Case 3 -

Hard Metal Disease (Giant Cell Interstitial Pneumonia) Andrew Churg University of British Columbia Vancouver, BC, Canada

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Clinical History A 34 yo male presented with a several month history of increasing shortness of breath. The shortness of breath was not precipitated by an acute illness. He was a nonsmoker. He had no pets at home. There was no recent travel history. He had worked for 10 years grinding saw blades at a small factory. CT scan showed diffuse ground glass infiltrates with small centrilobular nodules. Pulmonary function tests demonstrated a restrictive pattern with reduced diffusing capacity. A thoracoscopic lung biopsy was performed. Case 3 - Figure 1 - Whole mount image showing sharply demarcated airway centered lesions. Case 3 - Figure 2 - Lower power view showing interstitial inflammation and fibrosis centered around a respiratory bronchiole. Note intense lymphoid infiltrate. Characteristic airspace macrophages and giant cells can be seen. Case 3 - Figure 3 - High power view showing macrophages and giant cells in airspaces. Note that some of the giant cells have phagocytized macrophages, a typical finding in hard metal disease. After a diagnosis of hard metal disease was made, the patient ceased exposure and was treated with high dose steroids with considerable functional improvement. Diagnosis: Hard metal disease (giant cell interstitial pneumonia) Discussion: Hard metal (cemented tungsten carbide with cobalt) is a synthetic compound which approaches the hardness of diamond. It is used in applications which require strength and rigidity even at high operating temperatures, and is particularly valuable for cutting edges on tools, drills of all types including those used in mining, and high temperature bearings. The metal is prepared by first heating finely divided tungsten and carbon to form tungsten carbide; then cobalt, and sometimes titanium, tantalum or chromium carbide are added, and the mixture fused at high temperature to form the final product. The whole process generates very fine dust (mean particle size less than 2 microns). Some 30,000 workers in the US are exposed, including individuals who make hard metal, and those who use hard metal cutting tools if they grind the tools or operate the tools in cooling baths that leach cobalt from the metal. Hard metal exposure can produce interstitial fibrosis ("hard metal disease"), occupational asthma, and sometimes a syndrome resembling extrinsic allergic alveolitis, as well as contact dermatitis. Patients with interstitial fibrosis caused by hard metal usually present with shortness of breath; the interstitial process is generally either lower or mid zonal in chest radiographs. CT scans have most commonly been reported as showing ground glass infiltrates and centrilobular fine nodules, although diffuse honeycombing has been described in a few cases. Pulmonary function tests tend to show a restrictive abnormality. Histologically, hard metal disease is characterized by a distinctly centrilobular (ie, centered on the respiratory bronchioles) pattern of interstitial fibrosis and chronic interstitial inflammation, sometimes accompanied by a few eosinophils. Lymphoid nodules may be present. This picture is accompanied by a very variable number of airspace macrophages and giant cells, the latter sometimes extremely large and bizarre appearing; in some instances the giant cells phagocytize macrophages. With increasing disease severity the process spreads from centrilobular region to centrilobular region and the intervening parenchyma may show both interstitial inflammation/fibrosis and airspace macrophages and giant cells in a pattern reminiscent of desquamative interstitial pneumonia (DIP). This pattern was originally described by Liebow and labeled "giant cell interstitial pneumonia"(GIP). Fine black particles of hard metal can be found in in macrophages and giant cells, although they are usually scarce, and their appearance is in no way specific. Little or no birefringent material is present. Given a case which historically or histologically could be hard metal disease, analysis by energy dispersive x-ray spectroscopy performed on the biopsy tissue (including material from paraffin blocks or slides) is very helpful: the diagnosis is confirmed if one finds tungsten, since particles of tungsten are never present in the lungs of the general population. Occasionally particles of cobalt are also found, but this is infrequent, since cobalt is soluble in lung tissue fluid. A variety of animal and human data suggest that sensitization to cobalt is actually the cause of hard metal disease, and a process clinically and histologically identical to hard metal disease has been reported in diamond polishers who used cobalt grinding powder but had no exposure to hard metal (Demedts et al 1984). Unlike most other causes of interstitial fibrosis, many cases of hard metal disease respond well to steroids and removal from exposure, hence accurate and early diagnosis is crucial. Some cases progress to honeycombing, particularly if exposure to hard metal continues. Differential Diagnosis The differential diagnosis includes primarily entities in which there is interstitial inflammation and fibrosis centered on the respiratory bronchioles: In eosinophilic granuloma of lung (pulmonary Langerhans cell histiocytosis) the early lesions are highly cellular with little fibrosis and contain a mixture of eosinophils and Langerhans cells, the latter demonstrable with S-100 or CD1a. The lesions of eosinophilic granuloma frequently form cysts, a process that is not seen in hard metal disease. However, collections of alveolar macrophages can be found around the lesions of eosinophilic granuloma. Airway centered interstitial fibrosis is a newly described form of idiopathic interstitial pneumonia (Churg et al 2004) in which there is considerable scarring of the bronchioles with extension of the fibrosing process away from the airways. Unlike hard metal disease, the fibrosis is fine and paucicellular and there frequently is overlying bronchiolar cell metaplasia. Airspace macrophages and giant cells are not seen. CT scans show that there is considerable fibrosis around the proximal airways as well, again not a feature of hard metal disease. Extrinsic allergic alveolitis (EAA, hypersensitivity pneumonitis) typically demonstrates a small airway centered pattern of mild chronic interstitial inflammation, usually but not always accompanied by individual giant cells or poorly formed granulomas. Airspace macrophages are generally scarce in EAA. Desquamative interstitial pneumonia (DIP) shows a pattern of very diffuse interstitial inflammation with or without fibrosis and a prominent pattern of alveolar filling by macrophages; rare giant cells may be present but are not as large or bizarre as those seen in hard metal disease. Most important, DIP does not show any centrilobular predominance. References Bech AO, Kipling MD, Heather JC: Hard metal disease. Br J Indust Med 1962; 19: 239-252. Churg A, Colby TV: Diseases caused by metals and related compounds. In, Churg A, Green FHY: Pathology of Occupational Lung Disease, 2nd Edition. Baltimore; Williams and Wilkins, 1998. Pages 77-128. Churg A, Myers J, Suarez T, Gaxiola M, Estrada A, Mejia M, Selman M: Airway centered interstitial fibrosis: a distinct form of aggressive diffuse lung disease. Amer J Surg Pathol, in press. Coates EO, Watson JHL: Diffuse interstitial lung disease in tungsten carbide workers. Ann Int Med 1971; 75: 709-716. Davison AG, Haslam PL, Corrin B, Coutts II, Dewar A et al: Interstitial lung disease and asthma in hard-metal workers: Bronchoalveolar lavage, ultrastructural, and analytical findings, and results of bronchial provocation tests. Thorax 1983; 38: 119-128. Demedts M, Gheysens B, Nagels J, Verbeken E, Lauweryns J, ven der Eeckhout A et al: Cobalt lung in diamond polishers. Amer Rev Respir Dis 1984; 130: 130-135. Sprince NL, Chamberlin RI, Hales CA, Weber AL, Kazemi H: Respiratory disease in tungsten carbide production workers. Chest 1984; 86: 549-557.