The neural histogenetic origin of the oral granular cell tumor: An immunohistochemical evidence

Aims: Granular cell tumor (GCT) is a rare neoplasm that can appear in any site of the body, but most are located intraorally. Its histogenetic origin remains unclear. This report analyzes the immunoprofile of 15 cases of granular cell tumors, occurring in 13 women and 2 men and the lesions were located on the tongue or upper lip. Patient age ranged from 7 to 52. Methods: The patients demographic data and the cytological and architectural features of the lesions were analyzed in oral GCTs (n = 15). The lesions were also submitted to a panel of immunohistochemical stains with antibodies against S-100, p75, NSE, CD-68, Ki-67, Synaptofisin, HHF-35, SMA, EMA, Chromogranin, Progesterone, Androgen and Estrogen. Results: Among the fifteen cases analyzed, the most common location was the tongue (84.6%). Histologically, the tumors exhibited cellular proliferation composed mainly by polygonal cells presenting an abundant granular eosinophilic cytoplasm. The nuclei were central, and the cell membranes were moderately clear. No mitotic figures were observed. The immunohistochemical analysis showed positivity in all cases for S-100, p75, NSE and CD-68, and no immunoreactivity for Ki-67, Synaptofisin, HHF-35, SMA, EMA, Chromogranin, Progesterone, Androgen and Estrogen. Conclusion: The immunoprofile of granular cell tumors showed nerve sheath differentiation - lending support to their neural origin - and helping to establish a differential diagnosis between this lesion and other oral granular cell tumors, whether benign or malignant.

Importance of cone beam computed tomography for diagnosis of calcifying cystic odontogenic tumor associated to odontoma. Report of a case

The calcifying cystic odontogenic tumour (CCOT) is a rare benign cystic neoplasm not infrequently associated with odontoma. This report documents a case of CCOT associated with compound odontoma arising in the anterior maxilla in a 25-year-old woman. Conventional radiographs showed a large calcified mass with poorly visualized radiolucent margins. The extent and condition of the internal structure of the CCOT associated with odontoma was able to be determined based on radiographic findings from cone beam computed tomography. This advanced image technique proved to be extremely useful in the radiographic assessment of this particular neoplasm of the jawbones.

Expression of extracellular matrix proteins in adenomatoid odontogenic tumor

Altered expression of extracellular matrix (ECM) components has been reported in several pathologies; however, few ECM proteins have been evaluated in adenomatoid odontogenic tumor (AOT). The aim of this study was to analyze the expression and distribution of the ECM proteoglycans: biglycan and decorin; and glycoproteins: osteonectin, osteopontin, bone sialoprotein and osteocalcin in the AOT. Three-micrometer sections from paraffin-embedded specimens were evaluated employing a streptavidin-biotin immunohistochemical method with the antibodies against the proteins previously cited. Only the osteonectin was expressed in the epithelial cells. The eosinophilic amorphous material and the connective tissue showed expression of all components studied. The calcification foci expressed only osteopontin. In conclusion, the low expression of the components studied in neoplastic epithelial cells suggests that the epithelial cells act probably as stimulators of the expression by the stroma, which in turn can act as agonist or antagonist of the tumor growth. These results suggest that the components studied probably have a key role in the biological behavior of the AOT.

Fibronectin as an adjuvant in the diagnosis of oral inflammatory myofibroblastic tumor

Inflammatory myofibroblastic tumor is a distinctive lesion composed of myofibroblastic spindle shaped cells accompanied by inflammatory infiltrate that may arise in various organs. It is believed to be a noneoplastic inflammatory condition, although this is still controversial. The recognition of inflammatory myofibroblastic tumor as an entity is important especially to avoid unnecessary surgery. A few cases have been reported in the oral cavity. This report primarily presents a case of inflammatory myofibroblastic tumor that arose in the floor of mouth of a 23-year-old woman. The proliferating spindle cells were immunoreactive for vimentin, smooth muscle actin, and muscle specific actin and negative for desmin, AE1/AE3, S-100, CD68, MyoD1 and caldesmon. In an attempt to assess the potential neoplastic nature of this lesion, immunohistochemical expression of ALK protein was performed, although no immunoreactivity was detected. Also, the presence of well differentiated myofibroblasts identified by fibronectin is discussed, as well as the importance in establishing an immunoprofile to better consolidate the diagnosis. We conclude that the study of fibronectin in case series may aid the diagnosis as well as the prediction of the tumor course.

Glial fibrillary acidic protein in tumor types with cartilaginous differentiation

Glial fibrillary acidic protein (GFAP) is a member of the intermediary filament protein family. It is an important component of astrocytes and a known diagnostic marker of glial differentiation. GFAP is expressed in other neural tumors and pleomorphic adenoma and, less frequently, in cartilage tumors, chordomas, and soft tissue myoepitheliomas. The aim of this study was to evaluate the role of GFAP and its reliability in nonglial tumors as an immunohistochemical marker. We evaluated GFAP gene and protein expression using Q-PCR and immunohistochemistry, respectively, in 81 and 387 cases of soft tissue, bone tumors, and salivary pleomorphic adenomas. Immunohistochemistry staining for GFAP was observed in all osteosarcomas (8 cases), all pleomorphic adenomas (7 cases), in 5 of 6 soft tissue myoepitheliomas, and in 21 of 76 chondrosarcomas. By Q-PCR, GFAP was highly expressed in pleomorphic adenomas and, to a lesser extent, chondrosarcomas, soft tissue myoepitheliomas, and chondroblastic osteosarcomas. The results that we obtained by immunohistochemistry and Q-PCR were well correlated. GFAP is a potential marker for tumors with cartilaginous differentiation, supported by evidence that GFAP is expressed in certain cases of myoepithelial tumors by immunohistochemistry, including soft tissue myoepitheliomas, which are related to cartilaginous differentiation. These findings contribute significantly to the diagnosis of soft tissue myoepitheliomas with cartilaginous differentiation and chondroblastic osteosarcoma in mesenchymal tumors. Modern Pathology ( 2009) 22, 1321-1327; doi: 10.1038/modpathol.2009.99; published online 7 August 2009

Recurrent bilateral gingival peripheral calcifying epithelial odontogenic tumor (Pindborg tumor): A case report

Calcifying epithelial odontogenic tumor (CEOT) is an extremely rare, benign neoplasm, accounting for approximately 1% of all odontogenic tumors. Peripheral CEOTs commonly resemble oral hyperplastic or reactive lesions and are histologically similar to their intraosseous counterparts. We report an unusual case of multifocal peripheral CEOT. A 40-year-old female presented with bilateral soft, painful, erythematous, gingival swellings localized in premolar areas of the mandibular gingiva. The presumptive diagnosis was bilateral pyogenic granuloma. The masses were surgically excised under local anesthesia without bone curettage and both recurred 12 months later. Morphologic features, and histochemical and immunohistochemical tests revealed bilateral peripheral calcifying odontogenic epithelial tumor. There is no clinical or radiographic evidence of recurrence 3.5 years after excision. This multifocal phenomenon has been reported previously only for intraosseous CEOT. Gingival masses must be carefully evaluated for clinical and histologic evidence of neoplasia. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: e66-e71)

Peroxiredoxin I is differentially expressed in multiple myelomas and in plasmablastic lymphomas

BACKGROUND: Plasmablastic lymphoma (PBL) and multiple myeloma (MM) are B cell-derived malignancies that share many morphologic and immunophenotypic traits, making the differential diagnosis particularly complicated. We have recently demonstrated that peroxiredoxin I (PrdxI) is expressed in plasma cells but not in B lymphocytes, suggesting that its expression is development-associated. AIM: To analyze PrdxI expression in PBL and in MM in order to study its utilization as an additional diagnostic molecular tool. METHODS AND RESULTS: Eight cases of PBL and nine of MM were studied by immunohistochemistry. We have demonstrated that PrdxI expression is closely connected with the immunoglobulin production capacity of the cells, which means high in MM, but absent in PBL cases, except one, wherein few cells were stained. CONCLUSIONS: We hypothesize PrdxI as a component of the unfolded protein response (UPR), an adaptive pathway essential for plasma cell differentiation. As we have not detected immunoglobulin in our PBL cases, we suggest that UPR was not activated in the cells, accounting for the impediment of the developmental process, and for the inhibition of PrdxI expression observed. PrdxI could be considered an additional plasma cell functional marker and could also be speculated as a therapeutic target in the treatment of MM. Oral Diseases (2008) 14, 741-746

Response of human dental pulp capped with MTA and calcium hydroxide powder

Objectives: To compare the response of human dental pulp capped with a mineral trioxide aggregate (MTA) and Ca(OH)(2) powder. Methods and Material: Pulp exposures were performed on the occlusal floor of 40 permanent premolars. The pulp was then capped with either Ca(OH)(2) powder (CH) or MTA and restored with resin composite. After 30 days (groups CH30 and MTA30) and 60 days (groups CH60 and MTA60), the teeth were extracted and processed for HE and categorized in a histological score system. The data were subjected to Kruskal-Wallis and Conover tests (alpha=0.05). Results: In regard to dentin bridge formation, CH30 showed a tendency towards superior performance compared to MTA30 (p>0.05), although the products showed comparable results at day 60. In the item ""Inflammation"" and ""General State of the Pulp"" (p>0.05), CH showed a tendency towards presenting a higher inflammatory response. In the item ""Other Pulpal Findings,"" MTA and Ca(OH)(2) showed equal and excellent performance after 30 and 60 days (p>0.05). Conclusion: After 30 days, Ca(OH)(2) powder covered with calcium hydroxide cement showed faster hard tissue bridge formation compared to MTA. After 60 days, Ca(OH)(2) powder or NITA materials showed a similar and excellent histological response with the formation of a hard tissue bridge in almost all cases with low inflammatory infiltrate.

Chemokines and chemokine receptors coordinate the inflammatory immune response in human cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) includes different clinical manifestations displaying diverse intensities of dermal Inflammatory infiltrate Diffuse CL (DCL) cases are hyporesponsive and lesions show very few lymphocytes and a predominance of macrophages In contrast localized CL (LCL) cases are responsive to leishmanial antigen and lesions exhibit granulocytes and mononuclear cell infiltration in the early phases changing to a pattern with numerous lymphocytes and macrophages later in the lesion Therefore different chemokines may affect the predominance of cell infiltration in distinct clinical manifestations In lesions from LCL patients we examined by flow cytometry the presence of different chemokines and their receptors in T cells and we verified a higher expression of CXCR3 in the early stages of LCL (less than 30 days of infection) and a higher expression of CCR4 in the late stages of disease (more than 60 days of infection) We also observed a higher frequency of T cells producing IL-10 in the late stage of LCL Using immunohistochemistry we observed a higher expression of CCL7 CCL17 in lesions from late LCL as well as CCR4 suggesting a preferential recruitment of regulatory T cells in the late LCL Comparing lesions from LCL and DCL patients we observed a higher frequency of CCL7 in DCL lesions These results point out the Importance of the chemokines defining the different types of cells recruited to the site of the infection which could be related to the outcome of infection as well as the clinical form observed (C) 2010 American Society for Histocompatibility and Immunogenetics Published by Elsevier Inc All rights reserved

Absence of functional TLR4 impairs response of macrophages after Candida albicans infection

Candida albicans is recognized by phagocytic cells through a set of recognition receptors patterns. Recently, we showed the importance of TLR2 in the regulation of neutrophil survival after C. albicans infection. In the present work, we analyzed the involvement of TLR4 in the recognition of C. albicans by neutrophils and macrophages. Our results show that the absence of functional TLR4 resulted in lower chemotaxis of neutrophils to the site of infection, lower levels of TNF-alpha, CXCL1 and nitric oxide, and dissemination and persistence of the pathogen in lymph nodes and spleen. In vitro, the phagocytic activity, nitric oxide production and myeloperoxidase activity, CXCL1, IL-1 beta production by neutrophils from TLR4-defective mice were not changed. In contrast, macrophages from TLR4-defective mice demonstrated lower phagocytosis and lower levels of CXCL1, IL-1 beta and TNF-alpha. Together, these data demonstrate that TLR4 signals are important for the recognition of C. albicans by macrophages and their absence allows persistence of the infection.

The Role of Toll-Like Receptor 2 in the Recognition of Aggregatibacter actinomycetemcomitans

Background: Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) is a Gram-negative bacterium present in the oral cavity and is usually associated with localized aggressive periodontitis. Isolated antigens from A. actinomycetemcomitans can activate innate immune cells through Toll-like receptors (TLRs), which are molecules that recognize structural components conserved among microorganisms. In this study, we evaluate the role of TLR2 in the recognition of A. actinomycetemcomitans. Methods: Macrophages and neutrophils from knockout mice with targeted disruption of TLR2 (TLR2(-/-) mice) and wild-type mice were collected and used for the subsequent assays. The production of cytokines and chemokines was evaluated by enzyme-linked immunosorbent assay (ELISA), and the presence of apoptotic cells was determined by flow cytometry. In addition, the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced periodontal disease in TLR2(-/-) mice were examined. Results: The results show that TLR2-deficient mice developed more severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly higher bone loss and inflammatory cell migration to periodontal tissues. The inflammatory cell influx into the peritoneal cavities of TLR2(-/-) mice was three-fold lower than that observed for the littermate controls. A significantly diminished production of the cytokines tumor necrosis factor-alpha and interleukin-1 beta as well as the chemokine CC-ligand-5 in the peritoneal cavities of TLR2(-/-) mice was observed. In addition, a high frequency of apoptotic cells in the inflammatory exudates from TLR2(-/-) mice was observed. Phagocytosis and nitric oxide production was diminished in cells from TLR2(-/-) mice, facilitating the dissemination of the pathogen to the spleen. Conclusion: The results of this study highlight the involvement of TLR2 in recognizing A. actinomycetemcomitans and its essential role in controlling A. actinomycetemcomitans infection. J Periodontot 2009,80:2070-2019.

Polysaccharide fraction of Agaricus brasiliensis avoids tumor-induced IL-10 production and changes the microenvironment of subcutaneous Ehrlich adenocarcinoma

Subcutaneous Ehrlich tumor-bearing mice were treated with in situ inoculation of a P-glucan-rich extract of Agaricus brasiliensis (ATF), which reduced tumor growth. Histopathological analysis showed that the tumor masses of control mice (Ehr) presented giant tumor cells and many mitotic figures whereas the tumor tissue obtained from ATF-treated animals (Ehr-ATF) presented a lower frequency of both mitotic and giant cells, associated with a higher frequency of apoptotic cells than Ehr. Analysis of the lymphoproliferative activity of spleen cells showed that the treatment had a suppressive rather than a stimulatory effect. Spleen cells of the Ehr group produced higher in vitro levels of IL-10 than normal controls and this occurrence was partially avoided by treatment with ATF. Analysis of cytokine production by tumor-infiltrating cells (ELISpot) showed that ATF induced a higher number of IFN-gamma-producing cells at 7 and 14 days as well as reduction of IL-10-secreting cells at the latter time. Confocal microscopy analysis showed higher intensity of labeling of CD4+ and Mac-3+ cells in ATF-treated mice. Analysis of in situ expression of angiogenic growth factors showed a slight decrease of FGF-2 mRNA in Ehr-ATF animals (7th day) but not of VEGF-A or TGF-beta expression. This fraction could not directly lyse either lymphocytes or tumor cells and we speculate that antitumor effect of ATF could be due to induction of a selective migration of immunocompetent cells from the spleen to the tumor site and to the switch of cytokine production. (C) 2009 Elsevier Inc. All rights reserved.

Warthin Tumor of the Upper Lip: An Unusual Location of a Benign Salivary Gland Tumor

Warthin tumor (papillary cystadenoma lymphomatosum) is a benign salivary gland tumor involving almost exclusively the parotid gland. The lip is a very unusual location for this type of tumor, which develops only rarely in minor salivary glands. The case of 42-year-old woman with Warthin tumor arising in minor salivary glands of the upper lip is reported.

Biomechanical and Microscopic Response of Bone to Titanium Implants in the Presence of Inorganic Grafts

This study evaluated the biomechanical and microscopic response of previously grafted bone to titanium implants. The lower incisors of 16 rabbits were surgically extracted, and bilateral perforations communicating with the remaining sockets were created distally. A socket/perforation defect on each mandible was chosen at random to be immediately filled with a xenogenic graft, whereas the contralateral perforation was left to heal naturally and served as a paired control. After 60 days, titanium implants were installed in the previously operated areas. After periods of 2 and 6 months, the animals were killed, and the force necessary to retrieve implants as well as the bone-implant contact (BIC) and bone mass (BM) were quantified and statistically compared by 2-way analysis of variance and Tukey`s test (alpha = .05). No significant differences in removal torque were observed, either by time or by treatment condition. Differences in BIC and BM between experimental and control groups were not statistically significant through the intervals studied (P < .05). The presence of a xenogenic graft did not influence the microscopic tissue response to titanium implants or fixation into newly formed or mature bone.

Auditory steady state response in pediatric audiology

The main issue regarding pediatric audiology diagnosis is determining procedures to configure reliable results which can be used to predict frequency-specific hearing thresholds. Aim: To investigate the correlation between auditory steady-state response (ASSR) with other tests in children with sensorineural hearing loss. Methods: Prospective cross-sectional contemporary cohort study. Twenty-three children (ages 1 to 7; mean, 3 years old) were submitted to ASSR, behavioral audiometry, click audiometry brain stem response (ABR), tone burst ABR, and predicting hearing level from the acoustic reflex. Results: the correlation between behavioral thresholds and ASSR was (0.70- 0.93), for the ABR tone burst it was (0.73 -0.93), for the ABR click it was (0.83-0.89) only at 2k and 4 kHz. The match between the ASSR and the hearing threshold prediction rule was considered moderate. Conclusion: there was a significant correlation between the ASSR and audiometry, as well as between ABR click (2k and 4 kHz) and for the ABR tone burst. The acoustic reflex can be used to add information to diagnosis in children.