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TYPES OF INFLAMMATORY CELLS, LEUKOCYTOCLASIA, AND EXPENDABILITY OF LEUKOCYTES: THE COLOR OF INFLAMMATION
General: Neutrophils, eosinophils, mast cells, lymphocytes, and monocytes are leukocytes. For some processes, or at certain stages of some processes, neutrophils, having
collected in defects in tissue, remain relatively intact (S1C12P2-1). If clustered in loci and activated, they are
subjected (i.e., subject themselves) to an enzyme-, and mediator-rich medium (S1C11P1-1 &2). It is inherent in
these relationships that some of the clustered, activated leukocytes, in their functions, undergo lysis (S1C11P1-1);
they are expendable. In this process, nuclear debris is released into the zones of necrosis (S1C11P1-1 & 4); in some examples, the zones of necrosis are distinctly basophilic, a tinctorial quality imparted by the release of
nucleic acids into the tissue (S1C12P2-2-4). The reactions of neutrophils are often sequenced with the reactions of
monocytes (S1C12P2-5-7); one tends to follow the other with monocytes often being characterized as scavengers (S1C11P1-1-3).
Leukocytoclasia: In the process of reactive cytolysis, zones of inflammation become impregnated with fragments of nuclear debris (S1C12P2-2-4). They often acquire a basophilia; the infiltrates may contain fragments of the disrupted nuclei of dying
leukocytes (i.e., leukocytoclasia) (S1C11P1-3). The basophilia, which often is encountered in zones of necrosis (as
seen in rheumatoid nodules), is representative of the histologic influence of the breakdown products of neutrophils in the coloring of inflamed tissues. In some disorders, the zones of necrosis are brightly
eosinophilic (S1C18P8-1); they are rich in fibrin. The floor of a neurotic excoriation provides a good example of bright,
eosinophilic necrosis; the eosinophilia is of a type that might also be characterized as fibrinoid necrosis (S1C11P1-4).
Leukocytoclasia is not restricted to infiltrates which are rich in neutrophils. In some disorders, both neutrophils and monocytes commonly contribute to zones of basophilia (S1C15P5-2 & 3). This combination is commonly encountered in lesions of Sweet’s syndrome, and in pyodermas.
In some forms of inflammation, eosinophils are the preponderant, enzyme-rich, inflammatory cells (S1C30P20-4 & 5). They, like neutrophils, may disintegrate: they then release both nuclear debris, and eosinophilic,
enzyme-rich granules into the tissue. As a result, the affected connective tissue, in combination with condensed fibrin, becomes brightly eosinophilic.
Fibrin often contributes an acidophilia to zones of inflammation; such an alteration in connective tissue is characterized as fibrinoid degeneration or necrosis. Fibrin is a common
feature of zones of inflammation; it is relatively independent of the types of inflammatory cells in the neighboring tissue. The deposition of fibrin in tissue, in large part, is a consequence of altered vascular
permeability; deposits of fibrin are formed from fibrinogen in extravascular locations.
Neutrophils, connective tissue, and suppuration:
Infiltrates of neutrophils usually are the initial reacting cells in a variety of insults, and injuries to tissue. They are enzyme-rich cells with the ability to engulf, and kill, many microorganisms; in the act, they also produce lysis of damaged tissue. The role for neutrophils in inflammatory disorders is that of a phagocyte in which the engulfed material evokes a process of degranulation. Lytic enzymes are released into the site. The response is additional damage to involved tissue. In bacterial infections, a neutrophilic reaction, if allowed to evolve, is characterized by the eventual breakdown of both the neutrophils, and the locally altered tissue. This breakdown of tissue is manifested clinically by the formation of pus. The liquefied tissue becomes a purulent exudate, and the process is suppuration. The reaction histologically is suppurative necrosis. In suppurative necrosis, including that of pyoderma gangrenosum, the elastica is more resistant to the digestive enzymes of neutrophils than the collagenous component (S1C13P3-1-3).
In the process of repair, lytic defects in the dermis, as a consequence of inflammation, usually are inlaid with granulation tissue. In some resolving lesions, particularly the
pyodermas, the collagenous framework of the reticular dermis often is poorly represented, but the elastica will be prominent; it will appear to be hyperplastic. The perforating disorders include elastosis perforans
serpiginosum, perforating folliculitis, and “Kyrle’s disease;” in a small locus (i.e., the site of perforation), a zone of necrosis is characterized by lysis of collagen bundles, and by preservation of a collapsed
framework of elastic fibers. In some zones of suppuration in the reticular dermis, not only does elastica appear to be increased in amount, it may be altered qualitatively (i.e., deposits that are fibrinoid in
character may be found at the margins of the fibers; the fibers then appear to be lumpy-bumpy [bramble bush]; it should be noted that pre-elastin has fibrinoid qualities). The latter phenomena (i.e., lumpy-bumpy
elastic fibers) has been emphasized as a feature in penicillamine reactions. Altered elastica is also encountered in inflammatory disorders of connective tissue, such as elastofibroma dorsi, and Morton’s neuroma.
The apparent hyperplasia of elastica, seen in response to repair in some zones of suppurative necrosis, reflects the partial, or complete, destruction of collagen bundles by the suppurative process, and a collapse
of the elastic framework into the defects.
A zone, that is rich in the breakdown products of neutrophils, has a peculiar attraction for squamous epithelium. In response to inflammation, benign squamous epithelium may invade
the dermis; in its growth, it forms a column whose extremity will eventually abut upon the zone of inflammation or necrosis in the dermis. An invasive process of this type qualifies as a form of
pseudoepitheliomatous hyperplasia; it constitutes an extension of squamous epithelium beyond the domain of its native stroma (i.e., the adventitial dermis, including the papillary dermis and the perifollicular
sheath). These phenomena are well-illustrated in one of the perforating disorders, namely reactive perforating collagenosis (S1C14P4-1-4).
Similar phenomena may be encountered in the setting of “perforating” folliculitis (S1C14P4-5). It would be presumptuous
to assume that the invasion of benign squamous epithelium into the dermis occurs only in response to a zone of inflammation and necrosis in the dermis. In fact, in elastosis perforans, the presence of a band of
abnormal elastica in both the upper portion of the reticular dermis and the papillary dermis may be the stimulus for the invasion of benign squamous epithelium into the dermis. In this approach, the precursor lesion
is a form of nevus elasticus. In addition, the elastica of the nevus has the morphologic, and histochemical qualities of elastica of the reticular dermis, even though much of it is in the papillary dermis; the
abnormal elastica extends to the dermal-epidermal interface; it is PTAH positive.
The color of zones of necrosis on routine H&E sections reflects the material contributed to the zones from the products of inflammation, and from the reaction of tissue to
injury. Some of the lesions in the category of the necrotizing granulomas have a basophilia in the zones of necrosis that reflects a contribution of nucleic acids from disintegrating nuclei. If this reaction, in the
setting of an allergic, noninfectious process, is associated with peripheral palisades of histiocytes at the margins of the zones of necrosis, then the combination of features qualifies as a variant of a necrotizing
granulomatous collagenosis (palisaded granuloma). Basophilic granulomas are in part the result of the migration of neutrophils and histiocytes into zones of incipient necrosis. As the cells disintegrate, the
breakdown of the nuclei of these inflammatory cells contributes the intense basophilia of the fully developed zones of necrosis. This combination of features is characteristically seen in a rheumatoid nodule, and in
rheumatoid neutrophilic and granulomatous dermatitis, but may be seen in less developed patterns in association with other forms of connective tissue disease. Basophilic granulomas, of this type, differ from the
fibrinoid and mucinous deposits of classic lesions of granuloma annulare. They also differ from the intensely eosinophilic zones of necrosis which characterize both allergic granulomas, and the so-called flame
figures (S1C30P20-4 & 5) of Well’s syndrome (eosinophilic collagenosis).
INFLAMMATION AND THE DIRECTED GROWTH OF EPITHELIUM (PSEUDOEPITHELIOMATOUS HYPERPLASIA)
Pseudoepitheliomatous hyperplasia is basically a process affecting squamous epithelium; it usually is characterized as a response to inflammation. It is emphasized as a common feature of the response of skin to
infection, particularly as a response to some deep fungal infections, and some infections with acid fast bacilli. In a most limited locus, a similar response, with disintegrating neutrophils and monocytes at the
extremity of a column of hyperplastic, invasive squamous epithelium, also defines the common processes variously classified as perforating disorders, or transepithelial elimination. The process is mediated by
invasive epithelium, and basically is a response to a focus of inflammation. The epithelium, on making contact with dermal connective tissue, entraps connective tissue fibers of the reticular dermis. At points of
contact between epithelium and connective tissue, an inflammatory response is limited. The process initially is one of limited pseudoepitheliomatous hyperplasia, and sequestration of connective tissue. The
epithelium invades and disrupts connective tissue fibers; the fibers will be found in the interstitium of the invading epithelium. In the zone of basophilic necrosis at the interface between invasive epithelium and
the reticular dermis (a zone of necrosis in which the nucleic acids of disintegrating neutrophils contribute distinctive tinctorial qualities), elastic fibers (collagen having been digested in the zones of necrosis)
tend to clump, and acquire a bright eosinophilia (i.e., a fibrinoid quality).
In actinic (solitary) keratoacanthoma, the purported self-limited growth invites attributions supporting a role for inflammation. On the other hand, the cytological atypia, which is so common an attribute of lesions
in this category, can only be accommodated in concepts of progressive neoplasia. The atypia is mostly an attribute of the surface epithelium of actinically damaged skin and, in any case, has no relationship to
cyclic responses in follicular epithelium. The epithelium of a keratoacanthoma may be neoplastically programmed to respond in the extreme to the stimulations associated with inflammation.
INFLAMMATION AND THE DERMAL-EPIDERMAL INTERFACE
In some, noninfectious disorders, neutrophils are a prominent component. For some interface disorders, they probably contribute to the lysis of bonds of cohesion among keratinocytes, and between basal keratinocytes
and components of the basement membrane (i.e., the IgA autoimmune disorders). Their enzymes may also damage the cytoplasm of the basal keratinocytes in the region of the their attachment to the basement membrane
(partial cytolysis of basal keratinocytes). In pemphigoid (an IgG immunne disorder), similar forms of tissue damage commonly are associated with interface infiltrates of lymphocytes and histiocytes.
EPIDERMAL MUCINOUS AVENUES:
In psoriasiform epidermal hyperplasias, mucinous avenues among the keratinocytes are open to the surface. In the areas showing widening of the mucinous avenues, neutrophils often are found migrating into the upper
reaches of the epidermis; they eventually are transported into the parakeratotic caps. The migration of neutrophils into the epidermis in this manner is a psoriasiform quality. It is not peculiar to lesions of
psoriasis, but may also be seen in diverse disorders; examples include subcorneal pustular dermatosis, pemphigus, impetigo, and candidiasis.
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