Primary Pulmonary Choriocarcinoma After Human Chorionic Gonadotropin Normalization Following Hydatidiform Mole A Report of Two Cases

BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death.CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response to chemotherapy. Pulmonary lobectomy was performed, and hCG rapidly declined. During further chemotherapy, liver metastasis was detected by positron emission tomography. Right hepatectomy was performed, and hCG declined for 28 days, but increased again despite chemotherapy. This patient died from hepatic failure 3 years after diagnosis. Patient 2 presented with persistently high hCG, though the affected organ was not identified. Chemotherapy was unsuccessful. Patient reevaluation showed an isolated pulmonary mass. Pulmonary lobectomy was performed; 2 weeks later, hCG was normal and consolidation with 2 cycles of chemotherapy was administered. The patient has been in remission for 24 months. PPC was confirmed by histo pathology and immunohistochemistry in both cases. Gestational origin of the tumor was confirmed by molecular genetic analysis (polymorphic microsatellite markers).CONCLUSION: The possibility of choriocarcinoma cannot be overlooked in young women with an isolated pulmonary mass. Early diagnosis, prompt chemotherapy, and surgical resection in a specialized center improves the prognosis. (J Reprod Med 2010;55:311-316)

Vascular endothelial growth factor (VEGF) and VEGF-receptor expression in placenta of hyperglycemic pregnant women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hydatidiform Mole in Ectopic Pregnancy Clinical, Imaging, Pathological and Immunohistochemical Characteristics

OBJECTIVE: To determine the clinical, pathological, immunohistochemical and imaging characteristics of hydatidiform mole in ectopic pregnancy (HMEP) in all the cases admitted to the Department of Obstetrics and Gynecology, University Hospital of Caracas (HUC), Central University of Venezuela.STUDY DESIGN: Retrospective and comparative study, based on clinical records review of 2 groups: 10 cases with a diagnosis of HMEP and 20 cases with intrauterine hydatidiform mole (IUHM) admitted to the Obstetrics and Gynecology Department of HUC from 1996 to 2010. Clinical, pathological, immunohistochemical and imaging features were analyzed.RESULTS: The prevalence of HMEP in this study was 0.14:1,000 pregnancies; in this group the mean age was 28.8 years, and the mean gestational age at admission was 8.6 weeks. Both groups (HMEP and IUHM) were comparable in these last variables. Abdominal pain and genital bleeding were the most common clinical symptoms in the HMEP group, while it was vaginal bleeding in the IUHM group. Ultrasound findings were similar to those traditionally described in nonmolar ectopic pregnancy. Histology and immunohistochemistry showed that all cases of HMEP were partial mole.CONCLUSION: Although in this study the prevalence of HMEP was high, the size of the sample limits definitive conclusions. This study concludes that all cases of HMEP are partial mole. (J Reprod Med 2012;57:329-332)

Cell blocks allow reliable evaluation of expression of basal (CK5/6) and luminal (CK8/18) cytokeratins and smooth muscle actin (SMA) in breast carcinoma

Objective:Gene expression studies have revealed several molecular subtypes of breast carcinoma with distinct clinical and biological behaviours. DNA microarray studies correlated with immunohistochemical profiling of breast carcinomas using cytokeratin (CK) markers, Her2/neu, oestrogen receptor (ER), and basal myoepithelial cell markers have identified five breast tumour subtypes: (i) luminal A (ER+; Her2/neu-), (ii) luminal B (ER+; Her2/neu+), (iii) Her2 overexpression (ER-; Her2/neu+), (iv) basal-like (ER-; Her2/neu-, CK5/6 and 14+), and (v) negative for all markers. Luminal carcinomas express cytokeratins in a luminal pattern (CK8/18), and the basal-like type expresses CK5/6 and CK14 or basal epithelial cell markers. CK5/6, CK8/18, and smooth muscle actin (SMA) expression were assessed in cell blocks and compared with expression in surgical specimens.Methods:Sixty-two cases of breast carcinoma diagnosed by fine needle aspiration cytology with cell blocks and available surgical specimens were included. Cell blocks containing at least 10 high-power fields each with at least 10 tumour cells and surgical specimens were immunostained for CK5/6, CK8/18 and SMA.Results:Percentage sensitivity, specificity, positive predictive value, negative predictive value and accuracy were, respectively, 77, 100, 100, 92 and 94 for CK5/6; 98, 66, 96, 80 and 95 for CK8/18; and 92, 96, 85, 98 and 95 for SMA.Conclusion:The identification of CK5/6, CK8/18 and SMA by immunohistochemistry in cell blocks can be a reliable method that yields results close to those obtained in surgical specimens, and can contribute to the classification of breast carcinomas with luminal and basal expression patterns, providing helpful information in the choice of treatment and in the evaluation of prognostic and predictive factors.

Edema de Reinke: estudo da imunoexpressão da fibronectina, da laminina e do colágeno IV em 60 casos por meio de técnicas imunoistoquímicas

Edema de Reinke é doença crônica da laringe na qual a camada superficial da lâmina própria é expandida por muco espesso conferindo-lhe aspecto gelatinoso. Relaciona-se ao tabagismo e acomete, preferencialmente mulheres, as quais apresentam a voz mais grave. Suas características histológicas nem sempre conseguem diferenciá-lo das demais lesões benignas da laringe, havendo necessidade de técnicas histológicas adicionais. OBJETIVOS: Estudar a imunoexpressão da fibronectina, do colágeno IV e da laminina no edema de Reinke por meio de técnicas imunoistoquímicas. Estudo prospectivo. MATERIAL E MÉTODOS: Blocos histológicos de 60 casos cirúrgicos de edema de Reinke foram resgatados, submetidos a novos cortes e às reações imunoistoquímicas para fibronectina, laminina e colágeno IV pelo método da Avidina Biotina Peroxidase. Todos os pacientes eram fumantes e adultos, sendo 50 mulheres e 10 homens. RESULTADOS: As análises da imunoexpressão da fibronectina, do colágeno IV e da laminina foram mais expressivas no endotélio dos vasos (68,33%, 76,66%, 73,33%, respectivamente), e menos relevantes na membrana basal (25,0%, 5,0% e 3,3%, respectivamente). CONCLUSÕES: No edema de Reinke, a imunoexpressão da fibronectina, da laminina e do colágeno IV na membrana basal não apresentam relevância, havendo predomínio desses anticorpos no endotélio do vasos.

Vocal Polyps: Clinical, Morphological, and Immunohistochemical Aspects

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Vocal Fold Nodules: Morphological and Immunohistochemical Investigations

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin - An immunohistochemical survey of 476 primary and metastatic carcinomas

CDX2 is a recently cloned homeobox gene that encodes an intestine-specific transcription factor, expressed in the nuclei of epithelial cells throughout the intestine, from duodenum to rectum. While expression of CDX2 protein in primary and metastatic colorectal carcinomas has been previously documented, neither the sensitivity nor the specificity of CDX2 expression, as determined by immunohistochemistry, for colorectal adenocarcinoma has been determined. We performed an immunohistochemical survey of 476 tumors with a monoclonal antibody, CDX2-88, including 89 tumors from the colon and duodenum and 95 tumors from other gastrointestinal sites, including the esophagus, stomach, pancreatobiliary system, gastrointestinal carcinoids, and liver. CDX2 was expressed uniformly (that is, in 76-100% of tumor cells) in all but one of the evaluated colorectal and duodenal tumors. High-level expression of CDX2 was also found, however, in mucinous ovarian carcinomas and adenocarcinomas primary to the urinary bladder of which 64% and 100% were positive, respectively. Gastric, gastroesophageal, and pancreatic adenocarcinomas and cholangiocarcinomas all showed similar, heterogeneous patterns of CDX2 expression. Most tumors in each group showed CDX2 expression by a minority of cells, whereas a substantial minority of cases in each group was completely negative and a smaller minority was uniformly positive. Gastrointestinal carcinoids gave similarly varied results, but the majority (58%) was negative. Hepatocellular carcinomas showed no expression of CDX2. Only very rare examples of carcinomas of the genitourinary and gynecologic tracts, breast, lung, and head and neck showed significant levels of CDX2 expression. In this study of primary and metastatic epithelial tumors, uniform CDX2 expression is demonstrated to be an exquisitely sensitive and highly, but incompletely, specific marker of intestinal adenocarcinomas. Compared with villin, a previously described marker of GI adenocarcinomas, CDX2 demonstrated superior sensitivity and comparable specificity. CDX2 expression can be seen, however, in selected non-GI adenocarcinomas such as mucinous ovarian carcinomas and adenocarcinomas of the urinary bladder.

Biological differences between reflux stimulated proliferative stomal lesions and N-methyl-N '-nitro-N-nitrosoguanidine induced carcinomas in Wistar rats.

The morphology and evolution of epithelial lesions that developed at a gastrojejunal stoma due to reflux of duodenal contents were compared with MNNG-induced carcinomas in the pyloric mucosa of rats in a long term experiment. Random bred male Wistar rats were given MNNG in drinking water (100 mg/l) for 12 weeks and then one group was submitted to a gastrojejunal anastomosis at the greater curvature in the oxyntic mucosa, Untreated rats underwent either gastrojejunostomy or gastrotomy. The animals were killed at the 24th and 66th weeks of the experiment. The lesions obtained in the pyloric mucosa and in the mucosa of the gastrojejunal stoma were analyzed histologically using hematoxylin and eosin staining and immunohistochemistry for pepsinogen isoenzyme 1. Duodenal reflux induced proliferative lesions at the gastrojejunal junction that increased in incidence and size with time. Histologically they consisted of benign epithelial proliferation of gastric type. No evidence of malignant transformation within the gastric components of the proliferative lesions at the gastrojejunal stoma was observed even at the 66th week, Adenocarcinomas induced by MNNG in the pyloric mucosa increased in size during the experiment and were morphologically and histochemically distinct from the proliferative lesions at the gastrojejunal junction. In conclusion, proliferative lesions at the gastrojejunal stoma stimulated by duodenal reflux are biologically distinct from adenocarcinomas induced by MNNG in the pyloric mucosa. They do not seem to be precursor lesions of gastric carcinogenesis, as they do not undergo malignant transformation even after long-term, up to 66 weeks, follow-up. (C) 1999 Elsevier B.V. Ireland Ltd. All rights reserved.

Morphologic changes in the urethral epithelium in an ethanol-drinking rat strain (UChA and UChB)

The extreme use of ethanol causes metabolic and pathologic changes in testes and urogenital system in different animal species. The enzyme alcohol dehydrogenase (ADH) catalyses the conversion of ethanol into carcinogenic metabolite acetaldehyde which is partly excreted into the urine. However, papers relating the chronic ethanol consumption to the urethral morphology are unknown. This work evaluates the toxic effect of the chronic ethanol ingestion on the urethral epithelium of UChA and UChB rats. Conventional techniques of histology, histochemistry, immunohistochemistry and ultrastructural analysis were used. The analysis showed the presence of lipid drops and intercellular spaces in the epithelial cells in the urethra of UChA and UChB rats compared to control rats. Urethral neuroendocrine cell were observed and characterized for presenting vesicles containing electron-dense granules associated with nervous fibers. We conclude that the chronic consumption of ethanol induces the presence lipid drops in the epithelial cells of the urethra of UChA and UChB rats. The NE cells of the urethra of UChA and UChB rats did not show alterations under chronic effect of the ethanol. (C) 2007 Elsevier Ltd. All rights reserved.

Expression of cell cycle regulatory proteins in epithelial components of dental follicles

Dental follicle is a component of tooth germs, which remain adjacent to the crown of unerupted or impacted teeth. Under the influence of pathologic changes, however, dental follicles that possess reduced epithelium can proliferate into stratified squamous epithelium as far as originate dental cysts. In order to clarify the role of apoptosis and cellular proliferation herein, expression of p53 and PCNA was examined in epithelial components of dental follicles associated with impacted third molars by means of immunohistochemistry. A total of 40 cases was included in this study being 22 cases with reduced epithelium and 18 cases with stratified epithelium. Expression of p53 expression was weak or not detected in dental follicles with reduced and stratified squamous epithelium. By contrast, PCNA positive cells were evidenced in basal and supra basal layers of the stratified squamous epithelium and in reduced epithelium of dental follicles, but without any significant statistically differences between them (P > 0.05). In conclusion, these data suggest that dental follicles possess proliferative activity as depicted by PCNA-positive nuclei in some epithelial cells. However, the biological behavior of dental follicles during the late stage of dental eruptive process may not be associated with deregulation of death and/or cell proliferation.

Cigarette smoke affects apoptosis in rat tongue mucosa: Role of bcl-2 gene family

While it has been clearly demonstrated that smoking is the most significant exogenous factor involved in oral carcinogenesis, little is known about the global molecular and cellular changes that occur prior to the appearance of clinically detectable symptoms. Thus, the aim of this study was to investigate the expressivity of bcl-2, bax and PCNA in the rat tongue mucosa exposed to cigarette smoke by means of immunohistochemistry. A total of twelve male Wistar rats were distributed into 2 groups: negative control and experimental group exposed to cigarette smoke during 75 days. After experimental period, no histopathological changes in the tongue mucosa were detected in the negative control and the experimental group. on the other hand, an overexpression of bcl-2 was detected (p < 0.01) throughout all layers of the epithelium, whereas bax did not show significant differences (p > 0.05). Also, the labeling index for bcl-2 and bax showed an increase 75 days after cigarette exposure (p < 0.01). PCNA-labeling index did not show remarkable changes between groups. Taken together, our results show that bcl-2 is overexpressed in the rat tongue keratinocytes after cigarette smoke exposure.

Sewage sludge does not induce genotoxicity and carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo comparativo entre os métodos LSAB®+ e Herceptest® para a detecção de HER-2/neu em carcinoma de mama

INTRODUÇÃO: A hiperexpressão de human epidermal growth factor receptor (HER-2/neu) e a amplificação do seu gene são indicadores de formas mais agressivas do câncer de mama. A Food and Drug Administration (FDA) aprovou o teste denominado HercepTest® com a finalidade de selecionar pacientes com indicação para o uso de um anticorpo humanizado anti-HER-2/neu (trastuzumab), com efeito terapêutico comprovado. OBJETIVOS: O presente trabalho tem como objetivo comparar os resultados obtidos pelos métodos imuno-histoquímicos LSAB®+ com a utilização de anticorpo A0485 e HercepTest®. Material e métodos: Foram utilizados 50 casos de carcinoma de mama nos quais a pesquisa da hiperexpressão de HER-2 pelo método LSAB®+ já havia sido realizada. Foi repetida a pesquisa da hiperexpessão de HER-2/neu nos mesmos casos, utilizando-se o método do HercepTest®. RESULTADOS: 34 casos foram considerados negativos pelos dois métodos, com escore 0 pelo método HercepTest®. Destes, 12 obtiveram escore 1+ e 22 obtiveram escore 0 pelo método LSAB®+. em oito casos, o escore foi 2+ pelos dois métodos. Escore 3+ foi encontrado também em oito casos pelos dois métodos. DISCUSSÃO: O método mais prático utilizado em laboratório de rotina diagnóstica para investigar a hiperexpressão de HER-2/neu é o estudo imuno-histoquímico. em função de muitas variáveis, como tempo de fixação, tipo de fixador, duração da fixação, método de recuperação antigênica e tipo de anticorpo utilizado, pode haver divergência de resultados. CONCLUSÃO: O presente estudo concluiu que o método HercepTest®demonstrou resultados equivalentes aos resultados obtidos pelo método LSAB®+ em carcinoma de mama.

Critérios histopatológicos para diagnóstico de melanoma maligno cutâneo: análise comparativa de sua freqüência em lesões benignas e melanomas de pequena espessura (< 2 mm)

INTRODUÇÃO: A histopatologia convencional continua sendo o padrão-ouro no diagnóstico dos melanomas cutâneos, apesar do progresso da imuno-histoquímica e da biologia molecular. Os critérios microscópicos existentes para esse diagnóstico são numerosos, porém nenhum deles é específico para se afirmar que uma determinada lesão é maligna quando ele está presente, ou é benigna na sua ausência. Alguns critérios têm uma relevância maior para o diagnóstico em relação a outros. OBJETIVO: Este estudo propõe uma análise daqueles critérios considerados mais importantes, comparando sua presença em lesões melanocíticas benignas e melanomas. MATERIAL E MÉTODOS: Foram estudadas 33 lesões melanocíticas benignas (nevo de Spitz: 13; nevo de Reed: 6; nevo displásico: 6; nevo congênito: 3; nevo adquirido: 3; nevo combinado: 1; nevo recorrente: 1), bem como 101 casos de melanomas extensivo/superficiais: 25 intra-epidérmicos e 76 invasivos de pequena espessura (< 2 mm). RESULTADOS: Alguns critérios mostraram alta freqüência em lesões benignas, apresentando pouca especificidade, enquanto outros tiveram menor positividade nas benignas, e alta freqüência nas malignas, mostrando sua maior especificidade e importância no diagnóstico dos melanomas. CONCLUSÃO: Os cinco critérios que mostraram diferenças estatisticamente significativas na comparação com as lesões benignas foram (em ordem decrescente de freqüência): 1. proliferação linear de células isoladas na camada basal; 2. início e fim da lesão com células isoladas; 3. melanócitos na camada granular; 4. disseminação pagetóide extensa; 5. nucléolos grandes, irregulares ou múltiplos. Os melanomas de pequena espessura não apresentam parte dos critérios considerados mais importantes, como falta de maturação, necrose e mitoses profundas.