Intra thyroid thymic carcinoma: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Intrathyroid thymic carcinoma (ITC) is a malignant epithelial tumor with thymic differentiation within the thyroid gland. Its frequency is up to 0.15 % of all malignant thyroid tumors. It is frequently a low-grade tumor. The clinical status is often misleading to other more advanced tumors like cervical lymph node metastasis of nonkeratinizing squamous cell carcinoma, undifferentiated variant, dedifferentiated carcinoma, and medullary carcinoma of the thyroid. CASE PREPARATION: The patient came to us with the diagnosis of cervical lymph node metastasis of undifferentiated carcinoma. This patient was first diagnosed with cervical lymph node metastasis in the previous hospital. After having an ITC diagnosis, the patient was operated on the rennet of thyroid glands and had a low dose of radio-chemotherapy for recurrent prevention purposes. It is the first case of such a disease diagnosed at our hospital and also the first case reported in Vietnam. CLINICAL DISCUSSION: ITC is rare and appears similar to all thymic carcinoma variants. The most popular type is squamous carcinoma. Immunohistochemical stains are typical for thymic origin tumors with CD5, CD117 positive. ITC is often negative for monoclonal PAX8 but positive in this case (MRQ-50 clone, Sigma-Aldrich). This finding is an exciting one that should considered. CONCLUSION: Reporting the case increases the awareness of the disease, especially among Vietnam Doctors and patients.

Discovery and technical validation of high-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries.

BACKGROUND: Cervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy. RESULTS: Marker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12-100.00], and specificity of 91% [95% CI 62.26-99.53] to 96% [95% CI 79.01-99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00-1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77-70.84] to 89% [95% CI 67.20-98.03], specificity of 93% [95% CI 84.07-97.38] to 96% [95% CI 79.01-99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68-0.89] to 0.99 [95% CI 0.97-1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45-92.69], specificity 95% [95% CI 88.64-98.18], and ROC AUC = 0.925 [95% CI 0.878-0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11-80.44), specificity of 94% (95% CI 88.30-97.40), and ROC AUC = 0.884 (95% CI 0.822-0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers. CONCLUSIONS: This 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.

Prolonged response to first-generation tyrosine kinase inhibitor in a metastatic non-small cell lung cancer harbouring complex G719X and S768I mutations: A case report from Vietnam and literature review.

A complex of G719X and S768I mutations is infrequently observed, constituting less than 0.3% of all EGFR-positive non-small cell lung cancer (NSCLC), and the response to first-line TKIs is inconsistent in the literature. In this study, we report a patient with metastatic non-small cell lung cancer carrying rare EGFR compound mutations of G719X and S768I who benefited from first-line treatment with gefitinib in Vietnam. This patient had a prolonged response lasting over 44 months with first-generation TKI. He continued to take gefitinib without experiencing serious adverse events. NSCLC with a rare complex of G719X and S768I mutation revealed a good response to gefitinib.

Metachronous papillary thyroid carcinoma and hereditary breast carcinoma with BRCA1 mutation in a Vietnamese woman: A case report.

INTRODUCTION AND IMPORTANCE: Papillary thyroid carcinoma is the most common type of malignancy in endocrine tumor. Women with breast cancer have an increased risk of developing thyroid cancer. Especially, patients with BRCA1 germline variants, which belong to the DNA DSB repair system, there may be a genetic susceptibility to thyroid cancer. CASE PRESENTATION: This study investigated a 47-year-old Vietnamese female patient with BRCA1 mutation, namely NM_007294.3 (BRCA1): c.4998insA (p. Tyr1666Terfs), who developed PTC after one year of breast cancer treatment. CLINICAL DISCUSSION: Factors that are thought to increase the risk of thyroid cancer after breast cancer treatment include treatment methods, hormonal factors, genetic susceptibility, and others. A hypothesis is breast cancer with BRCA1 mutation increases the risk of thyroid cancer. CONCLUSION: Understanding the relationship between breast and thyroid cancer helps clinicians for well management of both diseases and also contributes to the development of new preventive strategies, diagnostics and therapeutics as so as a new research direction.

Clinical and paraclinical features, outcome, and prognosis of ovarian granulosa cell tumor: A retrospective study of 28 Vietnamese women.

Background: Granulosa cell tumor of the ovary is a rare disease and presents with two clinically and molecularly distinct subtypes: the juvenile and the adult type. GCT is considered as a malignant tumor with an indolent course and a tendency toward late recurrence. Purpose: To assess the clinical and paraclinical features, treatment findings, survival outcomes, and explored the prognostic factors in the granulosa cell tumor. Methods: The current study was conducted on 28 GCT patients who had surgical operations and adjuvant chemotherapy (stage IC-IV) by applying a retrospective cohort analysis. The clinical and paraclinical characteristics were recorded. Recurrent status was evaluated for analysis with clinical and paraclinical features and survival. All GCT patients' survival were analyzed by using Kaplan-Meier and Log-Rank models. Results: 17.9% of patients experienced a relapse and two patients died due to disease. The mean time from initial diagnose to recurrence was 40.21 months. The 5-year OS and DFS of stage I-II were 100% and 80.8%, and of stage III were 50% and 25%, respectively. In survival analyses, using the log-rank test, age ≥50 years, irregular menstruation, stage I-II, and absence of residual lesion were all significant predictors for the improved DFS. Stage I-II and absence of residual lesion were associated significantly with better OS. Mean of age, FIGO stage, and residual lesion during surgery had significant differences to recurrent rate (p < <0.05). The multivariate model revealed that these factors didn't remain as an independent prognostic variable. Conclusion: FIGO stage and residual lesion during surgery had significant differences in survival and recurrent rate.

Liquid biopsy uncovers distinct patterns of DNA methylation and copy number changes in NSCLC patients with different EGFR-TKI resistant mutations.

Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops after treatment. Although genetic and epigenetic alterations have each been shown to drive resistance to TKI in cell line models, clinical evidence for their contribution in the acquisition of resistance remains limited. Here, we employed liquid biopsy for simultaneous analysis of genetic and epigenetic changes in 122 Vietnamese NSCLC patients undergoing TKI therapy and displaying acquired resistance. We detected multiple profiles of resistance mutations in 51 patients (41.8%). Of those, genetic alterations in EGFR, particularly EGFR amplification (n = 6), showed pronounced genome instability and genome-wide hypomethylation. Interestingly, the level of hypomethylation was associated with the duration of response to TKI treatment. We also detected hypermethylation in regulatory regions of Homeobox genes which are known to be involved in tumor differentiation. In contrast, such changes were not observed in cases with MET (n = 4) and HER2 (n = 4) amplification. Thus, our study showed that liquid biopsy could provide important insights into the heterogeneity of TKI resistance mechanisms in NSCLC patients, providing essential information for prediction of resistance and selection of subsequent treatment.

Combined p53 and Bcl2 Immunophenotypes in Prognosis of Vietnamese Invasive Breast Carcinoma: A Single Institutional Retrospective Analysis.

BACKGROUND: Aberrant of p53 and Bcl2 genes cause changes in the quantity and quality of their proteins and contribute to the pathogenesis of some cancer types including breast cancer. Expression of p53 and Bcl2 were associated to adverse clinical outcomes in breast cancer. PURPOSE: To predict the survival outcomes of invasive breast cancer in Vietnam, using immunohistochemical expression of p53, Bcl2 proteins. METHODS: The current study was conducted on 526 breast cancer patients who had surgical operations, but had not received neo-adjuvant chemotherapy, from 2011 to 2014. The clinicopathological characteristics were recorded. Immunohistochemical staining was performed on p53, Bcl2 markers. Expression of p53 and Bcl2 were paired into different immunophenotypes for analysis with clinicopathological characteristics and survival. All breast cancer patients' survival were analyzed by using Kaplan-Meier and Log-Rank models. RESULTS: The presence of p53 protein was detected in 44.1%. Positive p53, and p53+Bcl2- immunophenotype were significantly associated with poorer prognostic features. In contrast, the positive Bcl2 protein accounted on 57.6%, and combination of p53-Bcl2+ were strong correlated with better clinicopathological parameters. Bcl2 positivity was observed in higher than the negative Bcl2 in the five-year OS (Overall survival) proportion (91.2 vs 79.4%, respectively) (p < 0.05). Multivariate analysis revealed that the expression of p53, Bcl2 or combinations of these 2 proteins was no longer remained as an independent prognostic variable. CONCLUSION: The Bcl2 positivity had a distinct OS and DFS (Disease free survival). The expression of p53 and Bcl2 are inversely correlated to clinical outcomes in breast cancer.