Intranodal Palisaded Myofibroblastoma: Another Mesenchymal Neoplasm With CTNNB1 (β-catenin Gene) Mutations: Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 18 Cases

• Published in: The American journal of surgical pathology Vol. 39; no. 2; pp. 197 - 205
• Main Authors: Laskin, William B, Lasota, Jerzy P, Fetsch, John F, Felisiak-Golabek, Anna, Wang, Zeng-Feng, Miettinen, Markku
• Format: Journal Article
• Language: English
• Published: United States by Lippincott Williams & Wilkins 01-02-2015
• Subjects: Adult; Aged; beta Catenin - genetics; Female; Humans; Immunohistochemistry; Lymph Nodes - metabolism; Lymph Nodes - pathology; Male; Middle Aged; Mutation; Neoplasms, Muscle Tissue - genetics; Neoplasms, Muscle Tissue - metabolism; Neoplasms, Muscle Tissue - pathology; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0147-5185; 1532-0979
• DOI: 10.1097/PAS.0000000000000299

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.