Anaplastic lymphoma kinase-(ALK-) positive large B-cell lymphoma (ALK+ LBCL) is a rare, aggressive tumor characterized by an immunoblastic or plasmablastic morphologic appearance, expression of ALK, CD138, CD45, EMA, and often IgA by immunohistochemistry, and characteristic chromosomal translocations or rearrangements involving the ALK locus. The morphologic and immunophenotypic overlap of this tumor with other hematologic and nonhematologic malignancies may result in misdiagnosis. The tumor has been identified in both pediatric and adult populations and demonstrates a male predominance. Presentation is most often nodal, particularly cervical. No association with immunocompromise or geographic location has been recognized. The most common gene rearrangement is between clathrin and ALK (t(2;17)(p23;q23)), resulting in the CLTC-ALK chimeric protein, although other fusions have been described. Response to conventional chemotherapy is poor. The recent introduction of the small molecule ALK inhibitor, crizotinib, may provide a potential new therapeutic option for patients with this disease. 1. Introduction Anaplastic lymphoma kinase-(ALK-) positive large B-cell lymphoma (ALK+ LBCL) was first described by Delsol and colleagues in 1997 [1] and is now listed as a distinct entity in the 2008 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues [2]. ALK+ LBCL is an aggressive tumor with a poor response to conventional therapies. Although it appears to be very rare, it may in fact be underrecognized due to its morphologic and immunophenotypic overlap with other hematologic and nonhematologic entities. Awareness of this diagnosis, particularly in a new era of ALK inhibitor therapies, is necessary for hematopathologists as well as general surgical pathologists. 2. Clinical Features and Epidemiology Fewer than 100 cases of ALK+ LBCL have been described in the literature (reviewed in [3–6], subsequent cases reported in [7–13]). The neoplasm has been diagnosed in both pediatric and adult age groups, ranging in age from 9 to 85 years old, with a median age of 37 to 44.5 years, and with a male predominance of 3–5？:？1. The proportion of patients under age 18 has been found to comprise approximately 15–20% of the total. One confirmed case occurring in a patient with the human immunodeficiency virus (HIV) has been reported [12]. In general, patients do not appear to be immunocompromised. Furthermore, patients with this tumor do not appear to be restricted geographically; cases have been reported from Europe, the United States, and Asia. Our institution
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