The Pathology of Lymphocytes, Histiocytes, and Immune Mechanisms in Mycobacterium tuberculosis Granulomas.

Granuloma formation is the pathologic hallmark of tuberculosis (TB). Few studies have detailed the exact production of cytokines in human granulomatous inflammation and little is known about accessory molecule expressions in tuberculous granulomas. We aimed to identify some of the components of the immune response in granulomas in HIV-positive and -negative lymph nodes. We investigated the immunohistochemical profiles of CD4+, CD8+, CD68+, Th-17, Forkhead box P3 (FOXP3) cells, accessory molecule expression (human leukocyte antigen [HLA] classes I and II), and selected cytokines (interleukins 2, 4, and 6 and interferon-γ) of various cells, in granulomas within lymph nodes from 10 HIV-negative (-) and 10 HIV-positive (+) cases. CD4+ lymphocyte numbers were retained in HIV- granulomas, whereas CD4+:CD8 + cell were reversed in HIV+ TB granulomas. CD68 stained all histiocytes. Granulomas from the HIV+ group demonstrated a significant increase in FOXP3 cells. Interleukin-2 cytoplasmic expression was similar in both groups. Interferon-gamma (IFN-γ) expression was moderately increased, IL-6 was statistically increased and IL-4 expression was marginally lower in cells from HIV- than HIV+ TB granulomas. Greater numbers of cells expressed IFN-γ and IL-6 than IL-2 and IL-4 in HIV- TB granulomas. This study highlights the varied cytokine production in HIV-positive and -negative TB granulomas and indicates the need to identify localized tissue factors that play a role in mounting an adequate immune response required to halt infection. Although TB mono-infection causes variation in cell marker expression and cytokines in granulomas, alterations in TB and HIV coinfection are greater, pointing toward evolution of microorganism synergism.

Nontuberculous mycobacteria in cervical lymphadenopathies of HIV positive and HIV-negative adults / Micobacterias no tuberculosas en linfadenopatías cervicales de adultos VIH positivos y VIH negativos

Background: Tuberculosis is a global public health problem, especially in emerging countries. Mycobacterium tuberculosis is the main cause of cervical lymphadenopathy; nontuberculous mycobacteria are relatively common in children and rare in adults. Objective: To identify and establish the frequency of infectious etiology by nontuberculous mycobacteria in Mexican adult patients with cervical lymphadenopathy. Methods: The study included 85 patients over 18 years with cervical lymphadenopathy; 45 were HIV-positive, 40 were HIV-negative; they had no history of tuberculosis treatment and were selected from a third-level hospital. It was carried out a biopsy of the lymph node for the histopathological study, a search for acid-fast bacilli, a tube culture to indicate growth of Mycobacterium BACTEC (MGIT-960) and identification of mycobacterial strain by PCR-RFLP (restriction fragment length polymorfism) of hsp65. Results: In 42 HIV-positive patients (93%), strains corresponded to Mycobacterium tuberculosis complex, two (4.4%) to M. intracellulare and one (2.2%) to M. gordonae. Among HIV-negative patients, 39 of strains (97.5%) corresponded to patients with M. tuberculosis complex and one strain (2.5%) to M. fortuitum. Conclusion: The presence of nontuberculous mycobacteria was found in 4.7% of all cases. Despite this low frequency, it must be taken into account as a possible cause of lymphadenopathy, since its prompt identification enables introducing specific treatment.

Introducción: la tuberculosis es un problema de salud pública mundial, sobre todo en países emergentes. El Mycobacterium tuberculosis es el principal causante de las adenopatías cervicales; las micobacterias no tuberculosas son relativamente frecuentes en el niño y raras en adultos. Objetivo: identificar y establecer la frecuencia de la etiología infecciosa por micobacterias no tuberculosas (MNT) en pacientes adultos mexicanos con linfadenopatias cervicales. Métodos: se estudiaron 85 pacientes mayores de 18 años, con linfadenopatía cervical, 45 con positividad al virus de la inmunodeficiencia humana (VIH) y 40 VIH negativos, sin antecedentes de tratamiento antituberculoso, seleccionados en un hospital de concentración de especialidad de tercer nivel. Se realizó biopsia de nodo linfático para su estudio histopatológico, búsqueda de bacilos ácido-alcohol resistentes, cultivo en el tubo indicador del crecimiento de Mycobacterium BACTEC (MGIT-960) y la identificación de cepa micobacteriana por PCR-RFLP (restriction fragment lenght polymorfism) de hsp65. Resultados: las cepas correspondieron al complejo Mycobacterium tuberculosis en 42 pacientes VIH positivos (93%), dos (4.4%) a M. intracellulare y una (2.2%) a M. gordonae. Las cepas correspondieron al complejo M. tuberculosis en 39 pacientes VIH negativos (97.5%) y una a M. fortuitum (2.5%). Conclusión: la presencia de MNT se encontró en 4.7% de todos los casos. A pesar de su baja frecuencia, deben ser tomadas en cuenta como posible causa de linfadenopatías, porque su identificación oportuna permite instaurar un tratamiento específico.

Reactivation of intraabdominal tuberculous lymphadenopathy after drug-eluting beads transcatheter arterial chemoembolization in a patient with hepatocellular carcinoma.

Owing to effective treatments and sanitary improvements, the incidence of latent tuberculosis infection (LTBI) has decreased. However, approximately one-quarter of the world's population is thought to have LTBI, and the reactivation of tuberculosis (TB) sometimes occurs in immunocompromised hosts. A 54-year-old man presented with a fever. The patient had past histories of alcoholic and hepatitis C virus-related cirrhosis and hepatocellular carcinoma (HCC). He was treated with drug-eluting beads transarterial chemoembolization (DEB-TACE) for HCC three times, beginning 10 months before his current visit. A computed tomography scan showed enlarged intraabdominal lymph nodes with calcification, and the interferon-gamma release assay for TB infection was positive. The patient was diagnosed with tuberculous reactivation. Anti-TB therapy was administered to the patient, after which we restarted TACE and the TB infection remains controlled. In this case, we presumed that DEB-TACE is associated with the reactivation of TB infection and that anthracycline increases the risk of reactivating TB infection. In summary, we experienced a case of TB reactivation during the clinical course of a patient with HCC who was treated with DEB-TACE. When patients with HCC are treated with TACE, their symptoms, laboratory data, and imaging results should be monitored when latent TB infections are suspected.

A case of abdominal tuberculosis lymphadenitis extending into the gallbladder and duodenum in a human T-cell lymphotropic virus type 1 carrier.

A 69-year-old man with a history of pulmonary tuberculosis presented with fever. He tested positive for the QuantiFERON TB-2G and human T-cell lymphotropic virus type 1 antibodies. Imaging revealed a mass in the neck of the gallbladder, with periportal lymph node enlargement and penetration into the duodenum. A definite diagnosis could not be made, even with a subsequent detailed examination. Finally, cholecystectomy and a lymph node biopsy were performed. Histopathology revealed a caseating granuloma in the lymph nodes and in the serosa of the gallbladder, and polymerase chain reaction was positive for tuberculosis. Therefore, the patient was diagnosed with abdominal tuberculosis lymphadenitis extending into the gallbladder and duodenum.

Tuberculous lymphadenitis: FDG PET and CT findings in responsive and nonresponsive disease.

PURPOSE: No data is available on the different FDG PET and CT findings in the lymph nodes (LN) of patients with HIV and tuberculosis (TB) who respond compared with those who do not respond to anti-TB treatment by 4 months after initiation of TB treatment. These findings were the focus of our study. METHODS: PET/CT scans performed at 4 months after initiation of TB treatment in 20 consecutive HIV patients were analysed. SUVmax values were obtained for all regions of LN involvement. The diameter of the LNs was measured and the CT enhancement (LNs showing peripheral rim enhancement with central low attenuation, PRECLO, in comparison with homogeneously involved LNs) and the calcification patterns of involved LNs assessed. The relationship between the PET and CT findings and the clinical outcome, response or nonresponse, was evaluated. RESULTS: FDG PET identified 91 sites of LN involvement, 20 of which were not identified by CT. SUVmax values were significantly higher in nonresponders (8 patients, SUVmax 11.2 ± 4.0, mean ± SD) when compared to responders (12 patients, SUVmax 2.6 ± 2.3; p = 0.0001). In ROC analysis (AUC 0.952) a cut-off value of 4.5 for SUVmax yielded a sensitivity and specificity of 95% and 85% for discriminating nonresponding from responding LNs. LNs were significantly larger in nonresponders (1.9 ± 0.4 cm) than in responders (1.4 ± 0.4 cm; p = 0.0001); the AUC in the ROC analysis was 0.76. PRECLO LNs were significantly larger (2.2 ± 0.3 cm) than homogeneous involved LN basins (1.5 ± 0.4 cm) and LN basins with calcification (1.4 ± 0.5 cm; p = 0.001). Using the presence of at least one LN basin with PRECLO as a criterion for nonresponse, responders could be separated from nonresponders with a sensitivity of 88% and a specificity of 66%. CONCLUSION: LNs responding to TB treatment could be differentiated from nonresponding LNs with a sensitivity and specificity of 95% and 85% using a SUVmax cut-off value of 4.5 and a sensitivity and specificity of 88% and 66% using the presence of at least one LN basin with PRECLO.

Diagnosis of tuberculous lymphadenitis in Ethiopia: correlation with culture, histology and HIV status.

SETTING: Butajira, Southern Ethiopia. OBJECTIVE: To compare the diagnostic capacity of the clinical criteria for tuberculous lymphadenitis (TBLN) with histological and/or culture results and to assess the association of human immunodeficiency virus (HIV) with tuberculosis (TB) lymphadenitis. DESIGN: Patients (n=171) were included in the study from October 2005 until July 2006 at Butajira Hospital. Laboratory tests were performed to confirm TBLN. HIV status was identified in TBLN patients and retrospectively in 1608 healthy individuals. RESULT: A total of 136/161 (84.5%) patients were diagnosed with TBLN by histology. TBLN was culture-confirmed in 107/156 (68.6%) patients. The sensitivity, specificity, positive and negative predictive values of histology were respectively 92.5%, 49%, 79.8% and 75% when compared to culture as gold standard. Patients positive for TBLN by cytology and Ziehl-Neelsen (ZN) were also positive by histology and culture. Among the 143 confirmed TBLN patients, nine (6.3%) were HIV-positive. Of the 1608 healthy individuals, 77 (4.8%) were HIV-positive. Younger age (P=0.0001), female sex (P=0.016), not being married (P=0.0001) and illiteracy (P=0.016) showed a strong association with HIV in healthy individuals. CONCLUSION: Clinical criteria alone over-diagnosed TBLN by 15.4% compared to histological and/or bacteriological results. The HIV prevalence in TBLN patients and healthy individuals was the same.

Mycobacterium avium intracellularae complex associated extrapulmonary axillary lymphadenitis in a HIV-seropositive infant--a rare case report.

Opportunistic infections by Mycobacterium avium intracellulare complex in HIV infected patients, though common in adults, are rarely seen in infants. We herewith report an interesting case of an eight month old infant presenting with isolated axillary lymphadenitis, later on diagnosed to be tubercular lymphadenitis by Mycobacterium avium intracellulare and finally proved to be seropositive for HIV infection born to previously undetected HIV seropositive parents.

Detection and comparative analysis of persistent measles virus infection in Crohn's disease by immunogold electron microscopy.

AIMS: To determine the specificity of persistent measles virus infection in intestinal samples from Crohn's disease patients using quantitative immunogold electron microscopy. To compare the results with samples from ulcerative colitis, a granulomatous inflammatory control (tuberculous lymphadenitis), and a positive control. METHODS: Formalin fixed, paraffin embedded intestinal tissue from patients with Crohn's disease was reprocessed and stained with antimeasles nucleocaspid protein primary antibody followed by 10 nm gold conjugated secondary antibody. Tissue samples were taken from granulomatous and non-granulomatous areas of the intestine. Intestinal samples from patients with ulcerative colitis, tuberculous lymphadenitis, or acute mesenteric ischaemia were similarly processed. Brain tissue from a patient with subacute sclerosing panencephalitis (SSPE) was used as the positive control. Duplicate sections of all tissues were processed without the primary antibody. Stained specimens were examined by electron microscopy. RESULTS: In Crohn's disease patients, 8/9 foci of granulomatous inflammation and 0/4 foci of non-specific inflammation were positive for measles virus. Of controls, 0/5 non-inflamed intestinal tissues, 1/8 tuberculous tissues, 1/5 ulcerative colitis tissues, and 1/1 SSPE tissues were positive. Gold grain counts per nuclear field-of-view in both Crohn's disease granulomas (43.29) and SSPE (36.94) were significantly higher than in tissues from patients with ulcerative colitis (13.52) or tuberculous lymphadenitis (15.875), and nongranulomatous areas of Crohn's disease (4.89) (p < 0.001, p < 0.001, p = 0.0006, respectively), with no significant difference between Crohn's disease and SSPE (p > 0.1). In both SSPE and Crohn's disease staining was confined to a small population of cells exhibiting characteristic cytopathology. CONCLUSION: These data support a role for measles virus in the aetiology of Crohn's disease.