Ultrasound in cervical traumatic neuromas after neck dissection in thyroid carcinoma patients: descriptive analysis and diagnostic accuracy.

Objective: Cervical traumatic neuromas (CTNs) may appear after lateral neck dissection for metastatic thyroid carcinoma. If they are misdiagnosed as metastatic lymph nodes (LNs) in follow-up neck ultrasound (US), unnecessary and uncomfortable fine-needle aspiration biopsy are indicated. The present study aimed to describe US features of CTNs and to assess the US performance in distinguishing CTNs from abnormal LNs. Subjects and methods: Retrospective evaluation of neck US images of 206 consecutive patients who had lateral neck dissection as a part of thyroid cancer treatment to assess CTN´s US features. Diagnostic accuracy study to evaluate US performance in distinguishing CTNs from abnormal LNs was performed. Results: Eight-six lateral neck nodules were selected for analysis: 38 CTNs and 48 abnormal LNs. CTNs with diagnostic cytology were predominantly hypoechogenic (100% vs. 45%; P = 0.008) and had shorter diameters than inconclusive cytology CTNs: short axis (0.39 cm vs. 0.50 cm; P = 0.03) and long axis (1.64 cm vs. 2.35 cm; P = 0.021). The US features with the best accuracy to distinguish CTNs from abnormal LNs were continuity with a nervous structure, hypoechogenic internal lines, short/long axis ratio ≤ 0.42, absent Doppler vascularization, fusiform morphology, and short axis ≤ 0.48 cm. Conclusion: US is a very useful method for assessing CTNs, with good performance in distinguishing CTNs from abnormal LNs.

Ultrasound in cervical traumatic neuromas after neck dissection in thyroid carcinoma patients: descriptive analysis and diagnostic accuracy

ABSTRACT Objective: Cervical traumatic neuromas (CTNs) may appear after lateral neck dissection for metastatic thyroid carcinoma. If they are misdiagnosed as metastatic lymph nodes (LNs) in follow-up neck ultrasound (US), unnecessary and uncomfortable fine-needle aspiration biopsy are indicated. The present study aimed to describe US features of CTNs and to assess the US performance in distinguishing CTNs from abnormal LNs. Subjects and methods: Retrospective evaluation of neck US images of 206 consecutive patients who had lateral neck dissection as a part of thyroid cancer treatment to assess CTN's US features. Diagnostic accuracy study to evaluate US performance in distinguishing CTNs from abnormal LNs was performed. Results: Eight-six lateral neck nodules were selected for analysis: 38 CTNs and 48 abnormal LNs. CTNs with diagnostic cytology were predominantly hypoechogenic (100% vs. 45%; P = 0.008) and had shorter diameters than inconclusive cytology CTNs: short axis (0.39 cm vs. 0.50 cm; P = 0.03) and long axis (1.64 cm vs. 2.35 cm; P = 0.021). The US features with the best accuracy to distinguish CTNs from abnormal LNs were continuity with a nervous structure, hypoechogenic internal lines, short/long axis ratio ≤ 0.42, absent Doppler vascularization, fusiform morphology, and short axis ≤ 0.48 cm. Conclusion: US is a very useful method for assessing CTNs, with good performance in distinguishing CTNs from abnormal LNs.

Thyroid collision tumor containing oncocytic carcinoma, classical and hobnail variants of papillary carcinoma and areas of poorly differentiated carcinoma

SUMMARY Collision tumors are rare and may comprise components with different behavior, treatments, and prognosis. We report an unprecedented case of aggressive thyroid collision tumor containing widely invasive oncocytic carcinoma (OC), classical and hobnail (HPTC) variants of papillary carcinoma, and poorly differentiated carcinoma (PDTC). The patient underwent total thyroidectomy, radioactive iodine therapy, and within months progressed with local recurrence, and pulmonary metastases requiring neck dissection, external radiotherapy and systemic treatment with sorafenib. The rapid progression, dedifferentiated metastatic lesions, and failure to treatments resulted in the patient´s death. The great variety of histological types and the evolution of this case were a challenge for the management of metastatic disease. Widely invasive OC, HPTC and PDTC are considered to have a worse prognosis. HPTC has never been reported as a component of a collision tumor. HPTC and PDTC should call attention to a possible higher-grade transformation.

Thyroid collision tumor containing oncocytic carcinoma, classical and hobnail variants of papillary carcinoma and areas of poorly differentiated carcinoma.

Collision tumors are rare and may comprise components with different behavior, treatments, and prognosis. We report an unprecedented case of aggressive thyroid collision tumor containing widely invasive oncocytic carcinoma (OC), classical and hobnail (HPTC) variants of papillary carcinoma, and poorly differentiated carcinoma (PDTC). The patient underwent total thyroidectomy, radioactive iodine therapy, and within months progressed with local recurrence, and pulmonary metastases requiring neck dissection, external radiotherapy and systemic treatment with sorafenib. The rapid progression, dedifferentiated metastatic lesions, and failure to treatments resulted in the patient's death. The great variety of histological types and the evolution of this case were a challenge for the management of metastatic disease. Widely invasive OC, HPTC and PDTC are considered to have a worse prognosis. HPTC has never been reported as a component of a collision tumor. HPTC and PDTC should call attention to a possible higher-grade transformation.

Molecular profile of Hürthle cell carcinomas: recurrent mutations in the Wnt/ß-catenin pathway.

OBJECTIVE: Genomic alterations in Hürthle cell carcinomas (HCC) include chromosomal losses, mitochondrial DNA mutations, and changes in the expression profile of the PI3K-AKT-mTOR and Wnt/ß-catenin pathways. This study aimed at characterizing the mutational profile of HCC. METHODS: Next-generation sequencing (NGS) of 40 HCC using a 102-gene panel including, among others, the MAPK, PI3K-AKT-mTOR, Wnt/ß-catenin, and Notch pathways. HCC was widely invasive in 57.5%, and lymph node and distant metastases were diagnosed in 5% and 7.5% of cases. During follow-up, 10% of patients presented with persistent/recurrent disease, but there were no cancer-related deaths. RESULTS: Genetic alterations were identified in 47.5% of HCC and comprised 190 single-nucleotide variants and 5 insertions/deletions. The Wnt/ß-catenin pathway was most frequently affected (30%), followed by MAPK (27.5%) and PI3K-AKT-mTOR (25%). FAT1 and APC were the most frequently mutated genes and present in 17.5%. RAS mutations were present in 12.5% but no BRAF mutation was found. There was no association between the mutational profile and clinicopathological features. CONCLUSIONS: This series of HCC presents a wide range of mutations in the Wnt/ß-catenin, MAPK and PI3K-AKT-mTOR pathways. The recurrent involvement of Wnt/ß-catenin pathway, particularly mutations in APC and FAT1, are of particular interest. The data suggest that mutated FAT1 may represent a potential novel driver in HCC tumorigenesis and that the Wnt/ß-catenin pathway plays a critical role in this distinct thyroid malignancy.

Laser Ablation of Benign Thyroid Nodules: A Prospective Pilot Study With a Preliminary Analysis of the Employed Energy.

BACKGROUND AND OBJECTIVES: To assess the effectiveness of ultrasound (US)-guided laser ablation of benign thyroid nodules (TNs) under different amounts of applied energy. STUDY DESIGN/MATERIALS AND METHODS: Thirty-four euthyroid patients with 5-18 ml TNs were enrolled: 21 (laser ablation) and 13 (clinical follow up) patients with a mean age of 56.2 ± 12.0 and 54.7 ± 14.7 years, respectively. The laser ablation protocol used a 1.064 mm wavelength diode laser source; 3.5 W output power; 1,100-1,500 J and 5-8 min/illumination; and one or two fibers/session. Clinical, laboratory, and US data were obtained immediately before treatment and at 6 and 12 months follow-up and were analyzed by Student's t test and Fisher's exact test. Low- and high-energy subgroups were subsequently defined, and the receiver operating characteristic (ROC) curves were calculated. RESULTS: Laser ablation follow-up showed an overall nodule volume reduction of more than 50%; improvement of symptoms and cosmetic complaints (P = 0.001); and stable laboratory data compared with the baseline and control groups. Minor complications were 9.5% ( n = 2). One or two fibers/session resulted in a similar nodule volume reduction among 10-18 ml nodules. Analysis of the applied energy suggested a 398.8 J/ml inferior cutoff (ROC curve: 0.889 sensitivity; 0.545 specificity) for the high-energy subgroup ( n = 14, mean 599.9 ± 136.5 J/ml) to reduce the nodule volume over time (-55.1% vs. -58.4%, P = 0.55). The low-energy subgroup ( n = 7, mean 240.2 ± 74.6 J/ml) did not show a persistent volume reduction ( P < 0.05) from the 6- to 12-month follow-ups (-56.6% vs. -53.7%). CONCLUSIONS: Laser ablation of benign TNs achieved technique efficacy at 12 months posttreatment, with clinical improvement and few minor side effects. A single fiber in a single session with a high deployed energy (>398.8 J/ml) may be associated with improved results, a finding to be confirmed with a larger series. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Diagnostic performance of thyroid ultrasound in Hürthle cell carcinomas

ABSTRACT Objective Hürthle cell carcinomas (HCCs) of the thyroid have been recently reclassified as a separate entity due to their distinct clinical and molecular profiles. Few studies have assessed the ability of preoperative characteristics in differentiating HCCs from Hürthle cell adenomas (HCAs) due to the low prevalence of both lesions. This study aimed to compare the preoperative features of HCCs and HCAs and evaluate the diagnostic performance of ultrasound in distinguishing between both. Subjetcs and methods Retrospective study including 101 patients (52 HCCs and 49 HCAs) who underwent thyroid surgery from 2000 to 2016. Clinical, ultrasonographic, and histological data were reviewed. Diagnostic performance of suspicious sonographic features was analyzed in 51 cases (24 HCCs and 27 HCAs). Results Hürthle cell neoplasms were predominant in females. Subjects ≥ 55 years represented 58% of the cases of HCCs and 53% of those of HCAs. Carcinomas were significantly larger (p < 0.001), and a tumor size ≥ 4 cm significantly increased the risk of malignancy (odds ratio 3.67). Other clinical, cytologic, and sonographic data were similar between HCCs and HCAs. Among the HCCs, the lesions were purely solid in 54.2%, hypoechoic in 37.5%, and had coarse calcifications in 12.5%, microcalcifications in 8.3%, irregular contours in 4.2%, and a taller-than-wide shape in 16.7%. Predominantly/exclusive intranodular vascularization was observed in 52.6%. Overall, 58% of the HCCs were classified as TI-RADS 4 or 5 compared with 48% of the HCAs. TI-RADS 4 or 5 had a specificity of only 51.8% and a positive likelihood ratio of 1.21. Conclusions Apart from the lesion size, no other preoperative feature adequately distinguished HCCs from HCAs. Sonographic characteristics raising suspicion for malignancy, which are mostly present in papillary carcinomas, were infrequent in HCCs. New tools must be developed to improve preoperative diagnosis and deferral of surgery in cases of adenomas.

Diagnostic performance of thyroid ultrasound in Hürthle cell carcinomas.

OBJECTIVE: Hürthle cell carcinomas (HCCs) of the thyroid have been recently reclassified as a separate entity due to their distinct clinical and molecular profiles. Few studies have assessed the ability of preoperative characteristics in differentiating HCCs from Hürthle cell adenomas (HCAs) due to the low prevalence of both lesions. This study aimed to compare the preoperative features of HCCs and HCAs and evaluate the diagnostic performance of ultrasound in distinguishing between both. SUBJETCS AND METHODS: Retrospective study including 101 patients (52 HCCs and 49 HCAs) who underwent thyroid surgery from 2000 to 2016. Clinical, ultrasonographic, and histological data were reviewed. Diagnostic performance of suspicious sonographic features was analyzed in 51 cases (24 HCCs and 27 HCAs). RESULTS: Hürthle cell neoplasms were predominant in females. Subjects ≥ 55 years represented 58% of the cases of HCCs and 53% of those of HCAs. Carcinomas were significantly larger (p < 0.001), and a tumor size ≥ 4 cm significantly increased the risk of malignancy (odds ratio 3.67). Other clinical, cytologic, and sonographic data were similar between HCCs and HCAs. Among the HCCs, the lesions were purely solid in 54.2%, hypoechoic in 37.5%, and had coarse calcifications in 12.5%, microcalcifications in 8.3%, irregular contours in 4.2%, and a taller-than-wide shape in 16.7%. Predominantly/exclusive intranodular vascularization was observed in 52.6%. Overall, 58% of the HCCs were classified as TI-RADS 4 or 5 compared with 48% of the HCAs. TI-RADS 4 or 5 had a specificity of only 51.8% and a positive likelihood ratio of 1.21. CONCLUSIONS: Apart from the lesion size, no other preoperative feature adequately distinguished HCCs from HCAs. Sonographic characteristics raising suspicion for malignancy, which are mostly present in papillary carcinomas, were infrequent in HCCs. New tools must be developed to improve preoperative diagnosis and deferral of surgery in cases of adenomas.

Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma.

BACKGROUND: Nuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2, transcription factor of antioxidative genes. In the presence of reactive oxygen species, Keap1 (Kelch-ECH-associating protein-1) inhibitor complex undergoes conformational changes disrupting Keap1-Nrf2 binding and Nrf2 translocates into nucleus. We evaluated the presence of mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs) and correlated them with clinical presentation. METHODS: Coding regions of NFE2L2 and KEAP1 were sequenced in 131 patients with PTC. Clinical and histopathological features were analyzed. Immunohistochemical analysis of Nrf2 expression was performed in mutated carcinomas. RESULTS: Although no mutations were found in NFE2L2, missense mutations in KEAP1 were observed in 6 patients with PTC (4.6%). Immunohistochemistry showed increased Nrf2 expression in nuclei of all mutated carcinomas, which presented poor prognostic features in histopathology. CONCLUSION: We identified mutations in KEAP1 associated with Nrf2 overexpression in PTC. Mutations favored disruption of inhibitory interaction Nrf2-Keap1 to enable increased antioxidant Nrf2 activity, possibly with prognostic consequences.

25-Hydroxyvitamin D and TSH as Risk Factors or Prognostic Markers in Thyroid Carcinoma.

OBJECTIVE: The increasing incidence of thyroid nodules demands identification of risk factors for malignant disease. Several studies suggested the association of higher TSH levels with cancer, but influence of 25-hydroxyvitamin D (25OHD) is controversial. This study aimed to identify the relationship of thyroid cancer with higher TSH levels and hypovitaminosis D and to evaluate their influence on prognostic characteristics of papillary thyroid carcinomas (PTC). METHODS: We retrospectively evaluated 433 patients submitted to thyroidectomy for thyroid nodules. Patients were categorized according to quartiles of TSH and 25OHD levels. Clinicopathological features were analyzed. RESULTS: Subjects with thyroid carcinomas were more frequently male and younger compared to those with benign disease. Their median TSH levels were higher and adjusted odds-ratio (OR) for cancer in the highest-quartile of TSH (> 2.4 mUI/mL) was 2.36 (1.36-4.09). Although vitamin D deficiency/insufficiency was prevalent in our cohort (84%), no significant differences in 25OHD levels or quartile distribution were observed between benign and malignant cases. Among 187 patients with PTC, analyses of prognostic features revealed increased risk of lymph nodes metastases for subjects with highest-quartile TSH levels (OR = 3.7, p = 0.029). Decreased 25OHD levels were not overtly associated with poor prognosis in PTC. CONCLUSIONS: In this cross-sectional cohort, higher TSH levels increased the risk of cancer in thyroid nodules and influenced its prognosis, particularly favoring lymph nodes metastases. On the other hand, no association was found between 25OHD levels and thyroid carcinoma risk or prognosis, suggesting that serum 25OHD determination may not contribute to risk assessment workup of thyroid nodules.

Thyroid disturbance related to chronic hepatitis C infection: role of CXCL10.

Association between autoimmune thyroid diseases (AITD) and hepatitis C is controversial, but may occur or worsen during alpha-interferon treatment. The mechanism responsible for autoimmune diseases in infected patients has not been fully elucidated. This study aims to evaluate the frequency of AITD in chronic hepatitis C and the association of chemokine (CXC motif) ligand 10 (CXCL10) and AITD. One hundred and three patients with chronic hepatitis C and 96 controls were prospectively selected to clinical, hormonal, thyroid autoimmunity and ultrasound exams, besides thyroxine-binding globulin (TBG) and CXCL10 measurements and hepatic biopsies. The frequency of AITD among infected subjects was similar to controls. TT3 and TT4 distributions were right shifted, as was TBG, which correlated to both of them. Thyroid heterogeneity and hypoechogenicity were associated with AITD. Increased vascularization was more prevalent in chronic hepatitis C.CXCL10 was higher in infected patients (p=0.007) but was not related to thyroid dysfunction. Increase in CXCL10 levels were consistent with hepatic necroinflammatory activity (p=0.011). In summary, no association was found between chronic hepatitis C and AITD. Infected subjects had higher TT3 and TT4 which were correlated to TBG. Increased CXCL10 was not associated to thyroid dysfunction in HCV-infected population.

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin.

OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation, including the analysis of the free T4, TSH, and antithyroid antibody levels, should be mandatory before therapy, and an early re-evaluation within three months of treatment is necessary as an appropriate follow-up.

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin

OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54 percent had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19 percent of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16 percent had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11 percent remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation, including the analysis of the free T4, TSH, and antithyroid antibody levels, should be mandatory before therapy, and an early re-evaluation within three months of treatment is necessary as an appropriate follow-up.