SUMMARY
Objective: The tuberculosis is responsible for 40% of cases of acute pericarditis, 7% from cases of cardiac tamponade, and 6% of cases of constrictive pericarditis. We report a case of tuberculous pericarditis diagnosed at Cardiology Center Iasi. 
Material and Methods: The study was made on surgical biopsic specimen, obtained by making a pleuro-pericardial window. The diagnosis was established by using routine morphological techniques. 
Results: The microscopical examination revealed characteristic morphological aspects corresponding to granulomatous inflammation of tuberculous origin represented by multiple granulomas with Langhans type giant cells and extensive caseous necrosis in a fibrotic pericardium, much thickened due to a long disease evolution. 
Conclusions: The study revealed the importance of establishing the etiological disease diagnosis for indicating a target effective treatment. 
Key words: tuberculous pericarditis, Langhans giant cells, caseous necrosis.
Abbreviations: Z-N=Ziehl-Neelsen, Myc.tbc.=Mycobacterium tuberculosis, P=pericarditis.

RESUME
Le but de travail: La tuberculose est responsable de 40 % des cases de pericardite aigue, 7 % des cases de la tamponade cardiaque, et 6 % des cases de pericardite constrictive. Nous rapportons un cas de pericardite tuberculose diagnostique au Centre de Cardiologie Iasi. 
Material et methode: L’etude a ete fait sur des pieces chirurgicales obtenues   par une breche pleuro-pericardique. Le diagnostique a ete etabli par l’utilisation des techniques usuales.
Resultates: L’examen microscopique a releve les aspectes morphologiques caracteristiques corespondent a l’inflammation granulomateuse tuberculeuses represantee   par : granulomes multiples avec des cellules geantes de type Langhans et de la necrose caseuse extensive dans un pericarde fibreuse, epaisse a cause d’une evolution prolongee de la maladie. 
Conclusion: L’etude a releve l’importance d’un diagnostique etiologique de la maladie  pour l’indication d’un traitement specifique. 
Mots clefs: pericardite tuberculose, cellules geantes de type Langhans, necrose caseuse. 
Abbreviations: Z-N=Ziehl-Neelsen, Myc.tbc.=Mycobacterium tuberculeuse, P=pericardite.
 

INTRODUCTION 
     The tuberculous pericarditis is a pericardial inflammatory disease caused by infections with Mycobacterium tuberculosis (Myc.tbc.) representing 4% from all cases of pericarditis. If the tuberculous pericarditis mortality was of 100% in the pre-antituberculous drug era, it was decreased at 40% by using antituberculous drugs, and today, the tuberculous cases are increasing due to Myc.tbc. drug resistance (1). 
The tuberculous pericarditis is producing at 1% of patients with active tuberculosis, 50% from them having an active pulmonary disease at presentation. The way of dissemination of the infection at patients without active pulmonary disease it is supposed to be secondary of the breaking in the pericardial space of the mediastinal lymph node with tuberculous limfadenitis (2). 
    There are known 4 clinical syndromes of pericardial disease represented by acute pericarditis, pericardial effusions, constrictive pericarditis and constrictive pericarditis with pericardial effusion (3). Morphologically, there are described 3 evolutive stages of the tuberculous pericarditis, such as: acute pericarditis (fibrinous or sero-fibrinous pericarditis), subacute pericarditis (granulomatous inflammation with caseous necrosis), and chronic pericarditis including 3 morphological subtypes (the thickening of the pericardium through pericardial fibrosis, the pericardial fibrosis with the focal obliteration of the pericardial cavity, and constrictive pericarditis) (3).
The diagnosis is difficult consisting in a variety of tests: positive Myc.tbc. cultures made from pericardial fluid (30-75% of cases are positive), positive smear stainings for acid fast bacilli made from pericardial fluid, polimerase chain reaction for Myc. tbc. ADN (is of great diagnostic advantage), positive tuberculinic test (is suggestive for diagnosis), positive treatment response at anti-tuberculous chemotherapy, identification of necrotizing granulomas on the pericardial biopsy, being diagnostic even in the abscence of the positive Ziehl-Neelsen (Z-N) smear staining, and typically, the pericardial fluid is sero-citrin with lymphocytosis, which is suggestive for tuberculosis (4, 5). In evolution, all patients with tuberculous pericarditis develop constrictive pericarditis (P) without treatment (6). The prevalence of the pericardial fibrosis decreases at 40% at patients with antituberculous drugs. Although the medical cure is effective in the most cases, is recommended early pericardectomy at all tuberculous pericarditis patients, due to the high risk of constrictive pericarditis (7, 8). 
 
 

MATERIAL AND METHODS 
    In a 51 years old female patient presenting with progressive dispnea and malaise, and having the previous diagnosis of pleuro-pericarditis of unknown etiology, established three months ago, the repeated hospital admission were indicated for draining the pleuro-pericardial fluid. The surgical biopsic specimen, obtained through a pleuro-pericardial window, was fixed in buffered 10% formalin for 12 hours and quite totally sampled. Samples were processed using routine paraffin embedding, cutting (5 mm) and hematoxilin-eosin (HE) and Van Gieson (VG) staining.
 
 

RESULTS 
     The study represents a case report of an unknown cause pericarditis diagnosed in a 51 years old female patient presenting repeated hospital admission for paracenthesis.  The laboratory tests were not relevant for Myc.tbc. etiology, showing a slight leucocytosis without lymphocytosis and negative Z-N smear staining. The chest X-ray evidentiated a large heart, a right micronodular apical sequelae and a pleural fluid reaction, predominant at the right base. The echocardiography didn’t show signs of cardiac tamponade but revealed a moderate postero-inferior and apical pericardial fluid. 
   The surgically intervention evidentiated a tickened fibrous pericardium and moderate effusion requiring a pleuro-pericardial drainage and a pleuro-pericardial window. The histological examination of the surgical biopsic specimen revealed a thick pericardium through an extensive fibrosis enclosing multiple specific tuberculous granulomas, with giant cells of     Langhans type and large areas of caseous necrosis permitting the diagnosis of subacute tuberculous pericarditis with chronic fibrotic evolution. The histology is illustrated by few photogrames showing: a thickened pericardium with areas of fibrosis and mononuclear inflammatory infiltrate  and zones of dense fibrosis with few granulomas and a chronic inflammation (Fig.1);  aggregates  of  macrophages  and  few giant cells  (Fig.2) and large areas of caseous necrosis (Fig. 3) representing tuberculous necrotising granulomatous lesion.

     
DISCUSSIONS AND CONCLUSIONS
     The present study describes a particular case of tuberculous pericarditis, with a long evolution presenting with atypical signs for a specific etiology. Symmers (7) considers that the tuberculous pericarditis account for 4% of all cases of acute pericarditis, and in some of the older series, for approximately 6% of all cases of cardiac tamponade. Silver  (10) reported also that the Myc. tbc. was found as the most frequent cause of pericardial disease, this etiology reflecting the diseases spectrum prevalating in an area. The two authors observed that the frequency of the tuberculosis has been progressively decreasing since the-mid-1950, due to the appearance on the market of anti-tuberculous drugs and also, an increasing in the last few years, this fact has been linked to the appearance of the multi-drug resistant Myc. tuberculosis.
   Colin (1) noted that the pericardium may be involved in tuberculosis usually in association with foci of tuberculosis elsewhere in the body, most commonly in the lung, as in our case. Symmers (7) showed that the tuberculous pericarditis occurred in approximately 2% of cases of pulmonary tuberculosis. Discussing about the way of dissemination, in our case, we appreciated that the spreading of the Myc.tbc. was made through lymphatic way from an old pleuro-pulmonary tuberculosis, demonstrated by an apical nodular sequelae and a moderate tuberculous pleuresis. We couldn’t demonstrate other tuberculous foci elsewhere in the body. 
   Referring to the general clinical manifestations and morphological reactions, a good review of the subject has been published by Hageman (9) who admitted that most patients with pericardial tuberculosis were in in the third to fifth decade of life, having an history of typical symptoms such as shortness of breath, coughing and weight loss and most of them having a positive tuberculosis test, except if they have skin test anergy. Radiographically, the signs of the pericardial disease didn’t differ too much, at our patient, from that reported in the literature, this examination being helpful in cases of pericardial effusions. As Symmers’ appreciation (7), the echocardiography was in our case the most helpful diagnostic non-invasive technique in detecting of the pericardial effusion.
 Silver (10) considers that a definitive diagnosis may be established by isolating the organism from pericardial fluid or pericardial biopsy, but the probability of obtaining a diagnosis is greatest, if both fluid and biopsy specimens are examined in the early effusive stages; we didn’t obtain a positive Z-N histological staining for Myc. tuberculosis. 
    Morphologically, it is well known, that the pericardium reacts to the various agents in a limited way. The basic known changes consist of fibrin, fluid and cells; the cellular reaction is various depending on the organism. Waller (6) described 3 morphological stages in the evolution of the tuberculous pericarditis: stage 1 (sero-fibrinous stage), corresponding with acute phase from actual Silver classification (10);
stage 2, corresponding with subacute phase from Silver classification, is characterised by effusion and thickened pericardium, appearance similar with our case; Waller appreciated that tubercles may be found, too; stage 3, corresponding with chronic phase from Silver classification, is defined by constriction and calcification. The effusion becomes less and the pericardium is thicker and may be fibro-caseous. In time this appearance disappears and a firm fibrous tissue remains. In that way the healing by fibrosis may lead to adhesions.
    Colin (1) found 10 patients with acute granulomatous P. In 9 patients, the resected pericardial tissue showed caseating granulomata consistent with tuberculosis. In our case, we found various appearances corresponding histologically with 2 stage showing a relative stratification of the lesions with intermixing borders, such as: a delicate in incontinous fibrinous exudate, continued by irregular organising fibrotic zone, enclosing small or large caseous necrotic areas with small tuberculous granulomas at their periphery. In our opinion, the significant fibrotic component demonstrated a long duration of the disease, and in the same time the important effusive component, was a prove of the persistence of the etiological agent. This extensive fibrotic component made difficult to identify it by using histological specific Z-N staining. Silver (10) appreciated that Myc. tuberculosis was demonstrable only in 6% of cases who underwent pericardectomy for chronic P. 
    Silver (10) and Colin (1) also appreciated that the constrictive P. develops finally, in almost all patients with untreated tuberculous P. requiring pericardectomy.  They also indicated an early combined medical therapy with anti-tuberculous drugs and steroids, for decreasing mortality and resulting in more rapid clinical improvement. In the Symmers’ reports (7) the mortality rate for pericardial tuberculosis was ranging from 3 to 40%, depending on the type of the treatment administered with or without steroids, and medical versus surgical. 
 

REFFERENCES 
1. Colin MB.  Pericarditis. In: Colin MB Ed. Heart Pathology.  Churchill Livingstone  1980, 265-272.
2. Blomm J. Pericarditis. In: Sternberg SS. Diagnostic Surgical Pathology. Ed. Raven Press, 1944: 1216-1217.
3. Virmani R. Tuberculous Pericarditis. In: Allen Burke and Renu Virmani. Atlas of Cardiovascular Pathology. Ed. AFIP. Washington DC 1966: 104-106.
4. Gilbert E. Pericarditis. In: Silverberg SG. Principles and Practice of Surgical Pathology and Cytopathology. Ed. Churchill Livingstone 1997, 1318-1321.
5. Brisson NA. Rapid diagnosis of tuberculosis by amplification of mycobacterial DNA in clinical samples. Lancet 1989; 2: 1069-1071.
6. Waller BF. Pericardial Disease. In: Waller BF. Pathology of the Heart and great vessels, The Mosby Company, 1998, 1173-1178.
7. Symmers WSC.  The pericardium. In: Symmers WSC. Cardiovascular System. Springer-Verlag, New York, 1980, 672-675. 
8. Muir P, Nicholson F et al: Chronic relapsing pericarditis. Lancet I: 804-7, 1989.
9. Hageman JH. Tuberculous pericarditis: a long term analysis of 44 cases. N Engl J Med, 1964; 270: 327-764.
10. Silver MD. Pericarditis. In Silver MD. Gotlieb AI. Eds. Cardiovascular Pathology. Churchill Livingstone 2001, 385-389.
 

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