We report on a patient with a new diagnosis of lymphomatoid papulosis (LyP) who was subsequently diagnosed with chronic lymphocytic leukemia (CLL). LyP is a CD30+ lymphoproliferative disorder characterized by recurrent papulonodular eruptions that appear malignant histologically but usually follow a benign and indolent course . In 9–18 % of patients, LyP may progress to malignancies such as mycosis fungoides, anaplastic large cell lymphoma, and Hodgkin’s disease (Table 1) [2–7]. To date, there has been one report of LyP associated with acute myeloblastic leukemia (AML)  and one report associated with small-cell lymphocytic B cell lymphoma .
Reported malignancies associated with lymphomatoid papulosis
Reported incidence of lymphoma development
Overall rate of associated hematologic malignancy
8 out of 53 cases (15 %)2
17 out of 123 cases (14 %)3
11 out of 84 (18 %)4
3 out of 35 cases (9 %)5a
Anaplastic large cell lymphoma
Follicular small-cleaved cell lymphoma
aCase series of pediatric patients
A previously healthy 78-year-old Caucasian woman presented to the dermatology clinic at our institution with a 5-month history of intermittent eruptions of a pruritic rash in the inguinal area, back, thighs, and legs. The rash consisted of erythematous, polymorphic papules that increased in size and coalesced into plaques over the lifespan of the lesion (Fig. 1). The skin lesions appeared in crops and spontaneously regressed within 2 months. In the referring physician’s assessment, two separate skin biopsies were performed and found to be inconclusive, demonstrating spongiotic dermatitis with an inflammatory infiltrate in the dermis. The patient received multiple steroid injections for a presumptive diagnosis of vasculitis, resulting in only temporary relief of symptoms. Laboratory work-up at that time was notable for a lymphocytosis to 62 % (reference range, 12–46 %) and an elevated absolute lymphocyte count of 4.3 K/μL (reference range, 0.7–4.0 K/μL). However, the patient was evaluated by a hematologist, and malignancy was ruled out due to an absolute lymphocyte count less than 15,000 and no evidence of adenopathy, thrombocytopenia, anemia, or organomegaly.
Due to recurrence of lesions, the patient was referred to our institution for further evaluation. She reported feeling well and denied fatigue, fever, chills, or weight loss. A third biopsy showed nonspecific findings and negative direct immunofluorescence. Despite initiating therapy with oral prednisone, the lesions continued to recur, and a fourth skin biopsy was obtained. This demonstrated a superficial- to mid-dermal mixed inflammatory infiltrate consisting of predominantly lymphocytes and histiocytes, with few neutrophils. The lymphocytes were large and atypical (Fig. 2a). Immunohistochemical stains were performed and stained positively for CD3, CD20, and CD30. The presence of CD3 highlights a predominance of T cells, whereas CD20 highlights a background of B cells. Staining for CD30 highlighted the larger, atypical Reed-Sternberg-like cells intermingled with inflammatory cells, with the background inflammatory cells greatly outnumbering the CD30-positive tumor cells (Fig. 2b). These findings were consistent with type A lymphomatoid papulosis. Methotrexate 5 mg weekly was added to her regimen, and she was referred to the lymphoma clinic for work-up for underlying malignancy. Upon reevaluation, laboratory tests revealed an elevated white blood cell count to 20.8 K/μL, with an absolute lymphocyte count of 12.2 K/μL (reference range, 1.0–5.1 K/μL). Flow cytometry of peripheral blood revealed expression of T cell antigen 5 and B cell antigens CD19, CD20, and CD23. There was strong intensity staining for CD45, and no significant CD34-positive blast population was identified. These findings were consistent with a monoclonal CD5-positive B cell lymphocytosis and were consistent with CLL, Rai stage 0. Thinking that the skin lesions could be a manifestation of her underlying CLL, the patient was begun on a single agent bendamustine 90 mg/m2. Despite therapy with one cycle, the patient had worsening rash and eosinophilia, and bendamustine was discontinued after one cycle. She also underwent a trial of therapy with brentuximab 1.8 mg/kg, but this was also discontinued after one cycle due to exacerbation of her rash. Despite worsening skin lesions and symptoms associated with LyP, the patient’s CLL was controlled, and thus therapeutic goals were shifted towards skin-directed therapy. Methotrexate was reinitiated at 20 mg weekly and then increased to 25 mg weekly, and the patient’s disease symptoms have been relatively controlled with systemic therapy with methotrexate 25 mg weekly, gabapentin 300 mg nightly, and topical steroid treatments including clobetasol 0.05 % ointment and triamcinolone 0.1 % ointment for affected areas of the body. Further considerations for symptom control in this patient includes phototherapy with ultraviolet B, which may alleviate the severe pruritis associated with the lesions, but would not likely be curative.
In the malignant course of lymphomatoid papulosis, it is more commonly associated with mycosis fungoides, Hodgkin’s lymphoma, and anaplastic large cell lymphoma. However, among several rarer communications, LyP has been associated with other diseases such as AML,  hypereosinophilic syndrome , nevoid basal cell carcinoma syndrome , and Waldenström’s macroglobulinemia . Although the pathogenesis in the evolution of LyP into malignancy is not definitively known, some theories propose that cytogenetic events, inadequate host response, or persistent antigenic or viral stimulation contribute to the progression into a malignant clonal T cell population . Others suggest that LyP may arise from an early, reactive, polyclonal lymphoid expansion that evolves into a clonal neoplastic process as host tumor surveillance function becomes overwhelmed . While LyP is a clonal T cell disorder, CLL and the frequently associated Hodgkin’s lymphoma are B cell disorders. Thus, the concomitant diagnosis of CLL with LyP in our patient may support the theory that LyP arises from an early stem cell or precursor cell defect, which can lead to both T and B cell disorders. This case highlights the need for collaboration between hematologists, dermatologists, and other care providers to appropriately evaluate patients with LyP.
Conflict of interest
The authors declare that they have no conflict of interest.