Metachronous intraductal papillary mucinous neoplasms disseminate via the pancreatic duct following resection.

Metachronous development of intraductal papillary mucinous neoplasms in the remnant pancreas following resection is a significant clinical burden. Our aim was to characterize the clinicopathological and molecular features of the patients with metachronous tumor development to identify predictive factors and the possible route(s) of dissemination. Seventy-four patients who underwent resection of intraductal papillary mucinous neoplasms with no invasive compartment or associated carcinoma were retrospectively analyzed. In patients with metachronous tumor development, targeted sequencing of 18 genes associated with pancreatic tumorigenesis and immunohistochemical detection of four proteins (p53, SMAD4, p16, and ß-catenin) were performed on both primary and metachronous tumors. The distributions of microscopic neoplastic lesions were examined at surgical margins and in apparently normal tissue apart from the primary tumor. During the median follow-up period of 52 months, 9 patients (12%) developed metachronous tumors in the remnant pancreas. Primary tumors located in the body/tail of the pancreas (odds ratio, 15; 95% confidence interval, 1.6-131) and of the pancreatobiliary type (odds ratio, 6.1; 95% confidence interval, 1.1-35.7) were identified as significant risk factors for subsequent metachronous tumor development. Eight of the nine patients shared molecular aberrations between their primary and metachronous tumors, suggesting migrations from the primary tumor to the pancreatic duct as the cause of metachronous tumor development. Our data suggest that these post-resection metachronous tumors develop by skip dissemination of the primary tumor, potentially via the pancreatic duct. The development of strategies to better predict and prevent this form of tumor progression is necessary.

Minor components of micropapillary and solid subtypes in lung invasive adenocarcinoma (≤ 3 cm): PET/CT findings and correlations with lymph node metastasis.

OBJECTIVE: To investigate the PET/CT findings in lung invasive adenocarcinoma with minor components of micropapillary or solid contents and its association with lymph node metastasis. MATERIALS AND METHODS: A total of 506 lung invasive adenocarcinoma (≤ 3 cm) patients who underwent a PET/CT examination and resection surgery were included. According to the proportion of solid/micropapillary components, the patients were classified into three groups: solid/micropapillary-negative (SMPN) (n = 258), solid/micropapillary-minor (SMPM; > 5% not predominant) (n = 158) and solid/micropapillary-predominant (SMPP; > 5% most dominant) (n = 90). The patients' PET/CT findings, including SUVmax, MTV, TLG and CT characteristics, and other clinical factors were compared by one-way ANOVA test. Logistic regression analysis was done to identify the most predictive findings for lymph node metastasis. RESULTS: The value of SUVmax, MTV, TLG and tumor size was highest in SMPP group, followed by SMPM and SMPN group (P < 0.001).The areas under the curve for SUVmax, MTV and TLG for node metastasis were 0.822, 0.843 and 0.835, respectively. Univariate analysis found that the SMPP and SMPM group had more lymph node metastasis than the SMPN group (P < 0.001). Furthermore, the lymph node metastasis group had higher CEA, SUVmax, MTV, TLG, tumor size and more pleural invasion (P < 0.001). Logistic regression analysis found that SMPP pathological type, SMPM pathological type, higher CEA and male patients were risk factors for lymph node metastasis (P < 0.01). CONCLUSIONS: Lung invasive adenocarcinoma with micropapillary or solid contents had higher SUVmax, MTV, TLG and tumor size and was associated with lymph node metastasis, even if they were not predominant.

Use of synthetic stomata in abdominal carcinomatosis. Case report and literature review.

BACKGROUND: The successful performance of ostomies for the treatment of different diseases has been described since 1706. We report herein the first case of successful ostomy utilizing a synthetic stoma created in a patient with peritoneal carcinomatosis. CLINICAL CASE: A 40-year-old woman presented with abdominal carcinomatosis due to psammomatous papillotubular adenocarcinoma consistent with primary ovarian carcinoma. The patient had negative estrogen and progesterone receptors and Ki-67 proliferative activity was 83%. She was initially treated with cytoreduction therapy, chemotherapy, and hyperthermic intraperitoneal chemotherapy. Because the patient presented with enteric perforations and the extensive tumor invasion and adhesions in all the intestinal segments made it impossible to create autologous decompression stomas, a synthetic stoma was constructed. CONCLUSIONS: Synthetic stomas can be a good treatment option when autologous stomas can not be created.

INTRODUCCIÓN: Desde el año 1706 se han descrito ostomías realizadas con éxito para el tratamiento de diferentes enfermedades; los autores describen el primer caso de éxito en una ostomía sintética en la carcinomatosis peritoneal. CASO CLÍNICO: Mujer de 40 años de edad con carcinomatosis abdominal por adenocarcinoma papilar tubulopapilar psamomatoso más consistente con cáncer primario de ovario, negativo a receptores de estrógenos y progesterona, con marcador Ki-67 al 83% de actividad. De modo inicial se trató con cirugía de citorreducción, quimioterapia, quimioterapia intraperitoneal hipertérmica y por último realización de estomas sintéticos debido a perforaciones entéricas e imposibilidad de realizar estomas descompresivos autólogos por la invasión tumoral extensa y adherencias de todas las asas intestinales. CONCLUSIONES: Los estomas sintéticos pueden ser una buena opción terapéutica cuando es imposible realizar estomas autólogos.

A rare case of pulmonary lepidic metastasis in patient with branch-type intraductal papillary mucinous carcinoma of the pancreas.

Pulmonary lepidic metastasis from intraductal papillary mucinous carcinoma (IPMC) of the pancreas is extremely rare. The patient was a 50s-year old male who was hospitalized in the department of respiratory in our hospital for the evaluation of ground-glass opacities in both lungs on computed tomography (CT) imaging. Steroid therapy was administered, as interstitial pneumonia was suggested; however, there was no improvement. A transbronchial lung biopsy (TBLB) revealed the possibility of distant lung metastases. Abdominal CT revealed pancreatic cystic lesions; the patient was, therefore, referred to our department for further evaluation. Endoscopic ultrasound revealed large multi-cystic lesion with mural nodule and wall thickness. A subsequent pancreatic juice cytology under endoscopic retrograde cholangiopancreatography revealed adenocarcinoma. As this was consistent with the pathological findings shown on TBLB, IPMC metastasis to the lung was diagnosed. In this case, it was considered that pulmonary lepidic metastasis from IPMC by CT imaging and pathological findings. Although the cases of pulmonary lepidic metastasis from gastrointestinal cancer are rare, we should consider these pathological conditions when pneumonia-like infiltration observed on imaging studies does not respond to treatment.

Micropapillary Cervical Adenocarcinoma: A Clinicopathologic Study of 44 Cases.

Micropapillary adenocarcinoma has been reported as an aggressive variant of adenocarcinoma in several organs, where it is associated with poor clinical outcome. This study reports the clinicopathologic features and outcomes of cervical adenocarcinomas with a micropapillary component (micropapillary cervical adenocarcinomas); this represents the largest reported study of these neoplasms. The study comprised 44 cervical adenocarcinomas of usual (human papillomavirus-related)-type (84%), mucinous, not otherwise specified (4.5%), gastric-type (4.5%), endometrioid (4.5%), and adenosquamous carcinoma (2%). The micropapillary component comprised >50% of the neoplasm in 34 cases (77%) (group 1), and 10% to 50% in 10 cases (23%) (group 2). Lymph node metastasis was present in 41 of 44 (93%) cases and typically the nodal tumor retained a prominent micropapillary morphology. Follow-up ranged from 7 to 123 months (mean, 65.9 mo). Seventeen of 44 (38.6%) patients had no evidence of disease on follow-up, 6/44 (13.6%) were alive with disease, and 21/44 (47.7%) died of disease. There were no survival differences between group 1 and group 2. On univariate analysis, lymph node metastasis (P=0.0015), lymphovascular space invasion (P=0.002), parametrial involvement (P=0.03), and depth of stromal invasion (P=0.045) were related to tumor recurrence. On multivariate analysis, lymph node metastasis (P=0.001), and extent of lymphovascular space invasion (P=0.027) were significant independent predictors of tumor recurrence. Our study shows that a micropapillary component in cervical adenocarcinoma may be associated with aggressive behavior and that a micropapillary architecture may occur within a variety of types of cervical adenocarcinoma.

[Multiple lung carcinoma: Primary or intrapulmonary metastasis?] / Adénocarcinomes pulmonaires multiples : primitifs ou métastases ?

Multiple lung carcinomas are 5 to 11,5% of lung carcinomas. The distinction between primary lung carcinomas from carcinomas with intrapulmonary metastasis is essential for optimal patient management. The histopathological analysis is very useful but it has to be completed by genotypic assessment using molecular biology (NGS). Molecular biology can also identify genetic alterations with therapeutic implications. We present the case of a patient with a history of surgery for multiple lung carcinomas diagnosed from 2013 to 2017.

Racial disparities of differentiated thyroid carcinoma: clinical behavior, treatments, and long-term outcomes.

BACKGROUND: The incidence of thyroid cancer in black Americans is significantly lower than that in white Americans, and the impact of race on the prognosis of thyroid cancer remains controversial. The purpose of this study was to determine the risk factors for survival in black and white patients and to compare the survival of differentiated thyroid carcinoma subtypes between these two races. We further investigated the association of lymph node and distant metastases with races. METHODS: This is a retrospective analysis using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. A total of 70,346 cases were included in our study. Patients' demographics and cancer- and treatment-related characteristics were compared between the black and white Americans using chi-square and Fisher's exact tests. For multivariate analysis, Cox proportional hazards regression were used to assess the association between potential risk factors and the survival in black and white patients. RESULT: Black Americans had a worse overall survival than white Americans (HR = 1.127, P = 0.002). While disease-specific survival (DSS) was comparable, the risk factors for DSS were different between white and black Americans. Black Americans had less lymph node metastasis of classical variant papillary thyroid carcinoma (CPTC, OR = 0.476, P < 0.001) and follicular variant papillary thyroid carcinoma (FVPTC, OR = 0.522, P < 0.001), but not follicular thyroid carcinoma (FTC). However, black Americans with FVPTC, but not CPTC or FTC, had a higher potential of distant metastasis (OR = 1.715, P = 0.026). Furthermore, only white patients with tumor > 2 cm and lymph node metastasis benefited from radioactive iodine. CONCLUSIONS: The risk factors for DSS were significantly different in white and black patients. The impact of race should be considered in treatment strategy for thyroid cancer.

Prognostic significance and adjuvant chemotherapy survival benefits of a solid or micropapillary pattern in patients with resected stage IB lung adenocarcinoma.

OBJECTIVE: To evaluate the prognostic significance and beneficiaries of adjuvant chemotherapy (ACT) in various histological patterns of stage IB lung adenocarcinoma according to the 8th tumor-node-metastasis (TNM) classification. METHODS: A total of 1131 patients with pathological stage IB lung adenocarcinoma according to the 8th TNM classification who underwent lobectomy or segmentectomy were enrolled in this study. Based on the proportion of solid/micropapillary components, the patients were classified into 3 groups: solid/micropapillary-negative (SMPN) (n = 719; median survival, 49.7 months; interquartile range [IQR]. 35.1-67.0 months), solid/micropapillary-minor (SMPM; >5% but not predominant) (n = 272; median survival, 38.8 months; IQR, 26.6-51.5 months) and solid/micropapillary-predominant (SMPP; >5% and the most dominant) (n = 140; median survival, 39.6 months; IQR, 26.8-52.5 months). The predictors of disease-specific survival and recurrence-free survival were investigated. To reduce selection bias, propensity score-matching analysis was implemented before survival data were compared. RESULTS: Our data show significant differences in survival rates based on the proportion of solid/micropapillary patterns. The SMPM group had significantly higher cumulative incidences of lung cancer-specific death (P = .000) and recurrence (P = .000) compared with the SMPN group, so did the SMPP group when compared with SMPM patients (P = .000 for both). Multivariate analysis showed that the SMPM and SMPP patterns were poor prognostic factors for disease-specific survival (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.12-3.09 and HR, 4.56; 95% CI, 2.69-7.71, respectively) and recurrence-free survival (HR, 1.64; 95% CI, 1.20-2.24 and HR, 2.43; 95% CI, 1.64-3.60, respectively), as were older age, male sex, smoking history, larger tumor size, necrosis, and abnormal pulmonary function. Survival analysis stratified by histological pattern showed that patients with the SMPP pattern who received ACT had obviously lower cumulative incidences of lung cancer-specific death (HR, 0.46; 95% CI, 0.22-0.93; P = .031) and recurrence (HR, 0.48; 95% CI, 0.26-0.88; P = .017). CONCLUSIONS: Solid/micropapillary patterns were associated with poor prognosis, even if they were not predominant. ACT contributed to survival benefits in the SMPP subgroup of patients with stage IB lung adenocarcinoma.

Aggressive Digital Papillary Adenocarcinoma With Multiple Organ Metastases: A Case Report and Review of the Literature.

Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland neoplasm with a high recurrence rate and metastatic potential. In this study, the authors describe a case that originally appeared to benign spiradenoma, but took an ominous course eventually resulting in the diagnosis of ADPA. A 73-year-old woman developed a gradually growing nodule on the second toe of her left foot, which she had first noticed 4 years previously. An excisional biopsy was performed followed by histological examination. The authors initially considered the tumor to be a benign spiradenoma and did not perform reexcision. However, she experienced local recurrence 24 months later, and multiple pulmonary metastasis 31 months later. On histological examination, both the primary and locally recurrent tumors were found to be composed of discrete and well-circumscribed solid nodules, lacking cystic space. All tumors (the primary tumor, locally recurrent tumor, and lung metastases) presented with a pattern of fused back-to-back tubular structures and myoepithelial differentiation confirmed by immunohistochemical examination. On the basis of these findings, the authors finally diagnosed ADPA with multiple pulmonary metastases. The patient underwent chemotherapy, but died of disease 49 months later. This case highlights the importance of high clinical suspicion of ADPA when digital lesions present.

[About 2 cases of ectopic sebaceous glands in esophagus: Endoscopic and histological correlations from biopsies and resected specimens]. / À propos de 2 cas de glandes sébacées ectopiques œsophagiennes : corrélations endoscopiques, et anatomopathologiques sur biopsies et pièces opératoires.

Sebaceous glands are cutaneous annexes located in the dermis. Focal spots of ectopy of these glands are frequently identified in ectodermal tissues: they represent Fordyce's disease. However, only a few cases of ectopic sebaceous glands have been mentioned in non-ectodermic tissue. Fordyce spots of esophageal location are unusual, and most of them have been diagnosed from biopsy specimens. We report two cases of ectopic sebaceous glands in esophagus, the first diagnosed from a resected specimen, the second from biopsies. A literature review is carried out.

Pretreatment Dynamic Contrast-Enhanced MRI Improves Prediction of Early Distant Metastases in Patients With Nasopharyngeal Carcinoma.

The identification of early distant metastases (DM) in patients with newly diagnosed, previously untreated nasopharyngeal carcinoma (NPC) plays an important role in selecting the most appropriate treatment approach. Here, we sought to investigate the predictive value of distinct MRI parameters for the detection of early DM.Between November 2010 and June 2011, a total of 51 newly diagnosed NPC patients were included. All of the study participants were followed until December 2014 at a single institution after completion of therapy. DM was defined as early when they were detected on pretreatment FDG-PET scans or within 6 months after initial diagnosis. The following parameters were tested for their ability to predict early DM: pretreatment FDG-PET standardized uptake value (SUV), MRI-derived AJCC tumor staging, tumor volume, and dynamic contrast-enhanced (DCE) values. The DCE-derived ve was defined as the volume fraction of the extravascular, extracellular space.Compared with patients without early DM, patients with early DM had higher SUV, tumor volume, DCE mean (median) ve, ve skewness, ve kurtosis, and the largest mean ve selected among sequential slices (P < 0.05). No differences were identified when early DM were defined only according to the results of pretreatment FDG-PET. Among different quantitative DCE parameters, the mean ve had the highest area under curve (AUC, 0.765). However, the AUCs of SUV, tumor volume, mean ve, ve skewness, ve kurtosis, or the largest mean ve selected among the sequential slices did not differ significantly from one another (P = 0.82).Taken together, our results suggest that DCE-derived ve may be a useful parameter in combination with SUV and tumor volume for predicting early DM. Dynamic contrast-enhanced MRI may be complementary to FDG-PET for selecting the most appropriate treatment approach in NPC patients.

Verification of WFA-Sialylated MUC1 as a Sensitive Biliary Biomarker for Human Biliary Tract Cancer.

BACKGROUND: The diagnostic accuracy of biliary cytology is limited. A novel sandwich enzyme-linked immunosorbent assay that combined Wisteria floribunda agglutinin (WFA) and anti-sialylated mucin 1 (MUC1) monoclonal antibody to target bile samples was recently developed. This study was designed to verify the diagnostic accuracy of WFA-sialylated MUC1 as a sensitive biliary biomarker for human biliary tract cancer. METHODS: Bile samples from 27 patients with benign disease and 174 patients with biliary tract cancer were analyzed. A receiver-operated characteristic curve analysis for biliary WFA-sialylated MUC1 and serum CA19-9 levels was performed to determine the cutoff value for the prediction of the presence of biliary tract cancer. RESULTS: Biliary WFA-sialylated MUC1 levels were significantly higher in the biliary tract cancer group compared with the benign group (P < 0.001). The cutoff value of WFA-sialylated MUC1 for discriminating biliary tract cancer was 10.5. The sensitivity of WFA-sialylated MUC1 in discriminating biliary tract cancer was much higher (82.2 %) than that of cytology (23.6 %) when this cutoff value was used. The cutoff value of serum CA19-9 for discriminating biliary tract cancer was 38 IU/L in the same cohort. All patients with biliary WFA-sialylated MUC1 and serum CA19-9 above the cutoff values had biliary tract cancer, and no patient with benign disease was categorized in this group. CONCLUSIONS: Biliary WFA-sialylated MUC1 is a useful biomarker for the differentiation of biliary tract cancer. The sensitivity of WFA-sialylated MUC1 was clearly higher than that of biliary cytology. Further data collection is necessary to validate the clinical usefulness of this biomarker.

Negative prognostic influence of micropapillary pattern in stage IA lung adenocarcinoma.

OBJECTIVES: There is uncertainty as to which factors determine the aggressiveness of lung adenocarcinoma with a micropapillary pattern (MPP). The present study aimed to clarify the influence of a MPP on the malignant aggressiveness of clinical stage IA lung adenocarcinoma. METHODS: We retrospectively examined 347 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection. We defined MPP-positive as accounting for ≥5% of the entire tumour. RESULTS: Forty-eight (14%) and 299 (86%) patients were MPP-positive and negative, respectively. Lymphatic (P = 0.003) and vessel (P = 0.029) invasion as well as lymph node metastasis (P = 0.002) were more frequent in the MPP-positive than negative group. Five-year disease-free survival (DFS) rates were significantly lower in the MPP-positive than negative group (69.7 vs 89.3%, P < 0.001). Multivariate analysis for DFS showed that MPP (P = 0.048), lymphatic invasion (P = 0.003) and vessel invasion (P = 0.002) were independent poor prognostic factors. In addition, higher proportions (<5%, 5-30% and ≥30%) of MPP were associated with a poorer prognosis (89.3, 76.0, and 48.1%, respectively; P < 0.001). The prognosis of patients with MPP-positive tumours and negative tumours harbouring lepidic and solid predominant growth patents did not differ (100 vs 96.8%, P = 0.564; 66.7 vs 62.5%, P = 0.791, respectively). On the other hand, the prognosis tended to be poorer for patients with papillary predominant MPP-positive tumours than for those with negative tumours (62.5 vs 82.5%, P = 0.075). CONCLUSIONS: MPP has an effect on tumour malignancy and patients with tumours harbouring a higher ratio of MPP or papillary predominant subtypes have worse survival.

The Prognostic Role of SOCS3 and A20 in Human Cholangiocarcinoma.

As an antagonist of the JAK/STAT pathway, suppressor of cytokine signaling 3 (SOCS3) plays an integral role in shaping the inflammatory environment, tumorigenesis and disease progression in cholangiocarcinoma (CCA); however, its prognostic significance remains unclear. Although tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) can decrease SOCS3 expression and is involved in the regulation of tumorigenesis in certain malignancies, its role in CCA remains unknown. In this study, we investigated the expression of SOCS3 and A20 in human CCA tissues to assess the prognostic significance of these proteins. The expression of SOCS3 and A20 was initially detected by western blot in 22 cases of freshly frozen CCA tumors with corresponding peritumoral tissues and 22 control normal bile duct tissues. Then, these proteins were investigated in 86 CCA patients by immunohistochemistry (IHC) and were evaluated for their association with clinicopathological parameters in human CCA. The results indicated that SOCS3 expression was significantly lower in CCA tumor tissues than in corresponding peritumoral biliary tissues and normal bile duct tissues. Conversely, A20 was overexpressed in CCA tissues. Thus, an inverse correlation between the expression of SOCS3 and A20 was discovered. Furthermore, patients with low SOCS3 expression or high A20 expression showed a dramatically lower overall survival rate. These proteins were both associated with CCA lymph node metastasis, postoperative recurrence and overall survival rate. However, only A20 showed a significant association with the tumor node metastasis (TNM) stage, while SOCS3 showed a significant association with tumor differentiation. Multivariate Cox analysis revealed that SOCS3 and A20 were independent prognostic indicators for overall survival in CCA. Thus, our study demonstrated that SOCS3 and A20 represent novel prognostic factors for human CCA.

Interleukin 27 -964A > G genetic polymorphism and serum IL-27p28 levels in Chinese patients with papillary thyroid cancer.

The aim of this study was to investigate the association between a potentially functional polymorphism (rs153109, -964A > G) in the promoter region of interleukin-27 (IL-27) gene and the risk of papillary thyroid cancer (PTC) in a Chinese population. Genotype of IL-27 -964A > G polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum IL-27p28 levels were determined using enzyme-linked immunosorbent assay (ELISA). No significant difference was noticed in IL-27 -964A > G polymorphism between PTC patients and healthy controls in the overall analysis. However, analysis of clinical features showed that PTC patients carrying the GG genotype or G allele had significantly decreased risks for developing lymph node metastasis compared with those carrying the AA genotype or A allele (GG vs. AA: OR = 0.38, 95 % CI, 0.20-0.72; G vs. A: OR = 0.63, 95 % CI, 0.44-0.86). Furthermore, ELISA results demonstrated that serum IL-27p28 levels were significantly decreased in PTC patients compared with those in controls (P < 0.05). Serum IL-27p28 levels in healthy controls with the GG genotype were significantly high compared with those carrying AA genotype or the AG genotype (P < 0.05). In conclusion, our results suggest that IL-27 -964A > G polymorphism may be associated with the decreased risk for lymph node metastasis of PTC.

Is endoscopic submucosal dissection safe for papillary adenocarcinoma of the stomach?

AIM: To identify the clinicopathological predictors of lymph node (LN) metastasis and evaluate the outcomes of endoscopic submucosal dissection (ESD) in papillary adenocarcinoma-type early gastric cancers (EGCs). METHODS: From January 2005 to May 2013, 49 patients who underwent surgical operation and 24 patients who underwent ESD for papillary adenocarcinoma-type EGC were enrolled to identify clinicopathological characteristics and predictive factors of LN metastasis and to evaluate the outcomes of ESD for papillary adenocarcinoma-type EGC. RESULTS: Most papillary adenocarcinoma-type EGCs were located in the lower third of the stomach and had an elevated macroscopic shape. The overall prevalence of LN metastasis was 18.3% (9/49). The presence of lymphovascular invasion was found to be a predictor of LN metastasis (P = 0.016). According to current indication criteria of ESD, 6 and 11 of the 49 patients had absolute and expanded indications for ESD, respectively. Two patients (11.8%) with expanded indication for ESD had LN metastasis. Of the 24 patients who underwent ESD, 13 (54%) achieved out-of-ESD indication, with 9 of those 13 patients undergoing surgical operation due to non-curative resection. CONCLUSION: The use of ESD should be carefully considered for papillary adenocarcinoma-type EGC with suspected ESD indication after pre-treatment work-up because of the higher frequency of LN metastasis and additional surgeries.

Detection of plasma BRAF(V600E) mutation is associated with lung metastasis in papillary thyroid carcinomas.

PURPOSE: The BRAF(V600E) mutation represents a novel indicator of the progression and aggressiveness of papillary thyroid carcinoma (PTC). The purpose of this study was to determine the clinical significance of free circulating mutant BRAF(V600E) in predicting the advanced disease of PTC. MATERIALS AND METHODS: Seventy seven matched tumor and plasma samples obtained from patients with both benign and PTC were analyzed for BRAF(V600E) mutation using a peptide nucleic acid (PNA) clamp real-time polymerase chain reaction (PCR). RESULTS: The BRAF(V600E) mutation was absent in tumor DNA samples obtained from patients with benign follicular adenomas or adenomatous goiter. In contrast, 49 of 72 (68.1%) PTC tumors were positive for the BRAF(V600E) mutation. Among them, 3 (6.1%) patients with PTC were positive for BRAF(V600E) mutation in plasma and tumor. However, all 3 patients (100%) had lateral lymph node and lung metastasis. CONCLUSION: These findings suggest that the BRAF(V600E) mutation can be detected using a PNA clamp real-time PCR in the blood of PTC patients with lung metastasis. Future studies are warranted to determine clinical significance of serum BRAF(V600E) mutation in large prospective studies.