Endocrine Abstracts

JOINT2944

Background: DHGTC and PDTC are rare, aggressive forms of TC with intermediate prognosis, thus posing significant therapeutic challenges.

Case-report-1: A 59-year-old male underwent total thyroidectomy with neck dissection and internal jugular vein thrombectomy due to a rapidly growing neck mass. Histopathological report revealed PDTC-70% with DHGTC foci-30%, 20/40 infiltrated lymph nodes (LNs) and tumor thrombus. Tumor molecular analysis (TMA) (AmoyDx® HANDLE Classic-NGS-Panel) revealed a PTEN-InDel (Intron 6, c.634+1G>C, p.?). Preoperative whole-body CT-scans performed due to elevated Tg:962.3ng/ml, revealed no distant metastases. However, a postoperative (4-weeks after CT-scans) 18FDG-PET CT-scan showed hypermetabolic activity in: thyroid bed, cervical/mediastinal LNs, sternum manubrium, and in a single lung nodule. Diagnostic (5mCi-¹³¹I) whole-body scan (WBS) showed no uptake in the lung or sternum. Radiotherapy was delivered to the manubrium (total dose:40Gy). In chest CT-scan 75-days after 18FDG-PET, disease progression was documented with a more than double increase in the size of the lung node, slight increase in cervical LNs and rising Tg:6851.49ng/ml. Systemic treatment (ST) with lenvatinib-20mg daily, pembrolizumab-200mg Q3W and denosumab-120mg once per month, was initiated. 90-days after, mixed response was documented by 18FDG-PET (regression of lung, sternum, and LNs metastases), three new small suspicious bone lesions (right acetabulum, left hip-bone, C7-vertebra) and a lesion invading the cricoid cartilage, while Tg decreased:394.24ng/ml.

Case-report-2: A 73-year-old female with a history of large, multifocal, locally invasive papillary TC and negative for distant metastases post-therapy ¹³¹I-WBS underwent revision surgery due to disease persistence. Histopathological report revealed widely invasive DHGTC with PDTC foci, which was in concordance with the revised by an expert pathologist first report. Chest CT-scan revealed multiple cannonball lung metastases while brain-MRI revealed 10 metastatic lesions; Tg:6325.17ng/ml. TMA revealed a BRAFV600E mutation. Stereotactic radiosurgery was performed to brain metastases (maximum dose:24Gy) with a lesion volume decrease up to 75% within two-months. ST treatment with dabrafenib 75mg-bid was initiated and a mixed response in lung was documented within 3-months while increased Tg:15679.18ng/ml, implied possible re-differentiation. Nevertheless, structural progression was documented after one-month with subsequent Tg decrease:10111.02ng/ml and Trametinib-2mg daily was added to the treatment. Mixed response in lung was documented within 2-months with increased Tg:20159.66ng/ml. Albeit mixed response, the patient succumbed to complications from lung metastases.

Conclusion: PDTC and DHGTC are rare, aggressive types of TC requiring a multidisciplinary approach. When and where to perform locoregional therapies in combination with the type of ST according to TMA is of paramount significance towards appropriate therapeutic management and precision medicine implementation.