Pulmonary malakoplakia associated with immunodeficiency by HTLV-1 and HIV Malacoplaquia pulmonar associada à imunodeficiência por HTLV-1 e HIV

First submission on 10/12/13; last submission on 26/05/14; accepted for publication on 26/05/14; published on 20/08/14 1. Resident in Pathological Anatomy at Instituto Nacional do Câncer (INCA) in Rio de Janeiro. 2. Pathologist at Hospital Central da Polícia Militar in Rio de Janeiro. 3. Postdoc in Hematopathology at MD Anderson Cancer Center-University of Texas; assistant professor at Department of Pathology-Universidade Federal do Rio de Janeiro (UFRJ). 4. PhD in Medicine-UFRJ; professor of Department of Pathology-UFRJ. ABStrACt


introDuCtion
Malakoplakia is a rare chronic granulomatous inflammatory disease of uncertain etiology, although studies point to failure in bacterial lysis in the lysosomes of macrophages, and the coexistence of immunossupression.Biopsy is essential in the differential diagnosis of malakoplakia and other diseases, in order to define appropriate therapeutic measures.In this paper, we report two cases of malakoplakia with pulmonary involvement.The first case report is in a patient with adult T-cell leukemia/lymphoma and human T-lymphotropic virus type I (HTLV-1); and the second case report is in a patient with human immunodeficiency virus (HIV), both evolving to death.

CASE rEPort 2
Male patient, 29 years of age, black, presented psychiatric disorder (aggressiveness), and, clinically, cough, purulent sputum, fever, and consumptive syndrome and oral candidiasis.Diagnostic investigation revealed pulmonary cavitary lesion in the upper lobe of left lung, and positive serology for anti-HIV.Established trial therapy for pulmonary tuberculosis, he evolved with clinical and radiological worsening after two months of treatment.Given this and the negativity of new microbiological examinations, it was indicated pulmonary lobectomy, with hypothesis of mycetoma in tuberculous cavity.Sputum examination showed Candida sp.yeast.In pulmonary specimen was diagnosed malakoplakia (Figure 5), and Rhodococcus equi isolated.During three months, he received medication for secondary prophylaxis to Rodococose, when progressed to death.
Although malakoplakia can affect many organs, it occurs most commonly in the urinary tract, representing 58%-80% of all cases.Within this prevail in descending order: bladder, ureter, pelvis, and renal parenchyma (1,3,6,10,11) .The gastrointestinal tract and retroperitoneal region are the secondary most affected sites (12%-15%) by the disease.Other locations are less affected such as brain, bone, lung, adrenal glands, thyroid, eyeball, among others (3,4,11) .Gupta et al. reported, in 1972, the first case of pulmonary malakoplakia, which showed multiple nodules in lower lobe, simulating metastasis (5) .Since then, only 17 cases have been reported.It may be present as a mass, simulating tumors, abscesses, or tuberculosis.Clinically, it varies from silent nodules to different manifestations, simulating bronchogenic carcinoma or tuberculosis.Malakoplakia should always be considered as a differential diagnosis, in order to prevent misinterpretation of large nodules with fast growth, such as tumors, avoiding unnecessary and radical surgeries (4,8) .Our cases report presented fever, cough, hemoptysis, weight lost, and chest pain, suggestive of neoplasia, tuberculosis, and e pneumonia.
Regarding the urinary tract, the infectious agents most commonly involved are Gram-negatives, mainly Escherichia coli (70%-80% of cases).In lungs, R. equi are predominat, especially in patients with acquired immunodeficiency syndrome (AIDS), which is the single bacterium isolated.One patient had Pneumocistis carinii in transbronchical biopsy, and in the other patient Candida sp. was detected during bacterioscopy of sputum smear, and R. equii in the pulmonary mass.
Although there are underlying diseases identified for triggering a major role in the emergence of malakoplakia, its pathogenesis remains unknown, with several theories that try to explain it.The most accepted theory holds that chronic bacterial infections in patients with chronic weakness or immunosuppression would cause a deficit of cyclic guanosine monophosphate (cGMP) in microtubule and defective macrophage, causing them to phagocyte bacteria, but, in contrast, they would be unable to digest them due to intra-lisosomal failure.This situation would lead to intracytoplasmic deposition of fragments from bacteria, iron, and calcium, which would form the MG bodies (1,3,6,9) .In support of this theory, many studies state that these inclusions represent intake and persistence of bacteria in macrophages (4,5) .One patient in this study had HTLV-1 infection (adult T-cell leukemia/lymphoma), and the other by HIV, i.e., both immunocompromised.
Histologically, lesions are mostly formed of collections of histiocytes with abundant, slight staining and vacuolated cytoplasm, and eosinophil granule cells (Von Hansemann cells) arranged beneath the epithelium surface.Some of these cells may contain amorphous, rounded cytoplasmic inclusions, with centers of concentric membranes, which are bacteria fragments with target or owl eye aspect, they are basophilic and PAS (periodic acid-Schiff) positives.Because they contain ferric salt and phosphate salt deposits, they are positive, respectively, to Pearls and Von Kossa, known as MG bodies (1,3,8,10,11) .It is also known, by the experience of most authors, that MG bodies are easily recognized by Papanicolaou, Diff-Quik, and hematoxylin-eosin staining (2) .
Eventually, regarding malakoplakia treatment, it is worth remembering that it is a self-limiting disease and, most often, with good prognosis.Therefore, it relies on eliminating the main etiological agents currently credited, and discontinuing immunosuppressive mechanism, when possible.Surgical treatment is reserved just to eliminate possible complications (4,7,9,11) .

figurE 1 -figurE 5 - 2 - 3 -
figurE 1 -Chest Radiography showing heterogeneous opacity in the anterior segment of the left upper lobe, rounded, with ill-defined borders, measuring about 6 cm