Primary Cutaneous ALK+ Anaplastic Large Cell Lymphoma With Minimal Bone Marrow Involvement: A Treatment Challenge

To The Editor, Paediatric anaplastic large cell lymphoma (ALCL) commonly presents with systemic involvement. Most cases are anaplastic lymphoma kinase positive (ALK+), having a translocation t(2;5)(p23;q35) resulting in overexpression of ALK protein [1]. Of these, up to 25% have a cutaneous manifestation. Primary cutaneous ALCL (pc-ALCL) presentations are rare and typically ALK negative (ALK−) [2]. We present a case of ALK+ pc-ALCL in a 13-year-old female with a single cutaneous chest lesion and bone marrow minimal disseminated disease (MDD), without radiological evidence of extranodal disease. The patient presented with a 3-month history of a 5 cm erythematous, flat lesion (Figure 1A) on her right upper chest wall. Following a 4 mm punch biopsy, the lesion evolved and regressed in size (Figure 1B). The patient was systemically well without significant personal or family history. Clinical examination revealed no additional lesions aside from primary lesion as described without lymphadenopathy or extranodal involvement. Histopathology confirmed ALK+ ALCL, with some features suggestive of small cell variant with CD30+ and CD4+, confirmed on central review (Figure 2). Positron emission tomography-computed tomography (PET-CT) showed no abnormal FDG uptake at the site of cutaneous disease or any other site. Cerebrospinal fluid screen was negative. Bilateral bone marrow aspirate and trephines (BMATs) were performed. The right-sided trephine biopsy identified two adjacent abnormal cells, which were ALK+ and CD30+ (Figure 2). Following international multidisciplinary team discussion regarding local (e.g., surgical excision) versus systemic treatment, due to the presence of MDD (albeit only two abnormal cells on trephine), systemic chemotherapy was commenced as per COG-ANHL12P1 protocol. After first two of total of six cycles administered, the patient achieved remission with normal BMAT results, and the skin lesion was no longer visible. The patient remains in remission more than 2 years later. Pc-ALCL typically presents as a large, often ulcerated solitary nodule that shows large pleomorphic, anaplastic or immunoblastic tumour cells with more than 75% being CD30+ [3, 4]. Paediatric pc-ALCL has an excellent prognosis with surgical excision or localised radiation [4]; however, anatomical site and future breast development were considered in our patient. Cutaneous recurrences occur in up to 40% and systemic progression in 12%–16% [4]. The presence of MDD, high-risk sites and small cell/lymphohistiocytic subtypes have been shown to have prognostic significance in this rare disease entity in paediatrics [1, 3, 4] as well as allowing accurate staging and providing support for targeted therapies. Chen et al. report that small cell/lymphohistocytic group had an event-free survival (EFS) of 55.7% (95% CI, 26.2–77.4) compared to non-small cell/lymphohistocytic group, which had an EFS of 87.4% (95% CI, 75.2–93.4) (p = 0.01). A limitation of this study was that only 58% (79/136) patients had pathological subtypes [1]. Currently, there is no consensus on treatment of multifocal pc-ALCL, and chemotherapy remains the standard for extranodal spread beyond local to regional lymph nodes [3, 5]. Multi-agent chemotherapy regimens are able to achieve an overall survival rate of around 90% [1]. The COG-ANHL12P1 protocol used in our patient is highly effective for paediatric ALCL as a group, with several other protocols in use as front-line and relapse management options [5]. Reported cases of cutaneous ALCL, particularly as a single lesion in addition to MDD, without any evidence of extranodal disease, are extremely scarce [2]. Multi-agent chemotherapy-related toxicity and long-term side effects must be considered alongside a positive response [1]. All authors have contributed and approved the final version of this manuscript. H.W. is supported by a My Room Peter McGrath Fellowship and The Kids’ Cancer Project; Col Reynolds PhD scholarship and the Bella Tripp Foundation. Consent was obtained from the patient and family to publish this case study and the accompanying images. The authors declare no conflicts of interest.