Endoscopic mucosal biopsies are useful in distinguishing granulomatous colitis due to Crohn's disease from tuberculosis

BACKGROUND: Intestinal tuberculosis and Crohn's disease are chronic granulomatous disorders that are difficult to differentiate histologically. AIMS: To characterise distinctive diagnostic features of tuberculosis and Crohn's disease in mucosal biopsy specimens obtained at colonoscopy. METHODS: Selected histological parameters were evaluated retrospectively in a total of 61 biopsy sites from 20 patients with tuberculosis and 112 biopsy sites from 20 patients with Crohn's disease. The patients were chosen on the basis of clinical history, colonoscopic findings, diagnostic histology, and response to treatment. RESULTS: The histological parameters characteristic of tuberculosis were multiple (mean number of granulomas per section: 5.35), large (mean widest diameter: 193 microm), confluent granulomas often with caseating necrosis. Other features were ulcers lined by conglomerate epithelioid histiocytes and disproportionate submucosal inflammation. The features characteristic of Crohn's disease were infrequent (mean number of granulomas per section: 0.75), small (mean widest diameter: 95 microm) granulomas, microgranulomas (defined as poorly organised collections of epithelioid histiocytes), focally enhanced colitis, and a high prevalence of chronic inflammation, even in endoscopically normal appearing areas. CONCLUSIONS: The type and frequency of granulomas, presence or absence of ulcers lined by epithelioid histiocytes and microgranulomas, and the distribution of chronic inflammation have been identified as histological parameters that can be used to differentiate tuberculosis and Crohn's disease in mucosal biopsy specimens obtained at colonoscopy.     

克罗恩病和肠结核的组织病理学研究

目的：明确克罗恩病和肠结核的组织病理学特征，找出异同点。方法：利用手术切除的肠结核和克罗恩病理标本，观察其组织病理学特征并比较。结果：克罗恩病的特征为裂隙性溃疡、非干酪样坏死性肉芽肿、肿膜下层增宽；肠结核的特征为干酪样坏死、粘膜下层闭锁，肉芽肿融合，组织切片有许多相似之处，如微肉芽肿，全层炎症等，结论：典型的肠结核和克罗恩病易于鉴别，但二者组织病理学的相似性，给部分病例的鉴别诊断带来困难。     

Recurrent Salmonella enteritidis sepsis and hepatic tuberculosis.

A 33 year old woman with recurrent Salmonella enteritidis sepsis is described. Penicillins, ceftriaxone, ciprofloxacin, and chloramphenicol could not eradicate the salmonellas but a combination of high dose ciprofloxacin and ceftriaxone for the eighth episode successfully cured the infection. The combination of ciprofloxacin and ceftriaxone may be a valuable therapeutic regimen in patients with recurrent salmonella sepsis. Prolonged intrahepatic cholestasis resulting from granulomatous hepatitis in this patient improved considerably with empiric ursodeoxycholic acid treatment. A liver biopsy specimen showing non-caseating epitheloid granulomas was positive for mycobacterial DNA by polymerase chain reaction. Repeated bronchoscopy with multiple biopsies eventually revealed caseating granulomas with acid fast bacilli in the lung biopsy specimens. Therefore, tuberculosis was diagnosed as the underlying disease and the cause of granulomatous hepatitis in this patient and tuberculostatic treatment was started. Polymerase chain reaction for mycobacterial DNA may be helpful in the differential diagnosis of hepatic granulomas when routine histological examination and culture of biopsy specimens are not diagnostic. Tuberculosis should be considered as one of the diseases predisposing to recurrent salmonella sepsis.     

Hepatobiliary tuberculosis

Tuberculosis is known to involve the liver in different ways. The term hepatobiliary tuberculosis refers to the localized form of hepatic tuberculosis as a distinct clinical entity, with signs and symptoms related to the hepatobiliary tract. Its clinical features and the different diagnostic aids used in its diagnosis are reviewed. Plain abdominal radiographs showing diffuse hepatic calcifications seen in approximately 50% of cases are almost diagnostic for hepatobiliary tuberculosis. Liver biopsies obtained either by ultrasound, computed tomography or laparoscopy, showing caseating granuloma usually establish the diagnosis. In the absence of caseation necrosis, a positive acid-fast bacillus (AFB) or culture for Mycobacterium tuberculosis is needed to establish the diagnosis. A polymerase chain reaction assay for the identification of Mycobacterium tuberculosis in liver biopsy specimens is a new development. Treatment is similar to that used for pulmonary tuberculosis. Quadruple therapy (using four anti-tuberculosis drugs) is recommended, generally for 1 year. For patients with obstructive jaundice, in addition to anti-tuberculous treatment, biliary decompression should be performed either by stent insertion during endoscopic retrograde cholangiopancreatology, by percutaneous transhepatic biliary drainage or by surgical decompression whenever feasible.     

Endoscopic diagnosis of segmental colonic tuberculosis.

We report colonoscopic findings in 29 proven cases of segmental colonic tuberculosis. The colonoscopic appearances of tuberculosis included: mucosal nodules and ulcers, stricture with nodules and ulcerations, and mucosal nodules with or without pseudopolypoid folds. In 12 (41%) of 29 patients colonoscopy biopsies enabled a histologic diagnosis to be made on the basis of typical granulomas. Culture of biopsy tissue on Lowenstein Jensen media isolated Mycobacterium tuberculosis in six (40%) of 15 patients. Combined histologic and bacteriologic evaluation established the diagnosis in 60% of patients. We conclude that even though target biopsy is an effective method of diagnosis, anti-tuberculous chemotherapy may be started on the basis of the endoscopic appearance if there is a high clinical suspicion of tuberculosis.     

The role of bronchoscopy in the diagnosis of pulmonary tuberculosis in patients at risk for HIV infection.

The present study was undertaken to clarify the role of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) in the diagnosis of pulmonary tuberculosis in patients at risk for human immunodeficiency virus (HIV) infection. We retrospectively identified 31 patients at risk for HIV who proved to have Mycobacterium tuberculosis on culture of at least one pulmonary specimen. All had pulmonary symptoms but initial sputum smears negative for acid-fast bacilli (AFB). All underwent fiberoptic bronchoscopy (FOB), including BAL and TBB; postbronchoscopy sputum was also collected in 19 patients. A specimen was considered to yield an immediate diagnosis when positive for AFB either on smear or histologic study; granulomas alone were considered positive when no other causes were identified. Overall, an immediate diagnosis was made by bronchoscopic specimens in 15 (48 percent) of 31 cases. TBB was the sole positive specimen in seven patients (23 percent). For comparison, similar specimens from 40 patients in whom M avium complex (MAC) grew on culture were also evaluated. An immediate identification of AFB was made in only four patients (10 percent). We conclude that the finding of AFB on staining of any pulmonary specimen is highly suggestive of tuberculosis, rather than MAC, and warrants institution of antituberculosis therapy. Of all bronchoscopic specimens, TBB provides the highest yield for an immediate diagnosis of tuberculosis.     

Ultrasound guided fine needle aspiration biopsy in mediastinal tuberculosis.

SETTING: Diagnosis of mediastinal tuberculosis (TB) is difficult due to non-specific clinical features and lack of characteristic radiographic features. Histopathological confirmation has often required computed tomography guided fine needle aspiration biopsy (FNAB) or even invasive procedures such as mediastinoscopy or open/surgical biopsy. FNAB under ultrasound (US) guidance can also be performed in this clinical setting. OBJECTIVE: To define the role of percutaneous US guided FNAB in the diagnosis of mediastinal tuberculosis. DESIGN: Twenty-six patients with a proven diagnosis of mediastinal TB formed the study group. Chest radiographs and sputum examination were negative. FNAB was performed via suprasternal (n = 20) and parasternal (n = 6) route under sonographic guidance using 22G spinal needle. Aspirates were considered positive for TB when epithelioid cell granuloma with caseation necrosis and/or the presence of Mycobacterium tuberculosis by acid-fast bacilli (AFB) or culture was demonstrated, indeterminate when epithelioid cell granulomas were seen but without caseation necrosis or AFB, and negative when aspirate contained non-representative material. RESULTS: A total of 30 biopsies were performed in the 26 patients, including repeat biopsy and biopsy of different sites in two patients each. FNAB was positive for TB in 20 of the 26 patients. In four, AFB were demonstrated, and in seven culture was positive for M. tuberculosis; in the remaining six patients, cytologic diagnosis was indeterminate in four and negative in two. No procedure related complications were noted. CONCLUSION: Ultrasound guided FNAB is a safe, effective technique in the diagnosis of mediastinal TB.     

Pancreatic tuberculosis: a rare cause of pseudoneoplastic obstructive jaundice

Isolated pancreatic tuberculosis is rare, and can mimic pancreatic carcinoma. We report a case of pseudoneoplastic pancreatic tuberculosis revealed by an obstructive jaundice in a 35-Year-old man. Surgical pancreatic histopathology showed a caseating granulomatous inflammation and diagnosis was confirmed by detection of Mycobacterium tuberculosis DNA using specific polymerase chain reaction-based assay (PCR). The patient was successfully treated with quadruple antituberculous therapy. In the context of the diagnostic work-up of a hypodense pancreatic mass, the diagnosis of tuberculosis relies on the presence of pancreatic caseating granulomas, that can be obtained by endosonography-guided biopsy, thus avoiding laparotomy.     

Tuberculous peritonitis of the wet ascitic type: clinical features and diagnostic value of image-guided peritoneal biopsy

BACKGROUND: Abdominal tuberculosis is still a medical problem in developing countries. AIMS: To analyse the clinical, laboratory, ultrasonography and computed tomography findings and to discuss the diagnostic approach of 19 patients with peritoneal tuberculosis. PATIENTS: Nineteen patients diagnosed in our department, with peritoneal tuberculosis (8 female, 11 male; mean age: 47.89 +/- 4.3 years) between 1996 and 2002, were studied retrospectively. METHODS: All clinical, laboratory, radiological findings, and diagnostic methods were reviewed. RESULTS: The most common symptoms and signs of the disease in these patients were abdominal pain, ascites, weight loss and night sweats. On conducting skin test, eight patients (42%) were found to be positive, while all the patients had elevated serum cancer antigen 125 levels, but acid-resistant bacilli could not be demonstrated on the direct preparation. In three patients (15.78%), the ascitic fluid culture was positive. The most common ultrasonographic and computed tomographic findings were ascites, septation in the ascites, peritoneal thickening, mesenteric and omental involvement. An abnormal chest X-ray, suggestive of previous tuberculosis was present in three patients. Diagnosis was made by image-guided percutaneous peritoneal biopsy in 18/19, and by histological examination of biopsy specimens obtained via laparoscopy in 1/19. Laparoscopy was only performed in 1 of the 19 patients due to lack of sufficient material for histological diagnosis by percutaneous biopsy. Of the biopsy specimens, 84% revealed caseating granulomas, while 16% were non-caseating. Acid-fast bacilli were seen on the Ziehl-Neelsen stain in 18 patients. CONCLUSIONS: Peritoneal tuberculosis should be considered in the differential diagnosis of exudative ascites. Image-guided percutaneous peritoneal biopsy seems to be a sufficient, safe and inexpensive method for diagnosis of peritoneal tuberculosis.     

Fulminant hepatic failure caused by tuberculosis.

A 54 year old Asian woman developed fulminant hepatic failure followed by renal failure. Because of a past history of possible tuberculosis, she was given antituberculous drugs. The chest x ray was normal. A transjugular liver biopsy showed caseating necrosis, granulomas, and acid fast bacilli indicative of miliary tuberculosis. Despite full supportive therapy, her condition deteriorated and she died. Postmortem examination showed widespread miliary tuberculosis; culture confirmed the presence of Mycobacterium tuberculosis. Tuberculosis causes fulminant hepatic failure rarely and only three cases have been described. In this, as with the other cases, hyponatraemia and hepatomegaly were features at presentation. This is the first report of treatment being given before death.     

Tuberculous pleural effusions: advances and controversies

On a global scale, tuberculosis (TB) remains one of the most frequent causes of pleural effusions. Our understanding of the pathogenesis of the disease has evolved and what was once thought to be an effusion as a result of a pure delayed hypersensitivity reaction is now believed to be the consequence of direct infection of the pleural space with a cascade of events including an immunological response. Pulmonary involvement is more common than previously believed and induced sputum, which is grossly underutilised, can be diagnostic in approximately 50%. The gold standard for the diagnosis of tuberculous pleuritis remains the detection of Mycobacterium tuberculosis in pleural fluid, or pleural biopsy specimens, either by microscopy and/or culture, or the histological demonstration of caseating granulomas in the pleura along with acid fast bacilli (AFB). In high burden settings, however, the diagnosis is frequently inferred in patients who present with a lymphocytic predominant exudate and a high adenosine deaminase (ADA) level, which is a valuable adjunct in the diagnostic evaluation. ADA is generally readily accessible, and together with lymphocyte predominance justifies treatment initiation in patients with a high pre-test probability. Still, false-negative and false-positive results remain an issue. When adding closed pleural biopsy to ADA and lymphocyte count, diagnostic accuracy approaches that of thoracoscopy. The role of other biomarkers is less well described. Early pleural drainage may have a role in selected cases, but more research is required to validate its use and to define the subpopulation that may benefit from such interventions.     

The value of fiberoptic bronchoscopy in diagnosis of smear negative pulmonary tuberculosis

Although mycobacterial culture positivity is the gold standard for the diagnosis, the initial approach to the diagnosis of pulmonary tuberculosis (PTbc) is the detection of acid-fast bacilli (AFB) in respiratory specimens as recommended by the World Health Organization. But the physicians have to make a decision for the patients whose sputum smears are negative or who can not produce sputum. Waiting for culture results with radiological follow up or empirical antituberculous therapy are the standard options. In our study we aimed to assess the diagnostic yield of fiberoptic bronchoscopy in patients, suspected to have tuberculosis, whose sputum smears were negative or who could not produce sputum. Fifty six patients who suspected to have PTbc with sputum smear negative were enrolled in the study (fiberoptic bronchoscopy and selective bronchial washings were done to all patients. Bronchial washings were obtained from the affected parts). Mucosal biopsies were done in patients in where endobronchial abnormalities were noted. Transbronchial biopsies were done in selected patients from the radiological localizations. Ziehl-Nielsen staining and culture in L?wenstein-Jensen medium were the microbiological studies. Typical granulomas were expected to detect on histopathologic examination. Bronchoscopic lavage smears were positive for Mycobacterium tuberculosis in 13 (23%) patients. Twenty eight (50%) patients had positive culture. Histopathological results confirmed tuberculosis in eight of 20 patients who had undergone mucosal biopsies, four of seven of transbronchial biopsies, two of three of needle aspiration biopsies. By bronchoscopic procedures early diagnosis was performed in 27 (48.21%) patients. We concluded that fiberoptic bronchoscopy has an important role in the diagnosis of patients suspected to have tuberculosis, whose sputum smears were negative or who could not produce sputum. It is useful and necessary in selected cases.     

The diagnosis of extrapulmonary tuberculosis in Malawi

There is little information on a country-wide basis in sub-Saharan Africa about how the diagnosis of extra-pulmonary tuberculosis (EPTB) is made. A country-wide cross-sectional study was carried out in 40 non-private hospitals in Malawi which register and treat (TB) patients in order to assess diagnostic practices in adults registered with EPTB. All patients aged 15 years and above in hospital on treatment for EPTB were reviewed usingTB registers, case note files and clinical assessment. There were 244 patients, 132 men and 112 women whose mean age was 36 years. In 138 (57%) patients, all appropriate procedures and investigations, commensurate with hospital resources, had been carried out. Of 171 EPTB patients with cough for 3 weeks or longer, 138 (81%) submitted sputum specimens for smear microscopy of acid-fast bacilli (AFB). A confirmed diagnosis ofTB was made in 15 (6%) patients based on finding AFB or caseating granulomas in specimens. In 157 (64%) patients, the diagnosis of EPTB was considered to be correct. In 46 (19%) patients the diagnosis was considered to be TB, although different from the type of EPTB with which the patient was registered. In 39 (16%) patients an alternative non-TB diagnosis was made and in two (1%) patients it was not possible to make a decision. Diagnostic practices need to be improved, and ways of doing this are discussed.     

内镜及病理学检查在克罗恩病和肠结核鉴别诊断中的价值

目的 评价内镜及组织病理学检查在克罗恩病和肠结核的鉴别诊断中的价值。方法 回顾性复习经手术证实的克罗恩病和肠结核各30例资料，对其临床、内镜表现、手术记录等进行分析，并重新审读病理切片。结果 内镜诊断克罗恩病的灵敏度、特异度和准确性分别为80．0％、25．6％和49．3％，而在肠结核中的灵敏度、特异度和准确性分别为86．7％、46．2％和63．8％。克罗恩病的病理学特征有非干酪样肉芽肿、粘膜下层增宽、裂隙样溃疡和淋巴细胞聚集；肠结核的病理特征有肠壁或肠淋巴结干酪样坏死、粘膜下层变窄或闭缩。结论 尽管找到了克罗恩病和肠结核的临床、内镜和组织病理学特征，但手术标本的组织病理学在鉴别诊断中仍起决定作用。     

Bronchoscopic aspiration and bronchoalveolar lavage in the diagnosis of sputum smear-negative pulmonary tuberculosis

The ability to make a definitive diagnosis in sputum smear-negative pulmonary tuberculosis by bronchoscopic aspiration, bronchoalveolar lavage (BAL), and examination of postbronchoscopy sputum were compared. Thirty-four patients with lesions on chest x-rays suspected of being pulmonary tuberculosis were entered into the study. The diagnosis of pulmonary tuberculosis was subsequently confirmed in 28 patients and the method of arriving at the final diagnosis was analyzed. A positive acid-fast bacilli (AFB) smear result was obtained in 4/28 (14%) of cases by a combination of bronchoscopic techniques and postbronchoscopy sputum examination. Prebronchoscopy sputum culture was positive in 12/28 (43%). Combined with bronchoscopy specimens, a positive AFB culture result was obtained in 26/28 (93%). Sputum examination, bronchoscopic aspiration, and BAL are complementary techniques and together they give a high yield of definitive diagnosis of pulmonary tuberculosis.     

Bronchoscopic aspiration and bronchoalveolar lavage in the diagnosis of sputum smear-negative pulmonary tuberculosis

The ability to make a definitive diagnosis in sputum smear-negative pulmonary tuberculosis by bronchoscopic aspiration, bronchoalveolar lavage (BAL), and examination of postbronchoscopy sputum were compared. Thirty-four patients with lesions on chest x-rays suspected of being pulmonary tuberculosis were entered into the study. The diagnosis of pulmonary tuberculosis was subsequently confirmed in 28 patients and the method of arriving at the final diagnosis was analyzed. A positive acid-fast bacilli (AFB) smear result was obtained in 4/28 (14%) of cases by a combination of bronchoscopic techniques and postbronchoscopy sputum examination. Prebronchoscopy sputum culture was positive in 12/28 (43%). Combined with bronchoscopy specimens, a positive AFB culture result was obtained in 26/28 (93%). Sputum examination, bronchoscopic aspiration, and BAL are complementary techniques and together they give a high yield of definitive diagnosis of pulmonary tuberculosis.     

Caseating hepatic granulomas in Hodgkin's lymphoma

A 68-year-old man presented with recurrent Hodgkin's lymphoma after a 9-year disease-free interval induced by chemotherapy. In addition to histological evidence of recurrent Hodgkin's disease, the liver biopsy specimen showed extensive caseating granulomas. Cultures of bone marrow and liver tissue tested negative for Mycobacterium tuberculosis. No antituberculous treatment was administered, and the patient had an excellent clinical response to additional chemotherapy for lymphoma. Hodgkin's lymphoma should be added to the list of disease entities associated with caseating granulomas in the liver.     

Colonic tuberculosis: Clinical features, endoscopic appearance and management

BACKGROUND: Although rare in the West, colonic tuberculosis is not an uncommon disease in developing countries. However, the clinical manifestations and radiological appearance of the disease are non-specific. In recent years, colonoscopy has been found to be very useful in diagnosing patients with colonic tuberculosis. METHODS: Clinical features, colonoscopic findings, histology and response to treatment were recorded in 50 patients with colonic tuberculosis. RESULTS: Abdominal pain, fever, anorexia, weight loss and diarrhoea were the common symptoms. The colonoscopic features consisted of ulcers (92%), nodules (88%), deformed caecum and ileocecal valve (42%), strictures (25%), multiple fibrous bands (8%) and polypoid lesions (6%). Segmental tuberculosis and lesions simulating carcinoma were seen in 22 and 16% of patients, respectively. Histological examination of the colonic biopsy specimens showed well-formed, non-caseating granulomas in 18%, collection of loosely arranged epithelioid cells in 40% and chronic non-specific inflammatory changes in 42% of the patients. Six patients needed surgical intervention. The other 44 patients responded well to anti-tuberculous therapy and became asymptomatic. CONCLUSIONS: It is concluded that colonoscopy is a useful method for diagnosing colonic tuberculosis. It is suggested that if the clinical picture and colonoscopic appearance are suggestive of tuberculosis and target biopsies reveal non-caseating granulomas, a collection of loosely arranged epithelioid cells, or even non-specific changes, then a therapeutic trial of anti-tuberculous drugs should be given and continued if there is clinical improvement.     

Differentiation between intestinal tuberculosis and Crohn's disease in endoscopic biopsy specimens by polymerase chain reaction

OBJECTIVES: It is difficult to differentiate intestinal tuberculosis from Crohn's disease because of similar clinical, pathological, radiological, and endoscopic findings. The purpose of this study was to investigate the value of polymerase chain reaction (PCR) assay in the differentiation intestinal tuberculosis from Crohn's disease, and compare the histopathological features of endoscopic biopsy of the two disorders. METHODS: A total of 39 endoscopic biopsy specimens from patients with intestinal tuberculosis and 30 specimens from patients with Crohn's disease were subjected to pathological analysis retrospectively, Ziehl-Neelsen stain, and PCR assay. RESULTS: Except for granuloma with caseation and confluence, which was the characteristic of intestinal tuberculosis, other pathological features of intestinal tuberculosis and Crohn's disease were very similar or were difficult to find in endoscopic biopsy specimens. The positivity rate by PCR in 39 intestinal tuberculosis specimens was 64.1% (25/39), but was zero by PCR in 30 Crohn's disease specimens. Moreover, in the tissues of intestinal tuberculosis with granulomas similar to those of Crohn's disease, there were 71.4% (10/14) positive by PCR, and there were 61.1% (11/18) positive in intestinal tuberculosis tissues without granulomas. CONCLUSIONS: Biopsy is of limited diagnostic value in the differentiation intestinal tuberculosis from Crohn's disease, and PCR is valuable in the differentiation between intestinal tuberculosis and Crohn's disease.     

Intestinal tuberculosis: bacteriological study of tissue obtained by colonoscopy and during surgery

The biopsy tissue obtained during surgery and colonoscopy from 28 cases of intestinal tuberculosis was utilized for isolation and identification of mycobacteria. The mycobacteria could be isolated in 12 (42%) of 28 patients. Colonoscopy can be a successful method of bacteriological diagnosis of intestinal tuberculosis. Mycobacteria were scarcely ever seen on histological sections. Combined use of guinea pig inoculation and culture was more rewarding than either alone. The yield of positive cultures was greater in tissue with caseation necrosis, though organisms were also recovered from tissues showing non-caseating granuloma and non-specific inflammation. The intestinal tissue gave more positive cultures (41%) than did lymph nodes (14%). The organisms were isolated in patients with or without pulmonary lesions and chemotherapy in the past. All the organisms were isolated as Mycobacterium tuberculosis.