Sarcomatoid mesothelioma and its histological mimics: a comparative immunohistochemical study.

AIMS: Differentiating sarcomatoid mesothelioma from other pleural-based spindle cell tumours by light microscopy can be challenging, especially in a biopsy. The role of immunohistochemistry in this differential diagnosis is not as well defined as it is for distinguishing epithelioid mesothelioma from adenocarcinoma. In this study, we investigate the utility of diagnostic immunohistochemistry for distinguishing sarcomatoid mesothelioma from its histological mimics, high-grade sarcoma and pulmonary sarcomatoid carcinoma. METHODS: We stained 20 mesotheliomas with sarcomatoid components (10 biphasic and 10 sarcomatoid mesotheliomas) for pan-cytokeratin, cytokeratin 5/6, calretinin, WT-1, thrombomodulin, and smooth muscle actin. Intensity and distribution of staining were assessed using a semiquantitative scale. Only tumours with unequivocal staining were considered positive for tabulation. We compared the immunophenotypic profiles of these tumours with 24 high-grade sarcomas, 10 pulmonary sarcomatoid carcinomas, and 16 epithelioid mesotheliomas. The sarcomatoid carcinomas were also stained for thyroid transcription factor-1 (TTF-1). RESULTS: Pan-cytokeratin stained 70% of sarcomatoid mesotheliomas, 17% of sarcomas, 90% of sarcomatoid carcinomas, and 100% of epithelioid mesotheliomas. Cytokeratin 5/6 and WT-1 stained most epithelioid mesotheliomas, but rarely stained sarcomas, sarcomatoid carcinomas, or the sarcomatoid components of mesothelioma. Calretinin and thrombomodulin each stained 70% of sarcomatoid mesotheliomas. However, calretinin was also positive in 17% of sarcomas and in 60% of sarcomatoid carcinomas, while thrombomodulin was positive in 38% of sarcomas and in 40% of sarcomatoid carcinomas. Smooth muscle actin was expressed in 60% of sarcomatoid mesotheliomas and in 58% of sarcomas, but in only 10% of sarcomatoid carcinomas. All 10 sarcomatoid carcinomas were negative for TTF-1. CONCLUSIONS: Mesothelioma shows decreased expression of epithelial and mesothelial epitopes in its sarcomatoid components. A wide immunophenotypic overlap exists among sarcomatoid mesotheliomas, sarcoma, and sarcomatoid carcinomas. Cytokeratin and calretinin have the most value in differentiating sarcomatoid mesothelioma from sarcoma. However, because sarcomatoid mesothelioma can occasionally be cytokeratin-negative, the distinction between it and sarcoma may become arbitrary. With the exception of smooth muscle actin, all the markers studied showed similar distributions in sarcomatoid mesothelioma and sarcomatoid carcinoma, including frequent calretinin and thrombomodulin expression in both tumours. Thus, immunohistochemistry plays a more limited role in the differential diagnosis of sarcomatoid tumours compared with epithelioid tumours. For sarcomatoid tumours involving the pleural lining, clinicopathological data, especially information about the gross appearance of the tumour (i.e. localized versus diffuse pleural-based mass), should be noted and carefully correlated with microscopic and immunohistochemical findings.

Lymphoscintigraphic technique to image canine esophageal lymph nodes.

Current noninvasive methods of imaging esophageal lymph nodes have an accuracy, specificity, and sensitivity of 70%. Using a flexible esophagoscope, technetium-99m antimony sulfide colloid was injected in the esophageal submucosa of six dogs who then underwent nuclear scans to identify lymph-node location. The euthanized animals underwent dissection of cervical, thoracic, and abdominal lymph nodes. Student's t-test showed no statistical difference in the number of lymph nodes visualized in the neck (3.5 +/- 0.6), parietal thorax (1.2 +/- 0.4), visceral thorax (2.2 +/- 0.7), and abdomen (1.0 +/- 0.0) on premorbid nuclear scans and in the number of radiolabeled lymph nodes found in the neck (3.2 +/- 0.9), parietal thorax (1.2 +/- 0.2), visceral thorax (1.8 +/- 1.0), and abdomen (1.2 +/- 0.2) on dissection of the carcass. The positions of the lymph nodes based on the premorbid nuclear scans matched the locations of the radiolabeled lymph nodes at dissection. Dissected tissue was pathologically confirmed as lymph node. The position and number of lymph nodes in the cervical, intrathoracic, and abdominal regions on nuclear scan correlated with the position and number of lymph nodes found on anatomic dissection. This technique may have a higher sensitivity and specificity than current noninvasive techniques in the staging of esophageal lymphatic metastasis.

Activity of dolastatin 10 against small-cell lung cancer in vitro and in vivo: induction of apoptosis and bcl-2 modification.

PURPOSE: Dolastatin 10 is a natural cytotoxic peptide which acts through the inhibition of microtubule assembly. Studies have suggested that such agents can induce apoptosis in association with bcl-2 phosphorylation. Since bcl-2 overexpression is common in small-cell lung cancer (SCLC), we evaluated the activity of dolastatin 10 in SCLC cell lines and xenografts. METHODS: In vitro growth inhibition was evaluated with a standardized MTT assay and apoptosis with fluorescent microscopy and a TUNEL assay. Immunoblot analysis and phosphatase digestion were used to determine bcl-2 modification. In vivo activity was evaluated in subcutaneous and metastatic SCLC xenograft models in SCID mice. RESULTS: Dolastatin 10 had growth inhibitory activity against four SCLC cell lines (NCI-H69, -H82, -H446, -H510) with IC50 values ranging from 0.032 to 0.184 nM. All four cell lines exhibited evidence of apoptosis after 48 h of exposure to 1.3 nM dolastatin 10. Immunoblot analysis revealed that 1.3 nM dolastatin 10 altered the electrophoretic mobility of bcl-2 in NCI-H69 and -H510 cells within 16 h of treatment. Incubation of protein extract from dolastatin 10-treated NCI-H69 and -H510 cells with calcineurin resulted in the disappearance of the altered mobility species, suggesting dolastatin 10-induced bcl-2 phosphorylation. In in vivo studies, 450 microg/kg of dolastatin 10 IV x 2 given after intravenous injection of NCI-H446 cells completely inhibited tumor formation. In established subcutaneous NCI-H446 xenografts, 450 microg/kg of dolastatin 10 IV induced apoptosis in the majority of tumor cells within 96 h, resulting in a log10 cell kill of 5.2 and an increase in median survival from 42 to 91 days. CONCLUSIONS: These findings suggest that dolastatin 10 has potent activity against SCLC and that the modulation of apoptotic pathways deserves further evaluation as an anticancer strategy.

Psychodynamic therapists' reservations about cognitive-behavioral therapy : implications for training and practice.

This article offers suggestions for psychodynamic therapists who encounter obstacles while learning cognitive-behavioral therapy (CBT) or working in settings where CBT is used. The authors discuss three types of questions commonly raised by psychodynamic therapists about CBT. These concern 1) the therapeutic relationship, 2) the focus of therapeutic interventions, and 3) the depth of change. To help psychodynamic therapists overcome obstacles to learning CBT, the authors focus on similarities between psychodynamic and cognitive-behavioral models in these three areas. They also examine differences between the models, including differences dependent on value judgments, and offer suggestions for making productive use of differences between the models in the training process.

A universal method for the mutational analysis of K-ras and p53 gene in non-small-cell lung cancer using formalin-fixed paraffin-embedded tissue.

The p53 tumor suppressor gene has been found to be altered in almost all human solid tumors, whereas K-ras gene mutations have been observed in a limited number of human cancers (adenocarcinoma of colon, pancreas, and lung). Studies of mutational inactivation for both genes in the same patient's sample on non-small-cell lung cancer have been limited. In an effort to perform such an analysis, we developed and compared methods (for the mutational detection of p53 and K-ras gene) that represent a modified and universal protocol, in terms of DNA extraction, polymerase chain reaction (PCR) amplification, and nonradioisotopic PCR-single-strand conformation polymorphism (PCR-SSCP) analysis, which is readily applicable to either formalin-fixed, paraffin-embedded tissues or frozen tumor specimens. We applied this method to the evaluation of p53 (exons 5-8) and K-ras (codon 12 and 13) gene mutations in 55 cases of non-small-cell lung cancer. The mutational status in the p53 gene was evaluated by radioisotopic PCR-SSCP and compared with PCR-SSCP utilizing our standardized nonradioisotopic detection system using a single 6-microns tissue section. The mutational patterns observed by PCR-SSCP were subsequently confirmed by PCR-DNA sequencing. The mutational status in the K-ras gene was similarly evaluated by PCR-SSCP, and the specific mutation was confirmed by Southern slot-blot hybridization using 32P-labeled sequence-specific oligonucleotide probes for codons 12 and 13. Mutational changes in K-ras (codon 12) were found in 10 of 55 (18%) of non-small-cell lung cancers. Whereas adenocarcinoma showed K-ras mutation in 33% of the cases at codon 12, only one mutation was found at codon 13. As expected, squamous cell carcinoma samples (25 cases) did not show K-ras mutations. Mutations at exons 5-8 of the p53 gene were documented in 19 of 55 (34.5%) cases. Ten of the 19 mutations were single nucleotide point mutations, leading to amino acid substitution. Six showed insertional mutation, and three showed deletion mutations. Only three samples showed mutations of both K-ras and p53 genes. We conclude that although K-ras and p53 gene mutations are frequent in non-small-cell lung cancer, mutations of both genes in the same patient's samples are not common. We also conclude that this universal nonradioisotopic method is superior to other similar methods and is readily applicable to the rapid screening of large numbers of formalin-fixed, paraffin-embedded or frozen samples for the mutational analysis of multiple genes.

Ameloblastic carcinoma of the maxilla.

Ameloblastic carcinoma is an unusual tumour. There have been a total of 34 cases of ameloblastic carcinoma in the English literature to date. Of these only 11 cases have occurred in the maxilla. The authors report the 12th such case. The histological classification for odontogenic carcinoma has been debated for many years and recently revised, thus differentiating between malignant ameloblastoma and ameloblastic carcinoma. The authors review the current literature regarding diagnosis and treatment of this unusual lesion, and support the use of the term malignant ameloblastoma for the tumours that metastasize in spite of their benign histological appearance, whereas, the ameloblastic carcinoma is referred to as the primary tumour with malignant transformation, regardless of its metastatic potential.

Energy expenditure and ventilatory responses during Siddhasana--a yogic seated posture.

Reports of energy expenditure and ventilatory responses to yogic seated posture of Siddhasana are lacking in literature. Various cardio-ventilatory responses were studied in states of the horizontal supine, chair-sitting and Siddhasana. It was observed that sitting in Siddhasana posture was characterised by greater minute ventilation, larger tidal volume, higher oxygen consumption, greater CO2 elimination, higher heart frequency greater oxygen pulse and lesser as compared with other two postures. These observations suggest that Siddhasana is a mild type of exercise and may have its application in conditions of low cardio-respiratory reserves especially in individuals in whom heavy exercises are contra-indicated.

Exposed eye area (EEA) in the expression of various emotions.

Exposed eye area (EEA) was measured in photographs of Indian adults who modeled six emotions--happiness, sadness, fear, anger, surprise, and disgust--as well as a neutral expression. The data were analyzed with a 2 x 6 (Eyes x Emotions) factorial analysis of covariance (ANCOVA). EEA for neutral expression was used as the covariate measure. The EEAs of the two eyes did not differ significantly during the expression of emotion. The EEAs for fear and surprise were significantly larger, and the EEA for disgust was significantly smaller than those for either other emotions or neutral expression.

Hemifacial display of emotion in the resting state.

The human face at rest displays distinguishable asymmetries with some lateralization of emotion or expression. The asymmetrical nature of the resting face was examined by preparing hemifacial composites, left-left, right-right, along with normal facial orientation. The left side and right side composites were constructed by using the lateral half of one side of the face and its mirror-reversal. The left side facial composites were found to be more emotional than the right side or normal facial orientations of neutral expressions.

Orbital prostheses.

This article presents the steps used in fabricating an orbital prosthesis. Major considerations such as selection of the spectacle frame and the artificial eye, eye alignment, and clay modeling are emphasized to ensure an esthetically acceptable prosthesis. A simple technique for construction of wax templates for fabrication of orbital prostheses in acrylic resin also was described.