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[The significance of bronchoscopic findings as a prognostic factor in inoperable adenocarcinoma of the lung].

The clinical value of bronchoscopic findings as a prognostic factor has been studied in 136 cases with an inoperable adenocarcinoma of the lung. The survival time in 107 cases with pathological bronchoscopic findings was significantly shorter than in 29 cases without pathological bronchoscopic findings. In the three subtypes of bronchoscopic findings, classified according to the tumor proliferation pattern, i.e. polypoid type, submucosal type and exposing type, the exposing type proved to have the worst prognosis. In addition, our study suggests that the level of infiltrated bronchus is related to the survival time. The more central the tumor infiltration, the worse the prognosis.

Adenocarcinoma↗

Pathology of human papillomavirus in the female genital tract.

Human papillomavirus (HPV) has emerged as a major factor in the genesis of intraepithelial and invasive neoplasms of the female genital tract. The strength of the relationship of HPV to genital neoplasia has been supported by studies involving epidemiologic, clinical, pathologic and molecular data. The many subtypes of HPV have been characterized into risk groups that reflect their propensity to be associated with cancer precursors and invasive disease. The strong correlation between HPV and squamous dysplasia suggests that classification of cervical intraepithelial lesions into similar risk categories should be possible. However, the clinical predictive value of HPV testing and typing remains controversial.

Female↗

HLA class II molecules (HLA-DR, -DP, -DQ) on cells in the human CNS studied in situ and in vitro.

Human leucocyte antigen (HLA) class II molecules expressed by antigen-presenting cells (APC) are major restriction elements in the interaction between APC and T cells of the CD4+ subtype. To explore the immune accessory function of cells in the central nervous system (CNS), we studied the expression of HLA-DR, -DP, and -DQ molecules on CNS cells in situ and in vitro. Reactive microglia and perivascular cells in multiple sclerosis lesions expressed all three HLA class II molecules, whereas microglia in the normal CNS expressed HLA-DR only. All three HLA class II molecules were up-regulated on cultured microglia after stimulation with interferon-gamma (IFN-gamma). Microglial stimulation of allogeneic CD4+ T cells in a mixed lymphocyte reaction (MLR) was effectively blocked using anti-HLA-DR monoclonal antibodies (mAb) but not using anti-HLA-DQ mAb. HLA class II-positive astrocytes and endothelial cells were not identified in normal or diseased CNS. Cultured astrocytes stimulated with IFN-gamma could, however, be induced to express HLA class II antigens of all subtypes, although great variability was observed between different donors. Our results indicate that although both microglia and astrocytes are capable of expressing all HLA class II subtypes in vitro, subtype expression differs between normal and pathological states in situ. Such selective expression may be associated with functional properties.

Adult↗

Multi-infarct dementia.

Vascular dementia and its most common subtype, multi-infarct dementia, are pathologically proven clinical entities. Their prevalence is not as high as previously thought, but they do represent a significant percentage of the population of demented patients. The diagnosis is more difficult to make than is the diagnosis of Alzheimer's disease; however, there are excellent criteria to guide the physician in making the diagnosis. At present the only treatment available is to control the risk factors responsible for the basic disease process; in the majority of cases this requires controlling hypertension.

Dementia, Multi-Infarct↗

[Significance, diagnosis and prognosis in the cytogenetic analysis in acute leukemias and myelodysplastic syndromes].

Cytogenetic analysis of leukemic cells has been shown to be a mandatory part of the diagnosis of malignant hemopathies. Recurring abnormalities may be divided into those exclusively found in myeloid disorders, those associated with lymphoid diseases and those detected in both types of hemopathy. Several of the common defects are characteristic of specific FAB types or subtypes and associated with clinico-pathologic manifestations. Cytogenetic abnormalities have served to identify relatively homogenous subsets of malignant hemopathies. In view of the significant progress realized in the treatment of malignant hemopathies, the assessment of prognostic factors is particularly important for therapeutic decision making. The chromosome status at diagnosis has proven to be a major prognostic indicator for survival and outcome in individual patients. This article will focus on the diagnostic and prognostic significance of the karyotype in de novo acute leukemia and primary myelodysplastic syndromes.

Acute Disease↗

G protein coupled R7G receptors.

We summarize here a number of properties that have been described for G protein coupled membrane receptors. These concern structure-function relationship, regulation of expression and activity and linkage with pathology. The existence of subfamilies and subtypes is discussed in terms of evolution and selectivity. A comparison is made between binding sites for small ligands such as monoamines and larger ligands such as peptides and glycohormones. Cross-talk of G protein coupled receptors with receptor tyrosine kinase pathways is also discussed. Finally, the role of mutations in modulating receptor activity is evaluated with respect to human disease.

Amino Acid Sequence↗

[Undifferentiated small cell carcinoma (oat-cell type) of the colon. Prognostic and therapeutic implications].

AIM: This report reviews the clinical and pathologic features of four patients with small-cell anaplastic carcinoma (SCAC) of the colon and describes in detail their histological and immunohistochemical characteristics. METHODS: Four patients with a SCAC of the colon diagnosed by conventional light microscopy, immunohistochemistry and ultrastructure were reviewed; clinical presentation, tumor location and spread, surgical procedure, adjuvant therapy and clinical outcome were recorded. RESULTS: There were two women and two man, with an average age of 55 (range, 40-66) years. Two tumors were located in the sigmoid and two in right colon. Cases 1, 3 and 4 were removed at laparotomy by segmental resection along with lymph nodes. All cases had liver metastases. Pathologic study identified out-cell subtype in all cases and two histopathologic patterns: pure SCAC (cases 2 and 4) and mixed exocrine-SCC differentiation (cases 1 and 3). Three patients were treated with cyclophosphamide, cisplatin and etoposide. Two patients (cases 2 and 4) died of widely metastatic disease; cases 1 and 3 had partial remission lasting 9 and 3 months, respectively. CONCLUSIONS: Due to extremely aggressive behavior of colon SCAC with early metastatic spread, CT scans of the chest-abdomen and radionuclide bone scan should be performed. In the presence of metastatic disease, multiagent chemotherapy with combined etoposide and cisplatin should be instituted.

Adult↗

[Drug-induced sleep disorders].

Drug-induced sleep disorders are classified into the following subtypes: a) insomnia, b) hypersomnia, c) pathological sleep d) others, those caused by medicine which can effect on circadian rhythm or sleep apnea. This paper described the relationship between several medical agents (neuroleptics, anti-depressants, anti-anxietics, anti-convulsants, psychostimulants, and drugs other than CNS-effective agents) and those effect on sleep and sleep stages. In the medicated patients, medical drugs are mainly responsible for their insomnia. However, it is sometimes difficult to find these drugs. The pathological sleep (i.e., delirium) are often developed following the drug-induced insomnia. Medication against insomnia (i.e., benzodiazepines) often exacerbates the pathological sleep. Therefore, common types of insomnia, drug-induced insomnia and pathological sleep should carefully be discriminated. Drug-induced rhythm-disorders and drug-induced sleep apnea remain to be studied. Future studies may clarify the effects of several drugs on these two disorders.

Anticonvulsants↗

Significance of the minor i and t determinants of hepatitis B virus in hepatocellular carcinoma.

Stored sera from asymptomatic hepatitis B virus (HBV) carriers and hepatitis B virus surface antigen-positive hepatocellular carcinoma (HCC) patients were tested for HBV subtypes, such as subtype determinants d, y, w, r and also antigenic determinants isoleucine (i) and threonine (t) by direct S gene nucleotide sequencing. Significant changes in minor i and t determinants in hepatocellular carcinoma patients with adr hepatitis B carriers were seen. The adr subtype with t determinant was present in 14/25 (56%) of HCC patients compared with only two of 28 (7%) in asymptomatic hepatitis B carriers (P<0.001). However, the adr subtype with i determinant was present in nine of 25 (36%) of the HCC patients and also present in 24/28 (86%) of asymptomatic carriers (P<0.001). No significant changes were seen with the adw subtypes. These results show that i and t minor determinant changes are more common with adr subtypes associated with HCC than with the adw subtype. Whether these subtle changes are pathologically relevant or only a polymorphism of hepatitis B genotypes will depend on subsequent follow-up studies.

Adult↗

Agreement among and within groups of pathologists in the classification of rhabdomyosarcoma and related childhood sarcomas. Report of an international study of four pathology classifications.

BACKGROUND: An International Pathology study was conducted to measure the agreement demonstrated among and within groups of pathologists involved in the categorization of childhood rhabdomyosarcoma according to four pathology classifications. Data concerning agreement and survival experience according to patho-new subtypes were used as a basis for selection of a proposed new pathologic classification. METHODS: A random sample of 800 eligible patients was chosen from the Intergroup Rhabdomyosarcoma Study II (IRS-II) and was reviewed by pathologists representing eight institutions. A 20% sample of the 800 patients was then reviewed by the pathologists to determine the level of agreement with their original classification. In each instance the patients were classified according to four pathology systems: the conventional system, the International Society for Pediatric Oncology system (SIOP), the National Cancer Institute (NCI) system, and the cytohistologic system. RESULTS: Among the groups of pathologists, the highest measure of agreement was a Kappa value of K = 0.451 for the conventional system, followed by K = 0.406 for the SIOP system, K = 0.384 for the NCI system, and K = 0.328 for the cytohistologic system. For reproducibility within the groups of pathologists, the highest measure of agreement was K = 0.605 for the conventional system, followed by K = 0.579 for the NCI system, K = 0.573 for the SIOP system, and K = 0.508 for the cytohistologic system. CONCLUSIONS: There was a general similarity between the agreement reached within the modified conventional, STOP, and NCI systems, with the modified conventional system having the highest Kappa values, and thus the highest measure of agreement, both among and within the groups of pathologists. Also, the subtypes of the conventional system demonstrated a highly significant relationship to survival time. Hence, based on criteria of reproducibilty and prognostic significance, the proposed classification will essentially be a modification of the conventional system with elements of the SIOP and NCI systems.

Adolescent↗

Pediatric surface osteosarcoma: clinical, pathologic, and radiologic features.

BACKGROUND: Osteosarcoma (OS) arising from the surface of bone is far less common than its intramedullary counterpart. Although surface OSs share some radiographic and clinical features, they can be divided into three distinct histologic subtypes. PROCEDURE: We reviewed the clinical, radiographic, and pathologic features of 14 cases of pediatric surface OS treated at St. Jude Children's Research Hospital between 1970 and 2003. RESULTS: Seven patients had parosteal, five had periosteal, and two had high-grade surface OS. The median age at diagnosis was 16.2 years (range, 13.6-18.5 years). Nine patients were male; 11 were Caucasian. None had metastatic disease at diagnosis. Primary tumor sites included distal femur (n = 6), mid to proximal femur (n = 4), and mid to proximal tibia (n = 4). All 14 patients were treated with surgery, and 7 (1 with parosteal, 4 with periosteal, 2 with high-grade tumors) received chemotherapy. One patient experienced pulmonary metastasis of periosteal OS 16 months and 43 months after diagnosis; long-term disease-free survival followed resection of the metastatic tumors. Twelve patients remained alive and disease-free a median of 10 years (range, 1.5-25.4 years) after diagnosis. One patient died of high-grade surface OS 1.8 years after diagnosis, and one patient with periosteal OS died of gastric cancer 18.2 years after diagnosis of OS. CONCLUSIONS: The histologic grade predicts the clinical behavior of pediatric surface OS. Complete resection is the treatment of choice regardless of tumor subtype. Whereas chemotherapy is not indicated for parosteal OS, its role in periosteal OS remains controversial.

Adolescent↗

The significance of the pathologic findings in endometrial cancer.

Endometrial carcinoma includes several specific subtypes which have differing prognostic implications. The two most common subtypes are adenocarcinoma, not otherwise specified (NOS), and adenoacanthoma. Also included in the adenocarcinoma NOS are secretory carcinoma and mucinous carcinoma which have the same natural history as do adenocarcinomas without these features. Fortunately, the above types have the best prognosis and constitute approximately 80% of all endometrial carcinomas. They also present the major diagnostic problem for the pathologist in distinguishing atypical hyperplasia and some of the metaplasias from well-differentiated carcinoma. The tendency would appear to be the over-interpretation of these hyperplastic lesions. Other subtypes have a much less favorable outlook. They include papillary carcinoma, adenosquamous carcinoma, glassy cell carcinoma and clear cell carcinoma. There are two distinct types of papillary carcinoma, the papillary clear cell and the papillary nonclear cell carcinoma. These can readily be separated, and should be, on the basis of prognostic implications. Other pathologic parameters play a significant role in patient management and in the estimation of prognosis. These include postsurgical pathological staging, measurement of depth of myometrial invasion, lymphatic and blood-vascular invasion, serosal involvement, local spread and, perhaps most importantly, tumor grade. Nuclear grading proved to be a better predictor of treatment outcome than did either the FIGO or WHO grading systems. This was especially true in adenocarcinoma NOS, adenoacanthoma and papillary carcinoma.

Adenocarcinoma↗

Anterior corneal dystrophy with dyscollagenosis (Reis-Bücklers type?).

Anterior corneal dystrophies involving Bowman's membrane and anterior stroma include several subtypes of uncertain etiology: the Reis-Bückler, Thiel-Behnke, Grayson-Wilbrandt, and "honeycomb" dystrophies. The clinical and pathologic features of these dystrophies overlap to such a degree that they may represent variations of the same entity. Typically, they all present symptoms beginning in childhood, have a dominant pattern of heredity, and manifest painful, recurrent corneal erosions. Some cases have also been interpreted as representing macular and granular dystrophy. In the present report, we describe a pedigree of affected patients whose corneal dystrophy shared many of the clinical and pathologic features of the Reis-Bücklers and allied subtypes but which differ from all in causing visual symptoms late in life and with minimal signs of recurrent erosion. Histopathology revealed a thickening of the anterior stroma by the addition of a partially disorganized and degenerating tissue in which collagen Type III (fetal or repair collagen) is intermixed with the normal (mature) Type I collagen in the entire stroma. This is accompanied by irregular swelling of the basal epithelial cells and hyperplasia of the basement membrane (collagen Type IV, laminin and fibronectin), suggesting an aberrant influence of the epithelium on collagen synthesis.

Aged↗

Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (</=20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours).

AIMS: A micropapillary pattern (MPP) in lung adenocarcinoma, characterized by papillary structures with epithelial tufts lacking a central fibrovascular core, has been reported to be a new pathological marker of poor prognosis. However, its clinicopathological and prognostic significance in small lung adenocarcinomas (</=20 mm) remains undetermined. A new histological classification of small lung adenocarcinoma proposed by Noguchi et al. has been found to be useful since it has defined surgically curable bronchioloalveolar carcinoma (BAC)-type tumours (Noguchi's type A and B) based on the absence of active fibroblastic proliferation. However, BAC-type tumours with active fibroblastic proliferation (Noguchi's type C), which is adenocarcinoma with mixed subtypes including BAC and invasive carcinoma in the new World Health Organization (WHO) classification, account for most of the small adenocarcinomas and represent a heterogeneous group ranging from minimal to overtly invasive cancer with variable prognoses. Therefore, in this study the aim was to investigate whether MPP can be an additional histological marker(s) to subclassify this heterogeneous group in small lung adenocarcinoma. METHODS AND RESULTS: One hundred and twenty-two cases of small lung adenocarcinomas (</=20 mm in maximum dimension) classified according to the new WHO classification and Noguchi's proposal were analysed with reference to the presence of MPP. Of the 122 cases, 67 (55%) were MPP-positive and 55 (45%) were MPP-negative. Lymph node metastasis and pleural invasion were significantly more frequent in the MPP-positive group: 74% and 66% in the positive group versus 26% and 34% in the negative group, respectively. The 5-year survival of the MPP-positive group was 54%, whereas that of the MPP-negative group was 81% (P=0.024). The 5-year survival rates of BAC (Noguchi's type A and B) (n=14), mixed BAC and invasive adenocarcinoma (Noguchi's type C) (n=85) and invasive adenocarcinoma (Noguchi's type D and F) (n=23) were 100%, 68% and 36%, respectively. In patients with mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours), the 5-year survival of the MPP-positive group (n=51) was 54%, significantly lower than that of the MPP-negative group (n=23) of 100% (P=0.02). CONCLUSIONS: MPP is a simple and distinct pathological marker to subclassify tumours with a significantly poor prognosis within small (</=20 mm) mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours).

Adenocarcinoma, Bronchiolo-Alveolar↗

Classification and subtype prediction of adult soft tissue sarcoma by functional genomics.

Adult soft tissue sarcomas are a heterogeneous group of tumors, including well-described subtypes by histological and genotypic criteria, and pleomorphic tumors typically characterized by non-recurrent genetic aberrations and karyotypic heterogeneity. The latter pose a diagnostic challenge, even to experienced pathologists. We proposed that gene expression profiling in soft tissue sarcoma would identify a genomic-based classification scheme that is useful in diagnosis. RNA samples from 51 pathologically confirmed cases, representing nine different histological subtypes of adult soft tissue sarcoma, were examined using the Affymetrix U95A GeneChip. Statistical tests were performed on experimental groups identified by cluster analysis, to find discriminating genes that could subsequently be applied in a support vector machine algorithm. Synovial sarcomas, round-cell/myxoid liposarcomas, clear-cell sarcomas and gastrointestinal stromal tumors displayed remarkably distinct and homogenous gene expression profiles. Pleomorphic tumors were heterogeneous. Notably, a subset of malignant fibrous histiocytomas, a controversialhistological subtype, was identified as a distinct genomic group. The support vector machine algorithm supported a genomic basis for diagnosis, with both high sensitivity and specificity. In conclusion, we showed gene expression profiling to be useful in classification and diagnosis, providing insights into pathogenesis and pointing to potential new therapeutic targets of soft tissue sarcoma.

Adult↗

Breast cancer in Western Australia in 1989: IV. Summary of histopathological assessment in 655 cases.

This study was part of a population-based survey of all cases of breast cancer diagnosed in Western Australia in 1989. The paper concerns histopathology reporting by pathologists in 655 cases of carcinoma of the breast in that year, before the introduction of mammographic screening programmes. Pathological features of the neoplasms are documented, and the extent to which information known to be of clinical or prognostic importance was included in the reports is analysed. 96.5% of all pathology reports included information on breast cancer subtype and, in 98.6% of cases with axillary dissection, the number of lymph nodes dissected, and the number containing metastatic tumor was stated. In 83.7% of cases of invasive carcinoma exact tumor dimensions were recorded. In 44.9% of cases histological grade was recorded, and information about excision margins was present in 60% of reports overall. The reporting of pathological features in many instances was limited by the way in which the specimen was handled prior to reception. At the time of the study, views about the importance of many aspects of histological assessment were still evolving. Even now, for example, consensus is still being reached on the value of histological grading in predicting prognosis and whether reliable histological assessment of such factors as extent of DCIS and completeness of excision of DCIS is possible. The introduction of mammographic screening since 1989 has provided a focus for wider discussion about the value of histological information in prognostication and patient management. A case is made to support the use of "check lists" for surgical pathology reports in cases of breast cancer.

Adolescent↗

Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases.

Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with decreased survival. High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA. Intracapsular carcinoma has a benign clinical course. Significant prognostic factors in CXPA include tumor stage, grade, proportion of carcinoma, extent of invasion, and proliferation index.

Actins↗

Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy.

The scientific dogma that multiple sclerosis (MS) is a disease caused by a single pathogenic mechanism has been challenged recently by the heterogeneity observed in MS lesions and the realization that not all patterns of demyelination can be modeled by autoimmune-triggered mechanisms. To evaluate the contribution of local tumor necrosis factor (TNF) ligand/receptor signaling pathways to MS immunopathogenesis we have analyzed disease pathology in central nervous system-expressing TNF transgenic mice, with or without p55 or p75TNF receptors, using combined in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling and cell identification techniques. We demonstrate that local production of TNF by central nervous system glia potently and selectively induces oligodendrocyte apoptosis and myelin vacuolation in the context of an intact blood-brain barrier and absence of immune cell infiltration into the central nervous system parenchyma. Interestingly, primary demyelination then develops in a classical manner in the presence of large numbers of recruited phagocytic macrophages, possibly the result of concomitant pro-inflammatory effects of TNF in the central nervous system, and lesions progress into acute or chronic MS-type plaques with axonal damage, focal blood-brain barrier disruption, and considerable oligodendrocyte loss. Both the cytotoxic and inflammatory effects of TNF were abrogated in mice genetically deficient for the p55TNF receptor demonstrating a dominant role for p55TNF receptor-signaling pathways in TNF-mediated pathology. These results demonstrate that aberrant local TNF/p55TNF receptor signaling in the central nervous system can have a potentially major role in the aetiopathogenesis of MS demyelination, particularly in MS subtypes in which oligodendrocyte death is a primary pathological feature, and provide new models for studying the basic mechanisms underlying oligodendrocyte and myelin loss.

Animals↗