Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.
Humans ; Urinary Bladder Neoplasms/genetics* ; Carcinoma, Transitional Cell/pathology* ; Urinary Bladder/pathology* ; Diagnosis, Differential ; Retrospective Studies ; Mutation ; Cystitis/genetics* ; Neoplasms, Glandular and Epithelial/diagnosis* ; Papilloma/diagnosis* ; Telomerase/genetics*

Humans ; Consensus ; Pancreatic Neoplasms/pathology* ; Pancreas/pathology* ; Specimen Handling ; Neoplasms, Glandular and Epithelial

Objective: To investigate the clinicopathological, immunophenotypic, and molecular genetic features of bronchial sialadenoma papilliferum (BSP). Methods: Four cases of BSP collected at the Shanghai Pulmonary Hospital from May 2018 to June 2021 were retrieved and analyzed. These cases were evaluated for their clinical, histological, immunohistochemical (IHC) and genomic features. The patients were followed up and relevant literature was reviewed. Results: All four patients were male, aged from 55 to 75 years (mean 62 years), with tumor diameter of 6 to 21 mm (mean 13.5 mm), and lesions were located in the left lower lobe (n=2), right lower lobe (n=1), and trachea (n=1). They were characterized by a combination of surface exophytic endobronchial papillary proliferation and an endophytic two-cell layered ductal structure. IHC staining showed that CK7 and EMA were strongly positive in ductal epithelium; p63, p40, CK5/6 were positive in ductal and papillary basal cells; SOX10 was positive in ductal epithelium and basal cells; S-100 was positive in basal cells and ductal epithelium in two cases. Next generation sequencing showed that two cases harbored BRAF V600E mutation. Conclusions: BSP is an extremely rare primary lung tumor arising from the salivary gland under bronchial mucosa. The primary treatment choice of this tumor is complete surgical resection. The diagnosis and differential diagnosis of this tumor depend on classic histomorphologic and IHC features, and BRAF V600E gene mutation can be detected.
Aged ; China ; Epithelium/pathology* ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasms, Glandular and Epithelial/pathology* ; Salivary Gland Neoplasms/surgery*

BACKGROUND: So far there's no tumor maker applied in diagnosis and treatment of thymic epithelial tumors. This study is to assess the correlation between serum cytokine 19 fragment (Cyfra 21-1) and clinicopathological features and prognosis of thymic epithelial tumors (TETs). METHODS: The clinical data of 159 patients with TETs in Shanghai Chest Hospital was retrospectively analysed. Patients were divided into groups according to different tumor stages and histotypes. Serum Cyfra 21-1 was thus compared. In addition, the possible relationship between perioperative serum Cyfra 21-1 level and the recurrent status was carrid out. RESULTS: Preoperative Cyfra 21-1 serum concentrations in patiants with advanced stage (T4) and thymic carcinomas were significantly higher than that in others (P<0.001, P<0.001, respectively). When the preoperative serum level exceeds the out-off of 1.66 ng/mL, it possibly indicates the recurrence during follow up. Furthermore, the sensitivity, specificity, and positive as well as negative predictive value (PPV and NPV) of postoperative Cyfra 21-1 to predict tumor recurrence were evaluated. At a cut-off of Cyfra 21-1 of 2.66 ng/mL, the sensitivity was 0.7, the specificity was 0.925, the PPV was 0.5 and the NPV was 0.966. CONCLUSIONS The elevated level of preoperative serum Cyfra 21-1 indicates an advanced stage of tumor or a more malignant histotype (thymic carcinoma). It also probably suggests a higher risk of tumor recurrence. During the oncological follow up, in addition to regular imaging examinations, the blood test of serum Cyfra 21-1 is also suggested to improve the diagnosis of tumor recurrence in order to improve the prognosis.
Biomarkers, Tumor ; blood ; Female ; Follow-Up Studies ; Humans ; Keratin-19 ; blood ; chemistry ; Male ; Middle Aged ; Neoplasms, Glandular and Epithelial ; blood ; diagnosis ; pathology ; Peptide Fragments ; blood ; Prognosis ; ROC Curve ; Retrospective Studies ; Thymus Neoplasms ; blood ; diagnosis ; pathology

BACKGROUND/AIMS: Endoscopic resection (ER) is a well-established treatment modality for gastric epithelial neoplasm. However, there is a discrepancy between forceps biopsy and ER specimen pathology, including a negative pathologic diagnosis (NPD) after ER. It has been suggested that pit dysplasia (PD) is a subtype of gastric dysplasia, and the aim of this study was to assess the significance of PD in cases with NPD after ER for early gastric neoplasms. METHODS: After ER, 29 NPD lesions that had an associated pretreatment forceps biopsy specimen, were correctly targeted during ER, and had no cautery artifact on the resected specimen were included in this study. RESULTS: Sixteen lesions showed PD and 13 had no neoplastic pathology. The initial pretreatment forceps biopsy diagnoses of 29 NPD lesions were low-grade dysplasia (LGD) in 17 lesions, high-grade dysplasia (HGD) in seven lesions, and adenocarcinoma in five lesions, which after review were revised to PD in 19 lesions, LGD in four lesions, adenocarcinoma in two lesions, and no neoplastic pathology in four lesions. Overall, nine lesions (31%) were small enough to be removed by forceps biopsy, four NPD lesions (14%) were initially misinterpreted as neoplastic lesions, and 16 PD lesions (55%) were misinterpreted as NPD lesions on ER slides. CONCLUSIONS: Approximately half of the lesions initially diagnosed as LGD or HGD were subsequently classified as PD. Therefore, including PD as a subtype of gastric dysplasia could reduce the diagnostic discrepancy between initial forceps biopsy and ER specimens.
Adenocarcinoma ; Artifacts ; Biopsy ; Cautery ; Diagnosis ; Neoplasms, Glandular and Epithelial* ; Pathology* ; Stomach ; Stomach Neoplasms ; Surgical Instruments

OBJECTIVE: To investigate trends in the incidence of epithelial ovarian cancer (EOC), according to histologic subtypes, in Korean women between 1999 and 2012. METHODS: Data from the Korea Central Cancer Registry recorded between 1999 and 2012 were evaluated. The incidences of EOC histologic subtypes were counted. Age-standardized incidence rates (ASRs) and annual percentage changes (APCs) in incidence rates were calculated. Patient data were divided into three groups based on age (<40, 40 to 59, and >59 years), and age-specific incidence rates were compared. RESULTS: Overall, the incidence of EOC has increased. Annual EOC cases increased from 922 in 1999 to 1,775 in 2012. In 1999, the ASR was 3.52 per 100,000 and increased to 4.79 per 100,000 in 2012 (APC, 2.53%; p<0.001). The ASRs in 2012 and APCs between 1999 and 2012 for the four major histologic subtypes were as follows (in order of incidence): serous carcinoma (ASR, 2.32 per 100,000; APC, 4.34%; p<0.001), mucinous carcinoma (ASR, 0.73 per 100,000; APC, -1.05%; p=0.131), endometrioid carcinoma (ASR, 0.51 per 100,000; APC, 1.48%; p=0.032), and clear cell carcinoma (ASR, 0.50 per 100,000; APC, 8.13%; p<0.001). In the sub-analyses based on age, clear cell carcinoma was confirmed as the histologic subtype whose incidence had increased the most since 1999. CONCLUSION: The incidence of EOC is increasing in Korea. Among the histologic subtypes, the incidence of clear cell carcinoma has increased markedly across all age groups since 1999.
Adenocarcinoma, Clear Cell/epidemiology/pathology ; Adenocarcinoma, Mucinous/epidemiology/pathology ; Adult ; Age Distribution ; Aged ; Carcinoma, Endometrioid/epidemiology/pathology ; Cystadenocarcinoma, Serous/epidemiology/pathology ; Databases, Factual ; Female ; Humans ; Incidence ; Middle Aged ; Neoplasms, Glandular and Epithelial/*epidemiology/pathology ; Ovarian Neoplasms/*epidemiology/pathology ; Registries ; Republic of Korea/epidemiology

OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. METHODS: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and < or = median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. RESULTS: Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. CONCLUSION: Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/biosynthesis/genetics ; Cystadenocarcinoma, Serous/*genetics/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Neoplasm Proteins/biosynthesis/genetics ; Neoplasms, Glandular and Epithelial/*genetics/metabolism/pathology ; Ovarian Neoplasms/*genetics/metabolism/pathology ; Prognosis ; Transcription Factors/biosynthesis/*genetics ; Tumor Cells, Cultured

OBJECTIVETo study the expression of P53 protein in the advanced ovarian serous adenocarcinoma and explore its potential correlation with the clinicopathological features and prognosis of ovarian cancer.

METHODSThe immunohistochemical staining was used to detect the expression of P53 protein in 183 patients with advanced ovarian serous adenocarcinoma. The correlation of P53 protein with the clinicopathological features and its significance in the assessment of prognosis were explored.

RESULTSThe P53 protein expression was positive in 62.8% of the patients. Chi-square test showed that the overexpression of P53 protein was positively correlated with the elevation of serum CA125 and the two-tier grading of ovarian serous adenocarcinoma (P<0.001, P=0.038). Univariate analysis suggested that the prognosis of patients was associated with two-tier grading (P=0.007), lymph node metastasis (P=0.036), preoperative serum CA125 level (P=0.002), and P53 overexpression (P<0.001). Multivariate analysis showed that the International Federation of Gynecology and Obstetrics stage (P=0.038), lymph node metastasis (P=0.002), and overexpression of P53 (P=0.001) were independent prognostic factors.

CONCLUSIONThe P53 protein expression is closely related to the prognosis of advanced ovarian serous adenocarcinoma and can be used as an important indicator for predicting the prognosis.

CA-125 Antigen ; blood ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Membrane Proteins ; blood ; Neoplasm Grading ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial ; metabolism ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Prognosis ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVE: Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. METHODS: We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged < or =40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. RESULTS: A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. CONCLUSION: FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Female ; *Fertility Preservation ; Humans ; Laparoscopy ; Live Birth ; Neoplasm Recurrence, Local/blood/diagnosis/*therapy ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial/drug therapy/*pathology/*surgery ; *Organ Sparing Treatments ; Ovarian Neoplasms/drug therapy/*pathology/*surgery ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Term Birth ; Treatment Outcome ; Young Adult

OBJECTIVE: Distal pancreatectomy with splenectomy may be required for optimal cytoreductive surgery in patients with epithelial ovarian cancer (EOC) metastasized to splenic hilum. This study evaluates the morbidity and treatment outcomes of the uncommon procedure in the management of advanced or recurrent EOC. METHODS: This study recruited 18 patients who underwent distal pancreatectomy with splenectomy during cytoreductive surgery of EOC. Their clinicopathological characteristics and follow-up data were retrospectively analyzed. RESULTS: All tumors were confirmed as high-grade serous carcinomas. The median diameter of metastatic tumors located in splenic hilum was 3.5 cm (range, 1 to 10 cm). Optimal cytoreduction was achieved in all patients. Eight patients (44.4%) suffered from postoperative complications. The morbidity associated with distal pancreatectomy and splenectomy included pancreatic leakage (22.2%), encapsulated effusion in the left upper quadrant (11.1%), intra-abdominal infection (11.1%), pleural effusion with or without pulmonary atelectasis (11.1%), intestinal obstruction (5.6%), pneumonia (5.6%), postoperative hemorrhage (5.6%), and pancreatic pseudocyst (5.6%). There was no perioperative mortality. The majority of complications were treated successfully with conservative management. During the median follow-up duration of 25 months, nine patients experienced recurrence, and three patients died of the disease. The 2-year progression-free survival and overall survival were 40.2% and 84.8%, respectively. CONCLUSION: The inclusion of distal pancreatectomy with splenectomy as part of cytoreduction for the management of ovarian cancer was associated with high morbidity; however, the majority of complications could be managed with conservative therapy.
Adult ; Aged ; *Cytoreduction Surgical Procedures ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Neoplasms, Glandular and Epithelial/mortality/pathology/*surgery ; Ovarian Neoplasms/mortality/pathology/*surgery ; *Pancreatectomy/adverse effects ; Postoperative Complications/epidemiology/therapy ; *Splenectomy/adverse effects ; Splenic Neoplasms/pathology/*secondary/*surgery