Tuberk Toraks 2014;62(3):248-252
Pulmoner malakoplaki: olgu sunumu ve literatürün gözden geçirilmesi
Deniz KÖKSAL1, Ayşenaz ÖZCAN2, Funda DEMİRAĞ3, Beril AKMAN4, Leyla Nesrin ACAR5, Erkmen GÜLHAN5,
1 Hacettepe Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, Ankara, Türkiye
1 Department of Chest Diseases, Faculty of Medicine, Hacettepe University, Ankara, Turkey
2 Ankara Atatürk Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi, Göğüs Hastalıkları Kliniği,
2 Department of Chest Diseases, Ankara Ataturk Chest Diseases and Chest Surgery Training and Research Hospital,
3 Ankara Atatürk Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi, Patoloji Kliniği, Ankara, Türkiye
3 Department of Patology, Ankara Ataturk Chest Diseases and Chest Surgery Training and Research Hospital, Ankara, Turkey
4 Ankara Güven Hastanesi, Nefroloji Bölümü, Ankara, Türkiye
4 Department of Nephrology, Ankara Guven ospital, Ankara, Turkey
5 Ankara Atatürk Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi, Göğüs Cerrahisi Kliniği,
5 Department of Chest Surgery, Ankara Ataturk Chest Diseases and Chest Surgery Training and Research Hospital,
6 Ankara Atatürk Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi, Nükleer Tıp Bölümü, Ankara, Türkiye
6 Department of Nuclear Medicine, Ankara Ataturk Chest Diseases and Chest Surgery Training and Research Hospital,
Malakoplakia is a rare inflammatory condition characterized by the accumulation of aggregates of histiocytes that contain concentrically layered basophilic inclusions called Michaelis-Gutmann bodies. It was first described by Michaelis and Gutmann in 1902 and later by Von Hanseman who named the lesion as "malakoplakia" meaning "soft plaque". It is usually an infectious process associated with a variety of bacterial infections and has been associated with immunocompromised states. Malakoplakia can form tumor-like nodules that clinically simulate malignancy in a variety of organs. It is commonly a disease of urinary tract, but it may involve any organ such as colon, stomach, lung, liver, bone, uterus, and skin (1). The occurrence of malakoplakia in lung is not common and a total of 38 cases have been reported in the current English written literature (2-28). In this paper, we aimed to present a case of pulmonary malakoplakia in a renal transplant recipient and to review the literature.
A 47-year-old male patient who had received a cadaveric renal transplant 18 months ago was referred to our clinic for the evaluation of an incidental solitary pulmonary nodule detected on chest radiography during routine follow-up. The patient was a former smoker with a smoking history of 25 pack-years. He was asymptomatic and there was no evidence of infection. He was on immunosupressive regimen that included tacrolimus 6 mg/day, mycophenolate sodium 1440 mg/day and prednisolone 5 mg/day. Physical examination was unremarkable. Routine laboratory analysis including complete blood count, basic metabolic panel, urine analysis were normal apart from a mild elevated creatinine level of 1.5 mg/dL. Anti-HCV was positive. The urine and sputum cultures were all negative for any pathogen. On chest radiography, there was an ill-defined solitary pulmonary nodule, 1.5 cm in diameter, on the left hemithorax. That nodule was not present on a previous chest radiography obtained 6 months ago. The positron emission tomography with computed tomography (PET/CT) showed an increased uptake of 18-fluorodeoxyglucose with a maximum standardized uptake value of 9.78 limited to the pulmonary nodule in the superior segment of left lower lobe (Figure 1). The patient was referred to chest surgery clinic for surgical excision with the suspicion of an early stage lung cancer. Since the frozen section was compatible with benign histology, the nodule was removed by wedge resection. As shown in Figure 2A, the histologic examination of the surgical specimens revealed sheets of histiocytes containing abundant eosinophilic cytoplasm and chronic inflammatory infiltrates of plasma cells and lymphocytes. Histiocytes were positive with CD68 and some histiocytes contained Michaelis-Gutmann bodies in periodic acid-schiff stain (PAS) (Figure 2). We failed to isolate any microbiological agent. After one and a half year follow-up time, the patient was stable with no dissemination of infection.
Herein we present a renal transplant recipient patient diagnosed as pulmonary malakoplakia after thoracotomy performed for the evaluation of a solitary pulmonary nodule. Malakoplakia is a distinct chronic granulomatous inflammatory disease seen mainly in immunocompromised hosts, caused by a variety of infectious agents, mostly bacteria. The pathogenesis of malakoplakia is unknown, but is considered as an abnormal response to bacterial infection mediated by an acquired defect in macrophage function. The macrophages show normal phagocytic activity but manifest abnormal intracellular killing or digestion of bacteria, probably secondary to defective lysosomal degranulation and impaired acidification of phagolysosomes (5). The diagnosis is made by demonstrating certain characteristic histological features such as Von Hansemann histiocyte and Michaelis-Gutmann bodies. The Michaelis-Gutmann bodies are formed by deposition of calcium and iron on residual bacterial glycolipids (2).
Malakoplakia rarely affects the pulmonary system. Most of the malakoplakia cases reported until 1971 have occurred in the genito-urinary tract and has been associated with Escherichia coli infections (29).In 1972, for the first time Gupta et al. was reported the autopsy findings of a pulmonary malakoplakia case. The patient was in a markedly debilitated health status presenting with involvement of lungs and vertebrae mimicking a metastatic carcinoma (2). Subsequently pulmonary malakoplakia cases were reported in individuals with organ transplant recipients, hematologic malignancies, lymphomas, alcohol abuse, acquired immunodeficiency syndrome (AIDS), diabetes mellitus, corticosteroid receivers, and finally immunocompetents (3,5-8,10-13,16,18,23,25-28). Table 1 represents the adult pulmonary malakoplakia cases (n= 38 cases) reported between 1972-2012, in the English written literature (2-28). Most of these cases were associated with an immunocompromised state, mostly AIDS and transplant recipients.
Pulmonary malakoplakia follows a subacute or chronic course with fever and non-specific symptoms. Pulmonary mass lesions, cavitating masses, cavitating pneumonias, and multiple pulmonary nodules are the most common radiological findings. There are also cases involving the pleura and the trachea (9,13,21,27). Our patient was presented with a solitary pulmonary nodule. He was asymptomatic and the nodule was detected on chest radiography during routine follow-up. We think that early diagnosis prevented the progression of disease.
Malakoplakia is associated with certain bacteria such as a gram-positive coccobasilli Rhodococcus equi and gram-negative bacilli E. coli (Table 1). Whereas genitourinary malakoplakia is usually associated with long standing urinary tract infection with gram-negative enteric basilli (mostly E. coli), R. equi has been implicated in the majority of cases with pulmonary malakoplakia. Lung lesions are mostly associated with AIDS. Pasteurella multocida was the opportunistic pathogen in a patient with AIDS (23). In the presented patient, we failed to isolate any bacteria. This was not a handicap for us since the single nodule was resected and we do not planned to give any antibiotic therapy.
The differential diagnosis of pulmonary malakoplakia includes pulmonary tuberculosis, primary or metastatic malignancies, and vasculitis such as Wegener's granulomatosis. Our patient had a solitary pulmonary nodule with an increased uptake on PET/CT and he underwent thoracotomy with the suspicion of early stage lung cancer.
The currently avaliable best treatment for malakoplakia is the combination a prolonged antibiotic therapy (quinolones, rifampin, macrolides, tetracyclins or combination of these drugs) using drugs with good penetration into macrophages and surgical resection of the infected tissue (9). Quinolone antibiotic treatment and surgical excision lead to the highest cure rates (90% and 81%, respectively). Specific intracellular penetration of quinolone antibiotics is a possible reason for the higher cure rate achieved with these antibiotics (30). The duration of treatment is not well defined. Duration of therapy can be affected by the site, extent of tissue involvement, type of isolated organism and immune status of the patient. Sometimes several months seem necessary for cure. Tapering or discontinuation of immunosupressive therapy whenever possible can also facilitate cure. Bethanechol chloride, a cholinergic agent, that is supposed to enhance macrophage bactericidal activity through raising cytoplasmic cyclic guanosine monophosphate level, has been tried in disseminated malakoplakia, however there is still no convincing evidence of its clinical efficacy (4). In our patient, after complete resection of the pulmonary nodule, there was no concensus about the need for a course of antibiotic therapy that we did not give any further therapy. After one and a half year follow-up time, the patient was stable with no dissemination of infection.
In conclusion, despite being a rare clinical entity, pulmonary malakoplakia should be kept in mind in the etiology of pulmonary nodules in transplant recipients. Its rarity might be due to underdiagnosis. Malakoplakia should be added to the list of unusual infectious disease occurring at unusual sites in immuncompromised hosts. Strong suspicion is required both clinically and histologically to diagnose this condition.
CONFLICT of INTEREST
Yazışma Adresi (Address for Correspondence)
Dr. Deniz KÖKSAL
Hacettepe Üniversitesi Tıp Fakültesi,
Göğüs Hastalıkları Anabilim Dalı,
ANKARA - TURKEY