Well-differentiated Thyroid Carcinoma Research Articles

Surgical Management of Tracheal Invasion by Well-Differentiated Thyroid Cancer.

Simple SummaryTracheal invasion is a poor prognostic factor in well-differentiated thyroid cancer. Appropriate resection can improve the prognosis and maintain the patient’s quality of life. Shaving resection for superficial tracheal invasion is minimally invasive because it does not involve the tracheal lumen, despite the problematic risk of local recurrence. Window resection for tracheal mucosal and luminal invasion provides good tumor control and does not cause postoperative airway obstruction; however, the need for surgical closure of the tracheocutaneous fistula is a disadvantage of this method. Circumferential (sleeve) resection and end-to-end anastomosis are highly curative, but the risk of fatal complications, such as anastomosis dehiscence, is a concern.Well-differentiated thyroid carcinoma (WDTC) is a slow-growing cancer with a good prognosis, but may show extraglandular progression involving the invasion of tumor-adjacent tissues, such as the trachea, esophagus, and recurrent laryngeal nerve. Tracheal invasion by WDTC is infrequent. Since this condition is rare, relevant high-level evidence about it is lacking. Tracheal invasion by a WDTC has a negative impact on survival, with intraluminal tumor development constituting a worse prognostic factor than superficial tracheal invasion. In WDTC, curative resection is often feasible with a small safety margin, and complete resection can ensure a good prognosis. Despite its resectability, accurate knowledge of the tracheal and peritracheal anatomy and proper selection of surgical techniques are essential for complete resection. However, there is no standard guideline on surgical indications and the recommended procedure in trachea-invading WDTC. This review discusses the indications for radical resection and the three currently available major resection methods: shaving, window resection, and sleeve resection with end-to-end anastomosis. The review shows that the decision for radical resection should be based on the patient’s general condition, tumor status, expected survival duration, and the treating facility’s strengths and weaknesses.

A Narrative Review of Genetic Alterations in Primary Thyroid Epithelial Cancer.

Thyroid carcinoma is the most frequent endocrine neoplasia. Different types of thyroid carcinoma are described: well-differentiated papillary thyroid carcinoma (PTC), poorly differentiated thyroid carcinoma (PDTC), follicular thyroid carcinoma (FTC), anaplastic thyroid carcinoma (ATC), and medullary thyroid carcinoma (MTC). MTC is inherited as an autosomal dominant trait in 25% of cases. The genetic landscape of thyroid carcinoma has been largely deciphered. In PTC, genetic alterations have been found in about 95% of tumors: BRAF mutations and RET rearrangements are the main genetic alterations. BRAF and RAS mutations have been confirmed to play an important role also in PDTC and ATC, together with TP53 mutations that are fundamental in tumor progression. It has also been clearly demonstrated that telomerase reverse transcriptase (TERT) promoter mutations and TP53 mutations are present with a high-frequency in more advanced tumors, frequently associated with other mutations, and their presence, especially if simultaneous, is a signature of aggressiveness. In MTC, next-generation sequencing confirmed that mutations in the RET gene are the most common molecular events followed by H-RAS and K-RAS mutations. The comprehensive knowledge of the genetic events responsible for thyroid tumorigenesis is important to better predict the biological behavior and better plan the therapeutic strategy for specific treatment of the malignancy based on its molecular profile.

Well-Differentiated Thyroid Carcinoma Presenting with Sternal Invasion: Complex Resection and Reconstruction in the COVID-19 Era

Background: Advanced thyroid malignancies may invade adjacent structures creating challenging approaches to surgical resection. Methods: We report a 48-year-old gentleman who was found to have a papillary thyroid cancer with invasion of the sternum. Results: The patient presented with pain and swelling in the upper chest. Computed tomography (CT) scanning demonstrated a paratracheal mass with invasion of the manubrium. Core needle biopsy demonstrated papillary thyroid cancer. Surgery was performed during the COVID-19 pandemic. En bloc total thyroidectomy with resection of the manubrium was performed. The defect was closed using a biological mesh, covered with a pectoralis major flap. Final pathology demonstrated a completely excised T4N1bM1 well-differentiated papillary thyroid carcinoma. The patient made an uneventful recovery. Conclusion: En bloc total thyroidectomy with sternal resection can be performed safely with low morbidity. Reconstruction of the sternal defect can be performed with biological mesh and pedicled muscle flap to reduce infection risk.

Robot-Assisted Thyroidectomy Versus Open Thyroidectomy in the Treatment of Well Differentiated Thyroid Carcinoma.

Background:The incidence of thyroid cancer has increased worldwide during the last decade, becoming the most common endocrine malignancy and accounting for 3.8% of new cancer diagnosis. Surgical resection, namely conventional thyroidectomy, remains at the frontline of therapy, as surgical outcomes are undoubtedly successful. Minimally invasive techniques gained popularity through the years, in terms of feasibility, safety, and cosmesis. However, endoscopic approach could be characterized by some limitations concerning thyroid surgery. Robotic technology with its unique features was introduced to overcome these limitations. Since then, robotic thyroidectomy has been used for both benign and malignant thyroid disease.Database:This study presents the use of robot-assisted transaxillary thyroidectomy in well-differentiated thyroid carcinoma through an extensive review of the literature in the PubMed database, including previous meta-analyses and case series.Conclusion:In terms of oncological efficacy, morbidity, and quality of life, outcomes seem comparable in thyroid cancer patients undergoing either open or robotic thyroidectomy. Surgical completeness also appears similar. Moreover, the rates of locoregional recurrence and survival outcome at 5 years are similar between the former and the latter, thus confirming the oncological value of robotic thyroidectomy for differentiated thyroid cancer. In order for more surgeons to adopt robotic approaches several issues need to be resolved, namely: expansion of robotic thyroidectomy in treating larger well-differentiated carcinomas and neck dissection, equipment costs, and prolonged operation times.

IGF2BP1 is the first positive marker for anaplastic thyroid carcinoma diagnosis

Anaplastic thyroid carcinomas (ATC) are rare, but represent the most lethal malignancy of the thyroid. Selective molecular markers and drivers distinguishing ATC from other thyroid carcinomas of follicular origin remain largely unknown, limiting advances in diagnosis and treatment. In a retrospective study, we analyzed gene expression in 36 ATC, 18 poorly differentiated, 132 papillary, and 55 follicular thyroid carcinoma, as well as 124 paired and unpaired normal thyroid tissues in three independent cohorts by RNA-sequencing and immunohistochemistry. RNA-sequencing data in the test cohort suggested selective ATC protein biomarkers. Evaluation of these revealed that ATCs are characterized by the de novo expression of various testis antigens, including melanoma-associated antigen A3 (MAGEA3), but most importantly the oncofetal IGF2 mRNA binding protein 1 (IGF2BP1). Shallow whole genome sequencing essentially excluded that IGF2BP1 upregulation results from gene copy number alterations. Immunohistochemical analyses in all three tumor cohorts confirmed the selective de novo expression of IGF2BP1 protein in ATC. In sum, 75% (27/36) of all tested ATC and 0.5% (1/204) of poorly and well-differentiated thyroid carcinoma tissue samples were positive for IGF2BP1 protein. This indicates that IGF2BP1 protein expression identifies ATC with a diagnostic odds ratio of 612 (95% CI: 74.6–5021). In addition, we found that MAGEA3 is exclusively, although less consistently upregulated in ATC, presenting with an odds ratio of 411 (95% CI: 23.8–7098.7). Importantly, we provide confirmatory evidence that IGF2BP1 and MAGEA3 expression distinguishes ATC from poorly differentiated thyroid carcinoma. IGF2BP1 furthermore identified ATC foci within low-grade follicular thyroid carcinoma. In conclusion, IGF2BP1 represents the most promising single-gene marker available for ATC, followed by MAGEA3, improving on current techniques. Robust markers are essential to help distinguish this high-grade malignancy from other thyroid carcinomas, to guide surgical decision making, therapy and post-resection/therapy monitoring strategies.

A Novel Nanoproteomic Approach for the Identification of Molecular Targets Associated with Thyroid Tumors.

A thyroid nodule is the most common presentation of thyroid cancer; thus, it is extremely important to differentiate benign from malignant nodules. Within malignant lesions, classification of a thyroid tumor is the primary step in the assessment of the prognosis and selection of treatment. Currently, fine-needle aspiration biopsy (FNAB) is the preoperative test most commonly used for the initial thyroid nodule diagnosis. However, due to some limitations of FNAB, different high-throughput “omics” approaches have emerged that could further support diagnosis based on histopathological patterns. In the present work, formalin-fixed paraffin-embedded (FFPE) tissue specimens from normal (non-neoplastic) thyroid (normal controls (NCs)), benign tumors (follicular thyroid adenomas (FTAs)), and some common types of well-differentiated thyroid carcinoma (follicular thyroid carcinomas (FTCs), conventional or classical papillary thyroid carcinomas (CV-PTCs), and the follicular variant of papillary thyroid carcinomas (FV-PTCs)) were analyzed. For the first time, FFPE thyroid samples were deparaffinized using an easy, fast, and non-toxic method. Protein extracts from thyroid tissue samples were analyzed using a nanoparticle-assisted proteomics approach combined with shotgun LC-MS/MS. The differentially regulated proteins found to be specific for the FTA, FTC, CV-PTC, and FV-PTC subtypes were analyzed with the bioinformatic tools STRING and PANTHER showing a profile of proteins implicated in the thyroid cancer metabolic reprogramming, cancer progression, and metastasis. These proteins represent a new source of potential molecular targets related to thyroid tumors.

Patient and tumor factors contributing to distant metastasis in well-differentiated thyroid cancer: a retrospective cohort study

BackgroundDistant metastasis in thyroid cancer significantly reduces survival in patients with well-differentiated thyroid carcinoma (WDTC). There is limited information available to clinicians regarding pathological features that confer a higher risk of distant metastasis (DM). This study aimed to identify patient and tumor factors that were associated with the development of DM over time in patients with WDTC.MethodsA retrospective cohort analysis of patients with WDTC (n = 584) at our institution was performed between 2007 and 2017. A total of 39 patients with DM and 529 patients with no DM (NDM) were included. Patient demographics, tumor characteristics and patient survival were compared between the DM and NDM groups using a univariate analysis. Multivariate Cox-proportional hazards model was used to evaluate the risk of developing distant metastasis over time. Kaplan-Meier analysis was used to compare survival between the DM and NDM groups.ResultsDistant metastasis had a substantial impact on disease-specific survival (DSS) at 5 and 10-years in the DM group; 71.0% (SE 8.4%) and 46.9% (SE 11.6%) respectively, compared to 100% survival in the NDM group (p < 0.001). The DM group had significantly higher proportions of males, lymphovascular invasion (LVI), nodal metastasis (NM), large tumor size (TS), extrathyroidal extension (ETE), positive resection margins, multifocality, follicular thyroid cancer (FTC), tall cell variant of papillary thyroid cancer (PTC), and Hurthle cell carcinoma (HCC), when compared to the NDM group (p < 0.05). A TS ≥ 2 cm (Hazard Ratio (HR) 1.370), NM (HR 3.806) and FTC (HR 7.068) were associated with a significantly increased hazard of developing distant metastasis in patients with WDTC.ConclusionsTS ≥ 2 cm, NM and FTC are associated with a significantly increased propensity for developing DM in our cohort of WDTC patients.Graphical abstract

Adrenal metastasis as the initial diagnosis of synchronous papillary and follicular thyroid cancer

BackgroundDifferentiated thyroid cancer uncommonly presents with distant metastases. Adrenal metastasis from differentiated thyroid cancer presenting as the initial finding is even less common.Case PresentationA 71-year-old male was incidentally found on chest CT to have bilateral thyroid nodules, which were confirmed on ultrasound. Fine needle aspiration of the dominant right 3.3 cm nodule contained histologic features most consistent with Bethesda classification III, and repeat fine needle aspiration revealed pathology consistent with Bethesda classification II. Follow-up thyroid ultrasound showed 1% increase and 14% increase in nodule volume at one and two years, respectively, compared to baseline. Prior to the second annual thyroid ultrasound, the patient was incidentally found to have a 4.1 cm heterogeneously enhancing mass in the right adrenal gland on CT of the abdomen and pelvis. Biochemical evaluation was unremarkable with the exception of morning cortisol of 3.2 µg/dL after dexamethasone suppression. The patient then underwent laparoscopic right adrenal gland excision, which revealed metastatic follicular thyroid carcinoma. Total thyroidectomy was then performed, with pathology showing a 4.8 cm well-differentiated follicular thyroid carcinoma of the right lobe, a 0.5 cm noninvasive follicular thyroid neoplasm with papillary-like nuclear features of the left lobe, and a 0.1 cm papillary microcarcinoma of the left lobe. Thyrotropin-stimulated whole body scan showed normal physiologic uptake of the remnant thyroid tissue without evidence of other iodine avid disease. The patient then received radioactive iodine. At follow-up 14 months after total thyroidectomy, he remains free of recurrent disease.ConclusionDespite following the recommended protocol for evaluation and surveillance of thyroid nodules, thyroid cancer can be challenging to diagnose, and may not be diagnosed until distant metastases are identified.

PO-0817: Implication of BRAF mutations in well-differentiated thyroid carcinoma.

PO-0817: Implication of BRAF mutations in well-differentiated thyroid carcinoma.

Pattern of Nodal Metastasis in Relation to Size of the Primary Tumour in Well-Differentiated Thyroid Carcinoma.

This study was conducted to see the pattern of neck node metastasis in relation to the size of primary tumour in Well-differentiated thyroid cancer. A prospective study on 50 patients was carried out in the Department of Head and Neck Surgery, Dr B. Borooah Cancer Institute from 1st August, 2018 to 31st July, 2019. All new cases who had not previously received treatment were included which were histopathogically proven. Residual and recurrent cases were not taken into account. Most common age-group affected was 21-30years (24%). It was more common in females (84%). Papillary thyroid cancer has been found to be the most common histological type of WDTC (88%), out of which the classical variant of PTC constitute 72%. 46% of them had tumour size > 4cm 88% cases had cervical neck node metastases, out of which 72% were unilateral and 16% were bilateral. The commonest level involved was level VI. There is a definite correlation (clinical and histological) between increased involvement of positivity of lymph node in relation to size of the primary tumour in well-differentiated thyroid carcinoma.

Late-onset distant metastases confer poor prognosis in patients with well-differentiated thyroid cancer.

Distant metastases from well-differentiated thyroid carcinoma (WDTC) occasionally occur over a wide range of time intervals after primary thyroid surgery. The prognostic impact of the timing of distant metastasis onset remains unclear. We retrospectively reviewed the clinicopathologic features and clinical outcomes of 57 patients with WDTC and distant metastases, and evaluated the mutational profiles of BRAF, RAS, and TERT promoter genes. All patients underwent thyroidectomy and radioactive iodine (RAI) ablation using the same treatment protocol. Synchronous distant metastases were defined as those detected within 12 months of the primary WDTC diagnosis. Metachronous metastases were considered early- and late-onset diseases if detected 1-5 and ≥5 years after the primary diagnosis, respectively. In all patients, the 5- and 10-year cancer-specific survival (CSS) rates after the diagnosis of distant metastasis were 86% and 57%, respectively. Late-onset (≥5 years) metachronous distant metastasis was associated with age of ≥55 years (P=0.043) and patients refractory to RAI therapy (P=0.026). TERT promoter mutations were associated with RAI refractivity (P=0.026). BRAF V600E and RAS mutations had no prognostic significance. Bone metastasis (P=0.002) and the onset time of distant metastasis (P=0.004) were associated with poor CSS. There was no significant difference in CSS between patients with synchronous distant metastases and those with early-onset (1-5 years) metachronous distant metastases. In the multivariate analysis, bone metastasis [hazard ratio (HR) =10.24; 95% confidence interval (CI): 1.25-83.74; P=0.030] and late-onset (≥5 years) metachronous distant metastasis (HR =5.20; 95% CI: 1.01-26.63; P=0.048) were independent predictors for worse CSS. The prognosis of patients with WDTC was poorer for late metachronously detected metastases than for synchronous or early metachronous metastases. Patients with distant metastasis occurring 5 years later after primary thyroid diagnosis should, therefore, be more carefully treated.

Characterization of BRAF mutation in patients older than 45 years with well-differentiated thyroid carcinoma

IntroductionPapillary thyroid carcinoma is the most frequent endocrine neoplasia and its incidence has tripled over the past 35 years. Although papillary thyroid carcinoma carries a good prognosis, 10%−30% of patients still develop recurrence and metastasis. Some clinical and genetic features are associated with worse prognosis. The most frequent mutation is the BRAF p.V600E, which has been associated with many clinical features of poor prognosis. However, many studies have produced controversial results without any association between BRAF mutation and clinicopathological features of poor prognosis. ObjectiveSince the prognostic value of BRAF mutations remains controversial, this study aims to investigate the importance of this mutation in therapeutic decisions for papillary thyroid carcinoma. MethodsTherefore, we evaluated whether the presence of BRAF mutation is associated with features of poor prognosis in 85 patients with papillary thyroid carcinoma older than 45 years treated at A.C. Camargo Cancer Center, from 1980 to 2007. BRAF mutation was evaluated by pyrosequencing. Statistical analysis was performed using SPSS. ResultsThe mean age of patients was 54 years (range: 45 − 77 years), 73 were women (85.8%) and 12 were men (14.2%). Among them, 39 cases (45.9%) presented extrathyroidal extension and 11 cases had recurrent disease. BRAF mutation was detected in 57 (67%) patients. No significant association was observed between BRAF mutation and gender (p = 0.743), age (p = 0.236), N-stage (p = 0.423), vascular and perineural infiltration (p = 0.085 or multifocality (p = 1.0). Although not statistically significant, the majority of patients with recurrent disease were BRAF positive (9 out of 11) (p = 0.325). Patients affected by BRAF mutation are associated with tumors larger than 1 cm (p = 0.034) and with extrathyroidal extension (p = 0.033). ConclusionAlthough BRAF testing is widely available, there are no consistent data to support improvement in outcomes from incorporating it into therapeutic decision for thyroid cancer.

Follicular Thyroid Carcinoma Presenting as a Humeral Mass: A Rare Case Presentation

Follicular thyroid carcinoma is the second most common cancer of the thyroid, which usually presents as a solitary thyroid nodule. Diagnosis of follicular thyroid cancer involving the appendicular skeleton is very rare. In this paper, we report a case of a 65-year-old woman who previously underwent partial lobectomy of the left thyroid gland, and who consequently presented with a 2-year history of gradually enlarging left arm mass. Initial whole-body bone imaging revealed a large osteolytic lesion in the humerus. An MRI (magnetic resonance imaging) of the left arm showed a heterogeneously enhancing, encapsulated, soft tissue mass with humeral involvement, and the initial impression was osteosarcoma versus fibrosarcoma. Biopsy reading of the humeral mass was morphologically compatible with a well-differentiated metastatic thyroid carcinoma. She subsequently underwent right lobectomy where histopathology showed Hashimoto’s thyroiditis. A slide review was requested and the biopsy of the humeral mass revealed adenocarcinoma with follicular architecture, compatible with a metastatic thyroid carcinoma. Meanwhile, the findings on the right thyroid lobe revealed a multinodular colloid adenomatous goiter with hyperplastic features in a background of Hashimoto’s thyroiditis. This report demonstrated a rare presentation of follicular thyroid carcinoma metastasizing to the humerus that can be confused with primary bone tumors, both clinically and radiologically. Early diagnosis and a high index of suspicion is foremost for immediate and appropriate management.

Contemporary evaluation and management of tall cell variant of papillary thyroid carcinoma.

The purpose of this review is to describe the contemporary evaluation and management of tall cell variant of papillary thyroid carcinoma with an emphasis on the clinical features. Tall cell variant of papillary thyroid carcinoma is the most common aggressive subtype. Within the last few years, the diagnostic criteria for this entity have evolved. Studies have elucidated a better understanding of the clinical implications and pathophysiology of this variant. In this review, the studies presented reflect cumulative and aggregated data from metaanalyses, systematic reviews, and large database investigations utilizing the current diagnostic criteria. Overall, tall cell variant of papillary thyroid carcinoma represents an aggressive subtype of well-differentiated thyroid carcinoma with more prevalent high-risk features and a poorer clinical outcome.

Is a Prophylactic Central Compartment Neck Dissection Required in Papillary Thyroid Carcinoma Patients with Clinically Involved Lateral Compartment Lymph Nodes?

The 2015 American Thyroid Association guidelines state that a prophylactic central compartment neck dissection (PCND) should be considered for patients with papillary thyroid carcinoma (PTC) and clinically involved lateral neck lymph nodes (cN1b). The purpose of our study was to determine the rate of central neck recurrence in select cN1b patients, with no evidence of clinically involved central compartment lymph nodes, treated without a PCND. After institutional review board approval, adult PTC patients with cN1b disease who were treated with a total thyroidectomy and lateral neck dissection were identified from an institutional database of 6259 patients who underwent initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients with gross extrathyroidal extension, distant metastases, or no preoperative imaging were excluded. Patients with evidence of clinically involved central compartment lymph nodes, on preoperative imaging or intraoperative evaluation, also were excluded. A total of 152 cN1b patients were included and categorized into non-PCND and PCND groups. Central neck recurrence-free probability (CNRFP) was calculated using the Kaplan-Meier method and log-rank tests. One hundred three patients (67.8%) did not have a PCND. With a median follow-up of 65months, the 5- and 10-year CNRFP was 98.4% in the non-PCND group and 93.6% in the PCND group (p = 0.133). Select PTC patients with cN1b disease but no evidence of clinically involved central compartment lymph nodes, on preoperative imaging and intraoperative evaluation, appear to have a low rate of central neck recurrence. These patients may not require or benefit from a PCND.

Prevalence and Risk of Metastatic Thyroid Cancers and Management Outcomes: A National Perspective.

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.

Miliary pulmonary metastases from well-differentiated pediatric thyroid carcinoma

Abstract Differentiated thyroid cancer (DTC) occurs rarely in the pediatric population, contributing to 1%–2% of childhood malignancies. Lung metastases have been reported to occur in 7%–30% in this age group. Moreover, pulmonary metastases presented with miliary pattern of micronodules are uncommon in pediatric cancer patients. In developing countries, miliary lung nodules are most frequently seen in pulmonary tuberculosis. However, we herein report a rare pediatric patient with miliary pulmonary metastases from well-differentiated thyroid carcinoma and discuss about differential diagnosis of miliary pattern of micronodules.

Successful Treatment of Cavernous Sinus Metastasis from Follicular Thyroid Carcinoma with Lenvatinib

Radioiodine-refractory distant metastases in well-differentiated thyroid carcinomas are rare but pose a significant diagnostic and management challenge. Follicular thyroid carcinoma which is a type of well-differentiated carcinoma, is known for its hematogenous spread. Various sites of distant metastasis have been described. We report the first-ever case of radioiodine-refractory metastasis at the cavernous sinus, arising from follicular thyroid carcinoma. The atypical site of metastasis and management complexity of radioiodine-refractory disease is discussed in this article.

SUN-483 A Retrospective Diagnosis of Malignant Struma Ovarii After Discovery of Pulmonary Metastases

Background: Malignant struma ovarii is a rare ovarian tumor that is histologically identical to differentiated thyroid carcinoma.1 We present a case of a struma ovarii that was recognized as being malignant only after the discovery of pulmonary metastases. Clinical Case: A 29 year old female presented to the hospital with acute right lower abdominal pain, suspicious for ovarian torsion. She underwent urgent right salpingoopherectomy and pathology demonstrated a mature cystic teratoma with benign struma ovarii. Two years later, a CT of the abdomen incidentally revealed bilateral pulmonary nodules. Review of the imaging showed that these pulmonary nodules were also present two years prior, and had since become larger. Video-assisted thoracoscopic surgery was performed and lung biopsy was positive for well-differentiated thyroid carcinoma. The patient then underwent total thyroidectomy which revealed a 0.3 x 0.3 cm infiltrative papillary thyroid cancer, follicular variant, without lymphovascular invasion. Thyroglobulin level decreased from 169 ng/mL pre-operatively to 80 ng/mL post-operatively, but then continued to be variable ranging from 56 to 252 ng/mL (1.6-50 ng/mL). Thyroglobulin antibodies remained negative.Pathology from right ovary was re-reviewed at a second institution and found to be consistent with highly differentiated thyroid carcinoma with characteristic nuclear features of papillary thyroid carcinoma.A diagnostic whole body I-131 scan showed uptake within the thyroid bed, bilateral lung nodules, left distal thigh and right mid thigh. These thigh lesions were not visualized on lower extremity ultrasound. After dosimetry was performed, the patient received radioactive iodine-131 200 mCI. Post-therapy scan six days later demonstrated uptake in the thyroid bed, bilateral lungs and bilateral thighs. About five months later, thyroglobulin level had decreased to 0.4 ng/mL with a suppressed TSH. A repeat CT chest demonstrated that the lung nodules had all decreased in size, largest from 0.5 cm to 0.3 cm. Conclusion: Careful examination of struma ovarii pathology should be performed to evaluate for malignant features since benign appearing histology can present diagnostic difficulty.2 In this case, thyroglobulin level was lower than reported in previous cases; however, sites of metastases were responsive to radioactive iodine therapy indicating well differentiated disease and a favorable prognosis.

Incidence and Mortality Risk Spectrum Across Aggressive Variants of Papillary Thyroid Carcinoma

While well-differentiated papillary thyroid carcinoma (WDPTC) outcomes have been well characterized, the prognostic implications of more aggressive variants are far less defined. The rarity of these subtypes has led to their consolidation as intermediate risk for what are in fact likely heterogeneous diseases. To analyze incidence, clinicopathologic characteristics, and outcomes for aggressive variants of papillary thyroid carcinoma (PTC). This cohort study used data from 2000 to 2016 from hospital-based and population-based US cancer registries to analyze aggressive PTC variants, including diffuse sclerosing (DSV), tall-cell (TCV), insular, and poorly differentiated (PDTC) subtypes. These variants were compared against WDPTC and anaplastic cases. Data analysis was conducted from January 2019 to October 2019. Age-adjusted incidence was calculated via annual percentage change (APC) using the weighted least-squares method. Overall survival and disease-specific survival were analyzed via Cox regression. Propensity-score matching was used to adjust survival analyses for clinical and demographic covariates. Collectively, 5447 aggressive PTC variants were identified (including 415 DSV, 3339 TCV, 362 insular, and 1331 PDTC cases), as well as 35 812 WDPTC and 2249 anaplastic cases. Over the study period, a substantial increase in aggressive variant incidence was observed (APC, 9.1 [95% CI, 7.33-10.89]; P < .001), surpassing the relative increases observed in WDPTC (APC, 5.1 [95% CI, 3.98-6.12]; P < .001) and anaplastic cases (APC, 1.9 [95% CI, 0.75-3.05]; P = .003; parallelism P < .007). Survival varied markedly based on histologic subtype, with a wide spectrum of mortality risk noted; 10-year overall survival was 85.4% (95% CI, 84.6%-86.3%) in WDPTC, 79.2% (95% CI, 73.6%-85.3%) in DSV, 71.9% (95% CI, 68.4%-75.6%) in TCV, 45.1% (95% CI, 40.2%-50.6%) in PDTC, 27.9% (95% CI, 20.0%-38.9%) in the insular variant, and 8.9% (95% CI, 7.5%-10.6%) in anaplastic cases (P < .001). These differences largely persisted even after adjusting for inherent differences in baseline characteristics by multivariable Cox regression and propensity-score matching. An upsurge in aggressive PTC incidence was observed at a rate beyond that seen in WDPTC or anaplastic thyroid carcinoma. Moreover, long-term survival outcomes for aggressive PTC subgroups exhibit heterogeneous clinical behavior and a wide range of mortality risk, suggesting that treatment should be tailored to specific histologic subtypes. Given increasing prevalence and disparate outcomes, further investigation to identify optimal therapeutic strategies is needed in these diverse, understudied populations.