{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:19:41Z","timestamp":1788365981157,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>Background: Serum calcitonin is commonly interpreted as a marker of tumor burden in medullary thyroid carcinoma (MTC), but patients with comparable tumor diameters may show markedly different calcitonin levels. This exploratory study aimed to derive cohort-specific, tumor diameter\u2013adjusted calcitonin secretory categories and examine their relationship with invasive pathological features. Methods: This retrospective single-center study included 70 unique patients with histopathologically confirmed MTC. Seventeen patients with preoperative serum calcitonin below the assay reporting limit (&lt;2 pg\/mL) were evaluated separately. In 53 patients with detectable calcitonin, residuals from a log-linear model of calcitonin according to dominant tumor diameter were divided into tertiles to define exploratory hyposecretory, normosecretory, and hypersecretory categories. Sensitivity analyses accounted for sex, metastatic lymph-node count, documented distant metastatic disease, and restriction to patients with pN0 disease and no documented distant metastasis. Results: Preoperative calcitonin correlated with dominant tumor diameter (Spearman rho = 0.644, p &lt; 0.001), and the primary model explained 45.2% of calcitonin variability (R2 = 0.452). The cohort-derived categories included 18 hyposecretory, 17 normosecretory, and 18 hypersecretory tumors. In a hypothesis-driven exploratory contrast, lymphovascular invasion (55.6% vs. 25.7%; nominal p = 0.040) and perineural invasion (33.3% vs. 8.6%; nominal p = 0.048) were more frequent in the hypersecretory category. However, the global three-group comparisons were not statistically significant (p = 0.135 and p = 0.117, respectively), and both false-discovery-rate-adjusted q values were 0.072. The tumor diameter\u2013calcitonin relationship remained significant after adjustment for sex and metastatic burden and in the pN0 subgroup without documented distant metastasis. Conclusions: The exploratory, cohort-derived hypersecretory category showed hypothesis-generating enrichment for lymphovascular and perineural invasion, but these associations did not meet the false-discovery-rate-adjusted significance threshold. External validation is required before these categories can be considered biologically established or clinically applicable.<\/jats:p>","DOI":"10.3390\/curroncol33090533","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:39:47Z","timestamp":1788363587000},"page":"533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Tumor Diameter: Exploratory Cohort-Derived Calcitonin Secretory Categories and Invasive Pathology in Medullary Thyroid Carcinoma"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2432-7334","authenticated-orcid":false,"given":"Adem","family":"Ozcan","sequence":"first","affiliation":[{"name":"Department of Surgical Oncology, Ankara Bilkent City Hospital, Ankara 06800, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-4052","authenticated-orcid":false,"given":"Gizem","family":"Gunes","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Ankara Bilkent City Hospital, Ankara 06800, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4259-3217","authenticated-orcid":false,"given":"Ali","family":"Bal","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Ankara Bilkent City Hospital, Ankara 06800, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Abdulkadir","family":"Unsal","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Ankara Bilkent City Hospital, Ankara 06800, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Furkan","family":"Savas","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Ankara Bilkent City Hospital, Ankara 06800, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6150-0226","authenticated-orcid":false,"given":"Mustafa Omer","family":"Yazicioglu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Ankara Bilkent City Hospital, Ankara 06800, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1210\/endrev\/bnad013","article-title":"Medullary thyroid cancer: Updates and challenges","volume":"44","author":"Gild","year":"2023","journal-title":"Endocr. 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