{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:37:02Z","timestamp":1760060222686,"version":"build-2065373602"},"reference-count":20,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Poorly differentiated thyroid malignancy, a rare histological type of aggressive thyroid malignancy with associated difficulties and gaps in its histological and molecular characterization, might lead to challenging clinical presentations that require a prompt multimodal approach. This case study involved a 56-year-old, non-smoking male with a rapidly developing goiter (within 2\u20133 months) in association with mild, non-specific neck compressive symptoms. His medical history was irrelevant. A voluminous goiter with substernal and posterior extension up to the vertebral bodies was detected using an ultrasound and computed tomography (CT) scan and required emergency thyroidectomy. He had normal thyroid function, as well as negative thyroid autoimmunity and serum calcitonin. The surgery was successful upon \u201cY\u201d incision, which was used to give better access to the retrosternal component in order to avoid a sternotomy. Post-operatively, the subject developed hypoparathyroidism-related hypocalcemia and showed a very high serum thyroglobulin level (&gt;550 ng\/mL). The pathological report confirmed poorly differentiated, multifocal thyroid carcinoma (with an insular, solid, and trabecular pattern) against a background of papillary carcinoma (pT3b, pN0, and pM1; L1; V2; Pn0; R1; and stage IVB). The subject received 200 mCi of radioiodine therapy for 6 weeks following the thoracic surgery. Whole-body scintigraphy was performed before radioiodine therapy and showed increased radiotracer uptake at the thyroid remnants and pre-tracheal levels. Additionally, single-photon emission computed tomography combined with CT (SPECT\/CT) was performed, and confirmed the areas of intense uptake, in addition to a moderate uptake in the right and left pulmonary parenchyma, suggesting lung metastasis. To conclude, an overall low level of statistical evidence exists regarding poorly differentiated malignancy in substernal goiters, and the data also remains scarce regarding the impact of genetic and molecular configurations, such as the BRAF-positive profile, in this specific instance. Furthermore, multimodal management includes additional diagnosis methods such as SPECT\/CT, while long-term multilayered therapy includes tyrosine kinase inhibitors if the outcome shows an iodine-resistant profile with a poor prognosis. Awareness remains a key factor in cases of a poorly differentiated carcinoma presenting as a rapidly growing goiter with substernal extension in an apparently healthy adult. A surgical approach, while varying with the surgeon\u2019s skills, represents a mandatory step to ensure a better prognosis. In addition to a meticulous histological characterization, genetic\/molecular features provide valuable information regarding the outcome and can further help with the decision to use new anti-cancer drugs if tumor response upon radioiodine therapy is no longer achieved; such a development is expected in this disease stage in association with a BRAF-positive configuration.<\/jats:p>","DOI":"10.3390\/diagnostics15162049","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T10:33:42Z","timestamp":1755254022000},"page":"2049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multilayered Insights into Poorly Differentiated, BRAFV600E-Positive, Thyroid Carcinoma in a Rapidly Developing Goiter with Retrosternal Extension: From En \u201cY\u201d Cervicotomy to SPECT\/CT-Positive Lung Metastases"],"prefix":"10.3390","volume":"15","author":[{"given":"Oana-Claudia","family":"Sima","sequence":"first","affiliation":[{"name":"Department of Clinical Endocrinology V, \u201cC.I. Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0326-1145","authenticated-orcid":false,"given":"Anca-Pati","family":"Cucu","sequence":"additional","affiliation":[{"name":"PhD Doctoral School, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 010825 Bucharest, Romania"},{"name":"Thoracic Surgery Department, \u201cDr. Carol Davila\u201d Central Emergency University Military Hospital, 010825 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana","family":"Terzea","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u201cC.I. Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-5666","authenticated-orcid":false,"given":"Claudiu","family":"Nistor","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Department, \u201cDr. Carol Davila\u201d Central Emergency University Military Hospital, 010825 Bucharest, Romania"},{"name":"Department 4\u2014Cardio-Thoracic Pathology, Thoracic Surgery II Discipline, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 0505474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florina","family":"Vasilescu","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u201cDr. Carol Davila\u201d Central Emergency University Military Hospital, 010825 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucian-George","family":"Eftimie","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u201cDr. Carol Davila\u201d Central Emergency University Military Hospital, 010825 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4402-7194","authenticated-orcid":false,"given":"Mihai-Lucian","family":"Ciobica","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Gastroenterology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Internal Medicine I and Rheumatology, \u201cDr. Carol Davila\u201d Central Military University Emergency Hospital, 010825 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai","family":"Costachescu","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Department, \u201cDr. Carol Davila\u201d Central Emergency University Military Hospital, 010825 Bucharest, Romania"},{"name":"Department of Radiology and Medical Imaging, \u201cDr. Carol Davila\u201d Central Emergency University Military Hospital, 010825 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-3835","authenticated-orcid":false,"given":"Mara","family":"Carsote","sequence":"additional","affiliation":[{"name":"Department of Clinical Endocrinology V, \u201cC.I. Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"},{"name":"Department of Endocrinology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Schipor, S., Publik, M.A., Manda, D., and Ceausu, M. (2025). Aggressive Thyroid Carcinomas Clinical and Molecular Features: A Systematic Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125535"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1016\/j.asjsur.2024.10.073","article-title":"Giant poorly differentiated thyroid carcinoma: A case report and literature review","volume":"48","author":"Lu","year":"2024","journal-title":"Asian J. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Boudina, M., Zisimopoulou, E., Xirou, P., and Chrisoulidou, A. 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