title: Intranodal palisaded myofibroblastoma: another mesenchymal neoplasm with CTNNB1 (β-catenin gene) mutations: clinicopathologic, immunohistochemical, and molecular genetic study of 18 cases.
abstract: Intranodal palisaded myofibroblastoma is a benign, lymph node-based myofibroblastic tumor of unknown pathogenesis. We report the clinicopathologic, immunohistochemical, and molecular genetic features of this rare entity. The study cohort consisted of 14 men and 4 women ranging in age from 31 to 65 (mean, 47; median 49) years with tumors arising in inguinal lymph nodes (n=15), a neck lymph node (n=1), and undesignated lymph nodes (n=2). Most individuals presented with a painless mass or lump. Possible trauma/injury to the inguinal region was documented in 4 cases. Tumors ranged in size from 1.0 to 4.2 (mean, 3.1; median; 3.0) cm. Microscopically, the process presented as a well-circumscribed, oftentimes pseudoencapsulated nodule (n=17) or nodules (n=1). Tumors consisted of a cellular proliferation of cytologically bland, spindled cells arranged in short fascicles and whorls within a finely collagenous (n=11) or myxocollagenous (n=7) matrix. In 12 tumors, scattered fibromatosis-like fascicles of spindled cells were noted. Histologic features characteristic of the process included nuclear palisades (n=16 cases), collagenous bodies (n=15), and perinuclear intracytoplasmic hyaline globules (n=10). Mitotic activity ranged from 0 to 8 (mean, 2; median, 1) mitotic figures/50 high-powered fields with no atypical division figures identified. Immunohistochemically, all tumors tested expressed smooth muscle actin and/or muscle-specific actin (n=5, each), and nuclear β-catenin and cyclin D1 (n=8, each). The latter 2 results prompted a screening for mutations in the β-catenin gene glycogen synthase kinase-3 β phosphorylation mutational "hotspot" region in exon 3 using polymerase chain reaction amplification and Sanger sequencing. Single nucleotide substitutions leading to missense mutations at the protein level were identified in 7 of 8 (88%) analyzed tumors and are responsible for the abnormal expression of β-catenin and cyclin D1. These results demonstrate that mutational activation of the β-catenin gene is likely a pivotal event in the pathogenesis of intranodal palisaded myofibroblastoma.
authors.affiliation: *Department of Pathology, Northwestern University, Chicago, IL †Laboratory of Pathology, National Cancer Institute (NCI), Bethesda ‡Department of Soft Tissue Pathology, Joint Pathology Center, Silver Spring, MD.
authors.forename: William B
authors.initials: WB
authors.lastname: Laskin
authors.forename: Jerzy P
authors.initials: JP
authors.lastname: Lasota
authors.forename: John F
authors.initials: JF
authors.lastname: Fetsch
authors.forename: Anna
authors.initials: A
authors.lastname: Felisiak-Golabek
authors.forename: Zeng-Feng
authors.initials: ZF
authors.lastname: Wang
authors.forename: Markku
authors.initials: M
authors.lastname: Miettinen
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009379:Neoplasms, Muscle Tissue / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin