Person:

Bongiovanni, Massimo

Papillary thyroid carcinoma with desmoid-type fibromatosis or nodular fasciitis like stroma is an extremely unusual and poorly understood subtype of papillary thyroid cancer. Although prior studies have demonstrated alterations in the Wnt/β-catenin signaling pathway in a few of these tumors, controversy still exists regarding the nature of the stromal spindle component. We have studied 9 cases of papillary thyroid carcinoma with prominent myofibroblastic stroma, including 8 men and 1 woman aged 20 to 58 years (mean age = 46). All cases displayed areas consistent with conventional papillary thyroid carcinoma embedded in abundant myofibroblastic-like stroma. The myofibroblastic stroma in 8 cases resembled desmoid-type fibromatosis and in one case it more closely resembled nodular fasciitis. By immunohistochemical staining, the stromal spindle component showed positivity for SMA and low MIB1 proliferation index in all cases, and strong nuclear positivity for beta-catenin in 8/9 cases. Stains for cytokeratin AE1/AE3 and PAX8 were positive in the epithelial elements but negative in the stromal component. Next generation sequencing was performed on 8 of 9 cases. CTNNB1 gene mutations were identified in 7/8 cases. BRAF mutations were identified in 3 cases and an NRAS mutation was identified in 1 case in the epithelial component. The case with fasciitis-like stroma was negative for beta-catenin by sequencing and immunostaining as well as negative for USP6 gene rearrangement. Our findings indicate that papillary thyroid carcinoma with prominent myofibroblastic stroma may represent more than one category of lesions.