Papillary thyroid carcinoma with nodular fasciitis-like stroma and β-catenin mutations should be renamed papillary thyroid carcinoma with desmoid-type fibromatosis

Abstract

Various histological variants of papillary thyroid carcinoma have been reported, some with clinical implications, some with peculiar, sometimes misleading morphologies. One of these rare and poorly characterized variants is papillary thyroid carcinoma with nodular fasciitis-like stroma, of which fewer than 30 cases have been documented, mostly as isolated reports. It is a dual tumor comprising a malignant epithelial proliferation that harbors typical features of conventional papillary thyroid carcinoma, admixed with a prominent mesenchymal proliferation resembling nodular fasciitis or fibromatosis. Thus, the terms papillary thyroid carcinoma with nodular fasciitis-like stroma and papillary thyroid carcinoma with fibromatosis-like stroma are used interchangeably; however, the former term suggests a self-limited and regressing disease, whereas the latter one suggests a recurrent and potentially aggressive one. Better genetic and ultrastructural characterization could lead to more appropriate terminology and management. We performed detailed clinicopathological and molecular analyses of two cases of PTC with prominent mesenchymal proliferation that developed in the thyroid gland of two male patients aged 34 and 48. In both cases, the epithelial component harbored a heterozygous somatic activating BRAF mutation (p.V600E). Also, in both cases, the mesenchymal component showed typical aberrant nuclear and cytoplasmic immunoreactivity for β-catenin and harbored a heterozygous somatic activating mutation in the corresponding CTNNB1 gene (p.S45P). This mutation has never been reported in thyroid stroma; in other tissues, it is typical of desmoid-type fibromatosis rather than nodular fasciitis-like stroma. We therefore propose that in cases of papillary thyroid carcinoma with a prominent mesenchymal component, mutations in CTNNB1 should be sought; when they are present, the term 'papillary thyroid carcinoma with desmoid-type fibromatosis' should be used. As the mesenchymal component of these tumors is not expected to concentrate radioactive iodine, special considerations apply to clinical evaluation and follow-up, which should be brought to the attention of the treating specialist.

Papillary thyroid carcinoma with desmoid-type fibromatosis: A clinical, pathological, and immunohistochemical study of 14 cases

“…We agree with the proposal by Rebecchini et al [5]. Microscopically, the stromal component is consistent with DTF and not with nodular fasciitis.…”

“…Toti et al [15] and Michal et al [16] reported that the DTF components were present at the tumor periphery. In the cases reported by Terayama et al [17], Ginter, et al [12], and Rebecchii et al [5], the distributions were central, mixed, and diffuse, respectively. In our study, 4, 1, 7, and 2 cases of PTC-DTF exhibited central, peripheral, mixed, and diffuse patterns, respectively.…”

“…Recently, Rebecchini et al reported 2 cases of PTC with nodular fasciitis-like stroma [5]. In the report, they proposed that the variant should be renamed PTC-DTF because the mesenchymal component showed aberrant nuclear and cytoplasmic immunoreactivity for beta-catenin and harbored a heterozygous somatic activating mutation in the corresponding CTNNB1 gene [5].…”

Immunohistochemical and Molecular Analyses Focusing on Mesenchymal Cells in Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis

“…Recently, Rebecchini et al [2] reported a mutation in exon 3 of CTNNB1 in the mesenchymal components of two cases of PTC with fibromatosis/nodular fasciitis-like stroma. The involvement of the activated Wnt/β-catenin pathway has not been observed in nodular fasciitis, so they proposed a more suitable term for this variant: PTC with desmoid-type fibromatosis (PTC-DTF) [2]. This study was designed to evaluate the prevalence of CTNNB1 mutations in more cases of PTC-DTF exhibiting aberrant nuclear and cytoplasmic immunoreactivity for β-catenin.…”

“…Because aberrant nuclear and cytoplasmic immunoreactivity for β-catenin is observed in the mesenchymal components, it has been suggested that activated Wnt signaling is involved in the stromal overgrowth of this variant [2].…”