Sublingual papillomas of cheetahs in southern Africa.

Nine distinct papillomaviruses (Lambdapapillomavirus) have been described in domestic and nondomestic cats, but not in cheetahs. These viruses have been associated with cutaneous papillomas or plaques, bowenoid in situ carcinomas, feline cutaneous squamous cell carcinomas (SCC), feline sarcoids, and oral (often sublingual) papillomas. Fourteen cheetahs from the AfriCat foundation (Namibia) and one from the Ann van Dyk Cheetah center (South Africa) presented with sublingual lesions reminiscent of sublingual papillomas. Two animals were biopsied and the histopathology revealed benign proliferative epithelial lesions with prominent thickening of the overlying squamous epithelium. Throughout the squamous epithelial layers were cells with nuclear enlargement, irregularity of the nuclear membranes and cell contours, focal hyperchromasia of the nuclei, and perinuclear halos, reminiscent of a virus-associated process as seen in papillomavirus infections. Thirteen more cheetahs were sampled and the tissue snap frozen for molecular characterization. Amplification and sequencing of the papillomavirus L1, E6, E7, and E1 gene regions was achieved with modified primers. Maximum likelihood phylogenetic analyses revealed all 15 cheetah papilloma samples were 99.99% genetically similar and closely related to, but genetically distinct from any known felinepapillomaviruses. All cheetahs were FIV and FeLV negative. The results suggest the samples identified in this study can be considered a previously undescribed or novel feline papillomavirus and the authors propose "Acinonyx jubatus papillomavirus type 1" (AjPV-1), within the Lambdapapillomavirus 1 genus (Family: Papillomaviridae).

Focal Palatitis (Previously Focal Palatine Erosions) in Captive Cheetahs (Acinonyx jubatus).

Focal palatine erosion (FPE) is a misleading term that is used in the literature to describe inflammatory lesions associated with depressions of the palatal mucosa in cheetah. Cheetahs have large cheek teeth and these depressions are formed to accommodate them. Previously FPE was only described as a mandibular molar tooth malocclusion on the hard palate due to suspected rotation and super eruption of the mandibular molar teeth of cheetahs aged 18 months and older. Two hundred and fifty six cheetahs (135 male, 121 female), originating from two independent facilities, had their oral cavities evaluated as part of an annual health visit over a decade. Ninety-nine cheetahs were seen once, 59 cheetahs were seen twice, 33 were seen three times, 43 on four occasions, 16 on five occasions, 5 on six occasions, and 1 cheetah was seen seven times. Apart from these clinical cases a prospective study on 5 cheetah cubs (3 male and 2 female) was conducted to document their skull development and mandibular molar tooth eruption over a period of 25 months. Of the 261 cheetahs observed none developed rotation or super eruption of their mandibular molar teeth. The term FPE is a misnomer as these inflammatory lesions were found in palatal depressions opposing any of the cusps of all of the cheetah mandibular cheek teeth. It consisted mainly of deep ulcerations, inflammation and oedema and also micro abscess formation. In severe cases oro-nasal fistulas were present. Of all the depressions present on the cheetah's palate, the large one palatal to the 4th maxillary premolar tooth was most commonly affected. In the five cubs evaluated prospectively, focal palatitis was evident from the 7 month evaluation, before all the permanent teeth erupted. Conservative treatment of the inflamed depressions by removing the foreign material through curettage and copious flushing reduced the grade of the inflammation when observed on follow-up. Focal palatine erosion is an incorrect term used to describe focal palatitis that occurs randomly in cheetahs. This focal palatitis is often associated with foreign material trapped in the palatal depressions. Conservative management is sufficient to treat these animals without odontoplasties.

Dental Pathology in a Wild Serval (Leptailurus serval) Population.

Members of the family Felidae suffer from a wide range of dental, oral and maxillofacial conditions that can cause significant morbidity and mortality. Although many dental, oral and maxillofacial anomalies of the domestic cat (Felis catus) also occur in wild felines, we could find no investigations of these conditions in servals (Leptailurus serval). The objective of this study was to describe the dental, oral and maxillofacial pathology of a wild serval population in South Africa. Detailed extraoral and intraoral examinations and full-mouth dental radiographs on 30 wild servals revealed 14 different dental conditions but no other oral or maxillofacial pathology.

Data Set for the Reporting of Oral Cavity Carcinomas: Explanations and Recommendations of the Guidelines From the International Collaboration of Cancer Reporting.

The International Collaboration on Cancer Reporting is a nonprofit organization whose goal is to develop evidence-based, internationally agreed-upon standardized data sets for each cancer site for use throughout the world. Providing global standardization of pathology tumor classification, staging, and other reporting elements will lead to the objective of improved patient management and enhanced epidemiologic research. Carcinomas of the oral cavity continue to represent a significant oncologic management burden, especially as changes in alcohol and tobacco use on a global scale contribute to tumor development. Separation of oral cavity carcinomas from oropharyngeal tumors is also important, as management and outcome are quite different when human papillomavirus association is taken into consideration. Topics such as tumor thickness versus depth of invasion, pattern of invasive front, extent and size of perineural invasion, and margin assessment all contribute to accurate classification and staging of tumors. This review focuses on the data set developed for Carcinomas of the Oral Cavity Histopathology Reporting Guide, with discussion of the key elements developed for inclusion.

Cancer Stem Cells in Head and Neck Carcinomas: Identification and Possible Therapeutic Implications.

The recurrence and/or lack of response of certain tumors to radio- and chemotherapy has been attributed to a small subpopulation of cells termed cancer stem cells (CSCs). CSCs have been identified in many tumors (including solid and hematological tumors). CSCs are characterized by their capacity for self-renewal, their ability to introduce heterogeneity within a tumor mass and its metastases, genomic instability, and their insensitivity to both radiation and chemotherapy. The latter highlights the clinical importance of studying this subpopulation since their resistance to traditional treatments may lead to metastatic disease and/or tumor relapse. Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common malignancy worldwide with the highest incidence occurring in East Asia and eastern and southern Africa. Several cellular subpopulations believed to have CSC properties have been isolated from HNSCCs, but at present, identification and characterization of CSCs remains an experimental challenge with no established or standardized protocols in place to confirm their identity. In this review we discuss current approaches to the study of CSCs with a focus on HNSCCs, particularly in the context of what this might mean from a therapeutic perspective.

Osseous Dysplasia with Gross Jaw Expansion: A Review of 18 Lesions.

Fourteen cases with 18 grossly expansive lesions diagnosed over a period of 15 years as either "familial gigantiform cementoma" or "osseous dysplasia with jaw expansion" in an African population sample were reviewed. Eight lesions occurred in the anterior mandible, the maxilla was affected by four, three patients presented with more than one lesion and the most common associated pathologies were tooth displacement, conventional non expanding florid osseous dysplasia and simple bone cyst. No history of similar lesions in relatives of the diseased were recorded. The radiolucent fibrous component contained globular bone deposits and cellular osteoid with trabecular differentiation which matured into radiodense mineralized masses. Resorption of the cellular bone created cavities which are proposed to represent the early stage of simple bone cyst formation. It is recommended that "expansive osseous dysplasia" replace the out-dated term "familial gigantiform cementoma". The differential diagnoses of expansive osseous dysplasias are discussed.

A novel technique for ventral orbital stabilization: the masseter muscle flap.

Loss of the caudal maxilla and ventral orbit after tumor resections can have negative functional and esthetic influences on the eye involved. This article reports on a case of a caudal maxillary acanthomatous ameloblastoma involving the ventral orbit that was resected and stabilized with a masseter muscle flap. The masseter muscle flap was generated from the superficial belly of the masseter muscle in order to close a defect in the orbital rim, created by a caudal maxillectomy. None of the published complications such as enophthalmos, excessive lacrimation, globe deviation, or strabismus were noted, 8 months following the procedure. The only clinical sign present at the time of re-evaluation was mild lacrimation. The authors propose the use of a masseter muscle flap as a viable technique in stabilizing the ventral orbit after caudal maxillectomy and ventral orbitectomy, preventing the complications associated with this surgery.

Dominant genetic aberrations and coexistent EBV infection in HIV-related oral plasmablastic lymphomas.

We present common cytogenetic features in the largest cohort of plasmablastic lymphoma (PBL) of the oral cavity published to date. This cohort included 45 patients, 32 of whom had a known HIV status, of which 31 were HIV positive. Ninety eight per cent of all PBL cases were known to be EBV positive. In line with previous studies, we found that rearrangements of the MYC gene was the most common genetic abnormality seen in 60% of cases with the immunoglobulin heavy chain (IGH) locus as a partner in 51% of cases. Additional complex genetic aberrations were frequent, in particular, an increased copy number of the CCND1 gene was seen in 41% of cases with true amplification of CCND1 in 15% of cases. Aneuploidy was also observed for the BCL6 gene in 28% of cases. Interestingly, rearrangements of both IGH genes were detected in 16% of cases with t(14;18) and t(11;14) respectively involved in conjunction with a t(8;14) in two cases. These bi-allelic IGH rearrangements have not been described before in oral PBL. Our results reinforce the notion that EBV infection and MYC rearrangements are important events in the pathogenesis of oral PBL. The genetic diversity and complexity observed in these cases, underlines the importance to genetically characterise PBL patients at presentation as this may inform the choice of more effective treatment modalities.

Plasmablastic lymphomas with light chain restriction - plasmablastic extramedullary plasmacytomas?

BACKGROUND: It is diagnostically difficult to differentiate plasmablastic lymphomas (PBLs) from plasma cell neoplasms with plasmablastic differentiation. Plasmablastic lymphomas are currently classified as 'PBL of the oral mucosa' and 'PBL with plasmacytic differentiation'. METHODS: Forty-five cases of PBL were retrieved from the Departments of Oral Pathology of the Universities of Pretoria and Limpopo, South Africa. Clinical features and HIV status were recorded and each case was classified as 'PBL of the oral mucosa type' or as 'PBL with plasmacytic differentiation'. Immunohistochemistry included: CD45, CD3, CD20, CD79a, CD38, CD138, MUM1, Ki-67 and kappa and lambda light chains. Positivity was recorded based on the percentage of positive staining cells as focal (5-20%); intermediate (20-70%) or diffuse (>70%). In situ hybridization was performed for Epstein-Barr virus (EBV) and HHV-8. Results were recorded as positive or negative. RESULTS: All cases showed some degree of plasmacytic differentiation. All were negative for CD20 with reactive T cells detected with CD3. Diffuse and strong positive staining was found with Ki-67 and MUM1, but variable immunoreactivity was found with CD79a, CD45, CD38 and CD138. Twenty cases (47%) showed light chain restriction. Epstein-Barr virus was detected in 44/45 cases and HHV-8 in none. CONCLUSIONS: The morphological classification of PBLs is not valid as all cases showed some degree of plasmacytic differentiation. We propose that PBLs with light chain restriction be reclassified as 'plasmablastic extramedullary plasmacytomas' and managed accordingly. The rest represents true PBLs. The true nature of these neoplasms as an entity should be further investigated with molecular and genetic studies.

An investigation of the role of oral epithelial cells and Langerhans cells as possible HIV viral reservoirs.

BACKGROUND: The role of the oral mucosa as a target of human immunodeficiency virus (HIV-1) infection and persistence is unclear. HIV-1 has been reported in oral epithelial cells, but this has not been confirmed. Cellular reservoirs may impede antiretroviral therapies and should be identified. This study was performed to determine the presence of HIV-1 in oral epithelial and Langerhans cells (LCs) of HIV-1-positive antiretroviral naïve patients. Non-invasive brush biopsy technique for future in vivo HIV research was also evaluated. METHODS: Oral mucosal cells were harvested from the buccal mucosae, dorsal tongue and the gingiva of the mandibular teeth of 35 HIV-1-positive patients using a Cytobrush Plus cell collector. Epithelial cells were purified from the samples by flow cytometric cell sorting using cytokeratin stains after which the epithelial cell samples were further purified and divided into superficial and deep epithelial cells by laser microdissection on Pap stained cytospin smears. LCs were picked up individually by laser microdissection from CD1a stained cytospin smears. Purified epithelial and LC samples were tested for the presence of HIV-1 DNA by polymerase chain reaction analysis. RESULTS: Ten of the patients had HIV-1 DNA in one or more of the sampled anatomical locations. No HIV-1 DNA could be demonstrated in any of the purified superficial or deep epithelial or LC samples. CONCLUSIONS: HIV-DNA can be found using non-invasive oral brush biopsies and should be investigated further as an experimental model for in vivo oral HIV research. Better ways to purify the different cell types should be investigated.

Human papilloma virus types in the oral and cervical mucosa of HIV-positive South African women prior to antiretroviral therapy.

BACKGROUND: To evaluate the prevalence of human papilloma virus (HPV) infection and types in the oral and cervix mucosa of treatment-naïve HIV-1-positive women with CD4 counts less than 300 cells per ml with no HPV-associated oral lesions. METHODS: Oral epithelium was harvested from the buccal mucosa and lateral borders of the tongue and cervical samples were collected from the endocervical area of 30 women, 22-64 years old. Cytobrush Plus cell collectors were used for sampling both anatomical areas. Genital pathology, obstetric and gynaecological history, co-morbid disease, hormone therapy, sexual behavior and smoking history were assessed via physical examination and clinical interviews. Special investigations included cervical Papanicolau smears, CD4 counts and HIV-1 viral loads. The linear array HPV test was used to determine HPV genotypes present in the specimens. RESULTS: Oral HPV were identified in 20% (n = 6) of the patients, of which two had infection with two HPV types. Genital HPV was found in 96.7% (n = 29) of the women, of which only 14 had cytological abnormalities on Papanicolau smear. Infection with multiple HPV types were present in 93.1% (n = 27) of the patients, with an average of four HPV types per individual. CONCLUSIONS: South African HIV-positive women with CD4 counts less than 300 cells per ml have a significant risk of cervical HPV strains and multiple strain infection of the cervix. The prevalence of HPV in normal oral mucosa was low but high-risk types were present. Limited correlation between oral HPV types and those identified in the cervical mucosa was found.

Diagnosis and management of odontogenic myxoma in a dog.

A three-year-old Jack Russell terrier dog was presented with a large gingival mass of the right mandible extending from the fourth premolar to the first molar teeth. Radiographic examination of the expansile mass revealed moth-eaten, honeycomb-like lyses of the mandible and extended into the mandibular alveolar canal based on computed tomography. The histopathological diagnosis of the biopsy was odontogenic fibromyxoma. Mandibulectomy with resection of the associated soft tissues was performed. Surgical management was curative with no clinical signs of disease 2-years after treatment. These neoplasms are slow growing, locally destructive tumors of odontogenic origin that have been described in the jaw of only one dog. In this paper, the clinico-radiological and pathologic features, diagnostic modalities as well as the factors that might influence treatment outcome of odontogenic myxomas are discussed. These odontogenic tumors are currently excluded from the WHO classification of odontogenic tumors in domestic animals and inclusion in future classifications systems is proposed.

Scanning electron microscopic study of the dentinal tubules in dog canine teeth.

Dentin adhesive restorative techniques are regularly used in veterinary dentistry. Knowledge of the microanatomic structure and properties of dentin is essential to ensure success in restorative procedures. The aim of this study was to describe the density and diameter of dentinal tubules in dog canine teeth using recently described standardized scanning electron microscopy techniques. The results showed dentin of dog canine teeth to be more oval-shaped with a higher tubular density and slightly larger tubular diameters compared with human teeth. These features suggest dog canine teeth have less intertubular dentin compared with human teeth, which may theoretically result in lower resin-dentin shear bond strengths.

Stenotic nasopharyngeal dysgenesis in the dachshund: seven cases (2002-2004).

Medical records of seven dachshunds with congenital nasopharyngeal stenosis from abnormally thickened palatopharyngeal muscles were reviewed. The intrapharyngeal ostium in all cases consisted of only a narrow slit. Dogs were presented with various clinical signs--the most common being dyspnea, expiratory cheek puff, salivation, pharyngeal dysphagia, oral dysphagia (to a lesser extent), and macroglossia. Diagnostic procedures included direct pharyngeal inspection, pharyngeal and thoracic radiography, fluoroscopy, lingual ultrasonography, biopsies in two dogs, and a postmortem examination in one dog. Diagnoses were readily made with radiographs and visual examinations. Macroglossia was confirmed with transcutaneous ultrasonography or a transmandibular finger test.

Flow cytometric evaluation of postmortem pulp DNA degradation.

During postmortem autolysis, cellular organelles and nuclear DNA break down into their constituent parts. DNA flow cytometric analysis was applied to study the denaturation of splenic cell DNA as a possible method for postmortem interval determination. DNA denaturation continued for 72 hours at a constant rate, with no intact DNA peaks thereafter. The value of using dental pulp tissue for flow cytometric determination of postmortem interval was investigated. The pulps of 57 routinely removed impacted third molars from patients 15 to 30 years of age were obtained. Pulp tissue was removed at 24, 48, 72, 96, 120, and 144 hours postextraction. Debris (degraded DNA) was defined as all signals left of the standardized mean 2n peak and expressed as a percentage of the total number of signals. In contrast to the splenic cell DNA, dental pulp tissue exhibited minimal DNA degradation by 144 hours postextraction, and no constant relation was found between time and DNA degradation during this time. In this study, pulp tissue was found to be unreliable to determine the early postmortem interval but might be of greater value in the later stages.