Adult systemic anaplastic large-cell lymphoma: recommendations for diagnosis and management

Abstract

Summary Systemic anaplastic large cell lymphomas (sALCLs) comprise a heterogeneous group of relatively rare T-cell non-Hodgkin lymphomas characterized by CD30 expression and other unifying pathologic features. ALK fusions are present in about 50% of cases. Pathological diagnosis can be challenging, particularly in ALK-negative cases. Though ALK-positive and ALK-negative sALCL are similar morphologically and immunophenotypically, they are separate entities with different genetics, clinical behavior, and outcomes. Evidence-based data evaluating treatment regimens are limited as randomized controlled trials are lacking and most prospective studies are too small to draw definitive conclusions. However, recent advances in molecular biology are bringing forth much needed knowledge in this field, and are likely to guide further targeted therapeutic development.

Crizotinib induces apoptosis and gene expression changes in ALK+ anaplastic large cell lymphoma cell lines; brentuximab synergizes and doxorubicin antagonizes

“…ALK‐positive ALCL also occurs in adults, usually younger patients, but ALK‐negative ALCL is more common in older adults. ALK‐negative ALCL includes relatively indolent forms of cutaneous or mucocutaneous disease that often show DUSP22 and/or IRF4 rearrangements, and systemic ALCL that is typically aggressive . Treatment of both ALK+ and ALK– systemic ALCL in adults is usually anthracycline based …”

Anaplastic large cell lymphoma, ALK-negative

“…ALCL, ALK-negative is typically treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like chemotherapy, often followed by autologous stem cell transplantation (Bennani-Baiti, Ansell et al 2016). New targeted agents such as brentuximab vedotin and histone deacetylase inhibitors have demonstrated efficacy in relapsed and refractory disease.…”

Skin involvement as the first symptom of rapidly progressive ALK-positive systemic anaplastic large cell lymphoma

“…ALK‐positive ALCL typically presents with peripheral adenopathy, often with accompanying B symptoms . Most patients are symptomatic with advanced stage disease at the time of presentation (stage III/IV in around 60% of cases) . Skin involvement is not rare, and often manifests as masses, multiple nodules or nonhealing ulcers.…”

“…5,6 Most patients are symptomatic with advanced stage disease at the time of presentation (stage III/IV in around 60% of cases). 7 Skin involvement is not rare, and often manifests as masses, multiple nodules or nonhealing ulcers. The liver, lungs and bone are three other common extranodal sites of involvement.…”