Lymphomatoid Papulosis

Updated: Oct 04, 2017
  • Author: John A Zic, MD; Chief Editor: William D James, MD  more...
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Overview

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 Macaulay [1] 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. These classifications were updated in 2008 by the WHO-EORTC, [2, 3, 4] and they were updated in 2016 by the WHO. [5] The 2016 classification described new subtypes of lymphomatoid papulosis with similar clinical behavior but atypical histologic/immunophenotypic features. It classifies lymphomatoid papulosis as an indolent T-cell lymphoproliferative disorder of the skin, under primary cutaneous CD30+ T-cell lymphoproliferative disorders, along with primary cutaneous anaplastic large cell lymphoma (pcALCL). 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. [6, 7, 8, 9]

Lymphomatoid papulosis is part of a spectrum of CD30 (Ki-1)–positive cutaneous lymphoproliferative diseases (CD30+ LPDs), including lymphomatoid papulosis, pcALCL, and borderline CD30+ lesions. Also see Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma.

Also see the Medscape articles Cutaneous MelanomaMalignant Melanoma, and Cutaneous T-Cell Lymphoma.

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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 2005 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. [10]

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, [11] 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 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. [12]

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Etiology

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. [13]

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Epidemiology

US frequency

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.

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.

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Prognosis

The prognosis of lymphomatoid papulosis (LyP) is good because most patients have a chronic, indolent course. A retrospective cohort analysis found that no patients with lymphomatoid papulosis died of the disease, and the overall survival rate was 92% at 5 and 10 years.

Physicians are guardedly optimistic about the prognosis because estimates indicate that as many as 4-25% of patients have a history of associated malignant lymphoma (ALCL, HD, MF) prior to, concurrent with, or subsequent to the diagnosis of lymphomatoid papulosis. [14, 15] Unfortunately, no clinical or histologic factors analyzed to date are predictive of worse outcomes in persons with lymphomatoid papulosis. A study suggested that fascin expression is increased in lymphomatoid papulosis cases associated with a malignant lymphoma. [16] Alterations in transforming growth factor-beta signaling are hypothesized to play a role in the progression of lymphomatoid papulosis to malignant lymphoma. Additionally, data have shown an increased risk of associated lymphomas in lymphomatoid papulosis cases with CCR3+ atypical cells or the 30M362 allelic form of the CD30 promoter.

Primary cutaneous anaplastic large cell lymphoma (pcALCL) is more likely than mycosis fungoides (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 2003 study. [17]

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.

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Patient Education

Instruct patients that they are not an infectious risk to others.

Instruct patients about local wound care of open crusted lesions. Lesions should be cleaned with mild soap and water twice daily, and topical petroleum ointment should be applied to prevent infection and aid healing. Crusted lesions should be covered with a loose adhesive bandages until healed.

Instruct patients to contact their physician if any of the following symptoms or signs develop that may herald the onset of infection or associated malignancy:

  • Fever, chills, night sweats, or weight loss
  • Persistent skin nodules or patches that do not regress over a 2- to 3-month period
  • Enlarged lymph node glands in the neck, groin, or axillae
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