Histopathological parameters reported in microinvasive oral squamous cell carcinoma: a systematic review.

BACKGROUND: Microinvasive oral squamous cell carcinoma (OSCCmi) is an incipient stage of oral cancer. Through this systematic review, we aim to assess patterns of histopathological outcomes reported in OSCCmi cases. MATERIAL AND METHODS: An online search in major databases was performed without period restriction, and 2,024 publications in English, Spanish and Portuguese were obtained. After screening and eligibility, 4 studies were selected. The risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Checklist. A descriptive synthesis was conducted. RESULTS: All 4 publications included were retrospective, reporting a total of 116 OSCCmi patients, with a male predominance (1.6:1) and a mean age of 55.9 years. The main parameters considered for microinvasion were tumor thickness (TT) (range 4-10mm) and depth of invasion (DOI) (range 0,02-5mm). Definition, cut-off values, and assessment of microscopic features were not standardized. Other relevant measures such as perineural or lymphovascular invasion and pattern of invasive front were barely described, and cytological/architectural characteristics were not discussed. CONCLUSIONS: TT and DOI are currently the primary histopathological criteria used to define OSCCmi. Nonetheless, the outcomes of this systematic review showed the absence of standardized quantitative parameters to render the diagnosis of microinvasive OSCC. Therefore, additional studies aiming to standardize histopathological features to diagnose OSCCmi are paramount.

Using virtual microscopy to deliver an integrated oral pathology course for undergraduate dental students.

Dental students in the United Kingdom usually study histopathology as part of their undergraduate curriculum and this has traditionally been delivered using light microscopes in laboratory classes. Beginning in 2005, the oral pathology course in Sheffield was gradually modified by the introduction of virtual microscopy with a focus on creating a more integrated, clinically orientated and dynamic approach to student teaching and learning in histopathology. The purpose of this paper is to describe how virtual microscopy has been used to enhance dental students' learning of oral pathology, and its role in facilitating an integrated oral disease curriculum in Sheffield.

Rapidly-growing buccal mass in a 6-month-old infant.

Lipoblastoma and lipoblastomatosis are rare benign tumours of fetal-embryonal adipocytes that usually present in young children, which is why they are not often included in the differential diagnosis of soft tissue lesions in infants. We describe a case of a 6-month-old infant with an intraoral buccal lipoblastoma.

Effects of recombinant human bone morphogenetic protein 7 (rhBMP-7) on the behaviour of oral squamous cell carcinoma: a preliminary in vitro study.

We investigated the effects of recombinant human bone morphogenetic protein-7 (rhBMP-7) on the behaviour of oral keratinocytes and head and neck squamous cell carcinoma (SCC) cells in vitro. Expression of all three BMP receptors was high (p<0.01), and rhBMP-7 exhibited significant dose-related inhibitory effects on the doubling time and viability of cancer cells (p<0.01), but not on the proliferation or viability of oral keratinocytes. It elicited no significant effect on the invasion of Matrigel in SCC of the head and neck. Results indicate that in cell culture, rhBMP-7 exerts antineoplastic effects. This should be tested in an orthotopic animal model to more closely replicate in vivo effects.

The roles of HOXD10 in the development and progression of head and neck squamous cell carcinoma (HNSCC).

BACKGROUND: HOX gene expression is altered in many cancers; previous microarray revealed changes in HOX gene expression in head and neck squamous cell carcinoma (HNSCC), particularly HOXD10. METHODS: HOXD10 expression was assessed by qPCR and immunoblotting in vitro and by immunohistochemistry (IHC) in tissues. Low-expressing cells were stably transfected with HOXD10 and the phenotype assessed with MTS, migration and adhesion assays and compared with the effects of siRNA knockdown in high-HOXD10-expressing cells. Novel HOXD10 targets were identified using expression microarrays, confirmed by reporter assay, and validated in tissues using IHC. RESULTS: HOXD10 expression was low in NOKs, high in most primary tumour cells, and low in lymph node metastasis cells, a pattern confirmed using IHC in tissues. Overexpression of HOXD10 decreased cell invasion but increased proliferation, adhesion and migration, with knockdown causing reciprocal effects. There was no consistent effect on apoptosis. Microarray analysis identified several putative HOXD10-responsive genes, including angiomotin (AMOT-p80) and miR-146a. These were confirmed as HOXD10 targets by reporter assay. Manipulation of AMOT-p80 expression resulted in phenotypic changes similar to those on manipulation of HOXD10 expression. CONCLUSIONS: HOXD10 expression varies by stage of disease and produces differential effects: high expression giving cancer cells a proliferative and migratory advantage, and low expression may support invasion/metastasis, in part, by modulating AMOT-p80 levels.

Endothelin-1 stimulates oral fibroblasts to promote oral cancer invasion.

AIMS: The aims of this study were to examine the role of endothelin-1 (ET-1), a pleiotropic peptide found at elevated levels in a number of malignancies and which has been shown to influence oral cancer cell behaviour via paracrine signalling pathways, on the phenotype of oral fibroblasts. MAIN METHODS: The effect of ET-1 on proliferation and migration of human primary oral fibroblasts was assessed using MTS and scratch assays, respectively. The ability of ET-1 to affect fibroblast contractility was analysed using type-I collagen gels. Changes in gene expression in oral fibroblasts exposed to ET-1 were examined using quantitative PCR. The invasiveness of oral cancer cells in the presence of conditioned media collected from ET-1 treated fibroblasts was determined using 2D Matrigel assays. KEY FINDINGS: Here we provide evidence that ET-1 increases the migration of oral fibroblasts and induces a more contractile phenotype which is not associated with changes in gene expression indicative of myofibroblast transdifferentiation. In addition we provide evidence that conditioned medium of ET-1-stimulated oral fibroblasts promotes invasion of OSCC cells in vitro. SIGNIFICANCE: In oral squamous cell carcinoma, a frequently fatal and increasingly common epithelial malignancy of the oral cavity, ET-1 is known to contribute to pro-migratory paracrine signalling between stromal fibroblasts and cancer cells. The ability of ET-1 to modulate the phenotype of human oral stromal fibroblasts, however, has not previously been reported. The findings presented here suggest that targeting the stromal endothelin system may be a viable and novel therapeutic strategy for invasive oral cancer.

Micrometastases and isolated tumour cells in sentinel lymph nodes in oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: The occurrence of micrometastases (MMs) and isolated tumour cells (ITCs) in oral sentinel lymph node (SLN) biopsy is poorly known, and the definitions and clinical significance of MMs and ITCs in SLN biopsy are controversial. We compared the UICC/TNM definitions of MMs and ITCs with our previously published sentinel node protocol to assess how the adoption of the UICC/TNM criteria would affect the staging of nodal micrometastatic disease. METHODS: Of 107 patients who had a SLN biopsy and pathology at 150 microm intervals, 35 with metastatic tumour were included. Eighty-six SLNs were reassessed using the UICC/TNM definitions for MMs and ITCs. Findings were linked to the final pathology in the subsequent neck dissection. RESULTS: Initial H&E sections showed metastases in 24 patients (in 34 out of 61 SLN), 8 of whom (9 SLNs) had MMs. Additional step serial sections revealed metastatic deposits in a further 11 patients (15 out of 25 SLNs were positive) which were reassessed as MMs (6 patients) or ITCs (5 patients). Subsequent neck dissection revealed additional metastases in 46% of patients with MM, whilst one of the ITC patients had subsequent neck metastases (20%). CONCLUSION: Despite some limitations, the UICC/TNM classification provides an objective, uniform method of detecting MMs and ITC's. Unlike in cases with ITC, metastases in other non-SLNs were common when a micrometastasis was detected in a SLN, indicating need for further treatment of the neck.

Ligneous alveolar gingivitis in the absence of plasminogen deficiency.

A case of localized, longstanding, asymptomatic ligneous gingivitis affecting the crest of the edentulous lower left posterior alveolar ridge (ligneous alveolar gingivitis) of a middle-aged Caucasian woman is presented. This patient did not have any associated ophthalmic lesions (ligneous conjunctivitis) and did not have a plasminogen deficiency.

Muscle injury and repair.

Muscle injury triggers a sequence of events that begin with a host inflammatory response that is followed by muscle fiber regeneration and new collagen synthesis. The inflammatory response involves at least three types of cells, including neutrophils, ED1+ macrophages, and ED2+ macrophages. A host of growth factors and cytokines appear to play a role in the inflammatory process and repair of the damaged tissue. Satellite cells play an integral role in normal development of skeletal muscle by providing a source for postmitotic myonuclei. In addition, the satellite cell is essential to the repair of injured muscle by serving as a source of myoblasts for fiber regeneration. At the same time muscle fiber regeneration is occurring, there is expression of types I and III collagen that under certain circumstances can lead to scarring and fibrosis. Current studies of treatment of muscle injury often incorporate investigations of basic principles of injury and repair together with clinical experience and principles in an effort to coordinate basic science and outcome studies.

Fluconazole-resistant Candida species in the oral flora of fluconazole-exposed HIV-positive patients.

The purpose of this study was to examine the effect of preceding fluconazole treatment on the oral mycologic flora and on the sensitivity of oral Candida albicans isolates to fluconazole. Saline oral rinses were collected from 89 HIV-positive patients, of whom 48 had been exposed to fluconazole and 41 were fluconazole-naive. The rinses were cultured on Sabouraud's and Pagano Levin agars, and yeasts were identified by standard methods. Fluconazole sensitivity of C. albicans isolates was measured by disk diffusion assay. C. albicans was isolated from 69% of patients who had received fluconazole and from 93% of the patients who were fluconazole-naive (p < 0.05). Nine other species of yeasts were also isolated, most commonly C. glabrata. Five patients previously exposed to fluconazole harbored fluconazole-resistant C. albicans, whereas no resistance was detected among the patients who were fluconazole-naive (p < 0.01). Sixteen of the patients who were fluconazole-exposed carried yeasts other than C. albicans, compared with only five patients in the fluconazole-naive group (p < 0.01). All of the fluconazole-resistant strains were isolated from patients with low CD4 counts (less than 100 cells/ml) and after lengthy fluconazole exposures. Nevertheless, patients in Charlotte, N.C., who had a greater mean fluconazole exposure time (10.25 +/- 1.41 months) than patients in Glasgow, UK, (0.65 +/- 0.18 months; p < 0.005), did not develop significantly more in vitro resistance or species diversity. This study indicates that long-term fluconazole treatment can have significant effects on the yeast flora of the mouth, particularly in a patient with a CD4 count of less than 100 cells/ml.

Pliometric contraction-induced injury of mouse skeletal muscle: effect of initial length.

For single pliometric (lengthening) contractions initiated from optimal fiber length (Lf), the most important factor determining the subsequent force deficit is the work input during the stretch. We tested the hypothesis that regardless of the initial length, the force deficit is primarily a function of the work input. Extensor digitorum longus muscles of mice were maximally activated in situ and lengthened at 2 Lf/s from one of three initial fiber lengths (90, 100, or 120% of Lf) to one of three final fiber lengths (150, 160, or 170% of Lf). Maximal isometric force production was assessed before and after the pliometric contraction. No single mechanical factor, including the work input (r2 = 0.34), was sufficient to explain the differences in force deficits observed among groups. Therefore, the force deficit appears to arise from a complex interaction of mechanical events. With the data grouped by initial fiber length, the correlation between the average work and the average force deficit was high (r2 = 0.97-0.99). Consequently, differences in force deficits among groups were best explained on the basis of the initial fiber length and the work input during the stretch.

The effects of antidepressant drugs on salivary flow and content of sodium and potassium ions in human parotid saliva.

Stimulated parotid saliva was collected, using the Carlson-Crittenden cup, from normal controls and patients on antidepressant drugs. The saliva from patients using amitriptyline, dothiepin (tricyclics), fluoxetine and paroxetine (selective serotonin re-uptake inhibitors; SSRI) was analysed for flow rate, [Na+] and [K+], and was compared with that from unmedicated, non-depressed volunteers for all variables. The tricyclic antidepressants produced a significant reduction in flow (amitriptyline, p < 0.01; dothiepin, p < 0.05), and consequent decrease in [Na+] and increase in [K+]. These effects were presumably due to muscarinic receptor blockade. The SSRIs produced no significant change in these variables. A prospective study of dothiepin in non-depressed patients confirmed that it decreases stimulated parotid flow. This finding also suggested that depression itself contributed little to the oral dryness observed in and reported by the depressed patients. The patients' subjective rating of oral dryness related well to a reduction in stimulated flow. This applied to those taking either tricyclics or SSRI, both showing a reduced flow rate relative to control (p < 0.001 and p < 0.05, respectively). This amounted to a 58% reduction in flow rate in the tricyclic group. The data suggest that measurement of stimulated parotid salivary flow is a reliable indicator of drug-induced oral dryness.