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Volume 43(6); December 2009
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Original Articles
Immunohistochemical and Molecular Characteristics of Follicular Patterned Thyroid Nodules with Incomplete Nuclear Features of Papillary Thyroid Carcinoma.
Hye Sook Min, Gheeyoung Choe, Nam Yun Cho, Gyeong Hoon Kang, Seong Hoe Park, So Yeon Park
Korean J Pathol. 2009;43(6):495-502.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.495
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  • 2 Citations
AbstractAbstract PDF
BACKGROUND
Follicular patterned thyroid nodules with incomplete nuclear features of papillary thyroid carcinoma (FTN-INPTCs) are difficult to diagnose, and their biological behavior and association with follicular variants of PTC (FVPTCs) have not yet been established. The aim of this study is to determine immunohistochemical and molecular characteristics of FTN-INPTCs. METHODS: We investigated immunohistochemical features (galectin-3, HBME-1, CK19, fibronectin-1, CITED1), BRAF V600E mutation and RASSF1A promoter methylation status in 30 FTN-INPTC cases, along with 26 FVPTCs, 21 follicular adenomas (FAs) and 14 nodular hyperplasias (NHs). RESULTS: Expression of galectin-3, HBME-1, CK19 and CITED1 was significantly higher in FTN-INPTCs than in FAs or NHs, but expression of galectin-3, CK19 and fibronectin-1 was lower in FTN-INPTCs than in FVPTCs. The BRAF V600E mutation was not detected in the benign nodules or FTN-INPTCs, whereas 57% of FVPTCs had the mutation. RASSF1A promoter methylation was higher in FTN-INPTCs than in benign nodules but there was no difference between FTN-INPTCs and FVPTCs. CONCLUSIONS: Our results represent the borderline immunohistochemical and molecular characteristics of FTN-INPTC. We conclude that FTN-INPTC is an intermediate lesion between a benign nodule and a FVPTC, and that it is pathogenetically related to FVPTC.
Transcriptional Regulation of Hepatic Stellate Cell Activation by siRNA for TGF-beta1.
Hoon Kyu Oh, Kyung Hyun Kim, Yoon Sup Keum, Chang Ho Cho, Jae Bok Park, Kwan Kyu Park
Korean J Pathol. 2009;43(6):503-508.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.503
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
The cytokine-induced activation of hepatic stellate cells (HSC) plays a major role in liver fibrosis. Quiescent HSCs undergo phenotypic transformation called "transdifferentiation" in response to viral, chemical or immune insults to the liver. The cytokine TGF-beta1 plays a key role in progressive liver fibrosis. Since small interfering RNA (siRNA) is a powerful tool for silencing gene expression post-transcriptionally, the present study aimed to determine whether synthetic TGF-beta1 siRNA down-regulates the expression of the TGF-beta1 gene in immortalized and activated rat HSCs (HSC-T6s). The study examined whether synthetic TGF-beta1 siRNA prevents rat HSCs activation and extracellular matrix (ECM) production.
METHODS
TGF-beta1 siRNA or a control (pU6) siRNA was added to HSC-T6 culture media. We then performed RT-PCR and western blot analyses for TGF-beta1 and ECM components (fibronectin, type-I collagen, and TIMP-1). RESULTS: TGF-beta1 siRNA significantly down-regulated expression of TGF-beta1 mRNA and protein and attenuated mRNA and protein expressions of type-I collagen, fibronectin, and TIMP-1, as compared to the control. CONCLUSIONS: TGF-beta1 siRNA can effectively down-regulate the expression of TGF-beta1 in rat HSC, resulting in significant inhibition of HSC activation and of ECM production. These data indicate that synthetic TGF-beta1 siRNA can be a useful treatment modality to prevent liver fibrosis.
Intron 1 Polymorphism, Mutation and the Protein Expression of Epidermal Growth Factor Receptor in Relation to the Gefitinib Sensitivity of Korean Lung Cancer Patients.
Mi Jin Kim, Kyeong Cheol Shin, Kwan Ho Lee
Korean J Pathol. 2009;43(6):509-516.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.509
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AbstractAbstract PDF
BACKGROUND
Epidermal growth factor receptor (EGFR) intron 1 polymorphism in non-small cell lung cancer (NSCLC) has been found to have therapeutic implications for the patients treated with EGFR tyrosine kinase inhibitors. However, its clinical significance as related to gefitinib responsiveness is still controversial. We examined CA repeat polymorphism in intron 1 of the EGFR gene and its relation with the EGFR gene mutation in NSCLC patients who were treated with gefitinib. METHODS: Sixty seven patients who were treated with gefitinib were analyzed for intron 1 polymorphism in the EGFR gene, the EGFR mutations and the EGFR protein expression. Two hundred twenty seven samples of NSCLC were analyzed for EGFR mutations. RESULTS: CA repeat was low in 27 patients (40.3%) and high in 40 (59.7%) patients. The response rate for gefitinib therapy was higher in the patient population with a low number of CA repeats in the EGFR gene (p=0.047) and in the patients with the mutated type of EGFR (p=0.048), though these two factors were not related. Thirty four patients (15.0%) harbored EGFR mutations. CONCLUSIONS: This study suggests that the intron 1 CA repeat polymorphism of the EGFR gene may serve as a predictor of the clinical outcome of NSCLC patients treated with gefitinib, and this without regard for EGFR mutation. Our data further supports the importance of EGFR mutations with regard to a distinct clinical profile and the prognostic implications for NSCLC patients.
Expression and Prognostic Significance of Serum Response Factor in Cholangiocarcinoma.
Shin Young Park, Kyu Yun Jang, Yo Na Kim, Hee Jin Kim, Ho Sung Park, Myoung Ja Chung, Hee Chul Yu, Baik Hwan Cho, Kyoung Ryul Kim, Woo Sung Moon
Korean J Pathol. 2009;43(6):517-522.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.517
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  • 2 Citations
AbstractAbstract PDF
BACKGROUND
Serum response factor (SRF) is a transcriptional factor that plays an important role in cell growth and differentiation for several types of cells. The expression of SRF in cholangiocarcinoma (CC) and its potential role has not been examined. The aim of this study was to determine the relationship between the expression of SRF in CC and the clinicopathological parameters, as well as patient survival.
METHODS
We analyzed the expression of SRF in 84 surgically resected cases of CC (33 cases of intrahepatic CC [ICC] and 51 cases of extrahepatic CC [ECC]) by using immunohistochemistry. RESULTS: The positive expression of SRF was detected in 48.8% of the cases of CC (42.4% in ICC, 52.9% in ECC). SRF was predominantly expressed in the CC cells with intense labeling in the nucleus. A SRF expression was significantly associated with the cell proliferation rate (Ki-67 labeling index, p=0.046) and poor patient survival (p=0.002). The tumor differentiation (p=0.038), the T category (p<0.001), lymph node and distant metastasis (p<0.001, p=0.009) and nerve and vessel invasion (p=0.010, p=0.012) were also found to be significantly associated with a poor CC prognosis. CONCLUSIONS: These results suggest that the SRF may play a role in the tumor cell proliferation of CC, and its expression in tumor cells can provide additional prognostic information.
Expression of E-cadherin and beta-catenin is Altered at Tumor Budding Sites, Whose Number is Associated with the Progression of Colorectal Carcinoma.
Tae Jung Jang
Korean J Pathol. 2009;43(6):523-527.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.523
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  • 7 Citations
AbstractAbstract PDF
BACKGROUND
Tumor budding is present in the stroma at the invasive margin of colorectal carcinomas (CRC). The disintegration of cell adhesion molecules is closely related to this process. This study investigated the role of tumor budding in the progression of CRC, and compared the expression of beta-catenin and E-cadherin between tumor budding and tumor center to determine whether epithelial-to-mesenchymal transitions (EMTs) occur in tumor budding. METHODS: The number of tumor budding (NTB) instances was determined in 58 cases of CRC, and immunoreactivities of E-cadherin and beta-catenin were compared at the tumor center and at the tumor budding site. Immunohistochemical staining for vimentin was also done.
RESULTS
Tumor budding was seen in 52 tumors (90%). There were significant associations between NTB and cliniopathologic parameters such as tumor depth, nodal metastasis and clinical stage. Expression of cytoplasmic and nuclear beta-catenin were significantly higher at tumor budding sites than in the tumor center. In contrast, expression of membranous and cytoplasmic E-cadherin were significantly higher in the tumor center than at the tumor budding sites. Vimentin was expressed at tumor budding foci of only 2 cases (3%).
CONCLUSIONS
This study suggests that EMT occurs at tumor budding, and that NTB may be a good marker for predicting a poor prognosis in CRC.
KIT/PDGFRA Expression and Mutation in Testicular Seminoma and Ovarian Dysgerminoma.
Song Yi Choi, Kwang Sun Suh, Yong Beom Kim, Hyun Jeong Lee, Eun Sun Kim, Mee Ja Park
Korean J Pathol. 2009;43(6):528-534.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.528
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
KIT and PDGFRA are tyrosine kinase receptors. Stem cell factor/KIT-mediated signaling plays a role in normal spermatogenesis, and the alteration of KIT is important in the pathogenesis of seminomas/dysgerminomas (SD). METHODS: To determine the role of expression and mutation of the KIT and PDGFRA genes, we analyzed 16 seminoma cases, 4 spermatocytic seminoma (SS) cases and 8 dysgerminoma cases for KIT and PDGFRA expression and mutation of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) using PCR-SSCP methods. RESULTS: KIT was immunohistochemically positive in all 24 SD cases, and one of four (25%) SS cases. PDGFRA was immunohistochemically evident in 16 of the 24 (66.6%) SD cases, and two of the four (50%) SS cases. KIT expression was significantly reduced in SS compared with seminoma (p=0.0035). Four cases (14.3%) displayed mutation in KIT exon 17 or PDGFRA exon 12. Distant metastasis was present in three cases (10.7%), one of which had a nonsense mutation in KIT. CONCLUSIONS: These results indicate that KIT is expressed in the majority of SD cases, but not in most SS cases. However, there was no significant correlation between the clinicopathologic features and mutation or expression of KIT and PDGFRA.
Characterization of Histopathological Features that Differentiate Hepatitis B Virus Infection from Acute Cellular Rejection.
Dong Eun Song, Dong Hwan Jung, Shin Hwang, Bong Hee Park, Eunsil Yu
Korean J Pathol. 2009;43(6):535-541.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.535
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  • 3 Citations
AbstractAbstract PDF
BACKGROUND
Differentiation of viral hepatitis from acute cellular rejection (ACR) after liver transplantation can be difficult because of overlapping histological features. Here we investigated clinicopathologic characteristics of 311 liver allograft biopsies and searched for characteristic histopathological features that would facilitate the differential diagnosis between hepatitis B virus (HBV) infection and ACR. METHODS: A retrospective clinicopathologic examination of 311 liver allograft biopsies consisting of clinically proven ACR or HBV infection was performed. Immunohistochemical staining for HBcAg and HBsAg was done for 64 allograft biopsies showing HBV infection. RESULTS: Moderate to severe bile duct damage, diffuse centrilobular necrosis and centrilobular inflammation (p<0.000, for each) were more frequently observed in cases of ACR, whereas diffuse acidophilic bodies and spotty necrosis (p<0.000, for each) were more prevalent in cases of HBV infection. Immunopositivity for HBcAg (n=60, 93.8%) was higher than that for HBsAg (n=14, 21.9%) CONCLUSIONS: The presence of moderate to severe bile duct damage, diffuse centrilobular necrosis and centrilobular inflammation was a characteristic feature of ACR, whereas diffuse distribution of acidophilic bodies or spotty necrosis was the only characteristic feature of HBV infection. HBcAg was a more sensitive immunohistochemical marker than HBsAg for detecting HBV infection in liver allograft biopsies.
Alteration of G1/S Cell Cycle Regulatory Proteins in Carcinogenesis of Cutaneous Squamous Cell Carcinomas.
Soyoung Im, Changyoung Yoo, Ji Han Jung, Hyun Joo Choi, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee
Korean J Pathol. 2009;43(6):542-549.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.542
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
Aberration of the cell cycle regulatory proteins has been reported to contribute to the development and progression of human malignancy. We studied the expression of G1/S cell cycle regulatory proteins to investigate the carcinogenesis in cutaneous squamous cell lesions. METHODS: We evaluated the expressions of p16, pRb, cyclin D1 and Ki-67 protein by immunonohistochemistry in cases of normal skin (n=15), seborrheic keratosis (SK; n=26), actinic keratosis (AK; n=30), Bowen's disease (BD; n=37), keratoacanthoma (KA; n=23), and squamous cell carcinoma (SCC; n=22). RESULTS: The Ki-67 expression gradually increased from SK, through AK, to BD. The expression of p16 was more increased in BD than that in AK. The decreased expressions of p16 and Rb, and the increased expression of cyclin D1 were observed to a greater degree in SCC than those in BD. The expressions of cyclin D1 and Ki-67 were higher in SCC than those in KA. CONCLUSIONS: The altered expressions of p16, Rb, and cyclin D1 were considered to be related to the carcinogenesis in the cutaneous squamous cell lesions. Therefore, immunohistochemical studies of the cell cycle regulatory proteins and a combined analysis may be helpful as an adjunct to the histomorphology in the diagnosis of cutaneous squamous cell lesions.
Comparison of Liqui-PREP(TM) and Conventional Preparations in Thyroid Fine Needle Aspiration.
Eun Su Park, Eun Yoon Cho, In Gu Do, Soon Jae Kim, Jung Hee Shin, Boo Kyung Han, Young Lyun Oh
Korean J Pathol. 2009;43(6):550-556.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.550
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  • 3 Citations
AbstractAbstract PDF
BACKGROUND
Liqui-PREP(TM) (LP) is a new liquid-based cytologic preparation that produces a thin layer of cells.
METHODS
Thyroid aspirates were obtained from 189 patients and divided to prepare pairs of conventional preparation (CP) and LP slides. The CP slides were routinely diagnosed by attending staffs and classified into the six categories. LP slides were independently evaluated by three cytopathologists and classified in an identical manner. Agreements between CP and LP diagnoses were investigated and interobserver variability of thyroid aspiration cytology results obtained using the LP method was determined using kappa values. RESULTS: CP and LP slides from 155 patients (83%) were identically classified by all of three cytopathologists. Concurrences between CP and LP diagnoses for the three cytopathologists were 89% (kappa=0.78), 92% (kappa=0.87), and 85% (kappa=0.70), respectively. Interobserver agreement among the three cytopathologists for LP slides ranged from substantial to almost perfect (kappa=0.84, 0.74 and 0.84). However, a lack of interobserver agreement was found for LP slides of the undetermined category as determined by original CP-based diagnoses. Moreover, cytomorphological alterations in the benign category appeared more worrisome for LP slides.
CONCLUSIONS
An awareness of the novel cytomorphologic changes induced by the LP method is needed to avoid misinterpretations.
Cytologic Features of Diffuse Sclerosing Variant of Papillary Carcinoma: Cytohistopathologic Analysis of 16 Cases.
Ja Seung Koo, Woohee Jung, Soonwon Hong, Hyunee Yim
Korean J Pathol. 2009;43(6):557-561.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.557
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AbstractAbstract PDF
BACKGROUND
The exact preoperative diagnosis of diffuse sclerosing papillary carcinoma (DSPC) is required for aggressive surgical treatment due to its extended involvement with thyroid and neck lymph nodes. The present study investigated the cytomorphologic characteristics of DSPC and identified cytologic features for preoperative diagnosis of DSPC. METHODS: A retrospective review of cytologic and histologic features of 16 patients diagnosed with DSPC after thyroidectomy and underwent preoperative fine needle aspiration cytology (FNAC) was performed.
RESULTS
Prominent psammoma bodies were observed in 16 (100%) and 10 (62.5%) cases of histology and FNAC, respectively. Lymphocytes were observed in nine (56.2%) and four (25.0%) cases, and squamous cells were noted in seven cases (43.7%) and one case (6.2%) on histology and FNAC, respectively. Nuclear grooves and inclusions, which are characteristics of papillary carcinoma, were observed in FNAC and histology slides in all 16 cases. CONCLUSIONS: DSPC displays prominent psammoma bodies and characteristic nuclear features of papillary carcinoma such as nuclear groove and inclusion in FNAC. However, the preoperative diagnosis of DSPC using only FNAC could be difficult due to the absence of other characteristic features such as lymphocytes and metaplastic squamous cells.
Case Reports
Hepatoid Thymic Carcinoma: A Case Report.
Jeong Hyeon Lee, Hyunchul Kim, Yang Seok Chae, Nam Hee Won, Jong Sang Choi, Chul Hwan Kim
Korean J Pathol. 2009;43(6):562-565.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.562
  • 2,843 View
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AbstractAbstract PDF
We report here on a rare case of hepatoid thymic carcinoma in a 34-year-old man. The patient complained of a high fever and headache, and a 6.6cm-sized anterior mediastinal mass was found on chest computed tomography (CT). There was no hepatic mass seen on abdominal CT. The resected mass consisted of epithelioid cells with abundant eosinophilic cytoplasm, pleomorphic vesicular nuclei and prominent nucleoli, and the mass was surrounded by thymic tissue. The tumor cells were immunopositive for cytokeratin 7, alpha-1-antitrypsin, hepatocyte staining, and epithelial membrane antigen, but they were negative for CD5, alpha-fetoprotein (AFP) and placental alkaline phosphatase, and this all led to a diagnosis of hepatoid thymic carcinoma rather than hepatoid yolk sac tumor. This entity should be included in the differential diagnosis of epithelioid thymic tumors.
A Case of Pancreatitis Presenting with Pancreatic Panniculitis: A Case Report.
Seong Hyun Kim, Sun Hee Chang, Hai Jin Park
Korean J Pathol. 2009;43(6):566-569.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.566
  • 2,868 View
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AbstractAbstract PDF
Pancreatic panniculitis is a rare disease in which necrosis of fat in the panniculus and other distant foci occur in the setting of pancreatic disease. The most common pancreatic disorders associated with pancreatic panniculitis are acute and chronic pancreatitis, especially the alcohol-related types and pancreatic carcinoma. We now report a case of pancreatic panniculitis in which skin eruptions, not abdominal symptoms, were the presenting symptom. A 45-year-old man presented with multiple erythematous tender subcutaneous nodules on the shins, arthralgia of both ankles and swelling of the left foot. He was diagnosed as having pancreatitis 15 months ago. Histopathologic findings of a skin biopsy showed focal fat necrosis with anucleated "ghost-like" fat cells with a thick shadowy wall. Laboratory evaluation revealed an increase in serum amylase and lipase. We diagnosed this patient's problem as pancreatic panniculitis associated with a relapse of pancreatitis.
Ovarian Endometrioid Adenocarcinoma with a Yolk Sac Tumor Component.
Dong Hae Chung, Sanghui Park, Hee Eun Kyung, Na Rae Kim, Seung Yeon Ha, Soyi Lim, Hyun Yee Cho
Korean J Pathol. 2009;43(6):570-574.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.570
  • 2,543 View
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AbstractAbstract PDF
Ovarian endometrioid adenocarcinoma (EAC) with a yolk sac tumor (YST) component is extremely rare. Only twelve cases have been reported in the English literature. We report here two additional cases of this rare tumor. The YST component showed classic microscopic features, and immunohistochemically stained positive for alpha-fetoprotein (AFP), but negative for cytokeratin 7 (CK7), epithelial membrane antigen (EMA), estrogen receptor (ER) and progesterone receptor (PR). The EAC appeared to blend into the YST in several areas and immunohistochemically stained positive for CK7, EMA, ER, and PR, but negative for AFP.
Myopathy due to Chronic Clevudine Therapy: A Case Report.
Jee Young Kim, Young Shin Yoon, Kee Duk Park, Heasoo Koo
Korean J Pathol. 2009;43(6):575-579.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.575
  • 2,581 View
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  • 2 Citations
AbstractAbstract PDF
A 40-year-old man with chronic hepatitis B complained of progressive weakness of the proximal muscles and edema of both legs. He had been receiving long-term clevudine (nucleoside analogue reverse transcriptase inhibitor, NRTI) therapy for his hepatitis. The serum creatine kinase level was increased on the laboratory tests. His electromyography showed a generalized myopathic process. The muscle biopsy showed numerous ragged-red fibers, degenerating myofibers with variable sized cytoplasmic bodies, the prominence of type 1 fibers with type 2 fiber atrophy and an endomysial mononuclear cell infiltration. The electron microscopic examination revealed necrotic myofibers, including extremely dysmorphic mitochondria with extensive loss, blunting and focal clumping of the cristae and concentric cristae. Although clevudine is known to be a less cytotoxic agent among the various NRTIs, careful clinical attention should be paid to the patients who are receiving long-term clevudine therapy for the occurrence of myopathy.
Spindle Cell/Pleomorphic Lipoma of the Oropharynx.
Mi Jin Gu, Kyung Rak Sohn, Jun Ho Park
Korean J Pathol. 2009;43(6):580-582.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.580
  • 2,685 View
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  • 3 Citations
AbstractAbstract PDF
We report a rare case of spindle cell/pleomorphic lipoma of the oropharynx. A 45-year-old woman presented with a 9-month history of a lump in 2001. A well demarcated polypoid, rubbery mass was found in the left vallecula and was surgically removed. The mass was diagnosed as a spindle cell lipoma. She revisited with the same complaint in 2008. Examination revealed another polypoid mass at the left aryepiglottic fold, near the previous excision site. The excised mass histologically consisted of mature fat cells, numerous bizarre giant cells, and bland spindle cells, features of a typical pleomorphic lipoma. This is the first case of recurrent oropharyngeal spindle cell/pleomorphic lipoma, showing histologic changes during the recurrence. Complete removal and follow-up are necessary for the treatment of this uncommon neoplasm.

JPTM : Journal of Pathology and Translational Medicine