RAS Mutation-Positive Follicular Variant of Papillary Thyroid Carcinoma Arising in a Struma Ovarii

Abstract

Struma ovarii is an ovarian mature teratoma composed exclusively or predominantly of thyroid tissue. Malignant transformation of struma ovarii is rare and poorly understood, although this process is thought to be similar to carcinogenesis in malignant tumors of differentiated thyroid tissue originating in the thyroid gland. Genetic alterations in the mitogen-activated protein kinase pathway, including mutations of BRAF, RAS, and RET genes, have been implicated in the development of differentiated thyroid carcinoma arising in the thyroid gland. We report here a case with RAS mutation detected in a malignant struma ovarii. The patient is a 38-year-old female who had a 2.4 cm ovarian cyst noted incidentally on a first trimester ultrasound. She proceeded to ovarian cystectomy post-delivery, with pathologic examination detecting a papillary thyroid carcinoma, follicular variant, arising in a cystic teratoma. The tumor was tested for BRAF, RAS, and RET/PTC mutations. HRAS codon 61 mutation was identified. This is the first report of RAS mutation detected in the follicular variant of papillary carcinoma arising in a struma ovarii. It provides evidence that tumors developing in this setting involve molecular mechanisms similar to those implicated in tumors developing in the thyroid gland.

Unilateral follicular variant of papillary thyroid carcinoma with unique KRAS mutation in struma ovarii in bilateral ovarian teratoma: a rare case report

“…Previous case series describe the presence of point mutations in BRAF, NRAS, HRAS , and RET/PTC rearrangements but none in the KRAS gene [6,15-17]. The present report therefore describes for the first time a KRAS codon 12 mutation in a case of PTC with a follicular growth pattern arising in SO in combination with bilateral teratoma [10-12].…”

“…The real incidence of malignancy in SO is unclear because of its rarity but the existing literature indicates that 5%–10% of such tumors are malignant with papillary and less frequently, follicular carcinoma being the most common [1-4]. It is believed that malignant transformation of SO has similar molecular features with and its prognosis corresponds to that of malignant tumors originating in the thyroid [5,6]. The molecular pathogenesis of papillary thyroid carcinomas (PTC) is largely associated with genetic alterations in the RET-RAS-RAF-MAPK pathway usually caused by RET/PTC rearrangements (13%–43%) or activating point mutations in the BRAF (29%–83%) or RAS- family genes (0 %–21 %).…”

“…The molecular pathogenesis of papillary thyroid carcinomas (PTC) is largely associated with genetic alterations in the RET-RAS-RAF-MAPK pathway usually caused by RET/PTC rearrangements (13%–43%) or activating point mutations in the BRAF (29%–83%) or RAS- family genes (0 %–21 %). These molecular alterations occur cumulatively in up to 70% of all follicular cell-derived thyroid carcinomas in a nearly mutually exclusive manner [6-9]. …”

A Case of Papillary Thyroid Carcinoma in Struma Ovarii and Review of the Literature

“…Kondo et al reviewed the pathogenetic mechanisms of thyroid follicular cell neoplasia and found mutations of BRAF (29%–69%), RET (13%–43%), and RAS (0%–21%) are most commonly seen in adult papillary thyroid carcinoma; RET rearrangements are more prevalent in adult tumors associated with previous radiation exposure [14]. Celestino et al reported a case of follicular variant of papillary thyroid carcinoma in a struma ovarii with NRAS mutation (Q61R) and a PAX8-PPARc rearrangement which fitted well with the similar results seen in cervical counterpart [18] and Coyne and Nikiforov reported HRAS codon 61 mutation in a case of follicular variant of papillary thyroid carcinoma in a struma ovarii [19]. Papillary carcinomas harboring RAS mutation almost always have the follicular variant histology.…”

Thyroid Histology

“…Malignant struma usually are treated surgically, and radioactive iodine may be effective in treating metastatic struma [ 44 ]. Although most patients with malignant struma do well, some have died from the disease, particularly if there was metastasis [ 45 ]. In a study of 88 cases of malignant struma ovarii, the survival rate was 89 % at 10 years and 84 % at 25 years [ 46 ] …”