Journal of Pathology and Translational Medicine

Review

Epstein-Barr Virus–Associated Lymphoproliferative Disorders: Review and Update on 2016 WHO Classification: Hyun-Jung Kim, Young Hyeh Ko, Ji Eun Kim, Seung-Sook Lee, Hyekyung Lee, Gyeongsin Park, Jin Ho Paik, Hee Jeong Cha, Yoo-Duk Choi, Jae Ho Han, Jooryung Huh; J Pathol Transl Med. 2017;51(4):352-358. Published online June 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.15

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Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.

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Original Article

Evaluation of the VE1 Antibody in Thyroid Cytology Using Ex Vivo Papillary Thyroid Carcinoma Specimens: Yon Hee Kim, Hyunee Yim, Yong-Hee Lee, Jae Ho Han, Kyi Beom Lee, Jeonghun Lee, Euy Young Soh, Seon-Yong Jeong, Jang-Hee Kim; J Pathol Transl Med. 2016;50(1):58-66. Published online December 14, 2015; DOI: https://doi.org/10.4132/jptm.2015.10.10

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Abstract PDF

Background
Recently, VE1, a monoclonal antibody against the BRAFV600E mutant protein, has been investigated in terms of its detection of the BRAFV600E mutation. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in thyroid cytology samples is rarely performed, and its diagnostic value in cytology has not been well established. In present study, we explored VE1 immunoexpression in cytology samples from ex vivo papillary thyroid carcinoma specimens in order to minimize limitations of low cellularity and sampling/targeting errors originated from thyroid fineneedle aspiration and compared our results with those obtained using the corresponding papillary thyroid carcinoma tissues. Methods: The VE1 antibody was evaluated in 21 cases of thyroid cytology obtained directly from ex vivo thyroid specimens. VE1 immunostaining was performed using liquid-based cytology, and the results were compared with those obtained using the corresponding tissues. Results: Of 21 cases, 19 classic papillary thyroid carcinomas had BRAFV600E mutations, whereas two follicular variants expressed wild-type BRAF. VE1 immunoexpression varied according to specimen type. In detection of the BRAFV600E mutation, VE1 immunostaining of the surgical specimen exhibited 100% sensitivity and 100% specificity, whereas VE1 immunostaining of the cytology specimen exhibited only 94.7% sensitivity and 0% specificity. Conclusions: Our data suggest that VE1 immunostaining of a cytology specimen is less specific than that of a surgical specimen for detection of the BRAFV600E mutation, and that VE1 immunostaining of a cytology specimen should be further evaluated and optimized for clinical use.

Citations

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Yukie YAMAYA
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Nidhi Anand, Tushar Agrawal, Anurag Gupta, Saumya Shukla, Roma Pradhan, Nuzhat Husain
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The immunocytochemical expression of VE‐1 (BRAF V600E‐related) antibody identifies the aggressive variants of papillary thyroid carcinoma on liquid‐based cytology
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Utility of the BRAF p.V600E immunoperoxidase stain in FNA direct smears and cell block preparations from patients with thyroid carcinoma
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Brief Case Report

Primary Gastric Histiocytic Sarcoma Reminiscent of Inflammatory Pseudotumor: A Case Report with Review of the Literature: Dakeun Lee, Young-Bae Kim, Sook Hee Chung, Sang-Ryung Lee, Cheul Su Byun, Sang-Uk Han, Jae Ho Han; Korean J Pathol. 2014;48(3):258-262. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.258

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Original Articles

Characteristics of Cutaneous Lymphomas in Korea According to the New WHO-EORTC Classification: Report of a Nationwide Study: Jae Ho Han, Young-Hyeh Ko, Yun Kyung Kang, Wan-Seop Kim, Yoon Jung Kim, Insun Kim, Hyun-Jung Kim, Soo Kee Min, Chan-Kum Park, Chan-Sik Park, Bong-Kyung Shin, Woo Ick Yang, Young-Ha Oh, Jong Sil Lee, Juhie Lee, Tae Hui Lee, Hyekyung Lee, Ho Jung Lee, Yoon Kyung Jeon, Hee Jeong Cha, Yoo-Duk Choi, Chul Woo Kim; Korean J Pathol. 2014;48(2):126-132. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.126

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Abstract PDF

Background

Previously, cutaneous lymphomas were classified according to either the European Organization for the Research and Treatment of Cancer (EORTC) or the World Health Organization (WHO) classification paradigms. The aim of this study was to determine the relative frequency of Korean cutaneous lymphoma according to the new WHO-EORTC classification system.

Methods

A total of 517 patients were recruited during a recent 5 year-period (2006-2010) from 21 institutes and classified according to the WHO-EORTC criteria.

Results

The patients included 298 males and 219 females, and the mean age at diagnosis was 49 years. The lesions preferentially affected the trunk area (40.2%). The most frequent subtypes in order of decreasing prevalence were mycosis fungoides (22.2%), peripheral T-cell lymphoma (17.2%), CD30+ T-cell lymphoproliferative disorder (13.7%), and extranodal natural killer/T (NK/T) cell lymphoma, nasal type (12.0%). Diffuse large B-cell lymphoma accounted for 11.2% of cases, half of which were secondary cutaneous involvement; other types of B-cell lymphoma accounted for less than 1% of cases.

Conclusions

In comparison with data from Western countries, this study revealed relatively lower rates of mycosis fungoides and B-cell lymphoma in Korean patients, as well as higher rates of subcutaneous panniculitis-like T-cell lymphoma and NK/T cell lymphoma.

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WHO Classification of Malignant Lymphomas in Korea: Report of the Third Nationwide Study.: Jin Man Kim, Young Hyeh Ko, Seung Sook Lee, Jooryung Huh, Chang Suk Kang, Chul Woo Kim, Yun Kyung Kang, Jai Hyang Go, Min Kyung Kim, Wan Seop Kim, Yoon Jung Kim, Hyun Jung Kim, Hee Kyung Kim, Jong Hee Nam, Hyung Bae Moon, Chan Kum Park, Tae In Park, Young Ha Oh, Dong Wha Lee, Jong Sil Lee, Juhie Lee, Hyekyung Lee, Sung Chul Lim, Kyu Yun Jang, Hee Kyung Chang, Yoon Kyung Jeon, Hye Ra Jung, Min Sun Cho, Hee Jeong Cha, Suk Jin Choi, Jae Ho Han, Sook Hee Hong, Insun Kim; Korean J Pathol. 2011;45(3):254-260.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.254

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Abstract PDF

BACKGROUND
The aim of study was to determine the relative frequency of malignant lymphoma according to World Health Organization (WHO) classification in Korea.
METHODS
A total of 3,998 cases diagnosed at 31 institutes between 2005 and 2006 were enrolled. Information including age, gender, pathologic diagnosis, site of involvement and immunophenotypes were obtained.
RESULTS
The relative frequency of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) was 95.4% and 4.6%, respectively. B-cell lymphomas accounted for 77.6% of all NHL, while T/natural killer (T/NK)-cell lymphomas accounted for 22.4%. The most frequent subtypes of NHL were diffuse large B-cell lymphoma (42.7%), extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (19.0%), NK/T-cell lymphoma (6.3%) and peripheral T-cell lymphoma (PTCL), unspecified (6.3%), in decreasing order. The relative frequency of HL was nodular sclerosis (47.4%), mixed cellularity (30.6%), and nodular lymphocyte predominant (12.1%) subtypes. Compared with a previous study in 1998, increase in gastric MZBCL and nodular sclerosis HL, and slight decrease of follicular lymphoma, PTCL, and NK/T-cell lymphoma were observed.
CONCLUSIONS
Korea had lower rates of HL and follicular lymphoma, and higher rates of extranodal NHL, extranodal MZBCL, and NK/T-cell lymphoma of nasal type compared with Western countries. Changes in the relative frequency of lymphoma subtypes are likely ascribed to refined diagnostic criteria and a change in national health care policy.

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Korean Pediatric/Adolescent Lymphoma: Incidence and Pathologic Characteristics.: Seung Sook Lee, Jin Man Kim, Young Hyeh Ko, Jooryung Huh, Chang Suk Kang, Chul Woo Kim, Yun Kyung Kang, Jai Hyang Go, Min Kyung Kim, Wan Seop Kim, Yoon Jung Kim, Hyun Jung Kim, Hee Kyung Kim, Jong Hee Nam, Hyung Bae Moon, Chan Kum Park, Tae In Park, Young Ha Oh, Dong Wha Lee, Jong Sil Lee, Juhie Lee, Hyekyung Lee, Sung Chul Lim, Kyu Yun Jang, Hee Kyung Chang, Yoon Kyung Jeon, Hye Ra Jung, Min Sun Cho, Hee Jeong Cha, Suk Jin Choi, Jae Ho Han, Sook Hee Hong, Insun Kim; Korean J Pathol. 2010;44(2):117-124.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.117

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Abstract PDF

BACKGROUND
The Hematopathology Study Group of the Korean Society of Pathologists conducted a nation-wide retrospective analysis of Korean pediatric lymphoma, to provide pathologic data on pediatric/adolescent lymphoma subtypes and features.
METHODS
All lymphoma cases of all age groups were collected during a recent 2 year-period (2005-2006) from 32 institutes in Korea. Among 3,686 lymphoma patients, 142 who were age 18 or less were classified according to the World Health Organization (WHO) classification.
RESULTS
Among 142 pediatric/adolescent lymphoma patients, Hodgkin lymphoma accounted for 21 (14.8%) and non-Hodgkin lymphoma (NHL) for 121 (85.2%). Hodgkin lymphoma appears to be more common in the pediatric/adolescent age group than in the all-ages group (14.8% vs 4.4%). T- and natural killer cell-NHL was more common in the pediatric/adolescent age group than in the all ages group (46.3% vs 22%). The majority of Korean pediatric/adolescent NHL cases was composed of Burkitt lymphoma, T- or B-lymphoblastic lymphoma, anaplastic large-cell lymphoma, and diffuse large B-cell lymphoma. For lymphoma patients under the age of 6 years, most had B-lymphoblastic or Burkitt lymphoma, which commonly presented at extranodal sites.
CONCLUSIONS
The distribution of lymphoma subtypes in the pediatric/adolescent age group is quite different from the distribution of adults, but it was quite similar to distribution in Western countries.

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A Case of Nasal Type Extranodal NK/T Cell Lymphoma Incidentally Detected in a Child
Ha Jin Oh, Sang Hyun Park, Hae In Jang, Dong Hoon Lee, Yoo Duk Choi, Hee Jo Baek, Hoon Kook
Clinical Pediatric Hematology-Oncology.2015; 22(1): 76. CrossRef

Case Reports

Emphysematous Pyelonephritis in Diabetic Nephropathy A report of two cases.: Jae Ho Han, Lucia Kim, Sung Eun Kim, Soon Won Hong, Hyeon Joo Jeong; Korean J Pathol. 1999;33(5):367-370.

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Abstract PDF: Diabetic nephropathy is characterized by one or a combination of the following lesions: (1) glomerular involvement with three distinctive patterns: diffuse glomerulosclerosis, nodular glomerulosclerosis, and exudative lesions; (2) arteriolo sclerosis; (3) urinary tract bacterial infection with pyelonephritis and sometimes emphysematous pyelonephritis. Emphysematous pyelonephritis is an uncommon life-threatening and acute suppurative infection of the kidney, and usually occurs in diabetic female patients. It is characterized by the production of intraparenchymal gas. Glucose fermentation has been considered the main cause of the gas formation. We presented two illustrative nephrectomy cases of emphysematous pyelonephritis in addition to the typical pathologic features of diabetic nephropathy.

Juvenile Granulosa Cell Tumor Arising in Undescended Testis: A case report.: So Ya Paik, Hae Youn Kang, Jae Ho Han, Woo Ick Yang, Seok Joo Han; Korean J Pathol. 1999;33(5):376-379.

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Abstract PDF: Juvenile granulosa cell tumor is rare but one of the common congenital testicular neoplasms. Although histological features are typical of its ovarian counterpart, testicular juvenile granulosa cell tumor has a distinctly different clinical presentation. We report a case of juvenile granulosa cell tumor arising in the cryptochid testis of a 4-day-old newborn. A 6 5 5 cm sized multilocular cyst containing thick, mucinous fluid was found in the peritoneal cavity. The external surface of the cyst was smooth and the septae were relatively thin. The cyst consisted of numerous mucin-filled, cystic follicles lined by cells having vacuolated cytoplasm and round to oval dark nuclei without grooves. Cells resembling granulosa cells of an ovarian follicle were also observed in the intervening stroma forming irregular solid nests.

Original Articles

Histopathologic Findings of Mastopathy in Diabetes Mellitus.: Jae Ho Han, Hee Jung Kim, Woo Hee Jung, Ki Keun Oh; Korean J Pathol. 1999;33(7):503-506.

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Abstract PDF: Diabetic mastopathy is a clinicopathologic entity which was first described as a dense fibrous breast mass in insulin-dependent diabetes mellitus. The purpose of this article was to document diabetic mastopathy histologically which had been diagnosed as fibrocystic disease and to avoid unnecessary surgical procedures in breast mass simulating malignancy in diabetic patients. We examined eight excisional breast biopsies from seven patients. Three diabetic patients with type I insulin-dependent diabetes mellitus presented with bilateral (2 patients) or unilateral (1 patient) rapidly growing palpable breast masses. Four patients with type II noninsulin-dependent diabetes mellitus presented with bilateral (2 patients) or unilateral breast mass (1 patient). One patient had no symptoms. All of them had late complications of diabetes mellitus such as nephropathy, neuropathy and retinopathy. Mammographic findings such as ill- defined mass density and asymmetric increased density suggested malignancy. However, all of them had been diagnosed as fibrocystic disease. On review, the most consistent pathologic finding was keloid-like stromal fibrosis. Others were ductitis or ductulitis, thickening of basement membrane of ducts or ductules, mononuclear perivasculitis and lobulitis. Six of eight breast satisfied all five criteria for diabetic mastopathy.

DNA Ploidy Analysis as a Prognostic Indicator in Phyllodes Tumor of the Breast.: Hee Jung Kim, Jae Ho Han, Woo Hee Jung, Hy De Lee; Korean J Pathol. 1999;33(7):507-516.

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Abstract PDF: DNA ploidy analysis using flow cytometry was performed on sixty six cases of phyllodes tumor of the breast including benign, low grade and high grade malignant phyllodes tumor. The rate of aneuploidy was 41.2% in high grade malignant phyllodes tumor and 4.8% in benign phyllodes tumor. No aneuploidy was noted in low grade malignant phyllodes tumor. The recurrence rate according to DNA ploidy pattern revealed 16.7% of aneuploidy and 7.7% of diploidy. In the aneuploid cases, the DNA index of high grade malignant phyllodes tumor was higher than benign phyllodes tumor. Morever, in diploid cases, %SG2M were significantly higher in high grade malignant phyllodes tumor. Therefore, we conclude that DNA ploidy analysis as well as histologic characteristics such as cellularity, pleomorphism of stromal cells and mitoses is useful parameters in the diagnosis, recurrence and prognostic predictors of phyllodes tumor.

Correlation of Ki-67, p53 and bcl-2 Expression with Grade and Behavior of Ependymoma.: Jae Ho Han, Tai Seung Kim; Korean J Pathol. 1999;33(9):723-728.

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Abstract PDF: Ependymomas constitute no more than 5 to 7% of all primary CNS neoplasm and their biologic behavior is difficult to predict by microscopic appearances. Recently, many studies have attempted to correlate biologic behavior with tumor proliferation index, tumor suppressor gene and oncogene using immunohistochemical stains. We evaluated 25 cases of surgically resected intracranial ependymomas for the proliferation activity using Ki-67, and expression of p53 and bcl-2 protein with regard to the prognosis. The cases were divided into 17 ependymomas (WHO Grade II), 3 papillary ependymomas (WHO Grade II), and 5 anaplastic ependymomas. Clinically, the patients were divided into two groups, recurrent (18 cases) or non-recurrent (7 cases). The Ki-67 proliferation index was significantly higher in the recurrent group (p<0.05) and in the younger ages (correlation index=0.534). Although Ki-67 proliferation index was higher in anaplastic ependymoma, it was not significant statistically (p>0.05). p53 protein expression tended to increase in the patients who had anaplastic ependymoma and in the recurrent group. bcl-2 expression was not correlated with histologic grade or recurrence of the tumor. We conclude that Ki-67 proliferation index and p53 expression are important markers for predicting biologic behavior of ependymoma.

Prognostic Implications of Ki-67 Labelling Index and p53, bcl-2 Protein Expression in the Primary Central Nervous System Lymphoma.: Jae Ho Han, Woo Ick Yang, Tai Seung Kim; Korean J Pathol. 2000;34(6):456-464.

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Abstract PDF: It has been claimed that CNS lymphoma, a rare neoplasm accounting for only a small fraction of malignant brain tumors, occurs with increasing frequency in immunologically normal as well as immunocompromised individuals. We investigated the prognostic value of Ki-67 index, p53, and bcl-2 oncoprotein expression in relation to the clinicopathological parameters in the primary CNS lymphoma patients. The tumors were graded by Kiel classification and the Working formulation and included 33 high-grade, 4 intermediate-grade, and 5 low-grade lymphomas. The phenotype was determined in 38 cases: 30 were B cell type and 8 were T cell type. All cases displayed variable degrees of nuclear Ki-67 staining from 1.0% to 92.0% (mean 51.1%). A highly significant correlation was established between the proportion of Ki-67 positive cells and the classification into grades (p=0.0002) and phenotypes (p=0.0002). Overexpression of p53 and bcl-2 protein was found in 37.1% and 51.4% of 35 patients, respectively. And p53 expression was significantly increased in B cell type (p=0.02). On Kaplan-Meier survival curve, the phenotype, grade of tumors, and p53 and bcl-2 protein expression were not correlated with overall survival. On multivariate analyses, overall survival was independently influenced by Ki-67 index. In conclusion, it is suggested that Ki-67 proliferating index is the most important marker for predicting biologic behavior of the primary CNS lymphoma.

Case Report

Chordoid Glioma: A Case Report.: Jang Hee Kim, Jae Ho Han, Chull Shim; Korean J Pathol. 2002;36(1):66-69.

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Abstract PDF: The chordoid glioma is a recently recognized rare neoplasm of the third ventricle and hypothalamus and, as the name implies, has a chordoid appearance. Using histological, immunohistochemical and ultrastructural studies, we report a case of a 32-year-old man with a chordoid glioma in the third ventricle. Magnetic resonance T1-weighted images of the brain with homogenous contrast enhancement revealed a well circumscribed, isointense mass occupying the third ventricle. Histologically, the tumor showed cords and clusters of epithelioid cells within a mucinous background along with lymphoplasmacytic infiltrate, and appeared to be reminiscent of a chordoma or chordoid meningioma. Immunohistochemically, the tumor cells were immunoreactive for glial fibrillary acidic protein, vimentin and CD34 but negative for epithelial membrane antigen. Ultrastructural study revealed round to spindle shaped cells with abundant cytoplasmic intermediate filaments and cytoplasmic zonation.

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