One Case of a Primary Papillary Thyroid Carcinoma in the Intrathoracic Lymph Node

The expression profiles of the galectin gene family in primary and metastatic papillary thyroid carcinoma with particular emphasis on galectin-1 and galectin-3 expression

We describe 11 cases (8 females, 3 males) of papillary thyroid carcinoma in children treated at St. Jude Children's Research Hospital over a 33-year period, and review the literature. Ages ranged from 7-25 years (median, 16 years). Six patients had primary papillary thyroid carcinoma. Five patients had secondary papillary thyroid carcinoma after treatment of Hodgkin's disease (n = 2), acute lymphoblastic leukemia (n = 2), and neuroblastoma (n = 1) with chemotherapy and cervical radiation. The typical presentation was either cervical lymphadenopathy or a thyroid mass of short duration. Treatment consisted of thyroidectomy, cervical lymph node dissection, and postoperative thyroid hormone replacement (n = 1), parathyroid reimplantation (n = 1), 131I ablation (n = 4), external-beam irradiation (n = 1), and chemotherapy with doxorubicin (n = 1) or carboplatin and topotecan (n = 1). Nine patients are alive without evidence of disease 3.0-22.4 years from diagnosis. One patient has persistent but stable disease 17.3 years after diagnosis. One patient relapsed with metastatic lung disease 0.3 years after the initial diagnosis. He continues to do well after a brief but unsustained complete radiographic remission of disease to combination chemotherapy with carboplatin and topotecan. Our review supports excellent long-term outcome for primary or secondary papillary thyroid carcinoma in pediatric patients although complications may require close follow-up in a multidisciplinary setting.

We describe 11 cases (8 females, 3 males) of papillary thyroid carcinoma in children treated at St. Jude Children's Research Hospital over a 33-year period, and review the literature. Ages ranged from 7–25 years (median, 16 years). Six patients had primary papillary thyroid carcinoma. Five patients had secondary papillary thyroid carcinoma after treatment of Hodgkin's disease (n = 2), acute lymphoblastic leukemia (n = 2), and neuroblastoma (n = 1) with chemotherapy and cervical radiation. The typical presentation was either cervical lymphadenopathy or a thyroid mass of short duration. Treatment consisted of thyroidectomy, cervical lymph node dissection, and postoperative thyroid hormone replacement (n = 11), parathyroid reimplantation (n = 1), 131I ablation (n = 4), external-beam irradiation (n = 1), and chemotherapy with doxorubicin (n = 1) or carboplatin and topotecan (n = 1). Nine patients are alive without evidence of disease 3.0–22.4 years from diagnosis. One patient has persistent but stable disease 17.3 years after diagnosis. One patient relapsed with metastatic lung disease 0.8 years after the initial diagnosis. He continues to do well after a brief but unsustained complete radiographic remission of disease to combination chemotherapy with carboplatin and topotecan. Our review supports excellent long-term outcome for primary or secondary papillary thyroid carcinoma in pediatric patients, although complications may require close follow-up in a multidisciplinary setting. Med. Pediatr. Oncol. 28:433–440, 1997. © 1997 Wiley-Liss, Inc.

Brain metastases of papillary thyroid carcinoma origin are derived from aggressive histologic variants and demonstrate similar adverse morphology in the metastatic lesion

Background Thyroglossal duct cysts (TGDC) are remnants of the thyroglossal duct tract that do not atrophy and disappear, instead undergoing cystic expansion and often presenting as a midline neck mass. Rarely, carcinomas of the thyroglossal duct cyst occur, either arising as a primary carcinoma or as a cystic metastasis from a primary thyroid cancer; the former are particularly rare. These thyroglossal duct cyst carcinomas most commonly present in the adult population. Case Report We present the case of a 32-year-old female without any significant past medical history who presented with a non-tender midline neck mass identified as a thyroglossal duct cyst and completely excised; pathology results were positive for a primary papillary thyroid carcinoma with a tumor measuring 1.3 cm in diameter within the TGDC. Thyroid Ultrasound also showed the presence of two nodules measuring 1.4 cm on the right and 1.2 cm on the left, respectively, with fine needle aspiration (FNA) of both the nodules confirming papillary thyroid carcinoma as well. Lymph node FNA was negative for metastatic carcinoma. The patient underwent a thyroidectomy which definitively confirmed both a classic papillary carcinoma as well as an encapsulated, non-invasive follicular variant. In keeping with the original finding of the patient having a primary thyroglossal duct cyst carcinoma, samples from the thyroidectomy had negative tumor margins, and were also negative for any angioinvasion, lymphatic invasion, or extrathyroidal extension. Conclusion While thyroglossal duct cysts are the most common type of congenital neck cyst, primary carcinomas arising from thyroglossal duct cysts are rare. Masses that occur anywhere along the thyroglossal duct tract should be investigated for malignancy, with additional investigation of the thyroid gland for either a primary or secondary thyroid cancer. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Thyroglossal duct cysts(TDC) are the most common congenital anomaly resulting in midline masses in children (70%in children and 1% in adults). The occurrence of carcinoma is extremely rare in children as compared to adults. Because of the classical clinical findings of TDC's preoperative diagnosis of malignancies within them are rarely done. Even fine needle aspiration cytology also less valuable in preoperative diagnosis. The final diagnosis is usually an incidental finding in histopathological examination of excised TDC's. We report a rare case of papillary thyroid carcinoma in a 17 year old girl and reviewed in the pertinent background of evidence based literature

Introduction/Objective Differentiating papillary thyroid hyperplasia from papillary thyroid carcinoma is made primarily on differences in key histologic and cytomorphologic features. These include architectural features such as invasion and nuclear changes such as chromatin pallor, nuclear grooves, and intranuclear pseudoinclusions. Distinguishing between these two diagnoses is not always straightforward in a minority of cases, as papillary thyroid hyperplasia nodules can be misinterpreted as papillary thyroid carcinoma and vice versa. This is because the nuclear changes can be subtle and be induced artificially by poor or inadequate formalin fixation. Immunostains such as cytokeratin 19 (CK19), galectin-3, and HBME1 may be used to distinguish between papillary thyroid hyperplastic nodules and papillary thyroid carcinoma; however, as immunostaining results are not always definitive, other more definitive ancillary tests are sometimes utilized such as molecular testing. Methods/Case Report Thyroid cases with indeterminate diagnoses (n=6) were obtained from the archives. Such cases included papillary thyroid hyperplasia and cases with descriptive diagnoses such as well-differentiated encapsulated and low-grade papillary carcinoma. Five cases of definitive papillary thyroid carcinoma and one case of follicular thyroid carcinoma (n=6) were used as a comparison group. Next generation sequencing (NGS) assays were performed using a custom SLIMamp targeted DNA solid tumor panel (Pillar Biosciences) and a targeted multi gene RNA fusion panel (Invitae). Results (if a Case Study enter NA) All of the definitive cases of papillary thyroid carcinoma showed characteristic mutations such as BRAF V600E as well as RNA fusions such as RET/PTC while all of the indeterminate cases did not show any detectable DNA mutations or RNA fusions, confirming their benign nature. A separate case that was signed out as non-invasive follicular thyroid neoplasm with papillary-like nuclear features showed an NRAS Q61R mutation and a novel ETV1-ERG fusion. Conclusion This study demonstrates the utility of molecular testing as an adjunct to histopathological evaluation in definitive diagnosis and differentiation of papillary thyroid hyperplasia from papillary carcinoma. Next generation sequencing with targeted DNA and RNA panels will be beneficial for both known and novel variant or fusion detection in suspect cases.

Primary papillary carcinoma arising from ectopic thyroid tissue in the cervical lymph node: A case report

Although tyrosine-phosphorylated or activated STAT3 (pY-STAT3) is a well-described mediator of tumorigenesis, its role in thyroid cancer has not been investigated. We observed that 63 of 110 (57%) human primary papillary thyroid carcinoma (PTC) cases expressed nuclear pY-STAT3 in tumor cells, preferentially in association with the tumor stroma. An inverse relationship between pY-STAT3 expression with tumor size and the presence of distant metastases was observed. Using human thyroid cancer-derived cell lines [harboring rearranged during transfection (RET)/PTC, v-RAF murine sarcoma viral oncogene homolog B (BRAF), or rat sarcoma virus oncogene (RAS) alterations], we determined that IL-6/gp130/JAK signaling is responsible for STAT3 activation. STAT3 knockdown by shRNA in representative thyroid cancer cell lines that express high levels of pY-STAT3 had no effect on in vitro growth. However, xenografted short hairpin STAT3 cells generated larger tumors than control cells. Similarly, STAT3 deficiency in a murine model of BRAFV600E-induced PTC led to thyroid tumors that were more proliferative and larger than those tumors expressing STAT3wt. Genome expression analysis revealed that STAT3 knockdown resulted in the down-regulation of multiple transcripts, including the tumor suppressor insulin-like growth factor binding protein 7. Furthermore, STAT3 knockdown led to an increase in glucose consumption, lactate production, and expression of Hypoxia-inducible factor 1 (HIF1α) target genes, suggesting that STAT3 is a negative regulator of aerobic glycolysis. Our studies show that, in the context of thyroid cancer, STAT3 is paradoxically a negative regulator of tumor growth. These findings suggest that targeting STAT3 in these cancers could enhance tumor size and highlight the complexities of the role of STAT3 in tumorigenesis.

TERT promoter (TERTp) mutations represent a common oncogenic event in sporadic thyroid follicular cell carcinogenesis. Though TERTp mutations have been statistically associated with aggressiveness and metastatic spreading, their involvement in lymph node metastases (LNMs) and / or distant metastases (DMs) development among papillary thyroid carcinoma (PTC) patients remains to be defined. To evaluate the role of TERTp mutations on metastatic tumor expansion, primary tumors (Pt) and matched LNMs and/or DMs were genotyped by means of PCR-direct sequencing in a cohort of 33 patients diagnosed of PTC, which had been previously analyzed for BRAF and RAS mutations. Focal changes in the growth pattern or microscopic grade within the Pt or the metastases were separately genotyped to determine the clonal/subclonal nature of TERTp mutations, their association with particular histological variants of PTC or their presence in intra-tumoral PDC-like foci. Results were correlated with clinico-pathological parameters of pour outcome and survival. The analysis of 99 tumor samples obtained from 33 PTC cases revealed that TERTp mutations were quite common (42.4%).The mutation C228T was much more common than the C250T (78,6% vs 21,4%). TERTp mutations did not correlate with specific PTC subtypes [CL-PTC, FV-PTC or Mixed-PTC] and were subclonal in half of the cases. The mutations segregated to LNMs in 73% of cases [100% CL-PTC and FV-PTC; 57% Mixed PTC]. In 2 Mixed-PTC cases the mutation seemingly originated the novo in the LNM. TERTp mutations were present in all samples of DM. While 71% of the cases mutated at TERTp bore the BRAFV600E mutation, the coexistence of TERTp and RAS mutations was exceptional. TERTp mutations were found to be significantly correlated with age ≥ 45 years old, high grade poorly differentiated PTC foci or nesting-PDC-like foci, stage at diagnosis or at last follow-up and patient status. A trend of correlation with male sex, vascular invasion, tumor recurrence and development of LNM during the follow-up was also seen. Tumor multifocality was inversely correlated with TERTp mutations. The coexistence of TERTp and BRAFV600E mutants did not increase the prognostic power of TERTp mutations alone. All of the patients who died of disease displayed TERTp mutations. Kaplan-Meier analysis revealed that patients with PTC bearing TERTp mutations had a poor prognosis showing a higher tumor recurrence probability [p= 0.0085] and a reduced disease specific survival [p<0.0001]. The coexistence of other mutations did not significantly increase the risk of recurrence or dying of disease. The study indicates that TERTp mutations: 1) are common in metastatic PTC; 2) are subclonal in half of the cases; 3) spread in most cases with metastatic cells to LNM and DM but do not drive the development of LNM; 4) identify PTCs patients with increased risk of recurrence and mortality; 5) represent “per se” a biomarker for poor outcome among PTCs Citation Format: Noa Feás Rodríguez, Miram Corraliza Gómez, Tomás Alvarez Gago, Juan José Mateos Otero, Raquel Muñoz Martínez, Ginesa Maria Garcia-Rostan. TERT promoter mutations in primary papillary thyroid carcinomas and matched local / distant metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5505. doi:10.1158/1538-7445.AM2017-5505

Introduction Health care statistics provides a solid evidence of increasing thyroid cancer prevalence in Latvia. However, in order to characterise the problem of thyroid cancer more completely, histological type and stage of carcinomas as well as demographic characteristics of the affected patients would be as important as the total burden of new cases. Aim of the study was to provide detailed characteristics of the spectrum of surgically treated primary thyroid carcinoma. Materials and methods. The study was designed as retrospective research. Archives of a single university hospital were searched for consecutive, surgically treated or histologically proved cases of primary thyroid carcinoma (2008 - 2012). Each case was characterised by histological type, local tumour spread, largest diameter of the carcinoma, patient’s age and sex as well as extent of surgical treatment. Descriptive statistics was carried out by CIA software. Results. Archive search yielded 323 primary thyroid carcinoma cases, including 255 cases (78.9%; 95% confidence interval (CI) = 74.2 - 83.0) of papillary carcinoma, 54 cases (16.7%; 95% CI = 13.1 - 21.2%) of follicular carcinoma and 7 cases (2.2%; 95% CI = 1.1 - 4.4%) of medullary and anaplastic carcinoma. Although the youngest cases (aged 18 and 20 years) were diagnosed with papillary and follicular carcinoma, respectively, the mean age did not show statistically significant differences between the groups. Strong female predominance was observed regardless of cancer type. Regarding local tumour spread, pT1a was significantly more frequent in papillary carcinoma: 50.2% (95% CI = 44.1 - 56.3) in contrast to 18.5% (95% CI = 10.4 - 28.9) in case of follicular carcinoma. Total thyroidectomy was the most frequent type of operation that was applied for 28.6 - 71.4% cases in relation to histological type. Conclusions. This is the first research work in Latvia that comprehends the overall review of the morphological spectrum of thyroid carcinoma in the surgical material. Papillary and follicular carcinomas are the most frequently identified types in accordance with the global data. Much less common morphological forms of thyroid tumours were also diagnosed - medullary carcinoma and anaplastic thyroid carcinoma. The large mean diameter of follicular carcinoma in the surgery material and the fact that more than half of follicular carcinomas are revealed as pT2-T3 tumours highlights the necessity for up-to-dated diagnostics and elaboration of reliable novel molecular tests.

Distant metastases (DM) are a rare occurrence in well-differentiated thyroid carcinoma. The aim of this study was to analyze the clinical, pathologic, and molecular features of primary thyroid carcinoma with low-risk histology that develop DM. A detailed clinicopathologic review and targeted next-generation sequencing were performed on a cohort of well-differentiated thyroid carcinoma lacking gross extrathyroidal extension, extensive vascular invasion, or significant lymph node metastases but exhibiting DM. Primary well-differentiated thyroid carcinoma with low-risk histologic features and DM was a rare occurrence, accounting for only 3% of metastatic non-anaplastic thyroid carcinoma. All 15 cases meeting the inclusion criteria harbored DM at presentation. The majority (11/15) of these tumors were follicular variant of papillary thyroid carcinoma (PTC), especially the encapsulated form (n = 8). The remaining patients harbored encapsulated Hürthle cell carcinoma (n = 2), encapsulated follicular carcinoma (n = 1), and an encapsulated papillary carcinoma classical variant (n = 1). Of the 12 encapsulated carcinomas, 10 had capsular invasion only and no vascular invasion. Ninety-two percent of the tumors exhibited extensive intra-tumoral fibrosis. Among the eight tumors that were subjected to next-generation sequencing analysis, a RAS mutation was the main driver (5/8), and TERT promoter mutation was highly prevalent (6/8). In four cases, TERT promoter mutations were associated with RAS or BRAF mutations. BRAF-mutated classical variant of papillary carcinoma also presented with DM but was less common (1/8). In 11/15 cases, the clinician was able to diagnose distant disease based on the clinical presentation. In 3/4 incidental cases that were genotyped, TERT promoter mutations were found. When DM occur in primary thyroid carcinoma with low-risk histology, they are almost always found at presentation. The majority are encapsulated follicular variant of PTC with capsular invasion only. TERT promoter mutations occur at a higher rate than that seen in PTC in general and may help explain the aggressive behavior of these histologically deceptive primary carcinomas.

To present a case of struma ovarii with a typical features and synchronous primary thyroid carcinoma and review the available literature to guide diagnosis and management of these tumors. We present a case from our hospital of a 55-year-old woman who had an adnexal mass with features concerning for papillary thyroid carcinoma and was ultimately determined to be struma ovarii with atypical features. Subsequent thyroid imaging and biopsy revealed a primary cervical thyroid carcinoma. We performed a PubMed search of published English language articles using the search terms "malignant struma ovarii," "metastatic struma ovarii," "struma ovarii with malignant transformation," "struma ovarii papillary thyroid carcinoma," "struma ovarii follicular thyroid carcinoma," and "struma ovarii with concurrent primary thyroid carcinoma." Literature review included 104 studies with a total of 195 patient cases. The average age at presentation was 44.9years. 25.1% of patients had metastatic disease at presentation, and 6.2% had synchronous primary carcinomas; all of which were located in the thyroid. Thyroid carcinoma arising in struma ovarii or mature cystic teratoma should prompt clinical evaluation and imaging of the thyroid given the possibility of synchronous primaries, metastases, and recurrence.

BackgroundThyroid cancer dedifferentiation is an unusual observation among young patients and is poorly understood, although a recent correlation to DICER1 gene mutations has been proposed.Case presentationA 28-year old patient presented with a sub-centimeter cytology-verified primary papillary thyroid carcinoma (PTC) and a synchronous lateral lymph node metastasis. Following surgery, histopathology confirmed a 9 mm oxyphilic PTC and a synchronous metastasis of poorly differentiated thyroid carcinoma (PDTC). Extensive molecular examinations of both lesions revealed wildtype DICER1 sequences, but identified a somatic ETV6-NTRK3 gene fusion and a MET germline variant (c.1076G > A, p.Arg359Gln). MET is an established oncogene known to be overexpressed in thyroid cancer, and this specific alteration was not reported as a single nucleotide polymorphism (SNP), suggestive of a mutation. Both the primary PTC and the metastatic PDTC displayed strong MET immunoreactivity. A validation cohort of 50 PTCs from young patients were analyzed using quantitative real-time PCR, revealing significantly higher MET gene expression in tumors than normal thyroid controls, a finding which was particularly pronounced in BRAF V600E mutated cases. No additional tumors apart from the index case harbored the p.Arg359Gln MET mutation. Transfecting PTC cell lines MDA-T32 and MDA-T41 with a p.Arg359Gln MET plasmid construct revealed no obvious effects on cellular migratory or invasive properties, whereas overexpression of wildtype MET stimulated invasion.ConclusionsThe question of whether the observed MET mutation in any way influenced the dedifferentiation of a primary PTC into a PDTC metastasis remains to be established. Moreover, our data corroborate earlier studies, indicating that MET is aberrantly expressed in PTC and may influence the invasive behavior of these tumors.

Despite the increasing recognition of PD-L1 as predictor of immunotherapeutic response in various malignancies, its role and prognostic significance in thyroid cancer remain underexplored and subject to debate. This study begins to address this gap by comprehensively analyzing PD-L1 expression in papillary thyroid carcinoma (PTC) and investigating its correlation with key clinicopathological variables. We conducted immunohistochemistry (IHC) to assess PD-L1 expression in whole-tissue sections from 121 primary papillary thyroid carcinoma (PTC) cases. We then analyzed the correlations between PD-L1 expression and various clinicopathological variables. PD-L1 expression was detected in 33.1% of papillary thyroid carcinomas (PTCs), predominantly exhibiting weak to moderate intensity. Notably, this study found no significant correlation between PD-L1 expression and various clinicopathological variables. The lack of association with traditional factors such as age, sex, histological subtype, and tumor size suggests the complex and multifaceted nature of PD-L1 regulation in PTC. Multivariate logistic regression analysis identified chronic lymphocytic thyroiditis with oncocytic metaplasia as the sole independent predictor of PD-L1 expression (P = 0.014), underlining the potential influence of the tumor microenvironment on immune checkpoint expression in PTC. Our study underscores the intricate interplay between chronic lymphocytic thyroiditis with oncocytic metaplasia and PD-L1 expression in papillary thyroid carcinoma. The observed link suggests a potential avenue for therapeutic intervention using anti-PD-1/PD-L1 therapies in surgery-refractory PTC. Understanding the dynamics of immune checkpoint regulation in the context of the tumor microenvironment is crucial for devising effective treatment strategies. Future research endeavors should delve deeper into the molecular mechanisms underlying this interaction and explore its implications for patient outcomes. As the field of immunotherapy continues to evolve, our findings contribute valuable insights into the complex immunological landscape of thyroid cancer.