UNASSIGNED: Tyrosine kinase inhibitors (TKIs) and immunotherapy have been proposed for advanced metastatic anaplastic thyroid cancer (ATC). We report a case of BRAF V600E-mutated ATC in which lenvatinib (L) plus pembrolizumab (P) enabled neoadjuvant treatment.
UNASSIGNED: A male patient aged 65 years presented with a rapidly enlarging left latero-cervical mass. Fine needle aspiration was suggestive of ATC. Surgical consultation excluded radical surgery. While awaiting molecular profile analysis and considering the fast evolution of the disease, treatment with L and P was started. L was started at a dose of 14 mg daily, while P was started at the standard regimen (200 mg every 3 weeks). After 1 month, computerized tomography showed a reduction in the mass with almost complete colliquative degeneration, and the carotid artery wall was free from infiltration. Radical surgery was performed. Histology confirmed papillary thyroid cancer (PTC) in the left lobe and ATC with extensive necrosis in the left latero-cervical lymph node metastasis. The margins were free of tumors (R0). A BRAF V600E mutation was present in both PTC and ATC. At the 1-year follow-up, the patient was free of disease.
UNASSIGNED: L and P in combination also appeared to be effective as a neoadjuvant treatment for BRAF V600E-mutated ATC. This combination treatment could be used when there is an opportunity for complete resection of the cancer, and as soon as possible. The intermediate dose of 14 mg of L appeared to be well tolerated and effective.

BACKGROUND: Anaplastic thyroid carcinoma(ATC) is a rare pathological type of thyroid malignancy. Primary squamous cell carcinoma of thyroid(PSCCT) is now considered as a subtype of ATC, hereinafter referred to as ATC-SCC subtype. ATC-SCC subtype combined with follicular thyroid carcinoma is exceedingly rare, with fewer cases reported. The ATC-SCC subtype is a highly invasive tumor with a poor prognosis for patients after metastasis occurs, and current treatment of this type of tumor is tricky.
METHODS: A 68-year-old female patient presented with a gradually growing swelling of right cervical region. Comprehensive auxiliary examinations and postoperative pathology confirmed the diagnosis of ATC-SCC subtype with follicular thyroid carcinoma, and the metastasis squamous cell carcinoma of the right cervical lymph nodes originates from ATC-SCC subtype. The patient received chemoradiotherapy postoperative. However, the residual cervical lymph nodes metastasis with squamous cell carcinoma still infiltrated surrounding structures in the neck extensively after palliative resection. The patient died 7 months after surgery.
CONCLUSIONS: Our case highlights that cervical lymph node metastasis may be a significant factor in the poor prognosis of ATC-SCC subtype. This malignancy should be detected and treated early.

Tracheal AERO stent collapse is a rare complication compared to bronchial AERO stent collapse due to differences in the nitinol framework thickness. A 58-year-old man with a bulky anaplastic thyroid carcinoma was referred to our hospital due to exacerbation of tracheal stenosis despite the administration of lenvatinib. His tracheal stenosis exhibited a severe extrinsic compression pattern with a length of 8 cm. Because tracheotomy was inappropriate, we placed an 18 × 80 mm AERO stent. Five months later, he was readmitted with severe dyspnea due to collapse of the distal portion of the stent caused by tumor growth. Because stent removal was difficult, we placed an additional AERO stent (18 × 60 mm) to cover the collapsed portion. The additional stent successfully expanded the collapse and improved his dyspnea. To our knowledge, this is the first case where a tracheal AERO stent collapse due to a poor prognosis tumor was treated with the stent-in-stent method.

BACKGROUND: The abscopal effect, in which radiation induces a systemic anti-tumour immune response, has been demonstrated with radiotherapy. Immunotherapy boosts the abscopal effect by facilitating the immune response to radiation. Radiotherapy and programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) blockade has resulted in the boosted abscopal effect in solid cancers, but its role in anaplastic thyroid cancer (ATC) is unknown. In this mini-review, we describe the abscopal effect and summarise its proposed underlying mechanisms. We then present a potential case of boosted abscopal effect in ATC.
METHODS: In our case presentation, we describe a 51-year-old female who presented with 3 weeks of rapidly enlarging thyroid mass. Examination revealed a 3-cm thyroid nodule which was Bethesda V on fine needle aspiration cytology (FNAC). Intraoperatively, there was a gross extrathyroidal extension into the cricoid cartilage. After total thyroidectomy, post-operative histopathology showed widely invasive follicular thyroid cancer with anaplastic transformation (>50%). Immunohistochemistry showed high PD-L1 expression [combined positive score (CPS) >70%]. Due to residual cricoid cartilage disease and several peri-hilar and lung metastases on positron emission tomography-computed tomography (PET-CT) scan, she underwent post-operative palliative radiotherapy and pembrolizumab. After two cycles of pembrolizumab, repeat PET-CT scan showed complete response (CR) of local and distant disease. She remained well for 32 months, before recent discovery of a right mandible bony metastasis planned for radiotherapy.
CONCLUSIONS: This case demonstrates exceptional response to radiotherapy and anti-PD-1 immunotherapy in ATC, potentially illustrating the first known abscopal effect in ATC with this treatment.

An 82-year-old woman was referred to our hospital because of a suspicious thyroid nodule. She was diagnosed with papillary microcarcinoma with a maximum diameter of 9 mm based on ultrasonography and fine-needle aspiration (FNA) cytology. She preferred observation without surgery. Her papillary carcinoma grew gradually and reached a maximum diameter of 19 mm after 23 months. At that time, ultrasonography showed an apparent change in the shape of the nodule as well as in its diameter. At the initial ultrasound examination, papillary microcarcinoma was demonstrated as a hypoechoic solid nodule with an irregular shape. No punctuate microcalcifications were shown. After 23 months, the preexisting nodule had expanded toward the common carotid artery. The expanded portion was round and well demarcated. FNA revealed that the expanded portion consisted of anaplastic thyroid carcinoma. She underwent hemithyroidectomy and lymph node dissection of the central compartment. She remained in good health for 18 months after surgery. Anaplastic thyroid carcinoma is generally found as an aggressive large tumor, and the ultrasound appearance of small anaplastic thyroid carcinoma is poorly understood at present. We successfully detected anaplastic transformation in the early period by ultrasonography and FNA. When observation is indicated for small papillary thyroid carcinoma, the change in the shape of the nodule as well as in its diameter should be carefully monitored by ultrasonography. FNA should be performed at a proper site on the nodule to avoid overlooking anaplastic transformation, as resection following the early detection of anaplastic transformation might bring a favorable prognosis.

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Anaplastic thyroid carcinoma, BRAF non-V600, NRAS, combination immunotherapy and targeted therapy, case report. Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer with a mortality rate near 100%. BRAF V600 and NRAS mutations are the most common drivers of ATC. While patients with BRAF V600-mutated ATC can be treated with BRAF-targeted therapy, there is no effective treatment for ATC driven by NRAS or non-V600 BRAF mutations. For patients with untargetable driver mutations, immunotherapy provides an alternative treatment option. Here, we present a metastatic ATC patient with PD-L1 positive (tumor proportion score of 60%) tumor and NRAS Q61R/BRAF D594N mutations, who progressed on PD-1 antibody sintilimab plus angiogenesis inhibitor anlotinib. The class 3 BRAF mutant D594N is sensitive to the inhibition of MEK inhibitor trametinib, and its oncogenic activity also depends on CRAF, which can be inhibited by BRAF inhibitor dabrafenib. For these reasons, the patient received a salvage treatment regime of dabrafenib, trametinib, and sintilimab, which resulted in a complete pathological response. To our best knowledge, this is the first report of successful treatment of ATC patients with concurrent NRAS/BRAF non-V600 mutations with the combination of immunotherapy and targeted therapy. Further investigation is required to decipher the mechanism by which the combination of dabrafenib/trametinib with PD-1 antibody overcomes initial immunotherapy resistance likely mediated by concurrent BRAF and NRAS mutations.

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BACKGROUND: Defects of the neck after palliative resection of exulcerated tumors could be reconstructed with different skin flaps.
METHODS: The present report describes the case of a 40-year-old Caucasian female patient with advanced anaplastic thyroid cancer. The exophytically growing, bad-smelling massive exulcerated tumor caused an esthetic defect, neck mobility restrictions, and mental state deterioration.
UNASSIGNED: Palliative debulking of the tumor was performed. The 10 × 5 cm skin defect of the neck was successfully reconstructed with an internal mammary artery perforator island flap. The donor site was closed primarily. The patient had an uneventful clinical course; the cosmetic results and mental state were very pleasing.
CONCLUSIONS: The present case illustrates that palliative resection of the tumor and plastic reconstruction of the neck defect promoted other treatments such as radiation or chemotherapy due to the improved local situation.

Anaplastic thyroid carcinoma with two distinct morphologies in two lobes with no intermixing is very rare and not reported earlier. Furthermore, osteoclastic variant of anaplastic thyroid carcinoma as well as primary squamous cell carcinoma without any differentiated components are also very rare with only few reported cases describing their cytological features. Herein, we are reporting a unique and first case of anaplastic thyroid carcinoma comprising of two distinct patterns osteoclastic variant and squamous cell carcinoma in different lobes in a 55-years-old lady with review of literature.