Roberta Poli1, Maria Scatolini2, Enrico Grosso2, Francesca Maletta3, Marco Gallo4, Daniele Liscia5, Anna Nelva6, Flora Cesario7, Giuseppe Forte8, Jasna Metovic9, Marco Volante9, Emanuela Arvat10, Mauro Papotti9. 1. Division of Internal Medicine, Ospedale degli Infermi, via dei Ponderanesi 2 Ponderano, 13875, Biella, Italy. rob.poli1979@libero.it. 2. Molecular Oncology Laboratory, Fondazione "Edo ed Elvo Tempia Valenta", via dei Ponderanesi 2, Ponderano, 13875, Biella, Italy. 3. Pathology Unit, AOU Città della Salute e della Scienza Hospital, via Santena 7, 10126, Turin, Italy. 4. Oncological Endocrinology, AOU Città della Salute e della Scienza di Torino Hospital, via Genova 3, 10126, Turin, Italy. 5. Pathology Unit, Ospedale degli Infermi, via dei Ponderanesi 2 Ponderano, 13875, Biella, Italy. 6. Endocrinology and Diabetology Unit, Ospedale degli Infermi, via dei Ponderanesi 2 Ponderano, 13875, Biella, Italy. 7. Division of Endocrinology, Diabetes and Metabolism, Santa Croce e Carle Hospital, Cuneo, Italy. 8. Pathology Unit, Santa Croce e Carle Hospital, via M Coppino 26, 12100, Cuneo, Italy. 9. Pathology Unit, Department of Oncology, University of Turin, via Santena 7, 10126, Turin, Italy. 10. Oncological Endocrinology, Department of Medical Sciences, University of Turin, via Genova 3, 10126, Turin, Italy.
Abstract
PURPOSE: Struma ovarii (SO) is a highly specialized ovarian teratoma, consisting of thyroid tissue. Rarely, carcinomas histologically identical to their thyroid counterparts may occur, and are comprehensively defined as malignant struma ovarii (MSO). Their optimal management is controversial, and the molecular profile of the malignant counterpart in the ovary is incompletely known. In this study, the clinicopathological and molecular features of six MSO from different Italian Institutions were analysed, to explore genetic profiles of potential therapeutic interest. METHODS: The histopathological features and immunoprofile (according to the known markers Galectin-3, HBME1, cytokeratin 19 and CD56) were reviewed. In addition, all cases underwent genetic analysis with a next-generation sequencing (NGS) hot spot cancer panel detecting mutations in 50 genes involved in cancerogenesis. RET/PTC rearrangements and TERT promoter alterations were also evaluated. RESULTS: Papillary carcinoma in all similar to its thyroid counterpart was found in five of six cases, including classical (two tumors) and follicular variant (three tumors) types. The last case was a poorly differentiated carcinoma. An activating gene mutation, was detected in five of six cases, including two NRAS, two BRAF, and one JAK3 oncogene mutations. No alterations were found in the other panel genes, nor in TERT promoter, or in RET chromosomal regions. CONCLUSIONS: MSO is a rare condition. Papillary carcinoma is the predominant malignant type, sharing both histomorphological and molecular features of its thyroid counterpart. Interestingly, the single case of poorly differentiated carcinoma displayed a JAK3 mutation. The presence of such driving mutation could be of potential interest in guiding postoperative treatment.
PURPOSE: Struma ovarii (SO) is a highly specialized ovarian teratoma, consisting of thyroid tissue. Rarely, carcinomas histologically identical to their thyroid counterparts may occur, and are comprehensively defined as malignant struma ovarii (MSO). Their optimal management is controversial, and the molecular profile of the malignant counterpart in the ovary is incompletely known. In this study, the clinicopathological and molecular features of six MSO from different Italian Institutions were analysed, to explore genetic profiles of potential therapeutic interest. METHODS: The histopathological features and immunoprofile (according to the known markers Galectin-3, HBME1, cytokeratin 19 and CD56) were reviewed. In addition, all cases underwent genetic analysis with a next-generation sequencing (NGS) hot spot cancer panel detecting mutations in 50 genes involved in cancerogenesis. RET/PTC rearrangements and TERT promoter alterations were also evaluated. RESULTS: Papillary carcinoma in all similar to its thyroid counterpart was found in five of six cases, including classical (two tumors) and follicular variant (three tumors) types. The last case was a poorly differentiated carcinoma. An activating gene mutation, was detected in five of six cases, including two NRAS, two BRAF, and one JAK3 oncogene mutations. No alterations were found in the other panel genes, nor in TERT promoter, or in RET chromosomal regions. CONCLUSIONS: MSO is a rare condition. Papillary carcinoma is the predominant malignant type, sharing both histomorphological and molecular features of its thyroid counterpart. Interestingly, the single case of poorly differentiated carcinoma displayed a JAK3 mutation. The presence of such driving mutation could be of potential interest in guiding postoperative treatment.