The biopsy in each of these conditions demonstrates a sawtooth rete ridge pattern with destruction of the basal layer, a band-like lymphoid infiltrate, and presence of Civatte bodies. Compact hyperkeratosis and beaded hypergranulosis are typically present. The cells of the stratum spinosum are enlarged and more eosinophilic than the normal epidermis. Vacuoles may be present in the lowest cells of stratum spinosum, but the basal layer is gone. An underlying band-like lymphoid infiltrate is common.

If neither parakeratosis nor eosinophils are noted, the changes are consistent with lichen planus. Lichenoid interface dermatitis with neither eosinophils nor parakeratosis may also be seen in BLK (lichen planus-like keratosis), lichenoid drug eruption, lichenoid GvHD, hypertrophic lupus erythematosus, and lichenoid regression of lentigo maligna. Clinical correlation is essential. Direct immunofluorescence (DIF) will distinguish hypertrophic lupus erythematosus (continuous granular band of immunoglobulins and complement plus cytoid bodies) from lichen planus (shaggy fibrin, cytoid bodies).

When parakeratosis is present, lichen planus is very unlikely. The differential diagnosis still includes BLK, lichenoid drug eruption, lichenoid GvHD, and lichenoid regression of a melanocytic lesion. Hypertrophic lupus erythematosus rarely demonstrates parakeratosis.

The presence of eosinophils strongly favors a diagnosis of lichenoid drug eruption. The presence of eosinophils weighs strongly against a diagnosis of lichen planus. They are rarely seen in hypertrophic lupus erythematosus, BLK, lichenoid GvHD, or lichenoid regression of a melanocytic lesion.

Fig 7-1 Interface versus spongiotic dermatitis (eos, eosinophils; PLEVA, pityriasis lichenoides et varioformis acuta; PLC, pleomorphic lobular carcinoma)

Pearl

An analogy that those with teenagers may appreciate:

• Lichen planus is like a strict parent: “You will not hang around with eosinophils or parakeratosis”

• Lichenoid drug eruption and the remaining lichenoid processes are more permissive: “You don’t have to have eosinophils or parakeratosis, but if you want to, it’s OK”

Fig 7-2 Lichenoid interface dermatitis

Late-phase (burnt-out) lichenoid dermatitis

Key features

• Effacement of the rete pattern

• Melanin pigment incontinence (melanoderma)

• Civatte bodies

Fig 7-3 Vacuolar interface dermatitis for comparison

Fig 7-4 Late-stage lichenoid dermatitis

Lichen planus

Key features

• Lichenoid interface dermatitis

• No parakeratosis or eosinophils

• Sawtooth rete ridges

Fig 7-5 Lichen planus

Lichenoid drug eruption

Key features

• Lichenoid interface dermatitis

• Typically has eosinophils

• Often has parakeratosis

Fig 7-6 Lichenoid drug eruption

Benign lichenoid keratosis

Key features

• Lichenoid interface dermatitis

• May have parakeratosis

• Rarely has eosinophils

• Solar lentigo commonly present at the margin

BLK usually presents as a solitary pearly pink macule on the trunk or an extremity. The biopsy is usually performed to rule out basal cell carcinoma. Most lesions represent lichenoid regression of benign solar lentigines. The earliest stage of evolution may show vacuolar interface dermatitis with a lymphocyte in every vacuole.

Fig 7-7 Benign lichenoid keratosis

Lichenoid graft-versus-host disease

Key features

• Lichenoid interface dermatitis

• May have parakeratosis

• Rarely has eosinophils

Fig 7-8 Lichenoid GvHD

Hypertrophic lupus erythematosus

Hypertrophic lupus erythematosus is lichenoid histologically. It is distinguished from lichen planus by the DIF pattern, occasional presence of basement membrane zone thickening or dermal mucin, and by clinical history and serologic findings. This is the form of chronic cutaneous lupus erythematosus that is most likely to give rise to invasive squamous cell carcinoma.

Fig 7-9 Hypertrophic lupus erythematosus

Lichenoid regression of lentigo maligna

Key features

• Lichenoid interface dermatitis

• Heavily sun-damaged skin

• Adjacent rete pattern may be effaced

• May have parakeratosis

• Rarely has eosinophils

Fig 7-10 Lichenoid regression within a lentigo maligna

Porokeratosis

Key features

• Cornoid lamella (column of parakeratosis at 45° angle, dyskeratotic cells below)

• Zone between cornoid lamellae may appear lichenoid or psoriasiform

Vacuolar interface dermatitis

Key features

• Basal layer intact

• Vacuoles within basal layer

• Rounded rete pattern

Vacuolar interface dermatitis with a lymphocyte in nearly every vacuole

Vacuolar interface dermatitis with a lymphocyte in nearly every vacuole is characteristic of mycosis fungoides (MF), pityriasis lichenoides, and the early evolving stage of a BLK. Rarely, a similar pattern may be seen in fixed drug eruption, lymphomatoid drug eruption, or lichen sclerosus.

Mycosis fungoides

The biopsy demonstrates epidermotropism of large atypical lymphocytes with little accompanying spongiosis. These lymphocytes show some tendency to form small aggregates and to line up along the dermal–epidermal junction. Papillary dermal fibrosis is prominent. The bare underbelly sign refers to the tendency for the superficial perivascular lymphoid infiltrate to predominate above the vessel, with few lymphocytes below the vessel. It has been likened to a vacuum cleaner sucking the lymphocytes towards the surface. Immunostaining and gene rearrangement studies can be helpful. Selective loss of CD7 expression in the atypical intraepidermal lymphocytes is a common finding. As the disease progresses from patch, to plaque, to tumor stage, atypical cells appear in the dermal infiltrate, and epidermotropism is lost.

Differential Diagnosis

The pattern of vacuolar interface dermatitis with a lymphocyte in every vacuole may also be seen in pityriasis lichenoides and the early stage of a BLK. The pattern of large dark nuclei with surrounding vacuoles at the dermal–epidermal junction may also be seen in lentigo maligna and lymphomatoid drug eruption.

Fig 7-11 Porokeratosis

Fig 7-12 Mycosis fungoides

Pityriasis lichenoides et varioliformis acuta (PLEVA)

Fig 7-13 Pityriasis lichenoides et varioliformis acuta (PLEVA)

The biopsy demonstrates vacuolar interface dermatitis with a lymphocyte in every vacuole. Keratinocyte necrosis, central ulceration, and crusting may be noted. Erythrocyte extravasation with transepidermal elimination of erythrocytes is common. The infiltrate is purely lymphoid, with a superficial and deep perivascular pattern. Prominent intravascular margination of neutrophils is typical. The infiltrate in PLEVA is characterized by CD8-positive cytotoxic T cells. A clone can often be detected by gene rearrangement studies.

Pityriasis lichenoides chronica

Key features

• Vacuolar interface dermatitis

• A lymphocyte in nearly every vacuole

• Transepidermal elimination of erythrocytes variable

Early stage of benign lichenoid keratosis

Key features

• Vacuolar interface dermatitis

• A lymphocyte in nearly every vacuole

Vacuolar interface dermatitis with vacuoles or cell death out of proportion to lymphocytes

Lupus erythematosus

Fig 7-14 Pityriasis lichenoides chronica

The features of discoid lupus erythematosus appear in a time-dependent fashion. Biopsies of acute lupus erythematosus show only vacuolar interface dermatitis. DIF will usually be negative at this stage. Subacute lesions of lupus erythematosus show vacuolar interface dermatitis, hyperkeratosis, and follicular plugging, as well as a variable dermal infiltrate. DIF is positive in about one-third of cases. Well-established discoid lesions (of at least 3 months’ duration) typically demonstrate strong DIF. Histologically, established discoid lupus erythematosus lesions are characterized by hyperkeratosis, follicular plugging, vacuolar interface dermatitis, basement membrane zone thickening, a patchy superficial and deep perivascular and periadnexal lymphoid infiltrate, and interstitial mucin. Underlying lupus panniculitis may be present.

Fig 7-15 Early benign lichenoid keratosis (BLK)

Fig 7-16 Acute lupus erythematosus

Fig 7-17 Subacute lupus erythematosus

Fig 7-18 Chronic discoid lupus erythematosus (BMZ, basement membrane zone)

Differential Diagnosis

1. Dermatomyositis may look identical to lupus erythematosus, although the former usually demonstrates epidermal atrophy.

2. Tumid lupus lacks interface changes.

3. Lichen striatus lacks dermal mucin.

4. Differential diagnosis of nodular lymphoid infiltrate – the seven Ls:

Lupus

Light (polymorphous light eruption): papillary dermal edema usually prominent

Lymphoma

Lymphocytoma cutis

Lichen striatus (eccrine coil involved like lupus)

Lymphocytic eruption of Jessner–Kanof

Lues (vacuolar interface dermatitis typically paired with elongation of rete, interstitial busy dermis, endothelial swelling, lymphocytes with ample cytoplasm or plasma cells

5. Viral exanthem (may have erythrocyte extravasation; lacks hyperkeratosis, papillary dermal fibrosis)

6. Drug eruption (may be mix of inflammatory patterns, lacks hyperkeratosis, papillary dermal fibrosis)

7. Phototoxic eruption (lacks hyperkeratosis, papillary dermal fibrosis)

Fig 7-19 Polymorphous light eruption

Fig 7-20 Lichen striatus

Polymorphous light eruption

Key features

• Plaque variant has papillary dermal edema and dense perivascular lymphoid infiltrate

• Papulovesicular variant is spongiotic

Lichen striatus

Key features

• Blaschkoid interface dermatitis

• Lymphoid aggregates perivascular and in eccrine coil

Dermatomyositis

Key features

• Similar to lupus erythematosus

• Typically demonstrates epidermal atrophy

Fig 7-21 Dermatomyositis

Syphilis

Key features

Vacuolar interface dermatitis together often with slender acanthosis

• Vacuolar interface dermatitis together with an interstitial pattern (busy dermis)

• Interface-predominant pattern may have an atrophic epidermis

• Neutrophils in the stratum corneum

• Plasma cells present in about two-thirds of cases

• Endothelial swelling obliterates the lumen of small vessels

• Perivascular lymphocytes and histiocytes with visible cytoplasm

Fig 7-22 Lues (syphilis)

Erythema multiforme

Key features

• Acute (normal) basket-weave stratum corneum

• Individual necrotic keratinocytes

• May progress to confluent epidermal necrosis

• Cell death out of proportion to lymphocytes

• In late stage, bulla and re-epithelialization occur

The typical picture of erythema multiforme includes a normal stratum corneum with “death and squalor” in the underlying epidermis. In the acute stage, the infiltrate is purely lymphoid.

Fig 7-23 Erythema multiforme

Toxic epidermal necrolysis

Key features

• Looks like erythema multiforme

Fig 7-24 Toxic epidermal necrolysis

Paraneoplastic pemphigus

Key features

• Acantholysis may or may not be present

• May be lichenoid

• May look like erythema multiforme (see Chapter 9)

Fig 7-25 Paraneoplastic pemphigus

Fixed drug eruption

The most important diagnostic feature is the mismatch between the normal stratum corneum and chronic changes in the superficial dermis. Fixed drug eruption is episodic. The biopsy is likely to occur during an acute inflammatory phase, but dermal changes from past episodes are present. The result is a normal stratum corneum, consistent with an acute process. In contrast, there is papillary dermal fibrosis, consistent with a chronic process. Pigment has had time to be carried to a perivascular location. The polymorphous infiltrate typically includes eosinophils and may include neutrophils.

Pearl

The normal stratum corneum whispers, “Look at me, I’m an acute process.” The papillary dermal fibrosis and pigment around vessels respond, “Liar! There are chronic changes in the dermis.”