Immunohistochemical expression of p63, epidermal growth factor receptor (EGFR) and notch-1 in radicular cysts, dentigerous cysts and keratocystic odontogenic tumors

The aim of this study was to assess the immunohistochemical expression of p63 protein, epidermal growth factor receptor (EGFR) and Notch-1 in the epithelial lining of radicular cysts (RC), dentigerous cysts (DC) and keratocystic odontogenic tumors (KOT). For this study, 35 RC, 22 DC and 17 KOT were used. The clinical and epidemiological data were collected from the patient charts filed in the Oral Pathology Laboratory, University of Ribeirão Preto, Brazil. Immunohistochemical reactions against the p63, EGFR and Notch-1 were performed in 3-µm-thick histological sections. The slides were evaluated according to the following criteria: negative: <5% of positive cells, low expression: 5-50% of positive cells, and high expression: >50% of positive cells. Moreover, the intensity of EGFR and Notch-1 expressions was also evaluated. Fisher's exact test and Spearman's correlation coefficients were used for statistical analysis, considering a significance level of 5%. Almost all cases demonstrated p63, EGFR and Notch-1 expressions. The p63 expression was significantly higher in KOT (p<0.001). Positive correlation between these immunomarkers was observed. These findings suggest the participation of p63, EGFR and Notch-1 in the development, maintenance and integrity of cystic odontogenic epithelial lining, favoring lesion persistence. The high expression of p63 in KOT suggests that it may be related to their more aggressive biological behavior and marked tendency to recurrence.

O objetivo deste estudo foi avaliar a expressão imunoistoquímica da proteína p63, receptor do fator de crescimento epidérmico (EGFR) e Notch-1 no revestimento epitelial de cistos radiculares (CR), cistos dentígeros (CD) e tumores odontogênicos queratocísticos (TOQ). Para este estudo, 35 CR, 22 CD e 17 TOQ foram utilizados. Os dados clínicos e epidemiológicos foram coletados das fichas dos pacientes arquivadas no Laboratório de Patologia Oral, Universidade de Ribeirão Preto, Brasil. Reações imunoistoquímicas contra p63, EGFR e Notch-1 foram realizadas em cortes histológicos de 3 µm. As lâminas foram avaliadas de acordo com os seguintes critérios: negativo <5% das células positivas, baixa expressão - 5%-50% das células positivas e alta expressão >50% das células positivas. Além disso, a intensidade de expressão de EGFR e Notch-1 foi também avaliada. Teste exato de Fisher e coeficiente de correlação de Spearman foram usados para análise estatística, considerando um nível de significância de 5%. Quase todos os casos demonstraram expressão de p63, EGFR e Notch-1. A expressão de p63 foi significativamente maior nos TOQ (p<0.001). Correlação positiva entre os imunomarcadores foi observada. Esses achados sugerem a participação de p63, EGFR e Notch-1 no desenvolvimento, manutenção e integridade do revestimento epitelial cístico, favorecendo a persistência das lesões. A alta expressão de p63 no TOQ sugere que ela pode estar relacionada ao comportamento biológico mais agressivo e marcada tendência a recorrência.

Wilms tumor 1 protein is not expressed in oral lymphangiomas

Lymphangiomas are benign hamartomatous lesions of lymphatic vessels. Wilms Tumor 1 (WT1) is a transcription factor that is activated in some human neoplasias. WT1 protein expression is observed in endothelial cells during angiogenesis and is a useful marker to distinguish between vascular proliferations and vascular malformations. The purpose of the present study is to report a case series of oral lymphangiomas together with an immunohistochemical investigation of WT1. Seventeen cases of oral lymphangioma were retrieved and reviewed. Immunohistochemical analysis of WT1 protein was performed and pyogenic granuloma samples were used as positive controls. The male/female ratio was 1.125 and most of the lesions occurred in young subjects. While pyogenic granuloma showed positive staining for WT1, the endothelial cells lining the thin-walled dilated lymphatic vessels of lymphangiomas were negative for this protein. The findings strengthen the idea that oral lymphangioma is a vascular malformation characterized by lymphatic dilatation without significant endothelial proliferation.

Os linfangiomas são tumores hamartomatosos benignos dos vasos linfáticos. O Wilms Tumor 1 (WT1) é um fator de transcrição que se encontra ativo em algumas neoplasias humanas. A expressão da proteína WT1 é observada em células endoteliais durante a angiogênese e pode ser um marcador útil para distinguir as proliferações vasculares das malformações vasculares. O objetivo deste estudo foi relatar uma série de casos de linfangiomas orais e avaliar a expressão imunoistoquímica da proteína WT1. Dezessete casos de linfangiomas orais foram recuperados e revisados. A análise imunoistoquímica foi realizada e amostras de granuloma piogênico foram utilizadas como controle positivo. A relação homem/mulher foi de 1,125 e a maioria das lesões acometeram pacientes jovens. Enquanto o granuloma piogênico mostrou uma imunopositividade para WT1, as células endoteliais da fina parede dos vasos linfáticos dilatados apresentaram-se negativas para esta proteína. Tais achados reforçam a idéia de que o linfangioma oral é uma malformação vascular caracterizada por dilatação linfática sem uma proliferação endotelial significativa.

Interleukin-1 beta and interleukin-8 in healthy and inflamed dental pulps

After aggression to the dental pulp, some cells produce cytokines in order to start and control the inflammatory process. Among these cytokines, interleukin-1 beta (IL-1β) and interleukin-8 (IL-8) emerge as important ones. OBJECTIVE: The purpose of this study was to analyze the location, distribution and concentration of these cytokines in healthy and inflamed dental pulps. MATERIAL AND METHODS: Twenty pulps, obtained from healthy third molars (n=10) and from pulpectomies (n=10) were used for the study, with half of each group used for immunohistochemistry and half for protein extraction and ELISA assays. Fibroblasts obtained from healthy dental pulps, stimulated or not by Escherichia coli lipopolysaccharide (LPS), in order to simulate aggression on the cell cultures, were also used and analyzed by ELISA for IL-1β and IL-8 as complementary information. Data obtained from immunohistochemistry were qualitatively analyzed. Data obtained from ELISA assays (tissue and cells) were statistically treated by the t-test (p<0.05). RESULTS: Immunohistochemically, it was observed that inflamed pulps were strongly stained for both cytokines in inflammatory cells, while healthy pulps were not immunolabeled. ELISA from tissues quantitatively confirmed the higher presence of both cytokines. Additionally, cultured pulp fibroblasts stimulated by LPS also produce more cytokines than the control cells. CONCLUSIONS: It may be concluded that inflamed pulps present higher amounts of IL-1β and IL-8 than healthy pulps and that pulp fibroblasts stimulated by bacterial LPS produce higher levels of IL-1β and IL-8 than the control group.

Molecular and cellular pathogenesis of autosomal recessive polycystic kidney disease

Autosomal recessive polycystic kidney disease (ARPKD) is an inherited disease characterized by a malformation complex which includes cystically dilated tubules in the kidneys and ductal plate malformation in the liver. The disorder is observed primarily in infancy and childhood, being responsible for significant pediatric morbidity and mortality. All typical forms of ARPKD are caused by mutations in a single gene, PKHD1 (polycystic kidney and hepatic disease 1). This gene has a minimum of 86 exons, assembled into multiple differentially spliced transcripts and has its highest level of expression in kidney, pancreas and liver. Mutational analyses revealed that all patients with both mutations associated with truncation of the longest open reading frame-encoded protein displayed the severe phenotype. This product, polyductin, is a 4,074-amino acid protein expressed in the cytoplasm, plasma membrane and primary apical cilia, a structure that has been implicated in the pathogenesis of different polycystic kidney diseases. In fact, cholangiocytes isolated from an ARPKD rat model develop shorter and dysmorphic cilia, suggesting polyductin to be important for normal ciliary morphology. Polyductin seems also to participate in tubule morphogenesis and cell mitotic orientation along the tubular axis. The recent advances in the understanding of in vitro and animal models of polycystic kidney diseases have shed light on the molecular and cellular mechanisms of cyst formation and progression, allowing the initiation of therapeutic strategy designing and promising perspectives for ARPKD patients. It is notable that vasopressin V2 receptor antagonists can inhibit/halt the renal cystic disease progression in an orthologous rat model of human ARPKD.

Subcutaneous panniculitis-like T cell lymphoma in a HIV positive patient.

Immunocompromised patients are at increased risk for developing certain malignant tumors, particularly aggressive B cell lymphomas and extranodal lymphomas like primary central nervous system lymphoma and primary effusion lymphoma. T cell lymphomas are uncommon in these patients. We report a rare case of subcutaneous panniculitis-like T cell lymphoma in a HIV positive patient who presented with multiple subcutaneous nodules.

Cytological features of lobular carcinoma of breast: how important are the intracytoplasmic lumina?

Lobular carcinoma is the most common pitfall in the cytodiagnosis of breast lesions. Of the cytological features described intracytoplasmic lumina are stressed by many authors as an important diagnostic feature. The present study aims at evaluating the importance of intracytoplasmic lumina in the cytodiagnosis of lobular carcinoma along with other cytological features. Fine needle aspirates from 11 cases of histologically proven classical lobular carcinomas of breast were reviewed. It was observed that the low cellularity, dispersed dyscohesive small cells, mild pleomorphism, nuclear moulding and Indian filing were the most important cytologic features which aid in the diagnosis of lobular carcinoma where as intracytoplasmic lumina were of little significance.

Cytological study of copper in oral submucous fibrosis.

BACKGROUND: Habitual arecanut chewing is associated with Oral Submucous Fibrosis (OSF). High copper content in arecanut plays a vital role in pathogenesis of OSF. This study evaluates the copper-staining pattern of buccal epithelial cells in oral cytological smears of non-chewers, chewers, and OSF. MATERIALS & METHODS: Alcohol fixed buccal epithelial smears of 10 histopathologically confirmed cases of OSF, 10 chewers without lesion, and 5 nonchewers were stained with modified Rhodamine technique and studied under the light microscope. Buccal epithelial smears of non-chewers dipped in copper sulphate solution were used as known positive for copper. RESULT: Copper appeared as shades of palered within the cytoplasm of chewers and did not show any stain in non-chewers. Intense red stain was seen in OSF smears as dark granules within the cytoplasm. CONCLUSION: Intense staining of copper in OSF buccal smears, than in the chewers supports the role of copper in the pathogenesis of OSF.

Cytological findings in iron deficiency anemia.

Iron deficiency anemia is a common condition in India. We made an attempt to study the cytological changes in the buccal mucosal cells of iron deficiency anemia, patients. Buccal mucosal cells were scraped from 40 iron deficiency anemia patients and were subjected to morphometric analysis. Results of the study showed there is an increase in the cellular diameter, nuclear diameter, and nuclear:cytoplasmic ratio of iron deficiency anemia patients when compared to the normal values.

Ultrastructural Studies of Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract (GIT). Although interstitial cells of Cajal has been suggested as origin of this tumor, the cytological and ultrastructural features of GISTs are heterogeneous and unclear. A total 10 cases of normal gastrointestinal tissue (control), 13 GISTs of the stomach (8), small intestine (3), mesocolon (1) and liver (1), and 2 gastrointestinal autonomic nervous tumor (GANT) of small intestine were ultrastructurally studied. Normal interstitial cells of Cajal (ICC) were abundantly present around the myenteric plexuses or individually scattered through the wall of GIT. ICC was characterized by slender cytoplasmic processes, well-developed endoplasmic reticulum (ER), mitochondria, Golgi apparatus, caveolae and intermediate filaments. The GISTs and GANTs had overlapping ultrastructures. The most common and important ultrastructural features of GISTs were rich villous cytoplasmic processes, dispersed intermediate filaments and abundant SER, and those of GANTs were neurosecretory granules and skenoid fibers. Compared with ICC, the GISTs and GANTs had remarkably reduced caveolae and gap junctions. Our study suggested that ultrastructural analysis gives much information to investigate lineage differentiation of neoplastic cells and make a differential diagnosis of these tumors from other mesenchymal tumors and between GISTs and GANTs.

Pale bodies in hepatocellular carcinoma

Histochemical, immunohistochemical and ultrastructural studies were performed on cases of hepatocellular carcinoma (HCC) with pale bodies (PB). HCC containing PBs was observed in 3 (5.5%) of 55 consecutively resected HCC cases. Histologically, a large number of hepatocytes displayed pale or eosinophilic staining of the cytoplasm, resulting in ground-glass appearance. They were aggregated in nodular pattern, or diffusely intermixed with other malignant hepatocytes. PBs were negative for periodic-acid Schiff and Masson's trichrome staining. The inclusions showed a strong positive reaction for fibrinogen and some of them were weakly positive for albumin but negative for hepatitis B surface antigen, hepatitis B core antigen, alpha-fetoprotein and alpha-1-antitrypsin. Ultrastructurally, PBs were membrane-bound and contained granular materials of moderate electron density, and were closely related to dilated rough endoplasmic reticulum. These findings support that PBs are secretory fibrinogen accumulated in cystic ER and that such intracellular accumulation possibly reflects a defective transport of fibrinogen.

Fine needle aspiration cytology of hepatocellular carcinoma.

Fine needle aspiration cytology (FNAC) is an extremely useful technique in the evaluation of hepatic masses. This study was undertaken with the aim of describing the morphological spectrum seen in fine needle aspirates from hepatocellular carcinoma (HCC) seen in our patients hailing from South India. Thirty two cases of HCC were studied. Trabacular pattern covered by endothelium was the most common. Pseudoglandular, spindle cell and dispersed patterns were also seen. Individual tumour cells were generally reminiscent of hepatocytes, and had a prominent nucleolus. The presence of intranuclear and intracytoplasmic inclusions were notable features. FNA cytology in HCC is sufficiently distinctive to form an invaluable tool in the diagnosis of this malignancy.

Androblastoma de ovario; aspectos clinico-patologicos presentacion de un caso / Clinicopathologycal aspects of a case of androblastoms of ovary

Presentamos un caso de androblastoma, en una paciente de 52 anos de edad, que acudio con un cuadro clinico de amenorrea y signos de virilizacion. El objetivo de este reporte es mostrar un caso de neoplasia rara entre los tumores ovaricos y analizar las caracteristicas clinicas y patologias.