We examined the relationship between nitrogen mustard (NM)-induced lymphomatoid papulosis (LyP) in patients with mycosis fungoides (MF). Ten patients were included who were initially diagnosed with MF and subsequently developed LyP in the setting of NM induced inflammation. The average time from initiation of NM therapy to development of LyP was 5.6 months. The majority of patients presented to their follow-up visit with new red bumps, most commonly located on the buttocks/lower extremities, with symptoms of pain and pruritus in 7/10 patients. In 9/10 patients the LyP lesions developed within/close to the MF lesions. Diagnosis was made clinically (6/10) or pathologically (4/10). On pathology, all of the lesions examined exhibited a wedge shaped dermal lymphoid infiltrate with large atypical CD30+ lymphocytes consistent with LyP. After diagnosis of LyP, NM was discontinued in 4/10 patients (2 had no recurrences over 8-month to 2-year follow up, 2 had frequent recurrences; both patients had lesions with a clonal TCR rearrangement). LyP of the remaining patients regressed spontaneously and NM was continued with less frequent applications. NM is a topical DNA alkylating agent that induces a local cytotoxic and immune response. We hypothesize that NM triggered a cutaneous inflammatory response, recruiting pro-inflammatory mediators, that led to the selection of a clonal CD30+ T-cell clone presenting as LyP. The fact that 9/10 patients developed the lesions within or near the MF lesions suggests that the malignant cellular background facilitated the developed of a CD30+ clone. The predominance of LyP in our MF patient population treated with NM suggests an association between these two entities. Although LyP is a benign CD30+ lymphoproliferative disorder, it is on the spectrum of disease with anaplastic large cell lymphoma and large cell transformation of MF. Thus, it is important for clinicians to recognize this non-life-threatening condition to avoid overtreatment and to provide adequate intervention including drug holiday, topical steroid use, and adequate skin care.

Nitrogen mustard-induced inflammation triggers lymphomatoid papulosis in patients with Mycosis Fungoides