens (SSEAs), alkaline phosphatase (ALP), Oct 4, Nanog, Sox 2 and Stat 3 gene expression, and forming embryoid bodies, were pooled in groups of two-three, embedded in fibrin glue and engrafted into osteochondral defects in the left medial femoral condyles of 3 allogeneic ewes (ES). Empty defects (ED) and defects filled with cell-free glue (G) in the condyles of the controlateral stifle joint served as controls. After euthanasia at 4 years post-engraftment, the regenerated tissue was evaluated by macroscopic, histological and immunohistochemical (collagen type II) examinations and fluorescent in situ hybridization (FISH) assay to prove the ES-like cells origin of the regenerated tissue. RESULTS: No teratoma occurred in any of the ES samples. No statistically significant macroscopic or histological differences were observed among the 3 treatment groups. FISH was positive in all the 3 ES samples. CONCLUSIONS: This in vivo preclinical study allowed a long-term evaluation of the occurrence of teratoma in non-immunosuppressed allogeneic adult sheep engrafted with allogeneic ES-like cells, supporting the safe and reliable application of ES cells in the clinic.

Multiloculated solitary (unicameral) bone cyst in a young dog.

A 20-month-old female spayed Staffordshire Terrier (22.3 kg) presented to the Orthopedic Surgery Service at North Carolina State University Veterinary Teaching Hospital for evaluation of a 6-week history of toe-touching to nonweight-bearing lameness in the right hind limb. Radiographs of the right stifle revealed a multiloculated lytic lesion of the distal femur, with a large open lytic zone centrally, numerous osseous septations peripherally, and focal areas of cortical thinning and loss. An aspirate of the right distal femoral lesion yielded mildly cloudy serosanguineous fluid. Cytologic examination of the fluid revealed a pleomorphic population of discrete cells that exhibited marked anisocytosis and anisokaryosis and a variable nuclear-to-cytoplasmic (N:C) ratio, which were interpreted as probable neoplastic cells, with few macrophages, and evidence of hemorrhage. Given the clinical signs of pain, lesion size, and concern for malignant neoplasia, amputation of the right hind limb was performed. Histologically, the lesion had undulating walls 1-3 mm thick with a continuous outer layer of dense fibrous tissue and an inner layer composed of reactive cancellous bone with no cortical compacta remaining. Remnants of thin fibrous or fibro-osseous septa projected from the bony wall into the cyst lumen. The final histologic diagnosis was a benign multiloculated solitary (unicameral) bone cyst of the distal right femur. Based on the histopathologic findings, it was speculated that the cells identified on cytology were a mixture of developing osteoclasts, osteoblasts, endothelial, and stromal cells. This is the first report describing the cytologic examination of a solitary bone cyst in veterinary medicine.

Identification of a Candidate Mutation in the COL1A2 Gene of a Chow Chow With Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a genetic disease that occurs in humans and animals. Individuals with OI exhibit signs of extreme bone fragility and osteopenia with frequent fractures and perinatal lethality in severe cases. In this study, we report the clinical diagnosis of OI in a dog and the use of targeted next-generation sequencing to identify a candidate autosomal dominant mutation in the COL1A2 gene. A 5-month-old male Chow Chow was examined with a fractured left humerus and resolving, bilateral femoral fractures. Radiographs revealed generalized osteopenia and bilateral humeral, radial, and femoral fractures. Targeted next-generation sequencing of genes associated with OI in humans (COL1A1, COL1A2, LEPRE1, SERPINH1, and CRTAP) revealed a G>A heterozygous mutation in the splice donor site of exon 18 of the COL1A2 gene (c.936 + 1G>A). The splice donor mutation was not detected among 91 control dogs representing 21 breeds. A comparative analysis of exon 18 and the exon-intron junction further showed that the mutated splice donor site is conserved among vertebrates. Altogether, these findings reveal a candidate autosomal splice donor site mutation causing OI in an individual Chow Chow.

MicroRNA29a Treatment Improves Early Tendon Injury.

Tendon injuries (tendinopathies) are common in human and equine athletes and characterized by dysregulated collagen matrix, resulting in tendon damage. We have previously demonstrated a functional role for microRNA29a (miR29a) as a post-transcriptional regulator of collagen 3 expression in murine and human tendon injury. Given the translational potential, we designed a randomized, blinded trial to evaluate the potential of a miR29a replacement therapy as a therapeutic option to treat tendinopathy in an equine model that closely mimics human disease. Tendon injury was induced in the superficial digital flexor tendon (SDFT) of 17 horses. Tendon lesions were treated 1 week later with an intralesional injection of miR29a or placebo. miR29a treatment reduced collagen 3 transcript levels at week 2, with no significant changes in collagen 1. The relative lesion cross-sectional area was significantly lower in miR29a tendons compared to control tendons. Histology scores were significantly better for miR29a-treated tendons compared to control tendons. These data support the mechanism of microRNA-mediated modulation of early pathophysiologic events that facilitate tissue remodeling in the tendon after injury and provides a strong proof of principle that a locally delivered miR29a therapy improves early tendon healing.