Original article
Lymphomatoid papulosis: Treatment response and associated lymphomas in a study of 180 patients

https://doi.org/10.1016/j.jaad.2015.09.013Get rights and content

Background

Lymphomatoid papulosis (LyP) is a CD30+ lymphoproliferative disorder, with a self-regressing clinical course and malignant histopathology.

Objective

The aim of this study was to evaluate characteristics, risk factors, associated malignancies, long-term outcome, and treatment of LyP in a large cohort representing the experience of the MD Anderson Cancer Center.

Methods

Patient charts and clinical and histopathologic data of 180 patients with LyP were retrospectively assessed.

Results

A total of 56.7% of patients was men. Histologic subtype A was found in 47.2%, type B in 17.2%, type C in 22.8%, type D in 7.8%, type E in 0.6%, and mixed subtype in 4.4% of the patients. One hundred fourteen lymphomas were observed in 93 patients, with mycosis fungoides (61.4%) and anaplastic large cell lymphoma (26.3%) being the most common forms. Risk factors for development of lymphoma included sex and histologic subtype. Number of lesions and symptom severity were not associated with lymphoma development. Patients with type D were less likely to have lymphomas. Treatment provided symptomatic relief but did not prevent progression to lymphoma.

Limitations

The limitation of this study is the retrospective study design.

Conclusion

Patients with LyP are at increased risk of associated lymphomas. Thorough patient counseling is needed and long follow-up periods are required to detect and treat secondary lymphomas.

Introduction

Lymphomatoid papulosis (LyP) is a rare CD30+ lymphoproliferative disorder. The estimated worldwide incidence is 1.2 to 1.9 cases per 1.000.000 people1 with a 10-year survival rate close to 100%.2 Although the peak incidence is in the fifth decade, any age group can be affected. Men are more likely to have LyP than women.3, 4

The first to report this disease was Dupont in 19655; 3 years later, Macaulay introduced the term lymphomatoid papulosis and described it as benign, self-regressing erythematous papules with malignant histology.6 By definition, LyP lesions are red or purple (sometimes pruritic) papules and nodules, measuring less than 2.0 cm. They occur as single or multiple crops and can affect any body part. In half of the patients, the lesions heal with scar formation.3 The tendency to regress spontaneously is characteristic for the disease and crucial to establish a clinical diagnosis.7 Larger nonregressing lesions, in contrast, would be expected in primary cutaneous anaplastic large cell lymphoma (ALCL) or mycosis fungoides (MF) tumor lesions with CD30+ expression.4

Over the years, the subclassification of LyP has become very precise and is a work in progress.8 The most common LyP subtype is type A, characterized by a wedge-shaped infiltrate with neutrophils, eosinophils, and histiocytes. Type B has small- to medium-sized lymphocytes with cerebriform nuclei, simulating features observed in MF. Type C has sheets of large CD30+ lymphocytes, resembling ALCL.9 Other rare types include type D, with predominantly CD8+ lymphocytic infiltrates10 and type E, characterized by angiodestructive infiltrates of small- to medium-sized lymphocytes expressing CD30 and CD8.11 A sixth, type F, is currently proposed and described as having a perifollicular infiltrate with folliculotropism.12

Previous smaller studies, including our first report of LyP patients 10 years ago, suggested a possible association of LyP and development of secondary lymphomas.3, 4, 13, 14, 15, 16 To date, no curative treatment for LyP is available.17 Information regarding the potential of aggressive therapy on prevention of secondary lymphomas is lacking.

The purpose of this study was to define LyP characteristics, risk factors, associated malignancies, long-term outcome, and response to currently available treatment options in a large cohort from the MD Anderson Cancer Center, Clinic for Cutaneous T-cell Lymphomas.

Section snippets

Patients

This was a retrospective study of patients with LyP seen at the MD Anderson Cancer Center, Houston between 1999 and 2015 aimed to bring continuity to our previously published cohort of 84 patients in the follow-up period from 1999 to 2005.16 The study protocol was approved by the institutional review board (#PA15-0324). A total of 237 patients with LyP were identified, searching the MD Anderson Cancer Center cutaneous T-cell lymphoma database. The diagnosis of LyP was made according to the

Statistical analysis

Basic summary statistics were used to describe demographic data, treatment types, and response. Continuous data are expressed as mean ± standard deviation (SD) or median (range), as appropriate. Categorical data were assessed using Pearson's χ2 test. Kaplan Meier time-to-event curves were used to study disease progression from time of LyP diagnosis to secondary lymphoma development. All analyses were performed using SPSS version 22.0 (SPSS Inc, Chicago, IL). P < .05 was considered statistically

Patient characteristics

A total of 180 patients were evaluated (Table I). Mean follow-up time was 60.5 ± 56.5 months. A male predominance was observed, with 56.7% being male. Most were white (77.2%). Mean age at diagnosis was 52.7 ± 17.2 years. There was no difference in age of disease onset for sex or ethnicity (P = .157; P = .816). The mean time from symptom onset to biopsy-proven LyP was 45.0 ± 75.4 months. Pruritus was reported to be the primary symptom in 55.3% of all patients. Half of the patients (51.6%) had

Discussion

Here we report our experience with LyP and provide the largest cohort of patients published to date. We address the key features of LyP, associated lymphomas, and currently available treatment options. In previous studies with smaller sample sizes, the prevalence of associated lymphomas with LyP varied considerably between 9.5% and 61%.3, 13, 14, 15 We observed that 93 patients (52%) had one or more secondary malignancies before, concomitant to, or after LyP diagnosis (Fig 3). A total of 26% of

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    Funding sources: None.

    Conflicts of interest: Dr Duvic: Seattle genetics (research funding for clinical trials and advisory board); all other authors have no conflict of interest to declare.

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