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

Abstract

BackgroundStruma ovarii (SO) is a rare form of ovarian mature teratoma in which thyroid tissue is the predominant element. Because of its rarity, the differential diagnosis between benign and malignant SO has not been clearly defined. 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.Case presentationWe report 35-year-old woman with bilateral ovarian cysts incidentally detected by ultrasound during the first trimester of pregnancy. Four months after delivery of a healthy child without complication she was admitted to the hospital for acute abdominal pain. Laparoscopic left adnexectomy was performed initially in a regional hospital; right cystectomy was done later in a specialized clinic. Intraoperative frozen section and a final pathology revealed that the cyst from the left ovary was composed of mature teratomatous elements, normal thyroid tissue (>50%) and a non-encapsulated focus of follicular variant of papillary thyroid carcinoma (PTC).Normal and cancerous thyroid tissues were tested for BRAF and RAS mutations by direct sequencing, and for RET/PTC rearrangements by RT-PCR/Southern blotting. A KRAS codon 12 mutation, the GGT → GTT transversion, corresponding to the Gly → Val amino acid change was identified in the absence of other genetic alterations commonly found in PTC.ConclusionTo the best of our knowledge, this is the first time this mutation is described in a papillary thyroid carcinoma arising in struma in the ovarii. This finding provides further evidence that even rare mutations specific for PTC may occur in such tumors. Molecular testing may be a useful adjunct to common differential diagnostic methods of thyroid malignancy in SO.

KRAS mutation positive mucinous adenocarcinoma originating in mature ovarian teratoma: Case report and review of literature

“…KRAS mutation may play an important role in malignant transformation of mature teratoma, which might simulate the molecular events underlying the carcinogenic process of colorectal carcinoma . Additional support for this assumption can be found in a recent report of malignant struma ovarii originating in mature teratoma with identified KRAS mutation in the sample, a mutation that is also present in some cases of thyroid carcinomas . This indicates that the common mutational drivers of various malignancies are also present in their somatic analogues in teratomas.…”

Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice

“…In humans, defects in the transition of PGCs to meiotically arrested oocytes, including aberrant mitosis and failure to maintain meiotic arrest predispose oocytes to tumorigenic transformation [ 6 , 16 , 17 ]. Genetic screening of ovarian cancer patients has revealed an association between OT development and mutations in genes that encode tumor suppressors and oncogenes including c-Kit , Pten , Kras and p53 [ 18 , 19 , 20 ]. Mutational inactivation of the tumor suppressor retinoblastoma protein 1 ( Rb1 ) gene has been detected in most types of human cancers, including human ovarian cancers and teratomas [ 19 , 21 , 22 ].…”

Extensive peritoneal implant metastases of malignant struma ovarii treated by thyroidectomy and 131I therapy

“…Furthermore, malignant struma ovarii has a similar molecular pathogenesis to malignant tumors originating in the thyroid, such as BRAF (b-raf proto-oncogene), RAS (retrovirus-associated DNA sequence) gene point mutations, and RET/PTC (RET proto-oncogene/papillary thyroid carcinoma) gene rearrangement, etc. [2,13–15] In our patient, the extensive abdominal and pelvic metastasis were detected 14 years after surgery for a left malignant ovarian ovarii. In addition, the patient had mild hyperthyroidism.…”