AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Pseudolymphoma is not a specific disease but rather an inflammatory response to known or unknown stimuli that results in a lymphomatous-appearing but benign accumulation of inflammatory cells. Resemblance to lymphoma is usually most apparent histologically, but some examples may also mimic lymphoma clinically. When known, the inciting agent should be included within the diagnosis. The term pseudolymphoma without modification should be reserved for idiopathic cases.

Localized, nodular pseudolymphomas are more common and typically mimic B-cell lymphoma (for further discussion, see Lymphocytoma Cutis). A variety of specific diseases are sometimes referred to as pseudolymphomas simply because they may resemble lymphoma. These disorders often show broad patches and plaques and often mimic cutaneous T-cell lymphoma. Examples include actinic reticuloid, lymphomatoid contact dermatitis, and lymphomatoid drug eruptions (see Images 2-3).

Pathophysiology

In persons with pseudolymphoma, lymphocytes and other inflammatory cells are recruited to the skin in response to known or unknown stimuli. Most cases are idiopathic. Cases with known etiology include reactions to tattoo dyes, jewelry (especially gold), insect bites, medications, folliculitis, trauma, infections, vaccinations, and contactants. A discrete subset of pseudolymphoma, borrelial lymphocytoma, primarily occurs in Europe in areas endemic for the tick Ixodes ricinus. It is a response to infection by Borrelia burgdorferi subsp afzelius conferred by a tick bite. Another subset of pseudolymphoma is the result of an unusual systemic response to medications, typically anticonvulsants (see Drug-Induced Pseudolymphoma Syndrome).

Frequency

International

No frequency data are available; the condition is uncommon but not rare.

Mortality/Morbidity

Pseudolymphoma is not associated with mortality. Localized variants rarely result in morbidity other than minor pain or pruritus. Rare cases have been described in which patients' pseudolymphoma has evolved into cutaneous lymphoma.

Race

Although 90% of reported patients with pseudolymphoma are white, racial predilection has not been established.

Sex

In reported cases of localized pseudolymphoma, the female-to-male ratio is approximately 2:1. No significant epidemiologic data are available regarding entities in the T-cell pattern pseudolymphoma spectrum.

Age

Individuals of any age may be affected, but localized, nodular pseudolymphoma is most common in early life. The mean age of onset is 34 years. Two thirds of patients are younger than 40 years at the time of biopsy. Approximately 8% of cases involve patients younger than 18 years. Borrelial pseudolymphoma is more common in children than in adults.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

• Patients with B-cell pattern pseudolymphoma present with complaints of a nodule or a group of discrete nodules, usually with minimal associated symptoms.
• Occasionally, cases present with pruritus or pain.
• Patients with T-cell pattern disease usually present with broader patches, which are often symptomatic.

Physical

• Examination of patients with B-cell pattern pseudolymphoma usually reveals a single nodule, from one to several centimeters in diameter. Although the lesions may be soft, they are more often firm. Typically, the lesions are red to purple in color, but they may show no coloration. Approximately three quarters of cases are localized. The remaining cases usually show grouped papules in a single defined region. More disseminated cases are rare. The most common site of involvement is the face (70%) followed by the chest and the upper extremities. Lesions are infrequent below the waist.
• Sites of predilection for borrelial pseudolymphoma include the earlobe, the nipple, the areola, the nose, and the scrotum (sites of low skin temperature).
• Patients with T-cell pattern pseudolymphoma typically present with broad, erythematous patches and/or plaques (see Image 1). Pseudolymphomatous actinic reticuloid affects sun-exposed areas. Lymphomatoid contact dermatitis demonstrates lesions in areas where the inciting agent has come in contact with the skin.

Causes

Most cases are idiopathic. Known inciting agents include tattoo dyes, jewelry (eg, gold earrings), insect bites, medications, folliculitis, trauma, vaccinations, irritants, and infection (eg, varicella-zoster virus, Borrelia species, molluscum contagiosum).

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Actinic reticuloid
Basal cell epithelioma (other adnexal tumors)
Lymphoma
Malignant B-cell lymphoma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Tests

• In some cases, the possibility of lymphoma cannot be excluded by histologic analysis. In such cases, analysis for immunoglobulin or T-cell receptor gene rearrangements may provide additional helpful information. If a clone is identified, it increases the likelihood of lymphoma. However, this test should not be considered definitive. Clonality has been documented in occasional pseudolymphomas and may be absent in some lymphoma samples. Clinical-pathologic correlation remains the criterion standard in this differential diagnosis.
• In patients with borrelial pseudolymphoma, antibodies to B burgdorferi may be identified in 50% of cases. Additionally, the organism may be identified in tissue via polymerase chain reaction (PCR) analysis.

Procedures

• Biopsy is necessary to establish a diagnosis of pseudolymphoma. An adequate sample extending well into the subcutis with avoidance of crush artifact is essential.

Histologic Findings

Lymphocytoma cutis must be differentiated from lymphoma. Most examples simulate B-cell lymphoma. The key histologic features that favor pseudolymphoma over lymphoma include the presence of a mixed infiltrate that includes histiocytes, eosinophils, and plasma cells, in addition to lymphocytes (see Image 4). The infiltrate in lymphocytoma cutis tends to be more superficially located, while most lymphomas are centered in the deep dermis or the subcutis. Lymphocytoma cutis typically shows germinal centers and tingible body macrophages. Occasional large lymphoid cells may be present; however, they rarely dominate the histologic picture.

Immunohistochemical staining may also be useful and generally shows a mixed B-cell and T-cell population. Staining for kappa and lambda light chains shows a polyclonal pattern of staining. Fresh, unfixed tissue may be required for adequate assessment of kappa/lambda labeling.

Some cases show a T-cell histologic pattern. Changes include a bandlike infiltrate in the papillary dermis, predominantly of small lymphocytes, with variable epidermotropism. Although these features mimic cutaneous T-cell lymphoma/mycosis fungoides, the clinical presentation is often characteristic.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

When the offending agent is known, its removal results in resolution. Cases documented to occur as a result of infection should be appropriately treated. In idiopathic cases, treatment is not mandatory. Cures may be affected via surgical removal, cryosurgery, or local irradiation. Some reports have noted a response to topical or injected corticosteroids and topical immunomodulators such as tacrolimus.

Patients with presumed pseudolymphoma in which the possibility of lymphoma cannot be excluded should be evaluated for the possibility of concurrent extracutaneous disease and followed for possible emergence of lymphoma.

Surgical Care

Simple excision of the involved site can be curative in some cases.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Drug Name	Betamethasone 0.05% Cream or Ointment (Diprolene, Betatrex)
Description	For inflammatory dermatosis responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability.
Adult Dose	Apply thin film bid for up to 2 wk
Pediatric Dose	<12 years: Not recommended
Contraindications	Hypersensitivity; viral, fungal, and bacterial skin infections
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Can cause atrophy of the skin with prolonged application; systemic absorption of topical steroids has produced HPA-axis suppression, glycosuria, hyperglycemia, and symptoms of Cushing syndrome in some patients, especially with prolonged use over wide body surface areas

Drug Name	Clobetasol (Temovate)
Description	Class I superpotent topical steroid; suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction.
Adult Dose	Apply bid for up to 2 wk; not to exceed 50 g/wk
Pediatric Dose	<12 years: Not recommended
Contraindications	Documented hypersensitivity; viral or fungal skin infections
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Can cause atrophy of the skin with prolonged application; systemic absorption of topical steroids has produced HPA-axis suppression, glycosuria, hyperglycemia, and symptoms of Cushing syndrome in some patients, especially with prolonged use over wide body surface areas

Drug Name	Fluocinonide cream or ointment 0.05% (Fluonex, Lidex)
Description	High-potency topical corticosteroid that inhibits cell proliferation; is immunosuppressive and anti-inflammatory.
Adult Dose	Apply sparingly bid for up to 2 wk
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; fungal, viral, or bacterial skin infections
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Can cause atrophy of the skin with prolonged application; systemic absorption of topical steroids has produced HPA-axis suppression, glycosuria, hyperglycemia, and symptoms of Cushing syndrome in some patients, especially with prolonged use over wide body surface areas

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Complications

• Occasional case reports have described evolution to lymphoma. A significant percentage of these cases may have represented histologically subtle lymphoma from the outset.

Prognosis

• If the offending agent is removed, resolution is achieved.
• Idiopathic examples tend to be chronic and indolent.
• Spontaneous regression may occur over the course of months or a few years.
• Recurrence has been noted.

Patient Education

• If the inciting stimulus is known, it should be subsequently avoided.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  This localized example of pseudolymphoma shows an ill-defined, thin, erythematous plaque.
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Media type:  Photo

Media file 2:  Pseudolymphomatous drug eruption due to captopril, marked by erythematous to purple papules, patches, and plaques.
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Media type:  Photo

Media file 3:  This erythrodermic pseudolymphoma (T-cell pattern) typifies drug-induced pseudolymphoma, which is most often secondary to anticonvulsant therapy.
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Media type:  Photo

Media file 4:  Biopsy specimens of pseudolymphoma vary substantially, but they most often exhibit a mixed inflammatory infiltrate with prominent lymphoid follicle formation.
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Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

• Braun RP, French LE, Felman R, et al. Cutaneous pseudolymphoma, lymphomatoid contact dermatitis type, as an unusual cause of symmetrical upper eyelid nodules. Br J Dermatol. 2000;143(2):411-4. [Medline].
• Brodell RT, Santa Cruz DJ. Cutaneous pseudolymphomas. Dermatol Clin. Oct 1985;3(4):719-34. [Medline].
• Burg G, Kerl H, Schmoeckel C. Differentiation between malignant B-cell lymphomas and pseudolymphomas of the skin. J Dermatol Surg Oncol. Apr 1984;10(4):271-5. [Medline].
• Choi TS, Doh KS, Kim SH, et al. Clinicopathological and genotypic aspects of anticonvulsant-induced pseudolymphoma syndrome. Br J Dermatol. 2003;148(4):730-6. [Medline].
• Connors RC, Ackerman AB. Histologic pseudomalignancies of the skin. Arch Dermatol. Dec 1976;112(12):1767-80. [Medline].
• Geerts ML, Kaiserling E. A morphologic study of lymphadenosis benigna cutis. Dermatologica. 1985;170(3):121-7. [Medline].
• Gutermuth J, Audring H, Roseeuw D. Disseminated cutaneous B-cell lymphoma mimicking pseudolymphoma over a period of six years. Am J Dermatolopathol. 2004;26(3):225-9. [Medline].
• Kempf W, Dummer R, Burg G. Approach to lymphoproliferative infiltrates of the skin. The difficult lesions. Am J Clin Pathol. Jan 1999;111(1 Suppl 1):S84-93. [Medline].
• Maubec E, Pinquier L, Viguier M, et al. Vaccination-induced cutaneous pseudolymphoma. J Am Acad Dermatol. 2005;52(4):623-9. [Medline].
• Ploysangam T, Breneman DL, Mutasim DF. Cutaneous pseudolymphomas. J Am Acad Dermatol. Jun 1998;38(6 Pt 1):877-95; quiz 896-7. [Medline].
• Rijlaarsdam U, Willemze R. Cutaneous pseudo-T-cell lymphomas. Semin Diagn Pathol. May 1991;8(2):102-8. [Medline].

Article Last Updated: Sep 12, 2006