RESUMO
BACKGROUND: Hereditary nonpolyposis colorectal cancer (Lynch/HNPCC syndrome) is based on a germline mutation inducing increased occurrence of colorectal cancer and extracolonic carcinomas in young age. The German HNPCC consortium aims to increase awareness for detection of hereditary colon cancer among patients and physicians. OBJECTIVES: Reliable detection of HNPCC patients is based on a thorough documentation of patients' medical history and on further diagnostics delivered by human genetics and surgical pathology. This manuscript presents a standardized diagnostic concept. METHODS: Relevant literature is reviewed and discussed and diagnostic parameters are outlined. In addition, operating figures of the German HNPCC consortium are presented. RESULTS: The German HNPCC consortium is based on an efficient cooperation between clinical physicians, human geneticists, and surgical pathologists. After a funding period from the Deutsche Krebshilfe, HNPCC diagnostics and preventive medical examinations were transferred into standard care in Germany. In total, 5770 families (8873 patients) were included in HNPCC diagnostics. To date, in 1296 families, mutations of the MLH1-, MSH2-, MSH6-, PMS2-, or EPCAM-gene have been detected. Furthermore, 612 pathogenic variants and 325 variants of unknown significance were found. CONCLUSIONS: Reliable detection of HNPCC patients is based on a standardized diagnostic concept, which has been established within the German HNPCC consortium.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias do Colo/complicações , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Alemanha , Humanos , MutaçãoRESUMO
Gastroesophageal reflux disease is a common disorder in humans and has been treated for the last 67 years using fundoplication. However, treatment results have generally not been satisfactory. Physiological and anatomic findings must be taken into account to improve the therapy technique. In this article, these are described using the example of paradoxical sphincters and the effect of NO signal molecules in the gastrointestinal tract.
Assuntos
Fundoplicatura/métodos , Fundo Gástrico/fisiopatologia , Fundo Gástrico/cirurgia , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/cirurgia , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Animais , Humanos , Camundongos , Óxido Nítrico/fisiologia , Complicações Pós-Operatórias/fisiopatologia , Recidiva , Especificidade da Espécie , Resultado do TratamentoRESUMO
CONTEXT: Primary aldosteronism (PA) is the most common cause of secondary hypertension. Aldosterone excess can cause DNA damage in vitro and in vivo. Single case reports have indicated a coincidence of PA with renal cell carcinoma and other tumors. However, the prevalence of benign and malignant neoplasms in patients with PA has not yet been studied. PATIENTS AND DESIGN: In the multicenter MEPHISTO study, the prevalence of benign and malignant tumors was investigated in 335 patients with confirmed PA. Matched hypertensive subjects from the population-based Study of Health in Pomerania cohort served as controls. RESULTS: Of the 335 PA patients, 119 (35.5%) had been diagnosed with a tumor at any time, and 30 had two or more neoplasms. Lifetime malignancy occurrence was reported in 9.6% of PA patients compared to 6.0% of hypertensive controls (P = .08). PA patients with a history of malignancy had higher baseline aldosterone levels at diagnosis of PA (P = .009), and a strong association between aldosterone levels and the prevalence of malignancies was observed (P = .03). In total, 157 neoplasms were identified in the PA patients; they were benign in 61% and malignant in 25% of the cases (14% of unknown dignity). Renal cell carcinoma was diagnosed in five patients (13% of all malignancies) and was not reported in controls CONCLUSION: Compared to hypertensive controls, the prevalence of malignancies was positively correlated with aldosterone levels, tended to be higher in PA patients, but did not differ significantly.
Assuntos
Aldosterona/sangue , Biomarcadores Tumorais/sangue , Hiperaldosteronismo/fisiopatologia , Hipertensão/fisiopatologia , Neoplasias/epidemiologia , Adulto , Idoso , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/diagnóstico , Prevalência , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Synovial sarcoma is a high-grade soft tissue malignancy characterized by a specific reciprocal translocation t(X;18), which leads to the fusion of the SS18 (SYT) gene to one of three SSX genes (SSX1, SSX2 or SSX4). The resulting chimeric SS18-SSX protein is suggested to act as an oncogenic transcriptional regulator. Despite multimodal therapeutic approaches, metastatic disease is often lethal and the development of novel targeted therapeutic strategies is required. Several expression-profiling studies identified distinct gene expression signatures, implying a consistent role of Wnt/ß-catenin signaling in synovial sarcoma tumorigenesis. Here we investigate the functional and therapeutic relevance of Wnt/ß-catenin pathway activation in vitro and in vivo. Immunohistochemical analyses of nuclear ß-catenin and Wnt downstream targets revealed activation of canonical Wnt signaling in a significant subset of 30 primary synovial sarcoma specimens. Functional aspects of Wnt signaling including dependence of Tcf/ß-catenin complex activity on the SS18-SSX fusion proteins were analyzed. Efficient SS18-SSX-dependent activation of the Tcf/ß-catenin transcriptional complex was confirmed by TOPflash reporter luciferase assays and immunoblotting. In five human synovial sarcoma cell lines, inhibition of the Tcf/ß-catenin protein-protein interaction significantly blocked the canonical Wnt/ß-catenin signaling cascade, accompanied by the effective downregulation of Wnt targets (AXIN2, CDC25A, c-MYC, DKK1, CyclinD1 and Survivin) and the specific suppression of cell viability associated with the induction of apoptosis. In SYO-1 synovial sarcoma xenografts, administration of small molecule Tcf/ß-catenin complex inhibitors significantly reduced tumor growth, associated with diminished AXIN2 protein levels. In summary, SS18-SSX-induced Wnt/ß-catenin signaling appears to be of crucial biological importance in synovial sarcoma tumorigenesis and progression, representing a potential molecular target for the development of novel therapeutic strategies.
Assuntos
Proteínas de Fusão Oncogênica/fisiologia , Sarcoma Sinovial/metabolismo , Via de Sinalização Wnt , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Perileno/análogos & derivados , Perileno/farmacologia , Pirimidinonas/farmacologia , Sarcoma Sinovial/tratamento farmacológico , Triazinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Lymph node metastases originating from soft tissue sarcomas are very rare and the reason for this is unclear. While this observation was less important in former times when ultraradical excision and amputation were the norm, modern reconstructive surgical treatment options have to take the possibility of lymphatic metastases into account.We attempted to identify parameters that may be predictive of lymphatic metastases in a cohort of 1,597 patients with soft tissue sarcomas of whom 26 patients (1.6 %) had regional lymph node (RLN) metastases. We studied these RLN metastases with recently described techniques that enabled us to histologically visualize lymphatic vessels.We conclude that sarcomas should not be evaluated from a histogenetic perspective but more on the basis of regional topography of the lymphatic vasculature. As we described previously, two different lymphatic systems should be differentiated: lymphatic vessel system I (LGS I) contains RLN and lymph vessels are mostly superficial; however, there are also vessels near large blood vessels of the extremities. System LGS II is more delicate and its vessels run into the musculature, a metastatic homing area of many sarcomas. Lymph vessels of system LGS II drain directly into veins without intervening lymph nodes. Sarcomas with LGS I drainage will form RLN metastases. In contrast, sarcomas with LGS II drainage will do so only after surgical resection if system LGS I has been opened.
Assuntos
Metástase Linfática/patologia , Sarcoma/patologia , Sarcoma/secundário , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Estudos de Coortes , Progressão da Doença , Extremidades/patologia , Extremidades/cirurgia , Humanos , Linfonodos/patologia , Vasos Linfáticos/patologia , Músculo Esquelético/patologia , Músculo Esquelético/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Reoperação , Fatores de RiscoRESUMO
Synovial sarcomas account for 5-10% of all soft tissue sarcomas and the majority of synovial sarcomas display characteristic t(X;18) translocations that result in enhanced transcription of the insulin-like growth factor-2 (IGF-2) gene. IGF-2 is an essential fetal mitogen involved in the pathogenesis of different tumours, leading to cellular proliferation and inhibition of apoptosis. Here we asked whether activation of IGF signalling is of functional importance in synovial sarcomas. We screened human synovial sarcomas for expression of IGF-2 and the phosphorylated IGF-1 receptor (IGF-1R), which mainly mediates the proliferative and anti-apoptotic effects of IGF-2. Since both the phosphatidylinositol 3'-kinase (PI3K)-AKT pathway and the MAPK signalling cascade are known to be involved in the transmission of IGF-1R signals, expression of phosphorylated (p)-AKT and p-p44/42 MAPK was additionally assessed. All tumours expressed IGF-2 and 78% showed an activated IGF-1R. All tumours were found to express p-AKT and 92% showed expression of activated p44/42 MAPK. To analyse the functional and potential therapeutic relevance of IGF-1R signalling, synovial sarcoma cell lines were treated with the IGF-1R inhibitor NVP-AEW541. Growth was impaired by the IGF-1R antagonist, which was consistently accompanied by a dose-dependent reduction of phosphorylation of AKT and p44/42 MAPK. Functionally, inhibition of the receptor led to increased apoptosis and diminished mitotic activity. Concurrent exposure of selected cells to NVP-AEW541 and conventional chemotherapeutic agents resulted in positive interactions. Finally, synovial sarcoma cell migration was found to be dependent on signals transmitted by the IGF-1R. In summary, our data show that the IGF-1R might represent a promising therapeutic target in synovial sarcomas.
Assuntos
Receptor IGF Tipo 1/fisiologia , Sarcoma Sinovial/metabolismo , Transdução de Sinais/fisiologia , Adulto , Antineoplásicos/farmacologia , Apoptose , Western Blotting/métodos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Imunofluorescência , Humanos , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas/farmacologia , Pirróis/farmacologia , RNA Mensageiro/análise , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sarcoma Sinovial/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Sublingual immunotherapy (SLIT) represents an alternative to subcutaneous immunotherapy. While antigen-presenting cells such as Langerhans cells (LCs) are thought to contribute to the effectiveness of SLIT, mast cells (MCs) most likely account for adverse reactions such as sublingual edema. As little is known about LCs and MCs within the oral cavity, we investigated their distribution in search for mucosal sites with highest LCs and lowest MCs density. METHODS: Biopsies were taken simultaneously from human vestibulum, bucca, palatum, lingua, sublingua, gingiva, and skin. Immunohistochemistry and flow cytometry were used to detect MCs, LCs and high affinity receptor for IgE (FcepsilonRI) expression of LCs. Mixed lymphocyte reactions were performed to assess their stimulatory capacity. RESULTS: Highest density of MCs was detected within the gingiva, while the lowest density of MCs was found within the palatum and lingua. However, sublingual MCs were located within glands, which might explain swelling of sublingual caruncle in some SLIT patients. Highest density of LCs was detected within the vestibular region with lowest density in sublingual region. Highest expression of FcepsilonRI was detected on LCs within the vestibulum. Furthermore LCs from different regions displayed similar stimulatory capacity towards allogeneic T cells. CONCLUSIONS: In view of our data, different mucosal regions such as the vestibulum might represent alternative SLIT application sites with potent allergen uptake. Our data might serve as a basis for new application strategies for SLIT to enhance efficiency and reduce local adverse reactions.
Assuntos
Dessensibilização Imunológica/métodos , Hipersensibilidade/imunologia , Células de Langerhans/imunologia , Mastócitos/imunologia , Mucosa Bucal/imunologia , Administração Sublingual , Contagem de Células , Humanos , Hipersensibilidade/terapia , Células de Langerhans/citologia , Mastócitos/citologia , Mucosa Bucal/citologia , Receptores de IgE/imunologia , Receptores de IgE/metabolismoRESUMO
BACKGROUND: Synovial sarcoma (SS) is a mesenchymal malignancy, which predominantly occurs at the lower extremities of young adults. Only 3 % of the SS show a primary manifestation in the head and neck region. METHODS: A retrospective chart review (years 2002 - 2006) of our Department of Otorhinolaryngology, head and neck surgery, School of Medicine, Bonn, Germany, was performed searching for patients with primary head and neck manifestations of SS. PATIENTS: Four patients (2 female, 2 male) with a median age of 21 (12 - 28) years were assessed at our facility. RESULTS: The location of the SS was the oropharynx respectively, infiltrating adjacent structures. 3 patients underwent radical surgery followed by chemotherapy, 2 in combination with irradiation. 1 patient underwent primary chemotherapy and irradiation. The histological diagnosis was a biphasic SS as well as a monophasic SS in 2 patients respectively. Fluorescence-in-situ-hybridization was performed in order to detect the distinctive chromosomal translocation t(X;18). 2 patients were in complete remission at the recent follow-up, 1 patient died 14 months after diagnosis due to a lethal carotidal haemorrhage. 1 patient was lost to follow-up. CONCLUSIONS: The aggressive character of the SS as well as its high recurrence rate afford a radical therapeutic scheme enclosing surgical, chemotherapeutical and radiological treatment as well as a thorough follow-up. The genetic translocation t(X;18) leads the way to the right diagnosis. The prognosis of head and neck SS must be considered as poor. SS should be taken into consideration in head and neck tumors of unclear nature.
Assuntos
Neoplasias Otorrinolaringológicas/diagnóstico , Sarcoma Sinovial/diagnóstico , Adolescente , Adulto , Biomarcadores Tumorais/análise , Criança , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Imageamento por Ressonância Magnética , Masculino , Mucina-1/análise , Estadiamento de Neoplasias , Neoplasias Otorrinolaringológicas/patologia , Neoplasias Otorrinolaringológicas/terapia , Sarcoma Sinovial/patologia , Sarcoma Sinovial/terapia , Vimentina/análiseRESUMO
Somatic epimutations in the MLH1 promoter mimic the phenotype of Lynch syndrome. To date, no somatic hypermethylation of the MLH1 promoter in the carrier of a pathogenic MLH1 germline mutation has been identified, prompting the recommendation that a germline mutation in MLH1 should only be sought in the absence of tumour tissue methylation. We aimed to determine whether methylation of the MLH1 promoter may coexist in carriers of a pathogenic germline mutation in MLH1. We examined the methylation status of the MLH1 promoter in 123 tumour tissue samples, demonstrating high microsatellite instability and loss of expression of a mismatch repair protein (60 cases with MLH1 germline mutation, 25 cases without mutation, 38 cases with MSH2 mutations), using combined bisulphite restriction analysis (COBRA) and SNaPshot analysis. Methylation of the MLH1 promoter was found in two patients with pathogenic germline mutations, one a carrier of a MLH1 mutation and the other a carrier of a MSH2 mutation. Our results demonstrate that methylation of the MLH1 promoter region does not exclude the presence of a germline mutation in a mismatch repair (MMR) gene. Hypermethylation of the MLH1 promoter may be present in most cases of sporadic colorectal cancers, but this does not exclude a diagnosis of Lynch syndrome.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Mutação em Linhagem Germinativa , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Colorretais Hereditárias sem Polipose/metabolismo , Metilação de DNA , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA/métodos , DNA de Neoplasias/genética , Humanos , Instabilidade de Microssatélites , Proteína 1 Homóloga a MutL , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismoRESUMO
AIMS: AP2alpha (TFAP2A) and AP2gamma (TFAP2G) transcription factors have been implicated in the control of proliferation, differentiation and apoptosis of normal breast epithelium and in breast cancer. The aim of this study was to provide a comprehensive analysis of the expression patterns of TFAP2A and TFAP2G in the developing fetal breast anlage with other relevant markers. METHODS AND RESULTS: Sixty fetal and one infant human breast specimens from 14 weeks of gestational age to 5 months old were examined. The primary breast outgrowth/nipple showed TFAP2A expression by the basal cells (week 14), followed later by cytokeratin (CK) 5 co-expression (week 17). Sprouting of the secondary outgrowths was characterized by HER-2+ invading cells. Preliminary ductal buds were lined by TFAP2G/HER-1-expressing myoepithelial precursors (week 19). Maturation of TFAP2A/CK18+ epithelia and TFAP2G/smooth muscle actin-positive myoepithelia proceeded in a distal-to-proximal manner beginning in the terminal end buds (week 22). CK5+ progenitor cells and CK5/TFAP2A or CK5/TFAP2G co-expressing intermediary glandular or myoepithelial cells were found in the terminal end buds of neonatal fetal breast tissue. CONCLUSIONS: AP2 transcription factors may play decisive pacemaker roles in initiating and coordinating budding and branching processes during formation of the fetal breast anlage, possibly via modulation of an epidermal growth factor receptor.
Assuntos
Mama/embriologia , Mama/metabolismo , Fator de Transcrição AP-2/biossíntese , Actinas/biossíntese , Biomarcadores , Feminino , Feto , Expressão Gênica , Humanos , Imuno-Histoquímica , Lactente , Queratina-18/biossíntese , Queratina-5/biossíntese , Masculino , Receptor ErbB-2/biossíntese , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/biossínteseRESUMO
Extraskeletal osteosarcoma (EOS) is a highly aggressive and exceedingly rare mesenchymal tumor. Due to the rare nature of the disease, the diagnosis can be difficult and is often confirmed only after diagnostic laparotomy and histopathology. We describe the clinical history, radiologic and histomorphologic presentation, and clinical management of a 61-year-old patient who presented with abdominal pain. Abdominal ultrasound and computerized tomography (CT) scan revealed a calcified intra-abdominal mass. Following an explorative laparotomy, histology showed a large extraosseous osteosarcoma of the small bowel mesentery. Therapy according to the Cooperative Sarcoma Study-96 (COSS-96) was commenced. Diagnosis, management, and outcome in the context of the current literature are discussed. To our knowledge, this is the first description of an extraosseous osteosarcomas in the small bowel mesentery in the literature.
Assuntos
Calcinose/diagnóstico , Neoplasias Intestinais/diagnóstico , Neoplasias de Tecido Ósseo/diagnóstico , Osteossarcoma/diagnóstico , Neoplasias Peritoneais/diagnóstico , Calcinose/patologia , Calcinose/terapia , Terapia Combinada , Diagnóstico Diferencial , Evolução Fatal , Humanos , Neoplasias Intestinais/patologia , Neoplasias Intestinais/terapia , Intestino Delgado/patologia , Masculino , Mesentério/patologia , Pessoa de Meia-Idade , Neoplasias de Tecido Ósseo/patologia , Neoplasias de Tecido Ósseo/terapia , Osteossarcoma/patologia , Osteossarcoma/terapia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: High microsatellite instability (MSI-H) occurs in about 15% of colorectal cancers (CRC) and clinical as well as pathological features differ from tumours exhibiting low microsatellite instability (MSI-L) or microsatellite stability (MSS). Conflicting data exists about the relevance of MSI in predicting the prognosis and benefit of 5-fluorouracil (5-FU) based chemotherapy in patients with CRC. We investigated the usefulness of MSI as a predictor of distinct clinical attributes influencing recurrence rate and disease-free survival (DFS) subject to the use of adjuvant or palliative chemotherapy with 5-FU in stage II- stage IV CRC. METHODS: We collected data and tumours of 416 consecutive stage I to IV CRC patients from 2000 to 2002, and followed them for a median time of 33 months. Microsatellite loci recommended by the National Cancer Institute were analysed. Cox proportional hazard modelling was used to compare clinical data and survival as well as associations for MSI and 5-FU treatment status of patients with MSI-H, MSI-L or MSS CRC. RESULTS: We identified 52 MSI-H (13%), 21 MSI-L (5%) and 343 MSS (82%) tumours. CRC with MSI-H tended to have a decreased likelihood of metastasising to regional lymph nodes (p=0.055), whilst age of diagnosis and tumour location did not differ. In an analysis that did not take into account the use of chemotherapy, univariate and multivariate analyses failed to show a difference between MSI-H and MSS groups with respect to disease-free and overall survival. Furthermore, survival under application of 5-FU did not correlate with MSI status. CONCLUSION: No clear influence of MSI status on overall survival and response to 5-FU chemotherapy was found.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Recidiva Local de Neoplasia/genética , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Análise de SobrevidaRESUMO
INTRODUCTION: Hereditary non-polyposis colorectal cancer (HNPCC) is a major form of familial colorectal cancer (CRC). It is diagnosed when either the Amsterdam criteria (AC) are fulfilled or mutations in one of the mismatch repair (MMR) genes have been identified. This project aims at estimating the proportion of HNPCC among unselected patients with CRC. PATIENTS AND METHODS: During a period of 2 years, a total of 351 non-selected patients with CRC were registered prospectively. 92 patients met the Bethesda criteria (9 of them fulfilled the AC) and 259 did not. 348 tumours were examined for microsatellite instability (MSI) and expression of MMR proteins. RESULTS: MSI-H and MSI-L were identified in 17 and 6%, respectively. Loss of MSH2 or MLH1 was found in 1.5 and 8.8%, respectively. Based on the results of tumour tissue analyses, 80 patients with MSI and/or loss of MSH2 or MLH1 expression were identified as candidates for germline mutation screening. DNA of 40/80 patients was available. These patients were screened for MSH2 and MLH1 mutations; 19/40 patients with MSI and normal MSH2 or MLH1 expression were screened for mutations in MSH6. Three patients had relevant MMR gene mutations and six variants of unknown functional relevance were detected. CONCLUSIONS: After adjusting for the cases not evaluable for germline mutations, 1.7% of the CRC patients had HNPCC proven by molecular genetics.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Mutação em Linhagem Germinativa , Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte/genética , Estudos de Coortes , Reparo do DNA , Proteínas de Ligação a DNA/genética , Alemanha/epidemiologia , Humanos , Instabilidade de Microssatélites , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Estudos ProspectivosAssuntos
Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Sarcoma/metabolismo , Sarcoma/patologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Humanos , Imuno-Histoquímica , Metástase Linfática , Sarcoma/secundárioRESUMO
BACKGROUND: Congenital intestinal lymphangiectasia is a rare disease in childhood, which may already cause protein-losing enteropathy in newborns. PATIENT, METHODS AND RESULTS: This is a case report of an infant with generalized edema and protein-losing enteropathy, in whom intestinal lymphangiectasia was diagnosed at the age of two months. Following repetitive intravenous albumin und gamma globulin infusions, the elimination of long-chain fats from the diet and the substitution with medium-chain triglycerides (MCT) led to an improvement of the protein-losing enteropathy. CONCLUSION: In newborns with low level of serum protein and edema protein-losing enteropathy caused by congenital lymphangiectasia might be considered as a differential diagnosis.
Assuntos
Hipoproteinemia/congênito , Linfangiectasia Intestinal/congênito , Enteropatias Perdedoras de Proteínas/congênito , Biópsia , Consanguinidade , Diagnóstico Diferencial , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Duodeno/patologia , Edema/etiologia , Edema/patologia , Endotélio Linfático/patologia , Humanos , Hipoproteinemia/diagnóstico , Hipoproteinemia/dietoterapia , Hipoproteinemia/patologia , Lactente , Mucosa Intestinal/patologia , Linfangiectasia Intestinal/diagnóstico , Linfangiectasia Intestinal/dietoterapia , Linfangiectasia Intestinal/patologia , Proteínas do Leite/administração & dosagem , Enteropatias Perdedoras de Proteínas/diagnóstico , Enteropatias Perdedoras de Proteínas/dietoterapia , Enteropatias Perdedoras de Proteínas/patologiaRESUMO
Sarcomatous malignancies only rarely develop regional lymph node metastases: about 2.7% of our evaluated cases. In this paper we provide evidence supporting a new hypothesis that two entirely separate lymph vascular systems exist in humans. One system (LGS I) exists in close proximity to the epithelium and drains into regional lymph nodes. Only sarcomas that originate in the epithelium or its immediate proximity are able to form regional lymph node metastases. The vast majority of sarcomatous malignancies (97.4% of cases) do not give rise to lymph node metastases, since they originate in proximity to a second, more deeply localized lymph node system (LGS II) in the mesenchymally derived tissues of the body. This second system has no connection to regional lymph nodes. Supporting evidence is provided by experience in the operative treatment of extremity lymphedema, PET-CT examinations, radionuclear lymphography, and scientific investigations using antibodies specifically directed at the elements of the lymph vascular system.
Assuntos
Metástase Linfática/patologia , Vasos Linfáticos/patologia , Tomografia por Emissão de Pósitrons , Sarcoma/secundário , Tomografia Computadorizada por Raios X , Epitélio/patologia , Humanos , Imuno-Histoquímica , Sistema Linfático/patologia , Mesoderma/patologia , Prognóstico , Sarcoma/patologiaRESUMO
A 73-year old healthy woman presented for pacemaker replacement. Chest X-ray showed an right upper lobe consolidation. CT-scan and bronchoscopy with bronchoalveolar lavage could not yield a specific diagnosis. Due to progression of the consolidation in a CT scan after 10 weeks another bronchoscopy with transbronchial biopsy was performed and yielded bronchiolo-alveolar carcinoma. The patient underwent resection of the right upper lobe and middle lobe with curative intent.
Assuntos
Adenocarcinoma Bronquioloalveolar/diagnóstico por imagem , Achados Incidentais , Neoplasias Pulmonares/diagnóstico por imagem , Marca-Passo Artificial , Síndrome do Nó Sinusal/terapia , Tomografia Computadorizada por Raios X , Adenocarcinoma Bronquioloalveolar/patologia , Adenocarcinoma Bronquioloalveolar/cirurgia , Idoso , Biópsia , Líquido da Lavagem Broncoalveolar , Broncoscopia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Seguimentos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Estadiamento de Neoplasias , PneumonectomiaRESUMO
During the last decade significant progress in molecular genetics and cell biology was made and numerous signal transduction pathways regulating cell growth, differentiation and survival were identified. It is now fairly well understood how accumulation of multiple genetic aberrations lead to deregulation of these signal transduction pathways and cause malignant transformation and tumour progression. Therefore, in many cases specific tumour phenotypes can be linked to specific genetic changes. As a result molecular diagnostics has become an important tool for tumour diagnositics that helps to discriminate specific entities. Further, determination of critical mutations leading to activation of important growth and survival signals can identify targets for specific tumour therapies. Gastrointestinal stromal tumours (GISTs) provide an excellent example of how activating mutations in receptor tyrosine kinases can be used as a tool to predict tumour biology and response to therapy by receptor inhibitors. During therapy secondary receptor mutations may cause resistance to therapy and thus may require additional combinatorial therapies. Therefore, predictive pathology and monitoring response to novel targeted therapies provide new challenges for pathologists and require a broad spectrum of techniques in molecular pathology.
Assuntos
Doenças Genéticas Inatas/patologia , Patologia/métodos , Patologia/tendências , Diferenciação Celular , Divisão Celular , Sobrevivência Celular , Fusão Gênica , Doenças Genéticas Inatas/genética , Humanos , Receptores de Superfície Celular/genética , Translocação GenéticaRESUMO
We report on a case of scedosporiosis in a 72-year-old German woman. Her disease started with a purulent ulceration of unknown course at her left foot. Soon after onset of oral antibacterial therapy she needed in-hospital treatment because of an acute pneumonia. The infection progressed despite the application of different antibiotics. Microscopic examination of tracheal fluid revealed fungal hyphae and therefore treatment with itraconazole was initiated. However, the patient developed renal failure, required mechanical ventilation and finally died in treatment-resistant septic shock. Post-mortem Scedosporium apiospermum was cultured from lung tissue taken during autopsy. This is the fourth case of human infection caused by Scedosporium species diagnosed in our laboratory during the last 4 years.