Age, not tumor size, modifies the association between extrathyroidal extension and long-term outcomes in patients with follicular cell-derived thyroid carcinoma

Background and objective: Thyroid cancer is the most common endocrine malignancy. This report aims to describe the pattern of thyroid cancer presentations at King Abdulaziz University Hospital, Jeddah. Methods: This was a retrospect chart review of all thyroid cancer cases diagnosed between 2001 and 2010 at King Abdulaziz University Hospital, Jeddah. We documented patients’ demographic and clinical data, including age at diagnosis, tumor type and size, extrathyroidal extension, and metastasis. Results: A total of 114 thyroid cancer cases were diagnosed from 2001 through 2010. Females comprise the majority of cases (female to male ratio of 4:1). The mean ages of patients diagnosed with different thyroid cancers were: papillary thyroid cancer, 39.6 years; follicular thyroid cancer, 43.2 years; medullary thyroid cancer, 55.8 years; and anaplastic thyroid cancer, 46.0 years. Papillary thyroid cancer was diagnosed in 88 cases (77%), follicular thyroid cancer in 19 cases (17%), medullary thyroid cancer in 5 cases (4%), and anaplastic thyroid cancer in 2 cases (2%). Conclusion: Thyroid cancers are more common among females. The disease is diagnosed at a relatively young age among our patients (40 years). Papillary thyroid cancer is the most common type of thyroid cancer.

BackgroundImmune checkpoint proteins have not been fully examined in follicular cell-derived thyroid carcinoma and medullary thyroid carcinoma (MTC). Anaplastic thyroid carcinoma (ATC) is one of the most aggressive carcinomas. Even multimodal treatment does not result in favorable clinical outcomes for patients with ATC. Anti-tumor immunity has therefore been highlighted as having therapeutic promise for ATC.MethodsWe examined a novel immune checkpoint receptor, T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT), in variable thyroid lesions: adenomatous goiter, follicular adenoma, and thyroid carcinoma (TC) using immunohistochemistry (IHC).ResultsOur IHC results showed that TIGIT expression was detected in cancer cells of MTC and high-grade TC: poorly differentiated thyroid carcinoma (PDTC) and ATC. Neoplastic cells were positive for TIGIT in four of five MTCs (80.0%), 17 of 31 ATCs (54.8%) and in 3 of 12 PDTCs (25.0%). TIGIT was not detected in any adenomatous goiters, thyroid benign tumors, or differentiated thyroid carcinoma (DTCs). Intriguingly, ATC cells showing pleomorphic/giant cell features were positive for TIGIT, while ATC cells with other cell morphologies lacked the immunoreactivity. Intra-tumoral immune cell was inclined to be enriched in TIGI-positive ATC. Although coexisting papillary thyroid carcinoma (PTC) components demonstrated high-grade microscopic features, neither the PTC nor follicular thyroid carcinoma (FTC) components expressed TIGT in any composite ATCs.ConclusionTIGIT was immunohistochemically found in MTC with high frequency and partially in high-grade TC. TIGIT expression in cancer cells may be beneficial for a potential utility in MTC and a subset of high-grade TC, especially ATC therapy.

Telomerase activation through induction of its catalytic component telomerase reverse transcriptase (TERT) expression is essential for malignant transformation. TERT promoter mutations namely C228T and C250T that stimulate TERT transcription and telomerase activation have recently been identified in many human malignancies. We thus determined these mutations and their biological and clinical implications in thyroid carcinomas in the present study. The TERT promoter was sequenced in 10 thyroid cancer cell lines and 144 tumors from 20 patients with anaplastic thyroid carcinoma (ATC), 51 with papillary thyroid carcinoma (PTC), 36 with follicular thyroid carcinoma (FTC), and 37 with medullary thyroid carcinoma (MTC). We identified C228T or C250T mutation in 6/8 of ATC cell lines, as well as in tumor tissue from 10/20, 13/51, 8/36 and 0/37 patients with ATC, PTC, FTC and MTC, respectively. In PTC patients, these mutations were exclusively present in the group with age >45 years (P<0.0001), and highly correlated shorter telomeres (P<0.0001) and distant metastasis (P=0.028). The previous radioactivity exposure did not induce the mutation. The presence of C228T or C250T was an independent predictor associated with shorter disease-related survival (DRS) in the entire cohort (P<0.0001), as well as among patients >45 years (P=0.021). ATC patients carrying the mutation survived shorter than those without mutations, although not statistically significant (P=0.129). The TERT promoter mutation was associated with overall survival (P=0.038) and DRS (P=0.058) of FTC patients. Taken together, age- and shorter telomere-dependent TERT promoter mutations occur frequently in follicular cell-derived thyroid carcinoma (ATC, PTC and FTC) but not in parafollicular cell-originated MTC, and may serve as a marker for aggressive disease and poor outcome.

Background: The 8th edition of the American Joint Committee on Cancer/tumor-node-metastasis (AJCC/TNM) staging system for differentiated thyroid cancer (DTC), implemented in January 2018, classifies patients >/= 55 years of age with gross extrathyroidal extension (ETE) of the primary tumor into the overlying strap muscles as prognostic stage II. However, it remains controversial as to whether or not gross ETE into the strap muscles is an independent predictor of recurrence, response to therapy, need for additional therapies, or overall survival. Using a case control study design, we evaluated the prognostic significance of gross ETE among adults.Methods: After obtaining IRB approval, we used the tumor registry at our institution to retrospectively identify 51 AJCC stage II patients with DTC aged >/= 55 years with gross ETE into only the strap muscles (51/2,225 patients). For each of the 51 cases, we identified one control who matched on all of the following important prognostic factors: age at diagnosis (± 5 years), sex, histology, size of tumor (± 1 cm), lymph node metastases, distant metastases, completeness of resection, receipt of radioactive iodine (RAI) therapy, and duration of follow-up (± 5 years). The controls (n=51) had no gross ETE.Results: In the 51 patients with gross ETE into only the strap muscles, the mean age at diagnosis was 64 years, 77% were female, 37% had lymph node metastases, and none had distant metastases. The average tumor size was 2.1 cm with the majority of patients (49/51) demonstrating papillary thyroid carcinoma (1 follicular thyroid carcinoma and 1 Hurthle cell thyroid carcinoma). Only 6% of patients (3/51) had incomplete resections and 92% (47/51) received RAI therapy. The mean duration of follow-up was 8 years.There were no statistically significant differences between the cases and controls on each of the pre-specified prognostic variables described in the methods. In addition, there were no statistically significant differences between the groups in terms of rates of recurrence: cases 18% (9/51) and controls 29% (15/51) (p=0.24), best response to initial therapy (excellent, biochemical incomplete, structural incomplete, or indeterminate response to therapy), and need for subsequent interventions including surgery, RAI, external beam radiation, or systemic therapy. Furthermore, there were no statistically significant differences between the cases and controls with respect to 10-year disease-free survival (cases 83% and controls 68%, p=0.90) and 10-year overall survival (cases 97% and controls 89%, p=0.10).Conclusions: In a case control analysis with a mean follow up of 8 years, the presence of ETE into the strap muscles was not an independent predictor of worse clinical outcomes in adults >/= 55 years old with DTC. These findings can be used to inform the future editions of the AJCC/TNM and American Thyroid Association staging systems for DTC.

ObjectiveThe incidence of papillary thyroid microcarcinoma (PTMC) has increased sharply during the past decades. Yet, whether or not nodal dissection should be performed remains controversial. This article aims to assess the high-risk factors associated with cervical lymph node metastasis (LNM) in patients with PTMC, which may potentially guide clinical management decision-making.MethodsMedical records of 449 PTMC patients who underwent thyroidectomy in our hospital from August 2016 to July 2017 were retrospectively reviewed. Clinical and pathological factors of the patients were anonymously extracted from the charts and analyzed.ResultThe patients were classified into two subgroups according to maximum tumor size measured through post-surgical pathology: smaller PTMC group (≤5 mm) and larger PTMC group (>5 mm). Larger tumor size was found to be associated with a higher rate of LNM (P = .001), particularly central lymph node metastasis (CLNM) (P = .001). Tumor size was also associated with extrathyroidal tumor extension (ETE) (P < .001), bilateral lesions (P = .015), and BRAFv600e mutation (P = .004). LNM was found to be more common in older patients (>55 y) (P = .030), and those with multifocal cancer (P < .001). In PTMC patients with unilateral lesions without ETE, tumor size was not significantly associated with LNM (P = .121).ConclusionsFor the PTMC population, tumor size was an independent risk factor for LNM, particularly for patients of old age (>55 y), and multifocality. However, in PTMC patients with unilateral lesions without extrathyroidal extension, tumor size was not related to the risk of LNM. These findings may potentially guide clinical decision-making in terms of cervical nodal dissection.

Differentiated carcinoma of the thyroid with extrathyroidal extension

Examine the prevalence and risk of metastasis in thyroid cancers and management outcomes. Retrospective analysis of the National Cancer Database, 2004-2014. The study population included adult (≥ 18 years) patients with thyroid cancer. Analysis included multivariate logistic regression and Cox hazard ratio modeling. A total of 152,979 patients were included. Distant metastasis was reported in 1,867 (1.22%) patients. The distribution of metastatic cases based on pathology and tumor size were as follows in descending order: papillary thyroid carcinoma (PTC) 1 to 4 cm (30.53%), PTC > 4 cm (19.34%), undifferentiated (UTC) > 4 cm (14.14%), PTC < 1 cm (8.46%), follicular thyroid carcinoma (FTC) > 4 cm (7.28%), FTC 1 to 4 cm (5.52%), medullary thyroid cancer (MTC) ≤ 4 cm (3.96%), MTC > 4 cm (3.91%), UTC ≤ 4 cm (3.32%), Hürthle (HCC ) > 4 cm (2.09%), and HCC 1 to 4 cm (1.45%). Significant predictors of distant metastasis, while controlling for tumor pathology and size, included older age, male gender, non-White minorities, presence of multiple comorbidities, minimal, gross extrathyroidal extension (ETE), lymphovascular invasion (LVI), and concomitant central and lateral lymph node metastasis (LNM) (P < .05 each). The risk of distant metastasis in the absence of nodal metastasis, ETE, and LVI was highest for FTC > 4 cm. Although the risk of metastasis in well-differentiated thyroid carcinoma (WDTC) is low, the prevalence of metastatic thyroid cancer is highest in WDTC population because it is the most common type of thyroid cancer. Certain pathological features, including minimal ETE and central LNM, are associated with a higher prevalence of metastatic disease. NA Laryngoscope, 131:237-244, 2021.

Medullary thyroid carcinoma (MTC) displays a wide variety of histopathological features, and several histological variants have been described. In follicular cell-derived thyroid carcinomas, there is a good correlation between genotype and phenotype. In this study, we investigated whether such a correlation is also present in MTC. The histopathological features were evaluated in a series of 66 molecularly characterised tumours and correlated with the clinical characteristics. Most MTC exhibited the classical variant (83.3%). Other variants included spindle cell (6.1%), pseudopapillary (4.5%), paraganglioma-like (3.0%), angiosarcoma-like (1.5%), and oncocytic follicular (1.5%). Tumours were classified into four groups: group 1, with somatic p.Met918Thr and p.Ala883Phe RET mutations; group 2, with other RET mutations; group 3, with RAS mutations; and group 4, without RET or RAS mutations. Tumours from groups 1 and 4 were typically associated with the classical variant, with abundant fibrosis, lymphovascular invasion, extrathyroidal extension, and more advanced stages of disease, whereas group 2 included histological variants other than the classical variant (namely, pseudopapillary and paraganglioma-like), with tumours that were highly cellular, less invasive, and with a better overall prognosis. In tumours from group 4, amyloid deposition was characteristically absent or low. The spindle cell variant appeared only in tumours from group 3, which had high cellularity and a degree of invasion and prognosis intermediate between groups 1 and 2, but better than group 4. The grade of fibrosis correlated directly with the clinical outcome. Our results support the idea that a genotype-phenotype correlation does, indeed, exist in MTC. However, further studies are warranted to confirm these findings in a larger sample size.

Background: Medullary thyroid cancer (MTC) can be associated with significant morbidity and mortality in advanced cases. Hence, we aimed to identify factors at the time of MTC surgery that predict overall survival (OS), disease-specific survival (DSS), locoregional recurrence/persistence (LR), and distant metastases (DM). Methods: We performed a retrospective study of clinicopathologic, radiological, and laboratory data in MTC patients who underwent thyroidectomy at Mayo Clinic from January 1995 to December 2015. Results: We identified 163 patients (mean age 48.4 years, 48% males), 102 with sporadic MTC and 61 with hereditary disease (n = 46 multiple endocrine neoplasia [MEN] 2A, n = 3 MEN 2B, n = 12 familial MTC) with a median follow-up time of 5.5 years. On univariate analysis, age >55 years, male sex, DM at the time of surgery (M1), lateral neck lymph node (LN) involvement (N1b), gross extrathyroidal extension (ETE), American Joint Committee on Cancer (AJCC) stage 3/4, tumor size (T) 3/4, tumor size, and postoperative calcitonin (Ctn) and carcinoembryonic antigen (CEA) were significant predictors of worse OS and DSS. On multivariable analysis, both gross ETE (hazard ratio [HR] 4.62, 6.58) and M1 (HR 5.11, 10.45) remained significant predictors of worse OS as well as DSS, while age >55 years (HR 3.21), male sex (HR 2.42), and postoperative Ctn (HR 1.002 for every 100 pg/mL increase) were significant only for worse OS. On univariate analysis, male sex, M1, N1b, gross ETE, stage 3/4, T 3/4, tumor size, number of LNs involved, and postoperative Ctn were significant predictors of LR and DM; age >55 years was additionally significant for DM. On multivariable analysis, gross ETE (HR 3.16, 5.93) and N1b (HR 4.31, 4.64) remained significant predictors of LR and DM; ratio of resected/involved LN (HR 10.91) was additionally predictive for LR and postoperative Ctn (HR 1.003 for every 100 pg/mL increase) for DM. Conclusions: Disease burden at initial surgery, especially gross ETE, lateral neck LN involvement, and DM, as well as the biochemical response to surgery appear to be more important than demographic factors in terms of MTC prognosis. These findings highlight the importance of rigorous perioperative assessment to better predict MTC outcomes.

The management of thyroid papillary microcarcinoma (PMC) is controversial. Total thyroidectomy, thyroid lobectomy/isthmectomy, and even no treatment have been proposed. We investigated the clinical course and prognostic factors for disease recurrence and distant metastasis in 445 patients with PMC. Data from 445 patients diagnosed with PMC in the period from 1978 to 2003 were reviewed and analyzed. Total thyroidectomy was performed in 404 patients and loboisthmusectomy in 41. Neck dissection took place in 226 patients (49.7%), with 166 of only the central compartment and 60 of both the central and lateral compartments. Radioiodine ((131)I) ablation treatment was given to 389 patients. Median tumor size was 7 mm (range 1-10 mm). PMC was multifocal in 156 cases (35%) and bilateral in 60 cases (13.5%). Extrathyroidal tumor extension (pT3) and neck lymph node metastasis (pN1) were present in 133 (30%) and 182 (40.9%) patients, respectively. Capsular invasion without extrathyroidal tumor extension was observed in 39 (8.7%) patients. Mean follow-up was 5.3 (range 1-26) years. Seventeen (3.8%) patients had recurrence or persistence of disease: neck recurrence (NR) in 12 (2.7%), distant metastasis (DM) in four (0.9%), NR + DM in one (0.2%). One patient (0.2%) died of the disease. Capsular invasion, extrathyroidal tumor extension (pT3), and neck lymph node metastasis at presentation (pN1) were the only independent risk factors for NR and/or DM occurrence (p < 0.05). Patients not showing these features, who were treated with loboisthmusectomy only, never experienced disease recurrence. Total thyroidectomy seems advisable in PMC with extrathyroidal extension and neck lymph node metastasis at presentation. Capsular invasion without extrathyroidal extension may suggest aggressive tumor behavior and require radical treatment.

Follicular cell derived thyroid carcinoma comprise a heterogeneous group of cancers with different clinical and morphological characteristics. Anaplastic thyroid carcinomas (ATC) represent less than 5% of all thyroid cancers but are responsible for more than 50% of thyroid cancer mortality, with a mean survival time from diagnosis of ∼3–6 months. ATC is characterized by local invasion, distant metastasis, chemo and radio-resistance. We showed that ~ 50% of ATCs up-regulated Twist1 with respect to normal thyroids as well as to poorly and well-differentiated thyroid carcinomas. Twist1 is a highly conserved basic helix-loop-helix transcription factor that plays an important role in the development and progression of human cancer. Knockdown of Twist1 by RNA interference in ATC cells reduced cell migration and invasion and increased sensitivity to apoptosis. The ectopic expression of Twist1 in papillary thyroid carcinoma cells (TPC) induced resistance to apoptosis and increased cell migration and invasion. In this dissertation, we have investigated the molecular mechanisms by which Twist1 exerts its biological effect in thyroid cancer cells. To this aim, we analyzed gene expression profiles of thyroid cancer cells ectopically expressing Twist1 in comparison to vector control cells. According to gene expression profile, the top functions enriched in TPC-Twist1 cells were: cellular movement, cellular growth and proliferation, cell death and survival. Silencing of the top ten up-regulated genes reduced viability of TPC-Twist1 and CAL62 cells. Silencing of COL1A1, KRT7, PDZK1 induced also cell death. Silencing of HS6ST2, THRB, ID4, RHOB, and PDZK1IP, also impaired migration and invasion of TPC-Twist1 cells. Chromatin immunoprecipitation showed that Twist1 directly binds the promoter of the ten up-regulated genes. q-RT-PCR on thyroid cancer samples showed that HS6ST2, COL1A1, F2RL1, LEPREL1, PDZK1 and PDZK1IP1 are over-expressed in thyroid carcinoma samples compared to normal thyroids. More recently we have conducted a miRNome expression profile of TPC-Twist1 cells in comparison to control. We identified a set of miRNA potentially regulated by Twist1. We then focused on miR-584 up-regulated by Twist1 in TPC cells. We showed that miR-584 is up-regulated in ATCs respect to normal thyroids and papillary thyroid carcinomas. The ectopic expression of miR-584 protected TPC cells from apoptosis induced by Doxorubicin and Staurosporine. Finally, we showed that miR-584 targets TUSC2 (tumor suppressor candidate 2). Thus, we have identified a set of mRNA and miRNA that mediates Twist1 biological effects in thyroid cancer cells. Transcription factors as Twist1 are generally believed to be difficult to target due to nuclear localization and lack of a specific groove for tight binding of a small molecule inhibitor. Thus, downstream targets of Twist1 could be more realistic for therapeutic intervention.

Extrathyroidal extension (ETE) is a determined factor of T3 and T4 stage of differentiated thyroid cancer (DTC) in American Joint Committee on Cancer. We aimed to compare clinical outcomes between different extent of ETE according to tumor size. Patients diagnosed with DTC were collected from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. They were categorized into two groups by presence of lymph node metastases (LNM) or distant metastases (DM): group A: no presence of LNM and DM, and group B: presence of LNM or DM. Each group was further divided into four groups according to tumor size: <1 cm, 1-2 cm, 2-4 cm, >4 cm. ETE was divided into three groups by the extent: no ETE, microscopic ETE, and macroscopic ETE. Kaplan-Meier method and log-rank test were used to analyze cancer-specific survival (CSS). 91,975 patients were included. In groups A and B, for tumor size 1 cm, there was no significant difference in CSS between no ETE and microscopic ETE, while a significant difference was observed between no ETE and macroscopic ETE. For tumor size >1 cm, there were significant differences in CSS (both no ETE vs. micro ETE and no ETE vs. macro ETE). We suggests that when tumor size is more than 1 cm, micro ETE is significantly associated with poorer outcome. T3 and T4 stages may take account into tumor size rather than merely based on the presence and extent of ETE. It may be prudent to revisit the omission of micro ETE in TNM staging.

Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was conducted to clarify the risk factors for cervical lymph node metastasis (central lymph node metastasis or lateral cervical lymph node metastasis) in MTC by meta-analysis, and to provide evidence-based basis for the treatment and prognosis of MTC. The literatures related to cervical lymph node metastasis in medullary thyroid carcinoma were searched in PubMed, Embase, Web of Science, Cochrane, CNKI and Wanfang databases, and statistical analysis was performed using Revman 5.3 and Stata 14.0 software. A total of 28 papers were included in this paper, and meta-analysis showed that the occurrence of central lymph node metastasis (CLNM) in MTC patients was significantly associated with tumor size (OR = 3.07, 95%CI: 2.04-4.63, P < 0.00001), multifocality (OR = 0.29, 95%CI: 0.19-0.44, P < 0.00001), bilaterality (OR = 3.75, 95% CI: 1.95-7.14, P < 0.0001), capsular invasion (OR = 9.88, 95% CI: 5.93-16.45, P < 0.00001) and extrathyroidal extension (OR = 5.48, 95% CI: 2.61-11.51, P < 0.00001). While the occurrence of lateral cervical lymph node metastasis (LLNM) in MTC patients was strongly correlated with gender (OR = 2.97, 95%CI: 2.46-3.58, P < 0.00001), tumor size (OR = 3.88, 95%CI: 1.90-7.92, P = 0.0002 < 0.05), multifocality (OR = 0.43, 95%CI: 0.35-0.51, P < 0.00001), bilaterality (OR = 2.93, 95% CI: 1.72-4.98, P < 0.0001), capsular invasion (OR = 8.44, 95% CI: 6.11-11.64, P < 0.00001), extrathyroidal extension (OR = 7.04, 95% CI: 5.54-8.94, P < 0.00001), margin of the tumor (OR = 4.47, 95% CI: 2.37-8.44, P < 0.00001), shape of the tumor (OR = 6.81, 95% CI: 3.64-12.73, P < 0.00001), preoperative calcitonin level (SMD = 1.39, 95% CI: 0.98-1.80, P < 0.00001), preoperative carcinoembryonic antigen level (SMD = 0.97, 95% CI: 0.74-1.20, P < 0.00001) and CLNM (OR = 19.70, 95% CI: 14.16-27.43, P < 0.00001). Tumor size, multifocality, bilaterality, capsular invasion and extrathyroidal extension are the main risk factors for developing CLNM in MTC patients; And risk factors for developing LLNM in MTC patients include: gender, tumor size, multifocality, bilaterality, capsular invasion, extrathyroidal extension, margin of the tumor, shape of the tumor, preoperative calcitonin level, preoperative carcinoembryonic antigen level and central lymph node metastasis. These risk factors can guide the individualized treatment plan and improve the prognosis of MTC patients.

The prognosis of the follicular variant of papillary thyroid carcinoma (FVPTC) falls between that of classical papillary thyroid carcinoma (cPTC) and follicular thyroid carcinoma (FTC) (1). FVPTC has lower mortality and less frequent distant metastases than FTC, but higher mortality and more frequent distant metastases than cPTC. FVPTC has fewer lymph node metastases and less frequent infiltrative disease and extrathyroidal extension than cPTC, but more than FTC. But is it a hybrid disease or a mixture of diseases? The pathological appearance of a follicular-patterned tumor with the nuclear features of cPTC suggests that FVPTC is a hybrid. However, the heterogeneous nature of the disease and the mutational profile of FVPTC strongly suggest that it is a mixture of diseases (2). It is the intersection of classical descriptive pathology and modern molecular biology that permits an understanding of this group of diseases.

A subset of follicular thyroid cancers (FTC) can dedifferentiate into anaplastic thyroid cancer (ATC), forming composite FTC/ATC tumors. The effect of this dedifferentiation on survival outcomes remains unclear. This study aimed to characterize the clinicopathologic features of composite FTC/ATC tumors and assess their disease-specific survival (DSS). The Surveillance, Epidemiology, and End Results (SEER) database (2000-2020) was used to identify patients with FTC, composite FTC/ATC, and ATC. Propensity score matching (PSM) was performed on the basis of age, sex, race, and histologic subtype. Clinicopathologic characteristics, DSS, and treatment outcomes were compared. A total of 60 patients with composite FTC/ATC were matched to 180 patients with FTC and 180 patients with ATC. Compared with FTC, composite tumors were associated with larger size (p < 0.001), extra-thyroidal extension (ETE) (p < 0.001), lymph node (p < 0.001) and distant metastases (p = 0.002), more external beam radiation (p < 0.001), and chemotherapy (p < 0.001), but less radioactive iodine (RAI) (p < 0.001). Compared with ATC, composite tumors showed less ETE (p = 0.01), fewer lymph node metastases (p = 0.01), less chemotherapy (p = 0.002), and more RAI (p = 0.002). The median survival of patients with co-FTC/ATC was 7 months (p < 0.001). Advanced age (hazard ratio, HR 1.05; 95% confidence intervals, CI 1.02-1.08) and incomplete thyroidectomy (HR 2.58, 95% CI 1.20-5.56) predicted worse DSS. Composite FTC/ATC tumors have survival outcomes that fall between those of FTC and ATC. Total thyroidectomy is a key component of treatment, as incomplete thyroidectomy is linked to poorer survival. Further research is needed to explore how the proportion of ATC within composite tumors influences survival outcomes.