DICER-1 Mutation Associated Sarcoma of Thyroid in An Adult Male

Abstract Introduction/Objective DICER-1 is an autosomal dominant tumor predisposition syndrome caused by germline DICER1 mutations. In the thyroid, it is associated with an early-onset multinodular goiter (MNG) and low-grade thyroid carcinomas. The aggressive variants thyroblastoma and poorly differentiated carcinoma are however seen in the pediatric age group. We report a case of DICER-1-associated (rhabdomyo) sarcoma without primitive components in an adult male. Methods/Case Report A 44-year-old healthy male with a family history of MNG, presented with a large left neck mass confirmed on imaging with largest 6.4cm, and extension into the mediastinum. FNA showed a malignant spindle cell- rich neoplasm with negative expression for Keratins, TTF-1, PAX-8, Calcitonin, INSM- 1 and SOX-10. The CEA and calcitonin were normal. The lymphoma was excluded by flow cytometry. The patient underwent a left thyroidectomy with central and left selective neck dissection. On gross examination, the left lobe of the thyroid was replaced by a tan- white, partially encapsulated solid mass. Microscopic examination revealed nests and sheets of ovoid to spindle- shaped cells with eosinophilic cytoplasm in fascicles with hypocellular areas with loose stroma. Foci of rhabdomyoblastic differentiation with straps cells, positive for desmin and myogenin were identified. Brisk mitotic activity and tumor necrosis were present. No primitive thyroid epithelium or blastemal component was identified. Tumor cells were negative for S100, SOX10 CD34, CD31, SMA, calponin, CD99, NKX2.2, SS18-SSX which excluded malignant peripheral nerve sheath tumor, angiosarcoma, leiomyosarcoma, Ewing’s sarcoma, and synovial sarcoma. Next-generation sequencing showed a DICER1 c.4517G>A (p.W1506) and c.5437G>C (p.E1813Q) mutation, both variants reported as germ-line variants. A final diagnosis of DICER-1-associated rhabdomyosarcoma was rendered. The patient underwent rehabilitation at another facility and lost to follow-up. Results (if a Case Study enter NA) NA Conclusion The case highlights the expanding spectrum of DICER-1-associated malignant tumors and the importance of keeping it in the differential diagnosis of unusual malignant tumors of the thyroid even in adults.