Traditionally, pathologists have used human biological material primarily for diagnostic purposes. More recently, advances in biomedical technology and changes in the research environment have placed new demands on pathologists and their handling of human materials. Moreover, these technological advances have required pathologists to be not only experts in diagnosis, but also managers of biobanks storing human biological material. Consequently, pathologists might now be confronted with unanticipated legal and ethical questions. We investigated seven examples of South Korean legislation concerning human biological material, including "The Bioethics and Safety Act" (2005), and we considered possible conflicts of interest between donors and researchers. We also reviewed international bioethical guidelines and legal precedents from several countries with special regard to pathologic glass slides, paraffin blocks, remaining specimens and other guidelines.
We conclude that a better understanding of the legal and ethical questions concerning human biological material leads pathologists to safer and more conscientious management of these samples.
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Proposal for the development of a human biological material management system for research hospitals Young-Joon Ryu, Hankyeom Kim, Sejin Jang Journal of the Korean Medical Association.2012; 55(3): 292. CrossRef
Seung Sook Lee, Jin Man Kim, Young Hyeh Ko, Jooryung Huh, Chang Suk Kang, Chul Woo Kim, Yun Kyung Kang, Jai Hyang Go, Min Kyung Kim, Wan Seop Kim, Yoon Jung Kim, Hyun Jung Kim, Hee Kyung Kim, Jong Hee Nam, Hyung Bae Moon, Chan Kum Park, Tae In Park, Young Ha Oh, Dong Wha Lee, Jong Sil Lee, Juhie Lee, Hyekyung Lee, Sung Chul Lim, Kyu Yun Jang, Hee Kyung Chang, Yoon Kyung Jeon, Hye Ra Jung, Min Sun Cho, Hee Jeong Cha, Suk Jin Choi, Jae Ho Han, Sook Hee Hong, Insun Kim
BACKGROUND The Hematopathology Study Group of the Korean Society of Pathologists conducted a nation-wide retrospective analysis of Korean pediatric lymphoma, to provide pathologic data on pediatric/adolescent lymphoma subtypes and features. METHODS All lymphoma cases of all age groups were collected during a recent 2 year-period (2005-2006) from 32 institutes in Korea. Among 3,686 lymphoma patients, 142 who were age 18 or less were classified according to the World Health Organization (WHO) classification. RESULTS Among 142 pediatric/adolescent lymphoma patients, Hodgkin lymphoma accounted for 21 (14.8%) and non-Hodgkin lymphoma (NHL) for 121 (85.2%). Hodgkin lymphoma appears to be more common in the pediatric/adolescent age group than in the all-ages group (14.8% vs 4.4%). T- and natural killer cell-NHL was more common in the pediatric/adolescent age group than in the all ages group (46.3% vs 22%). The majority of Korean pediatric/adolescent NHL cases was composed of Burkitt lymphoma, T- or B-lymphoblastic lymphoma, anaplastic large-cell lymphoma, and diffuse large B-cell lymphoma. For lymphoma patients under the age of 6 years, most had B-lymphoblastic or Burkitt lymphoma, which commonly presented at extranodal sites. CONCLUSIONS The distribution of lymphoma subtypes in the pediatric/adolescent age group is quite different from the distribution of adults, but it was quite similar to distribution in Western countries.
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A Case of Nasal Type Extranodal NK/T Cell Lymphoma Incidentally Detected in a Child Ha Jin Oh, Sang Hyun Park, Hae In Jang, Dong Hoon Lee, Yoo Duk Choi, Hee Jo Baek, Hoon Kook Clinical Pediatric Hematology-Oncology.2015; 22(1): 76. CrossRef
BACKGROUND The Src family kinases (SFKs) are involved in multiple aspects of tumorigenesis, such as, proliferation, migration, and angiogenesis, and are involved in the generation and progression of many types of tumors.
Furthermore, dasatinib, a general SFKs inhibitor was recently approved for use in chronic myeloid leukemia. This study was performed to evaluate the expression of Lyn, a member of the SFKs, in osteosarcoma tissues. METHODS One hundred and sixteen patients with osteoblastic osteosarcoma were selected for Lyn expression analysis. The correlation between Lyn expression in tumor sections and patients' clinicopathologic characteristics and the prognostic significance of Lyn expression were evaluated. RESULTS Lyn was found to be expressed in 52 of the 116 patients (44.8%), and Lyn positive tumor was found to be significantly associated with a lytic tumor pattern on plain radiographs (p = 0.04). Furthermore, those positive for Lyn showed longer metastasis free survival (5-year metastasis free survival, 65.2% for Lyn positive and 46.8% for Lyn negative; p = 0.06), though this was only marginally significant. CONCLUSIONS Lyn was found to be overexpressed in osteosarcoma tissues, and this overexpression was found to be correlated with osteolysis.
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Eight Aging-Related Genes Prognostic Signature for Cervical Cancer Meilin Yin, Yanhua Weng, Ferenc Olasz International Journal of Genomics.2023; 2023: 1. CrossRef
LYN expression predicts the response to dasatinib in a subpopulation of lung adenocarcinoma patients Yu Jin Kim, Sungyoul Hong, Minjung Sung, Min Jeong Park, Kyungsoo Jung, Ka-Won Noh, Doo-Yi Oh, Mi-Sook Lee, Ensel Oh, Young Kee Shin, Yoon-La Choi Oncotarget.2016; 7(50): 82876. CrossRef
Ji Yoon Bae, Hyung Kyung Kim, Hanna Kang, Ha Rin Cheong, Dong Eun Song, Sun Hee Sung, Heasoo Koo, Woon Sup Han, Jeong Kyong Lee, Tae Hun Kim, Kyu Won Chung, Min Sun Cho
BACKGROUND Regulatory T cells (Tregs) may contribute to the immunological hyporesponsiveness against hepatitis B virus (HBV), and this can result in chronic infection. Tregs suppress the T cell responses directed against HBV and they protect hepatocytes by down-regulating the immune responses that cause liver damage, but the role of Tregs has not been well characterized. METHODS Fifty four patients were selected and classified into three groups (12 were in the immune-tolerance phase, 35 were in the immune-clearance phase and 7 were in the asymptomatic virus carrier phase). We examined the frequency of CD3+, CD4+ & CD8+ T cells and forkhead box P3 (FoxP3)+ Tregs in the needle-biopsied liver tissue by performing immunohistochemistry. RESULTS The FoxP3+ Tregs were mainly located at the portal tracts. In the immune-clearance phase, the frequency of FoxP3+ Tregs was significantly increased compared to that of the immune-tolerance group and the asymptomatic carrier group. Increased FoxP3+ T cells were observed in the patients with a higher histologic inflammatory index. No correlation was observed among the numbers of FoxP3+ Tregs, the serum alanine aminotransferase level, detection of HBeAg and the HBV-DNA viral load. CONCLUSIONS FoxP3+ Tregs may play important roles in suppressing the immune response to HBV and the complete elimination of HBV.
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Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer Hanna Kang, Harin Cheong, Min Sun Cho, Heasoo Koo, Woon Sup Han, Kyung Eun Lee, Byung In Moon, Sun Hee Sung The Korean Journal of Pathology.2011; 45(1): 53. CrossRef
BACKGROUND Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. Expression of KIT protein (CD117) is an important diagnostic criterion of GIST. However, about 5% of GISTs are CD117 negative. Discovered on GIST 1 (DOG1) was introduced recently as a promising marker for GIST. We tested this new antibody in 105 GISTs tissue specimens, including 6 cases of metastatic GISTs, to determine the usefulness of DOG1 expression in the diagnosis of GISTs. METHODS We performed immunohistochemical (IHC) staining for DOG1 and CD117 on tissue microarrays that included 70 gastric GISTs, 29 small intestinal GISTs, 6 metastatic GISTs, 14 gastric leiomyomas and 16 gastric schwannomas. RESULTS DOG1 was positive in 98.1% (103/105) of GISTs and CD117 was positive in 97.1% (102/105) of GISTs. Only 1 case was negative for both markers. Two (66.7%) out of 3 GISTs tested CD117 negative were tested DOG1 positive. All leiomyomas and schwannomas were negative for both DOG1 and CD117. CONCLUSIONS DOG1 was highly expressed in GIST including CD117 negative cases. Adding DOG1 testing to the IHC panel for diagnosing GIST will help to identify GIST patients who are CD117 negative but may otherwise benefit from targeted therapy.
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Gastrointestinal tract spindle cell tumors with interstitial cells of Cajal: Prevalence excluding gastrointestinal stromal tumors So Jung Lee, Chung Su Hwang, Ahrong Kim, Kyungbin Kim, Kyung Un Choi Oncology Letters.2016; 12(2): 1287. CrossRef
BACKGROUND Cystic renal cell carcinoma has been reported to have a good prognosis. However, previous studies included cases of multilocular cystic renal cell carcinoma, which has an excellent prognosis, and renal cell carcinoma with cystic necrosis, which has an adverse prognosis. Therefore, we analyzed the prognostic influence of cystic change in clear cell renal cell carcinoma after excluding those morphological features. METHODS We identified 225 patients with clear cell renal cell carcinoma who underwent nephrectomy between 2001 and 2003. The clinicopathologic features were compared with clinical outcomes. RESULTS Cystic change in clear cell renal cell carcinoma (n = 66) was significantly associated with younger patient age (< 55), smaller tumor size (< or = 4 cm), lower pT stage (pT1, T2), M0 stage at initial diagnosis, lower tumor, node, and metastasis stage (I, II), and lower nuclear grade (1, 2). Patients with cystic change in clear cell renal cell carcinoma had significantly longer cancer-specific (p = 0.015) and progression-free survival (p = 0.004) than those without cystic change, by univariate analysis. Multivariate analysis revealed that cystic change significantly decreased the risk of cancer progression (risk ratio, 0.27; 95% confidence interval, 0.11 to 0.69). CONCLUSIONS In patients with clear cell renal cell carcinoma, cystic change is a good independent predictor for survival.
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Update on MRI of Cystic Renal Masses Including Bosniak Version 2019 Satheesh Krishna, Nicola Schieda, Ivan Pedrosa, Nicole Hindman, Ronaldo H. Baroni, Stuart G. Silverman, Matthew S. Davenport Journal of Magnetic Resonance Imaging.2021; 54(2): 341. CrossRef
Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome Ji-Hee Kim, Kyu-Hee Hwang, Sayamaa Lkhagvadorj, Jae Hung Jung, Hyun Chul Chung, Kyu-Sang Park, In Deok Kong, Minseob Eom, Seung-Kuy Cha The Korean Journal of Physiology & Pharmacology.2016; 20(3): 297. CrossRef
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BACKGROUND The histologic classification of renal cell carcinoma (RCC) is based on the cytoarchitectural features, yet sometimes this requires correlation with the immunophenotype. Alpha-methylacyl-CoA racemase (AMACR) and claudin-7 have recently been introduced as useful markers that are frequently expressed in papillary RCC (PRCC) and chromophobe RCC (ChRCC), respectively. The aims of this study are to evaluate the expressions of AMACR and claudin-7 in RCCs and to investigate whether they are helpful for making the histological classification of RCCs. METHODS Immunohistochemistry for CD10, RCC marker, cytokeratin (CK)7, CD117, AMACR and claudin-7 was performed for 104 RCCs, and these consisted of 54 clear cell RCCs (CCRCC), 26 PRCCs and 24 ChRCCs. RESULTS For diagnosing PRCC, the sensitivity and specificity of AMACR were 92.3% and 71.8%, respectively, and using AMACR(+)/CK7(+), the specificity was increased by 23.1% to 94.9%. For diagnosing ChRCC, the sensitivity and specificity of claudin-7 were 91.7% and 78.8%, respectively, and using claudin-7(+)/AMACR(-), the specificity was significantly improved (to 96.3%). For diagnosing CCRCC, CK7(-)/claudin-7(-)/CD117(-) was the most useful immunohistochemical panel (sensitivity, 96.3%; specificity, 98%). CONCLUSIONS AMACR and claudin-7 are helpful markers for the histologic classification of RCCs, and their diagnostic utility is strengthened when they are used as an immunohistochemical panel, AMACR(+)/CK7(+) for PRCC, claudin-7(+)/AMACR(-) for ChRCC and CK7(-)/claudin-7(-)/CD117(-) for CCRCC.
BACKGROUND This study was done to obtain comprehensive data on changes in the structural components of the enteric nervous system in pediatric patients with intestinal pseudo-obstruction (IPO). We evaluated routinely processed, in formalin-fixed tissues by quantitative morphometric analysis. In addition, we used formalin-fixed tissue to explore the possibility of using previously proposed diagnostic criteria to evaluate frozen serial sections for intestinal neuronal dysplasia (IND) type B and hypoganglionosis. METHODS We analyzed data for 19 IPO cases. Morphometric analysis for quantification of ganglia and ganglion cells (GCs) was done for the myentric and the submucous plexus. In addition, we determined the presence of immature GCs and the distribution of nerve fibers and interstitial cells of Cajal (ICC). RESULTS Nine patients showed combined hypoganglionosis, IND, and decreased ICC; others showed various combinations of these. Several morphometric factors were significantly different between patient groups as well as being different than the control group. CONCLUSIONS Our pediatric IPO cases showed extensive overlapping of pathological findings. And the findings suggest the utility of using previously proposed morphometrically measured factors in multiple frozen sections as diagnostic criteria for IND type B and hypoganglionosis in formalin-fixed tissue.
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Histomorphology of enteric neurons and enteric ganglia in different layers of human fetal colon Chacchu Bhattarai, Phanindra P. Poudel, Arnab Ghosh, Sneha G. Kalthur Journal of Taibah University Medical Sciences.2022; 17(4): 556. CrossRef
Diagnostic utility of Bcl-2 immunohistochemical expression in pediatric functional bowel obstruction cases with ganglionated specimens Lobna Abd El Fattah Mohamed, Nedal Ahmed Hegazy, Faten Abd El Aziz Ghazal, Ahmed Mohy El Din Zaki, Ahmed Bassiouny Radwan, Sarah Adel Hakim Annals of Pediatric Surgery.2022;[Epub] CrossRef
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Challenges in the diagnosis of intestinal neuronal dysplasia type B: A look beyond the number of ganglion cells Simone Antunes Terra, Anderson Cesar Gonçalves, Pedro Luiz Toledo de Arruda Lourenção, Maria Aparecida Marchesan Rodrigues World Journal of Gastroenterology.2021; 27(44): 7649. CrossRef
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BACKGROUND Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, many methods for the diagnosis of GIST have been developed including molecular diagnosis. METHODS We selected 90 cases of GIST that had presented at Kyungpook National University Hospital between 1998 and 2007. Tissue microarrays were made using core areas of tumor tissues. Immunohistochemical staining for c-kit, protein kinase C-theta, and platelet-derived growth factor receptor alpha (PDGFRA) was done. Direct sequencing of hot spot exonal areas for c-kit and PDGFRA were done using extracted DNAs of all 90 paraffin block tissues. RESULTS Among the 90 cases, 83.3% (75/90) were c-kit positive, 16.6% (15/90) were c-kit negative, 93.3% (84/90) were PDGFRA positive, and 6.6% (6/90) cases were PDGFRA negative. Fifteen cases of c-kit negative GIST included 1 case of PDGFRA negative and 5 cases of PDGFRA negative GIST were ckit positive. The one case in which both c-kit and PDGFRA were negative, showed a c-kit mutation in exon 11. CONCLUSIONS Combined immunohistochemical staining of c-kit, discovered on GIST 1 (DOG1) and PDGFRA is helpful for the diagnosis of GIST. When all staining tests are negative for immunoreactivity, c-kit mutation analysis for exon 11, 9 should be done. Genotyping of kit and PDGFRA do not need to be examined initially, if it is only for the diagnosis of GIST.
BACKGROUND DNA hypermethylation is a common epigenetic finding in human cancers and is closely associated with transcriptional silencing. In the present study, we investigated the proportion of colorectal neoplasms that showed the adenoma-carcinoma progression and vimentin gene methylation. METHODS Methylation status of the vimentin gene was examined in nontumoral mucosa, adenomas, and adenocarcinomas from 45 colorectal cancer patients who had adenoma and adenocarcinoma together. Methylation status was determined by bisulfite modification and the methylation-specific polymerase chain reaction. The expression of the vimentin gene product was also examined by immunohistochemistry. RESULTS Promoter methylation of vimentin was detected in 80% (36 out of 45 cases) of adenocarcinomas, 82.2% (37 of 45) of adenomas, and 28.9% (13 of 45) of normal epithelia, and the difference between neoplastic and normal specimens was statistically significant (p < 0.001). However, no significant correlations were observed between methylation frequency and clinicopathologic variables.
Immunohistochemically, vimentin expression was not observed in either normal epithelial cells or tumor cells. Protein expression and vimentin promoter methylation were not associated. CONCLUSIONS The frequency of aberrant methylation of the vimentin gene was high in colonic adenomas and adenocarcinomas. This result suggests that the methylation status of vimentin may be clinically beneficial in screening for colorectal cancer patients and may be helpful in clarifying colorectal cancer biology.
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Epigenetic Modifications as Biomarkers of Tumor Development, Therapy Response, and Recurrence across the Cancer Care Continuum Margaret Thomas, Paola Marcato Cancers.2018; 10(4): 101. CrossRef
Aberrant promoter methylation of beta‐1,4 galactosyltransferase 1 as potential cancer‐specific biomarker of colorectal tumors Maria Luana Poeta, Emanuela Massi, Paola Parrella, Pasquale Pellegrini, Mariangela De Robertis, Massimiliano Copetti, Carla Rabitti, Giuseppe Perrone, Andrea Onetti Muda, Francesca Molinari, Elena Zanellato, Stefano Crippa, Damiano Caputo, Marco Caricato, Genes, Chromosomes and Cancer.2012; 51(12): 1133. CrossRef
BACKGROUND Apolipoprotein D (Apo D) has recently been identified as a novel tumor suppressor gene. Apo D may have a profound effect on the carcinogenesis and progression of hepatocellular carcinoma. This study was designed to evaluate the expression of Apo D in hepatocellular carcinoma and to investigate the relationship between the expression of Apo D and the clinicopathological characteristics and the patients' survival. METHODS An immunohistochemical study was performed on the tumors and tissues from 43 hepatocellular carcinoma (HCC) patients with controls to determine the expression of Apo D protein. RESULTS Our data showed that a higher expression of Apo D was seen in 10 of 43 cases (23.3%), while a lower and no expression of Apo D was observed in 28 of 43 cases (65.1%) and 5 of 43 cases (11.6%), respectively. A reduced expression of Apo D was correlated with the tumor stage (p = 0.037) and tumor size (p = 0.017). However, the patients' 5-year survival was not associated with the expression of Apo D (p = 0.903). CONCLUSIONS The results suggest that a reduced Apo D protein expression may play an important role in HCC progression as associated with the tumor stage and size, but it does not affect the survival of HCC patients.
BACKGROUND Fine needle aspiration, which is known as the most accurate and cost-effective method for diagnosis of thyroid nodule, still may result in indeterminate cases that are pauci-cellular and show minor nuclear atypia, but most cases are associated with suspicion of papillary thyroid carcinoma (PTC). A B-type Raf kinase (BRAF) mutation was found in about half of PTCs and galectin-3 was expressed by malignant tumors, helping us to differentiate malignancies from benign lesions. METHODS Cases studied included histologically 44 confirmed PTC cases and 18 benign cases previously diagnosed as suspicious of PTC using cytologic examination. Cases were analyzed for galectin-3 expression by immunohistochemical staining and BRAF mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with a new restriction enzyme. RESULTS All 44 cases of PTC and 8 of 18 benign controls expressed galectin-3. BRAF mutations were found in only 9 of the 44 PTC cases. Assessment of galectin-3 expression demonstrated high sensitivity but low specificity.
Evaluation of BRAF mutation revealed high specificity and low sensitivity. CONCLUSIONS This study suggests that the combined application of these two methods for PTC of suspicious cytology is complementary.
Paraduodenal pancreatitis (PP) is a rare, distinct form of chronic pancreatitis, and it is related to alcohol abuse in middle-aged men. A 36-year-old man with a history of chronic recurrent pancreatitis for 4 years and alcohol abuse for 15 years presented with abdominal pain. Computed tomography revealed a multilocular cystic mass 3.2 x 3 x 3 cm in size and it was located within the muscular layer of the duodenal wall. The cysts were lined by a single layer of eosinophilic cuboidal epithelial cells that stained positively for mucin (MUC)1, MUC6, cytokeratin (CK)7 and CK19 and they stained negatively for MUC2, MUC5AC and CK5/6. Mild, chronic inflammatory reaction around the cystic wall, Brunner's gland hyperplasia and several clusters of heterotopic pancreatic tissue were noted. We report here on a case of PP and we demonstrated that the pancreatitis was of pancreatic ductal cell origin according to the MUC and CK expression patterns we observed on the immunohistochemical analysis.
Enteric duplication cysts are uncommon congenital anomalies whose embryogenesis remains unknown. We report here on an isolated enteric duplication cyst, that presents as an inguinal hernia. A 21-year-old woman was admitted with a month-long history of a palpable mass in the left groin.
Radiologically, a computed tomography scan revealed a 3.5 x 2.5 cm sized cystic mass in subcutaneous layers of the left suprapubic area. Microscopically, the cystic wall resembled gut wall. The wall was composed of two distinct muscle layers with the presence of Auerbach's plexus. On examining the entire sections of the cyst wall very carefully, no epithelial lining was found on the inner surface. The submucosa was slightly fibrotic. The diagnosis was a completely isolated enteric duplication cyst.
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We report here on a case of a rare, complex bronchopulmonary foregut malformation (BPFM) that was composed of an extralobar pulmonary sequestration communicating with an esophageal duplication cyst. A 33-year-old female presented with an incidentally detected chest mass. The computed tomography revealed a 7.5 x 4.0 cm sized heterogeneous, solid and cystic lesion in the right superior mediastinum.
Surgical resection demonstrated the solid portion to be isolated lung tissue invested in its own pleura. A unilocular cyst was communicating with the bronchus of the sequestrated lung, and microscopically the cyst was lined by squamous epithelium overlying the thick layers of smooth muscle. This case is important for understanding the spectrum of BPFMs and for differentiating a mediastinal mass, especially one at the unusual location.
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