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Purpose of Review: The aim of this study was to provide a timely and relevant review of the latest findings and explore appropriate management of aggressive variants of papillary thyroid cancer (AVPTC)., Recent Findings: In general, AVPTCs tend to exhibit more invasive characteristics, a lack of responsiveness to radioiodine, increased occurrences of regional spreading, distant metastases and higher mortality rates. Meanwhile, each variant showcases unique clinical and molecular profiles., Summary: Given the elevated risk of recurrence postsurgery, a more aggressive strategy may be necessary when suspected preoperatively, particularly for those presenting with invasive features. Decision on the extent of surgical treatment and adjuvant therapy is individualized and made by experienced clinicians and multidisciplinary teams based on the clinical presentation, presence of aggressive features and molecular profile. Future studies on development of personalized medicine and molecular target therapy may offer tailored treatment options., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: This study aims to explore the prognostic variables for elderly papillary thyroid microcarcinoma (PTMC) patients as well as create a nomogram that could predict the occurrence of cervical lymph node metastasis (CLNM) on the basis of a large population database with high quality.A total of 5165 PTMC patients from Surveillance, Epidemiology, and End Results database database were enrolled in the study. In the meantime, we retrospectively collected 205 PTMC patients who underwent thyroidectomy in our medical center as an external control to test the accuracy of the model. The independent predictors of survival were identified by multivariate Cox regression analysis. Risk factors were selected as nomogram parameters to develop a model to predict CLNM. The C-index and calibration plots were used to evaluate CLNM model discrimination. The predictive nomogram was further validated in the external validation set.76.8% of the enrolled patients underwent thyroidectomy. Overall survival and cancer-specific survival were significantly better in patients who underwent surgery than in those who did not (P < .001). Sex, tumor size, and extent of tumor were included in a multivariable logistic regression model to predict lymph node metastasis. The nomogram had good discrimination with a C-index of 0.71. The calibration curves showed perfect agreement between nomogram predictions and actual observations.Elderly PTMC patients who received a surgical approach without radiotherapy showed survival advantage than those with other treatment strategies. Moreover, a nomogram model was established to predict the risk of CLNM, which will help clinicians in making treatment decisions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Papillary thyroid carcinoma is one of the most common endocrine malignancies. Telomerase reverse transcriptase rs10069690 and rs2736100 polymorphisms have been studied in thyroid carcinomas with different ethnicity, but the results were inconsistent. Therefore, we evaluated the relationship between rs10069690 and rs2736100 polymorphisms and papillary thyroid carcinoma risk and furtherly investigated the associations of these polymorphisms with stimulated thyroglobulin (sTg) positivity and adverse reactions of I treatment in papillary thyroid carcinoma. Four hundred thirty-six papillary thyroid carcinoma patients and 345 controls of Chinese Han population were included in our study. Rs10069690 and rs2736100 were genotyped using improved multiple ligase detection reactions. Analysis of inheritance model was performed using the unconditional logistic regression. In our study, rs10069690 and rs2736100 were associated with papillary thyroid carcinoma risk, especially in females over 45 years of age (P = 0.002 and P = 0.032, respectively). Rs10069690 was associated with sTg positivity and with an rs10069690-related occurrence risk order of thyroglobulin antibody (Tg-Ab)(+) + Tg(+) > Tg-Ab(+) + sTg(-) > Tg-Ab(-) + sTg(+). Patients with the homozygous TT genotype of rs10069690 had an increased risk of neck discomfort (P = 0.033), while the homozygous CC genotype of rs2736100 had a decreased risk of gastrointestinal toxicity (P = 0.048). Our data demonstrated that rs10069690 and rs2736100 might be bio-indicators related to papillary thyroid carcinoma risk in females over 45 years of age and I treatment-related toxicity. In addition, rs10069690 may be a predictor of bad clinicopathological features and poor prognosis from a serological point of view.

Radioiodine refractory (RAIR) is the major cause of thyroid cancer-related death. In order to avoid needless Radioiodine (RAI) therapy, recognizing the RAIR cases in time is important for the patients to obtain more time for the effective therapy.Evaluate the ultrasound features of cervical metastatic lymph node in patients with RAIR differentiated thyroid cancer (DTC).Seventeen adult patients with histologically confirmed locally advanced or metastatic RAIR-DTC were prospectively enrolled. The ultrasound (US) characteristics of cervical lesions in patients with the RAIR-DTC were compared with cervical lymph node metastasis from 59 non RAIR-DTC cases.Among the 17 patients, cervical lymph node metastasis was found in 15 patients (88.3%). The cervical lesions of RAIR-DTC (mean size, 2.0 cm) were larger than that in non RAIR-DTC group (mean size, 1.30 cm). More multiple lesions and more lesions with visible flow were found in the RAIR Group, while fewer hyperechogenic punctuations were found in RAIR group (P < .05). The distant metastasis rates showed that RAIR-DTC led to a poorer prognosis than those of patients in the non RAIR Group (P < .01).Ultrasound can help distinguish metastasized cervical lymph nodes of RAIR-DTC patients from non RAIR-DTC patients. For RAIR-DTC patients, a long-term US evaluation should be performed.

To estimate the BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma (PTC), and the diagnostic value of BRAFV600E mutation status in thyroid nodules with indeterminate TBSRTC categories.A total of 4875 consecutive samples for thyroid ultrasound-guided fine-needle aspiration cytology (FNAC) and BRAF mutation analysis were collected from patients at Jiangsu Province Hospital on Integration of Chinese and Western Medicine. Among all the cases, 314 underwent thyroidectomy. According to TBSRTC categories, FNAC was performed for a preoperative diagnosis. ROC of the subject was constructed to evaluate the diagnostic value of these 2 methods and their combination.BRAF mutation in FNAC of thyroid nodules occurred in 2796 samples (57.35%). Of 353 nodule samples from 314 patients with thyroid operation, 333 were pathologically diagnosed as PTC. Of these PTC patients, 292 (87.69%) were found to have BRAF mutation in their preoperative FNAC. In 175 cytologically indeterminate thyroid nodules, BRAF mutation identified 88% of PTC. According to ROC data, BRAF mutation testing had an obviously higher sensitivity (87.69%) and specificity (100.00%) than TBSRTC. Combining BRAF mutation testing and TBSRTC achieved the largest AUC (0.954). For 41 PTC with a negative BRAF mutation in preoperative evaluation, the repeated BRAF mutation testing found out 12 samples with BRAF mutation. The true BRAF mutation rate of Chinese PTC patients was 91.29%.Chinese patients with PTC have a higher frequency of BRAF mutation. The BRAF mutation testing affords a high diagnostic value in thyroid nodules with indeterminate cytology.

Purpose of Review: To present the current status of knowledge regarding radiation-induced papillary thyroid cancer (RIPTC), defining its epidemiologic, pathologic, and clinical characteristics, with ensuing possible therapeutic and prognostic consequences., Recent Findings: Cumulative evidence shows that RIPTC resembles sporadic papillary thyroid cancer (PTC) of comparable age, both in terms of clinical-pathological features and prognosis. Therefore, more aggressive treatment does not seem to be required when managing RIPTC as its prognosis is comparable to that of never-irradiated patients., Summary: Radiation exposure in childhood is a well-documented risk factor for development of PTC. Therefore, increased exposure to medical or environmental radiation may be in part responsible, along with increased screening, of the recent burgeoning incidence of PTC. A specific morphological and molecular portrait of RIPTC is unlikely to exist. The more aggressive histologic and clinical features initially reported in radiation-induced cases are consistent with the expectations in nonradiation-related PTC of a comparable age. Aggressive histology, nodal, and distant metastases correlate with early age at onset rather than with radiation exposure. Although relapses are frequent in children, long-term cancer-specific mortality is approximately 1%, lower than that observed for adults and comparable between irradiated and nonirradiated cohorts. RIPTC does not require more aggressive surgery or more adjuvant treatments, as prognosis is as good as that of sporadic PTC when matched for stage and treatment received.

Purpose of Review: To highlight recent advances in our understanding of the nature of micropapillary thyroid carcinoma (mPTC), its evaluation and options of management based on risk., Recent Findings: A dramatic increase of the incidence of papillary thyroid carcinoma has been reported worldwide during recent decades, specifically those smaller than 10 mm (mPTC). Although not taking into consideration other risk factors for aggressiveness when describing tumours by their size, most of these newly diagnosed mPTC are indolent and active surveillance can be considered as valid option for their management., Summary: An increasing number of patients with mPTC will be encountered in clinical practice. Although it is difficult to assess the aggressiveness of a tumour on size criteria, less than a total thyroidectomy and active surveillance can be considered for the majority of patients with mPTC. Further trials should be performed to prove this as a valid option of management in the majority of these patients.

Rationale: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. However, the simultaneous occurrence of PTC and Hodgkin Lymphoma (HL) was rarely reported., Patient Concerns: We present a case of simultaneous BRAF-positive PTC and HL in a 17-year-old female., Diagnosis: She was referred to our clinic with a painless lump in her left neck. A highly suspicious thyroid nodule and multiple enlarged lymph nodes in the neck were found by ultrasonography examination. The suspicious nodule was diagnosed as PTC by fine needle aspiration cytology., Interventions: A total thyroidectomy with bilateral lymph node dissection was performed and the microscopic examination revealed a 2-cm PTC with BRAF mutation and HL (mixed cellularity) in the bilateral lymph nodes. PTC was postoperatively considered as T1bN0M0. Levothyroxine (125 μg/d) was administered to the patient for thyrotropin suppression therapy. Then the patient was referred to the Department of Hematology to receive 4 cycles of ABVD followed by 30 Gy involved-site radiotherapy and radioactive iodine (RAI) therapy for thyroid cancer., Outcomes: After two cycles of ABVD, multiple enlarged lymph nodes showed a significant response to the chemotherapy in the patient., Lessons: Simultaneous HL and BRAF-positive PTC is extremely rare. Biopsy of the suspicious lymph nodes should be performed to confirm malignancy metastasizing from PTC or other lesions. Similarly, in HL patients with suspicious thyroid nodule, ultrasound-guided fine needle aspiration of thyroid nodule should be performed to exclude thyroid malignancy.

Rationale: Malignant struma ovarii is extremely rare in the clinic. The diagnosis and modalities of treatment are still controversial. Here we describe a case of extensive peritoneal implant metastasis originating from malignant struma ovarii discovered 14 years after ovariectomy and chemotherapy., Patient Concerns: A 48-year-old female was admitted to our clinic due to hematochezia with a past history of left malignant struma ovarii. Enhanced computed tomography (CT) examination suggested multiple metastasis nodules in the abdomen and pelvic cavity., Diagnoses: Laparoscopy biopsy results of intraperitoneal nodules showed a metastasis of papillary thyroid carcinoma. While pathological examination after total thyroidectomy showed no definite malignant tumor component in the thyroid tissue. Finally, combined with the patient's past history of malignant struma ovarii, peritoneal implantation metastasis derived from the malignant struma ovarii was diagnosed., Interventions: The patient was treated by total thyroidectomy and iodine 131 (I) therapy. Post-therapy iodine scan and the single-photon emission computed tomography/computed tomography (SPECT/CT) fusion image showed iodine uptake in the distal descending colon, sigmoid colon, rectal lesions, and a larger lesion in the liver., Outcome: After treatment, although the thyroid globulin remained at a high level 3 months after treatment, the patient's hematochezia was relieved., Lessons: Therefore, thyroidectomy followed by adjuvant I treatment should be recommended in patients with malignant struma ovarii as metastatic risk is difficult to predict based on histopathologic examination.