High Mass Cell Density in Tuberculous Lymphadenitis

Mast cells are one of the main inflammatory cells involved in the pathogenesis of tuberculosis. Previous reports revealed that mast cells participated in both acute and chronic states of infection with Mycobacterium tuberculosis through direct contact or indirect enhancement by releasing mediators. The authors evaluated mast cell density on tissue sections of tuberculous lymphadenitis stained with 0.1% toluidine blue from 45 cases, all of which were retrieved from the surgical pathology files of King Chulalongkorn Memorial Hospital from 1999 to 2006. A number of mast cells were correlated semiquantitatively with granulomas which were formed by aggregation of epithelioid histiocytes, multinucleated giant cells, and caseous necrosis. We found that mast cell density was significantly increased in lymph nodes with greater granuloma involvement (p = 0.030) and multinucleated giant cell formation (p = 0.010). These findings indicate a significant correlation between mast cell density and the granulomatous formation responsible for M. tuberculosis. cape acute inflammatory cells are engulfed by mononuclear phagocytes and induce delayed type hypersensitivity (Szczepanik et al, 2003). Mycobacteria are actually first phagocytosed by alveolar macrophages and conveyed by these cells to draining lymph nodes, and sometimes disseminate through the blood to other parts of the lung and elsewhere in the body. Meanwhile, mononuclear phagocytes act as antigen presenting cells, giving organism-derived peptides to naive CD4 T lymphocytes via class II molecules, and often undergo morphologic transformation into epitheliumlike or epithelioid cells (Segovia-Juarez et al, 2004). Aggregations of these cells, usually surrounded by lymphocytes, are called granulomas. Epitheliod cells are able to fuse together to form multinucleated giant cells or Langhans giant cells. This lesion is usually evoked by relatively slowly dividing infectious agents such as mycobacteria. Interaction between mycobacteria-activated T-cells and macrophages results in direct toxicity to mycobacteria due to a lack of oxygen and contributes to necrotic caseous tissue damage (Guirado et al, 2006). SOUTHEAST ASIAN J TROP MED PUBLIC HEALTH 116 Vol 38 No. 1 January 2007 Mast cells, inflammatory cells typically found in relatively large numbers in the mucosa and near blood or lymphatic vessels, are likely to be one of the first inflammatory cells to make contact with infectious agents and, following activation, release proinflammatory cytokines, protease enzymes, and inflammatory mediators (Segovia-Juarez et al, 2004; Guirado et al, 2006). Additionally, mast cell mediators are indispensable for mobilizing and recruiting various other inflammatory cells to the site of infection. In vitro study demonstrated that mast cells can directly recognized protein antigens of M. tuberculosis and have the potential to play an active role in mediating host response (Muñoz et al, 2003). Moreover, mast cells participate in the chronic phase of host defense immunity, including delayed type hypersensitivity. Activated mast cells have to release vasoactive serotonin and TNF-α for endothelial activation and subsequent extravasation of circulating T cells as a first step in order to control infectious agents (McHale et al, 1999; Szczepanik et al, 2003). Although previous research demonstrated the cellular response to M. tuberculosis was enhanced by the chemical products of mast cells, quantity assessment of mast cells associated with granulomatous formation has never been done. This study investigated the correlation between mast cell numbers and several microscopic components of granulomatous inflammation, which are responsible for infection with M. tuberculosis. MATERIALS AND METHODS The authors selected 45 cases with granulomatous lymphadenitis between 1999 and 2006 retrieved from the surgical pathology files of King Chulalongkorn Memorial Hospital. All lymph nodes in our study were positive for M. tuberculosis, whether by culture or polymerase chain reaction technique. All four-micrometer-thick hematoxylin and eosin stained slides were reviewed. Components of granulomas, comprised of epithelioid histiocytes, caseous necrosis, and multinucleated giant cells were semiquantitatively stratified (Fig 1). Epithelioid histiocytes and caseous necrosis were scored as 1, 2, 3 or 4 when they were present in less than 25%, 26-50%, 50-75%, or more than 75% of lymph nodes, respectively. Distribution of multinucleated giant cells within the lymph nodes was considered as not seen, less than 1/3, 1/3 to 2/3 and more than 2/3 of areas. For mast cell determination, the sections were stained with 0.1% aqueous toluidine blue. The number of mast cells within or around granulomas were Fig 1–Caseous necrosis, surrounded by crowded palisading epithelioid histiocytes, some of which form multinucleated giant cells. Fig 2–Two mast cells with metachromatic stain (arrow) among scattered epithelioid histiocytes, forming