Oral superficial haemosiderotic lymphovascular malformation: a rare presentation.

We present an extremely rare case of a 53-year-old woman with an intraoral superficial haemosiderotic lymphovascular malformation (SHLM), also known as hobnail haemangioma. SHLM is a rare, benign, vascular tumour first described as targetoid haemosiderotic haemangioma, with only a handful of cases reported to present in the oral cavity. The diagnosis was established following complete surgical excision of the lesion, and after 14 months, there are still no signs of recurrence. Although SHLM is an uncommon condition, accurate and timely diagnosis is valuable in distinguishing these lesions from their more serious competing differential diagnoses.

Tumor-infiltrating macrophage and microvessel density in oral squamous cell carcinoma.

Tumor-associated macrophages (TAM) are the main cellular component in stroma of many tumors and participate in tumor angiogenesis. The aim of present study was to compare the microvascular density (MVD) and infiltrating macrophage density (IMD) in oral squamous cell carcinomas (OSCCs) with different histological grades. A histomorphometric analysis was performed after immunohistochemistry using antibodies such as von-Willebrand factor and CD68. A significant difference in MVD was found between well and moderately differentiated OSCCs (p<0.05). TAM were largely present in all studied tumors and the IMD was not different among OSCCs with different histological grades (p=0.381). Significant correlation between MVD and IMD was not observed (p=0.870). In conclusion, these results suggest that TAM and angiogenesis have an influence at different histological grades of OSCC. However, the lack of correlation between MVD and IMD could suggest that angiogenesis does not depend on the number of macrophages present in OSCC, but their predominant phenotype. Further studies involving distinct phenotypes of macrophages should be done to better understand the influence of TAM on the tumor angiogenesis.

Tumor-Infiltrating Macrophage and Microvessel Density in Oral Squamous Cell Carcinoma

Tumor-associated macrophages (TAM) are the main cellular component in stroma of many tumors and participate in tumor angiogenesis. The aim of present study was to compare the microvascular density (MVD) and infiltrating macrophage density (IMD) in oral squamous cell carcinomas (OSCCs) with different histological grades. A histomorphometric analysis was performed after immunohistochemistry using antibodies such as von-Willebrand factor and CD68. A significant difference in MVD was found between well and moderately differentiated OSCCs (p<0.05). TAM were largely present in all studied tumors and the IMD was not different among OSCCs with different histological grades (p=0.381). Significant correlation between MVD and IMD was not observed (p=0.870). In conclusion, these results suggest that TAM and angiogenesis have an influence at different histological grades of OSCC. However, the lack of correlation between MVD and IMD could suggest that angiogenesis does not depend on the number of macrophages present in OSCC, but their predominant phenotype. Further studies involving distinct phenotypes of macrophages should be done to better understand the influence of TAM on the tumor angiogenesis.

Macrófagos associados a tumores (MAT) representam o componente principal do estroma de muitos tumores, além de participar da angiogênese tumoral. Este estudo comparou a microdensidade vascular (MDV) e densidade de macrófagos infiltrando o tumor (DMIT) em carcinoma escamocelular da boca (CEC) com diferentes graus histológicos de malignidade. Análise histomorfométrica foi empregada após técnica imuno-histoquímica para os anticorpos fator von-Willebrand e CD68. Uma diferença significante entre MDV e carcinomas bem e moderadamente diferenciados foi observada (p<0,05). MAT estavam fortemente presentes em todos os tumores estudados e a DMIT não foi diferente entre os diferentes graus histológicos de malignidade do CEC (p=0,381). Correlação significante entre MDV e DMIT não foi observada (p=0,870). Em conclusão, os resultados desse estudo sugerem a influência de MAT e angiogênese nos diferentes graus histológicos de malignidade do CEC. Entretanto, a ausência de correlação entre MDV e DMIT sugere que a angiogênese não depende do número de macrófagos presentes neste tipo de câncer, mas do fenótipo predominante. Outros estudos devem ser realizados a fim de contribuir para melhor compreensão da participação de MAT na angiogênese tumoral.

Experimental study of antiangiogenic gene therapy targeting VEGF in oral cancer.

It is well known that tumor angiogenesis plays an important role in local growth and metastasis of oral cancer; therefore, inhibiting angiogenesis is considered to be effective for treating oral cancer. This study aimed to investigate the effectiveness of systemically available antiangiogenic gene therapy targeting vascular endothelial growth factor (VEGF), which is one of the most important angiogenesis accelerators. We administered a soluble form of VEGF receptor-expressing gene incorporated into adenovirus (AdVEGF-ExR) intraperitoneally to nude mice to which oral cancer cell lines (SAS, HSC-3, and Ca9-22) had been transplanted subcutaneously in vivo to inhibit angiogenesis and tumor proliferation. Then, we measured tumor volumes over time, and tumors were enucleated and examined histopathologically and immunohistologically at 28 days after AdVEGF-ExR administration. Compared to the controls to which we administered AdLacZ or saline, significant antiproliferative effects were observed (P < 0.05) in the AdVEGF-ExR administration group, and extensive tumor necrosis was found histopathologically. Immunohistochemical analysis with CD34 (NU-4A1) revealed tumor angiogenesis was suppressed significantly (P < 0.05), and that with ssDNA revealed apoptosis induction was significantly high (P < 0.05) in the AdVEGF-ExR group. However, analysis with Ki-67 (MIB-1) revealed tumor proliferative capacity was not significantly different between the groups. Consequently, we consider that AdVEGF-ExR administration achieved tumor growth suppression by inhibiting angiogenesis and inducing apoptosis, but not by inhibiting the proliferative capacity of tumor cells. Neither topical administration of a soluble form of VEGF receptor (sVEGFR) to the tumor nor a megadose was needed to achieve this inhibition effect. These results suggest gene therapy via sVEGFR would be an effective oral cancer therapy and benefit future clinical applications.

Detecting early oral cancer: narrowband imaging system observation of the oral mucosa microvasculature.

The aim of this study was to analyze and describe the intrapapillary capillary loops (IPCL), which are a feature of early oral neoplastic lesions, using a narrowband imaging (NBI) system. Forty-one patients (26 men, 15 women; mean age, 52.34 years; range, 23-83 years) presenting with non-neoplastic or neoplastic lesions, and normal cases, were examined using the prototype Evis Lucera Spectrum (Olympus Co.). The images were analyzed and an IPCL classification was devised. All normal cases (n=10) had regularly distributed capillary loops of the same shape (type I). Non-neoplastic lesions (n=8) had mild changes of the capillary loops (types II and III) and neoplastic lesions (n=23) were irregularly distributed and had several loop shapes (types III and IV). The microvascular organization of non-neoplastic lesions was notably different from that of neoplastic lesions. A brownish area was found in five cases of early carcinoma. The narrowband imaging system is a potential approach for clinically analyzing microvascular organization and IPCL. It could be useful for diagnosing oral squamous cell carcinoma at an earlier stage and for determining the margin of resection.

VEGF is up-regulated by hypoxic stimulation and related to tumour angiogenesis and severity of disease in oral squamous cell carcinoma: in vitro and in vivo studies.

The present study was aimed to speculate whether the up-regulation of VEGF in oral squamous cell carcinoma (OSCC) is associated with oxygen levels, tumor angiogenesis and severity of disease. Under different oxygen levels, VEGF protein production in two oral cancer cell lines was quantitatively documented by using ELISA kit. Correlations between expression of VEGF, microvessel density, and various clinico-pathologic factors were studied in forty patients with OSCC. VEGF production was continuously elevated in supernatants from both cell lines in respond to the drop of oxygen levels. When oxygen level decreased to 1%, there was a 2.1-fold and nearly a 2.9-fold elevation of VEGF production in TSCCa and GNM cell line, respectively. On hypoxia VEGF production also presented a time-dependent up-regulation in both oral cancer cell lines. VEGF positivity was correlated with regional lymph nodal involvement and clinical stage. Microvessel density was significantly higher in VEGF-positive tumors than in VEGF-negative tumors. The presence of hypoxia in oral cancers is partly responsible for the up-regulation of VEGF. The elevation of VEGF expression in OSCC tissues correlates with the increased microvessel density and severity of the disease.

[Effect of Angiogenesis inhibitor (TNP-470) on the morphology of GNM cell line in vitro].

OBJECTIVE: The purpose of this study was to investigate the effect of an angiogenesis inhibitor (TNP-470) on the ultra micro-structural morphological changes of GNM cell line, which was derived from human oral squamous cell carcinomas in vitro. METHODS: The GNM cells were cultured and, the effect of TNP-470 on ultra micro-structural morphological changes of GNM cells was observed under the inverted microscope, the scanning electron microscope (SEM) and the transmission electron microscope (TEM). RESULTS: Numerous round cells, shrinkage of cellular membrane and dead cells were observed 48 hours after 2 micrograms/ml of TNP-470 was added into the GNM cellular suspension. After 72 hours, GNM cells became shortened and, the number of microvilli of the cellular surface was observed under the SEM and TEM. A large number of GNM cells turned into necrosis, accompanying with the destruction of mitochondria and endoplasmic reticula. CONCLUSION: TNP-470 has a strong tumor cytotoxic effect on GNM cells, which may be due to its destructibility on mitochondria and endoplasmic reticula of GNM cells. TNP-470 can alter the surface structure of GNM cell membrane, which suggests that TNP-470 may interrupt the metastasis of GNM cells.

Gingival and cutaneous angiosarcoma.

Multiple oral and cutaneous nodular and papular reddish-blue lesions are described in the case of a 60-year-old woman. The duration of the lesions was more than 1 year, with the oral lesion preceding the skin lesions. Histopathological examination revealed malignant vascular tumour with changes consistent with angiosarcoma. Angiosarcoma is an extremely rare malignant tumour of the oral cavity, and the present case describes oral and skin lesions with a unique clinical behaviour.

The epulis vascularity. A morphometric study.

BACKGROUND: A computerised morphometric analysis of some vascularisation aspects of epulides is presented. The aim of this study is to evaluate the correlation between morphometric aspects and histological classification of epulides and to investigate its usefulness for the histopathologic diagnosis. METHODS: The study was carried out on epulides from 72 patients (30 males, 42 females, age-range 16-60). Epulides were fixed in alcohol, paraffin embedded, and stained with haematoxyilin eosin, thereafter epulides were histopathologically classified as granulomatous epulides, fibrous epulides and giant cell epulides. Images of histological samples were then digitised, and by an image analysis system some morphometric vessels characteristics were evaluated: percent image area occupied by vessels, vessels number, mean vessels area and standard deviation of vessels area. Finally, the correlation between morphometric data and the histological classification of epulides was evaluated. RESULTS: The statistic evaluation of morphometric data allowed to classify epulides in six groups characterised by a various degree of vascularisation, these groups showed a good correlation with histopathological classification. CONCLUSIONS: The morphometric analysis of vessels is a powerful aid for the histopathologic diagnosis and for a better knowledge of the etiopathogenetic factors of epulides.

Observations on the vascular structure of malignant tumours of the mandible using specimen arteriography.

OBJECTIVES: To investigate the vascular structure of different malignant tumours of the mandible. METHODS: Specimen arteriography was performed on seven cases of squamous cell carcinoma of gingiva and four sarcomas. RESULTS: Malignant tumours could be divided into two groups: (1) the hypervascular sarcomas in in which the arteries were dilated, distributed evenly and arranged in a bush-like pattern; and (2) hypovascular squamous cell carcinoma with scanty arteries distributed unevenly without dilatation; in some areas, the shape of arteries was irregular and arranged in a network pattern. CONCLUSIONS: The variation in vascular structure of malignant tumours of the mandible may be related to the outcome of regional chemotherapy.

Capillary hemangioma of the maxilla. A report of two cases in which angiography and embolization were used.

This article presents two clinical cases of capillary hemangiomas of the maxilla. Such lesions are rare, as demonstrated by the review of the literature included in this article. The presentation, differential diagnosis, histopathology, management, and follow-up for each case are discussed. Our rationale for approaching these types of lesions, as well as our opinion that microembolization should be considered as a first line approach to treatment, is presented.

[Epithelial dysplasia and invasive carcinoma of oral cavity showing punctation and atypical vessels].

We have experienced epithelial dysplasia and invasive carcinoma of oral cavity, showing punctation and mosaic like atypical vessels confirmed by usual photographing. Case 1: 42-year-old man. After resection of tongue leukoplakia, the punctation appeared in the distal region of resected wound. Pathological findings were epithelial dysplasia, and expansion of capillaries in the stromal papillae were close to the surface. Case 2: 55-year-old woman. Punctation and mosaic like atypical vessels were recognized in the buccal mucosa, extending from the gingival carcinoma. Pathological findings were epithelial dysplasia and carcinoma in situ in punctation, and early invasive carcinoma in mosaic. There were irregularly expanded capillaries in the stromal papillae being close to the surface at both mosaic and punctation area. Although punctation, atypical vessels and mosaic are the colposcopic findings of uterine cervical cancer, these findings may become diagnostic point of early oral cancer.