eMedicine Specialties > Dermatology > Lymphoma and Related Processes
Lymphomatoid Papulosis
Updated: Dec 16, 2009
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, lymphomatoid papulosis 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 lymphomatoid papulosis among the indolent cutaneous T-cell lymphomas. The rationale for classifying lymphomatoid papulosis 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
Lymphomatoid papulosis is part of a spectrum of CD30 (Ki-1)–positive cutaneous lymphoproliferative diseases (CD30+ LPDs), including lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma (pcALCL), and borderline CD30+ lesions. Also see Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma.
Also see the eMedicine articles Malignant Melanoma (dermatology focus), Malignant Melanoma (oncology focus), Cutaneous T-Cell Lymphoma, and Lymphoma, Cutaneous T-Cell.
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 lymphomatoid papulosis (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 lymphomatoid papulosis 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 lymphomatoid papulosis, and the 30M362 allelic form was associated with progression to other CD30+ lymphomas in lymphomatoid papulosis 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 lymphomatoid papulosis is seen almost universally, whereas regression occurs in approximately 25% of pcALCL cases. Therefore, the higher apoptotic index found in lymphomatoid papulosis 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.6
Frequency
United States
The prevalence of lymphomatoid papulosis 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
Lymphomatoid papulosis has a chronic, indolent course in most patients; however, estimates indicate that as many as 10-20% of lymphomatoid papulosis patients have a history of associated malignant lymphoma (ALCL, HD, or MF) prior to, concurrent with, or subsequent to the diagnosis of lymphomatoid papulosis. In a recent longitudinal study, no patients with lymphomatoid papulosis 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 lymphomatoid papulosis.
Race
Black persons may be less affected by lymphomatoid papulosis than persons of other racial groups.
Sex
No consistent sex predominance is found in studies of lymphomatoid papulosis, but some studies have reported a male-to-female ratio of 1.5-2:1.
Age
Lymphomatoid papulosis may develop at any age, but the peak incidence occurs in the fifth decade.
Clinical
History
- Most patients with lymphomatoid papulosis (LyP) 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.7,8
- 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, as demonstrated in the images below.
Lymphomatoid papulosis type C on the upper back of a 65-year-old woman with waxing and waning papulonodular eruptions for almost 10 years. The eruption was suppressed completely using methotrexate.
Lymphomatoid papulosis type A showing a cluster of pink papules and 2 crusted papules that resolved spontaneously in the left axilla of a 68-year-old man. The first symptoms developed in the popliteal fossa 8 years before erupting into more widespread papules 10 months before this photograph was taken.
- Some lesions develop a necrotic eschar before healing spontaneously. Occasionally, noduloulcerative lesions may be present, as in the image below.
Crusted ulcerated papule of lymphomatoid papulosis on the left hip of a 47-year-old woman with a longer than 20-year history of recurrent papulonodular eruption with spontaneous resolution.
- 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 (see image below), MF, or rarely, HD.
Large indurated plaques of anaplastic large cell lymphoma of 2-months' duration on the left lateral thigh of a 57-year-old man with a 5-year history of lymphomatoid papulosis. The lymphomatoid papulosis skin lesions (not pictured) were rarely larger than 6 mm.
- The skin distribution of lesions, characteristically, is on the trunk and extremities, although the palms and/or soles, face, scalp, oral mucosa,9 and anogenital area also may be involved.
- Evolving lesions have been described under dermoscopy. The initial papular lesion showed a vascular pattern of tortuous vessels radiating from the center. A white structureless area was seen around the vessels. More mature lesions, hyperkeratotic papules, looked similar except the vascular pattern in the center of the lesion was obscured. As the lesions progressed to necrotic ulcerations, the vascular pattern was only seen at the periphery, while the center of the lesions was a structure of brownish-gray areas. The final, or cicatricial phase, was similar except no vessel pattern was seen.10
Causes
- The etiology of lymphomatoid papulosis is unknown. Debate persists over whether (1) lymphomatoid papulosis is a benign chronic disorder of activated T cells responding to external or internal stimuli or (2) lymphomatoid papulosis 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 lymphomatoid papulosis lesions examined under electron microscopy.11
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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Further Reading
Keywords
lymphomatoid papulosis, 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
