Histopathologic review of granulomatous inflammation

Abstract

Granulomatous inflammation is a histologic pattern of tissue reaction which appears following cell injury. Granulomatous inflammation is caused by a variety of conditions including infection, autoimmune, toxic, allergic, drug, and neoplastic conditions. The tissue reaction pattern narrows the pathologic and clinical differential diagnosis and subsequent clinical management. Common reaction patterns include necrotizing granulomas, non necrotizing granulomas, suppurative granulomas, diffuse granulomatous inflammation, and foreign body giant cell reaction. Prototypical examples of necrotizing granulomas are seen with mycobacterial infections and non-necrotizing granulomas with sarcoidosis. However, broad differential diagnoses exist within each category. Using a pattern based algorithmic approach, identification of the etiology becomes apparent when taken with clinical context.The pulmonary system is one of the most commonly affected sites to encounter granulomatous inflammation. Infectious causes of granuloma are most prevalent with mycobacteria and dimorphic fungi leading the differential diagnoses. Unlike the lung, skin can be affected by several routes, including direct inoculation, endogenous sources, and hematogenous spread. This broad basis of involvement introduces a variety of infectious agents, which can present as necrotizing or non-necrotizing granulomatous inflammation. Non-infectious etiologies require a thorough clinicopathologic review to narrow the scope of the pathogenesis which include: foreign body reaction, autoimmune, neoplastic, and drug related etiologies. Granulomatous inflammation of the kidney, often referred to as granulomatous interstitial nephritis (GIN) is unlike organ systems such as the skin or lungs. The differential diagnosis of GIN is more frequently due to drugs and sarcoidosis as compared to infections (fungal and mycobacterial).Herein we discuss the pathogenesis and histologic patterns seen in a variety of organ systems and clinical conditions.

Granulomatous inflammation in BK polyomavirus–associated nephropathy

“…As expected in immunosuppressive states, the vast majority of cases are secondary to infections, among which mycobacterial and fungal etiologies predominate . In addition, viral infections, in particular adenovirus nephritis and less commonly cytomegalovirus infections may cause granulomatous inflammation . Similarly to the native kidney, hypersensitivity (allergic) granulomatous interstitial nephritis and sarcoidosis can also affect renal allografts …”

“…In addition, viral infections, in particular adenovirus nephritis and less commonly cytomegalovirus infections may cause granulomatous inflammation . Similarly to the native kidney, hypersensitivity (allergic) granulomatous interstitial nephritis and sarcoidosis can also affect renal allografts …”

Intramuscular vaccination of Atlantic lumpfish (Cyclopterus lumpus L.) induces inflammatory reactions and local immunoglobulin M production at the vaccine administration site

“…injection of oil‐based vaccine into lumpfish skin/muscle leads to infiltration of inflammatory cells that increased in numbers over time, eventually encompassing and developing granulomas around vaccine droplets within the tissue. Such reactions are a distinctive form of chronic inflammation, where granuloma formations within different organs are regarded as a hallmark of several infectious disorders, in addition to non‐infectious causes such as foreign bodies (Shah, Pritt, & Alexander, ). Late‐stage granulomas were clearly encapsulated by fibrous‐looking connective tissue, which is often seen as part of prolonged inflammatory vaccine reactions in fish (Poppe & Koppang, ).…”

Granulomatous responses in larval taeniid infections

“…Their most characteristic feature is the presence of macrophage phenotypes known as epithelioid cells and multinucleated giant cells (MNGCs). Epithelioid cells are large cells with irregular borders and round or oval nuclei typically situated distally with respect to irritating body . MNGCs are related but larger cell types with several nuclei, arranged towards the cell periphery or accumulated towards the distal pole with respect to the foreign entity.…”

“…Any focal accumulation of inflammatory cells that includes macrophages can be referred to as “granulomatous inflammation.” However, proper granulomas have a well‐defined organization . In the most organized type of immunological granuloma, epithelioid and MNGCs form a palisading rim around the pathogen and are surrounded by a cuff of lymphocytes, in which monocytes/macrophages with conventional morphologies also occur . The periphery of granulomas often additionally displays fibrotic reactions of varying intensity, in which fibroblasts lay down collagen.…”