Pulmonary Cryptococcosis Presenting With Lung Mass: Report of 7 Cases and Review of Literature.

Pulmonary cryptococcosis is commonly found in immunocompromised patients. This microorganism rarely infects immunocompetent individuals, and when it does, it causes mild symptoms. The radiological findings of this disease may involve an intrapulmonary mass that mimics lung tumor. The objective of this study was to review the clinicopathological information, radiological findings, and treatment of patients who presented with intrapulmonary mass due to cryptococcosis. This study collected data from 7 patients who were treated at Songklanagarind Hospital, Songkhla, Thailand, between 2009 and 2014. Their clinical data, radiological findings, pathological results, and treatment protocols were reviewed. The patients were 2 women and 5 men, ranging in age from 37 to 79 years old. One case was an immunocompromised host. Four cases experienced the chest symptoms of dyspnea, hemoptysis, and chronic cough. The most common location of mass was the left lower lobe (71%). Four cases had a history of bird contact. Lung lobectomy was performed in 3 cases (42%), and all of the patients were treated with oral fluconazole. An intrapulmonary mass caused by this microorganism is mainly found in immunocompetent patients. Treatment with the antifungal drug fluconazole is very effective.

Pneumonia: Features registered in autopsy material.

BACKGROUND: Despite improvements in clinical practice, pneumonia remains one of the leading causes of death worldwide. Pathologic findings from autopsy reports could provide more precise and valid data on characteristics of pneumonia patients. METHODS: We retrospectively reviewed autopsy reports of deceased patients admitted to the Institute for Pulmonary Diseases of Vojvodina in Sremska Kamenica, Serbia, between 1994 and 2003. The patients were classified into two groups: group 1 (n = 161) comprised patients in whom pneumonia was the main cause of death, while group 2 (n = 165) consisted of patients in whom pneumonia was confirmed at autopsy but had various different causes of death. RESULTS: From 1776 patients who underwent autopsy 326 (18.3%) were diagnosed with pneumonia. The most common underlying diseases were atherosclerosis (29.4%), chronic obstructive pulmonary disease (COPD) (26.7%), and malignancies (20.2%). Pneumonia was the main cause of death in 161 cases (group 1) while in group 2 major causes of death were heart failure (HF) (26.7%), acute myocardial infarction (AMI) (16.4%), and pulmonary embolism (PE) (10.9%). Multilobar involvement (91% vs.27%), pulmonary effusion (29% vs.14%), and lung abscess (23.6% vs.8.5%) were more frequently found in group 1, compared to group 2. CONCLUSION: In patients with pneumonia who underwent autopsy most common underlying diseases were atherosclerosis, COPD, and malignancies, while major causes of death were: progression of pneumonia, HF, AMI, and PE.

Splenomegaly in Sarcoidosis: Frequency, Treatment, Prognosis and Long-term Follow-up.

INTRODUCTION: The splenic involvement is common in sarcoidosis, but its real frequency is still obscure depending doubtless on the method of splenomegaly detection. Splenomegaly may be accompanied with pain or anemia, leucopenia and thrombocytopenia. OBJECTIVE: The aim of this study was to investigate the frequency of splenomegaly related to clinical characteristics of sarcoidosis and to solve the dilemma--whether to introduce medicaments, and when to perform splenectomy. METHODS: The method of the study is a retrospective and prospective analysis of the patients'material. RESULTS: The study included 540 patients with sarcoidosis in a 20-year period. Of them, 26% had splenomegaly detected by computerized tomography screening. Splenomegaly was more frequently registered in the patients with a longer history of sarcoidosis (38%), as compared to those with a shorter history of the disease (23%) (p < 0.05). Splenomegaly was more frequently registered in the patients with other extrapulmonary lesions detected (33%) than in those who had no extrapulmonary manifestations of sarcoidosis (17%) (p < 0.01). Indications, possible benefits and complications of splenectomy were analysed in 11 sarcoidosis patients undergoing this intervention for various reasons, of which the follow-up period ranged from one to 20 years. CONCLUSION: Splenomegaly was more frequent in chronic cases or in the patients with established sarcoid lesions of other extrapulmonary organs.The primary treatment of uncomplicated symptomatic splenic sarcoidosis includes medicamentous therapy. Occasionally, splenectomy is required. Prognostically, splenomegaly indicates an unfavorable course of the disease.

The sarcoid granuloma: 'epithelioid' or 'lymphocytic-epithelioid' granuloma?

BACKGROUND: This study aims to analyze the structure and quantities of cellular elements in sarcoid granulomas. METHODS: We investigated 34 transbronchial lung biopsy samples obtained from 34 sarcoid patients. The quantity and composition of the cellular elements inside a granuloma were determined by the quantitative stereometry method, employing the numerical density as a stereological method. RESULTS: A total of 102 sarcoid granulomas were analyzed. The central part of all granulomas was occupied by epithelioid cells. Besides these, giant cells, lymphocytes, macrophages and plasma cells were also seen. The mean numerical density of all the cells in the central part of a sarcoid granuloma was 111,751 mm-3. Lymphocytes prevailed in number, exceeding the total count of all other cells. With a mean numerical density of 74,321 mm-3, lymphocytes were twice as numerous as both epithelioid cells and macrophages with a mean numerical density of 37,193 mm-3. CONCLUSIONS: Lymphocytes are the predominant cell type in the central part of a sarcoid granuloma, significantly exceeding both epithelioid cells and macrophages in number, raising the question if the term "epithelioid granuloma", routinely used to designate sarcoid granulomas, is correct, or if it would be more logical to call them "lymphocytic-epithelioid granulomas" instead. TRIAL REGISTRATION: This study was supported by the Serbian Ministry of Science and Environmental Protection Grant Number 175006/2011.

Clinical trials in advanced stage lung cancer: a survey of patients' opinion about their treatment.

BACKGROUND: The major aim of this study was to investigate what patients with advanced stage lung cancer, enrolled in a clinical trial, thought about their treatment. We also wanted to investigate if there exist any characteristics that could influence patients' opinion about the clinical trial. PATIENTS AND METHODS: Over the period from June 2008 to June 2009, 59 eligible patients were enrolled in this study. The major inclusion criteria were: participation in a clinical trial, previously treated advanced stage lung cancer, and good performance status (ECOG 0-2). All patients were asked to answer a questionnaire designed to investigate their impressions about participation in a clinical trial. The questionnaire was deposited in a sealed box which was opened at the end of the study.We investigated a possible influence of age, gender, education, lung cancer stage, chemotherapy line and tumor type on the patients' opinion about some aspects of the clinical trial. RESULTS: The majority of the patients were aware they were participating in the clinical trial and a significant number of them were very satisfied with the treatment. Of the investigated factors, only the level of education had a statistically significant influence on some of the questions raised in the questionnaire. CONCLUSIONS: Patients participating in clinical trials are satisfied with their treatment, ready to proceed with it and would recommend it to other patients. It depends mainly on health professionals to maintain this level of confidence and justify their trust.

How to measure image quality in tissue-based diagnosis (diagnostic surgical pathology).

BACKGROUND: Automated image analysis, measurements of virtual slides, and open access electronic measurement user systems require standardized image quality assessment in tissue-based diagnosis. AIMS: To describe the theoretical background and the practical experiences in automated image quality estimation of colour images acquired from histological slides. THEORY, MATERIAL AND MEASUREMENTS: Digital images acquired from histological slides should present with textures and objects that permit automated image information analysis. The quality of digitized images can be estimated by spatial independent and local filter operations that investigate in homogenous brightness, low peak to noise ratio (full range of available grey values), maximum gradients, equalized grey value distribution, and existence of grey value thresholds. Transformation of the red-green-blue (RGB) space into the hue-saturation-intensity (HSI) space permits the detection of colour and intensity maxima/minima. The feature distance of the original image to its standardized counterpart is an appropriate measure to quantify the actual image quality. These measures have been applied to a series of H&E stained, fluorescent (DAPI, Texas Red, FITC), and immunohistochemically stained (PAP, DAB) slides. More than 5,000 slides have been measured and partly analyzed in a time series. RESULTS: Analysis of H&E stained slides revealed low shading corrections (10%) and moderate grey value standardization (10 - 20%) in the majority of cases. Immunohistochemically stained slides displayed greater shading and grey value correction. Fluorescent stained slides are often revealed to high brightness. Images requiring only low standardization corrections possess at least 5 different statistically significant thresholds, which are useful for object segmentation. Fluorescent images of good quality only possess one singular intensity maximum in contrast to good images obtained from H&E stained slides that present with 2 - 3 intensity maxima. CONCLUSION: Evaluation of image quality and creation of formally standardized images should be performed prior to automatic analysis of digital images acquired from histological slides. Spatial dependent and local filter operations as well as analysis of the RGB and HSI spaces are appropriate methods to reproduce evaluated formal image quality.

Texture- and object-related automated information analysis in histological still images of various organs.

OBJECTIVE: To create algorithms and application tools that can support routine diagnoses of various organs. MATERIALS: A generalized algorithm was developed that permits the evaluation of diagnosis-associated image features obtained from hematoxylin-eosin-stained histopathologic slides. The procedure was tested for screening of tumor tissue vs. tumor-free tissue in 1,442 cases of various organs. Tissue samples studied include colon, lung, breast, pleura, stomach and thyroid. The algorithm distinguishes between texture- and object-related parameters. Texture-based information-defined as gray value per pixel measure--is independent from any segmentation procedure. It results in recursive vectors derived from time series analysis and image features obtained by spatial dependent and independent transformations. Object-based features are defined as gray value per biologic object measured. RESULTS: The accuracy of automated crude classification was between 95% and 100% based upon a learning set of 10 cases per diagnosis class. Results were independent from the analyzed organ. The algorithm can also distinguish between benign and malignant tumors of colon, between epithelial mesothelioma and pleural carcinomatosis or between different common pulmonary carcinomas. CONCLUSION: Our algorithm distinguishes accurately among crude histologic diagnoses of various organs. It is a promising technique that can assist tissue-based diagnosis and be expanded to virtual slide evaluation.

Lung carcinoma-associated atypical adenomatoid hyperplasia, squamous cell dysplasia, and chromosome alterations in non-neoplastic bronchial mucosa.

This article analyzes phenotype and genotype alterations of the lung in association with lung cancer. The frequency of phenotype preneoplastic lesions (atypical adenomatoid hyperplasia (AAH) and squamous cell dysplasia (SCD)) was analyzed at distinct distances from the tumor boundary in 150 lung carcinomas. AAH was noted in 19/150 (13%) cases and more frequently seen in adeno carcinomas, squamous cell dysplasia was noted in 46/150 (31%) cases and more frequently seen in squamous cell carcinomas. The degree of cellular atypia decreased with increasing distance from tumor boundary in both AAH and SCD. At similar distances, genotype (chromosome) alterations of surrounding bronchial mucosa were studied in additional 55 primary and secondary lung tumors by karyotype analysis. Numerical chromosome aberrations occur frequently in primary lung carcinomas and adjacent bronchial mucosa, and affect at average 4.5/10 metaphases in primary lung cancer and 2/10 metaphases in metastases. Most abnormal metaphases were induced by chromosome losses, only few by additional copies, i.e. trisomy, etc. Losses of y chromosome were seen in both malignancy and adjacent bronchial mucosa, and interpreted as "tumor related", losses of chromosome 21 in adjacent bronchial mucosa were non-tumor related in adenocarcinoma and metastases, losses of chromosome 19 in adjacent bronchial mucosa occurred independently in squamous cell and large cell carcinomas. The data suggest the hypothesis that preneoplastic lesions in the lung might be partly induced by the tumor itself.

Atypical adenomatous hyperplasia of lung: its incidence and analysis of clinical, glycohistochemical and structural features including newly defined growth regulators and vascularization.

BACKGROUND: Adenomatous hyperplasia of the peripheral lung has been suggested to be a preneoplastic lesion leading to peripherally localized lung carcinomas. The paucity of data about cellular and vascular characteristics of this lesion in comparison to normal lung prompted this investigation. MATERIAL AND METHODS: We describe results of two investigations comprising 75 cases and 70 cases, respectively, with atypical adenomatous hyperplasia (AAH) of the lung, respectively: (a) a prospective study part with thorough analysis of surgical lung specimens (lobes and lungs) for light microscopical detection of the lesion; and (b) a retrospective study part with immuno- and lectin histochemical analysis of AAH and non-neoplastic lung parenchyma monitoring expression of growth-related markers and changes in vascularization patterns. Sections of the individual cases were examined by an image-analyzing system including automated measurement of staining intensities and structure analysis. RESULTS: The prospective study part revealed an incidence of AAH in 2/31 cases with squamous cell carcinoma and in 5/32 cases with adenocarcinomas. No relation to pT- or pN stages was detectable, high grade AAHs were seen to be close to the tumor lesions (<2 cm distance) and those with low grade at greater distances. Statistically significantly increased levels of expression of anti-apoptotic bcl-2, macrophage migration inhibitory factor (MIF) capable to suppress p53 activities, heparin-binding lectin, interleukin-2, galectin-1 and of binding sites for the endogenous lectins galectins-1, -3 and -7 were determined. In addition, alveolar-lining cells, which express these markers, formed spatial clusters, which harbor different levels of structural entropy. AAH displayed an increased level of vascularization characterized by regular size and increased number of newly formed vessels. INTERPRETATION: The prospective and retrospective study parts point to a close association of AAH with peripherally localized adenocarcinoma of the lung. AAH is characterized by pronounced alteration of expression of several growth-related markers and probably non-reversible changes in vascularization.