A rare case of highly differentiated follicular carcinoma in ovary with FGFR4 Gly388Arg polymorphism: a case report and literature review

Abstract

Background Highly differentiated follicular carcinoma (HDFCO) is a rare form of struma-derived thyroid-type carcinoma in ovary, defined as ovarian struma spreading beyond ovary but consisting of benign thyroid tissues. No more than 30 cases of HDFCO have been reported since it was first recognized in 2008. The clinicopathologic and molecular features of HDFCO remain unclear up till now. Case presentation A 38-year-old, para 1 gravida 5 woman has a long history of recurrent right ovarian cysts. Histological evaluation showed the tumor progressed from ovarian mature cystic teratoma (OMCT) to highly differentiated follicular carcinoma (HDFCO) during three relapses. Whole-exome sequencing revealed the germline FGFR4 Gly388Arg polymorphism. Repeated operations were performed to remove lesions for the first two relapses. On the third recurrence, the patient received radical surgery with subsequent thyroidectomy and radioactive iodine ablation. No evidence of disease was observed by February 2022 (8 months). Conclusions The germline FGFR4 Gly388Arg polymorphism may accelerate the malignant transformation of HDFCO, probably by working as a second hit in the developing spectrum.

Highly Differentiated Follicular Carcinoma of Ovarian Origin: A Systematic Review of the Literature

“…The ‘second-hit’ theory proposed by Henderson et al is supported by the recently published work by Bao et al, based on the significant heterogeneity of ovarian and distant disease tissue [ 17 , 30 ]. Specifically, the FGFR4 Gly388 Arg polymorphism has been identified as a key mutation in the developing process of the tumor [ 30 ].…”

“…The PRISMA flow diagram is presented in Figure 1 , and schematically describes the selection process and outcome. Finally, a total of 16 studies were included in the present analysis [ 10 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

“…In the remaining patients, the report was consistent with benign pathology other than struma ovarii, or not available. A history of HDFCO or struma peritonei was present in two patients, in both cases associated with a previous diagnosis of struma ovarii [ 25 , 30 ]. Interestingly, the only case reported to have parenchymal metastasis to the spleen, liver, and lung was associated with a previous diagnosis of “struma peritonei” that was surgically treated 12 years ago.…”

“…On a molecular level, HDFCO tissue lacks mutations commonly encountered in thyroid cancer [ 36 , 37 , 38 ]. The limited molecular analyses’ results suggest mutations of fibroblast growth factor receptor (FGFR) as the most significant epitope, influencing the tumor’s behaviour [ 30 ]. The ‘second-hit’ theory proposed by Henderson et al is supported by the recently published work by Bao et al, based on the significant heterogeneity of ovarian and distant disease tissue [ 17 , 30 ].…”

“…The limited molecular analyses’ results suggest mutations of fibroblast growth factor receptor (FGFR) as the most significant epitope, influencing the tumor’s behaviour [ 30 ]. The ‘second-hit’ theory proposed by Henderson et al is supported by the recently published work by Bao et al, based on the significant heterogeneity of ovarian and distant disease tissue [ 17 , 30 ]. Specifically, the FGFR4 Gly388 Arg polymorphism has been identified as a key mutation in the developing process of the tumor [ 30 ].…”