Pathological diagnosis of granulomatous lung disease: A review

Department of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Histopathology (Impact Factor: 3.45). 03/2007; 50(3):289-310. DOI: 10.1111/j.1365-2559.2006.02546.x
Source: PubMed


Granulomas in the lung are common diagnostic problems encountered by pathologists. They occur in a wide range of pulmonary conditions, ranging from common entities to uncommon ones and including both infections and non-infectious diseases. This review summarizes the main histological features that help distinguish various granulomatous lung diseases. It concentrates on the most important and common entities that may be encountered and emphasizes helpful features in the differential diagnosis.

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Available from: Ola El-Zammar, May 12, 2015
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    • "The granulomatous response is a complex host defense mechanism that has evolved to provide containment of infectious and/or environmental agents (Warren, 1976; El-Zammar and Katzenstein, 2007). The maintenance of this inflammatory process is dependent upon an inciting agent and the dynamic interactions amongst inflammatory mediators, various immune and inflammatory cells, and structural cells of the involved tissue (Chensue et al., 1994; Ulrichs and Kaufmann, 2006; Ramakrishnan, 2012). "
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    ABSTRACT: Granulomas represent a spectrum of inflammatory sequestration responses that may be initiated by a variety of agents, including non-infectious environmental factors and infectious microbial pathogens. Although this reaction is designed to be protective, the associated tissue injury is often responsible for a profound degree of pathology. While many of the mechanisms that sustain the development of the granuloma are enigmatic, it is accepted that the maintenance of this inflammatory process is dependent upon dynamic interactions between an inciting agent, inflammatory mediators, various immune and inflammatory cells, and structural cells of the involved tissue. The best studied of the host-dependent processes during granuloma development is the innate and adaptive immune response. The innate immune response by antigen-presenting cells [APCs; dendritic cells (DCs) and macrophages] is initiated quickly to protect from overwhelming pathogens, but with time, can also activate the adaptive immune response. APCs, essential regulators of the innate immune response, can respond to microbial ligands through Toll-like receptors (TLRs), which function in the recognition of microbial components and play an important role to link the innate and adaptive immune responses. CD4(+) T helper (Th) cells are essential regulators of adaptive immune responses and inflammatory diseases. Recently, the Notch system has been shown to be an important bridge between APCs and T cell communication circuits. In the present review, we discuss recent findings that explore the mechanisms in the linkage of innate and adaptive immunity, including granulomatous formation though TLRs and Notch activation.
    Frontiers in Immunology 01/2013; 4:10. DOI:10.3389/fimmu.2013.00010
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    • "Less is known about the mediators involved in production and healing of non-immune granulomas. Non-immune or foreign body granulomas in the lung may progress to local fibrosis [42] similar to the reaction to well-dispersed MWCNTs delivered to the lungs of rodents by pharyngeal aspiration [5]. The phenotype of activated macrophages in non-immune granulomas has not been characterized; however, arginase-1, a marker of M2 macrophage activation, is induced after 10-14 days following exposure to asbestos or MWCNTs in this in vitro model (Figure 8). "
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    ABSTRACT: The most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas accompanied by interstitial fibrosis in the lungs. In the mesothelium, a similar response is induced by high aspect ratio nanomaterials, including asbestos fibers, following intraperitoneal injection. This asbestos-like behaviour of some engineered nanomaterials is a concern for their potential adverse health effects in the lungs and mesothelium. We hypothesize that high aspect ratio nanomaterials will induce epithelioid granulomas in nonadherent macrophages in 3D cultures. Carbon black particles (Printex 90) and crocidolite asbestos fibers were used as well-characterized reference materials and compared with three commercial samples of multiwalled carbon nanotubes (MWCNTs). Doses were identified in 2D and 3D cultures in order to minimize acute toxicity and to reflect realistic occupational exposures in humans and in previous inhalation studies in rodents. Under serum-free conditions, exposure of nonadherent primary murine bone marrow-derived macrophages to 0.5 μg/ml (0.38 μg/cm2) of crocidolite asbestos fibers or MWCNTs, but not carbon black, induced macrophage differentiation into epithelioid cells and formation of stable aggregates with the characteristic morphology of granulomas. Formation of multinucleated giant cells was also induced by asbestos fibers or MWCNTs in this 3D in vitro model. After 7-14 days, macrophages exposed to high aspect ratio nanomaterials co-expressed proinflammatory (M1) as well as profibrotic (M2) phenotypic markers. Induction of epithelioid granulomas appears to correlate with high aspect ratio and complex 3D structure of carbon nanotubes, not with their iron content or surface area. This model offers a time- and cost-effective platform to evaluate the potential of engineered high aspect ratio nanomaterials, including carbon nanotubes, nanofibers, nanorods and metallic nanowires, to induce granulomas following inhalation.
    Particle and Fibre Toxicology 05/2011; 8(1):17. DOI:10.1186/1743-8977-8-17 · 7.11 Impact Factor
  • Arerugī = [Allergy] 12/1995; 44(11):1255-61.
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