Clinical usefulness of 18F-FDG PET/CT for initial staging and assessment of treatment efficacy in patients with lymph node tuberculosis.

INTRODUCTION: Few studies have evaluated the promising role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) and PET/computed tomography FDG PET/CT in evaluating and monitoring treatment response in patients with lymph node tuberculosis (LNTB). The aim of this clinical investigation was to assess the clinical usefulness of FDG PET/CT for initial tuberculosis staging and to determine the prognostic value of the decrease of 18F-FDG uptake during antibiotic treatment in LNTB patients. METHODS: We retrospectively reviewed 18 cases of LNTB admitted at a single center from 2004 to 2014. Medical records of patients who underwent two FDG PET/CT (>6 months interval), at initial staging and at the end of therapy were reviewed to determine the impact of FDG PET/CT on initial management of LNTB and response to therapy. Statistical analysis was performed using linear mixed-effects model. RESULTS: Thirteen cases of disseminated LNTB and five cases of localized LNTB were included in the study. Initial FDG PET/CT allowed guided biopsy for initial diagnosis in 5 patients and identified unknown extra-LN TB sites in 9 patients. Visual analysis follow-up of FDG PET/CT showed a complete metabolic response in 9/18 patients (all of whom were cured), a partial response in 7/18 (5 of whom were cured) and no response in 2/18 (all of whom were not cured). The semi-quantitative evaluation of 18F-FDG intensity decrease based on the maximum standardized uptake value (SUVmax), compared to targeted estimated decrease allowed to predict correctly a complete response to treatment in 14/18 cases. CONCLUSION: FDG PET/CT allows an accurate pre-therapeutic mapping of LNTB and helps for early TB confirmation. The SUVmax follow up is a potential tool for monitoring the treatment response.

Erythropoietin-producing tubercle granuloma in a hemodialysis patient.

BACKGROUND: We describe a case of a fever of unknown etiology that was caused by a caseating tubercle granuloma which produced erythropoietin. To our knowledge, this is the first report of an erythropoietin- producing granuloma. CASE PRESENTATION: A 48-year-old Japanese man with a 5-year history of maintenance hemodialysis for diabetic nephropathy presented with an intermittent fever over a few months. During febrile periods he developed erythema nodosum on his legs. Computed tomography showed axillary lymph node enlargement and this was further corroborated by a gallium scan that revealed high gallium uptake in these nodes. A Mantoux test was positive and an interferongamma release assay for tuberculosis diagnosis was also positive. Lymph node tuberculosis was suspected and the patient underwent lymphadenectomy. Histological analysis of the lymph nodes revealed a caseating granuloma that showed positive results on an acid-fast bacteria stain and a Mycobacterium tuberculosis polymerase chain reaction test. After lymphadenectomy, however, the patient's hemoglobin levels rapidly decreased from 144 to 105 g/L, and this was further compounded by a decrease in serum erythropoietin from 223 mIU/mL to 10.7 mIU/mL by postoperative day 21. We suspected the tubercle to be a source of the erythropoietin and this was further confirmed by in situ hybridization. CONCLUSIONS: We report for the first time ectopic erythropoietin production by a tuberculous lymph node. Our observations are substantiated by a postoperative decline in his erythropoietin level and a clinical requirement for erythropoietin treatment.

Immunohistochemistry using a Mycobacterium tuberculosis complex specific antibody for improved diagnosis of tuberculous lymphadenitis.

The clinical and histological criteria used to diagnose lymphadenitis caused by Mycobacterium tuberculosis complex organisms have poor specificity. Acid-fast staining and culture has low sensitivity and specificity. We report a novel method for diagnosis of tuberculosis that uses immunohistochemistry to detect the secreted mycobacterial antigen MPT64 on formalin-fixed tissue biopsies. This antigen has not been detected in non-tuberculous mycobacteria. Polymerase chain reaction (PCR) for amplification of IS6110 from DNA obtained from the biopsies was used as a gold standard. Fifty-five cases of granulomatous lymphadenitis with histologically suspected tuberculosis obtained from Norway and Tanzania were evaluated. Four known tuberculosis cases were used as positive controls, and 16 biopsies (12 foreign body granulomas and four other non-granulomatous cases) as negative controls. With immunohistochemistry, 64% (35/55) and with PCR, 60% (33/55) of granulomatous lymphadenitis cases were positive. Using PCR as the gold standard, the classical tuberculosis histology had sensitivity, specificity, positive and negative predictive values of 92, 37, 60, and 81%, respectively, and immunohistochemistry had sensitivity, specificity, positive and negative predictive values of 90, 83, 86, and 88%, respectively. The observed agreement between PCR and immunohistochemistry was 87% (kappa = 0.73). Immunohistochemistry with anti-MPT64 antiserum is a rapid, sensitive, and specific method for establishing an etiological diagnosis of tuberculosis in histologic specimens. Immunohistochemistry has the advantages over PCR of being robust and cheap, and it can easily be used in a routine laboratory.

Eosinophil chemotactic factors from granuloma of Kimura's disease, with special reference to T lymphocyte-derived factors.

The granuloma of patients with Kimura's disease characterized by tissue and peripheral blood eosinophilia was reviewed with respect to eosinophil infiltration. An infiltrate of inflammatory cells with histiocytes and a sprinkling of eosinophils were observed in the fibrous stroma surrounding the newly formed vessels. Mast cells were rarely seen in the areas where eosinophils were grouped together. Three different eosinophil chemotactic factors (ECF) were isolated from the granulomas of Kimura's disease. They were termed as low molecular weight (LMW), intermediate molecular weight (IMW), and high molecular weight (HMW)-ECF according to the profile on gel filtration (LMW-ECF, about 500; IMW-ECF, about 12,500; HMW-ECF, 45,000-70,000). In terms of their activity when extracted from the granuloma, LMW-ECF and HMW-ECF seemed to be major natural mediators for the tissue eosinophilia, whereas IMW-ECF was a minor one. In an in vitro system, it was shown that granuloma lymphoid cells produce spontaneously at least two ECF having similar properties to LMW- and HMW-ECF, respectively. By analysis with monoclonal antibodies, granuloma T cells, probably OKT4-positive cells, were shown to be responsible for the production of those two ECF. It was thus suggested that prolonged synthesis of LMW- and HMW-ECF by OKT4-positive T cells plays a crucial role in the local eosinophilia of Kimura's disease.

Immunohistochemical localization and distribution of S-100 proteins in the human lymphoreticular system.

Immunohistochemical localization of S-100b protein and S-100ao protein in human lymphoreticular system was studied by using monospecific antibody directed against either the alpha subunit or beta subunit of S-100 protein. S-100b protein immunoreactivity was detected in Langerhans cells, interdigitating reticulum cells, and histiocytosis X cells, but not in ordinary macrophages and blood monocytes. In contrast, S-100ao protein immunoreactivity was detected in blood monocytes, macrophages of lymph node, alveolar macrophages of lung, and small numbers of Kupffer cells of liver. S-100ao immunoreactivity was also detected in epithelioid cells, Langhans giant cells, and foreign body giant cells. The present findings suggest that the presence of S-100ao protein in the cytoplasm is one of the characteristic features of cells in the human mononuclear phagocyte system. The detection of S-100b, but not S-100ao, immunoreactivity in Langerhans cells and interdigitating reticulum cells also suggests that they are independent of the monocyte-macrophage system. S-100ao protein may be a novel cytoplasmic marker for cells of the human monocyte-macrophage system.