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Volume 50(2); March 2016
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Review
Sentinel Lymph Node in Breast Cancer: Review Article from a Pathologist’s Point of View
Sophia K. Apple
J Pathol Transl Med. 2016;50(2):83-95.   Published online January 12, 2016
DOI: https://doi.org/10.4132/jptm.2015.11.23
  • 15,635 View
  • 363 Download
  • 18 Citations
AbstractAbstract PDF
Breast cancer staging, in particular N-stage changed most significantly due to the advanced technique of sentinel lymph node biopsy two decades ago. Pathologists have more thoroughly examined and scrutinized sentinel lymph node and found increased number of small volume metastases. While pathologists use the strict criteria from the Tumor Lymph Node Metastasis (TNM) Classification, studies have shown poor reproducibility in the application of American Joint Committee on Cancer and International Union Against Cancer/TNM guidelines for sentinel lymph node classification in breast cancer. In this review article, a brief history of TNM with a focus on N-stage is described, followed by innate problems with the guidelines, and why pathologists may have difficulties in assessing lymph node metastases uniformly. Finally, clinical significance of isolated tumor cells, micrometastasis, and macrometastasis is described by reviewing historical retrospective data and significant prospective clinical trials.
Original Articles
Prognostic Implication of Semi-quantitative Immunohistochemical Assessment of CD20 Expression in Diffuse Large B-Cell Lymphoma
Chang Hwan Choi, Young Hoon Park, Joo Han Lim, Suk Jin Choi, Lucia Kim, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu
J Pathol Transl Med. 2016;50(2):96-103.   Published online February 15, 2016
DOI: https://doi.org/10.4132/jptm.2016.01.12
  • 7,758 View
  • 98 Download
  • 11 Citations
AbstractAbstract PDF
Background
Immunohistochemical demonstration of CD20 in diffuse large B-cell lymphoma (DLBCL) is prerequisite not only for the diagnosis but also for assigning patients to rituximab-containing chemotherapy. However, little is known about the impact of abundance of CD20 expression assessed by immunohistochemistry on the clinical outcome of DLBCL. We performed a semi-quantitative immunohistochemical analysis of CD20 expression in DLBCL to examine the prognostic implication of the level of CD20 expression. Methods: Pre-treatment diagnostic tissue samples from 48 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen were represented in a tissue microarray and immunostained for CD20. The relative abundance of CD20 expression was semi-quantitatively scored using a web-based ImmunoMembrane plug-in. Receiver operating characteristic curve analysis was used to determine a prognostically relevant cut-off score in order to dichotomize the patients into CD20-high versus CD20-low groups. Results: The levels of CD20 expression were heterogeneous among the patients, with a wide and linear distribution of scores. Patients in CD20-low group showed significantly poor clinical outcome. Conclusions: The levels of CD20 expression in DLBCL are heterogeneous among the patients with DLBCL. A subgroup of the patients with CD20 expression levels below the cut-off score showed poor clinical outcome.
Upregulated Neuro-oncological Ventral Antigen 1 (NOVA1) Expression Is Specific to Mature and Immature T- and NK-Cell Lymphomas
Eun Kyung Kim, Sun Och Yoon, Soo Hee Kim, Woo Ick Yang, Yoon Ah Cho, Soo Jeong Kim
J Pathol Transl Med. 2016;50(2):104-112.   Published online February 29, 2016
DOI: https://doi.org/10.4132/jptm.2016.02.08
  • 7,706 View
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  • 10 Citations
AbstractAbstract PDF
Background
Recent studies have revealed that the splicing factor neuro-oncological ventral antigen 1 (NOVA1) is enriched in fibroblasts and accumulated T cells of tertiary lymphoid structures. In the present study, we investigated NOVA1 expression in various subtypes of mature and immature T- and natural killer (NK)-cell lymphomas as well as in various B-cell lymphoma subtypes. Methods: NOVA1 immunoexpression was evaluated in hyperplastic palatine tonsils (n = 20), T- and NK-cell lymphomas (n = 177), diffuse large B-cell lymphomas (n = 151), and other types of B cell lymphomas (n = 31). Nuclear staining intensity and percentage of positive tumor cells were graded. NOVA1 mRNA expression was analyzed in various lymphoma cell lines. Results: Tumor cells of T- and NK-cell lymphomas showed higher expression levels of NOVA1 than did normal paracortical T cells, and 56.5% of T- and NK-cell lymphoma cases showed diffuse and strong expression. The NOVA1 expression level varied according to the subtype; it was higher in angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), and T lymphoblastic leukemia/lymphoma (T-LBL), but it was lower in ALK-positive ALCL. In almost all B-cell lymphomas, NOVA1 expression was very low or negative. NOVA1 mRNA was also expressed in Jurkat, a T-LBL cell line. Conclusions: The present findings suggest that NOVA1 upregulation may be involved in certain subtypes of T- and NK-cell lymphomas, but not in B-cell lymphomas. Upregulated NOVA1 expression seems to be a specific biological feature of activated T cells such as T- and NK-cell lymphomas.
Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis
Nayoung Han, Hannah Kim, Soo Kee Min, Sun-Ha Paek, Chul-Kee Park, Seung-Hong Choi, U-Ri Chae, Sung-Hye Park
J Pathol Transl Med. 2016;50(2):113-121.   Published online December 14, 2015
DOI: https://doi.org/10.4132/jptm.2015.10.30
  • 8,768 View
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  • 16 Citations
AbstractAbstract PDF
Background
The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because NAB2-STAT6 gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs. Methods: This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically. Results: In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers. Conclusions: Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases.
Prognostic Significance of Aquaporin 5 Expression in Non-small Cell Lung Cancer
Young Min Jo, Tae In Park, Hwa Young Lee, Ji Yun Jeong, Won Kee Lee
J Pathol Transl Med. 2016;50(2):122-128.   Published online February 8, 2016
DOI: https://doi.org/10.4132/jptm.2015.10.31
  • 10,213 View
  • 74 Download
  • 8 Citations
AbstractAbstract PDF
Background
Aquaporins are water channel proteins that play a major role in the movement of water in various human tissues. Recently, it has been found that aquaporins have influence in the carcinogenesis of human malignancies. We analyzed the prognostic impact of aquaporin 5 (AQP5) in non-small lung cancer (NSCLC). Methods: Seventy-six cases of NSCLC were studied, including 44 cases of adenocarcinoma (ADC) and 32 cases of squamous cell carcinoma (SQCC). Tissue microarray was constructed and immunohistochemical staining for AQP5 was performed. Results: AQP5 was positive in 59.2% of the total enrolled NSCLCs (63.7% in ADC and 53.1% in SQCC). The difference in expression of AQP5 according to the histologic grade of the tumor was significant (p<.047), but not in a serial order. When ADC and SQCC were separately evaluated, no significant difference was observed according to the histologic grade of the tumor (p=.076 in ADC and p=.631 in SQCC). No difference was observed between AQP5 expression and other demographic data and tumor characteristics. Disease-free survival (DFS) was higher in AQP5 negative cases than positive cases in ADC (p=.047), but no significance was found in SQCC (p=.068). We were unable to find a significance between AQP5 overexpression and overall survival in either ADC (p=.210) or SQCC (p=.533). Conclusions: AQP5 expression is associated with DFS in ADC of the lung and tumor grade of NSCLC. The present study suggests that AQP5 can be a prognostic factor of NSCLC.
Interobserver Variability of Ki-67 Measurement in Breast Cancer
Yul Ri Chung, Min Hye Jang, So Yeon Park, Gyungyub Gong, Woo-Hee Jung, The Korean Breast Pathology Ki- Study Group
J Pathol Transl Med. 2016;50(2):129-137.   Published online February 15, 2016
DOI: https://doi.org/10.4132/jptm.2015.12.24
  • 8,211 View
  • 99 Download
  • 15 Citations
AbstractAbstract PDF
Background
As measurement of Ki-67 proliferation index is an important part of breast cancer diagnostics, we conducted a multicenter study to examine the degree of concordance in Ki-67 counting and to find factors that lead to its variability. Methods: Thirty observers from thirty different institutions reviewed Ki-67–stained slides of 20 different breast cancers on whole sections and tissue microarray (TMA) by online system. Ten of the 20 breast cancers had hot spots of Ki-67 expression. Each observer scored Ki-67 in two different ways: direct counting (average vs. hot spot method) and categorical estimation. Intraclass correlation coefficient (ICC) of Ki-67 index was calculated for comparative analysis. Results: For direct counting, ICC of TMA was slightly higher than that of whole sections using average method (0.895 vs 0.858). The ICC of tumors with hot spots was lower than that of tumors without (0.736 vs 0.874). In tumors with hot spots, observers took an additional counting from the hot spot; the ICC of whole sections using hot spot method was still lower than that of TMA (0.737 vs 0.895). In categorical estimation, Ki-67 index showed a wide distribution in some cases. Nevertheless, in tumors with hot spots, the range of distribution in Ki-67 categories was decreased with hot spot method and in TMA platform. Conclusions: Interobserver variability of Ki-67 index for direct counting and categorical estimation was relatively high. Tumors with hot spots showed greater interobserver variability as opposed to those without, and restricting the measurement area yielded lower interobserver variability.
Comparison of Analytical and Clinical Performance of HPV 9G DNA Chip, PANArray HPV Genotyping Chip, and Hybrid-Capture II Assay in Cervicovaginal Swabs
Ho Young Jung, Hye Seung Han, Hyo Bin Kim, Seo Young Oh, Sun-Joo Lee, Wook Youn Kim
J Pathol Transl Med. 2016;50(2):138-146.   Published online January 13, 2016
DOI: https://doi.org/10.4132/jptm.2015.10.21
  • 6,625 View
  • 60 Download
  • 3 Citations
AbstractAbstract PDF
Background
Human papillomavirus (HPV) infection can be detected by using several molecular methods, including Hybrid-Capture II (HC2) assay and variable HPV DNA chip tests, although each method has different sensitivities and specificities. Methods: We performed HPV 9G DNA Chip (9G) and PANArray HPV Genotyping Chip (PANArray) tests on 118 cervicovaginal swabs and compared the results with HC2, cytology, histology, and direct sequencing results. Results: The overall and high-risk HPV (HR-HPV) positivity rates were 62.7% and 44.9% using 9G, and 61.0% and 30.5% using PANArray, respectively. The positivity rates for HR-HPV with these two chips were significantly lower than 55.1% when HC2 was used. The sensitivity of overall HPV positivity in detecting histologically confirmed low-grade cervical squamous intraepithelial lesions or higher was 88.7% for all three tests. The specificity was 58.5% for 9G and 61.5% for PANArray, which was significantly lower than the 72.3% for HC2. With the HR-HPV+ genotype threshold, the sensitivity decreased to 75.5% for 9G and 52.8% for PANArray, which was significantly lower than the 88.7% for HC2. Comparison of the two chips showed concordant results in 55.1% of the samples, compatible results in 16.9%, and discordant results in 28.0%, exhibiting poor agreement in detecting  certain HPV genotypes. Compared with direct sequencing, 9G yielded no discordant results, whereas PANArray yielded 31 discordant results (26.7%). Conclusions: Compared with HC2, the HPV genotyping tests showed lower sensitivity in histologic correlation. When the two chips were compared, the 9G was more sensitive and accurate for detecting HR-HPV than the PANArray.
Morphologic Analysis of Cytomegalovirus Infected Cells in Bronchial Washing Cytology: Comparison of Liquid-Based Preparation and Conventional Smear
Jae Yeon Seok, Jungsuk An, Seung Yeon Ha, Dong Hae Chung, Sangho Lee, Hyunchul Kim
J Pathol Transl Med. 2016;50(2):147-154.   Published online February 15, 2016
DOI: https://doi.org/10.4132/jptm.2015.12.25
  • 7,864 View
  • 66 Download
  • 2 Citations
AbstractAbstract PDF
Background
The cytopathic effects of cytomegalovirus (CMV) infection have been well described since the virus was first reported; however, the morphology of CMV infection has not been clearly studied. We examined the difference in detailed cytologic findings in bronchial washing cytology between liquid-based and conventionally prepared smears. Methods: Bronchial washing cytology was processed using either the conventional preparation (CP) or liquid-based preparation (LBP). Sixty-nine cells with typical cytopathic effects of CMV infection were detected on CP slides and 18 cells on LBP slides. Using the image analyzer, area, circumference, major axis, and minor axis of the cytoplasm, nucleus, and intranuclear inclusion were measured in singly scattered CMV-infected cells, and histiocytes were used as a control. Results: The mean cytoplasmic area of CMV-infected cells was 1.47 times larger than that of histiocytes in CP and 2.92 times larger in LBP (p<.05). The mean nuclear area of CMV-infected cells was 2.61 times larger than that of histiocytes in CP and 4.25 times larger in LBP (p<.05). The nucleus to cytoplasm ratio and intranuclear inclusion to cytoplasm ratio of the mean area, circumference, major axis, and minor axis in CP were larger than those in LBP (p<.05). Conclusions: The sizes of cytoplasm, nucleus, and intranuclear inclusion were larger in LBP than in CP, indicating that CMV-infected cells are easily detectable in LBP. However, the nucleus-to-cytoplasm ratio was larger in CP, suggesting that differentiation from malignancy or regenerative atypia requires caution in CP.
Case Studies
Clear Cell Adenocarcinoma Arising from Adenofibroma in a Patient with Endometriosis of the Ovary
Inju Cho, Sung-Chul Lim
J Pathol Transl Med. 2016;50(2):155-159.   Published online October 26, 2015
DOI: https://doi.org/10.4132/jptm.2015.08.07
  • 7,721 View
  • 104 Download
  • 2 Citations
AbstractAbstract PDF
Ovarian clear cell adenocarcinomas (CCACs) are frequently associated with endometriosis and, less often with clear cell adenofibromas (CCAFs). We encountered a case of ovarian CCAC arising from benign and borderline adenofibromas of the clear cell and endometrioid types with endometriosis in a 53-year-old woman. Regions of the adenofibromas showed transformation to CCAC and regions of the endometriosis showed atypical endometriotic cysts. This case demonstrates that CCAC can arise from CCAF or endometriosis.
An Adult Case of Bartter Syndrome Type III Presenting with Proteinuria
Eun Jung Cha, Won Min Hwang, Sung-Ro Yun, Moon Hyang Park
J Pathol Transl Med. 2016;50(2):160-164.   Published online January 11, 2016
DOI: https://doi.org/10.4132/jptm.2015.08.31
  • 7,695 View
  • 91 Download
  • 6 Citations
AbstractAbstract PDF
Bartter syndrome (BS) I–IV is a rare autosomal recessive disorder affecting salt reabsorption in the thick ascending limb of the loop of Henle. This report highlights clinicopathological findings and genetic studies of classic BS in a 22-year-old female patient who presented with persistent mild proteinuria for 2 years. A renal biopsy demonstrated a mild to moderate increase in the mesangial cells and matrix of most glomeruli, along with marked juxtaglomerular cell hyperplasia. These findings suggested BS associated with mild IgA nephropathy. Focal tubular atrophy, interstitial fibrosis, and lymphocytic infiltration were also observed. A genetic study of the patient and her parents revealed a mutation of the CLCNKB genes. The patient was diagnosed with BS, type III. This case represents an atypical presentation of classic BS in an adult patient. Pathologic findings of renal biopsy combined with genetic analysis and clinicolaboratory findings are important in making an accurate diagnosis.
Brief Case Reports
A Rare Case of Thymic Gangliocytic Paraganglioma
Jung Wook Yang, Joungho Han, Hyun Woo Lee, Soo Youn Cho, Hong Kwan Kim
J Pathol Transl Med. 2016;50(2):165-167.   Published online October 8, 2015
DOI: https://doi.org/10.4132/jptm.2015.07.15
  • 6,647 View
  • 46 Download
  • 5 Citations
PDF
Primary Neurilemmoma of the Thyroid Gland Clinically Mimicking Malignant Thyroid Nodule
Young Sub Lee, Jee Soon Kim, Arthur Minwoo Chung, Woo Chan Park, Tae-Jung Kim
J Pathol Transl Med. 2016;50(2):168-171.   Published online October 26, 2015
DOI: https://doi.org/10.4132/jptm.2015.08.26
  • 6,908 View
  • 63 Download
  • 2 Citations
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JPTM : Journal of Pathology and Translational Medicine