Expression Profile of Microenvironmental Factors in the Interface Zone of Colorectal Cancer: Histological-Stromal Biomarkers and Cancer Cell-Cancer-Associated Fibroblast-Related Proteins Combined for the Assessment of Tumor Progression.

INTRODUCTION: The characterization of tumor microenvironment (TME) related factors and their impact on tumor progression have attracted much interest. We investigated cancer cells and cancer-associated fibroblasts (CAFs) to evaluate biomarkers that are associated with neoplastic progression, observing them in different interface zones of colorectal cancer. METHODS: On 357 CRC tissue microarrays, using immunohistochemistry, we examined the associations of podoplanin and α-SMA expressed in cancer cells and CAFs and evaluated them in different areas: tumor core, invasive front, tumor budding, tumor-stroma ratio (TSR) scoring, and desmoplastic stroma. RESULTS: CAFs expressing α-SMA were found in more than 90% of the cases. Podoplanin+ was detected in cancer cells and CAFs, with positivities of 38.6% and 70%, respectively. Higher α-SMA+ CAFs and podoplanin+ cancer cells were observed predominantly at the TSR score area: 94.3% and 64.3% of cases, respectively. The status of podoplanin in CAFs+ was higher in the desmoplastic area (71.6%). Stroma-high tumors showed increased expression of α-SMA and podoplanin in comparison with stroma-low tumors. The status of podoplanin in cancer cells was observed in association with lymphatic invasion and distant metastasis. CONCLUSION: The substance of the CRC was composed predominantly of the surrounding stroma-α-SMA+ CAFs. Podoplanin expressed in the prognosticator zones was associated with unfavorable pathological features. The combination of histologic and protein-related biomarkers can result in a tool for the stratification of patients with CRC.

Geographic tongue and fissured tongue in 348 patients with psoriasis: correlation with disease severity.

Geographic tongue (GT) and fissured tongue (FT) are the more frequent oral lesions in patients with psoriasis. The aims of this study were to compare the prevalence of GT/FT between psoriasis group (PG) and healthy controls (HC) and investigate the correlation between GT/FT and psoriasis severity using the PASI and age of psoriasis onset. Three hundred and forty-eight PG and 348 HC were selected. According to the age of psoriasis onset, the individuals were classified as having early psoriasis and late psoriasis. The severity of vulgaris psoriasis was determined according to PASI. A follow-up was conducted in patients with psoriasis vulgaris (PV) with GT to evaluate the progression of oral and cutaneous lesions. The FT and GT were more frequent in PG than in HC. The incidence of GT was higher in patients with early psoriasis and that of FT in late-psoriasis. There is association between psoriasis intensity and GT; and a higher monthly decrease of PASI score in patients without GT. The presence of GT and FT is higher in PG than in the HC. GT is associated with disease severity and may be a marker of the psoriasis severity.

Inducible nitric oxide synthase/CD95L-dependent suppression of pulmonary and bone marrow eosinophilia by diethylcarbamazine.

RATIONALE: The mechanism of action of diethylcarbamazine (DEC), an antifilarial drug effective against tropical pulmonary eosinophilia, remains controversial. DEC effects on microfilariae depend on inducible NO synthase (iNOS). In eosinophilic pulmonary inflammation, its therapeutic mechanism has not been established. We previously described the rapid up-regulation of bone marrow eosinophilopoiesis in ovalbumin (OVA)-sensitized mice by airway allergen challenge, and further evidenced the down-regulation of eosinophilopoiesis by iNOS- and CD95L-dependent mechanisms. OBJECTIVES: We investigated whether: (1) DEC can prevent the effects of airway challenge of sensitized mice on lungs and bone marrow, and (2) its effectiveness depends on iNOS/CD95L. METHODS: OVA-sensitized BALB/c mice were intranasally challenged for 3 consecutive days, with DEC administered over a 12-, 3-, or 2-day period, ending at the day of the last challenge. We evaluated: (1) airway resistance, cytokine (IFN-gamma, IL-4, IL-5, and eotaxin) production, and pulmonary eosinophil accumulation; and (2) bone marrow eosinophil numbers in vivo and eosinophil differentiation ex vivo. MEASUREMENTS AND MAIN RESULTS: DEC effectively prevented the effects of subsequent challenges on: (1) airway resistance, Th1/Th2 cytokine production, and pulmonary eosinophil accumulation; and (2) eosinophilopoiesis in vivo and ex vivo. Recovery from unprotected challenges included full responses to DEC during renewed challenges. DEC directly suppressed IL-5-dependent eosinophilopoiesis in naive bone marrow. DEC was ineffective in CD95L-deficient gld mice and in mice lacking iNOS activity because of gene targeting or pharmacological blockade. CONCLUSIONS: DEC has a strong impact on pulmonary eosinophilic inflammation in allergic mice, as well as on the underlying hemopoietic response, suppressing the eosinophil lineage by an iNOS/CD95L-dependent mechanism.

Standardized Assessment of the Tumor-Stroma Ratio in Colorectal Cancer: Interobserver Validation and Reproducibility of a Potential Prognostic Factor.

The tumor stroma plays a relevant role in the initiation and evolution of solid tumors. Tumor-stroma ratio (TSR) is a histological feature that expresses the proportion of the stromal component that surrounds cancer cells. In different studies, the TSR represents a potential prognostic factor: a rich stroma in tumor tissue can promote invasion and aggressiveness. The aim of this study was to evaluate the reproducibility and determine the interobserver agreement in the TSR score. The stromal estimate was evaluated in patients diagnosed with colorectal adenocarcinoma (CRA), who underwent surgical resection. We also evaluated age, gender, and other anatomopathological features. Tumor-stroma ratio was calculated based on the slide used in routine diagnostic pathology to determine the T-status. Stromal percentages were separated into 2 categories: ⩽50%-low stroma and >50%-high stroma. The interobserver agreement in the TSR scoring was evaluated among 4 pathologists at different stages of professional experience, using 2 different ways to learn the scoring system. In total, 98 patients were included in this study; 54.1% were male, with a mean age of 61.9 years. Localized disease was diagnosed in 60.2% of patients. Stromal-poor CRA was predominant. The concordance between the TSR percentages of the 4 pathologists was substantial (Kappa > 0.6). There was greater agreement among pathologists for stromal-poor tumors. Substantial agreement and high reproducibility were observed in the determination of TSR score. The TSR score is feasible, suggesting that the presented methodology can be used to facilitate the determination of the stromal proportion of potential prognostic factor.

A simple technique to construct tissue macroarrays.

AIMS: In the diagnostic or research field, there is a need that the histopathological evaluation provides as much information as possible, with the shortest time and lowest cost. The development of the tissue microarray (TMA) technology has significantly facilitated and accelerated studies with tissue analyses using in situ technologies. Nevertheless, one of the most recognised limitations of TMA is that the small cores used to construct a TMA may not accurately represent characteristics of the whole tissue specimen. The aim is to present the technical aspects of a simple system to construct tissue macroarrays (TMaAs), its advantages and limitations, and some results of its use in for research purposes. METHODS: The study presents three possibilities of preparing the specimens with up to 6 mm diameter to be included into the TMaA paraffin block using our method. RESULTS: With this technique, it was possible to obtain glass slides with multiple whole fragments, which were used in five different studies. CONCLUSIONS: We presented a method for construction of multi-TMaA paraffin blocks, which is very simple for optimising laboratory techniques requiring paraffin-embedded tissue sections and can be easily implemented in any institution with a histology laboratory.

Evaluation of ICAM-1 expression and vascular changes in the skin of patients with plaque, pustular, and erythrodermic psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease. Pustular, erythrodermic, and extensive plaque psoriasis are responsible for systemic complications. Systemic capillary leak syndrome is the complication with greater progression to death and occurs due to vascular changes. PURPOSE: The aim of this study was to evaluate vascular changes through the expression of CD34 and ICAM-1 in plaque, pustular, and erythrodermic psoriasis. METHODS: The sample consisted of seven patients with erythrodermic psoriasis, 24 with moderate-severe plaque psoriasis, 14 with mild plaque psoriasis and 13 with pustular psoriasis. Patients were submitted to physical examination and skin biopsy for histopathological examination and immunohistochemical analysis with anti-CD34 and anti-ICAM-1 antibodies. Subsequently, tissue fragments were organized by groups using the Tissue Macroarray (TMA) technique to perform immunohistochemistry. RESULTS: In 58 patients, analysis of vessels using anti-CD34 demonstrated vascular immunostaining in superficial dermis and between dermal papillae. There were more blood vessels in erythrodermic psoriasis, followed by plaque psoriasis. In erythrodermic psoriasis, there were small and few tortuous blood vessels with great dilatation, while plaque psoriasis presented larger vessels that were less dilated and more tortuous. There was an intense and localized expression of ICAM-1 in endothelial and lymphocytic cells in all groups, with significant differences. CONCLUSIONS: Vascular alterations are important in psoriasis, with an increase in the number of blood vessels and ICAM-1 overexpression, especially in erythrodermic form. Therefore, vascular changes and the expression of intercellular adhesion molecules could help to diagnose the erythrodermic form of psoriasis.

Apocrine carcinoma in the parotid gland and in the submandibular region.

The objectives of this paper are to report a case of apocrine carcinoma and the discussion of aspects related to its diagnosis, treatment, and prognosis. Carcinomas with apocrine differentiation not related to extramammary Paget's disease, ductal breast carcinoma, Moll's glands adenocarcinoma and ceruminous glands carcinoma are very uncommon tumors. We report a case of a 51-year-old black woman who developed apocrine carcinoma lesions in the head and neck region. Two lesions involved her left parotid gland (first tumor and local recurrence), and other involved her submandibular skin. The microscopic aspects were as follows: infiltrative glandular epithelial neoplasm with moderate cellular and nuclear pleomorphism; neoplasic cells with polygonal or circular shape, large nuclei and eosinophilic and granular cytoplasm. The apical decapitation secretion was viewed in a large number of intra-cystic tumor cells. Moreover, we found areas with comedo-necrosis or PAS positive staining (with or without diastase). Based on cutaneous apocrine carcinoma compatibility of the microscopic aspects, we concluded that the tumor in the submandibular skin was probably the primary neoplasm. The patient was treated by surgical excisions, and no evidence of recurrent or metastatic disease has been seen after a follow-up period of 12 months.

Actinic prurigo of the lip: Two case reports.

Actinic prurigo is a photodermatosis that can affect the skin, conjunctiva and lips. It is caused by an abnormal reaction to sunlight and is more common in high-altitude living people, mainly in indigenous descendants. The diagnosis of actinic prurigo can be challenging, mainly when lip lesions are the only manifestation, which is not a common clinical presentation. The aim of this article is to report two cases of actinic prurigo showing only lip lesions. The patients were Afro-American and were unaware of possible Indian ancestry. Clinical exam, photographs, videoroscopy examination and biopsy were performed, and the diagnosis of actinic prurigo was established. Topical corticosteroid and lip balm with ultraviolet protection were prescribed with excellent results. The relevance of this report is to show that although some patients may not demonstrate the classical clinical presentation of actinic prurigo, the associated clinical and histological exams are determinants for the correct diagnosis and successful treatment of this disease.

Alterações eritrocitárias em pacientes com Lupus Eritematoso Sistêmico / Erythrocytic changes in patients with Systemic Lupus Erythematosus

Objetivo: Determinar as alterações eritrocitárias em pacientes com Lupus Eritematoso Sistêmico (LES), atendidos no Hospital Geral Universitário (HGU) Cuiabá/MT. Métodos: Amostras de sangue de 40 pacientes, do sexo feminino foram coletadas e processadas (automação ABX Pentra 80 – citometria defluxo). As análises estatísticas descritivas foram feitas com auxílio do software estatístico IBM SPSS 2.0. Resultados: Dos 40 pacientes analisados, 42,5% apresentaram anemia. As médias dos valores de hematócrito e dosagem de hemoglobina nos pacientes com anemia foram respectivamente de 29,7% e 9,9 g/dL, ao passo que naqueles nos quais não se observou quadro anêmico a média de hematócrito foide 41,1% e a de dosagem de hemoglobina 13,7g/dL. A anemia normocítica normocrômica foi a mais encontrada (64,7%) sendo observados, nessa situação, índices hematimétricos (VCM, HCM, CHCM e RDW) dentro dos valores de normalidade. As anemias macrocíticas e microcíticas tiveram a mesma representação percentual (17,6%). Entre as anemias macrocíticas, alterações hematimétricas, tais como, RDW aumentado, policromasia e reticulocitose observadas em alguns pacientes sugerem a possibilidade de processos hemolíticos comumente observados nessa patologia. Conclusão: Evidencia-se a necessidade de avaliar cuidadosa e frequentemente os achados do hemograma, pois é uma ferramenta importante na avaliação do paciente e da eficácia do tratamento.

Objective: We assessed the prevalence of erythrocytic changes in patients with SLE, at Cuiabá University General Hospital (UNIC-HGU). Methods: blood samples from 40 female patients were collected and processed (ABX Pentra 80 automation – flow cytometry). Descriptive statistical analyses were performed using IBM SPSS 2.0 statistical software. Results: 42.5% of the 40 patients showed lowered concentrations of hemoglobin. The hematocrit and hemoglobin dosage averages of the anemic patients were respectively of 29.7% and 9.9 gdL, while those without anemia showed 41.1% of hematocrit average and hemoglobin average dosage of 13,7gdL. Normocytic and normochromic anemia was the most prevalent, founded in 64.7% of the anemic patients, with normal hematimetric indices. In cases of macrocytic anemia, hematimetric changes, such as increased RDW, policromasy and reticulocytosis observed in some patients suggest hemolytic processes, commonly observed in these patients. Conclusion: Anemia was found in 42% of the patients and careful observation of the erythrocytic changes is an important tool in the follow up of LES patients.

Carcinoma apócrino na glândula parótida e na região submandibular / Apocrine carcinoma in the parotid gland and in the submandibular region

Os objetivos deste trabalho consistem na apresentacão de um caso de carcinoma apócrino e na discussão de aspectos relacionados ao seu diagnóstico, tratamento e prognóstico. Os carcinomas com diferenciacão apócrina que não correspondem aos casos de doenca extramamária de Paget, de carcinoma ductal de mama, de adenocarcinoma das glândulas de Moll e de carcinoma ceruminal são tumores muito raros. Relatamos o caso de uma paciente do sexo feminino, negra, com 51 anos, na qual duas lesões de carcinoma apócrino acometeram a parótida esquerda (processo inicial e recidiva) e uma lesão envolveu a pele da região submandibular do mesmo lado. O exame histopatológico destas lesões mostrou a presenca de neoplasia epitelial glandular infiltrativa com pleomorfismo celular e nuclear moderados; apresentando células poligonais ou arredondadas, com núcleos grandes e citoplasma eosinofílico e granular. Destacou-se a presenca de secrecão por decapitacão apical na maior parte das células tumorais voltadas para a luz das estruturas císticas neoplásicas. Adicionalmente, foi encontrada a presenca de focos de comedo-necrose e de material corado pelo PAS com e sem diastase. Apesar de não podermos definir com certeza qual a sede do tumor primário, com base nos aspectos histopatológicos compatíveis com o carcinoma apócrino cutâneo, consideramos que tenha sido, provavelmente, a lesão retirada da pele da região submandibular. A paciente foi submetida a tratamentos cirúrgicos e não apresentou alteracões após um ano de acompanhamento, depois da retirada do tumor recidivante na parótida.

Sífilis secundária: diagnóstico a partir das lesões orais / Secondary syphilis: diagnostic made by oral lesions

Introdução: a sífilis é uma doença infecto-contagiosa que se apresenta epidemiologicamente ascendente na saúde pública brasileira. Todos os profissionais da área de saúde devem estar atentos para as manifestações desta doença e para os possíveis locais de acometimento de lesões sifilíticas, inclusive manifestações bucais. Objetivo: relatar um caso clínico de sífilis recente que foi diagnosticado a partir de lesões intra-orais. Métodos: foram feitas a análise clínica e histopatológica das lesões do paciente, bem como exames laboratoriais (VDRL). Resultados: a associação dos achados anátomo-patológicos com o resultado positivo do VDRL confirmou a hipótese diagnóstica de sífilis. Conclusão: o conhecimento das manifestações orais da sífilis em todos os seus estágios por profissionais de saúde é de fundamental importância, para que os mesmos estejam capacitados a executar um diagnóstico correto e tratamento adequado.

O papel da neisseria gnorrhoeae na cavidade oral, uma revisäo da literatura / The role of neisseria gnorrhoeae in oral cavity, a literature review

Mudanças no comportamento sexual, início precoce da vida sexual e o uso de drogas constituem algumas das principais causas que têm contribuído para o incremento das doenças sexualmente transmissíveis. A gonorreia é uma doença infecciosa causada por um diplococo gram-negativo intracelular que tem predileçäo por mucosas. Logo, é surpreendente que a mucosa da cavidade oral näo seja infectada com mais frequência, que a relatada