title: Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases.
abstract: Abnormalities of chromosome 2p23 with expression of ALK1 and p80 occur in both inflammatory myofibroblastic tumor (IMT) and anaplastic large cell lymphoma. This immunohistochemical study investigates whether the ALK family of neoplasms includes fibroblastic-myofibroblastic, myogenic, and spindle cell tumors. Formalin-fixed paraffin-embedded archival tissues from 10 IMTs and 125 other soft tissue tumors were stained for ALK1 and p80 with standard immunohistochemistry. ALK1 and/or p80 reactivity was observed in a cytoplasmic pattern in IMT (4/10; 40%), malignant peripheral nerve sheath tumor (4/10; 40%), rhabdomyosarcoma (6/31; 19%), leiomyosarcoma (1/10; 10%), and malignant fibrous histiocytoma (1/11; 9%). No staining was observed in nodular fasciitis, desmoid, infantile myofibromatosis, infantile fibrosarcoma, synovial sarcoma, leiomyoma, or myofibrosarcoma. Alveolar rhabdomyosarcomas (4/16; 25%) displayed a distinctive dot-like cytoplasmic positivity. No cases displayed nuclear reactivity. Fluorescent in situ hybridization on 12 of the positive cases revealed a combination of abnormalities including ALK break-apart signals, nucleophosmin (NPM)/ALK fusions, or extra copies of 2p23. This study demonstrates that in addition to IMT, abnormalities of ALK1 and p80 expression with a variety of structural chromosomal changes are found in several sarcomas, especially rhabdomyosarcoma and malignant peripheral nerve sheath tumor. Although immunoreactivity in non-IMTs cannot distinguish between structural abnormalities involving 2p23 or additional copies of 2p23, it supports the concept of ALK involvement in a larger group of neoplasms, some of which have other documented clonal abnormalities. In IMT, immunohistochemistry for ALK1 and p80 is useful as an indicator of a 2p23 abnormality, but it must be interpreted in the context of histologic and other clinicopathologic data if used as an adjunct to differential diagnosis.
authors.affiliation: Department of Pathology, Primary Children's Medical Center and University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Cessna
authors.forename: Holly
authors.initials: H
authors.lastname: Zhou
authors.forename: Warren G
authors.initials: WG
authors.lastname: Sanger
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
authors.forename: Sheryl
authors.initials: S
authors.lastname: Tripp
authors.forename: Diane
authors.initials: D
authors.lastname: Pickering
authors.forename: Clark
authors.initials: C
authors.lastname: Daines
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Coffin
mesh_terms: D030201:Activin Receptors, Type I / Q000096:biosynthesis*; D030301:Activin Receptors, Type II; D000077548:Anaplastic Lymphoma Kinase; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000096:biosynthesis*; D002648:Child; D002869:Chromosome Aberrations; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003937:Diagnosis, Differential; D005350:Fibroma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007890:Leiomyosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis*; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D018224:Myofibromatosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009379:Neoplasms, Muscle Tissue / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018317:Nerve Sheath Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; C438384:P80 protein, Mycoplasma; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C425364:ACVRL1 protein, human; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II