title: Primary cutaneous ALCL with phosphorylated/activated cytoplasmic ALK and novel phenotype: EMA/MUC1+, cutaneous lymphocyte antigen negative.
abstract: Primary cutaneous anaplastic large-cell lymphoma (ALCL) ordinarily is distinguished from systemic ALCL by clinical presentation, absence of anaplastic lymphoma kinase (ALK) expression, and immunophenotype (CLA+, EMA/MUC1-). We present an exceptional case of an elderly man with primary cutaneous ALCL and no systemic disease for a 13-year period. Recurrent skin tumors in this patient were characterized by anaplastic, often multinucleated, cells infiltrating the lymphatics and associated with pseudoepitheliomatous hyperplasia. Cutaneous lymphocyte antigen was absent and EMA/MUC1, typical of systemic ALCL, was strongly expressed by the tumor cells. Remarkably, the tumor cells expressed a cytoplasmic-only variant of ALK protein, as reported in 3 previous cases of primary cutaneous ALCL. Fluorescence in situ hybridization revealed lack of rearrangements of the chromosome 2 ALK gene locus usually involved by translocation t(2;5) or other chromosomal rearrangements that generate nucleophosmin-ALK or the variant ALK fusions that occur in systemic ALCL. Nonetheless, the cytoplasmic ALK protein in the patient's tumor cells was shown to be phosphorylated/activated, suggesting a novel mechanism of ALK activation. Primary cutaneous ALCL of this novel subtype should be distinguished from systemic ALCL to ensure proper clinical management.
authors.affiliation: Department of Pathology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Marshall E
authors.initials: ME
authors.lastname: Kadin
authors.forename: Jack L
authors.initials: JL
authors.lastname: Pinkus
authors.forename: Geraldine S
authors.initials: GS
authors.lastname: Pinkus
authors.forename: Ivan H
authors.initials: IH
authors.lastname: Duran
authors.forename: Christine E
authors.initials: CE
authors.lastname: Fuller
authors.forename: Mihaela
authors.initials: M
authors.lastname: Onciu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Morris
mesh_terms: D017668:Age of Onset; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D008562:Membrane Glycoproteins; D018396:Mucin-1; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases