The t(2;5) translocation that involves the ALK gene accounts for about 80% of the ALCL cases (14) (Fig. 1). In the remaining cases, other variant rearrangements involving ALK gene are seen, including t(1;2)(q21;p23), inversion 2(p23;q35), t(2;3)(p23;q21), t(2;17)(p23;q23), and t(X;2)(q11-12;p23). In these uncommon rearrangements ALK gene is juxtaposed to TPM3, encoding a nonmuscle tropomyosin; TFG (TRCK fusion gene), encoding a polypeptide with a predicted coiled:coiled domain; ATIC, which encodes an enzyme, 5-aminoimidazole-4-carboximide-1-ß-D-ribonucleotide transformylase/inosine monophosphate cyclohydrolase, that participates in purine metabolism; CLTC, encoding the clathrin heavy-chain gene; or MSN, encoding moesin, a member of the protein 4.1 family of membrane-associated polypeptides(15-20).
ALK gene is translocated not only in ALCL, but also in inflammatory myofibroblastic tumor. Tropomyosin 4 and RANBP2 genes were found involved only in inflammatory myofibroblastic tumor, nucleophosmin and TRCK fusion gene in ALCL only, while tropomyosin 3, and clathrin heavy chain genes were found involved in rare cases of both ALCL and inflammatory myofibroblastic tumors (27,28). ALK has also been detected by immunohistochemistry in some sarcomas, particularly rhabdomyosarcoma (29). However, in most of the soft tissue tumors, except the inflammatory myofibroblastic tumors, it displayed merely low-level expression. It has also been described in some cases of neuroblastoma (30).
ALK1 can also be expressed in diffuse large B cell lymphoma (DLBCL). These are unique DLBCL with monomorphic large immunoblast-like cells, containing large central nucleoli, which tend to invade lymphatic sinuses. Superficially they resemble anaplastic large cell lymphoma (ALCL) but they lack CD30. These lymphomas express epithelial membrane antigen (as do ALCL), but also contain cytoplasmic IgA (31). In contrast, CD30-positive DLBCL are ALK1-negative.
ALK-positive ALCL usually present in young men, presenting with advanced disease (stage III or IV), are commonly associated with fever, and there is extra nodal involvement. However, they respond well to chemotherapy and have a favourable outcome (24,25). Interestingly, ALK-positive ALCL are consistently BCL2-negative (26).
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