Bup Woo Kim

Clinicopathologic Implications of the BRAFV600E Mutation in Papillary Thyroid Cancer: A Subgroup Analysis of 3130 Cases in a Single Center

BACKGROUNDnThe BRAF mutation has been shown to be associated with aggressive clinicopathologic characteristics of papillary thyroid cancer (PTC). However, several studies that analyzed hundreds of patients have not demonstrated any correlation. The objective of this study was to investigate the relationship of the BRAF mutation with clinicopathologic factors in a large group of homogenous PTC patients.nnnMETHODSnWe collected data of PTC patients who received curative resection of the thyroid gland and who had undergone BRAF mutation tests of their thyroid cancer tissue. Minor variant PTCs and mixed-type thyroid cancers were excluded in this analysis. Clinicopathologic characteristics, including age, sex, BRAF mutation, tumor histology, size, extrathyroidal extension, tumor margin, lymph node metastasis, multifocality, stage, and associated thyroid disease, were collected. The relationship of the BRAF mutation with clinicopathologic factors was analyzed in each homogenous histologic PTC.nnnRESULTSnThere were 3130 PTC patients who met the criteria, and these patients were divided into three major histologic groups: conventional PTC (n = 2947), diffuse sclerosing variant PTC (n = 98), and follicular variant PTC (n = 85). The BRAF mutation was variably detected in 75.3%, 61%, and 40% of patients, respectively. In conventional PTC cases, the BRAF mutation was significantly associated with large tumor size, extrathyroidal extension, and lymph node metastasis. Coexistent chronic lymphocytic thyroiditis was significantly less prevalent in the BRAF mutant group. Age, sex, and tumor margin status were not significantly correlated with the BRAF status. There was no evidence that any clinicopathologic factors were linked with the BRAF mutation status in diffuse sclerosing and follicular variant PTCs.nnnCONCLUSIONSnThe BRAF mutation was differentially detected in each histologic subtype of PTC and was strongly correlated with pathologic factors, most strongly with no coexistent chronic lymphocytic thyroiditis, in conventional PTC. The BRAF mutation is suggested to be a poor prognostic marker in conventional PTC, and the BRAF mutational analysis may lead to better management for individual PTC patients.

Skip lateral neck node metastases in papillary thyroid carcinoma.

BackgroundPapillary thyroid carcinomas (PTCs) are commonly associated with lymph node metastases (LNMs), which are thought to disseminate sequentially, first to the central compartment and later to the lateral compartment. However, a small number of patients have skip metastases to the lateral compartment without central LNMs. This study was performed to evaluate the clinicopathologic characteristics of skip metastases in PTC.MethodsWe reviewed the medical records of 147 patients who underwent total thyroidectomy with central neck dissection plus modified radical neck dissection (RND) for PTC. A single surgeon performed all operations. The patients were classified as either present or absent skip metastases. The clinicopathologic characteristics were statistically analyzed.ResultsSkip metastases were found in 32 patients (21.8%) and occurred commonly with primary tumors of the upper pole, and with tumors ≤1xa0cm in diameter. Skip metastases were less common in patients with multifocal disease. Patients with skip metastases had fewer metastatic lateral nodes that were more frequently found at a single level: mostly at level III (96.9%) and level II (34.4%).ConclusionsAlthough skip metastases occur in only a small number of patients, the lateral compartment should be carefully evaluated for skip metastases, even though primary tumors are either single focus, located in the upper pole, or ≤1xa0cm in diameter.

Recovery from Permanent Hypoparathyroidism After Total Thyroidectomy

BACKGROUNDnPermanent hypoparathyroidism after total thyroidectomy is a rare but potentially serious iatrogenic complication. The aim of this study was to investigate the rate of recovery from postoperative, permanent hypoparathyroidism in patients undergoing thyroidectomy without parathyroid autotransplantation.nnnMETHODSnThis study was a prospective case series with a postoperative follow-up of up to 3 years. We enrolled patients with thyroid cancer who underwent total thyroidectomy with central compartment dissection, with or without lateral neck dissection, and who had postoperative permanent hypoparathyroidism, defined as serum levels of intact parathyroid hormone (PTH) <15u2009pg/mL for at least 1 year. In the postoperative follow-up period, the serum levels of PTH and calcium were measured regularly. Recovery from permanent hypoparathyroidism was defined as return to normal serum levels of PTH (15-65u2009pg/mL) and calcium (8.5-10.1u2009mg/dL) without calcium and/or vitamin D supplementation.nnnRESULTSnIn the 1467 patients who underwent total thyroidectomy, 22 presented with permanent postoperative hypoparathyroidism. In 5 of these 22 patients, the PTH levels increased steadily and returned to normal in 27.6±2.9 months, after which supplementation of calcium and vitamin D could be discontinued.nnnCONCLUSIONSnAlthough recovery from permanent hypoparathyroidism is rare, patients should be monitored for serum PTH levels so that unnecessary treatments such as calcium and vitamin D supplementation can be avoided.

Postoperative biochemical remission of serum calcitonin is the best predictive factor for recurrence-free survival of medullary thyroid cancer: a large-scale retrospective analysis over 30 years.

The increase in thyroid screening in the general population may lead to earlier detection of medullary thyroid carcinoma (MTC).

Recurrence of papillary thyroid carcinoma in a remnant pyramidal lobe.

A 27-year-old woman underwent endoscopic total thyroidectomy because of the papillary thyroid carcinoma. The I whole-body scan following post-operative radioactive iodine treatment showed no significantly increased accumulation of iodine-131. One year after initial operation, lateral node enlargement was detected during routine ultrasonography. Fine-needle aspiration cytology confirmed metastatic papillary thyroid carcinoma. Computed tomography demonstrated multiple lymphadenopathies in the right internal jugular chain and a suspicious enhancing nodular lesion just beneath the hyoid bone (Fig. 1). A right modified radical neck dissection and regional dissection around the remnant pyramidal lobe were performed in a conventional manner. Operative findings showed multiple enlarged lymph nodes on the right internal jugular chain, which were dissected clearly with no complications, and the 1.5-cm nodular lesion in the remnant pyramidal lobe just beneath the hyoid bone was removed clearly. Post-operative histopathological examination revealed three out of 48 metastatic lymph nodes on the right internal jugular chain, and labelled the remnant pyramidal lobe lesion as papillary thyroid carcinoma. The thyroid pyramidal lobe (also called Lalouette’s lobe) represents the inferior part of the thyroglossal duct and arises from the isthmus of the thyroid gland. Although the pyramidal lobe is considered a common thyroid lobe, it is present in only about half of all individuals. If the pyramidal lobe is present, it is generally excised during thyroid surgery for thyroid carcinoma. Papillary thyroid carcinoma has a relatively good prognosis; however, recurrence ranges from 8.0% to 23.0%. The most common recurrence sites following total thyroidectomy are the central compartment lymph nodes and proper thyroid tissue of the thyroid bed. In the present case, the pyramidal lobe was spared in the initial operation and later hosted an unusual recurrence of malignancy. In conclusion, complete surgical resection of the thyroid, including the pyramidal lobe, is mandatory for treatment of papillary thyroid carcinoma.

Clinicopathologic features of solid variant papillary thyroid cancer.

Solid variant papillary thyroid cancer (SVPTC) is a rare type of thyroid malignancy whose clinical characteristics remain poorly defined. Therefore, we evaluated the characteristics of 14 patients with SVPTC treated at our institution.

Potential anti-cancer effect of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), a novel histone deacetylase inhibitor, for the treatment of thyroid cancer

BackgroundThyroid cancer has been indicated to have a higher global proportion of DNA methylation and a decreased level of histone acetylation. Previous studies showed that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. The goal of this research was to study the endoplasmic reticulum (ER) stress-mediated actions of the dominant histone deacetylase (HDAC) inhibitor, N-hydroxy-7-(2-naphthylthio) hepatonomide (HNHA), in thyroid cancer and to explore its effects on apoptotic cell death pathways.MethodsExperiments were achieved to conclude the effects of HNHA in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) cell lines and xenografts, as compared with two other established HDAC inhibitors (SAHA; suberoylanilide hydroxamic acid and TSA; trichostatin A).ResultsApoptosis, which was induced by all HDAC inhibitors, was particularly significant in HNHA-treated cells, where noticeable B-cell lymphoma-2 (Bcl-2) suppression and caspase activation were observed both in vitro and in vivo. HNHA increased Ca2+ release from the ER to the cytoplasm. ER stress-dependent apoptosis was induced by HNHA, suggesting that it induced caspase-dependent apoptotic cell death in PTC and ATC. PTC and ATC xenograft studies demonstrated that the antitumor and pro-apoptotic effects of HNHA were greater than those of the established HDAC inhibitors. These HNHA activities reflected its induction of caspase-dependent and ER stress-dependent apoptosis on thyroid cancer cells.ConclusionsThe present study indicated that HNHA possibly provide a new clinical approach to thyroid cancers, including ATC.

Overcoming the limitations of fine needle aspiration biopsy: detection of lateral neck node metastasis in papillary thyroid carcinoma.

Purpose Ultrasound (US) and US-guided fine needle aspiration biopsies (FNAB) are considered the modalities of choice for assessing lymph nodes suspected of containing metastases, but the sensitivity of FNAB varies and is specific to the operator. We analyzed the risk of FNAB providing false negative results of lateral neck node metastasis, and evaluated diagnostic accuracy of FNAB, in patients with papillary thyroid cancer. Materials and Methods FNAB was performed in 242 patients suspected of having lateral neck node metastasis on preoperative imaging. Thyroglobulin in the fine-needle aspirate washout (FNA wash-out Tg) and computed tomography enhancement (Hounsfield units) were measured. Patients with negative results on FNAB were examined by intraoperative frozen section. The false negative and true negative groups were compared. Results Of the 242 patients, 130 were confirmed as having lateral neck node metastases. In 74 patients, the metastasis was identified by FNAB. False positive results were observed in 2 patients (0.8%) and false negatives in 58 (44.6%). Risk analysis showed that patient age <45 years (p=0.006), tumor size >1 cm (p=0.008) and elevated FNA wash-out Tg (p=0.004) were significantly associated with false negative results on FNAB. The accuracy of FNAB increased significantly when combined with FNA wash-out Tg (p=0.003). Conclusion To reduce the false negative rate of FNAB, patient age (<45 years), tumor size (>1 cm) and FNA wash-out Tg (>34.8 ng/mL) should be considered in preoperative planning. Accuracy may be improved by combining the results of FNAB and FNA wash-out Tg.

Long-term outcomes of ethanol injection therapy for locally recurrent papillary thyroid cancer

The standard treatment regimen for locally recurrent lesions is total thyroidectomy, or complete removal of the recurrent thyroid lesion within the thyroid bed. However, reoperation increases the risk of complications and patients have to undergo general anesthesia. Percutaneous ethanol injection therapy represents a far less invasive procedure without general anesthesia and with lower risk of complications. Thirty-four patients who received PEIT at Yonsei University Medical Center between October 2002 and August 2009 for recurrent cervical nodal metastases of differentiated papillary thyroid cancer were included in this retrospective study. During a minimum follow-up of 60xa0months, treatment outcomes were determined by measuring the lesion size prior to the first injection and 3xa0months after the last injection. A total of 46 recurrent lesions were detected in 34 patients. Five patients underwent surgery and PEIT was administered to the remaining 19 and 22 lesions in the central compartment and lateral neck lymph nodes, respectively. Size increases were observed in seven (17.1%) lesions, whereas no changes in size and decreases were detected in 10 (24.4%) and 24 (58.5%) lesions. Patients with increased lymph nodes were significantly older (65.3xa0±xa014.4 vs. 48.2xa0±xa016.3xa0years; pxa0=xa00.02) and had smaller sizes (9.3xa0±xa01.0 vs. 12.3xa0±xa06.4xa0mm; pxa0=xa00.012). Although reoperation remains the first-line treatment for recurrent thyroid cancer, PEIT may be considered as a treatment option in selected patients with lesions larger than 1xa0cm who are ineligible for surgery or have refused reoperation.

The Clinical Significance of the Right Para-Oesophageal Lymph Nodes in Papillary Thyroid Cancer

Purpose Although guidelines indicate that routine dissection of the central lymph nodes in patients with thyroid carcinoma should include the right para-oesophageal lymph nodes (RPELNs), located between the right recurrent laryngeal nerve and the cervical oesophagus and posterior to the former, RPELN dissection is often omitted due to high risk of injuries to the recurrent laryngeal nerve and the right inferior parathyroid gland. Materials and Methods We retrospectively identified all patients diagnosed with papillary thyroid carcinoma who underwent total thyroidectomy with central lymph node dissection, including the RPELNs, between January 1, 2009 and December 31, 2013 at the Thyroid Cancer Center of Yonsei University College of Medicine, Seoul, Korea. Results Of 5556 patients, 148 were positive for RPELN metastasis; of the latter, 91 had primary tumours greater than 1 cm (p<0.001). Extrathyroidal extension by the primary tumour (81.8%; p<0.001), bilaterality, and multifocality were more common in patients with than without RPELN metastasis; however, there were no significant differences in age and sex between groups. A total of 95.9% of patients with RPELN metastasis had central node (except right para-oesophageal lymph node) metastasis, and the incidence of lateral neck node metastasis was significantly higher in patients with than without RPELN metastasis (63.5% vs. 14.3%, p<0.001). Forty-one patients underwent mediastinal dissection, with 11 patients confirmed as having mediastinal lymph node metastasis with RPELN metastasis on pathological examination. Conclusion RPELN metastasis is significantly associated with lateral neck and mediastinal lymph node metastasis.