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Volume 45(6); December 2011
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Original Articles
Comparison of the DNA Preservation in Neutral-Buffered Formalin Fixed Paraffin-Embedded Tissue and in Non-Buffered Formalin Fixed Paraffin-Embedded Tissue.
An Na Seo, Jae Hoon Kim, Dakeun Lee, Ji Yun Jeong, Ji Young Park
Korean J Pathol. 2011;45(6):549-556.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.549
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AbstractAbstract PDF
BACKGROUND
The preservation of optimized DNA and its extraction from formalin-fixed, paraffin-embedded (FFPE) tissues are important issues. There has been some doubt over whether 10% neutral-buffered formalin is an ideal fixation solution for DNA preservation over non-buffered formalin, as conventionally recommended. In this study, the correlation between the efficiency of DNA extraction from FFPE tissues and buffered formalin was evaluated.
METHODS
Several tissues with same conditions except fixatives were fixed in four different formalin solution groups and were routinely processed as paraffin-embedding protocols. DNAs were extracted from four different FFPE tissues that were stored for over 3 months and over 9 months. The quantity and quality of the DNAs were assessed with a NanoDrop ND-1000 spectrophotometer, and the polymerase chain reaction (PCR) amplification and degradation were analyzed via microchip electrophoresis. KRAS mutation analysis and microsatellite instability (BAT25) PCR were performed with each sample.
RESULTS
The results showed no remarkable difference in the four groups.
CONCLUSIONS
The study findings demonstrate that DNA preservation is fairly unaffected by a neutral buffer where there is short formalin manufacture period and an adequate formalin fixation time before embedding in paraffin.
Type and Incidence of Soft Tissue Sarcomas in Korea: 2001-2007.
Kyung Un Choi, Hae Youn Kang, Heasoo Koo, Mi Seon Kwon, Dong Hoon Kim, Mi Jung Kim, Su Jin Kim, Young Sill Kim, Chul Hwan Kim, Yong Koo Park, Hye Rim Park, Seung Sam Paik, Jin Young Yoo, Anhi Lee, Jae Hyuk Lee, Hyekyung Lee, Kyu Yun Jang, Young Chae Chu, Joon Hyuk Choi
Korean J Pathol. 2011;45(6):557-563.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.557
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AbstractAbstract PDF
BACKGROUND
The Korean Bone and Soft Tissue Pathology Study Group of the Korean Society of Pathologists conducted a nationwide retrospective analysis of soft tissue sarcoma (STS) to provide the clinicopathologic characteristics of STS within the population of the Republic of Korea.
METHODS
The cases of STS were collected during a 7-year period (2001-2007) from 19 institutes in Korea. All cases were classified according to the histologic criteria proposed by the World Health Organization. Clinicopathologic data were reviewed.
RESULTS
Data from 722 patients (median age, 50 years) were collected. Data showed a slight male predominance. The most frequent types of STS in decreasing order were liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and synovial sarcoma. STS occurred throughout the body, although approximately half (47.8%) were located in the extremities. The majority of STS was histologically classified as high grade with a large tumor size (>5 cm). The overall survival rate for the patients was 76.3% (median follow-up time, 26 months; range, 1 to 89 months). Histologic grade, tumor size, American Joint Committee on Cancer stage, tumor site, and resection status were prognostic. Significant independent adverse prognostic factors were large tumor size (>5 cm) and tumor site other than extremities.
CONCLUSIONS
We reported the distribution and characteristics of STS in the Republic of Korea.
Neoplastic Stromal Cells of Intracranial Hemangioblastomas Disclose Pericyte-derived Mesenchymal Stromal Cells-like Phenotype.
Yong Han Jung, Jeong Kim, Bo Mi Kim, Eun Kyoung Kim, Mi Seon Kang, Soojin Jung, Young Il Yang, Shin Kwang Khang
Korean J Pathol. 2011;45(6):564-572.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.564
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AbstractAbstract PDF
BACKGROUND
Stromal cells (SCs) of hemangioblastomas (HBs) have been regarded as true neoplastic components, but their ontogeny remains unclear. Convincing evidence suggests that embryonic mesenchymal cells may be the cells of origin of HBs. The aim of the present study was to investigate the immunophenotypic characteristics of neoplastic SCs using a set of markers against endothelial cells (ECs), vascular smooth muscle cells (vSMCs), mesenchymal stromal cells (MSCs), and pericytes.
METHODS
Intracranial HBs (n=46), angiolipoma (n=9), and pyogenic granuloma (n=11) were retrieved and the immunophenotypic profile of SCs was determined by immune stainings.
RESULTS
The MIB-1 labeling index was significantly higher in SCs compared to that of ECs and vSMCs, regardless of the type of lesion. The neoplastic SCs of HBs consistently expressed both MSC and pericyte markers, but did not express markers of ECs and vSMCs. Double immunofluorescent staining demonstrated that the neoplastic SCs of HBs expressing MSC or pericyte markers directly abutted onto the ECs of capillaries/venules.
CONCLUSIONS
The results suggest that the neoplastic SCs of HBs share the immunophenotypic profile and distribution with those of pericyte-derived MSCs. Thus, HBs might originate from a distinctive population of pericyte-derived MSCs in the central nervous system.
Prognostic Implication of Programmed Death-1-Positive Tumor-infiltrating Lymphocytes in Diffuse Large B-Cell Lymphoma.
Young Sin Ko, Young Ha Oh, Chan Kum Park, Wook Youn Kim, Hye Seung Han, So Dug Lim, Tae Sook Hwang, Wan Seop Kim
Korean J Pathol. 2011;45(6):573-581.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.573
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  • 2 Citations
AbstractAbstract PDF
BACKGROUND
Programmed death-1 (PD-1) is physiologically expressed by germinal center-associated helper T-cells and has an inhibitory effect on T-cell activity.
METHODS
We examined 63 cases of diffuse large B-cell lymphoma (DLBCL) and determined the number of PD-1-positive helper T-cells in a representative tumor area after immunohistochemical staining using a monoclonal antibody against PD-1. The PD-1-positive cells were counted in 3 high-power fields (HPFs; 400x).
RESULTS
Patients were divided into 2 groups: one with a high number of PD-1-positive cells (>20/HPF, n=33) and one with a low number of PD-1-positive cells (< or =20/HPF, n=30). The former group showed decreased overall survival, but at a statistically non-significant level (p=0.073). A high number of PD-1-positive cells was more common in patients at an advanced clinical stage and with high international prognostic index score (p=0.025 and p=0.026, respectively). The number of extranodal sites also somewhat correlated with the PD-1 staining status (p=0.071). However, the number of PD-1-positive cells was not associated with patient age, serum lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance score.
CONCLUSIONS
The high number of PD-1-positive cells might be associated with an unfavorable outcome in DLBCL patients.
Detection Limit of Monoclonal B-Cells Using Multiplex PCR and Laser-Induced Fluorescence Capillary Electrophoresis.
Sung Hak Lee, Yeonsook Moon, Byunghoo Song, Hyung Nam Lee, Ahwon Lee, Eun Sun Jung, Yeong Jin Choi, Kyo Young Lee, Chang Suk Kang, Gyeongsin Park
Korean J Pathol. 2011;45(6):582-588.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.582
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AbstractAbstract PDF
BACKGROUND
The identification of monoclonality has been widely used for making diagnoses of lymphoproliferative lesions. Awareness of the sensitivity and detection limit of the technique used would be important for the data to be convincing.
METHODS
We investigated the minimum requirement of cells and sensitivity of gel electrophoresis (GE) and laser-induced fluorescence capillary electrophoresis (LFCE) for identifying IgH gene rearrangement using BIOMED-2 protocols. DNA extracted from Raji cells were diluted serially with peripheral blood mononuclear cells (PBMNCs) DNA. DNA from mixtures of diffuse large B-cell lymphoma (DLBCL) and reactive lymph nodes were also serially diluted.
RESULTS
For Raji cells, the detection limit was 62 and 16 cell-equivalents for GE and LFCE, respectively. In the condition with PBMNCs mixture, 2.5% and 1.25% of clonal cells was the minimum requirement for GE and LFCE, respectively. In 23% of DLBCL cells in tissue section, the detection limit was 120 and 12 cell-equivalents for GE and LFCE, respectively. In 3.2% of DLBCL cells, that was 1,200 and 120 cell-equivalents for GE and LFCE, respectively.
CONCLUSIONS
These results show that LFCE method is more sensitive than GE and the sensitivity of clonality detection can be influenced by the amount of admixed normal lymphoid cells.
CD44s and CD44v6 Are Predominantly Expressed in the Non-germinal Center B-Cell-like Type of Diffuse Large B-Cell Lymphomas.
Kyueng Whan Min, Young Ha Oh, Chan Kum Park, So Dug Lim, Wan Seop Kim
Korean J Pathol. 2011;45(6):589-595.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.589
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AbstractAbstract PDF
BACKGROUND
CD44 protein is known as a homing cellular adhesion molecule that is linked to diverse cellular functions such as adhesion, migration and invasion, which are all important in cancer progression and metastasis. The expression of CD44 standard and variant isoforms (CD44 standard isoform [CD44s] and CD44 splice variants containing exon v6 [CD44v6], respectively) is associated with an unfavorable clinical outcome in various neoplasms.
METHODS
Forty patients who were diagnosed with diffuse large B-cell lymphoma (DLBCL) through biopsy at Hanyang University Hospital between 1996 and 2003 were included in this study. CD44 proteins expression was analyzed by immunohistochemical staining on a tissue microarray and the correlation of CD44 with the types of DLBCL and clinical parameters, including the factors defined by the International Prognostic Index, was evaluated.
RESULTS
A high CD44s and intermediate to strong CD44v6 expression, including cytoplasmic membranous staining patterns, was present in 35% (14/40) and 25% (10/40) of DLBCL patients, respectively. High CD44s expression was correlated significantly with non-germinal center B-cell-like types (non-GCB, p=0.004) and patients with old age (p=0.041).
CONCLUSIONS
High CD44s expression may be significantly associated with the non-GCB type compared to the GCB type and may be essential to the prediction of disease outcome in tumor stage III in DLBCL patients.
Prognostic Significance of Amplification of the c-MYC Gene in Surgically Treated Stage IB-IIB Cervical Cancer.
Tae Jung Kim, Ahwon Lee, Sung Jong Lee, Won Chul Lee, Yeong Jin Choi, Kyo Young Lee, Chang Suk Kang
Korean J Pathol. 2011;45(6):596-603.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.596
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AbstractAbstract PDF
BACKGROUND
Mutations of c-MYC have been described in cervical cancer. However, association between c-MYC gene status and its prognostic significance have not been clarified.
METHODS
Tissue microarray sections from 144 patients with stage IB-IIB cervical cancer treated by radical hysterectomy were analyzed by fluorescence in situ hybridization using a region-specific probe for c-MYC and a centromere-specific probe for chromosome 8.
RESULTS
Seventy five percent (108/144) of c-MYC gain and 6.9% (10/144) of c-MYC gene amplification were observed. c-MYC gene alteration was more frequently observed in squamous cell carcinoma than adenocarcinoma or adenosquamous carcinoma and were associated with low Ki67 labeling index (p=0.013). c-MYC amplification was not associated with clinicopathologic parameters except absence of bcl2 expression (p=0.048). Survival analysis revealed that patients with c-MYC amplification were significantly associated with higher risk of disease recurrence (p=0.007) and cancer related death (p=0.020). However, c-MYC gain was not associated with unfavorable outcome. Multivariate analysis proved c-MYC amplification as independent prognostic factors of shorter disease free survival and cancer-related death (p=0.028 and p=0.025, respectively).
CONCLUSIONS
c-MYC amplification, not gain, is an independent prognostic marker for shorter disease free and cancer specific survival in cervical cancer treated by radical hysterectomy.
Foreign Body Reaction and Expression of Matrix Metalloproteinases/Tissue Inhibitor of Metalloproteinase by Injection of Mineral Fibers in Rats.
Dong Kweon Seo, Jong Im Lee, Jung Ran Kim
Korean J Pathol. 2011;45(6):604-611.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.604
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AbstractAbstract PDF
BACKGROUND
The host response to natural fibers results in granuloma formation in an effort to limit tissue destruction. Matrix metalloproteinases (MMPs) are important molecules in the inflammatory granulomatous or reparative reaction. Here, we studied the foreign body reaction that occurs following natural fibers implantation by investigating MMPs and tissue Inhibitor of MMPs (TIMPs) in an in vivo model.
METHODS
Female Sprague-Dawley rats were treated with crocidolite fiber or fibrous talc via subcutaneous and intraperitoneal injections and immunohistochemistry was conducted to confirm the expression of MMPs and TIMP-2 in tissue sections.
RESULTS
We identified that mineral fibers elicited granulomas. Fibrous talc or intraperitoneal injection resulted in larger granulomas and severe tissue destruction compared with the lesions induced by crocidolite or subcutaneous injection. The expression of MMPs was elevated while granulomatous lesions were formed. The relative levels of MMPs were lower in the talc injected or intraperitoneal route models than those of crocidolite injected or subcutaneous injection models during the entire experiment.
CONCLUSIONS
These findings demonstrate that specific expression of MMPs/TIMP is inversely related to the grade of tissue destruction and suggest that expression of MMPs is required for promoting granuloma formation and limiting tissue destruction.
Cytomorphologic Features According to HPV DNA Type in Histologically Proven Cases of the Uterine Cervix.
In Ho Choi, So Young Jin, Dong Wha Lee, Dong Won Kim, Yoon Mi Jeen
Korean J Pathol. 2011;45(6):612-620.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.612
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AbstractAbstract PDF
BACKGROUND
This study investigated whether human papillomavirus (HPV) genotype is related to koilocytic changes in cervical cytology and histology, and what factors cause discrepancies among cytology, HPV DNA chip tests, and biopsies.
METHODS
We examined 174 of 949 cases histologically confirmed by both cytology and HPV DNA chip testing. We analyzed koilocytic changes in cytology and biopsies according to HPV genotype.
RESULTS
HPV-16 significantly coincided with nuclear size variation and hyperchromasia, although the cytomorphologic features correlated with other HPV genotypes were not statistically significant. By analyzing 68 cases in which there were discrepancies between the HPV DNA chip test and histological results, we confirmed that artifacts or glycogen acanthosis resulted in the over-diagnoses of four HPV-negative cases with normal cytology. Four diagnostic errors and four sampling errors were present in eight HPV-positive cases. The degree of nuclear size variation significantly influenced the cytologically under-diagnosed cases (p=0.006).
CONCLUSIONS
Other than HPV-16, HPV genotype exhibited no cytological or histological differences. The discrepancy between the results of HPV DNA chip test and histology was created by glycogen acanthosis, immature squamous metaplasia, artifacts, and sampling errors.
Cervical Cytologic Smears in Pap Solution vs ThinPrep: Smear Characteristics and Diagnostic Agreement.
Eunah Shin, Jin Kyu Park, No Won Park, Sang Bong Kim, Kyung Jong You, Jae Joon Lee, Woo Ick Yang
Korean J Pathol. 2011;45(6):621-625.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.621
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AbstractAbstract PDF
BACKGROUND
The Pap smear has brought about a dramatic improvement in the prevention of cervical cancer in women worldwide. In an effort to decrease the occasional false negatives in the Pap smear and further increase the screened population, ThinPrep Pap Test (TP), a fluid-based cytology collection method, has been developed. With preservation of claimed advantages of TP, we have developed a Pap test solution for manual preparatory process and compared our manually processed fluid-based Pap smear with TP to identify cytologic similarities and differences between the two methods.
METHODS
Cervical swipes of 204 patients were prospectively collected in the 'Pap solution' and also in PreservCyt solution for TP. Diagnoses and smear characteristics were compared.
RESULTS
The diagnoses of the paired smears agreed in 190 of the 204 cases (93.1%). The smear characteristics regarding overall cellularity and background cellularities were similar in the two methods and the stainability of the cells was virtually the same.
CONCLUSIONS
The 'Pap solution' has similar performance characteristics as TP in many aspects. With its advantages of cost-effectiveness and easier preparatory process, the 'Pap solution' can match previously implemented thin layer preparation.
Fine Needle Aspiration Cytology of Kikuchi's Lymphadenitis: with Emphasis on Differential Diagnosis with Tuberculosis.
Kang Min Han, Jai Hyang Go, Na Hye Myong, Wonae Lee
Korean J Pathol. 2011;45(6):626-631.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.626
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AbstractAbstract PDF
BACKGROUND
Although Kikuchi's lymphadenitis (KL) has been known to have characteristic cytological features, pathologists encounter difficulties in making a diagnosis with fine needle aspiration cytology (FNAC). The objective of this study was to assess the diagnostic pitfalls of KL with FNAC, particularly with emphasis on differential diagnosis with tuberculosis.
METHODS
FNAC of 10 patients with a histological diagnosis of KL and tuberculosis was reviewed.
RESULTS
Acidophilic cells were observed in all the 10 KL cases, even if the smears were insufficient. Crescentic histiocytes were seen in 8, granular background in 7, and karyorrhectic debris in 3 cases. Epithelioid histiocytes or neutrophils were not seen in any of the KL cases. Of the 10 cases of tuberculosis, acidophilic cells were observed in 6 cases, crescentic histiocytes in none of them, cheese-like background in 9, karyorrhectic debris in 8, epithelioid histiocytes in 4, and neutrophils in 8 cases.
CONCLUSIONS
The acidophilic cell could be the most sensitive but not the specific marker of KL with FNAC. The crescentic histiocytes might be the sensitive and considerably specific marker of KL. The cytological features distinguishing tuberculosis from KL may be cheese-like necrosis admixed with neutrophils and epithelioid histiocytes.
Case Reports
Systemic Plasmacytosis: A Case Report with a Review of the Literature.
Sung Hak Lee, Chang Young Yoo, Ji Han Jung, Jin Young Yoo, Suk Jin Kang, Chang Suk Kang
Korean J Pathol. 2011;45(6):632-638.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.632
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  • 3 Citations
AbstractAbstract PDF
Systemic plasmacytosis is an uncommon disorder characterized by widely disseminated macular skin eruptions composed of polyclonal lymphoplasmacytic infiltrates associated with variable extracutaneous involvement. An aggressive clinical course has been observed in a small number of patients, but most cases have followed chronic and benign clinical course without spontaneous remission. Previously reported cases of this entity have been described almost exclusively in Japanese patients. We recently experienced a case of systemic plasmacytosis in a 48-year-old Korean female patient. Initial skin biopsy specimen revealed patchy perivascular and periadnexal infiltrates of mature plasma cells. Serum immunoelectrophoresis revealed polyclonal hypergammaglobulinemia, and polyclonal plasmacytosis was noted on the subsequent biopsy specimens of left supraclavicular and axillary lymph nodes. Multiple tiny pulmonary nodules appeared six years after the initial cutaneous presentation and were found to be of the same histologic appearance. We herein report a rare case of systemic plasmacytosis with a review of the literature.
Maxillo-facial Extraskeletal Myxoid Chondrosarcoma: A Case Report and Discussion.
Ratnadeep Ganguly, Abhishek Mukherjee
Korean J Pathol. 2011;45(6):639-643.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.639
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AbstractAbstract PDF
In this report, we share our experience of a case of maxillo-facial extraskeletal myxoid chondrosarcoma, a very rare location for this neoplasm. In addition, a literature review is provided. The patient, a 61-year-old male, had a maxillary mass encroaching on the nasal cavity. After debulking, the tumor recurred, attaining its pre-surgical proportion in two months. The patient improved clinically with radiation and remained stable for about one year. However, he ultimately developed metastases in his lung which were treated with palliative chemotherapy with a good outcome lasting three months. We could find only eight reported cases of this tumor in the head region of which two are in the maxilla; hence, ruling out other primary sites is mandatory for a patient presenting with a primary head and neck mass. Surgical removal may be complicated because of the location. A combination of surgery and radiation is the management of choice, with palliative chemotherapy in metastasis.
A Cutaneous Myoepithelial Carcinoma Arising in a Papillary Eccrine Adenoma.
Ji Han Jung, Soyoung Im, Seok Jin Kang, Gyong Moon Kim, Ki Taik Han, Jin Young Yoo, Chang Suk Kang
Korean J Pathol. 2011;45(6):644-649.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.644
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  • 2 Citations
AbstractAbstract PDF
Cutaneous myoepithelial neoplasms and papillary eccrine adenomas (PEA) are rare conditions. Malignant tumors within a PEA are even rarer, with only one case reported to date. Herein, we present an extremely rare case of a cutaneous myoepithelial carcinoma arising in a PEA in a 70-year-old man presenting a solid mass in the left buttock. Histopathologically, most of the resected tumor revealed features consistent with the diagnosis of PEA. Some small nests and nodules were intermixed with the PEA and were present adjacent to the PEA. The tumor cells of nests and nodules showed ovoid to spindle shaped nuclei and slightly eosinophilic cytoplasm. Immunohistochemically, they were positive for both epithelial and myogenic markers, consistent with myoepithelioma. An inguinal lymph node with a metastatic lesion showed the same findings of myoepithelioma despite inconspicuous atypia. Our case showed malignant transformation of the myoepithelial cells at the outermost layers of the PEA.
Congenital Pulmonary Lymphangiectasia, Associated with Total Anomalous Pulmonary Venous Return.
Seong Wook Hwang, Mee Seon Kim, Po Eun Park, Tae In Park
Korean J Pathol. 2011;45(6):650-653.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.650
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AbstractAbstract PDF
Congenital pulmonary lymphangiectasia (CPL) is very rare. It shows diffuse pulmonary lymphatic dilatation without lymphatic proliferation. CPL can occur as a primary disorder or arise secondarily from other diseases such as the obstruction of pulmonary veins or lymphatics. The prognosis of CPL is very poor. Approximately 50% of infants are stillborn and most others usually die within the first day of life. The present case showed diffuse lymphangiectasia in the subpleural, interlobular, and peribronchovascular areas. The flat lining cells were immunohistochemically positive for D2-40 and CD31. CPL is usually diagnosed by clinicoradiological or postmortem examinations. However, our case was diagnosed by an antemortem lung biopsy. We report a case of CPL with total anomalous pulmonary venous return.

JPTM : Journal of Pathology and Translational Medicine