HISTOLOGIC PATTERNS (contributions of inflammation to the patterns)

We speak of inflammatory diseases as if the inflammatory cells are the initiators of the basic process. In fact, the inflammatory cells are attracted to sites of injury; they are migrants, having arrived after, and in response to, the initial insult. Having once been incorporated, as a contributor to the ensuing histologic changes, inflammatory cells significantly influence the damage, and repair of the affected tissue. Once the cellular and immune responses are established in the sites of injury, a cascade of secondary responses further alter the nature of the tissue in the affected site, but usually do so in a manner which has specificity only as a reaction pattern. Many of a pathologist's compartments of virtual images might be characterized as being representative of basic reaction patterns. The number of reaction patterns is limited in comparison with the number of inflammatory diseases.

THE SKIN

(MICROANATOMIC DIVISIONS)

The microanatomic segments of the skin provide a basis for the compartmentalization of both real and virtual images. In the evaluation of inflammatory processes by light microscopy, an understanding of the relationships between basic reactions of the skin and microanatomic divisions is indispensable. In this approach, the basic divisions and boundaries include:

1. epidermis

a. keratin layer

b. granular layer

c. functional superficial unit

d. functional basal unit

2. basement membrane zone (dermal-epidermal interface)

a. lamina lucida, lamina densa, anchoring fibrils, hemi-desmosomes, distinctive collagens, etc.

3. adventitial dermis

a. fibrous component of papillary dermis

b. fibrous component of adnexal adventitia

c. perivascular adventitia

d. perineural adventitia

e. elastic component

f. mucinous matrix

4. reticular dermis (structural components)

a. collagenous component

b. elastic component

c. interstitial (mucinous) component

5. reticular dermis (blood supply)

a. superficial plexus

b. deep plexus

c. lymphatics

6. subcutis (structural components)

a. fibrous component (septa)

b. adipose tissue

c. interstitial matrix

7. subcutis (blood supply)

a. septal plexus

b. lobular plexus

c. lymphatic plexus

THE INFLUENCE OF MICROANATOMIC COMPARTMENTS ON PATTERNS OF INFLAMMATION IN THE SKIN

In the interpretation of patterns of inflammation in the skin, attempts have been made to compartmentalize real and virtual images by giving attention to anatomic limits for the distribution of infiltrates. In this manner, it is possible to speak of infiltrates that are limited to the superficial portions of the dermis; infiltrates that are superficial and deep, and those that are deep. This approach relies on the distribution of infiltrates in relationship to the depth to which perivascular infiltrates extend, without assigning significance to the complex immunologic processes which determine why one of many potential sites is prone to attract inflammatory cells. In such an approach, depth to which infiltrates extend is an indication of the extent of infiltration along the vascular plexus without attention to specific anatomic compartments.

In addition to the microanatomic divisions and components, the types and distribution of reacting cells are to be evaluated in the interpretation of inflammatory diseases. In practice, across a range of diverse clinical settings, the histologic patterns of many inflammatory disorders have a basic sameness. Often the distribution of inflammatory infiltrates provides significant clues which serve to refine the commonness of the cellular response. In these refinements, the limits for the distribution of the inflammatory infiltrates commonly are defined by the localization of antigens, or antigen-antibody complexes; the primary sites of injury usually are defined by the localization of antigens and antigen-antibody complexes.

THE EPIDERMIS AND RESPONSES TO INFLAMMATION

TERMINAL DIFFERENTIATION: The epidermis has multiple roles. It is responsible for the formation of an impervious barrier along the skin surface. To this end, a portion of the epidermis is dedicated to a programmed, native form of cell death. For individual cells, the process (i.e., terminal differentiation) leading to the death of cells is manifested by an increase in the density, and in the amount of fibrils in the cytoplasm of committed keratinocytes. In the process of normal terminal differentiation, keratinocytes are progressively compacted to eventually become flattened, fibril-rich lamellae which collect along the surface of the skin. In this progressive alteration in the shape and fluidity of the cytoplasm of the committed cells, the interstitial spaces are obliterated by the formation of lipid membranes. The deposits of lipids are derived from specialized cellular organelles, the keratinosomes or Odland bodies. In addition, nuclei of the committed cells become densely compacted and progressively smaller. In normal progressions, cells move from the stratum malphigii to the granular layer; they then contribute to the keratin layer; in the process, the nuclei of the dying keratinocytes undergo lysis. The keratin layer is either loosely laminated, or more densely compacted.

The portion of the epidermis dedicated to terminal differentiation can be characterized as the superficial keratinocytic unit. The viable cells of the superficial unit generally are polygonal and have acidophilic cytoplasm. Their long axis is parallel to the surface of the skin, and tonofibrils are prominent in the cytoplasm. In this process of terminal differentiaion, the most superficial, viable cells are distinguished by deeply basophilic granules (keratohyalin) in their cytoplasm; such cells are granular cells.

BASAL EPIDERMAL UNIT (THE RESERVE UNIT): The remaining portion of the epidermis, between the superficial unit and the basement membrane, is the basal unit. It forms an interface with the dermis at the level of the basement membrane. Its contour at this interface is an accommodation that is readily modified in response to the various stresses to which the epidermis is commonly exposed. The basal unit forms the conduit for the transport of metabolites from the dermis into the epidermal domain. The fluidity of the interstitium of the basal unit of the epidermis is ideally suited for the transport of metabolites; it also provides for some elasticity in response to forces - forces that are generated in the environment, and physically impact upon the surface of the skin. The role of basal keratinocytes of the basal unit of the epidermis (that single layer of cells along the epidermal side of the basement membrane) is to maintain the integrity of the basement membrane, to contribute to the cohesive forces at the dermal-epidermal interface, to interact with both native basal melanocytes of the epidermis and migrant histiocytes, and, foremost, to contribute cells to the superficial unit of the epidermis at a rate commensurate with the exfoliation of keratinized cells along the surface of the skin. The cells of the basal unit tend to be rectangular. Their long axes tend to be perpendicular to the surface of the skin. Keratinocytes of the basal unit have basophilic cytoplasm. As a phenomenon of epidermal homeostasis, individual cells of the basal unit may die and undergo lysis; this form of cell death is homeostatic apoptosis.

LEVEL 2