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 beta-catenin and cyclin D1 (n = 8, each). The latter 2 results prompted a screening for mutations in the beta-catenin gene glycogen synthase kinase-3 beta 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 beta-catenin and cyclin D1. These results demonstrate that mutational activation of the beta-catenin gene is likely a pivotal event in the pathogenesis of intranodal palisaded myofibroblastoma.
