ALK-postive Large B-cell Lymphoma: Report of Two Cases and Review of the Literature

Abstract

Summary Anaplastic lymphoma kinase positive large B-cell lymphoma (ALK+ LBCL) is a rare variant of large B-cell lymphoma, but it rarely expresses B-lineage antigens (e.g CD20, CD79a) while showing an abnormal immunophenotype, such as positive for ALK, EMA, CD38, CD138. Only 55 cases of ALK+ LBCL have been reported so far in the published literature [1]. We present two additional cases of ALK+ LBCL, which were sent to our department for consultation from other hospitals. One was initially diagnosed as metastatic poorly differentiated carcinoma and the other was not able to be diagnosed. The two cases were finally diagnosed as “ALK+ LBCL” at our department of pathology (see below). The chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was given, respectively. Case 1 was given radiation therapy after chemotherapy, and case 2 wasn’t. Case 1, followed up for 16 months, was free of disease. Case 2 died at 8 months after the diagnosis. Due to the abnormal immunophenotype and rareness, the diagnosis of ALK+ LBCL is often difficult, even being misdiagnosed as carcinoma or plasma cell neoplasm. However, the treatment for these diseases is quite different from each another. Avoiding misdiagnosis of ALK+ LBCL is of great clinic importance. In this report, we describe the clinical, morphological, immunohistiochemical and cytogenetic features of the two ALK+ LBCL cases, reviewed 55 published cases, and compared the features with those of literature-reported cases. We came to the conclusions: ALK+ LBCL could affect non-adult and adult with a bimodal age distribution, with an average age of 12.5 years in the non-adult, and 43.5 years in the adult. ALK+ LBCL is a potential diagnostic pitfall for pathologists. Its diagnosis clues are that neoplastic cells are immunoblastic or/and plasmacytoid with prominent central nucleoli, positive for ALK, EMA and some markers of late (plasma cell-like) B-cell differentiation, like CD138, VS38 and immunoglobulins, negative for B-cell markers like CD20 and CD79a.  The investigation of involved genetic abnormality (CLTC-ALK fusion, or NPM-ALK rearrangement) contributes to confirm ALK+ LBCL. ALK+ LBCL has highly aggressive biobehavior and poor response to standard therapies. More patient case collection and prospective studies are needed.