Lymphomatoid Papulosis: Assessing Treatment Response and Associated Lymphomas in a Study of 180 Patients

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

Objective:The aim of the 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: This was a retrospective study of patients with LyP seen between 1999 and 2015. Patient charts, clinical and histopathological data were evaluated, searching the MD Anderson Cancer Center cutaneous T- cell lymphoma database. A total of 237 patients with the diagnosis of LyP were identified, with 180 patients meeting the inclusion criteria of both clinical diagnosis of LyP and confirmatory biopsy.

Results: A total of 56.6% of patients were male and 43.3% were female. The majority of patients were Caucasians (77.7%, n=139). The mean age at diagnosis was 52.7±17.2 years. The mean time from symptom onset to a biopsy proven diagnosis of LyP was 45.0±75.4 months. The majority of patients (51.6%, n=83) had less than twelve lesions at the worst time point. 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. Associated lymphomas (n=114) were observed in 93 patients with mycosis fungoides (61.4%, n=70) and anaplastic large cell lymphoma (26.3%, n=30) being the most common forms (Table). Men were 2.85 times

(95%CI: 1.55-5.24) more likely to develop a secondary lymphoma than women. Other risk factors for development of lymphoma included histologic subtypes B and C and older age. Number of lesions, symptom severity and ethnicity were not associated with lymphoma development. Patients with type D (CD8+) were less likely to develop lymphomas. Despite the high number of detected secondary malignancies, the prognosis of LyP is excellent. Only eight out of 180 evaluated patients died of their disease. A broad variety of treatment options are available for symptomatic relief only, since no treatment modality was found to prevent progression to lymphoma.

Conclusion: We could demonstrate that LyP is associated with other cutaneous and extra-cutaneous malignancies, the most common being MF and ALCL. To date the risk of developing associated lymphomas cannot be altered by medication. Long term follow-up exams and proper patient counseling are required to ensure early detection of evolving secondary malignancies.

Table 1.
A total of 114 hematologic malignancies were observed in 93 patients with lymphomatoid papulosis diagnosed before, concomitant and after diagnosis of lymphomatoid papulosis

Hematologic malignancy	Before (n=39)	Concomitant (n=28)	After (n=47)	All (n=114)
	%(n)	%(n)	%(n)	%(n)
MF (all stages)	17.5% (20)	17.5%(20)	26.3%(30)	61.4% (70)
MFIA	9.6% (11)	7.0% (8)	20.2%(23)	36.8%(42)
MFIB	4.4% (5)	4.4% (5)	2.6%(3)	11.4%(13)
MFIIA	1.0% (1)	-	-	1.0%(1)
MFIIB	1.0% (1)	1.0% (1)	1.0%(1)	2.6%(3)
MFIVA	-	1.0% (1)	-	1.0% (1)
FMFIA	-	1.8% (2)	1.0%(1)	2.6%(3)
FMFIB	1.8%(2)	1.0% (1)	-	2.6%(3)
FMFIIB	-	1.0% (1)	-	1.0% (1)
FMFIVA	-	-	1.0%(1)	1.0% (1)
Hypopigmented MF	-	-	1.0%(1)	1.0% (1)
Granulomatous MF	-	1.0% (1)	-	1.0% (1)
ALCL	12.3%(14)	7.0% (8)	7,0%(8)	26.3% (30)
HD	1.0%(1)	-	2.6%(3)	3.5%(4)
CLL	2.6%(3)	-	1.0%(1)	3.5%(4)
AML	-	-	1.0%(1)	1.0% (1)
B-cell lymphoma	-	-	1.8%(2)	1.8% (2)
LGL	1.0%(1)	-	1.0%(1)	1.8% (2)
Multiple Myeloma	-	-	1.0%(1)	1.0% (1)

Abbreviations: ALCL, anaplastic large cell lymphoma; AML, acute myeloid leukemia; CLL, chronic lymphatic leukemia; FMF, folliculotropic mycosis fungoides; HD, Hodgkin disease; LGL, T-cell large granular lymphocytic leukemia; MF, mycosis fungoides; n, number of lymphoma cases.