The cytology of inflammation is a branch of cytopathology which studies the morphological aspects of cells involved in inflammatory processes. The enormous cascade of biochemical events and cellular interactions which occur in inflammation, both in the acute phase and during its evolution to chronic inflammation, cause inflammatory cells to arrive at the site of the lesion. The number, type and transformations of these cells can be described and form the morphological basis for recognizing the causes and predicting the consequences of the inflammation.
The inflammatory cells described by the cytology of inflammation are all of haematopoietic origin. These cells pass the first phase of their life in the blood stream, as circulating leucocytes, or in the marginal pool, which represents a reserve for any emergency situation. In the absence of inflammatory stimuli, these cells finish their life when they are sequestered and destroyed in the organs with these functions. If, on the other hand, there is an inflammatory stimulus, the leucocytes move actively to the focus of the inflammation where they undergo morphological transformations which depend on the cause of the inflammation.
The morphology of the following leucocytes is analysed below:
- neutrophilic granulocytes (neutrophils)
- eosinophilic granulocytes (eosinophils)
- macrophages
- lymphocytes and plasma cells
Neutrophils (Fig. 1). These are small to medium-sized cells, about 8-9 mm in diameter, with a pale cytoplasm containing colourless granules and a nucleus typically formed of lobes interconnected by narrow bridges of condensed or hyperchromic chromatin.
Eosinophils (Fig. 2). These are similar in shape and size to neutrophils from which they differ above all by the cytoplasmic contents, which are orangey-coloured, roundish granules in the dog and rod-shaped granules in the cat. The nucleus is sometimes bi-lobed and the chromatin is condensed or hyperchromic.
Monocytes (Fig. 3). These are the largest leucocytes; they have a uniformly, weakly basophilic cytoplasm and an oval nucleus, often with a central indentation or irregular outline, containing finely reticular chromatin.
Lymphocytes (Fig. 4). These cells are the same size as granulocytes, have a round outline, a small amount of basophilic cytoplasm and a round nucleus with condensed chromatin.
CYTOLOGY OF INFLAMMATION
Each of the cells described above can intervene during an inflammatory process as the predominant type of cell or in combination with other classes.
The predominant type of cell in a focus of inflammation and the morphological changes that the cells undergo form the morphological information for recognizing the type of inflammation: this information is normally extremely useful for the direct or indirect identification of the causes of the inflammation, even in cases in which the causes are not objectively apparent.
The morphological characteristics of the various types of inflammation are described below.
Neutrophilic inflammation. This type of inflammation is sustained mainly by neutrophils (which account for at least 85% of the inflammatory cells present); the synonyms for this form of inflammation are suppurative and purulent inflammation (Fig. 5).
When inflammation is sustained by neutrophils it is essential to analyse the morphological appearance of these cells, which can be normally segmented or have undergone two fundamental changes: karyolysis or pyknosis.
A morphological appearance that remains within the norm is a finding usually associated with non-septic pathological processes with an immune-mediated cause, such as non-septic suppurative arthrosynovitis or sterile irritant conditions.
Karyolysis is the morphological appearance of the death of a neutrophil due, in particular, to the effect of bacterial toxins; it is characterized by the loss of the lobes and chromatin bridges of the nucleus, which becomes swollen and takes on a uniformly pale colour (Fig. 6). Together with the morphological changes to the nucleus, it is often possible to detect bacteria within the cytoplasm, which have entered the cell through the process of phagocytosis. When phagocytosed bacteria are present, the inflammation is called “septic suppurative” or “septic purulent”.
Pyknosis, on the other hand, is characterized by the transformation of the nucleus into a spherical, strongly basophilic clump (Fig. 7), which can fragment into similar little spheres in a process known as karyorrhexis (Fig. 8). This fragmentation is a result of nuclear apoptosis, the inflammatory cell’s prolonged stay in the site of injury, or, in some cases, sepsis.
Macrophagic inflammation. When the circulating monocytes leave the intravascular compartment to travel through tissues they take the name of histiocytes and then, following activation through the effect of the inflammatory processes, macrophages when they gain phagic properties. They are large cells with a roundish or oval nucleus, which is generally paracentral or eccentric and indented or with an irregular contour; there are usually vacuoles in the cytoplasm. Depending on the pathogenic event underlying the attraction of macrophages to the site of inflammation, there may be evidence of phagocytosis with engulfment of numerous causal factors, including infectious agents, cells, debris and foreign matter.
An inflammatory cell population consisting only of macrophages is rare and is generally related to uncommon pathological conditions such as xanthomatosis, macrophagic panniculitis or to some infections such as those caused by mycobacteria; more frequently the macrophages are associated with neutrophils and the process takes the name “suppurative and macrophagic inflammation”. Common causes of this type of inflammation include bacteria, fungi and protozoa (Fig. 9).
The inflammation is called “pyogranulomatous” when the macrophages show a tendency to organize themselves in so-called epithelioid aggregates (Fig. 10) or as foreign body giant cells (Fig. 11): in these cases the cause of the inflammation is generally foreign material, particularly keratin from adnexal rupture, fungi or parasites.
Eosinophilic inflammation (Fig. 12). As for macrophagic inflammation, pure eosinophilic inflammation is rare: the eosinophils are usually associated with neutrophils and sometimes also macrophages, lymphocytes and plasma cells. In the dog, eosinophilic inflammation is defined by a relative percentage of eosinophils of 5-10%, while in the cat, the eosinophils must represent at least 25-30% of the total inflammatory cells. In some inflammatory foci eosinophils can be associated with a variable number of mast cells, which are medium-sized or large cells with a cytoplasm typically full of dense eosinophilic granulation and a round nucleus with condensed chromatin (Fig. 13). The causes of eosinophilic inflammation are predominantly hypersensitivity phenomena, including eosinophilic granuloma, reactions to insect stings, bronchial asthma and some parasitic infestations such as cardiopulmonary filariasis or visceral larva migrans syndrome. Eosinophils can, however, concentrate at a pathological site under the effect of chemotactic attraction exerted by some cytokines produced, for example, by mast cell tumours or some types of lymphoma.
Lymphoplasmacytic inflammation (Fig. 14). As for the preceding two forms of inflammation, lymphocytic inflammation is rare; it is defined lymphoplasmacytic (or sometimes lymphoplasmacellular) because the lymphocyte component is generally associated with the presence of plasma cells, characterized by basophilic cytoplasm and a round, paracentral or eccentric nucleus with clumped chromatin. A morphological particular that aids the recognition of these cells is the presence of a colourless halo, which corresponds to the Golgi apparatus where the immunoglobulins that these cells produce are synthesised and processed.
Suggested readings
- Raskin RE, Meyer DJ, Canine and Feline Cytology, a Color Atlas and Interpretation Guide. St Louis, Missouri, Saunders, 2010.
- Cowell RJ, Tyler RD, Meinkoth JH. Diagnostic Cytology and Hematology of the Dog and Cat. 2nd ed. St Louis, Mo: Mosby, 1999
- McGavin MD, Zachary JF. Pathologic Basis of Veterinary Diseases, IV ed. St.Louis, Missouri, Mosby Elsevier, 2007.