Lymphomatoid Papulosis

Updated: Feb 07, 2025
  • Author: Edward J Zabawski, Jr, DO; Chief Editor: William D James, MD  more...
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Overview

Practice Essentials

Lymphomatoid papulosis (LyP) is a chronic papulonecrotic or papulonodular skin disease with histologic features suggestive of a malignant lymphoma. It is characterized by recurrent crops of papules at different stages of development that predominantly arise on the trunk and limbs; commonly, these are pruritic, but they may be asymptomatic. Eroded or ulcerated lesions may be painful. The papules heal spontaneously over 1-2 months, usually leaving slightly depressed oval scars. [1] LyP is part of a spectrum of CD30 (Ki-1)–positive (CD30+) cutaneous lymphoproliferative disorders (LPDs) that also includes primary cutaneous anaplastic large cell lymphoma (pcALCL) and borderline CD30+ lesions.

The 2016 World Health Organization (WHO) classification of lymphoid neoplasms described newer subtypes of LyP with similar clinical behavior but atypical histologic or immunophenotypic features. It classified LyP as an indolent T-cell LPD of the skin, under primary cutaneous CD30+ T-cell LPDs, along with pcALCL. [2] The 2018 WHO–European Organization for Research and Treatment of Cancer (EORTC) classification categorized LyP similarly. [3]

The rationale for classifying LyP as a cutaneous lymphoma is its association with other malignant LPDs; however, some experts have hesitated to classify this chronic skin disease as a true malignancy, because of its spontaneous resolution and benign clinical course. [4, 5, 6, 7]

LyP is not a homogeneous syndrome; the diagnosis requires a combination of clinical features and histopathologic and immunohistochemical findings. [8] Six different histologic subtypes have been recognized by the WHO-EORTC: A, B, C, D, E, and LyP with rearrangement 6p25.3. [3] Subtype A is the most common one, accounting for 75-80% of cases. [8] Single cases with a combination of subtypes have also been reported. [8] Several rare variants—such as folliculotropic (subtype F), [9] acral, [10] syringotropic, spindle cell, angioinvasive, pseudoepitheliomatous, intralymphatic, and granulomatous eccrinotropic [11] —have been reported but have not been formally recognized.

See also Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma, as well as Cutaneous Melanoma, Malignant Melanoma, and Cutaneous T-Cell Lymphoma.

Background

The term lymphomatoid papulosis (LyP) originally was used by Macaulay [12] in 1968 to describe "a self-healing rhythmical paradoxical eruption, histologically malignant but clinically benign." Because of its typical waxing and waning clinical course, LyP was previously considered a pseuodolymphomatous inflammatory process.

Subsequently, however, classification of cutaneous lymphomas evolved rapidly, and during consensus meetings in 2003-2004, the World Health Organization (WHO)–European Organization for Research and Treatment of Cancer (EORTC) classification grouped LyP among the indolent cutaneous T-cell lymphomas. These classifications were subsequently reviewed and updated by the WHO-EORTC in 2008, [13, 14, 15] by the WHO in 2016, [2] and again by the WHO-EORTC in 2018. [3]

Pathophysiology

The CD30 antigen is a type 1 transmembrane glycoprotein of the tumor necrosis factor (TNF) receptor superfamily. In addition to the CD30+ LPDs, 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+ lymphoproliferative disorders (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 2005 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. [16]

Genetic instability of tumor cells may lead to altered expression of apoptotic proteins and immune-regulatory molecules, such as transforming growth factor (TGF)-β. Other research has found overexpression of JunB, [17] 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 only about 25% of primary cutaneous ALCL (pcALCL) cases. Therefore, the higher apoptotic index found in LyP as compared with pcALCL is not surprising. The proapoptotic protein Bax is also expressed at high levels in CD30+ cutaneous LPDs 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. [18]

Etiology

The etiology of LyP is unknown. Debate persists over whether LyP is (A) a benign chronic disorder of activated T cells responding to external or internal stimuli or (B) an indolent T-cell malignancy localized to the skin and held in check by the host immune system.

A few investigators have discovered viruslike particles in LyP lesions examined under electron microscopy. [19]

Epidemiology

US statistics

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

Age-, sex-, and race-related demographics

LyP may develop at any age, but the peak incidence occurs in the fifth decade. No consistent sex predominance has been established in studies of LyP, but some studies have reported a male-to-female ratio of 1.5-2:1. Black persons may be less affected by LyP than persons of other racial groups.

Prognosis

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

Physicians tend to be guardedly optimistic about the prognosis because an estimated 4-25% of patients have a history of associated malignant lymphoma (ALCL, HD, or MF) before, concurrently with, or after the diagnosis of LyP. [20, 21, 22] Unfortunately, no clinical or histologic factors analyzed to date have proved to be predictive of worse outcomes in persons with LyP. Fascin expression may be increased in LyP cases associated with malignant lymphoma. [23] Altered TGF-β signaling may play a role in the progression of LyP to malignant lymphoma. Additionally, LyP cases with CCR3+ atypical cells or the 30M362 allelic form of the CD30 promoter.have shown an increased risk of associated lymphomas.

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 as tumors. Disease-specific survival at 5 and 10 years for pcALCL was 85% in a 2003 study. [24]

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.

Patient Education

Patients should be informed that they do not pose an infectious risk to others. They should be educated regarding 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 bandage until healed.

Patients should know 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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