Though herpes virus–associated pseudolymphoid proliferations are commonly linked to immunosuppression, they can be seen in immunocompetent subjects as well. The clinical presentation ranges from indurated erythematous plaques or nodules with or without accompanying vesicles, to small discrete papules (folliculitis).^1,2 These lesions are usually asymptomatic, but may be associated with pruritus, mild pain, or tenderness. The lesions may be clinically stable, progressively expand, or even wax and wane over time. In a review of 65 biopsies of cutaneous eruptions associated with herpes viruses, Leinweber et al.³ identified that approximately a third exhibited dense superficial and deep perivascular and periadnexal and interstitial dermal lymphoid infiltrates (Fig. 50-1A). In several of these cases, the typical viral cytopathic effects including amphophilic or eosinophilic intranuclear viral inclusions with margination of host chromatin, multinucleation, molding of the multiple nuclei, and ballooning degeneration of keratinocytes were only focal, involving isolated epidermal or adnexal cells (Fig. 49-1B).

The dermal infiltrates were composed predominantly of CD3⁺, CD4⁺, or CD8⁺ T lymphocytes, and CD20⁺ B lymphocytes were usually fewer in number.³ CD56 and TIA1 expression was also fairly common. Numerous atypical mononuclear cells with enlarged, hyperchromatic, convoluted nuclei were seen frequently; most of which were CD30⁺. In cases of herpetic folliculitis, the formation of germinal centers can occur with the presence of large centroblast-like CD20⁺ cells.⁴ Molecular studies using PCR for T-cell receptor-γ gene revealed polyclonal population in 50% and a monoclonal pattern in 25% of all tested cases; in which, expression of HSV DNA was confirmed as well.³

Cutaneous lymphoid infiltrates have also been reported in the setting of varicella-zoster inflammatory reactions, particularly in immunosuppressed patients.^5,6 In a case of post–zoster folliculitis, though monoclonal B- and T-lymphocyte proliferations were identified, there was prompt resolution of the lesions after antiviral therapy.⁷ VZV DNA could be demonstrated in some of these cases by PCR or in situ hybridization.⁶ In patients with HIV, anogenital HSV-2 infections often present as pseudolymphomas composed of dense dermal infiltrate composed predominately of polyclonal plasma cells as well as CD8⁺ T lymphocytes and can be difficult to control even with antiviral therapy.⁸

Patients with chronic lymphocytic leukemia are prone to exaggerated cutaneous reactions and can rarely present with erythematous papules or plaques at sites of prior herpes viral infections, representing an isomorphic phenomenon.⁹ Histologically, there is a dense dermal and subcutaneous lymphoid infiltrate composed of CD20⁺CD43⁺ neoplastic B lymphocytes, implicating cutaneous involvement of the patient’s leukemic process and not a pseudolymphoid reaction.

MCV typically induces self-limiting lesions, which are characterized histologically by hyperplastic epidermis composed of keratinocytes containing large intracytoplasmic inclusions that compress the nucleus against the cytoplasmic membrane, with almost no immune response.¹⁰ Cases of MCV folliculitis have also been described in the absence of epidermal involvement.¹¹ Rarely, a dense dermal inflammatory infiltrate composed of mononuclear cells has been described in association with trauma to the lesion, which may lead to release of the viral particles into the dermis (Fig. 49-1C). Such an immune response may also be spontaneous and often precedes clinical clearance of the lesions and was first described in 1977.¹² The inflammatory infiltrate is composed predominantly of CD3⁺CD8⁺ cytotoxic T cells admixed with CD8⁺CD56⁺ natural killer cells with a small fraction of CD20⁺ B lymphocytes, rare plasma cells, and eosinophils.¹³ CD30⁺ large atypical cells with vesicular nuclei and prominent nucleoli are also seen in variable numbers dispersed through the infiltrate or in clusters^14,15 (Fig. 50-1D). In addition, CD123⁺CD11c⁺CD16⁺ plasmacytoid dendritic cells are also present.¹⁶ Molecular studies reveal polyclonal populations of T and B lymphocytes.

Patients with advanced HIV infection may present with generalized erythroderma or indurated plaques and nodules similar to mycosis fungoides.^17,18 In contrast to mycosis fungoides, the lesions tend to be photo-distributed, commonly involving the extremities and face.¹⁷ Histologically, the lesions are characterized by superficial and mid-dermal mononuclear infiltrate composed predominantly of small-to-medium–sized lymphocytes admixed with eosinophils and plasma cells. There is a predominance of CD3⁺CD8⁺ lymphocytes that may have specific cytotoxicity against cells that express HIV1 Gag and Pol gene products.^19,20 In some cases, CD4⁺ cells may also be present in significant numbers. CD7 expression is usually preserved at least in a fraction of the cells. T-cell receptor rearrangements are not common. Recent reports have shown regression of these lesions after highly active antiretroviral therapy (HAART)²¹ or methotrexate therapy.¹⁹ In addition, patients with HIV are also prone to development of cutaneous lymphoid infiltrates in association with other viral infections.⁸