Proto-oncogene Pokemon in thyroid cancer: a potential promoter of tumorigenesis in papillary thyroid carcinoma

Background@#Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters. @*Methods@#Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed. @*Results@#Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006). @*Conclusions@#Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

Proto-oncogene Pokemon in thyroid cancer: a potential promoter of tumorigenesis in papillary thyroid carcinoma

Background@#Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters. @*Methods@#Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed. @*Results@#Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006). @*Conclusions@#Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

Is methylation analysis of SFRP2, TFPI2, NDRG4, and BMP3 promoters suitable for colorectal cancer screening in the Korean population?

BACKGROUND/AIMS: Colorectal cancer (CRC) screening using stool DNA was recently found to yield good detection rates. A multi-target stool DNA test (Cologuard®, Exact Sciences), including methylated genes has been recently approved by the U.S. Food and Drug Administration. The aim of this study was to validate these aberrantly methylated genes as stool-based DNA markers for detecting CRC and colorectal advanced adenoma (AA) in the Korean population. METHODS: A single-center study was conducted in 36 patients with AA; 35 patients with CRC; and 40 endoscopically diagnosed healthy controls using CRC screening colonoscopy. The methylation status of the SFRP2, TFPI2, NDRG4, and BMP3 promoters was investigated blindly using bisulfate-modified stool DNA obtained from 111 participants. Methylation status was investigated by methylation-specific polymerase chain reaction. RESULTS: Methylated SFRP2, TFPI2, NDRG4, and BMP3 promoters were detected in 60.0%, 31.4%, 68.8%, and 40.0% of CRC samples and in 27.8%, 27.8%, 27.8%, and 33.3% of AA samples, respectively. The sensitivities obtained using 4 markers to detect CRC and AA were 94.3% and 72.2%, respectively. The specificity was 55.0%. CONCLUSIONS: Our results demonstrate that the SFRP2, TFPI2, NDRG4, and BMP3 promoter methylation analysis of stool sample DNA showed high sensitivity but low specificity for detecting CRC and AA. Because of the low specificity, 4 methylated markers might not be sufficient for CRC screening in the Korean population. Further large-scale studies are required to validate the methylation of these markers in the Asian population and to find new markers for the Asian population.

Using Forceps Biopsy after Small Submucosal Dissection in the Diagnosis of Gastric Subepithelial Tumors

The current tissue sampling techniques for subepithelial tumors (SETs) of the gastrointestinal (GI) tract have limited diagnostic efficacy. We evaluated the diagnostic yield and safety of forceps biopsies after small endoscopic submucosal dissection (SESD biopsies) in the diagnosis of gastric SETs. A total of 42 patients with gastric SETs > 10 mm were prospectively enrolled between May 2013 and October 2014. A dual knife was used to incise the mucosa and submucosa and forceps biopsies were then introduced deep into the lesion. To compare SESD biopsies with EUS-FNA, we used the retrospective data of 30 EUS-FNA cases. The diagnostic yield of SESD biopsies was comparable to that of EUS-FNA (35/42, 83.3% vs. 24/30, 80.0%, P = 0.717). The mean procedure time of SESD biopsies was shorter than that of EUS-FNA (10 vs. 37 minutes, P < 0.001). There were no procedure-related adverse events in the both group. The pathological diagnoses in SESD biopsies group included 15 leiomyomas, 7 GISTs, 10 heterotopic pancreases, 2 lipomas, and one other lesion. SESD biopsies are an easy, effective and safe technique for the diagnosis of gastric SETs and its diagnostic yield is comparable to that of EUS-FNA. This technique may be a reliable alternative to conventional EUS-FNA (Clinical trial registration No. KCT0000730).

Traumatic Bowel Perforation and Inguinal Hernia Masking a Mesenteric Calcifying Fibrous Tumor

No abstract available.

MUC2 Expression Is Correlated with Tumor Differentiation and Inhibits Tumor Invasion in Gastric Carcinomas: A Systematic Review and Meta-analysis

BACKGROUND: While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinicopathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC). METHODS: The present study investigated the correlation between MUC2 expression and clinicopathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. RESULTS: MUC2 expression was found in 58 of 167 GCs (34.7%). MUC2-expressing GC showed lower primary tumor (T), regional lymph node (N), and tumor node metastasis (TNM) stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively). However, MUC2 expression was not correlated with Lauren's classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively) but not with Lauren's classification, pN stage, or pTNM stage. CONCLUSIONS: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.

A Rare Case of Acute Leukemic Presentation of Blastic Plasmacytoid Dendritic Cell Neoplasm without Cutaneous Lesions

No abstract available.

Associations between the Expression of Mucins (MUC1, MUC2, MUC5AC, and MUC6) and Clinicopathologic Parameters of Human Breast Ductal Carcinomas / 한국유방암학회지

PURPOSE: Mucins are members of the glycoprotein family expressed in benign and malignant epithelial cells. The aim of this study is to evaluate the relationships between the expression of mucins in breast ductal carcinoma and clinicopathologic parameters. METHODS: We constructed tumor microarrays based on 240 cases of invasive ductal carcinoma and 40 cases of ductal carcinoma in situ (DCIS) using formalin fixed, paraffin embedded tissues. We examined the expressions of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. RESULTS: MUC1 demonstrated cytoplasmic, membranous, apical, and combinative expressions. Other mucins demonstrated cytoplasmic expression. In invasive ductal carcinoma, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 93.6%, 6.2%, 4.8%, and 12.4% of cases, respectively; these rates were slightly, but not significantly, higher than observed in cases of DCIS. MUC1 expression was associated with estrogen receptor (ER) expression and negative MUC1 expression was associated with triple negativity. MUC6 expression was correlated with higher histologic grade, lymphatic invasion, lymph node metastasis, and HER2 positivity. No associations with any other clinicopathologic parameters were observed. CONCLUSION: Most invasive ductal carcinomas of the breast express MUC1, and this expression is associated with ER expression. MUC6 expression is correlated with some clinicopathologic parameters that are indicators of poor prognosis. To evaluate the role of MUC6 as a potential biomarker, further studies are warranted.

A Case of Elderly-Onset Crescentic Henoch-Schonlein Purpura Nephritis with Hypocomplementemia and Positive MPO-ANCA

Henoch-Schonlein purpura (HSP) is common in childhood and often self-limiting. There have been limited studies on elderly-onset HSP nephritis (HSPN). A 76-yr-old man was transferred to our hospital with a 1-month history of oliguria, abdominal pain, edema and palpable purpura in the legs. Three months ago, he was admitted to another hospital with jaundice, and consequently diagnosed with early common bile duct cancer. The patient underwent a Whipple's operation. Antibiotics were administrated because of leakage in the suture from the surgery. However, he showed progressive renal failure with edema and purpura in the legs. Laboratory investigations showed serum creatinine 6.4 mg/dL, 24-hr urine protein 8,141 mg/day, myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) 1:40 and C3 below 64.89 mg/dL. Renal biopsy showed crescentic glomerulonephritis, as well as mesangial and extracapillary Ig A deposition. We started steroid therapy and hemodialysis, but he progressed to end-stage renal failure and he has been under maintenance hemodialysis. We describe elderly onset HSPN with MPO-ANCA can be crescentic glomerulonephritis rapidly progressed to end stage renal failure.

Extranodal Follicular Dendritic Cell Sarcoma with Rapid Growth in Parapharynx: A Case Report

Follicular dendritic cell sarcoma (FDCS) is a rare malignancy arising from the antigen-presenting cells in the lymph node and extranodal tissue. We describe a 31-year-old male patient who presented with a swelling of the left parapharynx. The radiologic findings showed a 4.7x4.5x1.9 cm-sized, ill-defined mass in the left parapharyngeal space. A fine-needle aspiration cytology was performed and it showed scattered, irregular, cohesive clusters of tumor cells with a spindle-to-ovoid shape with irregular contours in a background of lymphocytes. Based on these findings, a diagnosis of spindle cell neoplasm was made. The surgically resected tumor was composed of elongated, ovoid or polygonal cells showing positive immunohistochemistry for CD21, CD23, and CD35. Postoperatively, the residual tumor was observed to undergo a rapidly growth. There is an overlap in the cytologic and histologic findings between FDCS of the parapharynx and other tumors. Pathologists should therefore be aware of its characteristics not only to provide an accurate diagnosis but also to recommend the appropriate clinical management.

Extranodal Follicular Dendritic Cell Sarcoma with Rapid Growth in Parapharynx: A Case Report

Follicular dendritic cell sarcoma (FDCS) is a rare malignancy arising from the antigen-presenting cells in the lymph node and extranodal tissue. We describe a 31-year-old male patient who presented with a swelling of the left parapharynx. The radiologic findings showed a 4.7x4.5x1.9 cm-sized, ill-defined mass in the left parapharyngeal space. A fine-needle aspiration cytology was performed and it showed scattered, irregular, cohesive clusters of tumor cells with a spindle-to-ovoid shape with irregular contours in a background of lymphocytes. Based on these findings, a diagnosis of spindle cell neoplasm was made. The surgically resected tumor was composed of elongated, ovoid or polygonal cells showing positive immunohistochemistry for CD21, CD23, and CD35. Postoperatively, the residual tumor was observed to undergo a rapidly growth. There is an overlap in the cytologic and histologic findings between FDCS of the parapharynx and other tumors. Pathologists should therefore be aware of its characteristics not only to provide an accurate diagnosis but also to recommend the appropriate clinical management.

Overexpressions of Cyclin B1, cdc2, p16 and p53 in Human Breast Cancer: The Clinicopathologic Correlations and Prognostic Implications

PURPOSE: The molecular mechanisms that are responsible for the initiation and progression of breast cancers are largely unknown. This study was to analyze the cyclin B1, cdc2, p53 and p16 tumor suppressor genes in human breast cancer. MATERIALS AND METHODS: To investigate the role of cyclin B1, cdc2, p53 and p16 in the pathogenesis and progression of breast carcinomas, 98 cases of breast cancers were examined by immunohistochemical method. The correlations of cyclin B1, cdc2, p53 and p16 expression with various clinico-pathologic findings were analysed. RESULTS: In the normal breast tissues, cyclin B1, cdc2 and p16 were weakly expressed, while p53 was not expressed. On the other hand, cyclin B1, cdc2, p53 and p16 were overexpressed in breast cancer, showing correlation between the expression of cyclin B1 and cdc2 and breast cancers (p=0.00). The overexpressions of cdc2 and p16 were correlated with an infiltrative tumor border pattern and this was statistically significant (p<0.05). In addition, the overexpression of cdc2 was correlated with histologic high grade carcinomas (p=0.00). CONCLUSION: Cyclin B1 and cdc2 appeared to be involved in the genesis or progression of breast cancers. In addition, the overexpressions of p16 and p53 may play important roles in more aggressive tumor and the overexpression of cdc2 is associated with progression of tumor to a higher grade of breast carcinomas. The deranged overexpressions of cyclin B1, cdc2, p16 and p53 may play an important role in human breast carcinogenesis.

Thoracic Splenosis: A Case Report and the Importance of Clinical History

We present a case of thoracic splenosis in a 42-yr-old man with a medical history of abdominal surgery for a penetration injury with an iron bar of the left abdomen and back. He had been in good condition, but a chest radiograph taken during a regular checkup showed a multinodular left pleura-based mass. Computed tomography (CT) showed that the mass was well-enhanced and homogeneous, indicating a sclerosing hemangioma. Following its removal by video-assisted thoracoscopic surgery, the mass appeared similar to a hemangioma, with marked adhesion to the left side diaphragmatic pleura and lung parenchyma. Frozen section showed that the lesion was a solid mass consisted with abundant lymphoid cells, suggesting a low grade lymphoma. On permanent section, however, the mass was found to be composed of white pulp, red pulp, a thick capsule and trabeculae and was diagnosed as ectopic splenic tissue, or thoracic splenosis. Review of the patient's history and chest CT at admission revealed that the patient had undergone a splenectomy for the penetration injury 20 yr previously.

Mycophenolate Mofetil-Related Colitis: A Case Report

Mycophenolate mofetil (MMF)-related colitis is one of the common causes of afebrile diarrhea in transplant patients. Pathologic diagnosis of MMF-related colitis is difficult because microscopic findings of MMF effects resemble those of graft-versus-host disease, inflammatory bowel disease and ischemic colitis. However, if diagnosed, MMF-induced colitis can be markedly improved by discontinuing the drug. A 70-year-old man having a history of transplantation presented with a one month history of afebrile diarrhea. Colonoscopy revealed patchy erosions. The colonoscopic biopsy specimen showed not only crypt disarray with degenerated crypts and scattered epithelial cell apoptosis, but also stromal inflammatory cell infiltration. A review of his medical records showed that he had been taking immunosuppressive drugs including MMF since his heart transplantation 6 years prior. The histologic findings of colonic mucosa were consistent with MMF-related colitis. After discontinuing MMF, the diarrhea quickly resolved and has not recurred for 10 months.

Living Donor Liver Transplantation in a Korean Child with Glycogen Storage Disease Type IV and a GBE1 Mutation

Glycogen storage disease type IV (GSD-IV) is an autosomal recessive disease caused by a deficient glycogen branching enzyme (GBE), encoded by the GBE1 gene, resulting in the accumulation of abnormal glycogen deposits in the liver and other tissues. We treated a 20-month-old girl who presented with progressive liver cirrhosis and was diagnosed with GSD-IV, as confirmed by GBE1 gene mutation analysis, and underwent living related heterozygous donor liver transplantation. Direct sequencing of the GBE1 gene revealed that the patient was compound heterozygous for a known c.1571G>A (p.Gly264Glu) mutation a novel c.791G> A (Arg524Gln) mutation. This is the first report of a Korean patient with GSD-IV confirmed by mutation analysis, who was treated successfully by liver transplantation.

Immunohistochemical Markers for Metastasis in Clear Cell Renal Cell Carcinoma

BACKGROUND: Renal cell carcinoma (RCC) is notorious for its high metastatic potential, and 30% of RCC patients present with metastatic disease at the initial presentation and 50% of them will develop metastasis or recurrence after radical surgery. METHODS: In an attempt to identify the best predictive marker(s) for metastasis in patients with clear cell RCCs (CRCCs), we examined the expression patterns of 7 metastasis/prognosis-related markers by constructing a tissue microarray including primary CRCC specimens from 30 metastatic and 60 nonmetastatic CRCCs. The markers we studied were Ki-67, MUC1, CD44s, PTEN, gelsolin, CA9 and p53. RESULTS: The expressions of Ki-67, PTEN, CD44s, gelsolin and p53 were increased, whereas those of MUC1 and CA9 were decreased in the metastatic CRCCs compared with the non-metastatic CRCCs. The receiver operating characteristic curve-area under the curve (AUC) value of Ki-67 was 0.671, which was the highest among the 7 markers. The optimal cut-off value, sensitivity and specificity of the Ki-67 expression were 1.67%, 86.7% and 41.7%, respectively. CONCLUSIONS: These results demonstrate that the Ki-67 expression was increased in metastatic CRCCs, and it had the highest predictive value among the 7 markers. This suggests that Ki-67 could be an excellent predictive marker for metastasis in CRCC patients.

Clinicopathological Analysis of Eight Cases of Idiopathic Portal Hypertension

BACKGROUND: Idiopathic portal hypertension (IPH) is a rare clinicopathologic entity that shows clinical evidences of portal hypertension with no pathologic features of cirrhosis. METHODS: The clinical and pathologic features of 8 cases with IPH were analyzed via the medical records along with the biopsy or resected liver specimens. RESULTS: Six patients were male and two were female. The chief complaints were sudden variceal bleeding in seven patients and abdominal pain in one patient. Six patients were treated with varix ligation and one was treated with splenectomy after the failure of bleeding control. One patient underwent a liver transplantation due to severe symptoms of portal hypertension. The prognosis of all the patients was excellent. Microscopically, the portal tracts were variably fibrotic, and the portal veins in them were sclerotic, obliterated or dilated in 7 cases; pathologic abnormalities were absent in 1 case. Cirrhosis was absent in all cases, while septal fibrosis was present in one resected liver. CONCLUSIONS: IPH is a minor cause of portal hypertension. However, a liver biopsy to show the subtle portal vascular changes and fibrosis in patients who have the clinical symptoms of portal hypertension is important for making the diagnosis of IPH.

Angiomatoid Fibrous Histiocytoma: A Case Report

We report on a case of angiomatoid fibrous histiocytoma located deep in subcutaneous tissue of the left shoulder in an 11-year-old boy. An ovoid firm mass was slowly increasing in size for 5 months without any pain or tenderness. The tumor was grossly multicystic, with dense fibrous capsule and it measured 7.5 x 7.5 x 4.0 cm. The locules contained hemorrhagic fluid, and the inner surface was purplish brown and trabecular. The septal solid areas were cellular, and they consisted of histiocytoid spindle cells that were arranged in a storiform or fascicular pattern. The tumor cells showed immuno-positivity for CD99, CD68 and desmin. These findings were compatible with angiomatoid fibrous histiocytoma of an uncommon location.