An approach to the interpretation of skin biopsies

The Lichenoid Reaction Pattern (“Interface Dermatitis”)

The lichenoid reaction pattern (“interface dermatitis”) (see Chapter 4 ) is characterized by epidermal basal cell damage, which may be manifested by cell death and/or basal vacuolar change (known in the past as “liquefaction degeneration”). The basal cell death usually presents in the form of shrunken eosinophilic cells, with pyknotic nuclear remnants, scattered along the basal layer of the epidermis ( Fig. 2.1 ). These cells are known as Civatte bodies. They are undergoing death by apoptosis, a morphologically distinct type of cell death seen in both physiological and pathological circumstances (see p. 50 ). Sometimes the basal cell damage is quite subtle, with only an occasional Civatte body and very focal vacuolar change. This is a feature of some drug reactions.

In the United States, the term interface dermatitis is used synonymously with the lichenoid reaction pattern, although it is not usually applied to the subtle variants. Its use in other countries is by no means universal. At other times, it is used for the morphological subset (discussed later) in which inflammatory cells extend into the basal layer or above. The term is widely used despite its lack of precision. It is warmly embraced as a diagnosis, but it is nothing more than a pattern, encompassing many clinical entities with diverse presentations, causes, and treatments.

A distinctive subgroup of the lichenoid reaction pattern is the poikilodermatous pattern , characterized by mild basal damage, usually of vacuolar type, associated with epidermal atrophy, pigment incontinence, and dilatation of vessels in the papillary dermis ( Fig. 2.2 ). It is a feature of the various types of poikiloderma (see p. 92 ).

The specific diagnosis of a disease within the lichenoid tissue reaction requires an assessment of several other morphological features, including the following:

• 1.

  The type of basal damage (vacuolar change is sometimes more prominent than cell death in lupus erythematosus, dermatomyositis, the poikilodermas, and drug reactions)

• 2.

  The distribution of the accompanying inflammatory cell infiltrate (the infiltrate touches the undersurface of the basal layer in lichen planus and its variants, early lichen sclerosus et atrophicus, and in disseminated superficial actinic porokeratosis; it obscures the dermoepidermal interface [so-called “interface dermatitis”] in erythema multiforme, paraneoplastic pemphigus, fixed drug eruptions, acute pityriasis lichenoides [PLEVA], acute graft-versus-host disease [GVHD], one variant of lupus erythematosus, and reactions to phenytoin [Dilantin] and other drugs; and it involves the deep as well as the superficial part of the dermis in lupus erythematosus, syphilis, photolichenoid eruptions, and some drug reactions)

• 3.

  The presence of prominent pigment incontinence (as seen in drug reactions, the poikilodermas, lichenoid reactions in dark-skinned people, and some of the sun-exacerbated lichen planus variants, such as lichen planus actinicus)

• 4.

  The presence of satellite cell necrosis (lymphocyte-associated apoptosis)—defined here as two or more lymphocytes in close proximity to a Civatte body (a feature of graft-versus-host reaction, regressing plane warts, subacute radiation dermatitis, erythema multiforme, and some drug reactions).

The diseases showing the lichenoid reaction pattern are listed in Table 2.1 .

The Psoriasiform Reaction Pattern

From a morphological standpoint, the psoriasiform tissue reaction (see Chapter 5 ) is defined as epidermal hyperplasia in which there is elongation of the rete ridges, usually in a regular manner ( Fig. 2.3 ).

It is acknowledged that this approach has some shortcomings because many of the diseases in this category, including psoriasis, show no significant epidermal hyperplasia in their early stages. Rather, dilated vessels in the papillary dermis and an overlying suprapapillary scale may be the dominant features in early lesions of psoriasis. Mitoses are increased in basal keratinocytes in this pattern, particularly in active lesions of psoriasis.

The psoriasiform reaction pattern was originally defined as the cyclic formation of a suprapapillary exudate with focal parakeratosis related to it. The concept of the “squirting dermal papilla” was also put forward with the suggestion that serum and inflammatory cells escaped from the blood vessels in the papillary dermis and passed through the epidermis to form the suprapapillary exudate referred to previously. This “concept,” although outmoded, is useful in considering early lesions of psoriasis in which dilated vessels and surface suprapapillary scale are often the only features. The epidermal hyperplasia that also occurs was regarded as a phenomenon secondary to these other processes .

Diseases showing the psoriasiform reaction pattern are listed in Table 2.2 .

The Spongiotic Reaction Pattern

The spongiotic reaction pattern (see Chapter 6 ) is characterized by intraepidermal intercellular edema (spongiosis) . It is recognized by the presence of widened intercellular spaces between keratinocytes, with elongation of the intercellular bridges ( Fig. 2.4 ). The spongiosis may vary from microscopic foci to grossly visible vesicles. This reaction pattern has been known in the past as the “eczematous tissue reaction.” Inflammatory cells are present within the dermis, and their distribution and type may aid in making a specific diagnosis within this group. This is the most difficult reaction pattern in which to make a specific clinico­pathological diagnosis; often a diagnosis of “spongiotic reaction consistent with …” is all that can be made.

The major diseases within this tissue reaction pattern (atopic dermatitis, allergic and irritant contact dermatitis, nummular dermatitis, and seborrheic dermatitis) all show progressive psoriasiform hyperplasia of the epidermis with chronicity ( Fig. 2.5 ). This change is usually accompanied by diminishing spongiosis, but this will depend on the activity of the disease. Both patterns may be present in the same biopsy. The psoriasiform hyperplasia is, in part, a response to chronic rubbing and scratching.

Six patterns of spongiosis can be recognized:

• 1.

  Neutrophilic spongiosis (where there are neutrophils within foci of spongiosis)

• 2.

  Eosinophilic spongiosis (where there are numerous eosinophils within foci of spongiosis)

• 3.

  Miliarial (acrosyringial) spongiosis (where the edema is related to the acrosyringium)

• 4.

  Follicular spongiosis (where the spongiosis is centered on the follicular infundibulum)

• 5.

  Pityriasiform spongiosis (where the spongiosis forms small vesicles containing lymphocytes, histiocytes, and Langerhans cells)

• 6.

  Haphazard spongiosis (the other spongiotic disorders in which there is no particular pattern of spongiosis).

The diseases showing the spongiotic reaction pattern are listed in Table 2.3(a) .

A seventh pattern, which is really a variant of haphazard spongiosis, combines epidermal spongiosis with subepidermal edema ( Fig. 2.6 ), which can vary from mild to severe, even forming subepidermal blisters. Its causes are listed in Table 2.3(b) .

The Vesiculobullous Reaction Pattern

In the vesiculobullous reaction pattern, there are vesicles or bullae at any level within the epidermis or at the dermoepidermal junction (see Chapter 7 ). A specific diagnosis can usually be made in a particular case by assessing three features—the anatomical level of the split, the underlying mechanism responsible for the split, and, in the case of subepidermal lesions, the nature of the inflammatory infiltrate in the dermis.

The anatomical level of the split may be subcorneal, within the stratum malpighii, suprabasal, or subepidermal. The mechanism responsible for vesiculation may be exaggerated spongiosis, intracellular edema and ballooning (as occurs in viral infections such as herpes simplex), or acantholysis. Acantholysis is the loss of coherence between epidermal cells. It may be a primary phenomenon or secondary to inflammation, ballooning degeneration (as in viral infections of the skin), or epithelial dysplasia. In the case of subepidermal blisters, electron microscopy and immunoelectron microscopy could be used to make a specific diagnosis in most cases. In practice, the subepidermal blisters are subdivided on the basis of the inflammatory cell infiltrate within the dermis ( Fig. 2.7 ). Knowledge of the immunofluorescence findings is often helpful in categorizing the subepidermal blistering diseases.

Table 2.4 lists the various vesiculobullous diseases, based on the anatomical level of the split and, in the case of subepidermal lesions, the predominant inflammatory cell within the dermis.