Intranodal Palisaded Myofibroblastoma

Abstract

Intranodal palisaded myofibroblastoma is a benign, lymph node-based myofibroblastic tumor of unknown pathogenesis. We report the clinicopathological, immunohistochemical, and genetic molecular features of this rare entity. The study cohort consisted of 14 males and 4 females 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 four 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, often times 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. Histological 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 (vimentin (n=3), smooth-muscle actin and/or muscle-specific actin (n=5, each), and nuclear beta-catenin and cyclin D1 (n=8, each). The latter two results prompted a screening for mutations in the beta-catenin gene glycogen synthase kinase-3 beta phosphorylation mutational “hotspot” region in exon 3 using PCR 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.

Recurrent Mutations within the Amino-Terminal Region of β-Catenin Are Probable Key Molecular Driver Events in Sinonasal Hemangiopericytoma

“…25 In contrast, CTNNB1 mutations in nasopharyngeal angiofibromas and palisaded myofibroblastoma of lymph node cluster within codons 32 to 37, whereas no mutations at serine 45 and threonine 41 have been documented. 30,31 In the current series of six SN-HPCs, we observed a similar pattern comparable to the latter two entities with predominant mutations of amino acids 33 to 35, and only one case displaying a mutation affecting serine 45. We cannot explain these interesting differences in the affected amino acid positions, but differential activation of components of Wnt signaling network and the b-catenin destruction complex in the probable different cells of origin of these distinct tumor entities may contribute to these different mutation signatures.…”

“…25,26,28,29 Moreover, recurrent mutations in the amino-terminal region of CTNNB1 have also been reported in 75% of nasopharyngeal (juvenile) angiofibromas, 30 and recently, in 88% of palisaded myofibroblastoma of lymph node (synonym: intranodal hemorrhagic spindle cell tumor with amianthoid fibers). 31 In both entities, CTNNB1 mutations were also accompanied by strong nuclear b-catenin immunoreactivity. 30,31 Nasopharyngeal (juvenile) angiofibroma is a rare lesion with striking predominance for young males.…”

“…31 In both entities, CTNNB1 mutations were also accompanied by strong nuclear b-catenin immunoreactivity. 30,31 Nasopharyngeal (juvenile) angiofibroma is a rare lesion with striking predominance for young males. It occurs in the posterolateral wall of the nasal cavity and the nasopharynx and is characterized by irregular vessels embedded in a fibrous stroma.…”

Fine-Needle Aspiration Cytology of Intranodal Palisaded Myofibroblastoma of the Inguinal Lymph Node

“…In the most recent case report, the FNA smears of IPM yielded scarce material; however, amianthoid fibers were present in a scrape cytologic specimen from the surgically resected lymph node [3]. A recent surgical pathology case report of a series of 18 cases of IPM shows 15 positive for variable numbers of round, stellate or elongated eosinophilic bodies [7]. These amianthoid fibers do not exist in other spindle cell neoplasms of the inguinal lymph node.…”

“…This cytologic feature has not been documented in other spindle cell neoplasms at this location. When in doubt, a panel of immunohistochemistry provides a more definitive diagnosis because the neoplastic spindle cells of IPM are positive for muscle actin [5], cyclin D1 [8] and beta-catenin [7], and are negative for S-100, CD34, melanocytic markers and cytokeratin.…”