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Volume 46(1); February 2012
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Review
CpG Island Hypermethylation in Gastric Carcinoma and Its Premalignant Lesions
Gyeong Hoon Kang
Korean J Pathol. 2012;46(1):1-9.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.1
  • 6,781 View
  • 42 Download
  • 17 Citations
AbstractAbstract PDF

Gastric cancers arise through a multistep process characterized by the progressive accumulation of molecular alterations in which genetic and epigenetic mechanisms have been implicated. Gastric cancer is one of the human malignancies in which aberrant promoter CpG island hypermethylation is frequently found. Helicobacter pylori and Epstein-Barr virus, which are known carcinogens for gastric cancer, are closely associated with enhanced hypermethylation of CpG island loci in gastric non-neoplastic epithelial cells and cancer cells, respectively. Aberrant CpG island hypermethylation occurs early in the multistep cascade of gastric carcinogenesis and tends to increase with the step-wise progression of the lesion. Approximately 400 genes that are actively expressed in normal gastric epithelial cells are estimated to be inactivated in gastric cancers as a result of promoter CpG island hypermethylation. In this review, a variety of information is summarized regarding CpG island hypermethylation in gastric cancer.

Original Articles
Clinicopathologic Features of Q Fever Patients with Acute Hepatitis
Miji Lee, Jae Jeong Jang, Yang Soo Kim, Sang-Oh Lee, Sang-Ho Choi, Sung-Han Kim, Eunsil Yu
Korean J Pathol. 2012;46(1):10-14.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.10
  • 6,943 View
  • 57 Download
  • 8 Citations
AbstractAbstract PDF
Background

Q fever caused by Coxiella burnetii presents with diverse clinical and pathological features including subclinical or cholestatic hepatitis. However, the pathological features of liver biopsies from patients with Q fever have not been well described.

Methods

Clinical features and pathological findings of liver biopsies were reviewed in seven cases of Q fever that were confirmed by serological, microbiological, or molecular tests.

Results

All cases presented with fever. Liver enzymes were mildly elevated except one case with marked hyperbilirubinemia. Characteristic fibrin ring granulomas were present in three cases, epithelioid granulomas with eosinophilic infiltration in two cases, extensive extravasated fibrins without ring configuration mimicking necrotizing granuloma in one case, and acute cholangitis without granuloma in one case. All cases were treated with antibiotics for 20 days. Six cases were completely cured, but one suffered from multiorgan failure.

Conclusions

C. burnetii infection is uncommon, but should always be considered in patients with acute hepatitis and fever. Because variable-sized circumferential or radiating fibrin deposition was a consistent feature of the present cases, Q fever can be strongly suggested by pathological features and confirmed by serological and/or molecular tests.

The Ratio of Atypical Ductal Hyperplasia Foci to Core Numbers in Needle Biopsy: A Practical Index Predicting Breast Cancer in Subsequent Excision
Jeong-Ju Lee, Hee Jin Lee, Jun Kang, Jeong-Hyeon Jo, Gyungyub Gong
Korean J Pathol. 2012;46(1):15-21.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.15
  • 8,316 View
  • 35 Download
AbstractAbstract PDF
Background

Although core needle biopsy (CNB) is considered to be the standard technique for histological diagnosis of breast lesions, it is less reliable for diagnosing atypical ductal hyperplasia (ADH). We therefore assessed the characteristics of CNB-diagnosed ADH that are more likely to be associated with more advanced lesions on subsequent surgical excision.

Methods

We retrospectively examined 239 consecutive CNBs, 127 of which were diagnosed as ADH following surgical excision, performed at Asan Medical Center between 1995 and 2010. Archival slides were analyzed for the number of cores per specimen, the number of ADH foci, and the ratio of ADH foci to number of cores (FC ratio).

Results

We found that ADH foci in 3 or more cores (p=0.003) and the presence of ADH in 3 or more foci (p=0.002) were correlated with malignancy following excision lesion. Moreover, an FC>1.1 was significantly associated with malignancy in the subsequent excision (p=0.000).

Conclusions

Including the number of ADH foci, the number of cores involved according to ADH, FC ratio, and histologic type in a pathology report of CNB may help in making clinical decisions about surgical excision.

Chemotherapy-Associated Hepatopathy in Korean Colorectal Cancer Liver Metastasis Patients: Oxaliplatin-Based Chemotherapy and Sinusoidal Injury
Soo Jeong Nam, Jai Young Cho, Hye Seung Lee, Gheeyoung Choe, Ja June Jang, Yoo-Seok Yoon, Ho-Seong Han, Haeryoung Kim
Korean J Pathol. 2012;46(1):22-29.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.22
  • 6,327 View
  • 58 Download
  • 11 Citations
AbstractAbstract PDF
Background

Although chemotherapy-related hepatic injury has been reported in colorectal cancer liver metastasis (CRLM) patients, the morphologic changes caused by chemotherapeutic agents and the effect of chemotherapy on postoperative outcome remain ill-defined. A comprehensive review of the morphologic changes in the post-chemotherapy non-neoplastic liver was performed and the clinical effect of preoperative chemotherapy in CRLM patients was analyzed.

Methods

Hematoxylin-eosin, Masson's trichrome and reticulin-stained slides from non-neoplastic livers obtained from 89 CRLM patients were analyzed, and the clinicopathologic features were correlated with the status of chemotherapy exposure.

Results

Histopathologic features of sinusoidal injury (sinusoidal dilatation, centrilobular perivenular fibrosis, parenchymal extinction lesions, small vessel obliteration, and hepatocyte plate disruption) were significantly more frequent in oxaliplatin-exposed livers (p<0.05). The extent of sinusoidal dilatation was positively correlated with increasing numbers of chemotherapy cycles (p=0.022). Abnormal preoperative liver function tests were more frequently seen (p<0.05) and postoperative total bilirubin was higher in the chemotherapy group (p=0.008). Postoperative morbidity was more common in the chemotherapy group (p=0.044).

Conclusions

Sinusoidal injury is frequently seen in oxaliplatin-treated livers, and its presence, especially when extensive, should be documented in surgical pathology practice. The recognition of sinusoidal injury may provide helpful guidelines for surgeons in deciding the extent of hepatic resection.

TNF-α and TNF-β Polymorphisms are Associated with Susceptibility to Osteoarthritis in a Korean Population
Lin Han, Joo Hyoun Song, Jung Hwan Yoon, Yong Gyu Park, Suk Woo Lee, Yoo Jin Choi, Suk Woo Nam, Jung Young Lee, Won Sang Park
Korean J Pathol. 2012;46(1):30-37.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.30
  • 8,312 View
  • 39 Download
  • 23 Citations
AbstractAbstract PDF
Background

The tumor necrosis factor (TNF) is believed to play an important role in the pathophysiology of osteoarthritis (OA). Evidence shows that genetic polymorphisms make substantial contributions to the etiology of OA.

Methods

We investigated the genotypes TNF-α and TNF-β in 301 OA patients and 291 healthy subjects as controls. We employed a polymerase chain reaction-restriction fragment length polymorphism and a polymerase chain reaction-single strand conformation polymorphism assay to identify the genotypes TNFA -G308A and TNFB +G252A, respectively.

Results

For TNFA -G308A, the percentages of genotypes GG, AG, and AA were 26.3% (79/301), 62.5% (188/301), and 11.3% (34/301) in OA patients and 88.7% (258/291), 11.3% (33/291), and 0% (0/291) in controls. For TNFB +G252A, the percentages of genotypes GG, AG, and AA were 15.3% (46/301), 41.9% (126/301), and 42.9% (129/301) in OA patients and 12% (35/291), 52.6% (153/291), and 35.4% (103/291) in controls. There were significant differences in genotypes and alleles of TNFA -308 between OA patients and controls (p<0.0001) and in alleles of TNFB +252 (p=0.0325). The risk of OA was significantly higher for carriers of the TNFA -308A allele and the TNFB +252 AA homozygote (p=0.0224).

Conclusions

The results suggest close relationships between TNFA -G308A and TNFB +G252A polymorphisms and individual susceptibility to OA in the Korean population.

Nuclear Image Analysis Study of Neuroendocrine Tumors
Meeja Park, Taehwa Baek, Jongho Baek, Hyunjin Son, Dongwook Kang, Jooheon Kim, Hyekyung Lee
Korean J Pathol. 2012;46(1):38-41.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.38
  • 5,211 View
  • 23 Download
  • 2 Citations
AbstractAbstract PDF
Background

There is a subjective disagreement about nuclear chromatin in the field of pathology. Objective values of red, green, and blue (RGB) light intensities for nuclear chromatin can be obtained through a quantitative analysis using digital images.

Methods

We examined 10 cases of well differentiated neuroendocrine tumors of the rectum, small cell lung carcinomas, and moderately differentiated squamous cell lung carcinomas respectively. For each case, we selected 30 representative cells and captured typical microscopic findings. Using an image analyzer, we determined the longest nuclear line profiles and obtained graph files and Excel data on RGB light intensities. We assessed the meaningful differences in graph files and Excel data among the three different tumors.

Results

The nucleus of hematoxylin and eosin-stained tumor cells was expressed as a combination of RGB light sources. The highest intensity was from blue, whereas the lowest intensity was from green. According to the graph files, green showed the most noticeable change in the light intensity, which is consistent with the difference in standard deviations.

Conclusions

The change in the light intensity for green has an important implication for differentiating between tumors. Specific features of the nucleus can be expressed in specific values of RGB light intensities.

Interobserver Variability in Diagnosing High-Grade Neuroendocrine Carcinoma of the Lung and Comparing It with the Morphometric Analysis
Seung Yeon Ha, Joungho Han, Wan-Seop Kim, Byung Seong Suh, Mee Sook Roh
Korean J Pathol. 2012;46(1):42-47.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.42
  • 6,394 View
  • 41 Download
  • 16 Citations
AbstractAbstract PDF
Background

Distinguishing small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is difficult with little information about interobserver variability.

Methods

One hundred twenty-nine cases of resected SCLC and LCNEC were independently evaluated by four pathologists and classified according to the 2004 World Health Organization criteria. Agreement was regarded as "unanimous" if all four pathologists agreed on the classification. The kappa statistic was calculated to measure the degree of agreement between pathologists. We also measured cell size using image analysis, and receiver-operating-characteristic curve analysis was performed to evaluate cell size in predicting the diagnosis of high-grade neuroendocrine (NE) carcinomas in 66 cases.

Results

Unanimous agreement was achieved in 55.0% of 129 cases. The kappa values ranged from 0.35 to 0.81. Morphometric analysis reaffirmed that there was a continuous spectrum of cell size from SCLC to LCNEC and showed that tumors with cells falling in the middle size range were difficult to categorize and lacked unanimous agreement.

Conclusions

Our results provide an objective explanation for considerable interobserver variability in the diagnosis of high-grade pulmonary NE carcinomas. Further studies would need to define more stringent and objective definitions of cytologic and architectural characteristics to reliably distinguish between SCLC and LCNEC.

Biologic Response to Carbonated Hydroxyapatite Associated with Orthopedic Device: Experimental Study in a Rabbit Model
Samira Jebahi, Mongi Saoudi, Riadh Badraoui, Tarek Rebai, Hassane Oudadesse, Zoubaier Ellouz, Hassib Keskese, Abdelfattah El Feki, Hafed El Feki
Korean J Pathol. 2012;46(1):48-54.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.48
  • 5,194 View
  • 39 Download
  • 6 Citations
AbstractAbstract PDF
Background

Carbonated hydroxyapatite (CHA) and related calcium phosphates have been studied for many years as implant materials due to their similarity with the mineral phase of bone. The main limitation of CHA ceramics as well as other bioactive materials is that they have poor mechanical proprieties. It is thought that the mechanical device can cause an increase in metabolic activity and bone healing. In this study we investigated the reactivity and tissue behaviour of implanted CHA biomaterial reinforced by mini external fixator.

Methods

The evaluation of biomaterial biocompatibility and osteogenesis was performed on a rabbit model over a period of 6 weeks by radiological, histological and scanning electron microscopy (SEM) coupled with energy dispersive X-ray SEM-energy-dispersive X-ray (EDX) analysis.

Results

While rabbits treated with CHA exhibited more bone formation, and fibrous tissue was observed when empty bone defects were observed. EDX analysis detected little calcium and phosphorus on the surface of the bone that was not implanted, while high content of calcium (62.7%) and phosphorus (38%) was found on the interface bone cement.

Conclusions

Bone repairing showed that the mini external fixator stimulated the ossification which was pushed when grafted by CHA. This effect may play an important role in the prevention of implant loosening.

Detection of Survivin and COX-2 in Thyroid Carcinoma: Anaplastic Carcinoma Shows Overexpression of Nuclear Survivin and Low COX-2 Expression
Young A Kim, Meesoo Chang, Young Joo Park, Ji Eun Kim
Korean J Pathol. 2012;46(1):55-60.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.55
  • 6,802 View
  • 50 Download
  • 5 Citations
AbstractAbstract PDF
Background

Overexpression of survivin, a member of the inhibitors of apoptosis protein, has been reported in various carcinomas, and its interaction with cyclooxygenase 2 (COX-2) results in accelerated tumor progression. The purpose of this study is to investigate the immunohistochemical expression of survivin and COX-2 in benign and malignant thyroid tissues and to define its association with pathologic and clinical features.

Methods

We examined expression of survivin and COX-2 by immunohistochemistry in 334 benign and malignant thyroid tissues and evaluated their clinical significance.

Results

Expression of survivin showed an increase along the spectrum of thyroid carcinoma progression; rarely positive in adenomatous goiter, moderately positive in papillary carcinoma, and strongly positive in anaplastic carcinoma (AC). Papillary microcarcinoma revealed the highest COX-2 positivity and AC demonstrated the lowest positivity among thyroid cancers. Node negative carcinomas showed higher COX-2 expression than node positive tumors. Survivin expression did not correlate with COX-2.

Conclusions

Our findings suggest that survivin overexpression may be related to the pathogenesis of AC and can be a predictor of disease progression. COX-2 may be involved in the early phase of thyroid carcinoma.

Detection of BRAFV600E Mutations in Papillary Thyroid Carcinomas by Peptide Nucleic Acid Clamp Real-Time PCR: A Comparison with Direct Sequencing
Dongjun Jeong, Yujun Jeong, Sungche Lee, Hyeran Lee, Wanju Lee, Hyungjoo Kim, Doosan Park, Soyoung Park, Wenxia Mu, Hyun-Deuk Cho, Mee-Hye Oh, Sung Soo Lee, Seung-Ha Yang, Chang-Jin Kim
Korean J Pathol. 2012;46(1):61-67.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.61
  • 8,709 View
  • 53 Download
  • 17 Citations
AbstractAbstract PDF
Background

Papillary thyroid carcinoma (PTC) of the thyroid is the most common endocrine malignancy. High prevalence of an activating point mutation of BRAF gene, BRAFV600E, has been reported in PTC. We assessed the efficiency of peptide nucleic acid clamp real-time polymerase chain reaction (PNAcqPCR) for the detection of BRAFV600E mutation in PTC in comparison with direct sequencing (DS).

Methods

A total of 265 thyroid lesions including 200 PTCs, 5 follicular carcinomas, 60 benign lesions and 10 normal thyroid tissues were tested for BRAFV600E mutation by PNAcqPCR and DS.

Results

The sensitivity and accuracy of the PNAcqPCR method were both higher than those of DS for the detection of the BRAFV600E mutation. In clinical samples, 89% of PTCs harbored the BRAFV600E mutation, whereas 5 follicular carcinomas, 50 benign lesions and 10 normal thyroid tissues lacked the mutation. The mutation was associated with aggressive clinical behaviors as extrathyroid invasion (p=0.015), lymph node metastasis (p=0.002) and multiple tumor numbers (p=0.016) with statistical significance.

Conclusions

The PNAcqPCR method is efficiently applicable for the detection of the BRAFV600E mutation in PTCs in a clinical setting.

Evaluation of Urine Cytology in Urothelial Carcinoma Patients: A Comparison of CellprepPlus® Liquid-Based Cytology and Conventional Smear
Seung-Myoung Son, Ji Hae Koo, Song-Yi Choi, Ho-Chang Lee, Yong-Moon Lee, Hyung Geun Song, Hae-Kyung Hwang, Hye-Suk Han, Seok-Joong Yun, Wun-Jae Kim, Eun-Joong Kim, Ok-Jun Lee
Korean J Pathol. 2012;46(1):68-74.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.68
  • 8,317 View
  • 68 Download
  • 9 Citations
AbstractAbstract PDF
Background

Urine cytology is an important test in the screening of urothlelial neoplasms. The conventional smear (CS) method of testing urine samples has a low sensitivity, approximately 50% result accuracy for detecting urothelial carcinomas, while liquid-based cytology (LBC) has much improved diagnostic accuracy, sensitivity, and specificity. The aim of this study was to compare the morphologic features and diagnostic efficacy of CellprepPlus® LBC with those of CS for urine cytology.

Methods

A total of 713 cases of urine specimens collected from November 2009 to September 2010 were included. All specimens were divided equally for the preparation of CellprepPlus® LBC and CS for each case.

Results

CellprepPlus® revealed more cellularity, a cleaner background and better cytomorphologic features, but it showed a less intact architectural pattern compared to that of CS. Of the 88 histologically confirmed cases, the diagnostic sensitivity for CellprepPlus® was 50% and higher than the 37.5% for CS. The specificity of both preparations was 100%.

Conclusions

The CellprepPlus® showed an improved quality of slides and provided better diagnostic accuracy, thus CellprepPlus® could be a first-line screening tool in urinary tract cytology.

Case Reports
A Soft Tissue Perineurioma and a Hybrid Tumor of Perineurioma and Schwannoma
Ji Young Park, Nam Jo Park, Sang Pyo Kim, Kun Young Kwon, Sang Sook Lee
Korean J Pathol. 2012;46(1):75-78.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.75
  • 5,939 View
  • 52 Download
  • 12 Citations
AbstractAbstract PDF

Perineuriomas are composed of differentiated perineurial cells. Perineuriomas have been recently recognized by the immunoreactivity for epithelial membrane antigen (EMA). Microscopically, perineuriomas show proliferation of spindle cells with wavy nuclei and delicate elongated bipolar cytoplasmic processes. The tumor cells are usually negative for the S-100 protein. Ultrastructurally, perineurial cells reveal slender, nontapered processes containing pinocytic vesicles and discontinuous basal lamina. Interestingly, hybrid tumors of benign peripheral nerve sheath tumor (PNST) have been recently reported by using immunohistochemical and ultrastructural investigations. Herein, we report a case of soft tissue perineurioma arising in the skin of a 56-year-old female; another case of a hybrid tumor of perineurioma and schwannoma in the posterior mediastinum occurred in a 53-year-old male, which is the first case of the hybrid PNST tumor reported in Korea.

Hyaline Vascular Castleman Disease Involving Renal Parenchyma and a Lymph Node: A Case Report
Ji Hyun Kwon, Soo Kee Min, Mi Kyung Shin, Yong Seong Lee, Young-Goo Lee, Young Hyeh Ko
Korean J Pathol. 2012;46(1):79-82.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.79
  • 6,441 View
  • 47 Download
  • 3 Citations
AbstractAbstract PDF

Castleman disease is a rare lymphoproliferative lesion that is predominantly found in the mediastinum. Retroperitoneal and pararenal localizations are very rare. We describe a 36-year-old man with a hyaline vascular type of Castleman disease involving renal parenchyma and a paraaortic lymph node. Most reported renal Castleman disease was plasma cell type with systemic symptoms. Herein, we report the first Korean case of the hyaline vascular type of Castleman disease involving the renal parenchyma and the paraaortic lymph node simultaneously.

Urachal Mucinous Tumor of Uncertain Malignant Potential: A Case Report
Jung-Woo Choi, Ju-Han Lee, Young-Sik Kim
Korean J Pathol. 2012;46(1):83-86.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.83
  • 7,422 View
  • 42 Download
  • 7 Citations
AbstractAbstract PDF

Urachal mucinous tumor of uncertain malignant potential is very rare and is characterized by a multilocular cyst showing the proliferation of atypical mucin-secreting cells without stromal invasion. As in ovarian and appendiceal borderline tumors, it represents a transitional stage of mucinous carcinogenesis in the urachus. In addition, this tumor may recur locally and develop into pseudomyxoma peritonei. Due to its scarcity and diagnostic challenges, we report a mucinous tumor of uncertain malignant potential arising in the urachus.

Mimicry of Minute Pulmonary Meningothelial-like Nodules to Metastatic Deposits in a Patient with Infiltrating Lobular Carcinoma: A Case Report and Review of the Literature
Hala Kfoury, Maria A. Arafah, Maha M. Arafah, Sami Alnassar, Waseem Hajjar
Korean J Pathol. 2012;46(1):87-91.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.87
  • 6,779 View
  • 48 Download
  • 4 Citations
AbstractAbstract PDF

Minute pulmonary meningothelial-like nodules (MPMNs) are incidentally found lesions in lung resection specimens and autopsies. MPMNs have been associated with neoplastic and non-neoplastic pulmonary conditions and occasionally with extrapulmonary diseases. We report a case of a female patient presenting with invasive lobular carcinoma of the breast and MPMNs, masquerading as metastatic deposits. We describe the morphological, immunohistochemical and ultrastructural features of MPMNs and emphasize the importance of their recognition for proper staging and treatment of patients. To our knowledge, this is the first case in the English literature describing this coexistence.


JPTM : Journal of Pathology and Translational Medicine