Diagnosis and typing of lung carcinomas by cytopathologic methods. A review of 108 cases

A correlative review was made of the type of cytology specimens (sputum, bronchial washing and bronchial brushing) together with the corresponding histopathologic specimens of 108 patients. One hundred patients had primary pulmonary carcinomas diagnosed histopathologically (84) or clinically (16); 5 had carcinomas metastatic to the lungs and 3 had apparently false-positive cytologic results for lung cancer. The correlative review was used to determine the diagnostic reliability of pulmonary cytopathologic techniques in the detection and classification of lung carcinomas (i.e., the sensitivity and accuracy). The overall sensitivities of sputum, bronchial washing and bronchial brushing cytology were 60%, 66% and 77%, respectively (p less than 0.05). Bronchial brushing had a higher sensitivity (80%) for peripheral and metastatic lesions than did sputum (37%) or bronchial washing (60%). The overall accuracies of sputum, bronchial washing and bronchial brushing cytology were 79%, 75% and 76%, respectively, which is not statistically different. Regardless of the sampling methods, cytologic typing of squamous-cell and small-cell carcinomas was highly accurate but was less satisfactory for the other types of lung carcinomas. In the 16 cases in which endoscopic biopsies were either not attempted or gave negative results, one or more pulmonary cytologic specimens showed malignant cells. It is concluded that: (1) pulmonary cytopathologic techniques have excellent sensitivity and accuracy in the diagnosis of lung carcinomas; (2) they may establish the diagnosis of pulmonary carcinomas when endoscopic biopsies give negative results; and (3) they are particularly helpful in cases in which endoscopic biopsies suffer from a low yield (peripheral lesions) or create a considerable danger to the patients (iatrogenic hemorrhage).     

A cladistic analysis of the Trichostrongyloidea (Nematoda).

A morphologically based cladistic analysis of 40 genera included within the Trichostrongyloidea (Amidostomatidae, Dromaeostrongylidae and Trichostrongylidae) is proposed. Two genera were used as outgroups, one from the Strongylina and the other from the Ancylostomatina. Seven genera do not appear in the matrix because some significant morphological characters remain unknown for these genera. Nonetheless, except for Moguranema which is excluded as incertae sedis, a likely systematic position could be assigned to them based on the morphological characters that are known. The classification which best fits the consensus tree is composed of three families. In adding the genera not included in the tree, we obtain: (i) Trichostrongylidae with three sub-families, Amidostomatinae (four genera), Filarinematinae (three genera) and Trichostrongylinae (five genera); (ii) Haemonchidae with two sub-families: Ostertagiinae (eight genera) and Haemonchinae (five genera); (iii) Cooperiidae with three sub-families: Libyostrongylinae (five genera), Obeliscoidinae n. subfam. (five genera) and Cooperiinae (ten genera). Dromaeostrongylus and Ortleppstrongylus, whose females have a caudal spine, are excluded from the Trichostrongyloidea and are placed in the Molineoidea. The hypotheses relating to the evolutionary history of the Trichostrongyloidea are: the origin of the superfamily could have occurred during the upper Cretaceous period. The two most ancient sub-families (Amidostomatinae and Filarinematinae) would be of Gwondwanan origin and evolved during the Paleocene period within Neotropical aquatic birds and within the Australian marsupials. The Trichostrongylinae would have arisen during the Eocene period within birds and then adapted to diverse archaic mammals in the Neotropical region on one hand and in the Nearctic region, on the other hand and lastly adapted to the Lagomorpha and subsequently to the Ruminantia. In both families originating from the Trichostrongylidae, the adaptation to the Lagomorpha may have taken place during the Oligocene but in a different way. In the Haemonchidae, the Ostertagiinae may have passed directly from the Neartic region to Europe. In the Cooperiidae, the adaptation to Lagomorpha may have occurred either within the Libyostrongylinae which may have remained in the Ethiopian region since the Paleocene, or, more likely, by the passage of the Obeliscoidinae from the Nearctic region to the Asian, through the Bering strait. In all cases, the adaptation of the Trichostrongyloidea of Lagomorpha to Ruminants apparently took place during the Miocene, mainly in the Palearctic and the Ethiopian regions.     

Loss-of-heterozygosity analysis of small-cell lung carcinomas using single-nucleotide polymorphism arrays

Human cancers arise by a combination of discrete mutations and chromosomal alterations. Loss of heterozygosity (LOH) of chromosomal regions bearing mutated tumor suppressor genes is a key event in the evolution of epithelial and mesenchymal tumors. Global patterns of LOH can be understood through allelotyping of tumors with polymorphic genetic markers. Simple sequence length polymorphisms (SSLPs, or microsatellites) are reliable genetic markers for studying LOH, but only a modest number of SSLPs are used in LOH studies because the genotyping procedure is rather tedious. Here, we report the use of a highly parallel approach to genotype large numbers of single-nucleotide polymorphisms (SNPs) for LOH, in which samples are genotyped for nearly 1,500 loci by performing 24 polymerase chain reactions (PCR), pooling the resulting amplification products and hybridizing the mixture to a high-density oligonucleotide array. We characterize the results of LOH analyses on human small-cell lung cancer (SCLC) and control DNA samples by hybridization. We show that the patterns of LOH are consistent with those obtained by analysis with both SSLPs and comparative genomic hybridization (CGH), whereas amplifications rarely are detected by the SNP array. The results validate the use of SNP array hybridization for tumor studies.     

Varied pathways of stage IA lung adenocarcinomas discovered by integrated gene expression analysis

Background: Discovery of the progression-associated genes and pathways in lung adenocarcinoma (LAD) has important implications in understanding the molecular mechanism of tumor development. However, few studies had been performed to focus on the changes of pathways in lung adenocarcinoma development using microarray expression profile.Result: We performed a meta-analysis of 4 LAD microarray datasets encompassing 353 patients to reveal differentially expressed genes (DEGs) between normal lung tissues and LAD of different stages. Overall, 1 838 genes were found to be dys-regulated, and the adipogenesis, circadian rhythm, and Id pathways were significantly changed. Interestingly, most of the genes from the same gene family (such as Interleukin receptor, Matrix metallopeptidase, Histone cluster and Minichromosome maintenance complex component families) were found to be up-regulated (or down-regulated). Real-time PCR (qRT-PCR) was applied to validate the expression of randomly selected 18 DEGs in LAD cell lines. In the pathway analysis among stages, Oxidative stress, Glycolysis/Gluconeogenesis and Integrin-mediated cell adhesion pathways, which were involved in cancer cell proliferation and metastasis, were showed to be significantly regulated in stages other than IA.Conclusion: Genes involved in adipogenesis and Id pathways might play important roles in development of LADs. The similar trend of expression of the gene family members suggested coordinate regulation in tumor progression. Three pathways (Oxidative stress, Glycolysis/Gluconeogenesis and Integrin-mediated cell adhesion pathways) significantly regulated in stages other than stage IA suggested that genes and pathways conferring invasive character might be activated in the preinvasive stage IB, while the Oxidative stress and the Glycolysis/Gluconeogenesis pathways might have strong connections to cisplatin-based chemotherapy. The insignificantly regulated three pathways in stage IA might be used in early-stage detection of LAD.     

Ultrastructure of macrocellular (large cell) carcinomas of the lung

The electronmicroscopic investigation of five lung tumors histodiagnosed as macrocellular carcinomas showed the ultrastructural monomorphism of large, variedly shaped neoplastic cells, lack of intercellular junctions, voluminous nuclei with many indentations of nuclear membrane, dispersed euchromatin, large and multiple nucleoli, and nuclear bodies. A reduced number of cytoplasmic organelles was characteristic for these cells, represented mainly by mitochondria, rare rough endoplasmic reticulum, free ribosomes rare Golgi vesicles and flattened tubules, and a various amount of tonofilaments. These features characterized the poorly differentiated proliferation forming these tumors. The elements of differential diagnosis from other poorly differentiated lung tumors (epidermoid and cylindrocubic) are discussed, allowing the consideration of this proliferation type with repressed differentiation and maturation as a real one in the framework of lung carcinomas.     

Electronmicroscopic observations on epidermoid (squamous cell) carcinomas of the lung

Five epidermoid (squamous cell) carcinomas of the lung histopathologically diagnosed were ultrastructurally analysed; special attention was given to the poorly differentiated-immature areas of proliferation. Wide intercellular spaces between irregular cytoplasms with protrusions and microvilli, a high incidence of indentations of nuclear membranes, a large amount of nuclear bodies, shape, size and structure anomalies of mitochondria, a great number of desmosomes and of tonofilaments and tonofibril bundles and their relations with desmosomes and with the finger-like cytoplasmic expansions were noticed. A few secretory granules were also present in these poorly differentiated-immature areas of epidermoid carcinomas of the lung.     

Fine needle aspiration cytology of inflammatory pseudotumor of the lung (plasma cell granuloma). Report of four cases

The fine needle aspiration (FNA) cytologic findings in four cases of inflammatory pseudotumor of the lung are described. Histologic material was available for comparison in three of the four cases. FNA of these lesions usually yielded moderately to poorly cellular smears. The smears showed a mixture of chronic inflammatory cells and tissue fragments, without a predominance of plasma cells. Characteristic cytologic findings were not observed. The cytologic findings can be distinguished from those of other circumscribed benign and malignant lesions, however. The diagnosis of an inflammatory pseudotumor of the lung may be suggested by a combination of roentgenographic (a localized density) and FNA findings, which may justify a more conservative surgical approach.     

Phylogeny of the Nemertodermatida (Acoelomorpha, Platyhelminthes). A cladistic analysis

The Nemertodermatida is a small group of worms, regarded as an order of the Platyhelminthes. The group is of special systematic interest because of its putative basal phylogenetic position in the Platyhelminthes. The phylogeny of the Nemertodermatida was estimated using paup 4.0 software for parsimony analysis. The analysis was based on 72 structural parsimony-informative characters totalling 184 different character states. All eight well described species of nemertodermatids were included in the ingroup. As outgroup were chosen species of the Acoela, Catenulida, Macrostomida and Xenoturbellida. A single most parsimonious tree was obtained with 140 steps and a consistency index (CI) of 0.80. The Nemertodermatida, Ascoparidae and Nemertodermatidae are shown as monophyletic taxa in the tree. The species Nemertoderma psammicola does not group with the other members of the genus Nemertoderma , hence criteria of phylogenetic taxonomy imply that N. psammicola should be renamed. A suggested new name is Sterreria psammicola gen. n .     

Osteomyelosclerosis. A histopathological study of osteomedullary lesions on 32 cases.

The pathological features of the osteomyleoproliferative syndrome development were studied by trephine biopsy on 32 cases out of which 28, lesionally characterized by myeloproliferation, reticulin hyperplasia, intravascular hematopoiesis, myelofibrosis, myeloslerosis, and osteosclerosis, were interpreted as primary osteomyelosclerosis. Dynamic relationships between the myelogenous tissue and the osteogenous one are emphasized in the development of disease.     

The simulation of histopathological diagnosis with the help of an automated image analysis system (VISIAC)

Simulation of the diagnostic algorithm in histopathology at 2 different light microscopical magnifications (x4, x40) for separating 7 diagnostic groups in lung pathology (healthy lung, healthy bronchus, lymphocytic inflammation, epidermoid-, adeno-, small cell, and large cell carcinoma) is presented. 140 cases were tested as a teaching set, 105 cases as learning set. Gray value distribution discriminates between healthy parenchyma and the diseases in all cases tested; minimum spanning tree discriminates between inflammation and carcinoma in all cases, and in between the carcinoma with 70% to 80% accuracy. The measurements may be used as additional aid in difficult diagnostic cases.     

Array CGH analysis reveals chromosomal aberrations in mouse lung adenocarcinomas induced by the human lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

Exposure to genotoxic carcinogens in tobacco smoke is a major cause of lung cancer. However, the effect this has on DNA copy number and genomic stability during lung carcinogenesis is unclear. Here we used bacterial artificial chromosome array-based comparative genomic hybridization to examine the effect of NNK, a potent human lung carcinogen present in tobacco smoke, on the major genomic changes occurring during mouse lung adenocarcinogenesis. Observed were significantly more gross chromosomal changes in NNK-induced tumors compared with the spontaneous tumors. An average of 5.6 chromosomes were affected by large-scale changes in DNA copy number per NNK-induced tumor compared with only 2.0 in spontaneous lung tumors (p = 0.017). Further analysis showed that gains on chromosomes 6 and 8, and losses on chromosomes 11 and 14 were more common in NNK-induced tumors (p 相似文献   

Giant cell carcinoma of the lung. A quantitative and histogenetic analysis of eight new cases

An analysis of the so-called giant cell carcinoma of the lung was performed in the light of eight new cases (five macrocellular and three cylindrocubic carcinomas) with different proportions of giant cells, and of a quantitative study of giant cells within the structure of 60 lung carcinomas, fifteen of each basic type of proliferation. Taking into account these data and those of the literature, it was concluded that giant cell carcinomas do not form either a basic type or a variant (subtype) of one of the lung carcinoma types, as suggested by WHO's typing (macrocellular). They represent, in author's conception, only particular forms of neoplastic proliferation in the lung, in which special conditions arising during the prolonged promotion phase influence mitosis, differentiation and/or maturation and modulation of cells composing the proliferating neoplastic foci. The large variations in the amount of giant cells also reflect these intervening actions.     

Biological aggressiveness evaluation in prostate carcinomas:immunohistochemical analysis of PCNA and p53 in a series of Gleason 6 (3+3) adenocarcinomas

We selected 63 prostate tumors with Gleason's grade 6 (3+3), commonly showing both tubular and cribrous patterns. We compared in both patterns the expression of two of the most used biologic markers: PCNA and p53, with the aim to verify the validity of the Gleason's grading system to compare the morphologic grade with biologic aggressiveness and prognostic value. We did not find any statistical difference in the protein immunopositivity, indicating that both patterns could have identical biologic behaviour; then we confirmed the validity of Gleason's system for considering both tubular and cribrous patterns as an intermediate grade of tumoral differentiation. Moreover, we found a linear relationship between the increase of PCNA and the accumulation of mutated p53; this datum could confirm the hypothesis that p53 mutation is a late event in prostate carcinogenesis.