Irit Allon

Stromal myofibroblasts accompany modifications in the epithelial phenotype of tongue dysplastic and malignant lesions.

Stromal myofibroblasts (SMF) associated with various types of carcinomas are believed to emerge under the influence of the tumor cells. Recent studies have shown that SMF may originate from fibroblasts within the tumor stroma or even from carcinoma cells by the process of epithelial-mesenchymal transition. The aim of this study was to investigate the concomitant expression of epithelial membrane antigen and α-smooth muscle actin in cells at the tumor-connective tissue interface in human tongue carcinoma, as a possible reflection of epithelial-mesenchymal transition. Given its key role in this process, expression of transforming growth factor-β in the malignant cells was assessed as well. Immunostaining with α-smooth muscle actin was performed on cases of hyperplasia (n = 16), mild dysplasia (n = 12), moderate-to-severe dysplasia (n = 11) and carcinoma (n = 22). Transforming growth factor-β assessment and double immunostaining with epithelial membrane antigen and α-smooth muscle actin were performed only in cases of carcinoma. SMF were significantly associated with carcinomas, while their number in pre-malignant lesions (hyperplasia and dysplasia) was significantly lower (P < 0.001). Although SMF were found in all carcinomas, they were heterogeneous in their frequency and patterns of distribution. In addition, 95% of the carcinomas expressed transforming growth factor-β and 41% exhibited cells positive for both epithelial membrane antigen and α-smooth muscle actin. SMF were almost exclusively associated with established carcinomas and not with pre-malignant lesions. Cells that co-expressed epithelial membrane antigen and α-smooth muscle actin can be a manifestation of epithelial-mesenchymal transition and, as such, may serve as a source for SMF in these tumors. These findings appear to be linked to the frequent expression of transforming growth factor-β by the malignant cells.

Decompression as a Treatment of Odontogenic Cystic Lesions in Children

PURPOSE To evaluate the efficiency of decompression in treating odontogenic cystic lesions of the jaws in children. MATERIALS AND METHODS All consecutive odontogenic cysts occurring in children and treated by decompression from 1994 to 2009 at 1 maxillofacial center were included in the present study. Clinical data included age, gender, jaw, histopathologic diagnosis, and decompression time. Radiologic data from panoramic radiographs before and after decompression included tooth involvement, locularity, location, involvement of adjacent vital anatomic structures, and cyst area. RESULTS Thirty-two odontogenic cystic lesions from 26 children (14 boys [53.8%] and 12 girls [46.2%]) treated with decompression were included. The average age at the time of presentation was 11.6 ± 3.3 years (range, 7 to 18 yr). The mandible was involved in 13 cases (40.6%) and the maxilla in 19 (59.4%). All cysts were unilocular at presentation. Twenty-seven cysts (84.4%) showed tooth involvement. The diagnoses consisted of dentigerous cysts (20 [62.5%]), keratocysts (9 [28.1%]), and radicular cysts (3 [9.4%]). The mean decompression period was 7.45 ± 2.6 months (2 to 14 months). The mean standard lesion area index changed from 12.7 ± 0.9 mm(2) (3.6 to 44 mm(2)) before compression to 2.3 ± 4.3 mm(2) (0 to 22.3 mm(2)) after decompression. The mean percentage of reduction (POR) was 82 ± 16% (49 to 100%). The POR was ranked as good in 22 lesions (69%), moderate in 9 lesions (28%), and poor in 1 lesion (3%). Surgery was performed for 15 lesions (47%). CONCLUSION Decompression results in good regeneration potential of the bone in the developing craniofacial skeleton of children. Children might benefit from a less invasive surgical protocol.

Is maspin immunolocalization a tool to differentiate central low-grade mucoepidermoid carcinoma from glandular odontogenic cyst?

Mucoepidermoid carcinoma (MEC) of the salivary glands has a low-grade variant (LGMEC), which may be found within the jawbones. LGMEC shares a number of histopathological similarities with glandular odontogenic cysts (GOC) of the jawbones. Maspin has been identified in several benign and malignant salivary gland neoplasms. We investigated the immunolocalization of maspin in LGMEC and GOC and evaluated its potential to distinguish between these two entities. Cases of LGMEC (n=6), GOC (n=8) and various odontogenic cysts with marked mucous metaplasia (OCMM, n=7), which served as controls, were immunohistochemically labeled for the binding of an antibody directed against maspin. Immunomorphometry was performed separately for maspin-immunopositive epithelial cells and epithelial-mucous cells in either their nuclear or cytoplasmic compartments. Results were presented as the volume fraction (Vv) of each element. The Vv of the maspin-immunopositive epithelial-mucous cytoplasm and nuclei was significantly higher in LGMEC than in GOC and OCMM (p<0.001 and p=0.026, respectively). In the epithelial cells, no significant differences were observed among the lesions (p>0.05). It is suggested that the high levels of maspin in the epithelial-mucous cells (in both cytoplasm and nuclei) in LGMEC may serve as a tool to distinguish it from GOC. This may be useful especially in equivocal cases and in small incisional biopsy samples.

Oral neurovascular hamartoma: a lesion searching for a name

BACKGROUND Neurovascular hamartoma (NVH), in particular in the oral cavity, is rarely described in the literature. The low number of cases may reflect a genuine rarity of the lesion, or it may be due to its being unrecognized and/or under-reported. OBJECTIVES To investigate clinical and microscopic features of oral NVH and to define microscopic diagnostic criteria with emphasis on the differential diagnosis. METHODS Archival cases diagnosed as oral NVH between 1999 and 2011 were retrieved; clinical and demographic data were collected, and a paired morphometric analysis was conducted, with each case of NVH a case of fibrous hyperplasia (FH) from the same oral location. The nerve bundle and blood vessel density were quantified in five microscopic fields at ×100 magnification. RESULTS The study group included 25 oral NVH, 11 men and 14 women, aged 6-76 years, (mean 44). The majority occurred in the tongue (54%), followed by the buccal mucosa and lower lip (17% each), clinically presenting as asymptomatic 0.25-2.5 cm exophytic masses. Microscopic characteristics included poorly circumscribed masses of closely packed nerve bundles and blood vessels in a loose matrix, containing minimal or no inflammation. The mean nerve bundle density was significantly higher in NVH (4.28 ± 1.26) in comparison with FH (0.27 ± 0.27), (P < 0.00001), and mean vessel density was significantly lower (5.98 ± 1.4 vs. 7.8 ± 1.9, respectively), (P < 0.0003). CONCLUSION Oral NVH may not be as rare as previously considered. Morphometric analysis demonstrated that NVH presents a separate distinct entity.

Metastatic Tumors to the Gingiva and the Presence of Teeth as a Contributing Factor: A Literature Analysis

BACKGROUND Gingiva that is prone to inflammation may serve as a pre-metastatic niche for the attraction of circulating malignant cells. The aim of this study is to analyze cases of metastatic lesions to the gingiva compared with cases metastasizing to other oral mucosal sites. The pathogenesis of gingival metastases is discussed, with emphasis on the role of inflammation. METHODS The English-language literature between 1916 and 2011 was searched for cases of metastatic lesions to the oral mucosa; only cases metastasizing in the oral mucosa, gingiva, and periodontium were included. RESULTS Two hundred seven cases were included. The gingiva was the most common site (60.4%), followed by tongue and tonsil. The most common primary sites were lung (24.2%), kidney (13.5%), skin (10.6%), and breast (8.7%). In 27%, the oral lesion was the first sign of a malignant disease. In most cases, the lesion appeared as an exophytic mass (96%) diagnosed clinically as a reactive gingival lesion. The presence of teeth was significantly associated with the development of gingival metastases: in 108 of 125 gingival metastases, the lesion was found adjacent to teeth (P <0.001; odds ratio = 8.2). The average life expectancy after diagnosis of the metastasis was 3.7 months. CONCLUSIONS The gingiva is the most common site for metastases to oral soft tissues, with strong association with the presence of teeth. This finding may be related to the role of inflammation in the attraction of metastatic cells to chronically inflamed gingiva.

Topical Simvastatin Improves the Pro-Angiogenic and Pro-Osteogenic Properties of Bioglass Putty in the Rat Calvaria Critical-Size Model

Objective was to describe the effect of bioactive glass putty with and without topical simvastatin on new bone formation in critical-sized defects of rat calvaria. A calvarial bone defect was created in 20 male Wistar rats and filled with bioactive glass alone (n = 10) or combined with simvastatin (n = 10). After 4 weeks, the defects were histomorphometrically evaluated for volume fraction (Vv) of woven bone, vessel density, bioglass quantity, and inflammation. Compared to the bioglass-only group, rats treated with simvastatin had greater Vv of blood vessels (3.3% ± 0.7 vs 1.6% ± 0.1, P = .0002) and new bone (2.3% ± 0.2 vs 1.8% ± 2.5, P = .003). The Vv of the bioglass remnants in the bioglass-only group was higher than in the group treated with simvastatin (2.4% ± 0.08 vs 1.7% ± 0.3, P < .0004). Chronic inflammation was noted in 1 rat from each group. Topical simvastatin seems to improve the pro-angiogenic and pro-osteogenic properties of bioglass putty in rat calvaria critical-size defects without significant inflammation.

Lipomatous tumors of the oral mucosa: histomorphological, histochemical and immunohistochemical features.

We conducted a comprehensive study of all lipomatous tumors of the oral mucosa (1996-2008) accessioned at the Department of Oral Pathology, Tel Aviv University, collected demographic data and analyzed multiple histomorphological features. Furthermore, we examined the immunostaining of aP2 (adipocyte lipid binding protein) and the polarization colors of picrosirius red (PSR)-stained collagen fibers in order to test their potential in differentiating between benign and malignant tumors. All cases were immunohistochemically stained with aP2 antibody; only tumors with considerable collagenous stroma were selected for the PSR staining. A total of 77 tumors were included in the study, 91% benign and 9% malignant. Fibrolipoma (37.7%) and lipoma (36.4%) were the most frequent tumors. Atypical lipomatous tumor (ALT) was the only type of malignancy. The most common location for the benign tumors was the buccal mucosa and for ALT, the tongue. Histomorphological features characteristic of malignant tumors were occasionally present also in the benign entities. Expression of aP2 was similar in all tumors, while the polarization colors of the PSR-stained collagen fibers differed significantly between ALT and benign tumors (p<0.05). Benign and malignant tumors occasionally show overlapping histomorphological features that require a meticulous examination. PSR staining with polarization microscopy could aid in differentiating malignant from benign tumors in equivocal cases.

Localized juvenile spongiotic gingival hyperplasia possibly originates from the junctional gingival epithelium-an immunohistochemical study.

To immunohistochemically evaluate the cytokeratin (CK) pattern of expression in localized juvenile spongiotic gingival hyperplasia (LJSGH) as compared with the gingival epithelium (GE).

Gold nanorods reflectance discriminate benign from malignant oral lesions

Nanoparticle-based contrast agents have been used as an imaging tool for selectively detecting cancerous processes. We aimed to evaluate the detection sensitivity of reflection measurements of gold nanorods (GNRs) bio-conjugated to anti-epidermal growth factor receptor (GNRs-EGFR) monoclonal antibodies in discriminating benign from premalignant and malignant human oral lesions. Tissue sections incubated with GNRs-EGFR and the reflectance spectrum was measured using hyperspectral microscopy. Reflectance intensity increased with the progression of the disease, lowest in the control group and increasing as the dysplastic changes increase (P<0.001 for linear trend of grade). Intensity was significantly higher in the moderate and severe dysplasias and cancer patients than in the controls and mild dysplasia (t test P=0.0003, Mann-Whitney P<0.0001). The GNRs reflection measurements can discriminate benign and mild dysplastic lesions from the more severe dysplasia and invasive cancer, suggesting an objective, not dependent on the qualification of a technician and with less interpretation errors.

Re-evaluation of common paradigms regarding the clinical appearance of oral mucosal malignancies

PURPOSE To evaluate the clinical appearance and rate of ulceration of oral mucosal malignancies, and to investigate the accuracy of clinical provisional diagnoses. METHODS A 10-year retrospective analysis, which included diagnostic biopsies of malignant tumors of the oral mucosa. The clinical provisional diagnoses were compared with final diagnoses. RESULTS Two hundred and twenty-seven oral mucosal malignant tumors were included. Squamous cell carcinoma and its variants accounted for the majority (78%) of all malignant tumors. The most common clinical presentations were non-ulcerated (59.7%) and ulcerated masses (20.4%). Only 11.9% presented as indurate ulcers. The highest ulceration rate of all malignancies was recorded for SCC, with only about half of SCC and its variants ulcerated at the time of biopsy. 31.1% of all malignancies were not clinically suspected to be malignant and did not even include a request to rule out malignancy. There was a better agreement between the clinical provisional diagnoses and microscopic diagnoses in the SCC group than in other types of malignancy (P < 0.001). CONCLUSION Within this study sample, non-ulcerated masses rather than indurate ulcers are the most common clinical appearance of oral mucosal malignancies, and even for SCC, that showed the highest ulceration rate at presentation, half were non-ulcerated. Approximately, one-third of oral mucosal malignancies were not suspected to be malignant prior to biopsy. Thus, the level of suspicion currently reserved for mucosal ulcers and ulcerated masses should also be applied to non-ulcerated oral mucosal masses.