Jee Young Han

Reclassifying Formerly Indeterminate Thyroid FNAs Using the Bethesda System Reduces the Number of Inconclusive Cases

Objective: To evaluate the effectiveness of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and to analyze the causes of unclear diagnoses following BSRTC adoption. Study Design: According to the BSRTC, we reclassified cytologic samples originally diagnosed as ‘indeterminate’ with sequential surgical resection. Then, we analyzed the causes of cases, which were recategorized as ‘atypia undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)’. Results: According to the BSRTC, 154 ‘indeterminate’ cases were reclassified as follows: unsatisfactory, n = 5 (3.2%); benign, n = 43 (27.9%); AUS/FLUS, n = 77 (50.0%); suspicious for a follicular neoplasm, n = 7 (7.1%); suspicious for a Hürthle cell neoplasm, n = 4 (2.6%); suspicious for malignancy, n = 15 (9.7%), and malignancy, n = 3 (1.9%). Then, the AUS/FLUS group was analyzed according to the scenarios proposed by the BSRTC. Fifty-nine (58.9%) cases of AUS/FLUS were due to suboptimal preparation. In addition, papillary microcarcinoma and coexisting Hashimoto’s thyroiditis caused inconclusive diagnoses. Conclusion: The BSRTC can be easily applied to thyroid fine-needle aspiration. We were able to reclassify indeterminate thyroid nodules into more detailed categories and thus reduce the number of cases classified as indeterminate. However, suboptimal preparation, papillary microcarcinoma, and coexisting Hashimoto’s thyroiditis precluded cytopathologists from making definitive diagnoses.

Endometrial stromal sarcoma of the small bowel: a case report and review of literature

Endometrial stromal sarcoma (ESS) is a rare mesenchymal neoplasm of the uterus, which is predominantly composed of endometrial stromal cells. When this feature is encountered in the extragenital area, the diagnosis is sometimes difficult especially if endometriosis is not present. We report a case of ESS arising in the small bowel without associated endometriosis in a 75-year-old woman and review the literatures for 16 cases of extrauterine extraovarian ESS. The most common site of the extrauterine extraovarian ESS is the gastrointestinal tract (8/16 cases). It is intimately associated with endometriosis (12/16 cases) as the case of ovarian ESS. Most ESSs were immunoreactive for CD10 (5/5 cases), progesterone receptor (10/10 cases), and estrogen receptor (9/11 cases), and negative for CD34 (0/7 cases). It may have a higher tendency for dissemination beyond its site of origin (12/16 cases) than its uterine counterpart. In conclusion, a careful morphological examination combined with immunohistochemical studies and consideration of ESS in the differential diagnosis would help in obtaining an accurate diagnosis in these rare circumstances.

Extrapulmonary Small Cell Carcinoma of the Liver: Clinicopathological and Immunohistochemical Findings

Patients with primary small cell carcinoma of the liver have rarely been described in medical literature. Knowledge of clinical, pathological and immunohistochemical properties remains limited. We described an 82-year-old female patient with primary small cell carcinoma of the liver. Histologically, the tumor showed typical morphology of a pulmonary small cell carcinoma. Immunohistochemically, the tumor revealed neuroendocrine differentiation; positive reaction for chromogranin, synaptophysin, CD56, and neuron specific enolase. The tumor was also positive for TTF-1 and c-kit but completely negative for hepatocyte, carcinoembryonic antigen, cytokeratin 7; 19; and 20. Herein, we discussed the clinical, pathological and immunohistochemical findings of extrapulmonary small cell carcinoma of the liver and reviewed the relevant literature.

PPARγ Agonist and Angiotensin II Receptor Antagonist Ameliorate Renal Tubulointerstitial Fibrosis

The peroxisome proliferator activated receptor (PPAR)γ agonist is used as antidiabetic agent with antihyperglycemic and antihyperinsulinemic actions. Beyond these actions, antifibrotic effects have been reported. We examined antifibrotic effects of PPARγ agonist and interaction with angiotensin receptor antagonist in the unilateral ureteral obstruction (UUO) model. After UUO, mice were divided to four groups: no treatment (CONT), pioglitazone treatment, L158809 treatment, and L158809+ pioglitazone treatment. On day 14, CONT mice showed severe fibrosis and all treated mice showed decreased fibrosis. The immunohistochmistry of PAI-1, F4/80 and p-Smad2 demonstrated that their expressions were increased in CONT group and decreased in the all treated groups compared to CONT. PAI-1 and p-Smad2 determined from Western blotting, among treated groups, was decreased compared to CONT group. The expression of TGF-β1 from real time RT PCR showed markedly increased in the CONT group and decreased in all treated groups compared to CONT. These data suggest the pioglitazone inhibited tubulointerstitial fibrosis, however, the synergism between pioglitazone and L158809 is not clear. Considering decreased expression of PAI-1 and TGF-β/Smad2 in the treated groups, PAI-1 and TGF-β are likely linked to the decreased renal tubulointerstitial fibrosis. According to these results, the PPARγ agonist might be used in the treatment of renal fibrotic disease.

Cytologic Evaluation of Low Grade Transitional Cell Carcinoma and Instrument Artifact in Bladder Washings

OBJECTIVE To identify key cytologic features for the separation of low grade transitional cell carcinomas (TCCs) from nonneoplastic lesions in bladder washings. STUDY DESIGN The cytomorphologic features of 95 bladder washing specimens showing papillary fragments, which included 50 low grade TCCs and 45 nonneoplastic lesions, were reviewed retrospectively. RESULTS Bladder washings from low grade TCCs showed papillary and irregular groups of cells with ragged borders, cytoplasmic homogeneity and subtle nuclear changes, such as increased nuclear/cytoplasmic ratio and irregular nuclear border. Bladder washings after instrumentation from nonneoplastic lesions of the bladder showed cellular specimens with cohesive, ball-shaped and papillary clusters with smooth borders lined with a denser-staining cytoplasmic collar. Reactive urothelial cells often displayed loose aggregates with irregular borders but no cytoplasmic collar. CONCLUSION In bladder washing cytology, nuclear changes and cytoplasmic homogeneity play a major role in the diagnosis of carcinoma.

Hyalinizing spindle cell tumor with giant rosettes arising in the lung: report of a case with FUS-CREB3L2 fusion transcripts.

Hyalinizing spindle cell tumor with giant rosettes (HSCT) is a very uncommon mesenchymal tumor that has similar morphological and biological features to the low‐grade fibromyxoid sarcoma (LGFMS). Lung involvement of HSCT is extremely rare, and only one case has been reported in the English‐language literature. Reported herein is a case of primary pulmonary HSCT that had FUS‐CREB3L2 fusion transcripts, a product of characteristic chromosomal abnormality t(7;16)(q33;p11) of HSCT and LGFMS. The patient was a 50‐year‐old woman who had a large solitary mass in the lung. Histologically, it was composed of bland spindle cells with variable cellularity deposited in a densely hyalinized stroma alternating with myxoid areas. Characteristic collagen rosettes were scattered in the cellular areas. Reverse transcription–polymerase chain reaction (RT‐PCR) assay using formalin‐fixed, paraffin‐embedded tissue detected FUS‐CREB3L2 fusion transcripts. Despite its bland morphology, it is known as low‐grade sarcoma and its recognition in the lung would be helpful for accurate diagnosis and proper management of this rare tumor. RT‐PCR for detection of FUS‐CREB3L2 fusion transcripts is a useful method for differential diagnosis of primary pulmonary HSCT.

Effects of Toll-like receptor antagonist 4,5-dihydro-3-phenyl-5-isoxasole acetic acid on the progression of kidney disease in mice on a high-fat diet.

Background Obesity-related metabolic disorders are closely associated with inflammation induced by innate immunity. Toll-like receptors (TLRs) play a pivotal role in the innate immune system by activating proinflammatory signaling pathways. GIT27 (4,5-dihydro-3-phenyl-5-isoxasole acetic acid) is an active immunomodulatory agent that primarily targets macrophages and inhibits secretion of tumor necrosis factor α [as well as interleukin (IL)-1β, IL-10, and interferon γ]. However, the effect of TLR antagonist on kidney diseases has rarely been reported. We investigated whether the TLR antagonist GIT27 has beneficial effects on the progression of kidney disease in obese mice on a high-fat diet (HFD). Methods Six-week-old male C57BL/6 mice were divided into three groups: mice fed with normal chow diet (N=4); mice fed with a HFD (60% of total calories from fat, 5.5% from soybean oil, and 54.5% from lard, N=4); and GIT27-treated mice fed with a HFD (N=7). Results Glucose intolerance, oxidative stress, and lipid abnormalities in HFD mice were improved by GIT27 treatment. In addition, GIT27 treatment decreased the urinary excretion of albumin and protein in obesity-related kidney disease, urinary oxidative stress markers, and inflammatory cytokine levels. This treatment inhibited the expression of proinflammatory cytokines in the kidneys and adipose tissue, and improved extracellular matrix expansion and tubulointerstitial fibrosis in obesity-related kidney disease. Conclusion TLR inhibition by administering GIT27 improved metabolic parameters. GIT27 ameliorates abnormalities of lipid metabolism and may have renoprotective effects on obesity-related kidney disease through its anti-inflammatory properties.

Clinicopathologic and Molecular Characteristics of Lung Adenocarcinoma Arising in Young Patients

Lung cancer rarely occurs in young patients. Recent studies have demonstrated that epidemiologic data are closely correlated to some molecular characteristics. We investigated the clinicopathologic characteristics of lung adenocarcinoma in young patients and evaluated immunohistochemically detected epidermal growth factor receptor (EGFR) mutation status and anaplastic lymphoma kinase (ALK) positivity. Among lung adenocarcinoma patients, 31 cases were of the ≤ 40 yr-old group and 261 cases of > 50 yr-old group. Young patients were more likely to be females (67.7% vs 40.2%), and nonsmokers (58.1% vs 45.2%) and more often had high TNM stage (stage IV was 80.6% vs 52.1%) and had a high rate of distant metastasis (51.6% vs 28.0%) compared with older patients. The signet ring cell feature was more common (25.8% vs 11.5%) and lepidic growth pattern was rarely present (3.2% vs 16.5%) in the adenocarcinoma of young patients. There was no significant survival difference between the two age groups. The rate of EGFR mutation status and ALK positivity did not show a statistical difference between two groups. In conclusion, lung adenocarcinoma of young patients demonstrates distinct pathologic features with frequent presence of a signet ring cell feature and rare occurrence of lepidic growth pattern. Further investigation for other genetic abnormalities would be needed.

Overexpression of c‐H‐ras p21 is correlated with vascular endothelial growth factor expression and neovascularization in advanced gastric carcinoma

ras Gene and its product (p21) have been reported to be associated with vascular endothelial growth factor (VEGF), which is one of the most important angiogenic factors, and tumor‐associated angiogenesis. We tried to evaluate the correlation between the expression of c‐H‐ras gene product p21 and angiogenesis in advanced gastric carcinoma.

DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury

Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.