Not bitten by the bug: A CD30+lymphoproliferative disorder masquerading as arthropod bites
Authors: Jacqueline McKesey, Travis Vandergriff, Heather Wickless
Journal: American Journal of Hematology (2017)

A 67-year-old healthy, Caucasian man presented to his family physician for three months of 50–100 red, crusted papules and nodules on his trunk and extremities which arose in crops, then spontaneously resolved over 3–4 weeks (Figure 1A,B). He denied constitutional symptoms. The first lesions appeared three days after returning from a hike in the Ozark Mountains of Arkansas, after which the patient's family physician diagnosed him with chigger bites and used hydrocortisone 2.5% ointment for treatment. The patient's wife, who went on the same trip, was unaffected. Despite several months of topical steroid treatment, new lesions continued to develop. Panels A and B: Inflammatory and necrotic papules in various stages of evolution on the extremities and trunk. A. Posterior lower extremities B. Trunk and upper extremity. Panels C and D: Lymphomatoid Papulosis (LyP), punch biopsy. C. Low power punch biopsy demonstrating a classic wedge-shaped infiltrate in LyP Type A. D. High power imaging shows a mixed inflammatory infiltrate including eosinophils and atypical lymphocytes. Photo credit: Dr. Heather Wickless, Dr. Travis Vandergriff, UT Southwestern Medical Center, Dallas, TX The lesions were biopsied, revealing large, atypical Reed-Sternberg-like Alk-1 negative, CD30-positive T-cells with admixed inflammatory infiltrate, characteristic findings of lymphomatoid papulosis.1 Lymphomatoid papulosis (LyP) is a rare, indolent CD30+ T-cell lymphoproliferative disease with clinical and histologic pitfalls due to its ability to mimic other benign and malignant diseases.2-4 LyP has an incidence of 1.2–1.9 cases per million population; has a slight male-predominance, and most often arises in the fifth decade of life.1, 2 The etiology of this disease is unknown; however, its pathogenesis may be related to acquired genetic instability of the CD30 receptor.5 Diagnosis of LyP is made by clinicopathologic correlation, as there are diagnostic pitfalls based on histological or clinical clues alone.2 For example, primary cutaneous anaplastic large cell lymphoma (pcALCL), another CD30+ lymphoproliferative disease, can be histologically indistinguishable from LyP. Clinicians must incorporate clinical history and exam to distinguish LyP from pcALCL to avoid invasive diagnostic and therapeutic procedures not indicated in LyP.6 The histology of LyP may also be mistaken for systemic Hodgkin or non-Hodgkin lymphoma, also leading to unnecessary imaging studies and use of multi-agent chemotherapy.2, 7 CD30+ proliferation can also be present in infectious processes, drug reactions, and even arthropod bites.2, 8, 9 LyP can be classified into histologic, morphologic, and immunophenotypic subtypes A-E by a skilled dermatopathologist. Treatment remains similar regardless of classification. Histologically, LyP type A, the most common variant, demonstrates a wedge-shaped infiltrate of large, atypical CD30+ T-cells that can be multinucleated, admixed with an inflammatory infiltrate (Figure 1C,D).1, 2 These findings must be correlated with clinical presentation, which is typically a history of chronic, recurrent, self-healing grouped or disseminated papules or nodules, often with central necrosis.6, 10 Patients typically do not have constitutional symptoms, laboratory abnormalities, or lymphadenopathy. The prognosis of LyP is favorable, following an indolent course with >90% 10-year survival.11, 12 No verified prognostic markers exist for LyP, but it has been proposed that male sex, T-cell receptor gene rearrangement, and LyP subtypes B and C are associated with increased risk of hematologic malignancies.13-15 Patients with LyP have a 4–25% increased risk of concomitant hematologic malignancies such as Hodgkin's disease, ALCL, or Mycosis Fungoides at the time of, prior to, or following LyP diagnosis, and LyP mortality is largely related to these malignancies.11, 12, 16 Clinicians have the responsibility to monitor for the development of constitutional symptoms, abnormal laboratory results, persistent skin nodules, and enlarged lymph nodes, all which can be markers for a more aggressive lymphoma.6, 12, 16 Treatment of LyP is largely anecdotal, with few large scale trials conducted.6 Nevertheless, the National Comprehensive Cancer Network (NCCN), European Organisation for Research and Treatment of Cancer (EORTC), International Society of Cutaneous Lymphoma (ISCL), and United States Cutaneous Lymphoma Consortium (USCLC), consensus recommendations include conservative management with observation, topical steroids, or psoralen-UVA light therapy for localized lesions, and the addition of methotrexate for more diffuse disease.6, 17 Low dose (10–25 mg) weekly Methotrexate is a first line oral agent.6 For recalcitrant cases, brentuximab-vedotin, a CD-30 targeted monoclonal antibody, can be used.17 Given our patient's multifocal disease, he was treated with once-weekly 25 mg methotrexate, with a >90% reduction of lesions at one month and maintenance of this response at eight months. Tapering methotrexate is a goal for most patients, but data on weaning therapy is scarce, with most cases requiring long-term treatment.6, 18 Our patient will be lowered by 2.5 mg quarterly to determine the lowest-possible dose to maintain adequate control of his disease. This case highlights the ability of LyP to mimic both benign and aggressive diseases and the need for clinicopathologic correlation to avoid long term sequelae and incurred costs of unnecessary and ineffective treatment. The authors have no conflict of interest. The study was not funded.