Ameloblastic fibroma (AF) and ameloblastic fibro-odontoma (AFO) are mixed odontogenic tumors (odontogenic tumors with induction) that are reported only rarely in dogs. These tumors are histologically complex and, to a degree, recapitulate the early stages of tooth development, comprising 2 types of tissue: neoplastic odontogenic epithelium, and induced ectomesenchyme (dental pulp). AFOs are distinguished from AFs by the additional presence of hard dental matrices such as dentin. Herein, we describe the key diagnostic features of AF and AFO in 4 young dogs.

Ossifying fibroma of the craniofacial bones is a fibro-osseous lesion characterized by varied patterns of bone formation in a fibroblastic stroma. Ossifying fibroma is a putatively benign lesion with no reports of malignant transformation or metastasis. Differentiation from other fibro-osseous lesions can be challenging necessitating synthesis of clinical, radiological and pathological findings. The molecular pathogenesis of ossifying fibroma is poorly understood but recent studies have reported MDM2 gene amplification and chromosomal copy number changes in a subset of ossifying fibromas. MDM2 amplification in ossifying fibroma, if true, presents a diagnostic problem because this genetic event, at least among craniofacial fibro-osseous lesions, was previously considered specific for low-grade osteosarcoma. In the present study, we investigated the utility of MDM2 and CDK4 immunohistochemistry, and fluorescence in situ hybridization for MDM2 gene amplification, in the diagnosis of 44 craniofacial bone ossifying fibromas. Focal MDM2 and CDK4 nuclear immunoreactivity was found in 11 and 1 ossifying fibromas, respectively, but none demonstrated MDM2 amplification by fluorescence in situ hybridization. A single tumor displayed MDM2 amplification without nuclear immunoreactivity to either MDM2 or CDK4. Our data suggest that while focal MDM2 and CDK4 nuclear expression may be detected in a minority of ossifying fibromas, this expression does not correlate with MDM2 amplification. In addition, MDM2 amplification is extremely rare in ossifying fibroma so the detection of this genetic abnormality should continue to raise concern for osteosarcoma.

Objective

Determine the prevalence, types, and geographical distribution of oral tumors in dogs in Switzerland to provide insights into demographics, tumor characteristics, and trends.

Methods

The medical and pathology records of dogs diagnosed with oral tumors from 2012 to 2022 were sourced from diagnostic laboratories in Switzerland. The focus was on histopathologically confirmed oral neoplasms. Inflammatory, viral, and cystic lesions were excluded. Geographic trends were analyzed by use of postal addresses, revealing local distributions.

Results

Of the 948 reports, 773 cases fulfilled the study's criteria. Benign tumors constituted 63% (487 of 773), with peripheral odontogenic fibroma being the most common (77.8% [379 of 487]). Among the malignant tumors, malignant melanoma was the most frequent (38.1% [109 of 286]), followed by squamous cell carcinoma (21% [60 of 286]) and fibrosarcoma (8% [23 of 286]). The locations of tumors varied, with a higher prevalence of malignant melanoma on the lips. Histopathologic findings indicated ulceration and necrosis were more common in malignant tumors. Significant differences were noted in the mitotic index between benign and malignant groups. No tumor predisposition was noted for any breed. Oral tumors were prevalent in older dogs (median age, 9.4 years).

Conclusions

The findings highlighted the predominance of benign tumors in dogs in Switzerland, with specific histopathologic features distinguishing benign from malignant cases.

Clinical relevance

Understanding the prevalence, types, and geographic distribution of oral tumors based on the representation in dogs in Switzerland may aid in early detection, appropriate diagnostic workup, and informed treatment planning for oral tumors in dogs.

BACKGROUND: Ossifying fibroma (OF) of the craniofacial skeleton is a fibro-osseous lesion characterized by various patterns of bone formation in a cellular fibroblastic stroma. The molecular landscape of OF remains mostly unknown. There are a few known pathogenic abnormalities in OF, including HRPT2 mutations in conventional OF and SATB2 translocations in juvenile psammomatoid OF. On the other hand, conflicting reports exist regarding MDM2 gene amplification and chromosomal copy number alterations (CNA) in OF. METHODS: Surgically removed biopsies and curettage specimens from OF patients were obtained. Clinical, radiographic, and pathologic features of tumors were reviewed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded blocks of tumor tissue. Capture-based DNA next-generation sequencing targeting the coding regions 529 cancer genes and select introns was performed. RESULTS: We identified 17 OF cases from 8 male and 8 female patients with mean age of 22 years (range 1-58 years). Nine case occurred in the gnathic bones and 8 in the extragnathic craniofacial bones. These cases included 3 juvenile psammomatoid OF, 6 conventional OF and 8 juvenile trabecular OF. Large-scale CNAs were present in 6 of 17 cases. Seven cases (41%) had focal amplifications including FOSB (n = 2, 11%), FOS (n = 4, 23%), COL1A1 (n = 4, 23%) and TBX3 (n = 5, 29%). Three cases (17%) had pathogenic CDC73 mutations. No cases showed focal MDM2 amplification. CONCLUSIONS: Here, we provided a comprehensive molecular characterization of OF that reveals a heterogeneous genetic profile with occasional large-scale CNAs (n = 6, 35%). FOS, FOSB, and TBX3 genes that regulate AP-1 transcriptional complex are frequently altered in OF (n = 7, 41%), chiefly in juvenile trabecular OF. These genes encode transcription factors that act as downstream effectors of the MAP kinase signaling pathway. MDM2 amplification is an exceedingly rare event in OF, if present at all, so identification of this event should continue to raise concern for low-grade gnathic osteosarcoma. In summary, our findings suggest that OF represents a heterogeneous group of tumors at the genetic level but dysregulation of the AP-1 pathway may play a role in pathogenesis of juvenile trabecular OF.

Oral focal mucinosis is a rare condition, clinically characterized by an asymptomatic swelling, without distinct, specific features, which occurs predominantly in adults of the female gender. Its clinical aspect leads to various differential diagnoses, and final diagnosis is only possible by means of histopathological exam, in which a well-delimited myxomatous area containing mucinous material is observed. In the present study, a review of the English-language literature about the lesion, was conducted, covering the period from 1974 to March 2015. We report two new cases, thereby contributing to the knowledge and differential diagnosis of this entity.

The canonical Wnt/β-catenin pathway is involved in the formation of craniofacial skeleton and oral tissues. Aberrant nuclear localization of β-catenin protein has been described in several human diseases including a subset of odontogenic tumors thereby suggesting an important role in tumor development. Fibro-osseous lesions of the craniofacial skeleton comprise several neoplastic, and reactive mesenchymal proliferations in which β-catenin status is unknown. To study this, we immunostained 171 fibro-osseous lesions for β-catenin protein and, for lesions with nuclear positivity, sequenced exon 3 of the CTNNB1 gene and exon 15 of the APC gene. Nuclear β-catenin immunostaining was detected in 34 (20 %) tumors with no correlation between nuclear positivity and either age, gender, or tissue decalcification status (p = 0.2, 0.17, 0.12, respectively). Absent nuclear β-catenin in fibrous dysplasia was the only diagnostically significant finding (p = 0.0034). A single point mutation at Asp56 of CTNNB1 was identified in one case of ossifying fibroma. A second ossifying fibroma and one desmoplastic fibroma demonstrated point mutations (Glu1317 and Glu1536, respectively [corrected] ) in the APC gene. These findings show that apart from fibrous dysplasia where nuclear β-catenin is rare, nuclear β-catenin staining has limited utility in discriminating among the craniofacial fibro-osseous lesions. The molecular mechanisms underlying nuclear β-catenin accumulation in the positive tumors is unlikely to be mediated by CTNNB1 exon 3 or APC exon 15 mutations in most cases.

Optical spectroscopy devices are being developed and tested for the screening and diagnosis of oral precancer and cancer lesions. This study reports a device that uses white light for detection of suspicious lesions and green-amber light at 545 nm that detect tissue vascularity on patients with several suspicious oral lesions. The clinical grading of vascularity was compared to the histological grading of the biopsied lesions using specific biomarkers. Such a device, in the hands of dentists and other health professionals, could greatly increase the number of oral cancerous lesions detected in early phase. The purpose of this study is to correlate the clinical grading of tissue vascularity in several oral suspicious lesions using the Identafi(®) system with the histological grading of the biopsied lesions using specific vascular markers. Twenty-one patients with various oral lesions were enrolled in the study. The lesions were visualized using Identafi(®) device with white light illumination, followed by visualization of tissue autofluorescence and tissue reflectance. Tissue biopsied was obtained from the all lesions and both histopathological and immunohistochemical studies using a vascular endothelial biomarker (CD34) were performed on these tissue samples. The clinical vascular grading using the green-amber light at 545 nm and the expression pattern and intensity of staining for CD34 in the different biopsies varied depending on lesions, grading ranged from 1 to 3. The increase in vascularity was observed in abnormal tissues when compared to normal mucosa, but this increase was not limited to carcinoma only as hyperkeratosis and other oral diseases, such as lichen planus, also showed increase in vascularity. Optical spectroscopy is a promising technology for the detection of oral mucosal abnormalities; however, further investigations with a larger population group is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant lesions.

Objective

Determine locoregional diagnostic yield of 4-site screening (head, neck, chest, and abdomen) to diagnose metastatic disease or clinically significant comorbid diseases in dogs with oral cancer.

Animals

381 dogs with histologically confirmed oral tumors.

Methods

Medical records from 381 dogs with histologically confirmed oral tumors that underwent preoperative screening were retrospectively reviewed.

Results

Skull and neck CT scan was performed on 348 patients. Bone lysis was present in 74.4% of tumors. Oral squamous cell carcinoma, sarcomas, and T2-T3 (> 2 cm) tumors had a significantly (P < .05) increased incidence of lysis compared to odontogenic and T1 (< 2 cm) tumors, respectively. Minor incidental findings were present in 60.6% of CT scans. Major incidental findings were found in 4.6% of scans. The risk of diagnosing an incidental finding increased by 10% and 20% per year of age for minor and major findings, respectively. Lymph node metastasis was diagnosed with CT or cytology in 7.5% of cases (10.7% of nonodontogenic tumors, 0% of odontogenic tumors). Oral malignant melanoma, oral squamous cell carcinoma, and T3 tumors had the highest prevalence of metastatic disease at the time of staging. The presence of bone lysis was not associated with cervical metastasis.

Clinical relevance

Major incidental findings were rare (< 5%) but primarily included secondary extraoral tumors. Lymphatic metastasis was diagnosed in 10.7% of nonodontogenic tumors, but cytology was not performed in the majority of cases and often included only a single mandibular node. Therefore, these results likely underestimate the incidence of lymphatic metastasis. Guided lymph node sampling is highly recommended, especially for oral malignant melanoma, squamous cell carcinoma, and T2-T3 tumors.

Objective

Determine diagnostic yield of chest, abdomen, and 4-site screening to diagnose metastatic disease and secondary diseases of prognostic significance in dogs with oral cancer.

Sample

Medical records from 381 dogs with histologically confirmed oral tumors that underwent preoperative screening were retrospectively reviewed.

Results

Thoracic metastasis was diagnosed in 4.9% (0.9% odontogenic, 6.5% nonodontogenic) of oral tumors. Oral malignant melanoma and multilobular osteochondrosarcoma were most at risk. Abdominal metastasis was diagnosed in 2% of oral tumors (0% odontogenic, 3.1% nonodontogenic) and cytologically confirmed in 2 cases (0.6% [2/295)] of all abdominal ultrasounds (AUS) 5.5% [2/36] of all AUS that had cytology). Both cases had oral malignant melanoma. Incidental disease was diagnosed in 53.1% and 81.3% of thoracic and abdominal screenings, respectively. Major findings were more common in AUS (7.8%) compared to thoracic screening (1.9%). The prevalence of incidental findings was similar for odontogenic and nonodontogenic tumors. Both metastasis and major findings were diagnosed more commonly with thoracic CT compared to radiographs. Metastasis or a major finding of prognostic significance was diagnosed in at least 1 test in 27.8% of patients that had head CT, lymph node cytology, thoracic screening, and AUS (n = 115).

Clinical relevance

Major incidental findings were more commonly detected with AUS and were diagnosed in 1 in every 12 patients. However, metastatic disease was most commonly detected with thoracic screening. When all 4 screening tests are performed, there is an approximately 1 in 4 chance of diagnosing metastasis or major significant disease regardless of tumor type.