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Volume 47(1); February 2013
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Review
Radiotherapy Response in Microsatellite Instability Related Rectal Cancer
Joo-Shik Shin, Thein Ga Tut, Tao Yang, C. Soon Lee
Korean J Pathol. 2013;47(1):1-8.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.1
  • 8,566 View
  • 72 Download
  • 24 Citations
AbstractAbstract PDF

Preoperative radiotherapy may improve the resectability and subsequent local control of rectal cancers. However, the extent of radiation induced regression in these tumours varies widely between individuals. To date no reliable predictive marker of radiation sensitivity in rectal cancer has been identified. At the cellular level, radiation injury initiates a complex molecular network of DNA damage response (DDR) pathways that leads to cell cycle arrest, attempts at re-constituting the damaged DNA and should this fail, then apoptosis. This review presents the details which suggest the roles of DNA mismatch repair proteins, the lack of which define a distinct subset of colorectal cancers with microsatellite instability (MSI), in the DDR pathways. Hence routine assessment of the MSI status in rectal cancers may potentially serve as a predictor of radiotherapy response, thereby improving patient stratification in the administration of this otherwise toxic treatment.

Original Articles
CHD1L Is a Marker for Poor Prognosis of Hepatocellular Carcinoma after Surgical Resection
Jiyeon Hyeon, Soomin Ahn, Cheol-Keun Park
Korean J Pathol. 2013;47(1):9-15.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.9
  • 6,117 View
  • 50 Download
  • 19 Citations
AbstractAbstract PDF
Background

The gene for chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) was recently identified as a target oncogene within the 1q21 amplicon, which occurs in 46% to 86% of primary hepatocellular carcinoma (HCC) cases. However, the prognostic significance of CHD1L in HCC remains uncertain. In this study, we investigated the roles of CHD1L in the prognosis of HCC.

Methods

We investigated the expressions of CHD1L in tumor tissue microarrays of 281 primary HCC patients who underwent surgical resection using immunohistochemistry. Prognostic factors of HCC were examined by univariate and multivariate analyses. The median follow-up period was 75.6 months.

Results

CHD1L expression was observed in 48 of the 281 HCCs (17.1%). CHD1L expression was associated with a younger age (p=0.033), higher Edmondson grade (p=0.019), microvascular invasion (p<0.001), major portal vein invasion (p=0.037), higher American Joint Committee on Cancer T stage (p=0.001), lower albumin level (p=0.047), and higher α-fetoprotein level (p=0.002). Multivariate analyses revealed that CHD1L expression (p=0.027), Edmondson grade III (p=0.034), and higher Barcelona Clinic Liver Cancer stage (p<0.001) were independent predictors of shorter disease-free survival.

Conclusions

CHD1L expression might be a prognostic marker of shorter disease-free survival in HCC patients after surgical resection.

Morphologic Analysis of Pulmonary Neuroendocrine Tumors
Seung Seok Lee, Myunghee Kang, Seung Yeon Ha, Jungsuk An, Mee Sook Roh, Chang Won Ha, Jungho Han
Korean J Pathol. 2013;47(1):16-20.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.16
  • 5,102 View
  • 33 Download
  • 2 Citations
AbstractAbstract PDF
Background

Few studies on how to diagnose pulmonary neuroendocrine tumors through morphometric analysis have been reported. In this study, we measured and analyzed the characteristic parameters of pulmonary neuroendocrine tumors using an image analyzer to aid in diagnosis.

Methods

Sixteen cases of typical carcinoid tumor, 5 cases of atypical carcinoid tumor, 15 cases of small cell carcinoma, and 51 cases of large cell neuroendocrine carcinoma were analyzed. Using an image analyzer, we measured the nuclear area, perimeter, and the major and minor axes.

Results

The mean nuclear area was 0.318±0.101 µm2 in typical carcinoid tumors, 0.326±0.119 µm2 in atypical carcinoid tumors, 0.314±0.107 µm2 in small cell carcinomas, and 0.446±0.145 µm2 in large cell neuroendocrine carcinomas. The mean nuclear circumference was 2.268±0.600 µm in typical carcinoid tumors, 2.408±0.680 µm in atypical carcinoid tumors, 2.158±0.438 µm in small cell carcinomas, and 3.247±1.276 µm in large cell neuroendocrine carcinomas. All parameters were useful in distinguishing large cell neuroendocrine carcinoma from other tumors (p=0.001) and in particular, nuclear circumference was the most effective (p=0.001).

Conclusions

Pulmonary neuroendocrine tumors showed nuclear morphology differences by subtype. Therefore, evaluation of quantitative nuclear parameters improves the accuracy and reliability of diagnosis.

Histopathological Causes of Late Liver Allograft Dysfunction: Analysis at a Single Institution
Eun Shin, Ji Hoon Kim, Eunsil Yu
Korean J Pathol. 2013;47(1):21-27.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.21
  • 5,881 View
  • 52 Download
  • 2 Citations
AbstractAbstract PDF
Background

We summarize our experience in the pathological diagnosis of late complications of liver transplantation (LT) to better understand the causes of late allograft dysfunction in a population mostly composed of patients with hepatitis B virus (HBV) infection.

Methods

We reviewed 361 post-transplant liver biopsies from 174 patients who underwent LT and first presented with liver function abnormalities 3 months post-procedure. The underlying diseases included HBV-associated liver disease (77%), toxic or alcoholic liver disease (10.3%), hepatitis C virus (HCV)-associated liver disease (8.6%), primary biliary cirrhosis (1.2%), primary sclerosing cholangitis (1.2%), and metabolic disease (1.7%).

Results

The three most common late complications were acute rejection (32.5%), recurrent disease (19.1%), and biliary complication (17.1%). Patients who underwent LT for HBV infection or for drug- or alcohol-related liver disease had a lower incidence of recurring disease than those who underwent transplantation for HCV infection. During post-transplantation months 3-12, acute rejection was the most common cause of allograft dysfunction and recurring disease was the leading cause for allograft dysfunction (p=0.039). The two primary causes of late allograft dysfunction have overlapping histological features, although acute rejection more frequently showed bile duct damage and vascular endothelialitis than recurring HBV infection, and recurring HBV infection had more frequent lobular activity and piecemeal necrosis.

Conclusions

The causes of late liver allograft dysfunction are closely associated with the original liver diseases and the period after LT. Careful attention is required for differential diagnosis between acute rejection and recurrent HBV.

Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes
Joo-Yeun Kim, Na Ri Shin, Ahrong Kim, Hyun-Jeong Lee, Won-young Park, Jee-Yeon Kim, Chang-Hun Lee, Gi-Young Huh, Do Youn Park
Korean J Pathol. 2013;47(1):28-35.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.28
  • 7,274 View
  • 84 Download
  • 52 Citations
AbstractAbstract PDF
Background

Gastric cancers with microsatellite instabilities (MSI) have been reported to be associated with favorable prognosis. However, the significance of the effect of MSI on the clinicopathological features, as well as its association with mucin phenotype, remains unclear.

Methods

MSI status was assessed in 414 cases of gastric cancer using polymerase chain reaction analysis of five microsatellite loci, as recommended by National Cancer Institution criteria. The expression of mucins (MUC5AC, MUC6, MUC2, and CD10) was assessed.

Results

Out of 414 total cases of gastric cancer, 380 (91.7%), 11 (2.7%), and 23 (5.6%) were microsatellite stable (MSS), low-level MSI (MSI-L), and high-level MSI (MSI-H), respectively. Compared to MSS/MSI-L, MSI-H gastric cancers were associated with older age (p=0.010), tumor size (p=0.014), excavated gross (p=0.042), intestinal type (p=0.028), aggressive behaviors (increase of T stage [p=0.009]), perineural invasion [p=0.022], and lymphovascular emboli [p=0.027]). MSI-H gastric cancers were associated with tumor necrosis (p=0.041), tumor-infiltrating lymphocytes (≥2/high power field, p<0.001), expanding growth patterns (p=0.038), gastric predominant mucin phenotypes (p=0.028), and MUC6 expression (p=0.016). Tumor necrosis (≥10% of mass, p=0.031), tumor-infiltrating lymphocytes (p<0.001), intestinal type (p=0.014), and gastric mucin phenotypes (p=0.020) could represent independent features associated with MSI-H gastric cancers. MSI-H intestinal type gastric cancers had a tendency for poor prognosis in univariate analysis (p=0.054) but no association in Cox multivariate analysis (p=0.197).

Conclusions

Our data suggest that MSI-H gastric cancers exhibit distinct aggressive biologic behaviors and a gastric mucin phenotype. This contradicts previous reports that describe MSI-H gastric cancer as being associated with favorable prognosis.

Finding and Characterizing Mammary Analogue Secretory Carcinoma of the Salivary Gland
Min Jung Jung, Joon Seon Song, Sang Yoon Kim, Soon Yuhl Nam, Jong-Lyel Roh, Seung-Ho Choi, Sung-Bae Kim, Kyung-Ja Cho
Korean J Pathol. 2013;47(1):36-43.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.36
  • 10,737 View
  • 87 Download
  • 63 Citations
AbstractAbstract PDF
Background

A new tumor entity of the salivary glands, mammary analogue secretory carcinoma (MASC) with ETV6-NTRK3 translocation, has recently been proposed. MASC was originally diagnosed as adenocarcinoma, not otherwise specified (ANOS), or acinic cell carcinoma (AciCC) by the current World Health Organization classification. We aimed to identify MASC cases by molecular tests, and to characterize their clinical, histological, and immunohistochemical features.

Methods

Thirty cases of MASC candidates were selected after review of 196 salivary gland tumors, and subjected to break-apart ETV6 fluorescence in situ hybridization (FISH), and immunohistochemical study for S100 protein, gross cystic disease fluid protein 15, DOG1, estrogen receptor, and progesterone receptor.

Results

Valid FISH results were obtained in 23 cases, and 13 positive cases were retrieved. MASCs were histologically varied, and the most frequent features observed in 10 cases were low-grade papillary/cystic/glandular patterns, intraluminal secretory materials, ovoid/wrinkled nuclei, and relatively abundant granular eosinophilic cytoplasms, corresponding to papillary-cystic or follicular types of AciCC. All cases showed diffuse immunopositivity for S100 protein. Three cases developed recurrences, but all patients remained alive.

Conclusions

MASC could be a molecularly well-defined salivary gland neoplasm, encompassing some portions of AciCC and ANOS, but its histological spectrum and clinical implication require further investigation.

Alteration of the E-Cadherin/β-Catenin Complex Is an Independent Poor Prognostic Factor in Lung Adenocarcinoma
Hyojin Kim, Seol Bong Yoo, Pingli Sun, Yan Jin, Sanghoon Jheon, Choon Taek Lee, Jin-Haeng Chung
Korean J Pathol. 2013;47(1):44-51.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.44
  • 8,848 View
  • 35 Download
  • 35 Citations
AbstractAbstract PDF
Background

Epithelial-mesenchymal transition (EMT) is an important step in the invasion and progression of cancer and in the development of chemoresistance by cancer cells.

Methods

To address the clinical significance of the EMT pathway in lung adenocarcinoma and the association of the pathway with histological subtype, we examined 193 surgically resected lung adenocarcinoma samples for the expression of representative EMT-related proteins (E-cadherin, β-catenin, and vimentin) by immunohistochemistry. Histological subtypes were classified according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. The results for EMT-related protein expression were analyzed for correlation with clinicopathological features and with survival.

Results

The loss of E-cadherin expression and aberrant β-catenin expression were significantly associated with larger tumor size, pleural invasion, lymphatic/vascular invasion, and advanced pathological stage (p<0.05). The alteration of the E-cadherin/β-catenin complex was least frequently observed in the lepidic-predominant group, but these associations were not statistically significant. In the multivariate analysis, altered E-cadherin/β-catenin complex expression was found to be an independent poor prognostic factor (p=0.017; hazard ratio, 1.926; 95% confidence interval, 1.119 to 3.314).

Conclusions

The alteration of the expression of the E-cadherin/β-catenin complex was associated with aggressive tumor behavior in lung adenocarcinoma.

Comparison of Direct Sequencing, PNA Clamping-Real Time Polymerase Chain Reaction, and Pyrosequencing Methods for the Detection of EGFR Mutations in Non-small Cell Lung Carcinoma and the Correlation with Clinical Responses to EGFR Tyrosin
Hyun Ju Lee, Xianhua Xu, Hyojin Kim, Yan Jin, Pingli Sun, Ji Eun Kim, Jin-Haeng Chung
Korean J Pathol. 2013;47(1):52-60.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.52
  • 9,166 View
  • 65 Download
  • 31 Citations
AbstractAbstract PDF
Background

The aims of this study were to evaluate the abilities of direct sequencing (DS), peptide nucleic acid (PNA) clamping, and pyrosequencing methods to detect epidermal growth factor receptor (EGFR) mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) samples and to correlate EGFR mutational status as determined by each method with the clinical response to EGFR tyrosine kinase inhibitors (TKIs).

Methods

Sixty-one NSCLC patients treated with EGFR TKIs were identified to investigate somatic mutations in the EGFR gene (exons 18-21).

Results

Mutations in the EGFR gene were detected in 38 of the 61 patients (62%) by DS, 35 (57%) by PNA clamping and 37 (61%) by pyrosequencing. A total of 44 mutations (72%) were found by at least one of the three methods, and the concordances among the results were relatively high (82-85%; kappa coefficient, 0.713 to 0.736). There were 15 discordant cases (25%) among the three different methods.

Conclusions

All three EGFR mutation tests had good concordance rates (over 82%) for FFPE samples. These results suggest that if the DNA quality and enrichment of tumor cells are assured, then DS, PNA clamping, and pyrosequencing are appropriate methods for the detection of EGFR mutations.

Fine Needle Aspiration Cytology of Thyroid Follicular Neoplasm: Cytohistologic Correlation and Accuracy
Changyoung Yoo, Hyun Joo Choi, Soyoung Im, Ji Han Jung, Kiouk Min, Chang Suk Kang, Young-Jin Suh
Korean J Pathol. 2013;47(1):61-66.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.61
  • 9,071 View
  • 54 Download
  • 15 Citations
AbstractAbstract PDF
Background

This study evaluated the accuracy of fine needle aspiration cytology (FNAC) in cases of follicular neoplasm (FN) on the basis of histologic diagnosis, and reviewed the cytologic findings of FN according to the FNAC.

Methods

Among the 66 cases diagnosed with thyroid FN by FNAC during the 7-year period from 2003 to 2009, 36 cases that had undergone thyroid surgery were available for review. Cytologic diagnosis was compared with the histologic diagnosis of each case.

Results

Among the 36 cases with a cytologic diagnosis of thyroid FN, histologic diagnosis was as follows: 20 follicular adenomas (55.6%), 3 Hurthle cell adenomas (8.3%), 2 follicular carcinomas (5.6%), 8 nodular goiters (22.2%), 2 papillary carcinomas (5.6%), and 1 Hashimoto's thyroiditis (2.8%), resulting in a diagnostic accuracy of FNAC for thyroid FN of 69.5%.

Conclusions

This study shows that FNAC for thyroid FN is a useful primary screening method because when FN is diagnosed by FNAC, the rate of FN histologic diagnosis is relatively high, however, adequate sampling and experience is a prerequisite for this procedure.

Case Studies
Epithelioid Trophoblastic Tumor: Clinicopathologic and Immunohistochemical Analysis of Three Cases
Woo Jung Sung, Hyeong Chan Shin, Min-Kyung Kim, Mi Jin Kim
Korean J Pathol. 2013;47(1):67-73.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.67
  • 7,649 View
  • 81 Download
  • 11 Citations
AbstractAbstract PDF

Epithelioid trophoblastic tumor is an unusual type of trophoblastic tumor. Here we report on the clinicopathologic and immunohistochemical features of three cases of epithelioid trophoblastic tumor. All three patients were of reproductive age and presented with vaginal bleeding and mild elevation of human chorionic gonadotropin (hCG). All patients underwent a hysterectomy. The tumors consisted of epithelioid intermediate trophoblastic cells that were mononucleated and eosinophilic, or showed clear cytoplasm on microscopic examination. One case presented with a focal choriocarcinoma component. Immunohistochemically, the tumors displayed diffuse positivity for cytokeratin 18, E-cadherin, epidermal growth factor receptor, and p53 and focal positivity for p63 and hCG. However, expression of α-inhibin and placental alkaline phosphatase was almost negative. Tests for human placental lactogen and epithelial membrane antigen were also negative in all cases.

Benign Triton Tumor: A Rare Entity in Head and Neck Region
Krishnappa Amita, S. Vijay Shankar, Kuchangi C. Nischal, Haleuoor B. Basavaraj
Korean J Pathol. 2013;47(1):74-76.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.74
  • 5,367 View
  • 38 Download
  • 10 Citations
AbstractAbstract PDF

Benign triton tumors (BTT) are very rare lesions composed of mature skeletal muscle and neural tissue. We report a case of a 14-year-old boy who presented with asymptomatic swelling of the chin over an 18-month duration which increased gradually to involve the left side of the lower lip. Clinically, a diagnosis of neurofibroma was made. Excisional biopsy confirmed the diagnosis of a BTT. Having an affinity for large nerve trunks like the brachial and sciatic, these tumors rarely occur in the head and neck region. When they do, they may involve the large central cranial nerve trunk and present as intracranial masses or involve the smaller peripheral nerve twigs and present as asymptomatic skin nodules, of which only four cases involving peripheral nerves are reported in the English literature. Here, we report the fifth documented case of a BTT involving the mental branch of the trigeminal nerve. A brief review of the literature is also provided.

Peripheral Primitive Neuroectodermal Tumor with Osseous Component of the Small Bowel Mesentery: A Case Study
Joon Mee Kim, Young Chae Chu, Chang Hwan Choi, Lucia Kim, Suk Jin Choi, In Suh Park, Jee Young Han, Kyung Rae Kim, Yoon-La Choi, Taeeun Kim
Korean J Pathol. 2013;47(1):77-81.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.77
  • 7,937 View
  • 41 Download
  • 6 Citations
AbstractAbstract PDF

A case of peripheral primitive neuroectodermal tumor of the small bowel mesentery with osseous component is reported. A 23-year-old man was admitted to our hospital because of acute severe abdominal pain. Abdominal computed tomography revealed a large solid and cystic, oval shaped mass, measuring 11.0×6.0 cm in the pelvic cavity. Histologically the resected lesion consisted of sheets of undifferentiated small round cells forming Homer-Wright rosettes and perivascular pseudorosettes, and showed areas of osteoid and bone formation. Immunohistochemical studies revealed that tumor cells expressed positivity against CD99 (MIC2), CD57, neuron-specific enolase, and vimentin. Fluorescence in situ hybridization study revealed Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement on chromosome 22q12. To the authors' knowledge this is the first documentation of a peripheral neuroectodermal tumor with osteoid and bone formation of the small bowel mesentery.

Brief Case Reports
Actinomycotic Brain Abscess Developed 10 Years after Head Trauma
Ki Yong Na, Ji-Hye Jang, Ji-Youn Sung, Youn Wha Kim, Yong-Koo Park
Korean J Pathol. 2013;47(1):82-85.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.82
  • 6,288 View
  • 37 Download
  • 1 Citations
PDF
Lipoma within Inverted Meckel's Diverticulum: A Case Report
Su-Mi Kim, Min-Jung Jung, Young-Ok Kim
Korean J Pathol. 2013;47(1):86-88.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.86
  • 5,071 View
  • 49 Download
  • 3 Citations
PDF
Fine Needle Aspiration Cytology of Postoperative Spindle Cell Nodule in Neck after Thyroidectomy: A Case Report
Myunghee Kang, Seung Yeon Ha, Hyun Yee Cho, Jungsuk An, Dong Hae Chung, Yoo Seung Chung
Korean J Pathol. 2013;47(1):89-91.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.89
  • 5,616 View
  • 33 Download
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JPTM : Journal of Pathology and Translational Medicine