Cribriform-Morular Variant of Papillary Thyroid Carcinoma in an 8-Year-Old Girl

Abstract

The description of the histological features and the immunohistochemical and molecular analyses of a case of cribriform-morular variant of papillary thyroid carcinoma in an 8-year-old girl with a family history of adenomatous polyposis is presented. The neoplasm was multifocal and bilateral, with a mixed pattern of solid, trabecular, and morular areas. The neoplasm showed angioinvasive behavior, extracapsular infiltration with extension to the perythyroidal muscles, and lymph node metastases. Tumor cells were positive for CAM 5.2, cytokeratins 5/6, TTF-1, HBME-1, galectin-3, and β-catenin. In addition, the molecular tests did not reveal BRAF mutations, RET/PTC rearrangement, APC mutation, or KRAS mutation.

Cribriform-morular variant of thyroid carcinoma: a neoplasm with distinctive phenotype associated with the activation of the WNT/β-catenin pathway

“…From the pooled data we collected, extrathyroidal extension was described in only five patients [31,53,56,58], and local recurrence in six [10,15,17,56]. Regional lymph node metastases were reported in 13/134 (10%) patients [7,9,15,21,22,36,40,48,51,56,60], and distant metastases in 6/107 (6%) patients, to lung (5 cases), bone (n = 2) and brain (n = 1) [10,22,37,51,56,60,73]. Death due to the thyroid carcinoma has been reported in 4 patients (3 women and 1 man), whose age ranged from 20 to 42 years (mean, 32).…”

Cribriform-morular variant of papillary thyroid carcinoma: a distinctive type of thyroid cancer

“…K-RAS mutation has been reported once in an 18-year-old woman with FAP and CMV-PTC by Giannelli and coworkers (Giannelli et al 2014). On the other hand, the other 7 cases tested in the literature were negative for RAS mutations (Rossi et al 2012, Nakazawa et al 2013, Kwon et al 2015, Brehar et al 2016, Oh et al 2016). It appears that RAS mutation is uncommon in CMV-PTC.…”

“…Multinational studies have demonstrated that BRAF mutation in papillary thyroid carcinoma is associated with increased mortality and cancer recurrent rate (Xing et al 2013(Xing et al , 2015. In the literature, BRAF mutation was tested in 18 cases of CMV-PTC (Rossi et al 2012, Nakazawa et al 2013, Giannelli et al 2014, Kwon et al 2015, Brehar et al 2016, Oh et al 2016, and the results showed that these cancers were negative for BRAF mutation. The absence of BRAF mutation in CMV-PTC may explain the relative indolent nature of this type of papillary thyroid carcinoma.…”

“…RET/PTC rearrangement is more commonly found in thyroid carcinomas in children and young adults as well as in papillary thyroid carcinomas 24:4 associated with radiation exposure (Klugbauer et al 1995, Nikiforov 2002. In CMV-PTC, 4 of the 6 cases (67%) tested in 4 different studies showed RET/PTC rearrangement (Soravia et al 1999, Rossi et al 2012, Giannelli et al 2014, Brehar et al 2016. Thus, RET/PTC rearrangement appears to be involved in the pathogenesis of a portion of papillary thyroid carcinomas in young patients.…”

Cribriform-morular variant of papillary thyroid carcinoma: a study of 3 cases featuring the PIK3CA mutation

“…The BRAF mutation, a substitution of a valine for a glutamic acid (V600E), represents the etiology leading to the major pathogenesis of PTC. However, BRAF mutations have never been found in CMV-PTCs [4,[9][10][11][12][13], and KRAS mutations have only been reported in a single case study (Table 1) [13]. PI3K/Akt signaling has been demonstrated as an additional essential modulator of Wnt activity [6,7].…”