LAS VEGAS – Although certain characteristics of lymphomatoid papulosis appear be associated with progression to lymphoma, the majority of patients will have a benign course of disease.
The recurrent papulonodular skin eruption lymphomatoid papulosis (LyP) can be a confusing dermatologic entity because it appears malignant histologically, but it usually follows a clinically benign and indolent course (Arch. Dermatol. 1968;97:23-30). And even the 10%-20% of patients who do progress to lymphoma tend to have less aggressive disease, said Dr. Lawrence E. Gibson, professor of dermatology at the Mayo Clinic in Rochester, Minn. The reasons for this disconnect are not yet known.
"Patients with LyP look like lymphoma under the microscope but have clinically indolent cutaneous disease. ... It is an example of a very important clinical-pathological relationship that really needs to be made to help us understand how to treat patients better," he said.
"The bottom line is most of our patients who have LyP do not go on to have aggressive lymphomas."
To identify which LyP patients are more likely to progress to lymphoma, Dr. Gibson, Dr. Rokea A. el-Azhary, Dr. Aieska de Souza, and their associates conducted a retrospective analysis of 123 patients seen at the Mayo Clinic between 1991 and 2008. The patients were followed for a mean of 4 years (range, 2 months to 14 years). The 65 males and 58 females had a mean age of 47 years (range, 1-83 years), and a mean of 14 lesions (range, 1-100). Most (88%) of the lesions were papules, with a reported mean duration of 5.5 weeks. Pruritis was present in 38% and scar formation in 58%, the researchers reported (J. Am. Acad. Dermatol. 2011 [doi:10.1016/j.jaad.2011.07.012]).
Hematologic malignancies were present in 17 patients (14%). Of those, 10 were cutaneous lymphomas – 8 mycosis fungoides (MF) and 2 anaplastic large-cell lymphomas (ALCL). Hodgkin lymphoma was present in three patients (including the two with ALCL), multiple myeloma or monoclonal gammopathy in three, and myelodysplastic syndrome in one.
"The bottom line is most of our patients who have LyP do not go on to have aggressive lymphomas. They certainly don’t have cytotoxic lymphomas. And if they have lymphoma, they usually have MF. I think that’s somewhat reassuring to us. And for the most part, most of the patients don’t have anything. They have a normal life," Dr. Gibson said at the seminar sponsored by Skin Disease Education Foundation (SDEF).
Of 97 LyP patients for whom original biopsy slides were available, the majority (69) had World Health Organization/European Organization for Research and Treatment of Cancer histologic classification type A, including 35 with immunophenotypic subtype CD8 and 34 with subtype CD4. Another 13 patients had type B lesions (8 CD4, 5 CD8), and 6 had type C, all of which were CD4. The other 9 patients had more than one histologic type (A, B, or C), and/or more than one immunophenotypic subtype (CD4 or CD8). They were designated mixed type.
Clinically, there were no distinguishing features among the subtypes. This finding contrasts with some previous reports that the CD8 subtype might predispose to worse disease outcome (Am. J. Pathol. 1999;155:483-92).
"Our findings indicated that the LyP subtype CD8 does not signify more aggressive disease, a poor prognosis, or an association with malignancy," Dr. Gibson and his colleagues wrote.
Hematologic malignancies were present in 5 of the 9 mixed-type patients (55.5%), compared with 4 of the 34 with A/CD4 (12%), 4 of the 35 A/CD8 (11.5%), 1 of the 8 B/CD4 patients (12.5%), and 1 of the 5 B/CD8 patients (20%). (Two of the 17 malignancies were excluded from analysis because original slides were not available.) The odds ratio for malignancy for the patients with mixed-type LyP versus all other types was a statistically significant 4.33 (P = .03).
In a molecular genetics substudy of 84 LyP lesions from 76 patients, 42 (50%) were positive for clonal T-cell receptor gene rearrangement (TCRGR), 34 (40%) were negative, and 8 (10%) showed equivocal results or had insufficient DNA for analysis. Among the LyP patients who had a hematologic malignancy, 9 of 11 (82%) had positive TCRGR, compared with 30 of 68 (44%) LyP patients without malignancy. That association was also significant, with an odds ratio of 5.7 (P = .02), noted the investigators.
"A positive T-cell receptor gene rearrangement or having more than one type of LyP may have a higher risk of progression to lymphoma, but the evidence is not hard and fast. ... The take-home message is most of these patients do just fine," Dr. Gibson said.