Alberto M. Marchevsky

Pulmonary complications of the acquired immunodeficiency syndrome: A clinicopathologic study of 70 cases

The pulmonary complications of 70 patients with the acquired immunodeficiency syndrome (AIDS) are reviewed. Pneumocystis carinii pneumonia (PCP), present in 67 per cent of the patients, was diagnosed by fiberoptic bronchoscopy with transbronchial biopsies in all of the patients except two adults, who required open lung biopsy, and two children, in whom the infection was detected only at autopsy. Other opportunistic infections, such as cytomegalovirus pneumonitis, mycobacterial infections, invasive candidiasis, toxoplasmosis, cryptococcosis, and histoplasmosis, were more difficult to diagnose by fiberoptic bronchoscopy. In only four cases were these conditions detected during life. Neoplasms and lymphoproliferative processes also presented diagnostic problems, and only one case each of Kaposis sarcoma and lymphoid interstitial pneumonitis were detected by fiberoptic bronchoscopy. In four other cases these conditions, as well as two pulmonary lymphomas, diffuse large cell immunoblastic type, were detected only at autopsy. Sixty-eight per cent of the patients in this study died, usually with progressive intractable respiratory failure and pulmonary complications that had not been diagnosed during life, including potentially treatable diseases, such as bacterial pneumonias, PCP, nontuberculous mycobacteria, invasive candidiasis, toxoplasmosis, and invasive aspergillosis. The need for earlier detection of pulmonary complications in patients with AIDS is discussed.

Oat cell carcinoma of the uterine cervix in a pregnant woman treated with cis-diamminedichloroplatinum

Abstract We report a case of oat cell carcinoma of the cervix whose diagnosis was established by light and electron microscopic studies. The patient was pregnant with a male fetus, and was given a course of cis -diamminedichloroplatinum before definitive surgical therapy. The effects of this treatment upon the tumor and the fetus are discussed.

Suppression of Cell Proliferation and Signaling Transduction by Connective Tissue Growth Factor in Non–Small Cell Lung Cancer Cells

Connective tissue growth factor (CTGF) is a secreted protein that belongs to CCN family. The proteins in this family are implicated in various biological processes, such as angiogenesis, adhesion, migration, and apoptosis. In this study, we explored the roles of CTGF in lung tumorigenesis. The expression levels of CTGF in 58 lung cancer samples were reduced by >2 fold in 57% of the samples compared with matched normal samples using real-time reverse transcription-PCR. These results were confirmed by immunohistochemical staining for CTGF in normal lung epithelia and lung cancer. Cellular proliferation was inhibited in non–small cell lung cancer (NSCLC) cell lines NCI-H460, NCI-H520, NCI-H1299, and SK-MES-1 by CTGF overexpression. Partially purified CTGF suppressed lung cancer cell growth. The growth inhibition caused by CTGF overexpression was associated with growth arrest at G0-G1 and prominent induction of p53 and ADP ribosylation factor. Most interestingly, overexpression of CTGF suppressed insulin-like growth factor-I–dependent Akt phosphorylation and epidermal growth factor–dependent extracellular signal-regulated kinase 1/2 phosphorylation. In summary, NSCLC cells expressed decreased levels of CTGF compared with normal lung cells; this lower expression has an effect on lung cancer cell proliferation and its cellular response to growth factors. Our data suggest that CTGF may behave as a secreted tumor suppressor protein in the normal lung, and its expression is suppressed in many NSCLCs. (Mol Cancer Res 2006;4(8):591–8)

Limited role of Ki-67 proliferative index in predicting overall short-term survival in patients with typical and atypical pulmonary carcinoid tumors

Pulmonary carcinoid tumors are currently classified as typical or atypical based on the mitotic index (2 per 10 hpf) and/or the presence of necrosis. Following incorporation of the Ki-67 index into the classification of GI carcinoid tumors, our oncologists have also been requesting this test as part of the work-up of pulmonary carcinoid tumors although there are currently no established criteria for interpreting Ki-67 index in these neoplasms. We utilized the Ariol® SL50 Image Analyzer system to measure the Ki-67 index in 101 pulmonary carcinoid tumors (78 typical and 23 atypical) and then correlated the Ki-67 index and the histological diagnoses in univariate and multivariable analysis with overall survival. The mean Ki-67 indices for the typical carcinoids (3.7 s.d.±4.0) and the atypical carcinoids (18.8 s.d.±17.1) were significantly different (P<0.001) although the frequency distributions of Ki-67 indices in the two groups overlapped considerably. Receiver operating characteristic curve analysis showed that a Ki-67 index cutoff value of 5% provided the best fit for specificity and sensitivity in predicting overall survival. Histological diagnosis and the Ki-67 index cutoff of 5% were each independently strong predictors of survival (P<0.001 and P=0.003, respectively). When considered together in multivariable analysis, histological diagnosis was the stronger predictor of overall survival and a Ki-67 index cutoff of 5% did not provide additional significant predictive survival information within either the typical carcinoid or the atypical carcinoid patient group. A few typical carcinoid patients with Ki-67 indices of 5% appeared to have worse survival after 5 years than those with Ki-67 indices <5%, but the data set was insufficiently powered to further analyze this. These findings do not provide best evidence for the routine use of Ki-67 index to prognosticate overall short-term survival in patients with pulmonary carcinoid tumors.

Lessons Learned From Mistakes and Deferrals in the Frozen Section Diagnosis of Bronchioloalveolar Carcinoma and Well-Differentiated Pulmonary Adenocarcinoma An Evidence-Based Pathology Approach

The frozen section diagnosis of lung nodules is difficult because inflammatory atypia and histologic artifacts can simulate a malignancy. From a total of 2,405 frozen sections examined, 143 cases were misdiagnosed or deferred, including 65 with reactive atypia (RA) and 35 bronchioloalveolar carcinomas or well-differentiated adenocarcinomas (BAC-AC), resulting in deferral and error rates of 4.36% and 1.58%, respectively. The presence of 25 pathologic features was evaluated by using an evidence-based pathology (EBP) approach. Of the pathologic features, 11 were significant at a P value of less than .05 but exhibited variable incidence in AC and RA. Positive likelihood ratios allowed for identification of the 5 most useful pathologic features for the diagnosis of AC: multiple growth patterns, anisocytosis, atypia more than 75%, macronucleoli, and atypical mitoses. Granulomas favored the diagnosis of RA. An EBP approach is helpful to stratify pathologic features according to their clinical applicability.

Oncocytic carcinoid of lung: an ultrastructural analysis.

A 52‐year‐old man with a typical carcinoid tumor of the lung in which the tumor cells displayed marked oncocytic metaplasia is presented. The clinicopathologic and ultrastructural differences with so‐called oncocytic of the lung are discussed. The potential of Kulchitsky cell derivatives to undergo oncocytic metaplasma is documented ultrastructurally.

Quantitative and immunocytochemical studies of APUD cells in airways and gut. The effects of priming with L-dopa and 5-HTP.

The amine precursor uptake and decarboxylase (APUD) cells in airways and small intestine of adult hamsters have been studied by quantitative, histochemical and immunocytochemical methods for the presence of argyrophilia, ACTH, hGH, calcitonin, bombesin and prolactin in control animals and following priming with two amine precursors: L-dopa and 5-hydroxytryptophane (5-HTP). APUD cells have been defined by the presence of intracytoplasmic argyrophilic granules. A method that related them to airway or gut perimeter length or total epithelial cell numbers has been applied. Calcitonin-like-immunoreactivity (CLIR) is present in epithelial cells in the tracheal epithelium and glands. The presence of ACTH, hGH, bombesin or prolactin is not detected. Priming with L-Dopa and 5-HTP results in up to 12 fold increases in densities of argyrophilic APUD cells in airways and ileum when ratios of APUD cells/100 nuclei are compared to those in control animals. Exposure to 5-HTP induces no significant changes in densities of cells with CLIR in the trachea but CLIR is not detected in animals exposed to L-DOPA. Ratios of APUD cells/100 epithelial cells appear to be more sensitive than those of APUD cells/mm in detecting significant changes in APUD cell densities. Priming with amine precursors is a valuable tool in quantitative studies of neuroendocrine cells.

Root Cause Analysis of Problems in the Frozen Section Diagnosis of In Situ, Minimally Invasive, and Invasive Adenocarcinoma of the Lung

CONTEXT Frozen sections can help determine the extent of surgery by distinguishing in situ, minimally invasive, and invasive adenocarcinoma of the lung. OBJECTIVE To evaluate our experience with the frozen section diagnosis of these lesions using root-cause analysis. DESIGN Frozen sections from 224 consecutive primary pulmonary adenocarcinomas (in situ, 27 [12.1%]; minimally invasive, 46 [20.5%]; invasive, 151 [67.4%]) were reviewed. Features that could have contributed to frozen section errors and deferrals were evaluated. RESULTS There were no false-positive diagnoses of malignancy. Frozen section errors and deferrals were identified in 12.1% (27 of 224) and 6.3% (14 of 224) of the cases, respectively. Significantly more errors occurred in the diagnosis of in situ and minimally invasive adenocarcinoma than in the diagnosis of invasive adenocarcinoma (P < .001). Frozen section errors and deferrals were twice as frequent in lesions smaller than 1.0 cm (P = .09). Features significantly associated with errors and deferrals included intraoperative consultation by more than one pathologist (P = .003) and more than one sample of frozen lung section (P = .001). Inflammation with reactive atypia, fibrosis/scar, sampling problems, and suboptimal quality sections were identified in 51.2% (21 of 41), 36.6% (15 of 41), 26.8% (11 of 41), and 9.8% (4 of 41) of the errors and deferrals, respectively (more than one of these factors was identified in some cases). Frozen section errors and deferrals had significant clinical impact in only 4 patients (1.8%); each had to undergo completion video-assisted thoracoscopic lobectomy less than 90 days after the initial surgery. CONCLUSIONS The distinction of in situ from minimally invasive adenocarcinoma is difficult in both frozen and permanent sections. We identified several technical and interpretive features that likely contributed to frozen section errors and deferrals and suggest practice modifications that are likely to improve diagnostic accuracy.

Evidence-Based Pathology: Systematic Literature Reviews as the Basis for Guidelines and Best Practices

CONTEXT Evidence-based medicine has been proposed as a new paradigm for the identification and evaluation of medical information. Best available evidence or data are identified and used as the basis for the diagnosis and treatment of individual patients. Evidence-based pathology has adapted basic evidence-based medicine concepts to the specific needs of pathology and laboratory medicine. OBJECTIVES To briefly review the history and basic concepts of evidence-based medicine and evidence-based pathology, describe how to perform and interpret systematic reviews, and discuss how to integrate best evidence into guidelines. DATA SOURCES PubMed (National Library of Medicine, Washington, DC) and Web of Science (Thompson Reuters, New York, New York) were used. CONCLUSIONS Evidence-based pathology provides methodology to evaluate the quality of information published in pathology journals and apply it to the diagnosis of tissue samples and other tests from individual patients. Information is gathered through the use of systematic reviews, using a method that is less biased and more comprehensive than ad hoc literature searches. Published data are classified into evidence levels to provide readers with a quick impression about the quality and probable clinical validity of available information. Best available evidence is combined with personal experience for the formulation of evidence-based, rather than opinion-based, guidelines that address specific practice needs.

Evidence based pathology and laboratory medicine

Evidence based pathology and laboratory medicine / , Evidence based pathology and laboratory medicine / , کتابخانه دیجیتال جندی شاپور اهواز