Cutaneous pseudolymphoma
Cutaneous lymphoid hyperplasia; lymphocytoma cutis (Spiegler-Fendt lymphocytoma — historic term, where "sarcoid" is used in the pre-Boeck sense of "sarcoma-like"; not related to granulomatous sarcoidosis); benign cutaneous lymphoid hyperplasia; pseudo-Sézary; pseudo-MF
Cutaneous pseudolymphoma is a benign reactive lymphoid proliferation of the skin that โ despite a histological appearance closely resembling cutaneous lymphoma โ pursues a benign clinical course and frequently resolves with removal of the precipitating cause. It is the most clinically important "great mimic" in cutaneous lymphoma practice: misdiagnosis as lymphoma leads to unnecessary chemotherapy, while misdiagnosis of true cutaneous lymphoma as pseudolymphoma leads to undertreatment. Common precipitants include Borrelia burgdorferi infection (Borrelial lymphocytoma cutis), drugs (anticonvulsants, antibiotics, antihypertensives, biologic agents), tattoo pigment (especially red), vaccination, insect bite, contact allergens and acupuncture. Diagnostic workup combines clinical correlation, comprehensive histology and immunophenotyping, T- and B-cell receptor clonality testing and staging to exclude true lymphoma. Many cases resolve spontaneously or with offending-cause removal; refractory cases respond to topical / intralesional steroids, antimicrobials, photodynamic therapy or low-dose radiotherapy.
Common precipitants
- Infections โ Borrelia burgdorferi (Borrelial lymphocytoma โ earlobe, nipple, scrotum), Treponema pallidum (secondary syphilis); molluscum contagiosum, herpes zoster.
- Drugs โ anticonvulsants (phenytoin, carbamazepine, lamotrigine), antibiotics (ฮฒ-lactams, dapsone), antihypertensives (ACEi, calcium channel blockers, ฮฒ-blockers), antidepressants (fluoxetine), biologics (anti-TNF), allopurinol, statins, ranitidine.
- Tattoos โ particularly red ink (cinnabar / mercury sulphide); also blue, black, green; lymphoid reactions can persist for years.
- Vaccinations / hyposensitisation injections / acupuncture.
- Insect / arthropod bites โ persistent nodular insect-bite reaction; mosquito, flea, tick, scabies, bedbug.
- Contact allergens โ gold, nickel.
- Idiopathic โ substantial proportion remain without identifiable cause.
Clinical features
- Solitary or grouped erythematous to violaceous papules, plaques or nodules.
- Predilection for face (cheek, nose, earlobe), upper trunk and arms.
- Asymptomatic or mildly itchy.
- Onset days to weeks after the precipitant.
- Often confused clinically with cutaneous B-cell lymphoma (PCMZL / PCFCL), CTCL plaque, sarcoidosis, leukaemia cutis, deep granuloma annulare.
Histology & clonality
- Dense dermal lymphoid infiltrate with reactive germinal centres ยฑ follicular dendritic-cell network.
- "Top-heavy" โ superficial-predominant infiltrate; contrasts with cutaneous B-cell lymphoma which is "bottom-heavy".
- Mixed B and T cells in physiological proportions; admixed plasma cells, eosinophils, histiocytes.
- Polyclonal light chain restriction (kappa : lambda ratio normal).
- T-cell and B-cell receptor clonality testing โ polyclonal in most pseudolymphomas, but monoclonality does not exclude pseudolymphoma (~10โ20% show clonality, particularly in long-standing or drug-induced cases).
- Differential by histology: cutaneous marginal-zone lymphoma, cutaneous follicle-centre lymphoma, MF (epidermotropism present), pcALCL (CD30+ large blasts).
Diagnostic workflow
- Detailed history โ drugs, infections, tattoos, vaccinations, insect bites, occupational exposures.
- Punch / excisional biopsy of representative lesion.
- Comprehensive immunohistochemistry, flow cytometry, T- and B-cell receptor clonality testing.
- Borrelia serology and PCR if Borrelial lymphocytoma is suspected (earlobe, scrotum, nipple location).
- Drug rechallenge contraindicated; instead, drug withdrawal trial.
- Staging (CT chest/abdomen/pelvis, FBC, LDH, peripheral blood flow cytometry) to exclude systemic lymphoma in any monoclonal or persistent case.
- Refer to cutaneous lymphoma MDT for any equivocal case.
Management
- Remove the precipitant โ discontinue offending drug, treat infection, consider tattoo excision.
- Antimicrobials โ doxycycline / amoxicillin for Borrelial lymphocytoma.
- Topical or intralesional corticosteroids.
- Topical tacrolimus.
- Cryotherapy, surgical excision, photodynamic therapy.
- Low-dose involved-field radiotherapy (4โ8 Gy) for refractory cases.
- Hydroxychloroquine, methotrexate โ for refractory generalised disease.
- Long-term follow-up โ small but real proportion (~5%) progress to true cutaneous lymphoma over years.
Prognosis
Generally benign with resolution after cause removal or symptomatic treatment. A small proportion (~5%) develop frank cutaneous lymphoma during long-term follow-up โ particularly cases that are clonal at presentation or fail to resolve despite cause removal. Long-term surveillance (annual review for 3โ5 years) is recommended.
References
- Ploysangam T et al. Cutaneous pseudolymphomas. J Am Acad Dermatol; 1998.
- Bergman R. Pseudolymphoma and cutaneous lymphoma โ facts and controversies. Clin Dermatol; 2010.
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