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At least 487 records · Page 27Linked to original sources

Salivary mucoepidermoid carcinoma: revisited.

Mucoepidermoid carcinoma (MEC) is a malignant epithelial neoplasm composed of varying proportions of mucous, epidermoid, intermediate, columnar, and clear cells and often demonstrates prominent cystic growth. MEC is usually subclassified as low, intermediate, or high grade on the basis of its histologic features, including the presence of cystic spaces, cellular differentiation, proportion of mucous cells, growth pattern, type of invasion, and cytologic atypia. Because even low-grade neoplasms may metastasize, the term mucoepidermoid tumor is inappropriate. The 3-level grading approach to tumor classification has found general acceptance among pathologists; differences in biologic behavior can be demonstrated even though clinical stage has become a better prognosticator. However, in the case of MEC, no universal agreement exists regarding which histologic grading criteria are most the useful, and grading has varied. These issues have led to the investigation of more subjective systems. We describe these new schemes, the histologic variants of MEC, and the ancillary methods that allow for further stratification of patients with MEC, especially for patients with grade 2 tumors, which have a variable and unpredictable clinical course.

Carcinoma, Mucoepidermoid↗

Oral white lesions with special reference to precancerous and tobacco- related lesions: conclusions of an international symposium held in Uppsala, Sweden, May 18-21 1994. International Collaborative Group on Oral White Lesions.

An international group of epidemiologists, clinicians and pathologists with a special interest in oral white lesions and their precancerous significance has reviewed earlier work on this topic and identified some of the problems associated with previous definitions, descriptions and classifications. Modifications to these definitions, descriptions and classifications have been proposed, accompanied by explanations of the reasons for identifying the need for changes to be made. Leukoplakia may be a provisional or definitive diagnosis dependent upon the circumstances of oral examination and the availability of other information. Guidelines are provided to assist in the application of the definitions of oral leukoplakia and illustrations depict the homogeneous and non-homogeneous clinical variants. Consideration is also given to the importance of a red component in a white lesion, or a lesion that is entirely red (erythroplakia). A new clinical staging procedure for oral leukoplakia is also proposed.

Erythroplasia↗

Episodic paroxysmal hemicrania: a further case and review of the literature.

Episodic paroxysmal hemicrania was delineated as a clinical entity only two years ago, separating patients whose attacks remained grouped in bouts lasting weeks, from those who started irregularly and lapsed into chronicity or began and continued in the chronic state. A further case of the episodic variety and a review of the nine previously recorded cases is reported. The division into episodic and chronic variants of paroxysmal hemicrania conforms with the classification of cluster headache. The similarity of the two conditions is emphasised although the response to indomethacin in paroxysmal hemicrania is a special feature.

Adult↗

Pharmacogenomic biomarkers.

Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

Drug Design↗

[Status epilepticus].

INTRODUCTION: Status epilepticus (SE) is a condition in which epileptic discharges are sufficiently prolonged or repeated so as to cause persistent changes in neurological function. DEVELOPMENT: At the present time the classification of SE seems to be incomplete and therefore provisional. However the broad subdivision into convulsive SE and non-convulsive SE is still useful in clinical practice when emergency treatment is required. The neuropathological changes are largely determined by the nature (excitory or inhibitory) and the duration of the event which originated the crisis. Tonic-clonic SE is only one of many variants of SE. However, unlike many others, it is a medical emergency which if not suitably treated may lead to permanent neurological damage. Neurone damage and death are the result of a series of parallel processes occurring at a systemic and neuronal level. Outstanding amongst the latter is the activation of a complex neurotoxic cascade. Better understanding of the physiopathological mechanisms occurring in SE would set the stage for a more logical use of treatment. CONCLUSIONS: With advances in the treatment of SE in recent years the prognosis of these patients has improved considerably. However, we should now consider the use of conventional anticonvulsant drugs alone to be insufficient, and that this should give way to polytherapy with neuroprotector agents.

Anticonvulsants↗

Nevus of Ota: a new classification based on the response to laser treatment.

BACKGROUND AND OBJECTIVE: For 60 years, Tanino's classification has been used to classify the extent of nevus of Ota. However, such classification not only fails to address variants such as phacomatosis pigmentovascularis but also cannot be used to predict the therapeutic outcome. Our objective is to retrospectively study our series of laser-treated patients with the aim of re-classifying nevus of Ota, so that such important issues can be taken into account. STUDY DESIGN/MATERIALS AND METHODS: One hundred nineteen patients that had received Q-switched laser treatment were recruited into the study. They were recalled for interview and examination for evidence of coexisting birthmarks and extracutaneous involvement. Two observers assessed the pre- and posttreatment clinical photographs for evidence of periorbital under-response (panda's sign), defined as the degree of periorbital laser clearing significantly less than clearing in the other area. RESULTS: A total of 47.8% of the patients with periorbital pigmentation were considered by the observers to have significant periorbital under-response (panda's sign). Additionally, 10.1% had other birthmarks, and extracutaneous involvement was seen in 31.4% of the patients. CONCLUSION: Periorbital under-response is commonly seen in patients with periorbital pigmentation. Taking this and other factors into consideration, we have proposed a new classification for nevus of Ota that allows for the prediction of the clinical outcome of laser treatment.

Adolescent↗

Eccrine angiomatous hamartoma: a multiple variant.

A case of multiple eccrine angiomatous hamartoma present in a boy since birth is reported. Clinically, this condition must be differentiated from other neonatal angiomatoses. Sometimes the clinical findings are nonspecific, whereas histologic examination may exclude angiomatoses with visceral involvement. In our case the hamartomatous nature of this tumor is documented also by the presence of pilar structures intimately related to the eccrine-angiomatous complex in one of two lesions histologically examined. Therefore, the histologic classification of eccrine angiomatous hamartoma into subgroups seems to be excessive.

Child, Preschool↗

Diagnosis and grading of chronic pancreatitis by morphological criteria derived by ultrasound and pancreatography.

The most commonly used modalities in the diagnosis of chronic pancreatitis are ultrasonography, computed tomography (CT) and endoscopic retrograde pancreatography (ERP). Computed tomography scanning is only of value in severe chronic pancreatitis. Both ultrasound and pancreatography are capable of showing ductal changes in mild forms of the disease, but comparison of the two methods has been difficult. A scheme of morphological criteria and descriptive terminology of pancreatitis was applied to 58 out of 85 patients with a firm clinical diagnosis of chronic pancreatitis. Twenty-seven patients were excluded from the study, four with a faulty clinical diagnosis and 23 with non-diagnostic pancreatograms. There was an exact classification into normal, equivocal, mild, moderate or marked chronic pancreatitis in 50 out of 58 patients (86%) and an almost perfect correlation (+ or - one grade) in 54 out of 58 (93%). There were four discrepancies. Ultrasound examination missed focal pancreatitis in the tail, a small cavity in the uncinate process and a variant of chronic pancreatitis. One ultrasound scan was of poor quality. Morphological grading by different techniques is feasible and use of this scheme can reduce diagnosis to a simple and specific set of rules.

Cholangiopancreatography, Endoscopic Retrograde↗

Gene-expression profiling reveals distinct expression patterns for Classic versus Variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma.

Merkel cell carcinoma (MCC) is a rare aggressive skin tumor which shares histopathological and genetic features with small-cell lung carcinoma (SCLC), both are of neuroendocrine origin. Comparable to SCLC, MCC cell lines are classified into two different biochemical subgroups designated as 'Classic' and 'Variant'. With the aim to identify typical gene-expression signatures associated with these phenotypically different MCC cell lines subgroups and to search for differentially expressed genes between MCC and SCLC, we used cDNA arrays to profile 10 MCC cell lines and four SCLC cell lines. Using significance analysis of microarrays, we defined a set of 76 differentially expressed genes that allowed unequivocal identification of Classic and Variant MCC subgroups. We assume that the differential expression levels of some of these genes reflect, analogous to SCLC, the different biological and clinical properties of Classic and Variant MCC phenotypes. Therefore, they may serve as useful prognostic markers and potential targets for the development of new therapeutic interventions specific for each subgroup. Moreover, our analysis identified 17 powerful classifier genes capable of discriminating MCC from SCLC. Real-time quantitative RT-PCR analysis of these genes on 26 additional MCC and SCLC samples confirmed their diagnostic classification potential, opening opportunities for new investigations into these aggressive cancers.

Biomarkers, Tumor↗

Pharmacogenomics in breast cancer: current trends and future directions.

Pharmacogenomics is the study of genetic variations between individuals to predict the risk of toxic side effects and the probability that a patient will respond to single- or multidrug chemotherapy. Breast cancer remains one of the most common cancers among women worldwide and is second only to lung cancer in cancer-related death. A better understanding of the mechanisms of initiation and progression of breast cancer is needed for early diagnosis and development of better therapeutic methodologies. Differences in cancer patients' responses to chemotherapy have often been attributed to pathogenesis and severity of the disease, drug interactions, patient's age, gender, nutritional status, organ functions and tumor biology. It is now well recognized that genetic variations in drug target genes, disease pathway genes and drug metabolizing enzymes can have greater influence on drug efficacy and toxicity. In addition, germline variants can be used to study breast cancer susceptibility, as well as the variable response to both drug and radiation therapy used in the treatment of breast cancer. This review discusses clinically relevant individual gene variations that influence breast cancer susceptibility and cancer therapy, as well as the microarray-based expression profiling studies that have great potential in cancer pharmacogenomics in terms of tumor classification, drug and biomarker discovery and drug efficacy testing.

Age Factors↗

[The diagnosis and correction of hemostatic system disorders during surgical coagulopathic hemorrhages in cancer patients].

The hemostasis system was examined before surgery, during the principal stages of the operative intervention, and in the early postoperative period in 280 patients with various malignant tumors. The volume of intraoperative blood loss varied from 280 to 14,000 ml. The studies revealed that the main factor causing the most profound disorders in the hemostasis system which lead to the development of grave coagulopathic hemorrhages is blood loss due to surgical trauma. Coagulopathic bleedings most frequently develop in case of at least a 3000 ml blood loss and course as different variants and stages of the syndrome of disseminated intravascular coagulation (DIC) or hemodilution coagulopathy. Massive blood loss was found to involve primarily damage of the platelet component of the hemostasis system, thrombocytopenia being paralleled by a drastic reduction of the aggregability of these cells, this, in turn, increasing bleeding from small vessels. Laboratory signs of acute DIC diagnosed during surgery anticipate its clinical manifestation. Working classification of operative bleedings and rapid methods for their diagnosis have been developed.

Adult↗

Characteristics of p53 and Smad4 immunohistochemistry in pancreatic ductal adenocarcinoma and validation by next-generation sequencing.

BACKGROUND: Mutations in four major driver genes -KRAS, CDKN2A, TP53, and SMAD4- are central to the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) and critically inform diagnosis, therapeutic decision-making, and prognostic assessment. Although next-generation sequencing (NGS) is widely regarded as the gold standard for detecting these mutations, its clinical application is often limited by suboptimal analytical efficiency and substantial economic cost. Among these genes, immunohistochemical (IHC) staining for the proteins encoded by TP53 and SMAD4 has been extensively adopted in routine pathology practice. However, standardized IHC pattern classification schemes and rigorous validation of their predictive accuracy for underlying genomic alterations remain lacking in PDAC. METHODS: We retrospectively enrolled 63 PDAC patients and systematically characterized the typical IHC expression patterns of p53 and Smad4. Targeted NGS was subsequently performed on all available tumor specimens, and the resulting mutational profiles were correlated with corresponding IHC findings. Diagnostic performance including sensitivity, specificity and accuracy of p53 IHC for predicting TP53 mutations and of Smad4 IHC for predicting SMAD4 mutations was rigorously evaluated. RESULTS: Among the four canonical driver genes, co-occurring double- or triple-gene mutations were prevalent; within TP53 and SMAD4, missense mutations constituted the most frequent variant type. Using NGS as the reference standard, we validated the diagnostic utility of a three-tiered p53 IHC classification system, particularly in fine-needle biopsy (FNB) specimens. Furthermore, we proposed a novel, refined Smad4 IHC pattern classification that incorporates an "intermediate" category, thereby expanding upon conventional binary interpretation. This new scheme achieved markedly improved mutation prediction accuracy (0.76) compared with traditional approaches (0.57). CONCLUSION: Our study highlights the complementary diagnostic value of p53 and Smad4 IHC relative to molecular testing in PDAC, especially when tissue is limited, as commonly encountered in FNB specimens. The newly established Smad4 IHC classification system, which integrates an intermediate expression category into the conventional two-tier framework, demonstrates superior clinical utility and enhances predictive accuracy for SMAD4 genomic alterations.

Humans↗

[Solid tumors in the child. New advances and the importance of histological sub-classifications. II. Tumors of the peripheral nervous system, soft tissue, liver and pancreas].

According to immunohistochemical, ultrastructural features of neural cells, and identical 11; 22 chromosome translocation, at least some extra osseous Ewing's sarcoma, as well as the malignant small cell tumor of the thoracopulmonary region (Askin's tumor) are actually classified as peripheral neuroepitheliomas. Embryonal rhabdomyosarcoma, including the botryoid variant, is now, when treated with appropriate chemotherapy, a tumor of relatively favorable histology. Its prognosis is still primarily related to clinical stage and location of tumor. The alveolar subtype of rhabdomyosarcoma (including its solid variant) has a less favorable prognosis. Hepatoblastoma (epithelial or mixt variants) have the same long term survival, also mainly related to stage. Pancreatoblastoma is a tumor with well differentiated cytopathology and prolonged course, compared with other pancreatic tumors.

Carcinoma, Hepatocellular↗

[Clinical patterns in the development of hypochondriac disorders within the framework of different mental illnesses].

The authors have examined 106 patients with hypochondriac states developing in the presence of various mental diseases. The patients are divided into three nosological groups: psychogenic, exogenic-organic, and endogenic. Variants of the hypochondriac syndrome occurring in each group of the disease are described. Characteristics of the time-course of hypochondriac symptomatology and the stages of the formation of hypochondriac disturbances in relation to their classification with one or another nosological group are outlined.

Adult↗

Clinical utility of grading criteria for submucosal invasion in the prognosis of T1 colorectal carcinomas.

BACKGROUND: The clinical utility of relative and absolute grading criteria for submucosal invasion in T1 colorectal carcinomas has been controversial. METHODS: In 51 T1 colorectal carcinomas, depth of submucosal invasion was graded either according to a modified Haggitt's classification (a relative criterion) or by direct measurement using a micrometer (an absolute criterion), and immunostaining for E-cadherin, alpha-catenin, beta-catenin, matrilysin, and CD44 variant 6 was performed on formalin-fixed, paraffin-embedded sections. The associations between lymph node metastasis or local recurrence (locoregional failure) and tumor budding, and clinicopathologic parameters and immunoreactivity were examined statistically. RESULTS: By univariate analysis, tumor budding, histology, and the co-expression pattern of nuclear beta-catenin and CD44 variant 6 were significantly associated with locoregional failure. The relative and absolute grading of submucosal invasion were not significantly associated with locoregional failure. Multivariate analysis showed that tumor budding alone was significantly associated with locoregional failure, and the association between the co-expression pattern of nuclear beta-catenin and CD44 variant 6, and locoregional failure was marginally significant ( P = 0.0502). Lymphatic invasion and absolute grading of depth and width of submucosal invasion were significantly associated with tumor budding, and the associations between tumor budding, and histologic differentiation and membranous alpha-catenin expression were marginally significant ( P = 0.06; P= 0.08), whereas, a relative grading of submucosal invasion was not significant ( P = 0.58). Analysis of variance showed that histologic differentiation and lymphatic invasion were independently and significantly associated with tumor budding ( P = 0.005; P < 0.001). CONCLUSIONS: These results suggest that the grading of submucosal invasion, either relative or absolute, may not be a useful risk factor for lymph node metastasis or local recurrence in T1 colorectal carcinomas.

Adult↗

CD44s expression correlated with the International Neuroblastoma Pathology Classification (Shimada system) for neuroblastic tumours.

AIM: CD44 is a cell adhesion molecule that plays an important role in the cascade of metastasis and progression of human malignant tumours. A large family of variants or isoforms, generated by alternative splicing of a single gene, has been reported to be involved in the malignant process by conferring metastatic potential to non-metastatic cells. The objective of this study was to compare the expression of CD44 standard molecule with the International Neuroblastoma Pathology Classification (INPC) for neuroblastic tumours, a histological grading system based on the Shimada system for predicting the clinical outcome in neuroblastic tumours. METHODS: Paraffin blocks of primary neuroblastic tumour were graded according to the INPC system into favourable and unfavourable histological types. Tumour tissues were then analysed with immunostaining using monoclonal antibodies against the CD44 epitope. RESULTS: In this retrospective study, 32 cases of primary neuroblastic tumour were collected. Based on the INPC system, 13 cases (40.6%) had a favourable histology while 19 cases (59.4%) were of unfavourable histology. CD44 standard (CD44s) expression was detected in 69.2% of neuroblastic tumours with favourable histological type while 89.5% of tumours with unfavourable histological type did not express CD44s staining. Statistically, there was significant correlation between morphological grading of neuroblastic tumours based on the INPC and the presence of CD44 staining (Fisher's exact test, P<0.05). CONCLUSION: This study shows that there is a significant correlation between CD44s expression and tumour histology based on the INPC in which CD44s non-expression is correlated with an unfavourable histological type and the expression of CD44s with a favourable type. Therefore, the analysis of CD44s expression should be recommended as an additional biological marker in the initial routine staging of the disease.

Antigens, Neoplasm↗

Schwannomatosis. An unusual variant of neurofibromatosis or a distinct clinical entity?

Multiple schwannomas have frequently been seen in patients with neurofibromatosis. Recently, the association of multiple cutaneous schwannomas, central nervous system tumors, and various neurologic deficits has been described in Japanese patients as a condition called schwannomatosis. We describe the first non-Japanese cases of schwannomatosis and compare and contrast this unusual condition with the well-known variants of neurofibromatosis. We conclude that the features of schwannomatosis are distinct and define a condition that does not fit into the current classification scheme of neurofibromatosis. The occurrence of multiple cutaneous schwannomas in the absence of cardinal features of neurofibromatosis may indicate the presence of central nervous system tumors or various neurologic deficits.

Adolescent↗

Biochemical and clinical aspects of the human flavin-containing monooxygenase form 3 (FMO3) related to trimethylaminuria.

Trimethylaminuria is a rare metabolic disorder that is associated with abnormal amounts of the dietary-derived trimethylamine. Excess unmetabolized trimethylamine in the urine, sweat and other body secretions confers a strong, foul body odor that can affect the individual's ability to work or engage in social activities. This review summarizes the biochemical aspects of the condition and the classification of the disorder into: 1) primary genetic form, 2) acquired form, 3) childhood forms, 4) transient form associated with menstruation, 5) precursor overload and 6) disease states. The genetic variability of the flavin-containing monooxygenase (form 3) that is responsible for detoxication and deodoration of trimethylamine is discussed and put in context with other variant forms of the flavin-containing monooxygenase (forms 1-5). The temporal-selective expression of flavin-containing monooxygenase forms 1 and 3 is discussed in terms of an explanation for childhood trimethylaminuria. Information as to whether variants of the flavin-containing monooxygenase form 3 contributes to hypertension and/or other diseases are presented. Discussion is provided outlining recent bioanalytical approaches to quantify urinary trimethylamine and trimethylamine N-oxide and plasma choline as well as data on self-reporting individuals tested for trimethylaminuria. Finally, trimethylaminuria treatment strategies and nutritional support are described including dietary sources of trimethylamine, vitamin supplementation and drug treatment and issues related to trimethylaminuria in pregnancy and lactation are discussed. The remarkable progress in the biochemical, genetic, clinical basis for understanding the trimethylaminuria condition is summarized and points to needs in the treatment of individuals suffering from trimethylaminuria.

Animals↗