Objective: To investigate the clinicopathological, immunohistochemical and molecular characteristics of low grade oncocytic tumors (LOT) of the kidney with CK7+/CD117- staining pattern for enhancing the understanding of renal LOT. Methods: The clinical data, histological morphology and immunophenotypes of seven renal LOT cases diagnosed at the Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine from January 2017 to April 2021 were analyzed. The patients were followed up. Among the seven patients, five underwent high-throughput DNA targeted sequencing, and their molecular characteristics were analyzed. Results: The patients' age ranged 59-82 years, with an average of 70 years. There were 2 males and 5 females. The boundary of the tumor was clear. The tumor cells had homogeneous eosinophilic cytoplasm and round or oval nuclei, with a perinuclear halo. Small basophilic nucleoli were conspicuous (WHO/International Society of Urological Pathology grade 2). In the hypercellular areas, the tumor cells were mainly arranged in dense solid or nest. In the stroma, there were dilated veins, thick-walled arterioles and thick collagen fiber bundles that divided the cells into pseudonodules. In the sparsely cellular area, the tumor cells were arranged in the so-called "tissue culture" fashion. In addition, the stroma contained fresh hemorrhagic foci and lymphoid aggregates. High-throughput sequencing of 5 cases revealed that one case harbored mTOR gene missense mutation and another case harbored TSC1 frameshift mutation. Conclusions: LOT of the kidney is an indolent tumor with an overall good prognosis. Pathologists should not misdiagnose it as renal oncocytoma and chromophobe renal cell carcinoma.
Adenoma, Oxyphilic/pathology* ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics* ; Carcinoma, Renal Cell/pathology* ; Collagen ; Female ; Humans ; Immunohistochemistry ; Kidney/pathology* ; Kidney Neoplasms/pathology* ; Male ; Middle Aged ; Proto-Oncogene Proteins c-kit/metabolism* ; TOR Serine-Threonine Kinases

OBJECTIVE: To assess the value of DNA methylation level of HYAL2 gene as a molecular marker for differential diagnosis of malignant and benign thyroid tumors. METHODS: DNA methylation of HYAL2 gene in tissue specimens of 190 patients with papillary thyroid cancer (PTC) and 190 age- and gender-matched patients with benign thyroid tumors was examined by mass spectrometry, and the protein expression of HYAL2 was detected immunohistochemically for another 55 pairs of patients. Logistic regression analysis was performed to calculate the odds ratio (OR) and evaluate the correlation of per 10% reduction in DNA methylation with PTC. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) was calculated to assess the predictive value of alterations in HYAL2 methylation. RESULTS: Hypomethylation of HYAL2_CpG_3 was significantly correlated with early-stage PTC (OR=1.51, P=0.001), even in stage I cancer (OR=1.42, P=0.007). Age-stratified analysis revealed a significantly stronger correlation between increased HYAL2_CpG_ 3 methylation and early-stage PTC in patients below 50 years than in those older than 50 years (OR: 1.89 vs 1.37, P < 0.05); ROC analysis also showed a larger AUC of 0.787 in younger patients. The results of immunohistochemistry showed that patients with PTC had significantly higher protein expressions of HYAL2 than patients with benign tumors. CONCLUSION The alterations of DNA methylation level of HYAL2 gene is significantly correlated with early-stage PTC, suggesting the value of DNA methylation level as a potential biomarker for differentiation of malignant from benign thyroid tumors.
Adenoma, Oxyphilic/genetics* ; Biomarkers, Tumor/metabolism* ; Cell Adhesion Molecules/metabolism* ; DNA Methylation ; GPI-Linked Proteins/metabolism* ; Humans ; Hyaluronoglucosaminidase/metabolism* ; Immunohistochemistry ; Middle Aged ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/pathology*

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.
Adenoma/*diagnosis/surgery ; Carcinoma, Hepatocellular/diagnosis ; Diagnosis, Differential ; Focal Nodular Hyperplasia/*diagnosis/surgery ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Liver/pathology ; Liver Neoplasms/*diagnosis/surgery ; beta Catenin/genetics/metabolism

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.
Adenoma/*diagnosis/surgery ; Carcinoma, Hepatocellular/diagnosis ; Diagnosis, Differential ; Focal Nodular Hyperplasia/*diagnosis/surgery ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Liver/pathology ; Liver Neoplasms/*diagnosis/surgery ; beta Catenin/genetics/metabolism

OBJECTIVETo investigate methylation status of Wif-1 and β-catenin expression in colorectal serrated lesions.

METHODSVarious colorectal lesions were collected including 52 cases of hyperplastic polyps, 41 cases of sessile serrated adenoma, 23 cases of traditional serrated adenoma, 24 cases of colorectal cancer and 24 cases of normal mucosa. All specimens were subject to immunohistochemical staining of β-catenin.SYBR Green PCR analysis of Wif-1 promoter methylation was performed in 29 cases of hyperplastic polyps, 29 cases of sessile serrated adenoma, 19 cases of traditional serrated adenoma, 14 cases of colorectal cancer and 16 cases of normal mucosa.

RESULTSAbnormal expression rates of β-catenin in normal mucosa, hyperplastic polyps, sessile serrated adenoma, traditional serrated adenoma and colorectal cancer were 12.5% (3/24), 59.6% (31/52), 63.4% (26/41), 73.9% (17/23) and 100.0% (24/24), respectively. The corresponding methylation rates of Wif-1 promoter were 2/16, 10/29 (34.5%), 16/29 (55.2%), 15/19 and 13/14 (P < 0.05), respectively. Abnormal β-catenin expression was positively correlated with Wif-1 promoter methylation in traditional serrated adenomas (r = 0.536, P < 0.05).

CONCLUSIONSAbnormal β-catenin expression and methylation rate of Wif-1 promoter are significantly higher in colorectal serrated lesions. Methylation of Wif-1 promoter may be related to the abnormal expression of β-catenin through activation of Wnt/β-catenin signaling pathway, which may contribute to the development of colorectal serrated lesions.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Adenoma ; genetics ; metabolism ; pathology ; Carcinoma ; genetics ; metabolism ; pathology ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; DNA Methylation ; Humans ; Hyperplasia ; Immunohistochemistry ; Intestinal Mucosa ; metabolism ; Intestinal Polyps ; pathology ; Repressor Proteins ; genetics ; metabolism ; Wnt Signaling Pathway ; beta Catenin ; metabolism

BACKGROUND/AIMS: This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions. METHODS: We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction. RESULTS: The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08). CONCLUSIONS: Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype.
Adenoma/*chemistry ; Aged ; Antigens, Bacterial/genetics ; Bacterial Proteins/genetics ; Carcinoma/*chemistry ; Cell Transformation, Neoplastic ; Core Binding Factor Alpha 3 Subunit/*analysis ; Female ; Gastric Mucosa/*chemistry/pathology ; Helicobacter Infections/*metabolism ; Helicobacter pylori/*genetics ; Humans ; Male ; Middle Aged ; Mucin 5AC/analysis ; Mucin-2/analysis ; Mucin-6/analysis ; Neprilysin/analysis ; Phenotype ; Precancerous Conditions/*chemistry/pathology ; Stomach Neoplasms/*chemistry

Adenoma ; genetics ; metabolism ; pathology ; surgery ; Adult ; Carcinoma, Renal Cell ; genetics ; metabolism ; pathology ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Diagnosis, Differential ; Diploidy ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Retrospective Studies ; S100 Proteins ; metabolism ; Vimentin ; metabolism ; WT1 Proteins ; metabolism ; Wilms Tumor ; metabolism ; pathology

Adenoma ; genetics ; metabolism ; pathology ; surgery ; Adult ; Carcinoma, Papillary ; genetics ; metabolism ; pathology ; Diagnosis, Differential ; Exons ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Mutation ; Nuclear Proteins ; metabolism ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroglobulin ; metabolism ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism

Adenoma, Acidophil ; metabolism ; Adult ; Angiomyolipoma ; genetics ; metabolism ; pathology ; Carcinoma, Renal Cell ; metabolism ; Codon ; Diagnosis, Differential ; Exons ; Female ; Follow-Up Studies ; Gene Deletion ; Genes, p53 ; Humans ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; Male ; Melanoma-Specific Antigens ; metabolism ; Middle Aged ; Retrospective Studies ; Tumor Suppressor Protein p53 ; genetics ; metabolism

OBJECTIVE: To explore whether oncogenes DJ-1 and HSP27 are associated with invasiveness of human pituitary adenoma. METHODS: Total proteins were extracted from samples of 20 invasive and 20 non-invasive pituitary adenomas and the expression of DJ-1 and HSP27 was analyzed by Western blot. The correlation of DJ-1and HSP27 with the invasiveness of pituitary adenoma was analyzed. RESULTS: The strong positive rates of DJ-1 and HSP27 in the 20 invasive pituitary adenoma were 70% (14/20) and 80% (16/20), respectively. The invasive group had significantly higher expression of DJ-1 and HSP27 proteins than the noninvasive group [10% (2/20), 10% (2/20), respectively]. There was a positive correlation between the expression of DJ-1, HSP27 proteins and the invasiveness of pituitary adenoma as judged by the Spearman rank correlation test (P<0.05). CONCLUSION The proliferative activity and abnormal expression of oncogenes DJ-1 and HSP27 may play a significant role in tumorigenesis and progression of pituitary adenoma. There was a significant correlation between the expression of DJ-1 and HSP27 and the invasiveness of pituitary adenoma.
Adenoma ; metabolism ; pathology ; Adult ; Biomarkers, Tumor ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; HSP27 Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Male ; Middle Aged ; Neoplasm Invasiveness ; Oncogene Proteins ; genetics ; metabolism ; Pituitary Neoplasms ; metabolism ; pathology ; Protein Deglycase DJ-1 ; Signal Transduction ; Young Adult