Central odontogenic fibroma: new findings and report of a multicentric collaborative study.

OBJECTIVE: The aim of this study was to describe the clinicopathologic and immunohistochemical characteristics of 14 cases of central odontogenic fibroma (COF), and the ultrastructural features of 2 of them. STUDY DESIGN: Collaborative retrospective study based on the records of 4 oral pathology diagnostic services in Latin America based on the current World Health Organization classification. RESULTS: There were 7 male and 7 female patients (mean age 31.8 years). Eight tumors occurred in the maxilla and 6 in the mandible. Thirteen cases were epithelium-rich and 1 epithelium-poor COF. Three were classified as hybrid COF with giant cell lesion. Mean size of the hybrid lesions were larger than pure COF (3.8 vs. 2.4 cm). Odontogenic epithelial islands were immunoreactive for cytokeratin (CK) AE1/AE3, CK5, CK14, CK19, and 34BE12 and negative for CK1 and CK18. Langerhans cells positive for S-100 and CD1a were found within the epithelial islands in 6/6 tested cases. CD68 was expressed in the giant cells of the hybrid lesions and in a few mononuclear cells of 2 cases of COF. Ki-67 index was <1% in all cases. In 6 tumors (42.8%), there were small globular eosinophilic droplets within the epithelial islands, which were positive for collagen type IV, and 9/13 cases (69.2%) were focally positive for smooth muscle actin. In addition to fibroblasts, myofibroblastic differentiation was found in the 2 cases studied ultrastructurally. CONCLUSIONS: Immunohistochemistry was useful to confirm the presence of epithelium and to exclude other central fibrous tumors. COF also contains a variable number of mast cells, Langerhans cells, and myofibroblasts, and further studies are needed to better understand the participation of these cells in COF histogenesis.

Comparative cytokeratin expression in the different cell types of salivary gland mucoepidermoid carcinoma.

Mucoepidermoid carcinoma is the most common malignant salivary gland tumor, composed of several different cell types, with controversial histogenesis. The aim of this study was to assess the expression of cytokeratins in mucoepidermoid carcinoma, comparing to cytokeratin expression in normal salivary glands, in order to establish a possible correlation between tumor cells immunostaining and mucoepidermoid carcinoma histogenesis and differentiation. Eighty cases of salivary gland mucoepidermoid carcinoma were immunohistochemically examined with the use of antibodies against cytokeratins 6, 7, 8, 13, 14, 18, and 19. Cytokeratin expression varied according to the cellular type: squamous cells presented high expression of cytokeratins 6, 7, 8, 14, 18, and 19; intermediate and mucous cells of cytokeratin 7; clear and columnar cells of cytokeratins 6, 7, 8 and the latter also expressed cytokeratin 18. Cytokeratin 13 expression was low in all cell types. Cytokeratin immunoexpression in mucoepidermoid carcinoma was variable according to the cellular type; but regardless of the cellular type studied, cytokeratins 7 and 13 were, respectively, constantly high and low expressed. The immunoprofile of the normal salivary glands was variable according to the component but, in general, cytokeratin profile in mucoepidermoid carcinoma showed similarity to the immunoexpression on the excretory duct unit of normal salivary glands.

Hepatoblastomas and liver development: a study of cytokeratin immunoexpression in twenty-nine hepatoblastomas.

Hepatoblastomas (HBs) recapitulate liver development. It is possible that HBs result from malignant transformation of hepatic precursor cells, and they may reflect a blockage in normal development. Here we study the expression of cytokeratins (CKs) in order to delineate the immunoprofile and relationship with liver development, as well as vimentin and alphafetoprotein (AFP), of HBs. Immunohistochemistry was performed in a tissue microarray (TMA) containing representative areas of 18 HBs (fetal and/or embryonal and/or mesenchymal); we also reviewed 11 cases not included in the TMA. No cases stained for CKs 1, 5/6, 7, 10, 13, 15, 16, 20, and 34betaE12. CK8 stained 73.07% of fetal, 50% of embryonal, and 18% of mesenchymal areas. CK18 stained 100% of epithelial areas. CK19 staining was intense and diffuse in 100% of embryonal samples, but it was weaker in fetal areas (66.66%). AE1 stained epithelial areas in all cases, and it stained 29.41% of mesenchymal areas. AE3 stained 84.61% of embryonal and 60% of fetal components. AE1/AE3 showed stronger staining in embryonal (100%) than in fetal areas (76.92%). Vimentin staining was strong in embryonal (66.66%) and mesenchymal (84.61%) components but weak in fetal areas (8%). Alphafetoprotein was positive in only 20% of fetal and 70% of embryonal areas. Our results support the hypothesis that immunoexpression of HBs follows the stages of normal liver development. Embryonal areas look less differentiated, expressing vimentin and biliary epithelium CKs, whereas fetal areas display a more developed phenotype, similar to that of mature hepatocytes. These data aid in understanding the ontogenesis of HBs and may be used in histopathological diagnosis.

Cytokeratins and dermatology.

Cytokeratins are fibrous intermediate-filament protein polymers present in almost all animal cells. Their function is related to epithelium structural maintenance, protection from mechanical trauma, and possibly communication between adjacent cells or cytoplasm components. Today there are 20 known cytokeratins, classified according to their molecular weight and pH as type I or acidic (cytokeratins 9-20) and type II or neutral-basic (cytokeratins 1-8). Cytokeratins are always expressed in specific pairs for each type of tissue, composed of one unit of type I and one unit of type II. Primary structural defects of cytokeratins are associated with various keratinization impairments. Two of the better characterized defects are bullous epidermolysis and epidermolytic hyperkeratosis. Anti-cytokeratin monoclonal antibodies are being used for diagnostic purposes to characterize the origin of poorly differentiated tumors and metastatic solid tumors.

Calcifying odontogenic cyst: clinicopathological features and immunohistochemical profile of 10 cases.

BACKGROUND: Calcifying odontogenic cyst (COC) is an uncommon odontogenic lesion with few studies describing its immunohistochemical profile and proliferative activity reported in the literature. METHODS: Clinical and histological features and immunohistochemical expression of cytokeratins, Mel-CAM (CD146), bcl-2, PCNA and ki-67, in 10 cases of COC were studied. RESULTS: All 10 cases affected the maxilla, eight intraosseous and two peripheral. Five central cases were cystic and three were cystic associated with odontoma, and the two extraosseous showed solid histological pattern; immunohistochemistry was positive for cytokeratins 8, 14, 19, AE1/AE3 and 34betaE12 and bcl-2 in all cases, and Mel-CAM in six cases. Proliferative activity was greater in the epithelium of central cystic COC in relation to COC associated with odontoma and peripheral lesions. CONCLUSION: Calcifying odontogenic cysts showed odontogenic cytokeratin profile and bcl-2 and Mel-CAM expression indicate that these proteins may be involved in the development of COC. There were no recurrences after surgery, irrespective of their proliferative activity.

The cribriform features of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma: cytokeratin and integrin expression.

Cribriform areas are common features of both adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. Both are malignant salivary gland tumors that share similar histologic patterns, but with marked distinct clinical behavior. This study was undertaken to improve the accuracy of the histopathology diagnostic process, using an immunohistochemical panel to differentiate adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma, with special concern to the common cribriform areas shared by these tumors. Three-microm serial sections of these tumors were submitted to the streptavidin-biotin peroxidase immunotechnique against the monoclonal antibodies anticytokeratins 7, 8, 14 and 19, and anti-integrins beta1, beta3, and beta4. In the neoplastic lobules of adenoid cystic carcinoma cribriform type, the spaces were mainly surrounded by cells negative for the cytokeratins and integrins studied. In the solid type of adenoid cystic carcinoma, the microcystic areas were caused by spaces lined by neoplastic luminal cells positive for cytokeratins and presenting integrins concentrated in the apical pole of these cells. The cribriform areas of polymorphous low-grade adenocarcinoma were composed of cords of luminal cells, positive for cytokeratins and showing integrins disposed in a bipolar pattern. We concluded that cribriform areas of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma are histologically similar, although not identical. Indeed, their cellular composition is distinct and can be distinguishable from one another by the proteins of the cytoskeleton, by the integrins, or both.

Keratinas: biología celular y significado funcional normal y patológico / Keratins: cell biology and it normal and pathological functional significance

Las Keratinas (Ks), son filamentos intermedios que forman parte del citoesqueleto de las células epiteliales. Pueden expresarse en los epitelios simples (Ks. 7, 8, 19 y 20) y en epitelios estratificados (Ks. 1, 2, 5, 9, 10, 11, 16). La diferente expresión de estas proteínas multigénicas del citoesqueleto está ligada a programas de diferenciación celular específicos (OSBORN & WEBER, 1983; NAGLE, 1988); por ello, el estuio de las Ks. tiene singular importancia en el conocimiento de nuevos aspectos de la Histología e Histopatología, como también de la Biología del Desarrollo. Además, la evaluación de las Ks. mediante técnicas de inmunofluorescencia o inmunohistoquímicas es útil en la correcta identificación y caracterización de las células normales, displásicas y neoplásicas (OSBORN & WEBER, NAGLE). Los distintos patrones de expresión de las Ks. se correlacionan con el grado de diferenciación de células epiteliales inmaduras, y, pór ello, con el grado de diferenciación de los tumores malignos. (FUCHS & GREEN, 1980; FRANKE et al. 1981b; MOLL et. al. 1892a; SCHAAFSMA & RAMAEKERS, 1994). Por último, la valoración de los cambios de inmunoexpresión de Ks. es útil para el diagnóstico diferencial entre metaplasias escamosas típicas y atípicas, incluyendo las displasias epiteliales moderadas y severas y las neoplasias intraepiteliales anteriormente denominadas carcinomas in situ (MOLL et. al., 1982a; TSENG et. al., 1982; QUINLAN et. al., 1985; HUSZAR et. al., 1986; GIGI-LEITNER et. al., 1986; HEID et. al., 1988)

Is there an interspecific diversity of the thymic microenvironment?

Thymic epithelial cells (TEC) heterogeneity suggests the existence of functional subsets. Anti-cytokeratin (Anti-CK) monoclonal antibodies (MAb), markers of epithelial differentiation, have been used to detect TEC subsets in rodents and humans. These MAb revealed a different topography of CK-defined TEC subsets in mice and humans, leading us to carry out a comparative study of mammalian thymuses. Our study showed that the distribution pattern of cytokeratins in the thymic epithelium is complex and unique, with coexpression of CK typical of simple and stratified epithelia. Moreover, we demonstrated an interspecific diversity of CK expression within the thymic lobules. Interestingly, such diversity was not a general phenomenon for the expression of any thymic microenvironmental proteins, because the location of extracellular matrix components was essentially similar in the mammalian species studied.

Modulation of cytokeratin expression in the hamster thymus: evidence for a plasticity of the thymic epithelium.

Cytokeratin (CK) expression was investigated, by means of immunocytochemistry, in the hamster thymic epithelium during ontogeny, as well as in primary cultures and upon glucocorticoid hormone treatment in vivo. As compared to the distribution pattern of distinct monoclonal antibody-defined cytokeratins in the normal adult thymus, CK modulation was evidenced in the three situations studied. During thymus ontogeny, both cytokeratins of simple lining epithelia, as CK8 and CK18, as well as the CK1/CK10 pair (typical marker of terminal stage of keratinization), were expressed since early stages of thymus development. They were located in the central region of thymic lobules preceding the cortical-medullary distinctions. This differed from what had been previously shown for mouse thymus ontogeny, revealing that the interspecific diversity in the distribution pattern of thymic cytokeratins occurred early in fetal life. A modulation of CK expression was also detected when hamster thymic epithelial cells (TEC) were led to grow in culture, with a down-regulation of CK19 contrasting with an enhancement of CK18 expression. This diverged from the maintenance of the in situ pattern when human TEC were cultured. Last, in vivo hydrocortisone treatment, known to increase the numbers of KL1+ cells in the mouse thymus medulla, promoted a cortical expression of the CK1/CK10 pair in the hamster thymus. Taken together, our findings demonstrate a continuous plasticity of the thymic epithelium, at least regarding cytokeratin expression, and enlarge the concept of interspecific diversity of intrathymic CK distribution in conditions as morphogenesis, in vitro system, and responsiveness to glucocorticoid hormone treatment.

Citoqueratinas y filagrina en psoriasis del cuero cabelludo: estudio inmunohistoquímico del folículo píloso en anágeno / Cytokeratins and philagrins in scalp psoriasis: inmunohistochemical study in the anagen hair follicles

Moderada a severa caída del cabello en psoriasis del cuero cabelludo se ha reportado. Sin embargo, la etiología de la alopecia en esta enfermedad aún no se conoce. El objetivo de nuestro estudio fue investigar, mediante inmunohistoquímica (técnica de APAAP), si el folículo piloso anágeno de cuero cabelludo afectado de psoriasis presenta cambios en la distribución de citoqueratinas y filagrina comparado con el folículo piloso de sujetos normales. La porción infraseboglandular del folículo piloso anágeno psoriático no presenta diferencias en la expresión de citoqueratina y filagrina en relación a los controles. En la porción supraseboglandular, el acrofundíbulo psoríatico muestra marcadas diferencias, similares a aquellas de la epidermis interfolicular. Los anticuerpos monoclonales anticitoqueratinas CK 8.12 Y PKK 2 marcan las capas suprabasales en la epidermis interfolicular como también en el acroinfundículo, mientras que normalmente se expresan sólo en la capa basal. Los anticuerpos monoclonales KL-1 U y CK 8.60 que marcan la capa basal y las citoqueratinas 1 y 2 (RPN 1161) no presentaron cambios en su patrón normal de marcaje de las capas suprabasales. Filagrina se mostró parcial totalmente ausente en las áreas paraqueratósicas de la epidermis interfoliar como también en la porción distal del acroinfundículo psoriático, mientras que la porción proximal se mostró prácticamente normal. De nuestros resultados concluimos que: 1) la porción no-permanente del folículo piloso anágeno psoriático no presenta cambios en la expresión de citoqueratinas y filagrina en comparación con los controles; 2) la caída del cabello en psoriasis debe atribuirse, por ejemplo, a efectos traumáticos de procedimientos terapéuticos y/o por la inflamación crónica que afecta a la porción permanente del folículo piloso