(1)
Department of Pathology, Sinai Hospital of Baltimore Pathology, Baltimore, MD, USA
Keywords
InflammationGranulomaFungiVirusesParasitesBacteriaAcuteChronicLet’s review the types of inflammatory responses you may see. It seems very basic, but learning to differentiate inflammatory changes from dysplastic ones is a fundamental goal in pathology training.
Acute Inflammation
Acute changes are the result of recent tissue damage, either from trauma, ischemia, toxins, or infection. Features include the following:
● Vascular congestion
● Edema
● Fibrinous exudate
● Tissue damage and/or necrosis
● Neutrophils (or polymorphonuclear leukocytes, often shortened to “polys”)
Note that when a pathologist says “acute inflammation,” it is synonymous with neutrophils and does not necessarily imply an acute clinical time course. Acute injury can be followed by resolution (healing), fibrosis or scar, abscess formation (Figure 3.1), or a chronic inflammatory stage. Evidence of recent damage and reparative changes includes granulation tissue, hemosiderin, lipid-laden macrophages, and fibroblast proliferation.
Figure 3.1.
Acute inflammation and abscess formation. This example of the acute inflammatory response shows collections of neutrophils (abscess formation, 1), extravasated blood (2), prominent capillaries (3), and fibrin accumulation (4). Inset: the mixed inflammatory infiltrate includes plasma cells (PC), neutrophils (N), eosinophils (Eo), and lymphocytes (L).
Granulation tissue has a characteristic look of a watery or myxoid background with sparse fibroblasts floating in it and a proliferation of inflammatory cells (all types) and capillaries (Figure 3.2). The endothelial cells of the capillaries can become quite plump and prominent, resembling epithelial cells or glands.
Figure 3.2.
Granulation tissue is characterized by a loose myxoid background with fibroblasts and inflammatory cells and by prominent capillaries with plump endothelial cells and thick walls. The stroma appears condensed and thickened around the capillaries, giving them a pink halo (arrow).
Biopsy site changes , a term often used to indicate evidence of a recent procedure, includes fibroblast proliferation (early scar), foreign-body-type giant cells, suture material, foamy macrophages, fat necrosis, and inflammation. It has a more solid look than granulation tissue (Figure 3.3). Scar tissue implies that a dense thick collagen has replaced the normal structures. In the skin, a dermal scar is evidenced by a homogeneous pink layer of collagen and absence of adnexal structures (Figure 3.4).
Figure 3.3.
Biopsy site changes. In this subcutaneous specimen, collagen has replaced most of the fat cells, and foamy histiocytes can be seen ingesting some residual fat (arrow). Inset: Hemosiderin in macrophages (golden yellow to brown granules) can be seen in sites of prior trauma or bleeding.
Figure 3.4.
Dermal scar . Dense pink collagen has replaced the adnexal structures and displaced the subcutaneous fat in this biopsy site.
Chronic Inflammation
Chronic changes are the result of repetitive or sustained tissue damage due to trauma, ischemia, toxins, infection, or autoimmune processes. Features include the following:
● Increased vascularity and/or fibrosis (attempts to heal)
● Tissue destruction or obliteration of normal structures
● Lymphocytes, macrophages*, plasma cells, eosinophils
*What is a macrophage ? The precursor is a circulating monocyte, part of the myeloid lineage of blood cells (myeloid generally refers to cells in the granulocyte and monocyte groups, although it can also mean all cells that mature in the bone marrow, i.e., the opposite of lymphoid). The monocyte leaves the circulation and becomes a tissue macrophage. It can differentiate into organ-specific resident macrophages, such as microglia, Kupffer cells, and alveolar macrophages. It can also go to an area of inflammation and become activated, participating in the immune response. Activated macrophages are also called histiocytes and may be “epithelioid,” as in a granuloma, and “foamy,” as in lipid-laden (xanthomatous), hemosiderin-laden, or full of mucin or melanin. Finally, macrophages can acquire multiple nuclei to become a Langerhans giant cell (ring of nuclei) or a foreign-body-type giant cell (scattered nuclei).
Histologically, histiocytes have a bland and fade-into-the-background look to match their name (literally, “tissue cell”). They have pale-pink granular cytoplasm, sometimes with chunky phagocytosed bits of material, and indistinct cell borders (Figure 3.5). The nuclei are pale with crisp outlines, oval in shape, and often grooved. In tissue, a collection of histiocytes appears as an ill-defined pink area that is easy to miss. The nuclei often stream in a circular pattern like fish swimming in a barrel. Foamy macrophages are stuffed with lipid debris or organisms and can have an almost signet-ring appearance.
Figure 3.5.
Histiocytes appear as pale folded nuclei within an area of inflammation; the cell borders are indistinct, but the nuclei are surrounded by light pink cytoplasm (circle). Compare the pale chromatin to that of the neighboring lymphocyte (arrowhead).
We usually refer to the presence of lymphocytes as chronic inflammation. Lymphocytes plus neutrophils equals acute and chronic inflammation. In the gastrointestinal tract, instead of acute we use active, such as active chronic gastritis or active chronic inflammatory bowel disease. Inactive disease in the gastrointestinal tract means increased lymphocytes and plasma cells but no neutrophils. Eosinophils, which are grouped under chronic inflammation, have a bilobed nucleus and big red granules. They are usually an indication of an immune/IgE response, such as allergy or parasites.