S4C12P4-Erythema Multiforme

S4C12P4-1: This pattern is lichenoid; it is fairly cell-rich, but just at the dermal-epidermal interface. Lymphocytes and histiocytes mingle among keratinocytes of the basal unit of the epidermis. To the left, inflammatory cells are collected in an irregular lytic defect of the epidermal domain. The infiltrates generally are mostly on the epidermal side of the basement membrane. Centrally, in the basal unit, keratinocytes have begun to form incomplete whorls about degenerating keratinocytes and associated inflammatory cells. Above this damaged basal unit, plump, acidophilic, pale keratinocytes have formed a whorl. Several necrotic cells (“apoptotic cells”) are isolated among the regenerating keratinocytes.  This whorl, in the superficial unit, is migrating upward in the epidermis in concert with less affected cells of the superficial unit of the epidermis; it has migrated out of the basal unit. Viable keratinocytes forming the whorl have committed to terminal differentiation; the cytologic feature of the cells forming the whorl are a histologic marker for cells committed to terminal differentiation. This is a lesion of erythema multiforme. Parakeratosis is not a regular feature of erythema multiforme; it presence at the surface of the skin probably is an marker for a lesion late in its evolution; it may reflect the severity of the reaction. Small clusters of extravasated red blood cells are fairly common.

S4C12P4-2: In this area of a lesion of erythema multiforme, the damage to the basal layer and the defensive response of the surviving epidermis has resulted in a pattern in which some cells, showing features indicating a committment to terminal differentiation, extend to the basement membrane zone. This quality may be less indicative of lysis of all basal keratinocytes, and more an indication that in many lichenoid reactions the host response is a transfer of cells from the physiologic state of basal unit homeostasis to one of reactive terminal differentiation. In the process, inter-cellular spaces are closed (formation of lipid rich, intercellular membranes) and keratinocytes begin the process of cell death that leads to the formation of an altered keratin layer. There are occasional necrotic keratinocytes in the basal layer of the epidermis. It is about these necrotic cells that surviving keratinocytes proliferate and then form migratory whorls. These whorls, in their migrations upward, carry the necrotic cells with them to the skin surface. The high component of histiocytes in the dermis is a characteristic feature of the infiltrates of erythema multiforme, but are also common in a variety of lichenoid reactions. The histiocytes are migratory forms; they appear as wavy, naked nuclei.

S4C12P4-3: In this localized area in the basal unit of the epidermis, the cytopathic changes are cytolytic and coagulative. Lymphoid cells and histiocytes intermingle among the keratinocytes. The whorls, that have formed about necrotic, pigmented keratinocytes, are in the nature of reparative changes. They effect a toilet of the damaged basal unit of the epidermis and facilitate the reparative process. In contrast to the kinetics of a lichen planus-like process, the necrotic debris in a lesion of erythema multiforme and in erythema multiforme-like processes is delivered to the surface, not the papillary dermis (as are the colloid bodies of a lichen planus-like reaction). This example of erythema multiforme is cell-poor at the dermal-epidermal interface.

S4C12P4-4: The papillary dermis at the dermal-epidermal interface is edematous in this lesion of erythema multiforme. Many of the cells in the zone of papillary dermal edema (zone of pallor) are migratory histiocytes. Degenerating basal keratinocytes and neighboring histiocytes are pigmented; the pigment serves as a marker for damaged basal keratinocytes. The necrotic cells of lytic defects in the basal unit and of whorls in the superficial unit are also pigmented. This feature identifies the necrotic keratinocytes as basal cells which, in response to the damaging effects of the lichenoid reaction, have lost their domain in the basal unit. They become clustered among viable cells of the superficial unit.

S4C12P4-5: This lesion of erythema multiforme shows small intra-epidermal vesicles. In the region of the red arrow, the defects have reticulated qualities. In the region of the blue arrow on the right, a portion of the vesicle is symmetrically rounded; it has spongiotic qualities. The green arrows point to areas of damage in the basal unit of the epidermis.

S4C12P4-6: Blue arrows identify areas of lichenoid reaction with damage to the basal unit (basal layer). The green arrow points to an intraepidermal vesicle which is reticulated and spongiotic. Focally, the papillary dermis is pale, widened, and edematous (erythema multiforme).

S4C12P4-7: Basal keratinocytes are shrunken and pigmented. The reticulated vesicular component is a result of ballooning and lysis of keratinocytes of the basal unit. Although the disease clinically was erythema multiforme , interestingly some of the nuclei contain acidophilic bodies compatible with condensed, intranuclear viral inclusions (red arrows). Cytolytic cytopathic changes are represented.

 

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