Initial panel of immunocytochemical markers for identification of primary carcinoma site for effusions and peritoneal washings from women.

INTRODUCTION: In women, most malignant effusions are from breast and ovary primary carcinomas that have metastasized to body cavity fluids (pleural, peritoneal and pericardial). When carcinoma is diagnosed in effusions, it is not possible to identify its site of origin solely by cytology (morphology); therefore, immunocytochemistry is used as a complementary method. There are no immunocytochemical markers with 100% sensitivity and specificity for identifying carcinoma primary site. The markers most used are TTF-1 for the lung, GATA-3 for the breast, and PAX-8 for the ovary. The aim of this study was to evaluate the sensitivity and specificity of a panel including these markers for detecting the primary site of carcinoma in effusions. METHODS: Samples of pleural, pericardial, and peritoneal effusions and peritoneal washings with carcinoma of known primary site from women (n = 60) and men (n = 18) were prepared by using the cell block method, and immunocytochemistry was performed to evaluate the expression of primary site markers (TTF-1, PAX-8, and GATA-3). RESULTS: In women, the breast was the most frequent primary site of metastatic carcinoma to both pleural and pericardial cavities, followed by the lung, whereas the ovary was the most frequent primary site of carcinoma within peritoneal effusions and washings, followed by the gastrointestinal tract (stomach or intestine). The expected profiles for carcinomas of the most common primary sites were: breast (GATA-3 (+), PAX-8 (-), TTF-1 (-)), ovary (PAX-8 (+), GATA-3 (-), TTF-1 (-)), lung (TTF-1 (+), PAX-8 (-) GATA-3 (-)) and gastrointestinal tract (PAX-8 (-), GATA-3 (-), TTF-1 (-)). These were observed in 88.23% (45/51) of women's samples with carcinoma from these primary sites. By using TTF-1 as the sole primary site marker, 6.25% of carcinomas of primary site other than the lung would have been misdiagnosed. CONCLUSION: An initial panel of markers including GATA-3, PAX-8, and TTF-1 allows, with high sensitivity and specificity, the identification or exclusion of frequent primary sites of carcinoma in effusions from women. Our results highlight the importance of using a panel of markers to avoid misidentification of the primary site of tumor.

Intradermal injections with 0.5% minoxidil for the treatment of female androgenetic alopecia: A randomized, placebo-controlled trial.

Female androgenetic alopecia is one cause of alopecia in women, although the ideal treatment for this condition remains far from defined. The objective of this study was to evaluate the efficacy and safety of intradermal injections with 0.5% minoxidil for the management of female androgenetic alopecia in a randomized, placebo-controlled trial. A total of 54 women diagnosed with female androgenetic alopecia were divided into two groups: one group received intradermal injections of 0.5% minoxidil, and the other received 0.9% saline. Biopsy, trichogram, Trichoscan (Tricholog GmbH, Freiburg, Germany), and self-assessment findings were used to evaluate the outcomes of treatment with minoxidil. In the treated group, there was a significant increase in the terminal-to-vellus hair ratio (P < .001) and in the percentage of anagen hairs (P = .048) and an improvement in hair loss and volume (P = .021 and P = .028, respectively). These results show that intradermal injections with minoxidil were more effective than placebo (P < .001) in the treatment of female androgenetic alopecia with a good safety profile.

P16 as a marker of carcinoma in effusions and peritoneal washing.

BACKGROUND: Considering the potential of p16 as a marker for diagnosis, prognosis and therapeutic response, the aim of this study was to assess its presence, via immunocytochemistry, in metastatic carcinoma of different primary sites and histological types obtained from effusions and peritoneal washings. A total of 118 samples including 85 of metastatic carcinoma and 33 samples of benign effusion/peritoneal washing were prepared by the plasma/thromboplastin method. Immunocytochemistry reactions were performed on cell block sections using antibodies against p16, claudin-4, MOC-31, calretinin, HBME and CD68. RESULTS: P16 overexpression was observed in 88.23% of all carcinoma samples. All cervix adenocarcinoma samples showed p16 overexpression. Overexpression in adenocarcinomas of ovary, lung and breast was observed in 93.75, 93.10 and 75% of the samples, respectively. Overexpression was observed in all different histological types analyzed: small cell carcinoma (lung), squamous cell carcinoma (cervical) and urothelial carcinoma (bladder). The specificity of p16 for carcinoma detection was of 96.96%. CONCLUSION: Overexpression of p16 was observed in most metastatic carcinoma, from different primary sites and histological types, obtained from effusions and peritoneal washings. Due to its high frequency of overexpression in metastatic carcinoma, p16 may play a possible role in tumor progression and it may be considered as a complementary diagnostic marker depending on histological type and primary site of carcinoma.

Anti-EpCAM antibodies for detection of metastatic carcinoma in effusions and peritoneal wash.

Epithelial cell adhesion molecule (EpCAM) has been used as diagnostic/prognostic marker and therapeutic target. The aim of the present study was to compare immunoreactivity of antibodies against distinct epitopes in the ectodomain of EpCAM for detection of carcinoma from different primary sites and of different histological types in effusions and peritoneal wash. Two antibodies against epitopes in the EGF-like domain I (clones Moc-31 and Ber-EP4) and one antibody against the epitope in the cysteine-poor region (158210) of EpCAM were used (all commercially available). Independently of the clone used, EpCAM overexpression was observed in almost all samples when all the adenocarcinoma samples were analyzed together. By using Moc-31, EpCAM overexpression was observed in all samples of adenocarcinoma. Absence of EpCAM overexpression was observed in a few adenocarcinoma samples at some sites of tumor origin, including ovary, breast and stomach, when Ber-EP4 and 158210 were used. Regarding carcinomas aside from adenocarcinomas, histological types, such as squamous cell, urothelial and small cell carcinoma showed different degrees of EpCAM expression according to the antibody used. In squamous cell carcinoma, overexpression was observed only with the clone 158210. It was concluded that, overall, most samples of metastatic carcinoma from effusions showed overexpression of EpCAM. However, there are significant variations in its detection according to the primary site, histological type of the carcinoma and depending on the antibody used. Thus, the use of more than one type of anti-EpCAM antibody would increase the chance of its detection in metastatic carcinoma effusion.

Study of the efficacy of N-methyl glucamine antimoniate (SbV) associated with photodynamic therapy using liposomal chloroaluminium phthalocyanine in the treatment of cutaneous leishmaniasis caused by Leishmania (L.) amazonensis in C57BL6 mice.

BACKGROUND: Pentavalent antimonials remain first-line drugs in the treatment of cutaneous leishmaniasis (CL); however, adverse effects and drug resistance have led to the search for less toxic and more effective treatments. As an alternative, topical phthalocyanine has been studied and its efficacy and low toxicity demonstrated. We aimed to study the in vivo efficacy of N-methyl glucamine antimoniate (NMG) associated with photodynamic therapy (PDT) with topical liposomal chloroaluminium phthalocyanine (AlClPC) in the treatment of experimental CL by L. amazonensis. METHODS: Experimental study with 54 C57BL6 isogenic mice divided into 9 groups including uninfected control, untreated control, PDT with AlClPC + NMG at doses of 10 and 20 mgSbV/Kg/day. The criteria to evaluate the treatment efficacy were: paw diameter, amastigote count, culture, viability test and parasite counts using MTT (3-bromo-4,5-dimethylthiazol-2,5-diphenyl-tetrazolium bromide). RESULTS: Treatment of CL with the association of NMG20 + PDT with AlClPC showed significant reduction of paw diameter, amastigote count, cultures, viability test and parasite counts. Parasite reduction occurred at the 10th and 20th days of treatment and 60 days after treatment ended, indicating that parasites did not multiply again. The NMG10 + PDT group with AlClPC presented results equivalent to gold-standard treatment (20 mgSbV/kg/day). Biochemical and histopathological evaluation showed minor changes. CONCLUSION: Treatment of CL caused by L. amazonensis with NMG20 mgSbV/kg/day + PDT with AlClPC was more effective than the traditional NMG20 mgSbV/kg/day.

PD-L1 May Mediate T-Cell Exhaustion in a Case of Early Diffuse Leishmaniasis Caused by Leishmania (L.) amazonensis.

Introduction: Diffuse cutaneous leishmaniasis (DCL) is a rare disease form associated with Leishmania (L.) amazonensis in South America. It represents the "anergic" pole of American Tegumentary Leishmaniasis, and the explanation for its resistance to treatment remains elusive. We aimed to study some possible immunological mechanisms involved in the poor DCL treatment response by evaluating some cell surface molecules obtained from a patient with DCL by flow cytometry. Case presentation: A 65-year-old DCL patient who initially failed to respond to the standard treatment for the disease showed vacuolated macrophages filled with amastigotes in lesion biopsy, and L. (L.) amazonensis was identified through ITS1PCR amplification. The Leishmania skin test and indirect immunofluorescence analysis revealed negative results. Peripheral blood from the patient was collected after a few months of treatment, when the patient presented with no lesion. Peripheral blood mononuclear cells were analyzed ex vivo and in vitro after 48 h of stimulation with soluble L. (L.) amazonensis antigen (SLA). Cell death, surface molecules, and intracellular molecules, such as IFN-γ and granzyme B, were analyzed in the cells using flow cytometry. Analysis of the surface markers showed an increased expression of the inhibitory molecule programmed death ligand 1 (PD-L1) in the monocytes restimulated with SLA (approximately 65%), whereas the negative controls were 35% positive for PD-L1. Conversely, compared with the negative controls, we observed a decrease in CD4+IFN-γ+ T cells (8.32 versus 1.7%) and CD8+IFN-γ+ T cells (14% versus 1%). We also observed a relevant decrease in the granzyme B levels in the CD8+ T cells, from 31% in the negative controls to 5% after SLA restimulation. Conclusion: The dysfunctional activation of PD-L1 inhibitory pathway after Leishmania antigen stimulation and reduced levels of IFN-gamma and granzyme B-producing cells could be closely related to unresponssiveness to standard drug treatment of DCL patient.

A panel of markers for identification of malignant and non-malignant cells in culture from effusions.

The aim of the present study was to identify cell types in primary culture from malignant and non-malignant effusions. Effusion samples were subjected to cytology and culture. Immunocytochemistry was performed in cytological slides to evaluate malignancy (positivity for malignancy markers) and in culture slides for identification of cell types in growth. A total of 143 effusion samples (pleural n=76; peritoneal n=37; pericardial n=4; and peritoneal lavage n=26) were analyzed. Cell growth was observed in 34.9% of all samples and immunocytochemistry for identification of cell types in culture slides was conclusive in 90% of them. In non-malignant samples (n=28), growth of mesothelial cells, macrophages and of both cell types was identified in 82.14, 10.71 and 7.14%, respectively. In malignant samples (n=17, all carcinomas), growth of malignant epithelial cells and of both malignant epithelial and mesothelial cells was identified in 41.17 and 23.52%, respectively. In the remaining 35.29% of malignant samples, the only cells in growth were mesothelial and/or macrophages instead of malignant epithelial cells. In conclusion, in culture of malignant effusions, mesothelial cells may be simultaneously identified with malignant epithelial cells. Besides, mesothelial cells and macrophages may be the only cells identified in malignant effusion culture. Therefore, a broad panel of cell markers should be used for unmistakable identification of cells in studies of effusion primary culture. The ideal malignant effusion sample to obtain culture of neoplastic cells should be that without the presence of mesothelial cells and macrophages.

Wade's histoid leprosy in a 14-year-old teenage boy.

Wade's histoid leprosy (HL) is a rare variant of multibacillary leprosy, with characteristic clinical, immunologic, histopathologic, and bacteriologic features. It is associated with resistance to sulfa drugs or polychemotherapy and is rarely observed in patients who have not undergone prior treatment. Clinically, HL resembles keloid or dermatofibroma. Furthermore, HL is rare in children and is difficult to diagnose even by experts. This report describes a case of HL in a 14-year-old Brazilian boy, who presented with multiple nodular and tumor-like lesions, simulating keloids. He had not undergone prior treatment with anti-leprosy drugs, which accentuates the relevance of this case report.

Wade's histoid leprosy in a 14-year-old teenage boy

Abstract Wade's histoid leprosy (HL) is a rare variant of multibacillary leprosy, with characteristic clinical, immunologic, histopathologic, and bacteriologic features. It is associated with resistance to sulfa drugs or polychemotherapy and is rarely observed in patients who have not undergone prior treatment. Clinically, HL resembles keloid or dermatofibroma. Furthermore, HL is rare in children and is difficult to diagnose even by experts. This report describes a case of HL in a 14-year-old Brazilian boy, who presented with multiple nodular and tumor-like lesions, simulating keloids. He had not undergone prior treatment with anti-leprosy drugs, which accentuates the relevance of this case report.

Síndrome de Peutz-Jeghers: novos dados e bases moleculares sobre uma doença rara / The Peutz-Jeghers syndrome: new data and molecular bases on a rare disease

A síndrome de Peutz-Jeghers é uma associação de polipose no trato gastrointestinal do tipo familiar e pigmentação melânica mucocutânea, particularmente nos lábios, mucosa bucal e polpa digital. Há poucas décadas, algumas centenas de casos haviam sido descritos na literatura, o que torna a doença não tão rara. O objetivo deste trabalho foi relatar casos clínicos em que os pacientes eram portadores da síndrome. Em um dos casos, tia e sobrinha evidenciaram a implicação genética da doença. Dados clínicos, bases moleculares e resultados histopatológicos, com a utilização de anticorpos (Ac) monoclonais, mostram a relevância do trabalho. Portadores crônicos da síndrome após décadas, ainda não diagnosticados, procuram o cirurgião-dentista para tratamentos diversos, dando-lhe oportunidade e responsabilidade na detecção da doença, devido ao risco de desenvolvimento de tumores malignos no trato gastrointestinal.

The Peutz-Jeghers syndrome is a familiar association of polyposis in the gastrointestinal tract and melanic mucocutaneous pigmentation, particularly in the lips, oral mucosa and fi ngertips. A few decades few hundred cases had been described in the literature wich makes the disease not so rare. The objective of this study is to report clinical cases where patients were carriers of the syndrome. In one of the cases the aunt and nice showed the genetic implication of the disease. Clinical data, molecular basis and histopathological results with monoclonal antibodies (Ac), show the relevance of this work. Chronic carriers of the syndrome after decades, still undiagnosed, seek the dentist for various treatments giving him the opportunity and responsibility to detect the disease due to the risk of development of malignant tumors in the gastrointestinal tract.

IMP3 expression in gastric cancer: association with clinicopathological features and HER2 status.

BACKGROUND: The aim of this study was to evaluate the expression of IMP3, an independent poor prognostic factor for many cancers, and its association with clinicopathological features and HER2 status. METHODS: Gastrectomy specimens from 106 patients were evaluated by immunohistochemistry and fluorescence in situ hybridization. RESULTS: HER2 overexpression was found in 4.71 % of the samples. A negative association was observed between HER2 overexpression and grade of differentiation. No association was observed between HER2 overexpression and status of surgical margins, vascular invasion, perineural invasion, nodal metastasis and depth of invasion. Among all specimens of gastric cancer, 67.92 % were positive for IMP3. Expression of IMP3 was significantly higher in specimens with vascular invasion, perineural invasion, nodal metastasis and higher depth of invasion. HER2 overexpression was detected in only 5.55 % of IMP3 positive specimens. CONCLUSIONS: IMP3 expression was frequently observed in gastric cancer and was associated with poor prognostic clinicopathological features. A survival benefit with HER2 therapy should be expected for the minority of patients with IMP3 positive specimens. Studies should be conducted to evaluate the response to HER2 therapy of gastric cancer expressing IMP3.

Synchronous Bilateral Warthin Tumors: A Case Report

Introduction: Warthin tumor is described as papillary cystadenoma lymphomatosum and is the second most common tumor of the parotid glands. Bilateral synchronous incidence is rare, occurring in 7 to 10% of the cases. It is more common in males between 60 and 70 years of age and is closely related to smoking. There is slow growth and the condition is a delimited nodule of regular outlines; it has low rates of malignant progression and recurrence. Objective: Report a case of synchronous bilateral Warthin tumor occurring in an elderly patient, and review incidence and peculiarities of this tumor. Case Report: A 78-year-old man who used to smoke had a history of mild pain in the topography of right parotid three weeks ago. Patient with hypertension, diabetes and a longtime smoker (smoking a pack per day for 32 years) noticed a progressive bulging in the right parotid region for about 2.5 years ago, and noticed another progressive bulging (althought in the left parotid region), for about one year ago. Patient denied fever, redness, skin lesions and pain during this period until last three weeks, when he sought medical attention for a mild pain in the right facial region. The patient underwent cervical magnetic resonance imaging that showed tumor lesions in both parotids. Fine needle aspiration revealed a typical lesion of epithelial oxyphilic cells associated with reactive lymphoid proliferation, suggesting Warthin tumor. The patient underwent two superficial parotidectomies, and the histopathologic result from both tumors of parotid glands showed papillary cystadenoma lymphomatosum. Conclusion: The occurrence of synchronous bilateral Warthin tumor is extremely rare, and anamnesis and physical examination, as well as some complementary examinations, are important means for diagnostic evaluation. Confirmation of the diagnosis can only be obtained through a histopathologic study. A superficial or total parotidectomy is the recommended treatment for the disease...

Synchronous bilateral warthin tumors: a case report.

Introduction Warthin tumor is described as papillary cystadenoma lymphomatosum and is the second most common tumor of the parotid glands. Bilateral synchronous incidence is rare, occurring in 7 to 10% of the cases. It is more common in males between 60 and 70 years of age and is closely related to smoking. There is slow growth and the condition is a delimited nodule of regular outlines; it has low rates of malignant progression and recurrence. Objective Report a case of synchronous bilateral Warthin tumor occurring in an elderly patient, and review incidence and peculiarities of this tumor. Case Report A 78-year-old man who used to smoke had a history of mild pain in the topography of right parotid three weeks ago. Patient with hypertension, diabetes and a longtime smoker (smoking a pack per day for 32 years) noticed a progressive bulging in the right parotid region for about 2.5 years ago, and noticed another progressive bulging (althought in the left parotid region), for about one year ago. Patient denied fever, redness, skin lesions and pain during this period until last three weeks, when he sought medical attention for a mild pain in the right facial region. The patient underwent cervical magnetic resonance imaging that showed tumor lesions in both parotids. Fine needle aspiration revealed a typical lesion of epithelial oxyphilic cells associated with reactive lymphoid proliferation, suggesting Warthin tumor. The patient underwent two superficial parotidectomies, and the histopathologic result from both tumors of parotid glands showed papillary cystadenoma lymphomatosum. Conclusion The occurrence of synchronous bilateral Warthin tumor is extremely rare, and anamnesis and physical examination, as well as some complementary examinations, are important means for diagnostic evaluation. Confirmation of the diagnosis can only be obtained through a histopathologic study. A superficial or total parotidectomy is the recommended treatment for the disease.

Mosaic epidermolytic ichthyosis--case report.

Epidermolytic ichthyosis is a rare autosomal dominant disease that manifests at birth with fragile blisters and erosions that evolve into hyperkeratotic lesions associated or not with erythroderma. When the disease is associated with a mutation in cytokeratin 1, it may be related to hyperkeratosis of palms and soles, but this is not usually found when cytokeratin 10 is mutated. The disease can present in a mosaic form, due to post zygotic mutation of the gene involved, constituting an individual formed by two populations of genetically distinct cells - one carrier of the mutation and the other without it. We report a case of mosaic epidermolytic ichthyosis diagnosed in a female patient.

Amelanotic metastatic cutaneous melanoma / Melanoma metastatico amelanotico cutaneo

Dermatoscopy of melanocytic lesions has guided the decision of when or not to biopsy a lesion. The use of this tool has increased clinical examination's sensitivity and specificity in 89% and 96% respectively. However, dermatoscopic evaluation of amelanotic or hypomelanotic melanomas, as well as metastases, can be difficult. There is still no standardization for the analysis of these pathologies, which relies mostly on their vascular pattern. We describe the dermatoscopy of acral metastatic amelanotic melanoma.

A dermatoscopia das lesões melanocíticas tem auxiliado na decisão de biopsiar ou não uma lesão. A utilização desta ferramenta aumentou a sensibilidade e a especificidade do diagnóstico para 89% e 96%, respectivamente. No entanto, a avaliação dermatoscópica de melanomas amelanóticos ou hipomelanóticos, bem como a de metástases cutâneas, pode ser difícil. Ainda falta uma padronização para a análise destas patologias, que se baseia, majoritariamente, no seu padrão vascular. Descreve-se a dermatoscopia de melanoma metastático amelanótico acral.

Mosaic epidermolytic ichthyosis - case report / Ictiose epidermolitica em mosaico - relato de caso

Epidermolytic ichthyosis is a rare autosomal dominant disease that manifests at birth with fragile blisters and erosions that evolve into hyperkeratotic lesions associated or not with erythroderma. When the disease is associated with a mutation in cytokeratin 1, it may be related to hyperkeratosis of palms and soles, but this is not usually found when cytokeratin 10 is mutated. The disease can present in a mosaic form, due to post zygotic mutation of the gene involved, constituting an individual formed by two populations of genetically distinct cells - one carrier of the mutation and the other without it. We report a case of mosaic epidermolytic ichthyosis diagnosed in a female patient.

A ictiose epidermolítica é doença autossômica dominante rara que se manifesta ao nascer com bolhas frágeis e erosões que evoluem para lesões hiperceratóticas associadas ou não a eritrodermia. Quando associada à mutação da citoqueratina 1 pode estar relacionada à hiperceratose palmoplantar, porém quando o defeito está relacionado à mutação da citoqueratina 10, este achado não é comumente encontrado. A doença pode ainda se manifestar em forma de mosaicismo somático, devido a mutação pós zigótica do gene envolvido, formando um indivíduo com duas populações de células geneticamente distintas, uma com a mutação e outra sem a mutação. Relata-se um caso de ictiose epidermolítica em mosaico em paciente do sexo feminino.

Cytological diagnosis of paracoccidioidomycosis: a report of four cases.

Paracoccidioidomycosis (PCM) is a common deep mycosis in South America caused by Paracoccidioides brasiliensis, a dimorphic fungus. Biopsy is the most frequent diagnostic method. The aim of this article is reporting four cases of PCM, in which intraoral involvement simulated squamous-cell carcinoma and was diagnosed by exfoliative cytology. We highlight this diagnostic tool as a simple, low cost, painless, noninvasive, and fast diagnostic method for PCM.

Amelanotic metastatic cutaneous melanoma.

Dermatoscopy of melanocytic lesions has guided the decision of when or not to biopsy a lesion. The use of this tool has increased clinical examination's sensitivity and specificity in 89% and 96% respectively. However, dermatoscopic evaluation of amelanotic or hypomelanotic melanomas, as well as metastases, can be difficult. There is still no standardization for the analysis of these pathologies, which relies mostly on their vascular pattern. We describe the dermatoscopy of acral metastatic amelanotic melanoma.