Cutaneous pseudolymphoma (CPL) is a reactive polyclonal T- or B-cell lymphoproliferative process that develops in reaction to diverse known and un-known stimuli, which can be localized or disseminated in the skin. Pseudolymphomas are also denominated cutaneous lymphoid hyperplasia (CLH), which better describes their benign clinical course. Sarcomatosis cutis, lymphocytoma cutis, lymphadenosis benigna cutis, pseudolymphoma of Spiegler and Fendt, and actinic reticuloid are other accepted terminologies to describe CPL (1, 2). Most cases of CPL are of unknown origin. Reactive responses that can result in CPL include responses to contact dermatitis, lichenoid pigmented purpuric dermatosis, lichen sclerosus et atrophicus, the inflammatory stage of morphea, secondary syphilis, lupus panniculitis, arthropod reactions, nodular scabies, viral infections (orf, milker’s nodule, herpes simplex/zoster, and molluscum contagiosum), tattoo dye, vaccinations, trauma, jewellery for pierced ears, such as gold, acupuncture, infections with Borrelia burgdorferi or leishmaniasis, and drug reactions (3). Drugs associated with the development of CPL include anticonvulsants, antipsychotics, antihypertensives, cytotoxics, antirheumatics, antibiotics, anxiolytics, antihistamines, antiarrythmics, sex steroids, lipid-lowering agents, and more recently, anti-tumour necrosis factor (TNF)-α agents, tocilizumab, and cyclosporine (1, 4–6). Although they appear more often in the skin, pseudolymphomas have also been described in other organs, such as the eye, tongue, parotid gland, larynx, gastrointestinal tract, lung, kidney, and breast.
In order to diagnose CPL it is important to understand that neither clinical nor histological features alone allow correct classification as lymphoma or pseudolymphoma. Only a combination of clinical signs, histological features and the course of the disease can result in the correct diagnosis. Sometimes a careful drug history, serological tests and patch tests may help to distinguish CPL from lymphoma.
Nevertheless, and because progression of CPL to malignant lymphoma can occur, perhaps induced by persistent antigenic stimulation, regular follow-up of the patient is mandatory. However, progression to cutaneous lymphoma has been observed in only a minority of cases.
Clinical signs and course
Clinically, CPL may present as papules, infiltrated plaques and nodules, less frequently as persistent erythema or exfoliative erythroderma. Even though there is no single clinical feature that proves a malignant or benign lesion, multiple nodules or plaques substantiate the suspicion of a malignant lymphoma. Lymphadenopathy is also more suggestive for lymphoma. Nonetheless, the mixed type of B- and T-cell CPL may also show lymphadenopathy.
CPLs are a group of diseases that exhibit a lymphocyte-rich infiltrate, which either clinically and/or histologically simulate cutaneous lymphomas.
A wide range of causative agents has been described, and treatment may thus be difficult. Many different modalities have been reported. Following a systematic review of the literature of the last 25 years we suggest that treatment options should be chosen based on the specific aetiology. While there are a considerable number of publications on the histopathology and classification of CPL, reports on treatment options are lacking, with much of the published work not disclosing any information about successful treatments and (long-term) outcomes. More reports of cases of CPL are needed, whether successfully treated or not, in order to avoid publication bias under-reporting poor outcomes or overestimating the response rates. Randomized controlled trials are difficult due to the rarity of CPL, and a gold standard therapy cannot be suggested. Treatment choice should be made individually for each patient according to aetiology and localization. A large proportion of cases of CPL are idiopathic and, if no surgical excision is performed, watchful follow-up is highly recommended due to the possible progress of CPL to malignant lymphoma.