Beryllium Detection in Human Lung Tissue Using Electron Probe X-Ray Microanalysis Kelly J
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Beryllium Detection in Human Lung Tissue using Electron Probe X-Ray Microanalysis Kelly J. Butnor, M.D., Thomas A. Sporn, M.D., Peter Ingram, Ph.D., Sue Gunasegaram, M.D., John F. Pinto, M.D., Victor L. Roggli, M.D. Department of Pathology, University of Vermont, Burlington, Vermont (KJB); Department of Pathology, Duke University Medical Center, Durham, North Carolina (TAS, PI, VLR); and Departments of Pathology (SG) and Internal Medical (JFP), St. Rose Dominican Hospital, Henderson, Nevada available, and can be performed using routine par- Chronic berylliosis is an uncommon disease that is affin sections. caused by the inhalation of beryllium particles, dust, or fumes. The distinction between chronic be- KEY WORDS: Atmospheric thin-window energy dis- rylliosis and sarcoidosis can be difficult both clini- persive X-ray analysis, Beryllium, Chronic beryllio- cally and histologically, as both entities can have sis, Sarcoidosis, Scanning electron microscopy. similar presentations and exhibit nonnecrotizing Mod Pathol 2003;16(11):1171–1177 granulomatous inflammation of the lungs. The di- agnosis of chronic berylliosis relies on a history of Beryllium is a naturally occurring metal that is exposure to beryllium, roentgenographic evidence found in a number of minerals, such as beryl ore, of diffuse nodular disease, and demonstration of with unique physicochemical properties that make beryllium hypersensitivity by ancillary studies, such it suitable for a variety of industrial and technologic as lymphocyte proliferation testing. Additional sup- applications. Although it is the second lightest port may be gained by the demonstration of beryl- known metal, beryllium is more rigid than steel, has lium in lung tissue. Unlike other exogenous partic- an unusually high melting point, and is an excellent ulates, such as asbestos, detection of beryllium in conductor of heat and electricity (1). Commonly human lung tissue is problematic. The low atomic alloyed with other metals, such as copper and alu- number of beryllium usually makes it unsuitable for minum, beryllium is an important component in conventional microprobe analysis. We describe a the manufacture of aerospace equipment, comput- case of chronic berylliosis in which beryllium was ers, electronics, industrial ceramics, nuclear reac- detected in lung tissue using atmospheric thin- tors and weapons, dental prostheses, and even window energy-dispersive X-ray analysis (ATW some golf clubs. EDXA). A woman with a history of occupational Despite its desirable properties, beryllium and exposure to beryllium at a nuclear weapons testing beryllium-containing compounds are toxic to hu- facility presented with progressive cough and dys- mans. The adverse pulmonary effects of beryllium pnea and a nodular pattern on chest roentgeno- became evident during the first half of the 20th graph. Open lung biopsy showed nonnecrotizing century, with the development of acute chemical granulomatous inflammation that was histologi- pneumonitis in beryllium extraction workers (2). cally indistinguishable from sarcoidosis. Scanning Subsequently, disease similar to sarcoidosis was de- electron microscopy and ATW EDXA demonstrated scribed in workers who were exposed to beryllium particulates containing beryllium within the granu- phosphors used to produce fluorescent lamps (3). lomas. This application of EDXA offers significant Improved industrial practices and limitations im- advantages over existing methods of beryllium de- posed on workplace exposure have markedly re- tection in that it is nondestructive, more widely duced the incidence of beryllium-induced lung dis- ease, in particular, acute beryllium pneumonitis (4). However, an acceptable substitute for beryllium Copyright © 2003 by The United States and Canadian Academy of has not been identified for many applications. Con- Pathology, Inc. VOL. 16, NO. 11, P. 1171, 2003 Printed in the U.S.A. sequently, an estimated 807,000 individuals are Date of acceptance: July 18, 2003. presently at risk of developing beryllium disease (5). Address reprint requests to: Kelly J. Butnor, M.D., Fletcher Allen Health Care, MCHV Campus, Smith 246B, 111 Colchester Avenue, Burlington, VT Unlike acute beryllium disease, which manifests 05401; fax: 802-847-4155; e-mail: [email protected]. as a chemical pneumonitis, chronic berylliosis, or DOI: 10.1097/01.MP.0000094090.90571.ED chronic beryllium disease, is a systemic disorder 1171 believed to result from delayed-type hypersensitiv- oximetry on room air at rest showed an arterial ity to beryllium. It is characterized by nonnecrotiz- oxygen saturation of 96%. Pulmonary function tests ing granulomatous inflammation in the lungs and demonstrated mild restrictive lung disease and a several other organs. Remarkably similar clinical very mild reduction in diffusing capacity. Ancillary and histopathologic features can be seen in sar- studies included serologic tests for coccidioidomy- coidosis. Although a history of occupational expo- cosis, which were negative. The clinical impression sure is usually apparent, detection of elevated levels was sarcoidosis. Open biopsy of the right lung was of beryllium in lung tissue may be helpful in estab- performed. Following histopathologic examination, lishing the diagnosis. the patient was counseled to avoid further exposure Several techniques are employed for detection of to beryllium in the workplace. Lymphocyte prolif- beryllium in lung tissue, including electron energy eration testing for beryllium was also performed, loss spectroscopy (6), laser microprobe mass anal- which was positive. In the 14 months subsequent to ysis (7), and secondary ion mass spectrometry (8). diagnosis, the patient has experienced some symp- Although highly sensitive, these modalities are rel- tomatic relief with Flovent, and her pulmonary atively expensive and not widely available in the function tests have remained stable. clinical setting. At least1goflung tissue is required by some of these techniques, most of which destroy the tissue undergoing analysis (9). Pathologic Findings Conventional energy-dispersive X-ray analysis Grossly, the lung parenchyma was gray with a (EDXA) is a nondestructive technique that has been rubbery, nodular consistency. Histologic sections in use for Ͼ30 years. In such instruments, the showed clusters of well-formed nonnecrotizing cooled lithium-drifted silicon detector [Si(Li)] is granulomas with multinucleated giant cells, mainly protected in a vacuum by a thin beryllium window. along bronchovascular bundles (Fig. 1). The sur- Elements of atomic number Ն fluorine (Z ϭ 9) can rounding parenchyma showed mild chronic inter- be detected by conventional EDXA, but low-energy stitial inflammation, but fibrosis and honeycomb- X-rays are absorbed by the beryllium window. ing were absent. Examination with polarizing light Newer polymeric atmospheric thin-window (ATW) microscopy demonstrated minute round birefrin- EDXA detectors are theoretically capable of detect- gent particles in the granulomas, which were pre- ing lower atomic number elements such as beryl- dominantly within the cytoplasm of multinucleated lium (Z ϭ 4) (10). To our knowledge, detection of giant cells. beryllium in human lung tissue using EDXA has not A beryllium-free carbon disc was examined in a been reported. JEOL-JSM 6400 scanning electron microscope We report a case of a woman with a history of (JEOL USA, Inc., Peabody, MA) equipped with a beryllium exposure who developed cough and pro- Robinson backscatter electron image detector gressive dyspnea, accompanied by bilateral hilar (ETP-USA/Electron Detectors, Inc., Rocklin, CA), a adenopathy and nodular parenchymal disease. Ex- Gresham Sirius 30 mm2 X-ray detector (Gresham amination of lung tissue by scanning electron mi- Scientific Instruments Ltd., Buckinghamshire, En- croscopy (SEM) and ATW EDXA demonstrated par- gland), and a 4pi Analysis microanalyzer and pulse ticles of beryllium within granulomas. processor (4pi Analysis, Inc., Durham, NC). An ac- celerating voltage of 5 keV was used. The disc was probed, and the low energy threshold discriminator CASE REPORT was set to allow acquisition of X-ray pulses of ap- proximately 0.04 keV and greater, while excluding Clinical History pulses from the zero energy reference peak. This The patient was a 40 year-old Caucasian female ensured that no spurious peaks would be visualized nonsmoker. Her past medical history was signifi- in the region corresponding to beryllium (~ 0.11 cant for allergic rhinitis and depression, for which keV). A pure beryllium grid was then mounted on she took Zyrtec and Effexor. She was exposed to an aluminum disc and examined in a similar man- beryllium through her employment as a geologist at ner. With negative backscattered electron imaging a nuclear weapons testing facility. (BEI), the beryllium grid appeared bright on a The patient was in her usual state of good health darker aluminum background (Fig. 2). EDXA until 2 years before presentation, at which time she yielded peaks for beryllium. A 128 ϫ 128 pixel developed a persistent cough and dyspnea on ex- (beam current, ~10-8 amps, 6 sec/pixel dwell time) ertion, associated with bilateral hilar adenopathy elemental X-ray image set showed distributions and diffuse nodular pulmonary parenchymal dis- consistent with the morphology of the grid and its ease on chest radiographs. Physical examination specimen support (Fig. 2) (11). Beryllium and the disclosed normal chest auscultation. There were no aluminum support were clearly visualized,