Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive malignancy. Due to limited treatment options and a rapid, lethal clinical course, it is associated with a poor prognosis. Although ATC accounts for less than 2% of all thyroid carcinomas, it contributes to significant thyroid carcinoma-related mortality (14–39%) [1]. The median overall survival (OS) for patients diagnosed with ATC ranges from 3 to 6 months. Due to its advanced and invasive nature, ATC is always classified as stage IV. This staging is categorised into subgroups, with stage IVA indicating intrathyroidal involvement, stage IVB involving gross extrathyroidal extension or cervical lymph node metastases, and stage IVC representing the presence of distant metastases. Among the driver mutations identified in ATC, the BRAFV600E mutation is recognised as the predominant one, present in approximately 45% of ATC cases [2]. Early assessment of tumour genetics plays a crucial role in expanding therapeutic options and providing tailored treatment approaches.
An 86-year-old female patient was referred to our hospital in spring 2023 after self-detecting a cervical mass. Her medical history revealed anaemia due to iron deficiency, arthropathy, mild bilateral sensorineural hearing loss, and presbycusis. Pathological examination of the cervical mass preceded by ultrasound-guided biopsy confirmed the presence of anaplastic thyroid carcinoma with the BRAFV600E mutation. At this stage, the mass was unresectable, and in September 2023 the patient initiated treatment with dabrafenib and trametinib. A follow-up positron emission tomography (PET) scan in October 2023 revealed an enlarged thyroid gland with a mass in the right lobe measuring approximately 32 × 30 mm (Fig. 1A). The mass exhibited hypermetabolic borders along the medial tracheal area [maximum standardized uptake (SUV)max: 8.7)], suggesting malignancy. Additionally, asymmetry of glottic uptake suggested possible paresis of the right vocal cord, necessitating further evaluation. There were no suspicious locoregional or distant adenopathies and no evidence of infiltration in the cervical lymphatic regions, thorax, or abdomen. In January 2024, a follow-up computed tomography (CT) scan demonstrated a reduction in the mass size from 35 × 32 mm to 26 × 25 mm (Fig. 1B). The cervical study revealed no significant adenopathies; also, no morphological alterations were observed in the upper mediastinum.
Based on the patient’s positive response to oncological treatment, the Endocrine Tumours Committee recommended proceeding with surgery. Total thyroidectomy and central lymph node removal were planned. During the surgical procedure, the patient underwent a right hemithyroidectomy and removal of ipsilateral central regional lymph nodes. However, the left hemithyroidectomy could not be completed due to a loss of signal and suspicion of a right recurrent laryngeal nerve injury. Subsequent pathological examination of the obtained specimen revealed the presence of anaplastic thyroid cancer within the right thyroid lobe (Fig. 2). The tumour was described as a distinct, well-defined mass measuring 22 × 16 mm. Additionally, the examination identified nine nodes, of which 4 were classified as macrometastatic and 2 as micrometastatic, corresponding to metastasis from a differentiated papillary carcinoma. The pathological stage was determined as ypT4aN1aM0.
The patient’s postoperative period was uneventful, maintaining good overall condition, stable haemodynamics, and no fever. The patient did not report any swallowing difficulties or shortness of breath, but mild dysphonia was observed. The patient was discharged with instructions for follow-up visits and scheduled outpatient appointments, while continuing the dabrafenib and trametinib therapy.
The management of ATC is shifting towards a personalised medicine approach, with an emphasis on genetic evaluation and targeted therapies [2]. Dabrafenib and trametinib combination therapy has been approved by the Food and Drug Administration (FDA) for unresectable or metastatic ATC, and it has shown promising results in patients with the BRAFV600E mutation. Studies have shown a promising overall response rate (ORR) of 56% and an estimated overall survival (OS) of 51.7% at 12 months [3]. Surgical intervention, aiming for complete resection, remains an essential component of treatment, and neoadjuvant approaches have demonstrated improved outcomes. A systematic review by Hu et al. provides evidence of the survival advantages associated with surgical resection in cases of stage IVA and IVB disease, particularly when achieving an R0/R1 resection [4]. The largest study evaluating neoadjuvant targeted therapy followed by surgical resection demonstrated a 1-year OS of 93.6% and a 2-year OS of 80.3% [5].
Anaplastic carcinoma is an uncommon but aggressive condition of thyroid cancer. Its treatment is mainly related to palliative modalities where surgery has had a poor role. New treatments can improve life expectancy by reducing tumours and providing potential patients access to surgical options.
Conflict of interest
All authors declare that they have no conflicts of interest.
Funding
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