Adenocarcinoma, Follicular ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; Carcinoma, Renal Cell ; genetics ; metabolism ; pathology ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Kidney Diseases, Cystic ; genetics ; metabolism ; pathology ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; Translocation, Genetic

Carcinoma, Renal Cell ; classification ; diagnosis ; genetics ; pathology ; Chromosomes, Human ; Humans ; Immunohistochemistry ; methods ; Kidney Neoplasms ; classification ; diagnosis ; genetics ; pathology ; Translocation, Genetic

Biomarkers, Tumor ; Breast Neoplasms ; classification ; diagnosis ; genetics ; pathology ; Carcinoma, Basal Cell ; classification ; diagnosis ; genetics ; pathology ; Genes, BRCA1 ; Humans ; Mutation

In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC.
Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; pathology ; Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; genetics ; pathology ; Mutation ; Prognosis

OBJECTIVETo investigate the value of fluorescence in situ hybridization (FISH) detection of human telomerase RNA component (hTERC) gene amplification in screening of cervical lesions.

METHODSA total of 146 post-thinPrep cytology test (TCT) samples were analyzed using FISH by two-color interphase probe targeting hTERC gene at chromosome 3q26 and the data were compared with the cytological and histological results.

RESULTSFISH analysis was successful in 120 cases (20 cases of normal and 100 abnormal cases by TCT). Gene amplification of hTERC by FISH had a positive correlation with the cytological (r = 0.465, P < 0.01) and histological grade results (r = 0.610, P < 0.01). Extra copies of hTERC were seen in 28.6% (6/21) of CINI, 61.1% (11/18) of CINII, 75.0% (18/24) of CINIII and 91.7%(22/24) of squamous cell carcinoma, respectively. None (0/13) of the inflammation cases showed hTERC amplification. The sensitivity and specificity for detecting high grade lesions by FISH were 77.3% (51/66) and 82.4% (28/34); and the positive and negative predictive values were 89.5% and 65.1%, respectively. The rate of hTERC gene gain in high grade lesions was significantly higher than that in the low grade lesions (χ(2) = 32.550, P < 0.01). Combined with the high copy numbers, the sensitivity for detecting high grade lesions was increased to 81.2%.

CONCLUSIONSDetection of hTERC gene amplification by FISH improves the screening efficiency of high-risk cervical epithelial lesions. The presence of high copy numbers of hTERC correlates with the presence of high grade cervical dysplasia.

Adult ; Aged ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; pathology ; Cervical Intraepithelial Neoplasia ; diagnosis ; genetics ; pathology ; Female ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; RNA ; genetics ; Telomerase ; genetics ; Uterine Cervical Neoplasms ; diagnosis ; genetics ; pathology ; Uterine Cervicitis ; diagnosis ; genetics ; pathology ; Young Adult

OBJECTIVETo evaluate the association between BRAF(V) 600E mutation and pathological features in papillary thyroid carcinoma (PTC).

METHODSThe raleted studies were searched through Medline, PubMed, and Web of Science, and meta-analysis was used to calculate the OR and 95%CI of the study results.

RESULTSA total of 52 studies including 12 029 PTC patients was identified. The prevalence of BRAF(V) 600E mutation in PTC was 57.85%. There was a closed association between the BRAF(V) 600E mutation and pathological features, including advanced TNM stage (OR = 1.89, 95%CI 1.58-2.27), lymph node metastasis (OR = 1.74, 95%CI 1.42-2.14), multifocality (OR = 1.25, 95%CI 1.07-1.46), and recurrence (OR = 2.26, 95%CI 1.25-4.09) of PTC. For Asians with PTC, the association between the BRAF(V) 600E mutation and pathological features was indicated for advanced TNM stage (OR = 1.56, 95%CI 1.24-1.96) and lymph node metastasis (OR = 1.57, 95%CI 1.25-1.99). For Europeans with PTC, the association between the BRAF(V) 600E mutation and pathological features was indicated for advanced TNM stage (OR = 2.63, 95%CI 2.10-3.30), lymph node metastasis(OR = 1.97, 95%CI 1.19-3.25), and multifocality (OR = 1.35, 95%CI 1.01-1.80).

CONCLUSIONThere were associations between the BRAF(V) 600E utation and advanced TNM stage, lymph node metastasis, multifocality, and recurrence of PTC.

Carcinoma ; diagnosis ; genetics ; pathology ; Carcinoma, Papillary ; Humans ; Lymphatic Metastasis ; Mutation ; Neoplasm Recurrence, Local ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; diagnosis ; genetics ; pathology

OBJECTIVETo investigate the clinical significance of atypical squamous cells of unknown significance (ASCUS) with abnormal DNA ploidy in the early diagnosis of cervical lesions.

METHODSEight thousand four hundred and forty-eight patients were included in this study and all had DNA quantitative analysis and cervical liquid-based cytology. Among 1041 cases with DNA aneuploidy and/or abnormal cervical liquid-based cytology and additional cervical biopsy, histological review was performed in 247 ASCUS cases with abnormal DNA ploidy.

RESULTS(1) Among 8448 cases, 7877 were normal or benign, 426 were ASCUS, 45 were ASC-H, 55 were LSIL and 22 were HSIL by TBS diagnosis. The presence of 1-2 abnormal DNA ploidy cells was detected in 15.3% (65/426) of ASCUS, 11.1% (5/45) of ASC-H, 9.1% (5/55) of LSIL, and 0 (0/22) of HSIL. The presence of ≥ 3 abnormal DNA ploidy cells was detected in 39.0% (166/426) of ASCUS, 75.6% (34/45) of ASC-H, 76.4% (42/55) of LSIL, and 95.5% (21/22) of HSIL. (2) A total of 67 cases of CIN 2, CIN 3 or cancers were found in 247 patients with ASCUS by colposcopy biopsies, of which 13.9% (5/36) had 1-2 abnormal DNA ploidy cells, 45.5% (56/123) had ≥ 3 abnormal DNA ploidy cells and 6.8% (6/88) had normal DNA polidy. ASCUS with 1-2 abnormal DNA ploidy cells and with ≥ 3 abnormal DNA ploidy cells were compared. The difference was statistically significant (χ(2) = 11.79, P < 0.01). But the difference between ASCUS with 1-2 abnormal DNA ploidy cells and normal DNA ploidy had no statistical significance (P > 0.05).

CONCLUSIONSASCUS with ≥ 3 abnormal DNA ploidy cells has higher risk for developing CIN 2, CIN 3 or invasive carcinoma. The application of DNA quantitative analysis and cervical liquid-based cytology test can help in guiding clinical follow-up and treatment options in patients with ASCUS.

Adenocarcinoma ; diagnosis ; genetics ; pathology ; Adolescent ; Adult ; Aged ; Aneuploidy ; Carcinoma in Situ ; diagnosis ; genetics ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; pathology ; Cervical Intraepithelial Neoplasia ; diagnosis ; genetics ; pathology ; Colposcopy ; DNA, Neoplasm ; genetics ; Female ; Humans ; Middle Aged ; Uterine Cervical Dysplasia ; diagnosis ; genetics ; pathology ; Uterine Cervical Neoplasms ; diagnosis ; genetics ; pathology ; Young Adult

Renal cell carcinoma (RCC) is an important contributor to cancer-specific mortality worldwide. Targeted agents that inhibit key subtype-specific signaling pathways have improved survival times and have recently become part of the standard of care for this disease. Accurately diagnosing and classifying RCC on the basis of tumor histology is thus critical. RCC has been traditionally divided into clear-cell and non-clear-cell categories, with papillary RCC forming the most common subtype of non-clear-cell RCC. Renal neoplasms with overlapping histologies, such as tumors with mixed clear-cell and papillary features and hybrid renal oncocytic tumors, are increasingly seen in contemporary practice and present a diagnostic challenge with important therapeutic implications. In this review, we discuss the histologic, immunohisto-chemical, cytogenetic, and clinicopathologic aspects of these differential diagnoses and illustrate how the classification of RCC has evolved to integrate both the tumor's microscopic appearance and its molecular fingerprint.
Biopsy, Large-Core Needle ; Carcinoma, Renal Cell ; classification ; diagnosis ; genetics ; pathology ; DNA Copy Number Variations ; DNA, Neoplasm ; genetics ; Diagnosis, Differential ; Humans ; Kidney Neoplasms ; classification ; diagnosis ; genetics ; pathology

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*

This is the first report of papillary thyroid carcinoma combined with multiple endocrine neoplasia type 1 (MEN1) in Korea. MEN1 is a hereditary disease comprising neoplastic disorders such as pituitary, parathyroid and pancreatic neuroendocrine tumor, such as gastrinoma. But papillary thyroid cancer was never regarded as its component before in Korea. Herein we present a 39-year-old woman who manifested typical features of MEN1 with a coincidental papillary thyroid carcinoma. Although the family history of MEN1 was definite, her genetic analysis of DNA had revealed no germline mutation in MEN1 gene locus. Unidentified culprit gene unable us further genetic study to find LOH (loss of heterogeneity) in 11q13, the possible explanation of papillary thyroid carcinoma as a new component of MEN1. As we have first experienced a case of MEN1 combined with papillary thyroid carcinoma in Korea, we report it with the review of literature.
Adult ; Carcinoma, Papillary/genetics/*pathology ; Diagnosis, Differential ; Female ; Humans ; Multiple Endocrine Neoplasia Type 1/genetics/*pathology ; Mutation ; Proto-Oncogene Proteins/genetics ; Thyroid Neoplasms/genetics/*pathology