eMedicine Specialties > Dermatology > Lymphoma and Related Processes

Lymphomatoid Papulosis

Author: John A Zic, MD, Director of Cutaneous Lymphoma Clinic, Assistant Professor, Division of Dermatology, Vanderbilt University Medical Center
Contributor Information and Disclosures

Updated: Mar 20, 2008

Introduction

Background

Lymphomatoid papulosis (LyP) is a chronic papulonecrotic or papulonodular skin disease with histologic features suggestive of a malignant lymphoma. The disease is characterized by recurrent crops of pruritic papules at different stages of development that predominantly arise on the trunk and limbs. The papules heal spontaneously over 1-2 months, usually leaving slightly depressed oval scars.

The term lymphomatoid papulosis originally was used by Macaulay1 in 1968 to describe "a self-healing rhythmical paradoxical eruption, histologically malignant but clinically benign." Due to the typical waxing and waning clinical course, LyP was previously considered a pseuodolymphomatous inflammatory process. However, the classification system for cutaneous lymphomas has evolved rapidly, and, during consensus meetings in 2003-2004, the World Health Organization—European Organization for Research and Treatment of Cancer (WHO-EORTC) classification grouped LyP among the indolent cutaneous T-cell lymphomas. The rationale for classifying LyP as a cutaneous lymphoma is its association with other malignant lymphoproliferative disorders; however, some experts hesitate to classify this chronic skin disease as a true malignancy because of its spontaneous resolution and benign clinical course.2,3,4

LyP is part of a spectrum of CD30 (Ki-1)–positive cutaneous lymphoproliferative diseases (CD30+ LPDs), including LyP, primary cutaneous anaplastic large cell lymphoma (pcALCL), and borderline CD30+ lesions.

The eMedicine articles Malignant Melanoma (dermatology focus), Malignant Melanoma (oncology focus), Cutaneous T-Cell Lymphoma, and Lymphoma, Cutaneous T-Cell also may be of interest.

Additionally, the Medscape CME course Understanding the Evolving Role of Immunotherapy in the Treatment of Malignant Melanoma and Melanoma Resource Center may be helpful.

Pathophysiology

The CD30 antigen is a type 1 transmembrane glycoprotein of the tumor necrosis factor receptor superfamily. In addition to the CD30+ lymphoproliferative diseases, malignant lymphomas such as Hodgkin disease (HD), node-based systemic anaplastic large cell lymphoma (ALCL), and mycosis fungoides (MF) with large cell transformation may express the CD30 antigen.

The pathophysiology of CD30+ LPDs, including LyP, is largely unknown. CD30 signaling is known to have an effect on the growth and survival of lymphoid cells, and one hypothesis is that genetic instability and accumulated genetic defects may have a role in the development of LyP and the progression to associated neoplasms. In a recent study, the 30M377 allelic form of the CD30 promoter microsatellite repressive element was associated with the development of LyP, and the 30M362 allelic form was associated with progression to other CD30+ lymphomas in LyP patients.

Genetic instability of tumor cells may lead to altered expression of apoptotic proteins and immune-regulatory molecules, such as transforming growth factor-beta. Other research has found overexpression of JunB,5 part of the AP-1 transcription factor complex involved in cell proliferation and apoptosis, in virtually all CD30+ lymphomas. Consequently, JunB is a potential target for experimental therapy in patients with these tumors.

Spontaneous regression of LyP is seen almost universally, whereas regression occurs in approximately 25% of pcALCL cases. Therefore, the higher apoptotic index found in LyP compared with pcALCL is not surprising. The proapoptotic protein Bax is also expressed at high levels in CD30+ cutaneous lymphoproliferative diseases and may play a crucial role in mediating apoptosis of tumor cells. Another recent study suggested that the death-receptor apoptosis pathway mediated by Fas-associating protein with death domain (FADD) may be responsible for the varying biologic behaviors of CD30+ LPDs involving the skin.

Frequency

United States

The prevalence of LyP is estimated to be 1.2-1.9 cases per million population. The CD30+ cutaneous lymphoproliferative disorders account for approximately 25% of cutaneous T-cell lymphoma cases.

Mortality/Morbidity

LyP has a chronic, indolent course in most patients; however, estimates indicate that as many as 10-20% of LyP patients have a history of associated malignant lymphoma (ALCL, HD, or MF) prior to, concurrent with, or subsequent to the diagnosis of LyP. In a recent longitudinal study, no patients with LyP died of the disease.

pcALCL is more likely than MF to manifest as an ulcerated tumor and palpable lymph nodes. MF is the most common variant of cutaneous T-cell lymphoma and is characterized by the development of red patches or plaques in sun-protected areas. MF is more likely to manifest as patches and plaques than tumors. Disease-specific survival at 5 and 10 years for pcALCL was 85% in a recent study.

Associated lymphomas more rarely include immunoblastic lymphoma, lethal midline granuloma (currently considered as natural killer cell lymphoma in many patients), and systemic lymphocytic lymphoma. In most patients, the malignancy develops many years after the diagnosis of LyP.

Race

Black persons may be less affected than other racial groups.

Sex

No consistent sex predominance is found in studies, but some studies have reported a male-to-female ratio of 1.5-2:1.

Age

LyP may develop at any age, but the peak incidence occurs in the fifth decade.

Clinical

History

  • Most patients describe the gradual onset of an asymptomatic to mildly pruritic papular eruption.
    • Papules appear in crops and resolve spontaneously within 2-8 weeks.
    • Waxing and waning of the crops of papules may continue for decades.
  • Unless accompanied by systemic lymphoma, most patients have no constitutional symptoms.

Physical

  • Unless accompanied by systemic lymphoma, physical findings are limited to the skin and, very rarely, the oral cavity.6
  • The primary skin lesions are described as follows:
    • Each erythematous papule evolves into a red-brown, often hemorrhagic, papulovesicular or papulopustular lesion over days to weeks (see Media File 1 and Media File 4). Some lesions develop a necrotic eschar before healing spontaneously. Occasionally, noduloulcerative lesions may be present (see Media File 2).
    • Each papule heals within 2-8 weeks, leaving a hypopigmented or hyperpigmented, depressed, oval, and varioliform scar.
    • Large nodules and plaques may take months to resolve. Carefully evaluate solitary ulcerated nodules, plaques, or masses for CD30+ ALCL, MF, or rarely, HD (see Media File 3).
  • The skin distribution of lesions, characteristically, is on the trunk and extremities, although the palms and/or soles, face, scalp, and anogenital area also may be involved.

Causes

  • The etiology of LyP is unknown. Debate persists over whether (1) LyP is a benign chronic disorder of activated T cells responding to external or internal stimuli or (2) LyP is an indolent T-cell malignancy localized to skin and held in check by the host immune system.
  • A few investigators have discovered viruslike particles in LyP lesions examined under electron microscopy.

More on Lymphomatoid Papulosis

Overview: Lymphomatoid Papulosis
Differential Diagnoses & Workup: Lymphomatoid Papulosis
Treatment & Medication: Lymphomatoid Papulosis
Follow-up: Lymphomatoid Papulosis
Multimedia: Lymphomatoid Papulosis
References
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References

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  2. Slater D. The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants. Br J Dermatol. 2005;153:874-880. [Medline].

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  15. Clarke LE, Bayerl MG, Bruggeman RD, Mauger D, Ioffreda MD, Abou-Elella A, et al. Death receptor apoptosis signaling mediated by FADD in CD30-positive lymphoproliferative disorders involving the skin. Am J Surg Pathol. Apr 2005;29(4):452-9. [Medline].

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  31. Willemze R, Beljaards RC. Spectrum of primary cutaneous CD30 (Ki-1)-positive lymphoproliferative disorders. A proposal for classification and guidelines for management and treatment. J Am Acad Dermatol. Jun 1993;28(6):973-80. [Medline].

  32. Wood GS, Crooks CF, Uluer AZ. Lymphomatoid papulosis and associated cutaneous lymphoproliferative disorders exhibit a common clonal origin. J Invest Dermatol. Jul 1995;105(1):51-5. [Medline].

  33. Yagi H, Seo N, Ohshima A, Itoh T, Itoh N, Horibe T, et al. Chemokine receptor expression in cutaneous T cell and NK/T-cell lymphomas: immunohistochemical staining and in vitro chemotactic assay. Am J Surg Path. Sept 2006;30(9):1111-19. [Medline].

  34. Yamaguchi T, Ohshima K, Karube K, Kawano R, Nakayama J, Suzumiya J, et al. Expression of chemokines and chemokine receptors in cutaneous CD30+ lymphoproliferative disorders. Br J Dermatol. May 2006;154(5):904-909. [Medline].

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Further Reading

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Keywords

Macaulay disease, Macaulay's disease, LyP, T-cell lymphoma, T cell lymphoma, cutaneous lymphoma, mycosis fungoides, MF, Hodgkin disease, Hodgkin lymphoma, Hodgkin's disease, Hodgkin's lymphoma, HD, lymphoproliferative disease, lymphoproliferative disorder, LPD, anaplastic large cell lymphoma, ALCL, primary cutaneous anaplastic large cell lymphoma, pcALCL

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Contributor Information and Disclosures

Author

John A Zic, MD, Director of Cutaneous Lymphoma Clinic, Assistant Professor, Division of Dermatology, Vanderbilt University Medical Center
John A Zic, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Gregory J Raugi, MD, PhD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle
Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, 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

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

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