eMedicine Specialties > Dermatology > Lymphoma and Related Processes

Lymphocytoma Cutis

Christine J Ko, MD, Assistant Professor, Departments of Dermatology and Pathology, Yale University School of Medicine
Jon H Meyerle, MD, Assistant Professor, Department of Dermatology, Johns Hopkins University School of Medicine; Consulting Staff, Laboratory Director, Department of Dermatology, Walter Reed Army Medical Center and National Naval Medical Center; Earl J Glusac, MD, Professor, Departments of Pathology and Dermatology, Yale University School of Medicine

Updated: Oct 22, 2008

Introduction

Background

Lymphocytoma cutis is not a specific disease. Rather, it is a response to a variety of known and unknown stimuli that results in the accumulation of lymphocytes and other inflammatory cells in a localized region. Lymphocytoma cutis is known to simulate lymphoma, as reflected primarily by the histologic findings. However, it is a reactive process and generally has a benign course. When known, the inciting agent should be included in the diagnosis. The term lymphocytoma cutis or pseudolymphoma without modification should be reserved for idiopathic cases.

Related articles include Cutaneous B-Cell Lymphoma and Cutaneous T-Cell Lymphoma. Additionally, the Medscape Skin Cancer Resource Center may be of interest.

Pathophysiology

In lymphocytoma cutis, lymphocytes and other inflammatory cells are recruited to a localized area of the skin in response to known or unknown stimuli. Most cases are idiopathic. Lymphocytoma cutis is not considered a lymphocytic response to malignancy.

Cases with known etiologies involve a reaction to tattoo dye, jewelry (especially gold), arthropod bites, medications, folliculitis, trauma, infections (ie, with Borrelia burgdorferi, molluscum contagiosum), vaccinations, and acupuncture.

A discrete subset of lymphocytoma cutis, borrelial lymphocytoma, occurs primarily in Europe, in areas in which the Ixodes ricinus tick is endemic. This form of the disease is a response to an infection due to Borrelia burgdorferi subsp afzelius that is transmitted by a tick bite.¹

Frequency

United States

No data are available.

International

No data are available. The condition is uncommon but not rare. A discrete subset of lymphocytoma cutis, borrelial lymphocytoma, occurs primarily in Europe, in areas in which the I ricinus tick is endemic.

Mortality/Morbidity

Lymphocytoma cutis is not associated with mortality. It is rarely associated with morbidity other than minor pain or pruritus. It generally heals without scarring.

Race

No racial predilection is noted.

Sex

The female-to-male ratio in reported cases is approximately 2:1.

Age

Individuals of any age may be affected, but lymphocytoma cutis is most common in early adulthood.

The mean patient age at onset is 34 years. Approximately 8% of cases involve patients younger than 18 years.
Two thirds of patients are younger than 40 years at the time of biopsy.
Borrelial lymphocytoma is more common in children than adults and is most often observed in Europe.

Clinical

History

Patients present with a nodule or group of discrete nodules, usually with minimal associated symptoms.
Occasionally, pruritus or pain is noted.

Physical

Examination usually reveals a single nodule with a diameter of one to several centimeters.
Although the lesions may be soft, they are more often firm.
Typically, the lesions are red to purple but can be absent of color as well.
Approximately three quarters of the cases involve localized lesions.
- The remaining cases usually involve grouped papules in a single defined region.
- More disseminated cases are rare.
The most common site of involvement is the face (70%).
Next most common sites are the chest and upper extremities.
Lesions below the waist are uncommon.
Sites of predilection for Borrelial lymphocytoma are sites with low skin temperature, including the following:
Earlobes
Nipples and areolae
Nose
Scrotum

Causes

Most cases are idiopathic. Known inciting agents include the following:

Tattoo dye
Jewelry (eg, gold earrings)
Arthropod (insect and spider) bites
Medications²
Folliculitis
Trauma
Vaccinations
Materials that come into direct contact with the skin or are injected into the skin (eg, gold, aluminum)
Infection (eg, varicella-zoster virus, Borrelia species, molluscum contagiosum, Helicobacter pylori)
Sites where acupuncture needles were inserted

Differential Diagnoses

Lymphomatoid Papulosis
Syphilis

Workup

Laboratory Studies

Biopsy is necessary to establish a diagnosis of lymphocytoma and exclude cutaneous lymphoma.
An adequate sample is essential. The specimen should be obtained by extending well into the subcutis while avoiding crush artifact.

Other Tests

In some cases, the possibility of lymphoma cannot be excluded by means of histologic analysis and immunostaining. In such cases, analysis for immunoglobulin or T-cell receptor genetic rearrangements may provide additional helpful information.
- If a clone is identified, it increases the likelihood of lymphoma.
- The results of this test should not be considered definitive.
- Clonality is reported in occasional pseudolymphomas and may be absent in some lymphoma samples.
- Clinical-pathologic correlation remains the criterion standard in the differential diagnosis.^3,4,5
Antibodies to B burgdorferi may be identified in 50% of patients with borrelial lymphocytoma. The organism can be identified in tissue by means of polymerase chain reaction analysis.

Histologic Findings

Lymphocytoma cutis must be differentiated from lymphoma. Most cases of lymphocytoma cutis have a nodular inflammatory infiltrate and can simulate B-cell lymphoma.⁶ The key histologic features that suggest lymphocytoma cutis instead of lymphoma include the presence of a mixed infiltrate that includes histiocytes, eosinophils, and plasma cells, in addition to lymphocytes.⁷ In lymphocytoma cutis, the infiltrate tends to be top-heavy, whereas most lymphomas are centered in the deep dermis or subcutis. Samples of lymphocytoma cutis typically have germinal centers and tingible body macrophages (see Media File 5). Occasionally, 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 with a high MIB-1 + proliferative index. Staining for kappa and lambda light chains reveals a polyclonal pattern. Fresh, unfixed tissue may be required for adequate assessment of kappa and/or lambda labeling. Some cases have a T-cell histologic pattern. Changes include a bandlike infiltrate in the papillary dermis, which predominantly includes small lymphocytes with variable epidermotropism. Although these features mimic those of cutaneous T-cell lymphoma or mycosis fungoides, the clinical presentation is characteristic.⁸

Treatment

Medical Care

When the offending agent is known, its removal results in disease resolution.
Cases that occur as a result of infection should be treated appropriately.
In idiopathic cases, treatment is not mandatory.
In severe cases, local radiation therapy can be effective.
Some report a response to topical or injected corticosteroids as well as topical immunomodulators such as tacrolimus.
Patients with presumed lymphocytoma cutis in whom lymphoma cannot be excluded should be examined for the possibility of concurrent extracutaneous disease. Careful follow-up is required to evaluate the possible emergence of lymphoma.

Surgical Care

Surgical removal or cryosurgery may be effective in some cases.

Follow-up

Complications

Rare case reports describe evolution to lymphoma.
Histologically, a significant percentage of these cases may have represented lymphoma from the outset.

Prognosis

Spontaneous regression often occurs.
If the inciting agent is removed, the condition typically resolves.
Idiopathic cases tend to be chronic and indolent.
Local recurrence has been noted.

Patient Education

If the inciting stimulus is known, it should be avoided.
For excellent patient education resources, visit eMedicine's Skin, Hair, and Nails Center. Also, see eMedicine's patient education article Molluscum Contagiosum.

Multimedia

Media file 1: This example of lymphocytoma cutis shows a localized, erythematous-to-brown, ill-defined plaque.

Media file 2: Lymphocytoma cutis of the shoulder, composed of flesh-colored or erythematous nodules in small groups.

Media file 3: This photograph of lymphocytoma cutis caused by an arthropod bite shows an erythematous scaling patch of the scalp with localized secondary alopecia.

Media file 4: A mixed inflammatory infiltrate with germinal centers is indicative of lymphocytoma cutis.

Media file 5: Well-developed lymphoid follicles in a background of mixed inflammatory cells with small lymphocytes are typical of lymphocytoma cutis.

References

Colli C, Leinweber B, Müllegger R, Chott A, Kerl H, Cerroni L. Borrelia burgdorferi-associated lymphocytoma cutis: clinicopathologic, immunophenotypic, and molecular study of 106 cases. J Cutan Pathol. Mar 2004;31(3):232-40. [Medline].
Albrecht J, Fine LA, Piette W. Drug-associated lymphoma and pseudolymphoma: recognition and management. Dermatol Clin. Apr 2007;25(2):233-44, vii. [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].
Wantzin GL, Hou-Jensen K, Nielsen M, Petri J, Thomsen K. Cutaneous lymphocytomas: clinical and histological aspects. Acta Derm Venereol. 1982;62(2):119-24. [Medline].
van Vloten WA, Willemze R. The many faces of lymphocytoma cutis. J Eur Acad Dermatol Venereol. Jan 2003;17(1):3-6. [Medline].
Duncan SC, Evans HL, Winkelmann RK. Large cell lymphocytoma. Arch Dermatol. Oct 1980;116(10):1142-6. [Medline].
Geerts ML, Kaiserling E. A morphologic study of lymphadenosis benigna cutis. Dermatologica. 1985;170(3):121-7. [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].
Connors RC, Ackerman AB. Histologic pseudomalignancies of the skin. Arch Dermatol. Dec 1976;112(12):1767-80. [Medline].

Keywords

cutaneous B- or T-cell pseudolymphoma, cutaneous lymphoid hyperplasia, pseudolymphoma without modification, pseudolymphoma of Spiegler and Fendt, sarcoidosis of Spiegler and Fendt, cutaneous lymphomatous hyperplasia, lymphadenosis benigna cutis, cutaneous lymphoplasia, Ixodes ricinus, Borrelia burgdorferi subsp afzelius, varicella zoster, molluscum contagiosum

Contributor Information and Disclosures

Author

Christine J Ko, MD, Assistant Professor, Departments of Dermatology and Pathology, Yale University School of Medicine
Christine J Ko, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and International Society of Dermatopathology
Disclosure: Nothing to disclose.

Coauthor(s)

Jon H Meyerle, MD, Assistant Professor, Department of Dermatology, Johns Hopkins University School of Medicine; Consulting Staff, Laboratory Director, Department of Dermatology, Walter Reed Army Medical Center and National Naval Medical Center
Jon H Meyerle, MD is a member of the following medical societies: American Academy of Dermatology and Sigma Xi
Disclosure: Nothing to disclose.

Earl J Glusac, MD, Professor, Departments of Pathology and Dermatology, Yale University School of Medicine
Earl J Glusac, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Günter Burg, MD, Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, Switzerland
Günter Burg, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, International Society for Dermatologic Surgery, North American Clinical Dermatologic Society, and Pacific Dermatologic Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Daniel S Loo, MD, Associate Professor of Dermatology, Residency Program Director, Department of Dermatology, Tufts Medical Center
Daniel S Loo, MD is a member of the following medical societies: American Academy of Dermatology and Association of Professors of Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Further Reading