BPI-ALCL is associated with occasional mutations in one or two genes but has not been reported to be associated with products of gene translocations or rearrangements. ALK-positive anaplastic large cell lymphoma
Signs and symptoms
ALK-positive ALCL occurs mostly but not exclusively in children and young adults and is slightly more common in males. Most individuals present with stage III or IV (i.e. advanced) disease. They evidence systemic symptoms including B symptoms such as fever, night sweats, and weight loss in 75% of cases; lymph node enlargement (90%) including those in the mediastinum (36%); and lymphomatous lesions in the skin (26%), bone (14%), soft tissues (15%), lung (12%), and/or liver (8%). Tumor cells are found in the bone marrow in up to 40% of the cases when immunohistochemical analysis is performed. Involvement of the central nervous system or a leukemia-like circulation of malignant cells in the blood occurs only very rarely. Most patients, including up to 90% of young children and adolescents, have circulating autoantibodies directed against the ALK fusion protein expressed by their tumor cells. Diagnosis
ALK-positive ALCL is diagnosed by histological and immunological examinations of involved tissues, typically lymph nodes. These tissues have lymphoma-like infiltrates that have variable numbers of ALCL "hallmark" cells, i.e. cells with kidney- or horseshoe-shaped nuclei that strongly express CD30 as detected by immunohistochemistry and an ALK fusion protein as detected by fluorescence in situ hybridization. These cells are scattered throughout the infiltrates.
The histology of palpable masses exhibit a different pathological picture: the tumor masses have multinodular areas that consist of necrosis or fibrous tissue interspaced with areas that consist of large neoplastic cells that have abundant cytoplasm and abnormally shaped nuclei within a fibrotic and chronic inflammatory cell background. Again, typical ALCL-defining "hallmark" cells may be difficult to find in these masses. The effusions show abundant, uniform-appearing, non-cohesive large cells with irregularly-shaped nuclei, prominent nucleoli and abundant cytoplasm. The histology and pathological features of diseased lymph nodes and tissues outside of the breast implant are indistinguishable from those seen in ALK-negative ALCL. The neoplastic cells in the capsules, effusions, and tissues strongly and uniformly express CD30, CD4 (75–84% of cases), EMA (48–90%), CD43 (86-95%), CD45 (44-74%), and in a far fewer percentage of cases various other marker proteins. These cells do not express ALK and often lack the characteristic surface marker proteins of T-cells. Identification of the status of these markers helps diagnose the disease. Gene and molecular abnormalities
No chromosome translocations, chimeric genes, or fusion proteins have been described in BIA-ALCL although the neoplastic cells in the disease have been described to have gene copy number variations involving gains in gene copies on the p arm of chromosome 19 and losses of gene copies in the p arms of chromosome 10 and 1. The neoplastic cells in BIA-ALCL show mutations of the STAT3 gene in 64% of cases and reports of mutations in JAK1, JAK3, DNMT3A, and TP53 genes.