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Sara Donato Endocrinology Department, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal

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Helder Simões Endocrinology Department, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal
NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

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Valeriano Leite Endocrinology Department, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal
NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal

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Introduction: Struma ovarii (SO) is a rare ovarian teratoma characterized by the presence of thyroid tissue in more than 50% of the tumor. Malignant transformation is rare and the most common associated malignancy is papillary thyroid carcinoma (PTC). Pregnancy may represent a stimulus to differentiated thyroid cancer (DTC) growth in patients with known structural or biochemical evidence of disease, but data about malignant SO evolution during pregnancy are rare. We present the first reported case of a pregnant patient with malignant SO and biochemical evidence of disease. Case Presentation: A previously healthy 35-year-old female diagnosed with a suspicious left pelvic mass on routine ultrasound was submitted to laparoscopic oophorectomy which revealed a malignant SO with areas of PTC. A 15-mm thyroid nodule (Bethesda V in the fine-needle aspiration cytology) was detected by palpation and total thyroidectomy was performed. Histology revealed a 15 mm follicular variant of PTC (T1bNxMx). Subsequently, she received 100 mCi of radioactive iodine therapy (RAIT) with the whole-body scan showing only moderate neck uptake. Her suppressed thyroglobulin (Tg) before RAI was 1.1 ng/mL. She maintained biochemical evidence of disease, with serum Tg levels of 7.6 ng/mL. She got pregnant 14 months after RAIT, and during pregnancy, Tg increased to 21.5 ng/mL. After delivery, Tg decreased to 14 ng/mL but, 6 months later, rose again and reached 31.9 ng/mL on the last follow-up visit. TSH was always suppressed during follow-up. At the time of SO diagnosis, a chest computed tomography scan showed 4 bilateral lung micronodules in the upper lobes which were nonspecific, and 9 months after diagnosis, a pelvic MRI revealed a suspicious cystic nodule located on the oophorectomy bed. These lung and pelvic nodules remained stable during follow-up. Neck ultrasonography, abdominal MRI, and fluorodeoxyglucose-positron emission tomography showed no suspicious lesions. Discussion/Conclusion: As for DTC, pregnancy seems to represent a stimulus to malignant SO growth. This can be caused by the high levels of estrogen during pregnancy that may bind to receptors in malignant cells and/or by the high levels of hCG which is known to stimulate TSH receptors.

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Daniela Cavaco Department of Endocrinology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Sara Carvalhal Department of General Surgery, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Valeriano Leite Department of Endocrinology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

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Advanced papillary thyroid carcinoma (PTC) with cutaneous metastases may cause pain, ulceration, and bleeding. Electrochemotherapy (ECT) is a minimally invasive treatment of tumors located in the skin and subcutaneous tissue. The electric pulses potentiate the toxicity of cytostatic agents entering the tumor cell. It is highly effective especially to relieve pain and improve the quality of life. The adverse events are local and transient. A case of progressive metastatic PTC who developed bleeding cutaneous metastases treated with ECT is described.

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Inês Cosme I Cosme, Endocrinology, Unidade Local de Saúde Santa Maria, Lisbon, Portugal

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Ana Figueiredo A Figueiredo, Endocrinology, Instituto Português de Oncologia de Lisboa, Lisboa, Portugal

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Sara Pinheiro S Pinheiro, Endocrinology, Instituto Português de Oncologia de Lisboa, Lisboa, Portugal

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Valeriano Leite V Leite, Endocrinology, Instituto Português de Oncologia de Lisboa, Lisboa, Portugal

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Thyroid carcinoma (TC) incidence increased over the past 50 years. The explanation for this is not consensual.

Objective: Compare incidental vs. non-incidental TC (ITC vs. NITC) regarding demographic, clinical, histological data and 5-year clinical outcomes.

Design: Retrospective analysis of 225 papillary TC (PTC) cases that completed a 5-year follow-up.

Methods: Created 2 groups: ITC (including the incidentalomas) and NITC (cases of palpable or visible nodules or with thyroid compressive complaints).

Results: Included 225 PTC (122 were ITC). There were 95 women in ITC and 78 in NITC. ITC patients were significantly older (53.3±14.8 vs 47.2±17.7, p=0.006). Groups had no differences in family history of TC. ITC mean tumour size was smaller (19.1±9.2 vs 28.6±16.2, p<0.01). Tumours >20mm comprised 36.1% of ITC and 58.2% of NITC. We found no differences in tumour multifocality, histological thyroiditis, aggressive PTC subtypes, capsule or lymph-vascular invasion and gross extrathyroidal extension. There were no differences regarding the number of patients submitted to RAI or in RAI activity. pTMN staging showed higher prevalence of T3a and T4 cases (p<0.01), and M1 status (p=0.025) in NITC. There were no differences in the rates of persistence of disease. Logistic regression showed that the diagnostic modality had no impact on the 5-year clinical outcome.

Conclusions: ITC patients were older and had smaller tumours. NITC showed no worst histological features or 5-year clinical outcome. Approximately, one third of ITC had diameters >20mm. As even large tumours can be ITC, overdiagnosis can be the most likely cause for the TC increasing incidence.

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Tiago Nunes da Silva Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Edward Limbert Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Valeriano Leite Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Purpose: The role of thyroglobulin (Tg) in predicting death and recurrence risk in patients with poorly differentiated thyroid carcinoma (PDTC) is not well established. We aimed to analyze Tg levels following total thyroidectomy and adjuvant radioiodine treatment (RAI) in PDTC patients and correlate Tg levels with survival and recurrence. Methods: A retrospective analysis was conducted on 101 patients with PDTC who were treated between 1986 and 2010. Among them, 38 had no distant metastases at presentation, were managed by total thyroidectomy and adjuvant RAI, and had negative anti-Tg antibodies. An unstimulated Tg level < 1 ng/mL was used as a cut-off point for undetectable Tg levels. Association of patient and tumor characteristics with Tg levels was examined by χ<sup>2</sup> test. Overall survival, disease-specific survival (DSS), and recurrence-free survival (RFS), stratified by Tg levels, were calculated by the Kaplan-Meier method and compared by the log-rank test. Results: Compared to patients with undetectable Tg, cases with detectable Tg had a lower probability of achieving free surgical margins (21.7 vs. 46.7%; p = 0.04), higher node status (73.3 vs. 21.8%; p = 0.005), decreased 5-year DSS (65 vs. 100%; p = 0.009), and worse 5-year RFS (32 vs. 84%, p = 0.010), with a significant number of patients having a recurrence in the first year (50 vs. 12.5%; p = 0.021). Patients with detectable Tg levels also showed worse locoregional (55.6 vs. 90.9%; p = 0.014) and distant control (5-year distant control of 46.9 vs. 91%; p = 0.017). Conclusions: Our results suggest that detectable Tg levels after surgery and RAI in a subset of PDTC patients appear to predict a higher rate of death and recurrence.

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Francisco Sousa Santos Endocrinology Department, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
Endocrinology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Rita Joana Santos Endocrinology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Valeriano Leite Endocrinology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Faculty of Medical Sciences of Lisbon, Lisbon, Portugal

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Background: Radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) is a rare form of DTC which poses a therapeutic challenge due to the scarcity of effective treatment options. In recent years several tyrosine kinase inhibitors targeting specific molecular pathways involved in its pathogenesis have been investigated, such as sorafenib, lenvatinib, and sunitinib. These appear to be associated with improved progression-free survival (PFS). Objectives: We aim to describe our experience with sorafenib and sunitinib in the treatment of RAI-refractory metastatic DTC and to evaluate and compare their efficacy and adverse effect profiles. Method: A total of 28 patients with RAI-refractory metastatic DTC were included – 26 had first-line treatment with sorafenib (8 subsequently switched to sunitinib, most due to disease progression) and 2 with sunitinib. We evaluated PFS and best radiological response achieved with each agent as primary endpoints. The secondary objective was to describe adverse effects and safety profile. Results: Mean PFS was 10.8 months with sorafenib and 6 months with sunitinib as a second-line treatment. Best overall response was partial remission (PR) with either agent – PR rate of 30.7% with sorafenib and 37.5% with second-line sunitinib. All treatment courses had registered adverse effects and 13.9% justified definitive treatment cessation. Conclusions: Sorafenib and sunitinib appear to be effective treatment options in delaying disease progression of patients with RAI-refractory metastatic DTC, with an acceptable safety profile. Interestingly, sunitinib appears to show some efficacy even in patients who experience disease progression on sorafenib.

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Pedro Marques Endocrinology Department, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal

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Valeriano Leite Endocrinology Department, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal
NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

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Maria João Bugalho Endocrinology Department, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal
NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

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Background: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. The widespread use of neck ultrasound (US) and US-guided fine-needle aspiration cytology is triggering an overdiagnosis of PTC. Objective: To evaluate clinical behavior and outcomes of patients with PTCs ≤2 cm, seeking for possible prognostic factors. Methods: Clinical records of cases with histological diagnosis of PTC ≤2 cm followed at the Endocrine Department of Instituto Português de Oncologia, Lisbon between 2002 and 2006 were analyzed retrospectively. Results: We identified 255 PTCs, 111 were microcarcinomas. Most patients underwent near-total thyroidectomy, with lymph node dissections in 55 cases (21.6%). Radioiodine therapy was administered in 184 patients. At the last evaluation, 38 (14.9%) had evidence of disease. Two deaths were attributed to PTC. Median (±SD) follow-up was 74 (±23) months. Multivariate analysis identified vascular invasion, lymph node and systemic metastases significantly associated with recurrence/persistence of disease. In addition, lymph node involvement was significantly associated with extrathyroidal extension and angioinvasion. Median (±SD) disease-free survival (DFS) was estimated as 106 (±3) months and the 5-year DFS rate was 87.5%. Univariate Cox analysis identified some relevant parameters for DFS, but multivariate regression only identified lymph node and systemic metastases as significant independent factors. The median DFS estimated for lymph node and systemic metastases was 75 and 0 months, respectively. Conclusions: In the setting of small PTCs, vascular invasion, extrathyroidal extension and lymph node and/or systemic metastases may confer worse prognosis, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

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Claudia Matta-Coelho Serviço de Endocrinologia, Hospital de Braga, Braga, Portugal
Center for Health Technology and Services Research (CINTESIS), Porto, Portugal

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Joana Simões-Pereira Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

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Helena Vilar Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Valeriano Leite Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

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Background/Aims: Overall, 2–13% of patients with thyroid cancer develop bone metastases (BM). In addition to decreased survival, patients with BM may present skeletal-related events (SRE) that impair the quality of life. Our objectives were to characterize clinical features, treatment approaches, and outcomes of patients with thyroid cancer and BM. Material and Methods: We identified patients diagnosed with thyroid carcinoma of follicular origin and BM followed at the Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Lisbon, Portugal, from 1991 to 2017. SRE were defined as the need for bone irradiation, bone surgery, spinal cord compression, or pathologic fractures. Results: The final cohort consisted of 86 patients, with a median follow-up time of 54 months (IQR 22.8–82.8), mainly women (67.4%), and a median age of 64 years (IQR 53.6–71.2). BM was the initial presentation of thyroid cancer in 36.0% of the patients. Bone involvement was multiple in 59.3% of the cases. Papillary carcinoma was the most frequent histological type, present in 47.7% of the patients, of which 56.1% presented the follicular variant. SRE were found in 76.7% of the patients. The most frequent SRE was radiotherapy (66.3%). Treatment with bisphosphonates was initiated in 19.8% of the patients. The 5-year specific survival was 60%, whereas the 10-year specific survival decreased to 50%. There were no differences in 5- or 10-year specific survival regarding gender, the occurrence of SRE, or histological type. However, patients with initial radioiodine non-avid lesions had a lower 5- and 10-year specific survival (p = 0.002). Discussion: The high frequency of patients with SRE was notable. The follicular variant of papillary thyroid cancer was the variant most commonly associated with BM, reflecting a more similar behavior to follicular carcinoma than the classic variant.

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Daniela Rodrigues Cavaco Department of Endocrinology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Ana Alves Rafael Department of General Surgery, CUF Academic Center – Hospital CUF Sintra and Hospital CUF Cascais, Lisbon, Portugal

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Rafael Cabrera Department of Pathology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Helena Vilar Department of Endocrinology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Valeriano Leite Department of Endocrinology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
NOVA Medical School/New University of Lisboa, Lisbon, Portugal

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Diffuse thyroid lipomatosis is a rare histopathological condition of unknown etiology, characterized by diffuse fatty infiltration of the thyroid stroma, which can result in diffuse goiter with compressive symptoms. We report a case of a 46-year-old man with 1-year history of progressive goiter enlargement with compressive symptoms. Imaging studies revealed multiple coalescent nodules. The patient underwent surgery, and the microscopic appearance revealed a diffuse infiltration of thyroid stroma by mature adipose tissue with associated amyloid deposition. A final diagnosis of diffuse lipomatosis of the thyroid gland was established. This patient represents one of the few reported cases of diffuse lipomatosis with coexisting deposition of amyloid protein of the thyroid gland and contributes to the better understanding of this extremely rare condition.

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Mafalda Marcelino Department of Endocrinology, Armed Forces University Hospital, Lisbon, Portugal
Department of Endocrinology, Portuguese Institute of Oncology, Lisbon, Portugal

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Pedro Marques Department of Endocrinology, Portuguese Institute of Oncology, Lisbon, Portugal

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Luis Lopes Department of Endocrinology, Armed Forces University Hospital, Lisbon, Portugal

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Valeriano Leite Department of Endocrinology, Portuguese Institute of Oncology, Lisbon, Portugal

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João Jácome de Castro Department of Endocrinology, Armed Forces University Hospital, Lisbon, Portugal

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A 70-year-old male was referred with hyperthyroidism and multinodular goiter (MNG). Thyroid ultrasonography showed 2 nodules, one in the isthmus and the other in the left lobe, 51 and 38 mm in diameter, respectively. Neck CT showed a large MNG, thyroid scintigraphy showed increased uptake in the nodule in the left lobe, and fine-needle aspiration biopsy showed a benign cytology of the nodule in the isthmus. The patient declined surgery and was treated with methimazole. After being lost to follow-up for 3 years, the patient returned with complaints of dyspnea, dysphagia, and hoarseness; he was still hyperthyroid. Cervical CT showed a large mass in the isthmus and left lobe with invasion of surrounding tissues, the trachea, the esophagus, and the recurrent laryngeal nerve. Bronchoscopy showed extensive infiltration and compression of the trachea to 20% of its caliber. A tracheal biopsy revealed an anaplastic thyroid carcinoma. The tumor was considered unresectable, and radiotherapy was given. One month later, the patient died. The association between a toxic thyroid nodule and anaplastic thyroid carcinoma has apparently not been reported so far.

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João Roque Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar Universitário Lisboa Norte, Hospital de Santa Maria, Lisbon, Portugal

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Tiago Nunes Silva Endocrinology, Diabetes and Metabolism Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
NOVA Medical School | Faculdade de Ciências Médicas of Universidade NOVA de Lisboa, Lisbon, Portugal
Unidade Investigação Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Catarina Regala Endocrinology, Diabetes and Metabolism Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Ricardo Rodrigues Unidade Investigação Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Valeriano Leite Endocrinology, Diabetes and Metabolism Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
NOVA Medical School | Faculdade de Ciências Médicas of Universidade NOVA de Lisboa, Lisbon, Portugal
Unidade Investigação Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Background and objective

Lenvatinib showed promising results in a subgroup of patients with poorly differentiated thyroid carcinoma (PDTC) in the SELECT trial. Our aim was to report the effectiveness and tolerability of lenvatinib in our series of PDTC patients.

Methods

Medical records of eight consecutive patients with PDTC treated with lenvatinib in a single center between January 2019 and October 2022 were retrospectively reviewed. Inclusion criteria were PDTC diagnosis based on Turin criteria and evidence of disease progression in the previous 6 months.

Results

Eight PDTC patients received an average dose of lenvatinib of 18.1 mg for a median duration of treatment of 10.3 months. The baseline Eastern Cooperative Oncology Group performance status was ≥2 in 50% of patients. Two patients had unresectable primary tumor. Seven patients showed extrathyroidal disease, particularly mediastinal lymph nodes (85.7%), lung (71.4%), and bone (71.4%). The disease control rate was 100%, with partial response and stable disease in 12.5 and 87.5%, respectively. The median time to best overall response was 3 months, and the median duration of response was 7.5 months. Median progression-free survival was 12 months and median overall survival was not reached. At 6, 12, and 18 months, overall survival was 87.5, 71.4, and 57.1%, respectively. All patients experienced drug-related adverse effects (AEs). Four (50%) had dose reductions and two (25%) had temporary treatment interruptions. Lenvatinib was stopped in two patients due to grade ≥3 AEs.

Conclusion

Lenvatinib is an effective treatment for real-world PDTC patients. Adequate management of comorbidities and AEs increases treatment tolerability and minimizes dose reductions.

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