Objective:To investigate the risk factors of recurrence after surgical resection of differentiated thyroid carcinoma combined with iodine-131 and TSH（Thyroid stimulating hormone） inhibition therapy. Methods:From January 2015 to April 2020, the clinical data of patients with structural recurrence and without recurrence were retrospectively collected after surgical treatment combined with iodine-131 and TSH inhibition therapy in the First Medical Center of PLA General Hospital. The general conditions of the two groups of patients were analyzed and the measurement data in line with the normal distribution was used for comparison between groups. For measurement data with non-normal distribution, the rank sum test was used for inter-group comparison. The Chi-square test was used for comparison between the counting data groups. Univariate and multivariate regression analyses were used to determine the risk factors associated with relapse. Results:The median follow-up period was 43 months（range 18-81 months） and 100 patients（10.5%） relapsed among the 955 patients. Univariate analysis showed that tumor size, tumor multiple, the number of lymph node metastases>5 in the central region of the neck, and the number of lymph node metastases>5 in the lateral region were significantly correlated with post-treatment recurrence（P<0.001, P=0.018, P<0.001, P<0.001）. Multivariate analysis showed that tumor size（adjusted odds ratio OR: 1.496, 95%CI: 1.226-1.826, P<0.001）, tumor frequency（adjusted odds ratio OR: 1.927, 95%CI: 1.003-3.701, P=0.049）, the number of lymph node metastases in the central neck region>5（adjusted odds ratio OR: 2.630, 95%CI: 1.509-4.584, P=0.001） and the number of lymph node metastases in the lateral neck region>5（adjusted odds ratio OR: 3.074, 95%CI: 1.649-5.730, P=0.001） was associated with tumor recurrence. Conclusion:The study showed that tumor size, tumor multiple, the number of lymph node metastases in the central region of the neck>5 and the number of lymph node metastases in the side of the neck >5 are independent risk factors for recurrence of differentiated thyroid cancer after surgical resection combined with iodine-131 and TSH inhibition therapy.
Humans ; Thyroid Cancer, Papillary/surgery* ; Lymphatic Metastasis/pathology* ; Retrospective Studies ; Neck Dissection ; Thyroidectomy/adverse effects* ; Neoplasm Recurrence, Local/pathology* ; Thyroid Neoplasms/surgery* ; Risk Factors ; Adenocarcinoma ; Thyrotropin ; Lymph Nodes/pathology*

Humans ; Thyroid Neoplasms/pathology* ; Carcinoma, Papillary/pathology* ; World Health Organization ; Adenocarcinoma, Follicular/pathology*

Humans ; Female ; Carcinoma, Intraductal, Noninfiltrating/surgery* ; Thoracic Wall/pathology* ; Adenocarcinoma, Papillary ; Breast Neoplasms/surgery* ; Carcinoma, Ductal, Breast/pathology*

Objective: To investigate the clinicopathological features, immunophenotype and gene alterations of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA). Methods: Fifteen case of TL-LGNPPA diagnosed at Zhejiang Cancer Hospital (5 cases) and the First Affiliated Hospital, Zhejiang University School of Medicine (10 cases) from November 2011 to August 2020 were collected. Clinical and pathological examinations, immunohistochemical staining and next-generation sequencing were performed. The clinicopathological and molecular characteristics were summarized, and relevant literature was reviewed. Results: Fifteen patients were identified and included. Their median age was 36 years (range, 20-60 years). The male-female ratio was 1.0∶1.1. The most common symptoms were epistaxis and nasal obstruction. The neoplasms were located on the roof of the nasopharynx or the posterior margin of the nasal septum. The pathological features included complex papillary and glandular structures mainly composed of single or pseudostratified cubic and columnar cells, with mild to moderate cytological atypia. In some cases, spindle cell features, nuclear grooves, ground glass nuclei, squamous metaplasia, or scattered psammoma bodies were identified. In addition, nuclear polar reversal cells, hobnail cells and micropapillary structures were found, but have not been reported in previous literature. Immunohistochemistry showed that the tumor cells were diffusely positive for TTF1, CK7, vimentin and CKpan; focally positive for p40, CK5/6 and p16; and negative for Tg, NapsinA, CK20, CDX2, S-100 and PAX8. The Ki-67 positive rates ranged from 1% to 20% and were≤10% in thirteen cases (13/15). EBER in situ hybridization was negative in all cases. DNA sequencing of 6 specimens was performed and all specimens were found harboring gene mutations (EWSR1, SMAD2, ROS1, JAK3, GRIN2A, ERRCC5, STAT3, and TET2), but no hot spot gene alterations were found. No MSI-H and MMR related gene changes were detected. All tumors showed low tumor mutation burden. All 15 patients underwent endoscopic surgery, and only 1 of them underwent radiotherapy postoperatively. All patients were recurrence free and alive at the end of follow-up periods (range: 23 to 129 months). Conclusions: TL-LGNPPA is a rare indolent tumor of the nasopharynx and exhibits a unique morphology and immunophenotype. Endoscopic resection is an effective treatment for TL-LGNPPA with excellent overall prognosis.
Humans ; Male ; Female ; Adult ; Thyroid Gland/pathology* ; Adenocarcinoma, Papillary/pathology* ; Nasopharyngeal Neoplasms/pathology* ; Protein-Tyrosine Kinases ; Proto-Oncogene Proteins ; Nasopharynx/pathology* ; Biomarkers, Tumor

Humans ; Adenocarcinoma of Lung/pathology* ; Adenocarcinoma/pathology* ; Lung Neoplasms/pathology* ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Adenocarcinoma, Papillary/pathology*

We describe herein histologic, immunohistochemical, and molecular findings and clinical manifestations of a rare case of an extremely well differentiated papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis is still met with controversy. A recently reported entity of well-differentiated tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is different from FVPTC in its papillary architecture, and also from WDT-UMP in its recurrence and metastatic pattern. These morphologically deceptive entities harbored diagnostic difficulties in the past because the diagnosis depended solely on histology. However, they are now diagnosed with more certainty by virtue of immunohistochemical and molecular studies. We experienced a case of EWD-PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and manifested recurrence with lymph node (LN) metastasis 7 years later. After another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally positive for CK19, negative for galectin-3, and focally negative for CD56. Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations. A large cohort of EWD-PTC should be included in further study.
Adenocarcinoma, Follicular/pathology/secondary ; Adult ; Carcinoma, Papillary, Follicular/pathology/*secondary ; Female ; Galectin 3/analysis ; Humans ; Hyperplasia/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Skull Neoplasms/*secondary ; Thyroid Neoplasms/*pathology

OBJECTIVE: Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC), they contribute disproportionately to endometrial cancer deaths. Sufficient clinical information regarding treatment and prognosis is lacking. The aim of this study is to evaluate treatment outcomes in a rare cancer cohort based on the experience at two tertiary care cancer centers. METHODS: Clinicopathologic data were retrospectively collected on 279 patients with UPSC and UCCC treated between 1995 to 2011. Mode of surgery, use of adjuvant treatment, and dissection of paraaoritc lymph nodes were evaluated for their association with overall survival (OS) and progression-free survival (PFS). RESULTS: 40.9% of patients presented with stage I disease, 6.8% of patients presented with stage II disease and 52.3% of patients presented with stages III and IV. Median follow-up was 31 months (range, 1 to 194 months). OS and PFS at 5 years were 63.0% and 51.9%, respectively. OS and PFS were not affected by mode of surgery (open vs. robotic approach; OS: hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.28 to 1.62; PFS: HR, 0.78; 95% CI, 0.40 to 1.56). Adjuvant treatment was associated with improved OS in stages IB-II (HR, 0.14; 95% CI, 0.02 to 0.78; p=0.026) but not in stage IA disease. There was no difference in OS or PFS based on the performance of a paraaoritc lymph node dissection. CONCLUSION: Minimally invasive surgical staging appears a reasonable strategy for patients with non-bulky UPSC and UCCC and was not associated with diminished survival. Adjuvant treatment improved 5-year survival in stages IB-II disease.
Adenocarcinoma, Clear Cell/pathology/secondary/*therapy ; Aged ; Chemotherapy, Adjuvant ; Cystadenocarcinoma, Papillary/pathology/secondary/*therapy ; Cystadenocarcinoma, Serous/pathology/secondary/*therapy ; Female ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Professional Practice ; Radiotherapy, Adjuvant ; Retrospective Studies ; Robotic Surgical Procedures ; Survival Analysis ; Treatment Outcome ; Uterine Neoplasms/pathology/*therapy

OBJECTIVE: In this study we utilized the Surveillance, Epidemiology and End-Results (SEER) registry to identify risk factors for lymphatic spread and determine the incidence of pelvic and para-aortic lymph node metastases in patients with uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) who underwent complete surgical staging and lymph node dissection. METHODS: Nine hundred seventy-two eligible patients diagnosed between 1998 to 2009 with International Federation of Gynecology and Obstetrics (FIGO) 1988 stage IA-IVA UPSC (n=685) or UCCC (n=287) were identified for analysis. Binomial logistic regression was used to determine risk factors for lymph node metastasis, with the incidence of pelvic and para-aortic lymph node metastases reported for each FIGO primary tumor stage. The Cox proportional hazards regression model was used to determine factors associated with overall survival. RESULTS: FIGO primary tumor stage was the only independent risk factor for lymph node metastasis (p<0.01). The incidence of pelvis-only and para-aortic lymph node involvement according to the FIGO primary tumor stage were as follows: IA (2.3%/3.8%), IB (7.5%/5.2%), IC (22.5%/16.9%), IIA (20.8%/13.2%), IIB (25.7%/14.9%), and III/IV (25.7%/24.3%). Prognostic factors for overall survival included lymph node involvement (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.09 to 1.85; p<0.01), patient age >60 years (HR, 1.70; 95% CI, 1.21 to 2.41; p<0.01), and advanced FIGO primary tumor stage (p<0.01). Tumor grade, histologic subtype, and patient race did not predict for either lymph node metastasis or overall survival. CONCLUSION: There is a high incidence of both pelvic and para-aortic lymph node metastases for FIGO stages IC and above uterine papillary serous and clear cell carcinomas, suggesting a potential role for lymph node-directed therapy for these patients.
Adenocarcinoma, Clear Cell/epidemiology/pathology/*secondary/surgery ; Adult ; Aged ; Aged, 80 and over ; Aorta, Abdominal ; Cystadenocarcinoma, Papillary/epidemiology/pathology/*secondary/surgery ; Cystadenocarcinoma, Serous/epidemiology/pathology/*secondary/surgery ; Female ; Humans ; Incidence ; Kaplan-Meier Estimate ; Lymph Node Excision ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Pelvis ; SEER Program ; United States/epidemiology ; Uterine Neoplasms/*epidemiology/pathology/surgery

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.
Adenocarcinoma, Papillary/*genetics/secondary ; Adult ; Aged ; Carcinoma/*genetics/pathology ; DNA Mutational Analysis ; DNA, Neoplasm/*genetics ; Female ; Humans ; Lung Neoplasms/*genetics ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Neoplasm Staging ; *Peptide Nucleic Acids ; Prospective Studies ; Proto-Oncogene Proteins B-raf/*genetics ; Real-Time Polymerase Chain Reaction ; Thyroid Neoplasms/*genetics/pathology

OBJECTIVETo correlate morphological features with mutations of epidermal growth factor receptor (EGFR) in lung adenocarcinomas.

METHODSAccording to 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification, a total of 72 surgically resected lung adenocarcinomas were collected and classified into different histological subtypes and different cell types (hobnail, columnar and polygonal). EGFR gene mutation was detected with the amplification refractory mutation method provided by the EGFR mutation test kit. The correlation between these subtypes and EGFR mutations were evaluated.

RESULTSMutations of EGFR were detected in 48.6% (35/72) of lung adenocarcinomas; 19del and L858R were major mutational types (88.6%, 31/35). EGFR mutations were associated with female gender, non-smoking status, and well to moderately differentiated tumor histology. EGFR mutation types were not associated with age, smoking index, lymph node metastasis, stage, status of whether have or not have inclusion bodies or psammoma bodies and mitotic level. Correlations were observed between acinar and papillary adenocarcinoma subtypes and EGFR mutations according to the new classification. EGFR mutation was rare in the subtype of solid adenocarcinoma with mucin production and almost never observed in special subtypes (mainly mucinous and colloid adenocarcinoma). In addition, EGFR mutation was associated with the hobnail cell type.

CONCLUSIONLung adenocarcinomas of predominate acinar and papillary histological subtypes with hobnail cell morphology are good predictors for EGFR mutations.

Adenocarcinoma ; genetics ; pathology ; Adenocarcinoma, Mucinous ; genetics ; pathology ; Adenocarcinoma, Papillary ; genetics ; pathology ; Female ; Genes, erbB-1 ; Humans ; Lung Neoplasms ; genetics ; pathology ; Lymphatic Metastasis ; Male ; Mutation ; Receptor, Epidermal Growth Factor ; genetics ; Sex Factors ; Smoking