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Volume 46(6); December 2012
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Original Articles
Expression of c-Met Is Different along the Location and Associated with Lymph Node Metastasis of Head and Neck Carcinoma
Ji-Young Choe, Ji Yun Yun, Soo-Jeong Nam, Ji Eun Kim
Korean J Pathol. 2012;46(6):515-522.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.515
  • 5,547 View
  • 40 Download
  • 16 Citations
AbstractAbstract PDF
Background

Activation of the c-Met pathway is involved in cancer progression and the prognosis. We aimed to identify any association of c-Met protein expression with a number of clinicopathologic variables including infection of human papillomavirus and Epstein-Barr virus (EBV) in head and neck carcinomas (HNCa).

Methods

Eighty-two cases were enrolled in this study. Expression of c-Met and p16 was investigated immunohistochemically. EBV was detected by in situ hybridization and amplification of the c-Met gene by fluorescence in situ hybridization.

Results

The c-Met protein was expressed in 41.5% (34/82), and gene amplification was found in 1.4% (1/71). High expression of c-Met was associated with the primary location of the tumor; the hypopharynx showed the highest expression, followed by the oral cavity, larynx, and nasal cavity. Squamous cell carcinoma expressed c-Met more frequently than undifferentiated carcinoma. Also, p16 immunoreactivity or EBV infection was associated with the tumor location and well-differentiated histologic type, but were not linked to c-Met expression. The patients with positive c-Met expression showed frequent lymph node metastasis.

Conclusions

Activation of the c-Met pathway might be involved in a subset of HNCa. Cases showing positive c-Met expression should be carefully monitored because of the high probability of lymph node metastasis.

Expression of SIRT1 and DBC1 in Gastric Adenocarcinoma
Youngran Kang, Woon Yong Jung, Hyunjoo Lee, Eunjung Lee, Aeree Kim, Baek-hui Kim
Korean J Pathol. 2012;46(6):523-531.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.523
  • 7,148 View
  • 43 Download
  • 26 Citations
AbstractAbstract PDF
Background

Sirtuin 1 (SIRT1) and deleted in breast cancer 1 (DBC1) are known as tumor suppressor or promoter genes. This may be due to their diverse functions and interaction with other proteins. Gastric adenocarcinoma is one of the most common malignancies, but little is known about its carcinogenesis. Therefore, we investigated the association of immunohistochemical expression of SIRT1, DBC1, p53, and β-catenin and their variable clinicopathological characteristics.

Methods

We obtained samples from 452 patients who underwent gastrectomy. Tissue microarray blocks were constructed and immonohistochemical staining was performed.

Results

Expression of DBC1 and SIRT1 was associated with lower histologic grade, intestinal type of Lauren classification, and lower pT (p<0.001) and pN stage (DBC1, p=0.002; SIRT1, p<0.001). Association between absence of lymphatic invasion, and SIRT1 (p=0.001) and DBC1 (p=0.004) was observed. Cytoplasmic β-catenin expression was associated with lower histologic grade, pT, pN, tumor-node-metastasis (TNM) stage, DBC1 (p<0.001), and SIRT1 (p=0.001). Expression of SIRT1 and DBC1 was not associated with p53 (p=0.063 and p=0.060). DBC1 was an independent good prognostic factor in multivariate analysis (p=0.012).

Conclusions

SIRC1 and DBC1 can be considered to be good prognostic factors in gastric adenocarcinoma.

Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers
Kyungbin Kim, Won Young Park, Jee Yeon Kim, Mee Young Sol, Dong Hun Shin, Do Youn Park, Chang Hun Lee, Jeong Hee Lee, Kyung Un Choi
Korean J Pathol. 2012;46(6):532-540.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.532
  • 7,229 View
  • 36 Download
  • 11 Citations
AbstractAbstract PDF
Background

Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis.

Methods

Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC).

Results

CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers.

Conclusions

The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy.

Clear Cell Papillary Renal Cell Carcinoma: A Report of 15 Cases Including Three Cases of Concurrent Other-Type Renal Cell Carcinomas
Jeong Hwan Park, Cheol Lee, Ja Hee Suh, Kyung Chul Moon
Korean J Pathol. 2012;46(6):541-547.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.541
  • 6,176 View
  • 53 Download
  • 20 Citations
AbstractAbstract PDF
Background

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently established subtype of renal epithelial tumor. The aim of this study was to identify the diagnostic criteria of CCPRCC with an emphasis on immunohistochemical studies, and to report three cases with concurrent other-type renal cell carcinoma (RCC).

Methods

A total of 515 RCC patients that consecutively underwent surgical resection at Seoul National University Hospital from 1 January 2010 to 31 December 2011 were screened. Each case was reviewed based on the histologic features and was evaluated immunohistochemically.

Results

A total of 15 CCPRCCs were identified, which composed 2.9% of the total RCCs. The mean age was 52 years, and the average tumor size was 1.65 cm. All 15 cases showed low nuclear grade, no lymph node metastasis and no distant metastasis. The CCPRCCs showed variable architectural patterns including cystic, trabecular, papillary, and acinar. All of the cases showed moderate to intense immunoreactivity for cytokeratin 7 (CK7). CD10 was negative or showed focal weak positivity. Three cases had concurrent other-type RCC, including a clear cell RCC and an acquired cystic disease-associated RCC.

Conclusions

The strong CK7 and negative or focal weak CD10 expression will be useful for the diagnosis of CCPRCC.

The Definition of Minimal Extrathyroid Extension in Thyroid Pathology by Analyzing Sizable Intra- and Extrathyroid Blood Vessels
Hyae Min Jeon, Beom Jin Lim, Hang-Seok Chang, SoonWon Hong
Korean J Pathol. 2012;46(6):548-553.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.548
  • 7,679 View
  • 37 Download
  • 7 Citations
AbstractAbstract PDF
Background

To define the exact boundary of the intrathyroid and extrathyroid aspects of a gland when determining the extent of cancer invasion, we plan to clarify the definition of sizable vascular structures, which is one of the helpful histologic clues in determining a minimal extrathyroid extension. We hypothesized that arterial wall thicknesses in extrathyroid soft tissue would be significantly different from the arteries in the thyroid parenchyma.

Methods

Twenty cases of papillary carcinoma were selected. The numbers and wall thicknesses of the arteries and arterioles in intrathyroid and extrathyroid tissue were evaluated. The absence of nerve tissue in the thyroid gland was confirmed using the S-100 protein immunohistochemical stain.

Results

The comparison of the mean thicknesses of the total arteries between the extrathyroid and intrathyroid tissues in the retrospective study (26.88 µm vs. 15.07 µm, respectively) and the prospective study (35.24 µm vs. 16.52 µm, respectively) revealed significant differences (p=0.000). The greatest thickness of the intrathyroid arteries was 67.93 µm.

Conclusions

According to our results, the study showed that the extrathyroidal arteries were significantly thicker than the intrathyroidal arteries. We suggest that the sizable blood vessels of extrathyroidal arteries should be greater than 67.93 µm in thickness.

Methylation and Immunoexpression of p16INK4a Tumor Suppressor Gene in Primary Breast Cancer Tissue and Their Quantitative p16INK4a Hypermethylation in Plasma by Real-Time PCR
Jae Jun Lee, Eunkyung Ko, Junhun Cho, Ha Young Park, Jeong Eon Lee, Seok Jin Nam, Duk-Hwan Kim, Eun Yoon Cho
Korean J Pathol. 2012;46(6):554-561.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.554
  • 5,982 View
  • 44 Download
  • 16 Citations
AbstractAbstract PDF
Background

The p16INK4a gene methylation has been reported to be a major tumorigenic mechanism.

Methods

We evaluated the methylation status of the p16INK4a genes in 231 invasive breast cancer and 90 intraductal carcinoma specimens using a methylation-specific polymerase chain reaction and p16 protein expression using immunohistochemistry. The quantity of cell-free methylated p16INK4a DNA in the plasma samples of 200 patients with invasive breast cancer was also examined using a fluorescence-based real-time polymerase chain reaction assay.

Results

The frequencies of p16INK4a methylation in invasive and intraductal tumors were 52.8% (122/231) and 57.8% (52/90), respectively. The p16 protein was overexpressed in 145 of the 231 invasive carcinomas (62.8%) and 63 of the 90 intraductal carcinomas (70%). High p16 expression in invasive carcinomas correlated significantly with a high histologic grade, a negative estrogen receptor and progesterone receptor status, p53 immunoreactivity and high Ki-67 expression with immunohistochemistry. In addition, the methylation index of p16INK4a was significantly higher in the cancer patients than the normal controls (p<0.001).

Conclusions

High p16 immunoreactivity correlated with a loss of differentiation in breast carcinomas and high frequency of p16INK4a promoter methylation in both invasive and intraductal carcinomas, suggesting it may be involved in the pathogenesis of breast cancer.

Construction of High-Density Tissue Microarrays at Low Cost by Using Self-Made Manual Microarray Kits and Recipient Paraffin Blocks
Chang Hwan Choi, Kyu Ho Kim, Ju Young Song, Suk Jin Choi, Lucia Kim, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu
Korean J Pathol. 2012;46(6):562-568.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.562
  • 8,050 View
  • 73 Download
  • 10 Citations
AbstractAbstract PDF
Background

Advances of tissue microarray (TMA) technology have enabled simultaneous in situ analysis of biomarker expression in a large number of archived pathology specimens. However, the relatively high cost of TMA construction may hamper many researchers from using this essential tool of modern pathology research. We discuss methods for making TMA kits and recipient blocks for manual construction of high-density TMAs at low cost.

Methods

Ordinary cannula piercing needles, hypodermic needles, bone marrow biopsy needles, metallic ink cartridges of ballpoint pens, and disposable skin biopsy punches were used to construct self-made manual TMA kits. The recipient blocks were manufactured by boring holes in the conventional bare paraffin blocks. A mini electric hand drill and a microcompound table assembled on a drill stand were used to maximize the capacity of the recipient blocks.

Results

By using TMA kits made from cannula piercing needles (16- and 18-gauge), it was possible to construct TMAs with 1 mm×140 cores, 0.6 mm×320 cores, 2 mm×70 cores, 3 mm×35 cores, and 5 mm×12 cores. The capacity of the recipient blocks could be dramatically increased by drilling holes.

Conclusions

Construction of TMAs using self-made TMA kits is an inexpensive alternative to construction of TMAs using commercial devices.

Diagnostic Difficulties in Fine Needle Aspiration of Benign Salivary Glandular Lesions
Hye Jung Jo, Hyo Jung Ahn, Soojin Jung, Hye-Kyoung Yoon
Korean J Pathol. 2012;46(6):569-575.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.569
  • 5,907 View
  • 47 Download
  • 8 Citations
AbstractAbstract PDF
Background

The diagnostic accuracy of fine needle aspiration cytology (FNAC) of salivary lesions is relatively high, but cytologic interpretation might be confusing if the sample is lacking typical cytologic features.

Methods

There were 77 cases of benign salivary lesions, consisting of pleomorphic adenoma (PA) in 61 cases, Warthin's tumor (WT) in 12 cases, and other benign lesions in 4 cases. The causes of the discrepancies between the FNAC and the histologic diagnoses were evaluated.

Results

Major discrepancies were noted in 4 of the 61 PA cases, and in 1 of 12 WT cases. The causes of the major discrepancies were a mislabeled site in 1 PA and 1 WT case, and an interpretation error in 3 PA cases. Minor discrepancies were more common in the WT cases (7 of 12 cases) than in the PA cases (11 of 61 cases). The causes of the minor discrepancies were a mislabeled site in 1 PA and 1 WT case, an inadequate sample in 7 PA and 2 WT cases, a lack of typical cytomorphology in 2 PA and 2 WT cases, and an interpretation error in 1 PA and 2 WT cases.

Conclusions

To increase the diagnostic accuracy in the benign salivary lesions, recognition of both characteristic and less typical cytomorphology is needed.

Fine-Needle Aspiration Cytology of Pleomorphic Carcinomas of the Lung
Hee Seung Choi, Hyesil Seol, Il Yeong Heo, Chang Won Jung, Soo Youn Cho, Sunhoo Park, Jae Soo Koh, Seung-Sook Lee
Korean J Pathol. 2012;46(6):576-582.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.576
  • 5,891 View
  • 32 Download
  • 5 Citations
AbstractAbstract PDF
Background

Pleomorphic carcinoma (PC) is a rare pulmonary malignancy. Because of its rarity and histological heterogeneity, cytopathologists might suspect PC only rarely on the basis of its cytological specimen. In addition, cytological findings from fine needle aspiration (FNA) specimens have rarely been described. Hence, we investigated the cytological features of FNA in the cases of PC.

Methods

We reviewed 7 FNA specimens of PC. The patients had undergone surgical resection at the Korea Cancer Center Hospital between 2007 and 2011. The cytological features of PC were assessed and compared with the histopathological features of the corresponding surgical specimen. Immunocytochemical analysis with cytokeratin and vimentin was performed on the cell blocks.

Results

The tumor cells were either dispersed or arranged in loose aggregates, and generally lacked any glandular or squamous differentiation. Pleomorphic or spindle shape tumor cells were observed, and mono-, bi-, or multi-nucleated giant cells were frequently observed. The background showed necrosis and contained numerous lymphocytes and neutrophils. Immunocytochemically, the tumor cells were positive for cytokeratin and vimentin.

Conclusions

PC displays characteristic cytological features. It might therefore be possible to make an accurate diagnosis of PC by assessing the degree of nuclear atypia.

Case Reports
Rosai-Dorfman Disease: Report of a Case Associated with IgG4-Related Sclerotic Lesions
Bong-Hee Park, Da Hye Son, Myung-Hwan Kim, Tae Sun Shim, Hee Jin Lee, Jooryung Huh
Korean J Pathol. 2012;46(6):583-586.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.583
  • 5,977 View
  • 48 Download
  • 5 Citations
AbstractAbstract PDF

We describe a rare case of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) associated with a six-year history of autoimmune pancreatitis, which was controlled by steroid treatment. The patient presented with multiple, cervical and thoracic lymphadenopathy and abnormal, nodular opacities in the lung. Histologically, Rosai-Dorfman disease with numerous IgG4-positive cells was identified in a subcutaneous lymph node in the patient's left forearm. The patient recovered uneventfully with steroid treatment.

Adenolipoma of the Skin Arising at Neck Region
Hyun Seung Lee, Yoon Sang Song
Korean J Pathol. 2012;46(6):587-589.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.587
  • 6,758 View
  • 43 Download
  • 1 Citations
AbstractAbstract PDF

We report here a case of adenolipoma of the skin, an unusual variant of lipoma, arising on the neck. A 56-year-old man visited our hospital due to an anterior neck mass. An excisional biopsy was performed. The mass revealed a tan-yellow soft cut surface. We could not find any difference from other lipoma on gross inspection. Microscopically, the mass showed proliferation of mature adipocytes admixed with several eccrine units. The eccrine units were demonstrated by periodic acid-Schiff-positive granules in the secretory portions and by positivity of smooth muscle actin in the myoepithelial cells surrounding the eccrine glands. The tumor was completely excised, and the patient has been followed up without any evidence of recurrence so far.

Multiple Jejunal Myeloid Sarcomas Presenting with Intestinal Obstruction in a Non-leukemic Patient: A Case Report with Ultrastructural Observations
Na Rae Kim, Woon Kee Lee, Jong In Lee, Hyun Yee Cho
Korean J Pathol. 2012;46(6):590-594.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.590
  • 5,295 View
  • 57 Download
  • 3 Citations
AbstractAbstract PDF

Myeloid sarcoma is a rare extramedullary myeloid tumor, which is frequently misdiagnosed when no evidence of leukemia is initially observed. Here, we report on a peculiar case of a 49-year-old man afflicted with multiple masses in the jejunum, the superior mesentery, and the serosa of the transverse colon, without leukemic manifestation. The tumor was composed of undifferentiated small round cells containing eosinophilic cytoplasm, which were negative for myeloperoxidase, nonspecific esterase, lysozyme, terminal deoxynucleotidyl transferase, leukocyte common antigen, CD3, CD4, CD15, CD20, CD30, CD43, CD56, CD68/PG-M1, CD79a, human melanoma black-45, c-kit, and CD34 with positivity only for CD68/KP1, CD99, and vimentin. Under electron microscopy, those cells had abundant membrane-bound cytoplasmic granules that measured 200 to 300 nm in diameter, which were consistent with granulocytic azurophilic granules. The tumor was finally diagnosed as a myeloid sarcoma. The presence of non-leukemic myeloid sarcomas showing immunonegativity for conventional myeloid-leukemic markers necessitated a diagnosis by ultrastructural observation.

Novel Mutation in PRKAR1A in Carney Complex
Ko Un Park, Hyun-Sook Kim, Seung Kwan Lee, Woon-Won Jung, Yong-Koo Park
Korean J Pathol. 2012;46(6):595-600.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.595
  • 8,517 View
  • 51 Download
  • 2 Citations
AbstractAbstract PDF

A case of Carney complex in a Korean patient is presented. The patient had the characteristics of Carney complex including skin lesions, positive family history, and multiple myxomas including a superficial angiomyxoma in the perianal area. An extensive genetic analysis revealed a novel mutation in the protein kinase A type I-a regulatory subunit (PRKAR1A) gene, but not in the phosphodiesterase type 11A (PDE11A) gene. This is the first case wherein extensive genetic studies were performed in a patient with Carney complex in Korea.

Pulmonary Calciphylaxis Associated with Acute Respiratory and Renal Failure Due to Cryptogenic Hypercalcemia: An Autopsy Case Report
Na Rae Kim, Jin Won Seo, Young Hwan Lim, Hyoung Suk Ham, Wooseong Huh, Joungho Han
Korean J Pathol. 2012;46(6):601-605.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.601
  • 6,449 View
  • 35 Download
  • 5 Citations
AbstractAbstract PDF

Metastatic calcification is rare; it is found during autopsy in patients who underwent hemodialysis. Diffuse calcium precipitation of small and medium-sized cutaneous vessels, known as calciphylaxis, can result in progressive tissue necrosis secondary to vascular calcification. This condition most commonly involves the skin; however, a rare occurrence of visceral calciphylaxis has been reported. Here we report on an autopsy case. Despite a thorough evaluation, and even performing an autopsy, the underlying cause of acute-onset hypercalcemia, resulting in the production of pulmonary calciphylaxis and metastatic renal calcification associated with acute respiratory and renal failure, could not be determined. Metastatic calcification often lacks specific symptoms, and the degree of calcification is a marker of the severity and chronicity of the disease. This unusual autopsy case emphasizes the importance of rapidly progressing visceral calciphylaxis, as well as its early detection.

Cervical Lymphadenopathy Mimicking Angioimmunoblastic T-Cell Lymphoma after Dapsone-Induced Hypersensitivity Syndrome
Min Young Rim, Junshik Hong, Inku Yo, Hyeonsu Park, Dong Hae Chung, Jeong Yeal Ahn, Sanghui Park, Jinny Park, Yun Soo Kim, Jae Hoon Lee
Korean J Pathol. 2012;46(6):606-610.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.606
  • 6,912 View
  • 55 Download
  • 5 Citations
AbstractAbstract PDF

A 36-year-old woman presented with erythematous confluent macules on her whole body with fever and chills associated with jaundice after 8 months of dapsone therapy. Her symptoms had developed progressively, and a physical examination revealed bilateral cervical lymphadenopathy and splenomegaly. Excisional biopsy of a cervical lymph node showed effacement of the normal architecture with atypical lymphoid hyperplasia and proliferation of high endothelial venules compatible with angioimmunoblastic T-cell lymphoma. However, it was assumed that the cervical lymphadenopathy was a clinical manifestation of a systemic hypersensitivity reaction because her clinical course was reminiscent of dapsone-induced hypersensitivity syndrome. A liver biopsy revealed drug-induced hepatitis with no evidence of lymphomatous involvement. Intravenous glucocorticoid was immediately initiated and her symptoms and clinical disease dramatically improved. The authors present an unusual case of cervical lymphadenopathy mimicking angioimmunoblastic T-cell lymphoma as an adverse reaction to dapsone.


JPTM : Journal of Pathology and Translational Medicine