| Abstract|| |
Malakoplakia of lung is an unusual condition that has been reported to occur in association with immunocompromised state, particularly in those with acquired immunodeficiency syndrome. We present two cases of pulmonary malakoplakia in immunocompetent individuals. The diagnosis was made on histopathological examination of surgically resected specimen.
Keywords: Immunocompetent host, malakoplakia, pulmonary
|How to cite this article:|
Gupta K, Thakur S. Pulmonary malakoplakia: A report of two cases. Indian J Pathol Microbiol 2011;54:133-5
| Introduction|| |
Malakoplakia is an unusual disease of poor macrophage digestion. It was first described in early years of 20th century by Michaelis and Gutmann in the bladder and later by von Hansemann who named the lesion malakoplakia meaning "soft plaque." th It is a histological diagnosis characterized by accumulation of benign macrophages or Von Hansemann cells, associated with pathognomonic intracellular or extracellular basophilic inclusion termed Michaelis-Gutmann (M-G) bodies.
It most frequently occurs in the genitourinary tract; however, remote cases have been reported in many other organs including colon, stomach, lung, liver, bone, uterus, and skin. The occurrence of malakoplakia in the lung is not common and less than 30 cases have been described previously. ,,,,,,,,
Underlying diseases and immunosuppression are thought to play a role in the pathogenesis but a few cases occur without these associations as in our case report.Here we report two cases of pulmonary malakoplakia with different clinico-radiological profiles and without any history or investigations suggesting immunodeficiency status.
| Case Reports|| |
A 62-year-old male, a case of right lung mass lesion, was referred to our institute for evaluation and management. He had history of cough with expectoration for 3 months with occasional streaking of blood. There were inconsistent febrile episodes but otherwise the patient was maintaining a healthy life without any malaise or loss of weight. His past medical history included hypertension for last 6 years and was on amlodipine and lisinopril.
Evaluation of the case demonstrated a normal hemogram and baseline biochemical profile. The bronchoscopic findings were normal, and on spirometry, borderline airway obstruction without restriction was noted. Sputum smears were negative for acid fast bacilli on Ziehl-Neelsen (ZN) stain. Review of serial chest radiograph revealed a gradually enlarging round density with poorly defined margins in right mid zone. A computed tomography scan revealed a cavitated right upper lobe lesion measuring 6.50 × 7.19 cm, along with associated pleural thickening. Image guided aspiration cytology of the lesion revealed few scattered macrophages and bronchial epithelial cells. Thoracotomy was performed which revealed dense adhesions in the right side of thoracic cavity. The upper and middle lobes of right lung were removed and sent to the pathology department.
A 38-year-old male, known case of loculated empyema, received anti-tubercular treatment (ATT) for 9 months. He was later admitted to the hospital with history of cough with sputum and chest pain for 15 days. In the past (10 years ago), he took ATT for extrapulmonary tuberculosis (EPTB). The acid fast bacilli (AFB) positivity was not demonstrated on both the occasions.
Chest X-ray and ultrasound examination revealed right side loculated empyema. USG guided aspiration yielded dark brown pus-like material which was reported as nonspecific purulent exudate (AFB -ve). The spirometry showed mild airway obstruction with moderate reduction of forced vital capacity (FVC). The patient underwent surgery and right pneumonectomy was done. The right lung was sent for sent for histopathology examination.
In case 1, gross finding revealed a 6 × 7 cm, ill-defined lesion in right upper lobe with a central cavity filled with dirty brown material [Figure 1]. The cavity was surrounded by firm grayish white area. In case 2, the lung specimen was partly non-crepitant and covered with firm, thick pleura. The cut surface of upper lobe revealed a cavity measuring 2.5 cm D filled with dirty brown material. The surrounding area was firm and fibrotic. On microscopy, sheets of macrophages along with scattered lymphocytes and plasma cells were noted in both the cases. The macrophages had abundant pink granular cytoplasm and few extracellular and intracellular targetoid M-G bodies were noted. These M-G bodies could be highlighted by periodic acid Schiff (PAS) [Figure 2] and Prussian blue stain [Figure 3]. The surrounding lung parenchyma showed variable degree of fibrosis and chronic inflammation. Rest of the lung tissue was unremarkable.
|Figure 1: Pulmonary malakoplakia: gross appearance; the cut surface of the lung shows a grayish white, ill-defined lesion with central cavitation|
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|Figure 2: Photomicrograph of lung shows the proliferation of polygonal granular macrophages with M-G bodies (PAS, ×200)|
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|Figure 3: M-G bodies highlighted by Perls' Prussian blue (iron stain, ×1000)|
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The postoperative course was uneventful.
In both the cases, specimens were received in formalin containers, and no culture could be done.
| Discussion|| |
Malakoplakia is an uncommon chronic granulomatous inflammatory disorder of uncertain etiology characterized by tumor-like aggregates of benign macrophages containing characteristic intracellular calcified M-G bodies.
The exact pathogenesis of the disease is not well appreciated. It has been suggested that basic defect is a cyclic 3´,5´-guanosine monophosphate dehydrogenase deficiency which results in a decrease in lysosomal breakdown and diminished microbial killing, leading to an incomplete elimination of bacteria from macrophages and monocytes.Deposition of calcium and iron on residual bacterial glycolipid forms the M-G body, which is considered pathognomonic for malakoplakia. These M-G bodies stain with PAS diastase, von Kossa stain and Perls' Prussian blue. Electron microscopically, the M-G bodies show concentric crystalline laminations with a dense central zone containing partially digested bacteria and a thin outer zone.
The cellular structure of malakoplakia changes as the disease process progresses, which leads to three histological phases postulated by Smith  in a study of malakoplakia of urinary bladderEarly prediagnostic: Infiltrate of plasma cells, Von Hansemann type macrophage with the absence of M-G bodies and eosinophils.
Clinical phase: Sheets of large macrophages containing granular cytoplasm along with lymphocytes and plasma cells. M-G bodies present in macrophages.
Fibrosing stage: Islands of macrophages with M-G bodies set in a fibrous stroma formed by collagen bundles.
Histologically, the cases reported here would be considered to be in the classical phase.
There is no sex preponderance when sites outside the urinary tract are affected, but females exhibit more urinary tract involvement. Adults are affected much more than children. Malakoplakia is associated with infection by various bacteria and fungi. In the urinary tract, the organism involved is usually Escherichia More Details coli, but in the lungs Rhodococcus equii is generally involved, although rare cases associated with other infections are described.In majority of the reported cases of pulmonary malakoplakia in AIDS patients, R. equii was the only organism isolated. Immunosuppression, chronic infection and increased steroid exposure are thought to predispose to its development.A small number of cases have been described in the lung. Gupta et al. th reported the first case of pulmonary malakoplakia in 1972, which presented as multiple lower-lobe nodules mimicking metastatic malignancy. Subsequently, cases were reported in individuals with organ transplant, Hodgkin's disease, alcohol abuse and AIDS. So far, there is no case report of pulmonary malakoplakia in India, and to our knowledge, only one case report of lung malakoplakia in immunocompetent host is there.  In our two cases, laboratory investigation revealed no signs of immunodeficiency.
With regard to prognosis, malakoplakia is a heterogenous disease with different patterns of aggressiveness. Variation in its clinical behavior could be related to the location of disease and degree of local invasion at the time of diagnosis and treatment. Clinically and macroscopically, pulmonary malakoplakia can simulate tumors, abscesses or pneumonitis-like tuberculous infections. Patients may have nonspecific symptoms and radiographic findings. In the absence of a careful inspection for M-G bodies, the histologic features may be incorrectly interpreted. Accumulations of histiocytes with granular cytoplasm can occur in immunosuppressive disorders, particularly AIDS, as a response to a number of infectious disorders. These include Mycobacterium avium-intracellulare complex, Cryptococcus neoformans, and Histoplasma capsulatum. Acid fast and fungal stains usually exclude these possibilities. Whipple disease occasionally involves the lung, but the histiocytes are more likely to be interstitial in location, lack M-G bodies, and show characteristic PAS-positive bacillary inclusions. Endogenous lipoid pneumonia may show intra-alveolar foamy macrophages secondary to airway obstruction, but lacks M-G bodies and bacteria. Finally, renal cell carcinoma with clear cell features is usually easily dismissed because malakoplakia cells express macrophage markers rather than cytokeratin.
In both our cases, diagnosis of malakoplakia was not suspected clinically. One of the cases mimicked malignancy and another was of loculated empyema. No history of immunosuppressed state was obtained, though one of the cases had chronic empyema. Diagnosis was made on thorough histopathological analysis.
Clinically, malakoplakia is difficult to diagnose because the clinical appearance varies from silent nodules to various manifestations mimicking bronchogenic carcinoma or tuberculosis in the respiratory system. Misinterpreting the large, rapidly growing nodules of malakoplakia as tumors might lead to unnecessary radical surgical intervention. Fortunately, treatment in most cases is limited to therapeutic measures - the ideal option being fluoroquinolone antibiotic treatment. Surgery is reserved for cases with extensive involvement and instability of the patient. A biopsy is therefore essential not only for confirming the disease but also for discarding other possible pathologies. We believe strong suspicion is required both clinically as well as histologically to appreciate this condition. Though there is an increased incidence of malakoplakia in immunosuppressed or immunodeficient patients, the localized nature of the disease argues against generalized immunodysregulation.
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Department of Pathology, LRS Institute of TB and Respiratory Diseases, Sri Aurobindo Marg, New Delhi - 110 030
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]