BRAF V600E Mutation In Patients Research Articles

The association between BMI and BRAFV600E mutation may differ by primary tumor size.

Previous reports suggest that a high body mass index (BMI) increases the risk of thyroid carcinoma. However, it remains unclear whether a high BMI is associated with the risk of the BRAFV600E mutation. We aimed to assess whether a high BMI is associated with an increased risk of the BRAFV600E mutation. We screened 6558 PTC patients who had undergone BRAFV600E mutation testing between January 2009 and December 2017. After exclusion, 6438 PTC patients were enrolled. We used logistic regression, and restricted cubic spline plots of the adjusted odds ratios (ORs) were illustrated to model the relationship between BMI and the BRAFV600E mutation. Of the 6438 patients, 5102 (79.2%) had the BRAFV600E mutation, and 4954 (76.9%) were female. The median BMI was 23.8 (21.6-26.2) kg/m2. The primary tumor size was ≤1 cm in 4226 patients (65.6%) and >1 cm in 2212 patients (34.4%). The BRAFV600E mutation was significantly associated with high BMI only in patients with a primary tumor size >1 cm (OR: 1.034; 95% CI: 1.003-1.065; P = 0.029), whereas no clear association was found in patients with a primary tumor size ≤1 cm (OR: 1.007; 95% CI: 0.984-1.030; P = 0.570). Gender was not a significant factor in either group. Our study found that a higher BMI was positively associated with the BRAFV600E mutation in patients with a primary tumor size >1 cm. These results suggest that the association between BMI and the BRAFV600E mutation status differs depending on primary tumor size. Obesity has been suggested as a potential risk factor for thyroid carcinoma. The aim of this study was to assess the association between BMI and the BRAFV600E mutation. In this study, the BRAFV600E mutation was significantly associated with a high BMI only in a primary tumor size >1 cm (OR: 1.034; P = 0.029). No clear association was found in patients with a primary tumor size ≤1 cm (OR: 1.007; P = 0.570). The association between BMI and the BRAFV600E mutation status differs depending on the primary tumor size.

In brief: Dabrafenib (Tafinlar) and trametinib (Mekinist) for glioma.

The oral kinase inhibitors dabrafenib (Tafinlar – GSK) and trametinib (Mekinist – Novartis) have been approved by the FDA for use together for a sixth indication: treatment of low-grade glioma (LGG) with a BRAF V600E mutation in patients ≥1 years old who require systemic therapy.

In brief: A new indication for dabrafenib (Tafinlar) and trametinib (Mekinist) combination therapy.

The oral kinase inhibitors dabrafenib (Tafinlar – GSK) and trametinib (Mekinist – Novartis) have received accelerated approval by the FDA for use together for a fifth indication: treatment of unresectable or metastatic solid tumors with a BRAF V600E mutation in patients ≥6 years old who have progressed following prior treatment and have no satisfactory alternative treatment options.

Preoperative BRAFV600E mutation detection in thyroid carcinoma by immunocytochemistry.

The BRAFV600E (BRAF) mutation is present in 40-50% of papillary thyroid carcinomas (PTC) and has been associated with more aggressive clinicopathological characteristics of PTC. The aim of this study was to evaluate different methods for preoperative identification of the BRAF mutation in PTC using cytological and histological specimens. Prospectively collected preoperative cytological clots from patients with suspected PTC were tested with BRAF immunocytochemistry (ICC) and the Cobas Test (PCR). In addition, histological specimens were tested with BRAF immunohistochemistry (IHC) and the Cobas Test. All nodules were histologically examined. Fifty-three patients were included in the study. Complete mutation testing was available in 32 patients. The main reason for exclusion was insufficient cell content in the cytological specimen. Twenty-seven nodules were histologically diagnosed as PTC, and 41% (n = 11) of PTCs were BRAF ICC positive. All non-PTC nodules were negative by BRAF ICC. In 26 nodules, all four BRAF tests were concordant, while discordant test results were found in six nodules. ICC was in accordance with the consensus BRAF status in five of these nodules, while BRAF status was undetermined in one nodule. BRAF ICC showed high concordance with the Cobas Test and a low rate of false negative stain. These results indicate that BRAF ICC may be a feasible method for preoperative detection of the BRAFV600E mutation in patients with PTC.

Dramatic Therapeutic Response to Dabrafenib Plus Trametinib in BRAF V600E Mutated Papillary Craniopharyngiomas: A Case Report and Literature Review.

BackgroundCraniopharyngioma is a rare intracranial tumor, with a high morbidity rate due to its common refractiveness to conventional treatments. BRAF V600E mutation has recently been identified as the principal oncogenic molecular driver of papillary craniopharyngiomas (PCP), one of the two main variants of craniopharyngioma.Case PresentationA 49-year-old man with recurrent craniopharyngioma, harboring BRAF V600E mutation, has been treated with targeted therapy based on a combination of a BRAF-inhibitor, dabrafenib (150 mg, orally two times daily), and a MEK-inhibitor, trametinib (2 mg, orally two times daily). Before starting treatment, the patient was symptomatic: he lamented confusion, dysphasia, and intense fatigue, that did not allow him to work normally. After just one cycle of treatment, the patient showed an important clinical improvement, reporting a progressive regression of the basal symptoms, hinting at a rapid and dramatic response, which was confirmed at the first radiological assessment. Thus, treatment was continued and at the time of writing, the treatment is still ongoing (total duration of treatment: 14 months) and it is well tolerated, with very good quality of life: the patient has no limitations in daily activities and he has even been able to restart to work.ConclusionThe use of targeted therapies—as a clinical practice or in clinical trials—represents an important therapeutic alternative and a great evolution for patients' prognosis vs. the standard of care, historically represented by unselected chemotherapies. The discovery of the BRAF V600E mutation in patients with PCP is very rare, resulting in a lack of data on the efficacy of the combination of dabrafenib and trametinib.

Oncological evaluation in the perioperative period using cfDNA with BRAF V600E mutation in patients with colorectal cancer

The detection of circulating cell-free DNA (cfDNA) by liquid biopsy is reported to provide prognostic information in colorectal cancer (CRC). Although the frequency of BRAF V600E mutation in CRC is less than 10%, it is associated with poor responses to conventional chemotherapy. We conducted a prospective study to investigate the relationship between the perioperative mutant allele frequency (MAF) of BRAF V600E and tumor recurrence, and to evaluate the possibility of early detection of recurrence. Among 362 patients who underwent radical resection, cfDNA was extracted from the perioperative blood of 11 CRC patients with BRAF V600E mutation and analyzed using the digital polymerase chain reaction (dPCR) system. The median follow-up time was 22 months, and there were four cases of recurrence. Although there was no correlation between recurrence and the perioperative MAF of BRAF V600E, tumor diameter was correlated with the MAF (p = 0.024), and the MAF increased with time in two patients from whom additional samples were obtained prior to recurrence. In this study, we identified a correlation between the pathological tumor diameter and the MAF, but it was difficult to predict recurrence by measuring cfDNA with BRAF V600E mutation in the perioperative period of radical resection of CRC.

Presence of TERT ± BRAF V600E mutation is not a risk factor for the clinical management of patients with papillary thyroid microcarcinoma

BackgroundThe management of papillary thyroid microcarcinomas with TERT ± BRAF V600E mutations remains controversial owing to their potential associations with tumor aggressiveness. This study evaluated the clinical implications of these mutations in management of patients with papillary thyroid microcarcinomas. MethodsBetween June 2019 and October 2020, surgical specimens from 504 consecutive patients with papillary thyroid microcarcinomas were obtained at a tertiary hospital. The mutation statuses of TERT promoter and BRAF V600E were assessed by polymerase chain reaction. The prevalence and relationships of TERT ± BRAF V600E mutations with clinical, radiological, and pathological characteristics were evaluated. ResultsOf 504 patients with papillary thyroid microcarcinomas, TERT ± BRAF V600E mutations were found in 3.2% (16/504). Of these 16 patients, 93.8% (15/16) of papillary thyroid microcarcinomas with TERT promoter mutations also harbored BRAF V600E mutations. Correlation analysis showed that TERT ± BRAF V600E mutations were not associated with aggressive clinical, radiological, or pathological features (P > .05). The presence of lymph node metastasis was not associated with mutation status (P = .834). ConclusionTERT ± BRAF V600E mutations in patients with papillary thyroid microcarcinomas are not associated with any unfavorable clinicopathological features, including lymph node metastasis status.

Fine-needle Aspiration Washout Precipitation Specimens: An Acceptable Supplement to Genetic Mutation Detection of Thyroid Nodules.

Objectives: Thyroid nodules are common in adults, but only some of them are malignant. Ultrasound-guided fine-needle aspiration (FNA) is widely applied as a reliable and minimally invasive technique for evaluating thyroid nodules. However, the scarcity of FNA biopsy specimens poses a challenge to molecular diagnosis. This study aimed to evaluate the feasibility of FNA washout precipitation specimens as an effective supplement to the thyroid genetic test. Methods: A total of 115 patients with thyroid nodules were enrolled in our study. The BRAF V600E mutation status was detected in all FNA washout precipitation specimens and biopsy formalin-fixed paraffin-embedded (FFPE) specimens using an amplification refractory mutation system PCR (ARMS-PCR). All patients underwent cytological diagnoses; 79 patients also underwent surgery for histopathological analysis. Results: All the 115 samples were successfully analyzed using both FNA washout precipitation and biopsy FFPE specimens. The results showed that the BRAF V600E status detected in 96 FNA washout precipitation specimens were consistent with that in FNA biopsy FFPE specimens, including 41 BRAF V600E positive and 55 BRAF V600E negative, achieving a concordance rate of 84.4% (kappa = 0.689). Furthermore, the BRAF V600E mutation status using FNA washout precipitation specimens provided a 100.0% positive predictive value for diagnosing papillary thyroid carcinoma in patients with The Bethesda system for reporting thyroid cytopathology (TBSRTC) V. Besides, the BRAF V600E mutation status was positive in 90.9% (10/11) FNA washout precipitation specimens from patients with capsule invasion, achieving a higher overall sensitivity of 100.0%, compared with 57.1% of FNA washout precipitation specimens from patients without capsule invasion. Conclusion: These results suggested that FNA washout precipitation specimens might be a valuable supplementary sample type for detecting the BRAF V600E mutation in patients with thyroid nodules, especially with thyroid capsule invasion.

DdPCR Analysis Reveals BRAF V600E Mutations Are Infrequent in Isolated Pituitary Langerhans Cell Histiocytosis Patients.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a highly variable clinical presentation affecting people of all ages. Mutations in BRAF V600E are the most identifiable molecular alteration in LCH although its incidence in pediatric patients with isolated pituitary stalk involvement is not well described. Pediatric patients with LCH and isolated pituitary stalk involvement typically present with central diabetes insipidus. Diagnosis requires a transcranial biopsy which often yields scant tissue. We sought to determine the prevalence of BRAF V600E mutations in patients with isolated pituitary stalk LCH using digital droplet polymerase chain reaction because this method requires minimal tumor DNA. We identified 8 patients with isolated pituitary stalk thickening who underwent a biopsy at Children's Hospital Colorado from January 2001 to December 2019, as well as 6 patients with systemic LCH diagnosed by biopsy in the same period as a comparison. Only one out of the 8 patients with isolated thickened pituitary stalk was found to have a detectable BRAF V600E mutation. Five out of the 6 patients with systemic LCH had a detectable BRAF V600E mutation. In our series, BRAF V600E mutations are rare in pediatric patients with LCH and isolated pituitary stalk involvement.

Artificial intelligence to predict the BRAFV600E mutation in patients with thyroid cancer.

PurposeTo investigate whether a computer-aided diagnosis (CAD) program developed using the deep learning convolutional neural network (CNN) on neck US images can predict the BRAFV600E mutation in thyroid cancer.Methods469 thyroid cancers in 469 patients were included in this retrospective study. A CAD program recently developed using the deep CNN provided risks of malignancy (0–100%) as well as binary results (cancer or not). Using the CAD program, we calculated the risk of malignancy based on a US image of each thyroid nodule (CAD value). Univariate and multivariate logistic regression analyses were performed including patient demographics, the American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TIRADS) categories and risks of malignancy calculated through CAD to identify independent predictive factors for the BRAFV600E mutation in thyroid cancer. The predictive power of the CAD value and final multivariable model for the BRAFV600E mutation in thyroid cancer were measured using the area under the receiver operating characteristic (ROC) curves.ResultsIn this study, 380 (81%) patients were positive and 89 (19%) patients were negative for the BRAFV600E mutation. On multivariate analysis, older age (OR = 1.025, p = 0.018), smaller size (OR = 0.963, p = 0.006), and higher CAD value (OR = 1.016, p = 0.004) were significantly associated with the BRAFV600E mutation. The CAD value yielded an AUC of 0.646 (95% CI: 0.576, 0.716) for predicting the BRAFV600E mutation, while the multivariable model yielded an AUC of 0.706 (95% CI: 0.576, 0.716). The multivariable model showed significantly better performance than the CAD value alone (p = 0.004).ConclusionDeep learning-based CAD for thyroid US can help us predict the BRAFV600E mutation in thyroid cancer. More multi-center studies with more cases are needed to further validate our study results.

The Effect of BRAF V600E Mutation on Lymph Node Involvement in Papillary Thyroid Cancer.

Papillary thyroid cancer (PTC) is the most common well-differentiated thyroid cancer. Lymph node (LN) metastasis is frequently seen in PTC. The effect of BRAFV600E mutation on PTC-associated LN metastasis has not been clearly established. Therefore, we aimed to evaluate the effect of the BRAFV600E mutation in patients with PTC on regional LN metastasis. Between January 2013 and 2017, sixty-three PTC patients who underwent central lymph node dissection were included into the study. The patients were divided into two groups according to the pathology results of the LN dissection, and these groups were compared for positive BRAFV600E mutations and other clinicopathological findings. BRAFV600E mutation was found to be more significant in the pLN1 group (p= 0.005). Multivariate analysis revealed that nodule size, microcalcifications, and BRAFV600E mutation were associated with lymph node metastasis independent of other parameters. ROC analysis also evaluated the adequacy of the BRAFV600E mutation in predicting the presence of LN involvement. AUC: 0.738 (95%CI:0.6110.866,p: 0.002). In our study, independent of other parameters, BRAFV600E gene mutation was found to be effective on lymph node involvement.

Molecular Profiling of Follicular Variant of Papillary Thyroid Cancer.

The molecular features of the follicular variant of papillary thyroid cancer are closely related to the clinical behavior of the tumor and the prognosis of the disease. BRAF-V600E mutations in patients with a follicular variant of papillary thyroid cancer have not been identified; however, the majority of patients had T3-4N0M0 stage of the disease. Changes in the expression of transcription and growth factors and AKT/m-TOR signaling pathway components were detected. In addition, hyperexpression of m-TOR and 4EBP1 kinases and CAIX enzyme was shown compared to the classical variant of papillary thyroid cancer, where an increase in the nuclear factor NF-κB p65 and c-RAF kinase expression was observed.

599P - Clinical impact of BRAF V600E mutations in patients (pts) with resectable solitary colorectal liver metastases (CRLM)

BackgroundPatients (pts) who underwent a curative resection for solitary colorectal liver metastasis (CRLM) have a relatively favorable prognosis. Clinical impact of BRAF V600E mutations in those pts remains unclear. MethodsConsecutive pts who had undergone initial hepatectomy for histologically confirmed solitary CRLM were included. Tumor RAS (KRAS/NRAS)/BRAF V600E mutation tests were centrally performed by a PCR method. The association between BRAF V600E mutation and survival outcome in pts with resectable solitary CRLM was retrospectively investigated. ResultsFrom Jan 2005 to Dec 2017, 218 pts were included with a median follow-up of 52 months (m). BRAF mutant (mBRAF) was observed in 5 (2.3%) pts, while mRAS was in 92 (42.2%) pts and RAS/BRAF wild-type (wRAS/BRAF) was in 121 (55.5%) pts. mBRAF was associated with a higher serum CA19-9 level at pre-hepatectomy (p=0.03). Median longest diameter for solitary CRLM were similar among three cohorts (19mm vs. 25mm vs. 27mm, p=0.21). However, all the mBRAF pts experienced early recurrence within 9 m. In the univariate analysis, mBRAF was associated with a worse survival in terms of both recurrence-free survival (RFS) with the hazard ratio (HR) of 8.68 for mBRAF vs. wRAS/BRAF (mBRAF vs. mRAS vs. wRAS/BRAF; median, 4.8 m vs. 17.1 m vs. not reached, p<0.001: 3-year RFS rate, 0% vs 39.6% vs 56.2%, p<0.001) and overall survival (OS) with the HR of 20.8 for mBRAF vs. wRAS/BRAF (mBRAF vs. mRAS vs. wRAS/BRAF; median, 14.4 m vs. not reached vs. not reached, p<0.001: 3-year OS rate, 20.0% vs 78.9% vs 94.9%, p<0.001). In the multivariate analysis, mBRAF was strongly associated with a worse survival and had the highest HR among all the indicators in terms of both RFS (HR: 5.0, 95% CI: 1.8–13.8, p<0.001) and OS (HR: 15.4, 95% CI: 5.2–45.5, p<0.001). ConclusionsAmong resectable solitary CRLM pts, mBRAF was rare (2.3%). However, given that all the mBRAF pts experienced early recurrence and the striking value of HRs in the univariate and multivariate analyses on both RFS and OS, mBRAF itself may become the most relevant indicator beyond known clinicopathological indicators in pts with resectable solitary CRLM. A novel treatment strategy for these patients is warranted. Clinical trial identificationUMIN000034557. Legal entity responsible for the studyThe authors. FundingThe National Cancer Center Research Development Fund, Japan (Research number: 30-A-8, Principal investigator: Shinichiro Takahashi). DisclosureT. Yoshino: Research grant / Funding (self): Novartis Pharma K.K.; Research grant / Funding (self): MSD.K.K.; Research grant / Funding (self): Sumitomo Dainippon Pharma Co., Ltd.; Research grant / Funding (self): Chugai Pharmaceutical Co., Ltd.; Research grant / Funding (self): Sanofi K.K.; Research grant / Funding (self): Daiichi Sankyo Company, Limited; Research grant / Funding (self): PAREXEL International Inc.; Research grant / Funding (self): Ono Pharmaceutical Co., Ltd. H. Taniguchi: Research grant / Funding (self): Takeda; Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): Sysmex; Honoraria (self): Chugai; Honoraria (self): Taiho; Honoraria (self): Eli Lilly. All other authors have declared no conflicts of interest.

Role of ultrasonographic features and quantified BRAFV600E mutation in lymph node metastasis in Chinese patients with papillary thyroid carcinoma

The association between cervical lymph node metastasis (LNM) and ultrasonographic features as well as BRAFV600E mutations in patients with papillary thyroid carcinoma (PTC) remained controversial. This study investigated the association between LNM and ultrasonographic features as well as BRAFV600E mutation in Chinese patients with PTC. A total of 280 patients with PTC in China were included in this study. 108 had cervical lymph node metastasis, while 172 had not. Younger age (<45years) and several ultrasonographic features were significantly associated with cervical LNM (Ps < 0.05). The BRAFV600E mutation was detected in 81.0% of patients with PTC (226/280). The status of BRAFV600E mutation was not associated with cervical LNM. However, Ct values by PCR and intensity of reactions by immunohistochemistry (IHC) for BRAFV600E expression had shown significant difference between group with and without LNM. Furthermore, an increased proportion of LNM was also found with the incremental intensity of IHC for BRAFV600E expression from weak to strong reaction after adjusted potential confounders. Further studies are required to verify this association and explore the intrinsic mechanism.

FDA Approval Summary: Vemurafenib for the Treatment of Patients with Erdheim-Chester Disease with the BRAFV600 Mutation.

On November 6, 2017, the U.S. Food and Drug Administration (FDA) granted regular approval to vemurafenib for the treatment of adult patients with Erdheim-Chester disease (ECD) with BRAFV600 mutation. ECD is a type of histiocytosis, a rare disorder characterized by an abnormal accumulation and behavior of cells of the mononuclear phagocytic system, which includes antigen-processing cells, dendritic cells, monocytes, or macrophages. Recently published data confirm a frequency of 54% of BRAFV600E mutations in patients with ECD.Approval was based on a cohort of 22 patients who received 960 mg of vemurafenib twice daily within the VE Basket Trial (MO28072), a single-arm, multicenter, multiple cohort study. Patients in the ECD cohort had histologically confirmed ECD with BRAFV600 mutations that were refractory to standard therapy. The ECD cohort achieved an overall response rate of 54.5% (95% confidence interval: 32.2-75.6), with a complete response rate of 4.5%. With a median duration of follow-up of 26.6 months, the median duration of response has not been reached. The most frequently reported adverse reactions (>50%) in the ECD cohort were arthralgia, rash maculo-papular, alopecia, fatigue, electrocardiogram QT interval prolonged, and skin papilloma. The median treatment duration for ECD patients in this study was 14.2 months. This article describes the FDA review of the vemurafenib efficacy supplement for patients with ECD with BRAFV600 mutations. IMPLICATIONS FOR PRACTICE: Vemurafenib, an oral monotherapy targeting a mutation in BRAF, is the first U.S. Food and Drug Administration approval for the treatment of Erdheim-Chester disease (ECD). ECD is an extremely rare hematopoietic neoplasm that represents clonal proliferation of myeloid progenitor cells. ECD may involve bone and one or more organ systems, primarily affecting adults in their 5th and 7th decades of life, with a slight male predominance. This approval provides an effective and reasonably safe therapy for patients with a serious and life-threatening condition for which no approved therapy exists.

Association Between BRAFV600E Mutation and the American College of Radiology Thyroid Imaging, Reporting and Data System in Solitary Papillary Thyroid Carcinoma

The purpose of this study was to evaluate the associations between BRAFV600E mutation, the American College of Radiology (ACR) thyroid imaging, reporting and data system (TI-RADS) on ultrasound and clinicopathological characteristics in patients with a solitary papillary thyroid carcinoma (PTC). This retrospective study included 397 patients with a solitary PTC, proved pathologically. BRAFV600E mutation status was detected in postoperative samples by real-time fluorescent polymerase chain reaction. Associations of BRAFV600E mutation with the ACR TI-RADS and clinicopathological characteristics were analyzed. In this study, the incidence of BRAFV600E mutation was 81.4% (323/397) in patients with a solitary PTC. Univariate analyses showed that BRAFV600E mutation was significantly associated with margin, higher ACR TI-RADS point scores, and Hashimoto's thyroiditis. In multivariate analyses, lobulated or irregular margin was independently associated with BRAFV600E mutation in total solitary PTC. Furthermore, both in total solitary PTC and papillary thyroid microcarcinoma, BRAFV600E mutation was associated with ACR TI-RADS point scores, which was positively correlated with the risk of BRAFV600E mutation. There was no significant relationship between BRAFV600E mutation and ACR TI-RADS point scores in PTC >10 mm. In addition, Hashimoto's thyroiditis had a significant negative association with BRAFV600E mutation. A lobulated or irregular margin of the thyroid nodule is independently associated with BRAFV600E mutation in patients with PTC. In addition, higher ACR TI-RADS point scores is an independent risk factor for BRAFV600E mutation, and ACR TI-RADS point scores is positively associated with the risk of BRAFV600E mutation in solitary PTC, especially in papillary thyroid microcarcinoma. Our findings may be helpful for preoperative identification and medical management of PTC patients with BRAFV600E mutation.

Prognostic impact of BRAF V600E mutation in patients with non-metastatic colorectal cancer with microsatellite instability: A systematic review and meta-analysis.

3597Background: Colorectal cancer (CRC) displaying high levels of microsatellite instability (MSI-H) has been associated with improved survival in colorectal cancer. MSI-H CRC is also known to be e...

Prevalence and clinical significance of BRAFV600E mutation in patients with papillary thyroid cancer

Prevalence and clinical significance of BRAFV600E mutation in patients with papillary thyroid cancer

Association between the BRAF V600E mutation and ultrasound features of the thyroid in thyroid papillary carcinoma.

The aim of the present study was to investigate the association between the BRAF V600E mutation and ultrasound features of the thyroid in papillary thyroid carcinoma (PTC). Fresh thyroid carcinoma tissue and paracarcinoma tissue were obtained from 34 patients undergoing surgery for PTC. The BRAF V600E mutation was detected by PCR amplification and direct DNA sequencing. The thyroid ultrasound results were compared between patients with and without the BRAF V600E mutation. Eighteen out of 34 cases were identified with the BRAF V600E mutation (52.9%), while 16 cases did not have the BRAF V600E mutation (47.1%). Additionally, no BRAF V600E mutation was detected in paracarcinoma tissue in the 34 cases. The results of ultrasound imaging suggested that there were no significant differences in tumor size, whether the border was clear, or in tumor calcification (presence or absence) between patients with and without BRAF V600E mutation (P>0.05). The BRAF V600E mutation rate was high in patients with PTC. There was no significant correlation between BRAF V600E mutation and thyroid ultrasound features. Thyroid ultrasound features are therefore unable to predict the presence of the BRAF V600E mutation in patients with PTC.

Clinicopathological features and BRAFV600E mutations in patients with isolated hypothalamic-pituitary Langerhans cell histiocytosis.

BackgroundIsolated hypothalamic-pituitary Langerhans cell histiocytosis (HPLCH) is very rare. We investigated the clinicopathological characteristics, endocrine function changes, BRAFV600E mutations and treatments of isolated HPLCH.MethodsWe identified seven patients with isolated HPLCH by reviewing the clinical and pathological files in our hospital from 2007 to 2015. The clinical characteristics of the seven patients were retrospectively reviewed, especially the endocrine function changes. Immunostaining and mutation profiling of BRAFV600E were performed.ResultsThe seven HPLCH patients included three men and four women, aged 9–47 years. All patients presented with symptoms of central diabetes insipidus (CDI), and four displayed anterior pituitary hypofunction as well. Magnetic resonance imaging showed hypothalamic-pituitary axis involvement in all patients. There was no evidence for the involvement of other organs in all seven patients. Langerhans cell histiocytosis was confirmed by neuroendoscopic procedures, and immunohistochemical staining showed that all cases (7/7) were positive for CD68, CD1a, Langerin, and S-100. The BRAFV600E mutation was detected in three of the six cases (3/6). Six patients had follow-up information; all received desmopressin acetate and high-dose corticosteroid therapy, and two patients received radiotherapy.ConclusionsOur study indicated that all patients with isolated HPLCH had CDI as the earliest symptom, and more than half of the patients had anterior pituitary deficiencies. The BRAFV600E mutation is a common genetic change in HPLCH patients. Treatment of HPLCH patients is difficult, and the progressive loss of endocrine function is irreversible in most cases.