Victor Angelo Martins Montalli

Tubular variant of basal cell adenoma shares immunophenotypical features with normal intercalated ducts and is closely related to intercalated duct lesions of salivary gland.

The morphological criteria for identification of intercalated duct lesions (IDLs) of salivary glands have been defined recently. It has been hypothesised that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of histological patterns, and the tubular variant is the one that presents the strongest resemblance with IDLs. The aim of this study was to analyse the morphological and immunohistochemical profiles of IDLs and BCAs classified into tubular and non‐tubular subtypes, to determine whether or not IDL and tubular BCA represent distinct entities.

In vitro cytokine expression in in situ-like areas of malignant neoplasia

OBJECTIVES The myoepithelial cells exert important effects regulating the transition of an in situ to an invasive carcinoma. This cell has been associated with a tumour suppressor phenotype due to its ability to inhibit tumour growth as well as its immunomodulatory role in cancer behaviour. DESIGN In order to correlate the cancer cell growth and the role of cytokines in regulating the neoplastic process, we have attempted to simulate an in vitro model of tumorigenesis, which mimics a situation where in situ neoplastic cells of carcinoma are surrounded by benign myoepithelial cells from pleomorphic adenoma. To certify the formation of in situ-like neoplasic areas, the cells were immunostained with vimentin and AE1/AE3, markers for tumoral benign myoepithelial cells and squamous cell carcinoma lineage, respectively. We investigated the correlation of the cancer cell growth with the releasing of IL-4, IL-6 and IL-10 associated with the immune response. The cytokines levels were evaluated using ELISA. RESULTS In in situ neoplastic areas, IL-6 amounts were higher released when compared with IL-4 and IL-10, in all studied periods. Interestingly, the peak of IL-6 release fits with the predominance of malignant cells in the culture. CONCLUSIONS The present results demonstrated that, in this in vitro condition, the myoepithelial cells were not able to suppress the tumour cell proliferation even with high secretion of IL-4 by benign myoepithelial cells which at the beginning is supposed to act as an anti-tumour agent. In addition, these cells favoured the tumour growth by excessive production of IL-6 and IL-10.

Signet-ring cell change in adenoid cystic carcinoma: a clinicopathological and immunohistochemical study of four cases

Signet‐ring cell (SRC) change has not been reported in adenoid cystic carcinoma (ACC). The aim of this study was to describe the clinicopathological and immunohistochemical findings in four cases of ACC with SRCs (ACC‐SRC), in which the relative proportion of the SRC component ranged from 25% to 50%.

Mammaglobin and DOG‐1 expression in polymorphous low‐grade adenocarcinoma: an appraisal of its origin and morphology

BACKGROUND Polymorphous low-grade adenocarcinoma (PLGA) remains a diagnostic challenge for most pathologists due to its large spectrum of histological patterns. In this study, the expression of two new markers recently described for salivary gland tumors was studied in PLGA. METHODS The morphology of 33 cases of PLGA was carefully evaluated using hematoxylin-and-eosin-stained sections and confirmed by immunohistochemistry for cytokeratin 7, vimentin, and S-100. Periodic acid-Schiff with diastase digestion was also used. The expression of mammaglobin and DOG-1 was carried out using the EnVision System. Mammaglobin was assessed according to the percentage of positively stained tumor cells, while DOG-1 was evaluated according to its presence and site. For MCM-2 and Ki-67, markers of proliferation, the labeling index of cell nuclei positivity was evaluated using total cell number. The ETV6-NTRK3 fusion was examined by fluorescence in situ hybridization analysis. RESULTS The histological patterns of the tumor were classified as lobular or non-lobular. For the non-lobular pattern, tubular, cribriform, glomeruliform, trabecular, and papillary patterns were observed. Mammaglobin was present in all PLGA cases, and its expression was stronger (P = 0.01) in the lobular than in the non-lobular pattern. The expression of DOG-1 was present in the apical portion and cytoplasm of the cells. Proliferation markers were low for all cases independent of histological pattern. CONCLUSIONS Polymorphous low-grade adenocarcinoma has been confirmed to originate from the intercalated duct and to feature high expression of mammaglobin in its lobular pattern resembling that of mammary secretory analogue carcinoma, except for the ETV6 gene rearrangement.

Presence of Cells in Fresh-Frozen Allogeneic Bone Grafts from Different Tissue Banks

Bone replacement materials have been widely used to reconstruct atrophic jawbones. Based on previous reports demonstrating the presence of viable cells in bone blocks even after processing by musculoskeletal tissue banks for orthopedic use, the aim of this study was to evaluate the presence of cells in bone blocks from three Brazilian tissue banks for maxillary reconstructions. All samples were processed by the respective tissue banks, according to the guidelines of the Brazilian National Sanitary Surveillance Agency. Three samples were removed from each block for subsequent histological processing and stained using hematoxylin & eosin. Further evaluation included section staining by the Feulgen method and ultrastructural analysis using scanning electron microscopy (SEM). Light microscopy images from all bone samples showed presence of osteocyte-like cells in all groups and intense Feulgen staining, demonstrating presence of DNA in bone even after tissue processing. The ultrastructural analysis showed red blood cells in lacunae within the bone tissue. In conclusion, despite bone tissue processing by the musculoskeletal tissue banks, cells may be found within the bone used for allogeneic grafts.

In vitro evaluation of the suppressor potential of conditioned medium from benign myoepithelial cells from pleomorphic adenoma in malignant cell invasion

Tumoral invasion process is the result of a complex interaction between the tumor cells and microenvironment which plays an important role in modulating the growth and invasion of the cancer. The myoepithelial cells, present in glandular organs such as the breast and salivary glands, seem to exert paracrine effects on the glandular epithelium, acting as natural tumor suppressors. To verify the influence of the benign myoepithelial cells in the invasion of malignant cells, simulating an in situ carcinoma ex pleomorphic adenoma, we have cultured three different high-potential invasive malignant tumors (breast ductal adenocarcinoma, melanoma and oral squamous cell carcinoma) in conditioned medium of myoepithelial cells from salivary gland pleomorphic adenomas using transwell chambers with 8-μm pores membrane coated with matrigel. After 96 h, quantitative analyses of the results were performed by calculating the invasion index (number of cells that invaded in relation to the total number of cells). The results showed that there was a reduction of the invasion index mean for the three different malignant tumors. This study supports a tumoral suppressor function of the myoepithelial cells from pleomorphic adenoma in in vitro invasion process.

Establishment of a primary culture of polymorphous low grade adenocarcinoma cells

OBJECTIVE The aim of the present study was to establish a primary cell culture derived from polymorphous low grade adenocarcinoma (PLGA). DESIGN The neoplastic cells were derived from a 57-year-old female patient diagnosed with PLGA. A fragment of the tumor was collected and submitted to enzymatic digestion followed by centrifugation on a Percoll gradient. The cell population was characterized by means of immunofluorescence and detection of PRKD1 gene mutations. RESULTS Epifluorescence analysis of the primary culture revealed that the malignant epithelial cells were predominantly polygonal in shape and positive for cytokeratin 7, vimentin, and S100. The doubling time of the cell culture was 86.73h. The restriction digestion assay showed that the neoplastic cells possess PRKD1 gene mutations. CONCLUSION The establishment of primary cell culture derived from PLGA should be considered a useful tool for molecular analysis of this salivary gland tumor.

Oral arteriovenous hemangioma in patient with hepatitis C.

To the Editor, Arteriovenous hemangioma represents a benign vascular skin lesion, first described in 1956,1 which typically appears in the skin of the extremities. Clinically, it appears as a small solitary painless papule. An association with chronic liver disease has been occasionally reported (Table 1). Occurrence in the oral cavity is rare, with only few cases reported involving the buccal sulcus, hard palate and soft palate.2 Herein, we report the case of a 46-year-old woman who had suffered from chronic active hepatitis associated with hepatitis C virus infection for 10 years and had received interferon therapy. The patient developed a symptomatic, solitary, dome-shaped reddish nodule, 15 mm in diameter, within the tongue dorsum (Fig. 1A). Histopathologically, the lesion consisted of a nonencapsulated proliferation of dilated blood vessels of various sizes within the lamina propria and the submucosa of the tongue. These proliferating blood vessels consisted of intermingled thick-walled and thin-walled vessels that resembled arteries and veins. Vessels were lined by single-layered endothelium and contained red blood cells (Fig. 1B). Toluidine blue staining revealed an increased number of mast cells near the wall vessels. These histopathological findings led to the diagnosis of arteriovenous hemangioma.

Factors that may influence polymorphous low-grade adenocarcinoma growth

There is mounting evidence on the importance of some biological processes in tumor growth, such as vascular supply, apoptosis, autophagy, and senescence. We have investigated these processes in polymorphous low-grade adenocarcinoma (PLGA), in an attempt to identify those that are relevant for this particular lesion. We analyzed 31 cases of PLGA using immunohistochemistry to antibodies against CD34 and CD105 to detect blood vessels; against D2-40 to detect lymphatic vessels; against Bax, Bcl-2, and survivin to explore cell apoptosis; and against Beclin and LCB3 to investigate autophagy and against p21 and p16 to assess senescence. Our results showed that PLGA growth does not depend on newly formed vessels but only on preexisting vasculature. Furthermore, PLGA is promoted by autophagy, sustained by both anti-apoptotic and anti-senescence signals, and stimulated by Bcl-2 and survivin.

Effects of Photobiomodulation on SOFAT, A T-cell-derived Cytokine, May Explain Accelerated Orthodontic Tooth Movement

Orthodontic tooth movement is based on mechanical forces inducing bone remodeling, and several methods have been proposed to increase tooth movement, including photobiomodulation. This study evaluated, in an animal model, the effects of photobiomodulation on SOFAT—a secreted osteoclastogenic factor of activated T cells and RANK‐L during tooth movement. The results showed that tooth displacement, RANK‐L and SOFAT levels were significantly greater compared to Control group. SOFAT may play an important role in bone remodeling during orthodontic movement, possibly increasing the osteoclast cells at the compression area and bone remodeling activity.