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Respiration 2005;72:95-100 (DOI: 10.1159/000083409)

 Outline

• Key Words
• Abstract
• Introduction
• Case Report
• Pathologic Findings
• Discussion
• References

• Author Contacts
• Article Information
• Publication Details
• Drug Dosage / Copyright

  Key Words

• Malakoplakia, pulmonary
• Tuberculosis

  Abstract

Pulmonary malakoplakia is a disease that is difficult to diagnose because its symptoms vary from those mimicking bronchogenic carcinoma to pneumonitis-like tuberculous infections. Malakoplakia is an unusual inflammatory condition characterized by the accumulation of macrophages with diagnostic Michaelis-Gutmann bodies. In this study, an immunocompromised patient with a tumor mass in the upper lobe of the right lung coexisting with hilar node enlargement is presented. A thoracoscopic biopsy revealed pulmonary malakoplakia with tuberculosis of the hilar lymph node. Microbiologic cultures were positive for acid-fast positive bacilli from the hilar node specimen, and negative for any other microorganisms such as Rhodococcus equi, but positive for Escherichia coli from the lung specimen. The significance of these findings and the coincidental association between malakoplakia and tuberculosis are discussed.

Copyright © 2005 S. Karger AG, Basel

 Introduction

Malakoplakia is a rare xanthogranulomatous inflammation characterized by the proliferation of histiocytes that contain concentrically layered basophilic inclusions called Michaelis-Gutmann (M-G) bodies. Malakoplakia can form tumor-like nodules that clinically simulate malignancy in a variety of organs, but it most commonly affects the urinary tract.

Malakoplakia is usually associated with bacterial infection, and most cases occur with Escherichia coli infection [1]. However, other gram-negative and gram-positive bacteria, including mycobacteria as well as fungi, may also be seen [2]. An underlying debilitating state and immunosuppression are frequently noted and can play a role in the pathogenesis of this disease [3]. The occurrence of malakoplakia in the lung is not common [4], and less than 30 cases have been described previously [1, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16]. This patient presented with pulmonary malakoplakia which coexisted with tuberculosis of the hilar node simulating malignancy in an immunocompromised patient. To the best of my knowledge, this is probably the second case report of this unusual disorder.

 Case Report

A 84-year-old woman was admitted to hospital because of fever, cough, hemoptysis and right chest pain. Her past medical history included diabetes mellitus and asthma with steroid therapy, and, 5 years ago, right nephrectomy for renal stone and hydronephrosis with xanthogranulomatous pyelonephritis. Three years ago, right tuberculous pleurisy was also noted. Antituberculous drugs combined with isoniazid (300 mg, orally, q.d.) and rifampin (600 mg, orally, q.d.) given for 6 months resulted in relief for over 2 years.

A chest radiograph (fig. 1, 2) revealed dense consolidative infiltrates with no evidence of cavitation in the right upper lobe and hilar enlargement. A CT scan revealed an irregular mass in the upper lobe of the right lung (fig. 3). Cultures of the sputum and bronchioalveolar lavage fluid yielded no evidence of any microorganisms. Bronchial and transbronchial biopsy tissue revealed nonspecific inflammation. There was no evidence of granuloma, viral inclusions, or malignancy. Then, thoracoscopic examination was performed, and the lung and hilar node were biopsied. Intraoperative frozen section diagnosis revealed organized pneumonia with granulomatous inflammation of the hilar node. Cultures from the lung tissue disclosed E. coli and from the hilar node acid-fast tuberculous bacilli. Rhodococcus equi was not identified in the lung tissue culture. Gram stain failed to demonstrate gram-positive coccobacilli.

Fig. 1. Chest radiograph (posteroanterior view) showing a dense mass-like infiltrate in the right upper lobe with hilar node enlargement.

Fig. 2. Chest radiograph (lateral view) showing a dense mass.

Fig. 3. Chest CT showing an irregular mass in the right upper lung.

 Pathologic Findings

A thoracoscopic biopsy specimen from the lung revealed macrophage proliferation with finely granular to vacuolar cytoplasm (fig. 4). Occasionally, cells demonstrated classic intracellular M-G bodies (fig. 5) pathognomonic for malakoplakia. These inclusion bodies were positive for PAS, von Kossa (fig. 6B) and Prussian blue stain (fig. 6A). There were also areas of lymphocytes and plasma cell infiltrates. The lymph node tissue revealed caseous granulomatous inflammation with scattered Langhans' giant cells (fig. 7) and the presence of numerous acid-fast-positive mycobacterial bacilli by Ziehl-Neelsen stain (fig. 6C). Previous pathologic slides from nephrectomy specimens with multiple sections stained with PAS, von Kossa, and Prussian blue were reviewed. M-G bodies were not identified.

Fig. 4. Photomicrograph of the lung showing sheets of histiocytes intermingled with lymphocytes and plasma cell infiltrates. HE. ×100.

Fig. 5. Photomicrograph of the lung showing an intracellular target-like inclusion body (M-G body, arrow). HE. ×400.

Fig. 6. Photomicrographs showing an iron-positive target-like inclusion body (M-G body; Prussian blue stain, ×1,000; A), a calcium-positive target-like inclusion body (von Kossa stain. ×1,000; B) and a cluster of acid-fast positive tuberculous bacilli (Ziehl-Neelsen stain, ×1,000; C).

Fig. 7. Photomicrograph of the lymph node showing caseous granulomatous inflammation with Langhans'giant cells. HE. ×100.

She was discharged on combined therapy with ciprofloxacin (500 mg, orally, b.i.d.), erythromycin (250 mg, orally, t.i.d.) and antituberculous drugs (isoniazid and rifampin). A follow-up chest radiograph demonstrated improvement in the infiltrates in the upper lobe of the right lung and hilar area. At the 4-month follow-up, the patient was in good health.

 Discussion

Malakoplakia is a rare but distinctive type of chronic xanthogranulomatous inflammation usually affecting the urinary tract of women [5]. Defective host immunity and concomitant bacterial infection of tissue are both thought to be the pathogenetic factors in the development of malakoplakia. It is suggested to occur because of an impairment in the normal degradation process of phagocytosed material and in particularly of bacteria within histiocytes, although the exact mechanism remains to be determined. The residual debris then acts as a nidus for mineralization and M-G body formation.

Immunosuppression, chronic infection and increased steroid exposure are thought to predispose to its development [17]. Pulmonary malakoplakia is a relative unusual site of the disease, with less than 30 cases having been reported in total. In 1972, Gupta et al. [18] reported the first case of pulmonary malakoplakia: autopsy revealed the involvement of multiple organs, mimicking metastatic malignancy. The bacterial entity including R. equi [7, 8, 10, 11, 15, 16], Pasteurella multocida [12], E. coli, Mycobacterium avium intracellulare [2] and Mycobacterium tuberculosis has been implicated.

Involvement of the lung by malakoplakia may occur as a solitary dense mass-like lesion or a multifocal lesion or as part of a systemic involvement, mimicking malignancy. The radiographic combination of pulmonary consolidation and adenopathy may be confused with cancer as in the present case. The transbronchial biopsy may be diagnostic. On the other hand, examination of the transbronchial biopsy specimens in patients without an endobronchial mass may not be sufficient to establish the diagnosis, because these lesions rarely involve the bronchial mucosa and they show mostly nonspecific inflammation. An open-lung biopsy or even a lobectomy may be necessary to obtain diagnostic tissue. A thoracoscopic biopsy was performed to get a definitive diagnosis in the current case based upon histological and microbiologic findings. Pulmonary malakoplakia is a disease that is difficult to diagnose because its symptoms may vary from those mimicking bronchogenic carcinoma to pneumonitis-like tuberculous infection. In addition, they all have nonspecific symptoms and radiographic findings. Furthermore, pathological tissue should be carefully examined for the evidence of malakoplakia. It is possible that malakoplakia may be underdiagnosed in some cases.

The differential diagnosis of pulmonary malakoplakia includes pulmonary tuberculosis, malignancy (primary lung cancer and metastatic lesions) and vasculitis (Wegener's granulomatosis). In the current case, pulmonary malakoplakia coexisted with tuberculosis of the hilar lymph node simulating primary lung cancer with node metastasis. It has been suggested that malakoplakia was not directly related to the tuberculous infection, since there were no granulomas, either caseating or healed, in the lung tissue, and special staining for acid-fast bacilli was negative. Therefore, malakoplakia and tuberculosis may have occurred coincidentally. Govender and Essa [19] reported a case of malakoplakia with tuberculosis presenting as soft tissue mass in the left anterior neck following treatment of pulmonary tuberculosis. It is postulated that the association or coincidence of malakoplakia with sarcoidosis, mycosis and mycobacterial infections and other debilitating disorders, such as diabetes mellitus, or an immunocompromised state following steroid therapy may suggest an altered host immunity and a failure of the immune system to resolve a low-grade infection.

One unique finding in the present case was the associated xanthogranulomatous pyelonephritis. Malakoplakia and xanthogranulomatous pyelonephritis are regarded as unususal but varied proliferative response to inflammation. Both are characterized by the presence of foamy histiocytes and are frequently related to E. coli infection. The combination of malakoplakia, tuberculosis, and xanthogranulomatous pyelonephritis has not been reported to occur in the same individual previously. Except for extensive lesions, conservative antibiotic treatment appears to be adequate in eradicating the disease.

In conclusion, malakoplakia of the lung should be considered in the differential diagnosis of mass-like, cavitary lesions of the lung in immunocompromised patients. Malakoplakia following or concomitant with tuberculosis and xanthogranulomatous pyelonephritis is very rare. A relationship between malakoplakia and tuberculosis is questionable. The actual relationship remains to be proven and requires further studies. The diagnosis is based on histopathological examination, and conservative antibiotic treatment is effective.

  References

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Hoeven KH, Dookhan DB, Petersen RO: Cytologic features of pulmonary malakoplakia related to Rhodococcus equi in an immunocompromised host. Diagn Cytopathol 1996;15:325-328.

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Stanton MJ, Maxted W: Malakoplakia: A study of the literature and current concepts of pathogenesis, diagnosis and treatment. J Urol 1981;125:139-146.

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Gupta R, Schuster R, Christian W: Autopsy finding in a unique case of malakoplakia. Arch Pathol 1972;93:42-48.

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Govender D, Essa AS: Malakoplakia and tuberculosis. Pathology 1999;31:280-283.

  Author Contacts

Leou-Chuan Pang, MD, FCAP
Department of Pathology, Chang Gung Hospital
Chang Gung University School of Medicine
Linkou Taoyuan, Taiwan (ROC)
E-Mail linkoupang@yahoo.com

  Article Information

Received: August 19, 2003
Accepted after revision: December 1, 2003
Number of Print Pages : 6
Number of Figures : 7, Number of Tables : 0, Number of References : 19

  Publication Details

Respiration (International Journal of Thoracic Medicine)

Vol. 72, No. 1, Year 2005 (Cover Date: January-February 2005)

Journal Editor: C.T. Bolliger, Cape Town
ISSN: 0025-7931 (print), 1423-0356 (Online)

For additional information: http://www.karger.com/res

  Drug Dosage / Copyright

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