Journal of Pathology and Translational Medicine

Original Article

Analysis of Histologic Features Suspecting Anaplastic Lymphoma Kinase (ALK)-Expressing Pulmonary Adenocarcinoma: In Ho Choi, Dong Won Kim, Sang Yun Ha, Yoon-La Choi, Hee Jeong Lee, Joungho Han; J Pathol Transl Med. 2015;49(4):310-317. Published online June 22, 2015; DOI: https://doi.org/10.4132/jptm.2015.05.13

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Background
Since 2007 when anaplastic lymphoma kinase (ALK) rearrangements were discovered in non-small cell lung cancer, the ALK gene has received attention due to ALK-targeted therapy, and a notable treatment advantage has been observed in patients harboring the EML4/ALK translocation. However, using ALK-fluorescence in situ hybridization (FISH) as the standard method has demerits such as high cost, a time-consuming process, dependency on interpretation skill, and tissue preparation. We analyzed the histologic findings which could complement the limitation of ALK-FISH test for pulmonary adenocarcinoma. Methods: Two hundred five cases of ALK-positive and 101 of ALK-negative pulmonary adenocarcinoma from January 2007 to May 2013 were enrolled in this study. The histologic findings and ALK immunohistochemistry results were reviewed and compared with the results of ALK-FISH and EGFR/KRAS mutation status. Results: Acinar, cribriform, and solid growth patterns, extracellular and intracellular mucin production, and presence of signet-ring-cell element, and psammoma body were significantly more often present in ALK-positive cancer. In addition, the presence of goblet cell-like cells and presence of nuclear inclusion and groove resembling papillary thyroid carcinoma were common in the ALK-positive group. Conclusions: The above histologic parameters can be helpful in predicting ALK rearranged pulmonary adenocarcinoma, leading to rapid FISH analysis and timely treatment.

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Ryuko Tsukamoto, Hiroyuki Ohsaki, Sho Hosokawa, Yasunori Tokuhara, Shingo Kamoshida, Toshiko Sakuma, Tomoo Itoh, Chiho Ohbayashi
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Update on the potential significance of psammoma bodies in lung adenocarcinoma from a modern perspective
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Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in ALK-Rearranged NSCLC
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The prevalence of ALK rearrangement in pulmonary adenocarcinomas in an unselected Caucasian population from a defined catchment area: impact of smoking
Birgit G Skov, Paul Clementsen, Klaus R Larsen, Jens B Sørensen, Anders Mellemgaard
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Anaplastic lymphoma kinase immunohistochemistry in lung adenocarcinomas: Evaluation of performance of standard manual method using D5F3 antibody
D Jain, K Jangra, PS Malik, S Arulselvi, K Madan, S Mathur, MC Sharma
Indian Journal of Cancer.2017; 54(1): 209. CrossRef
Clinicopathological Features and Therapeutic Responses of Chinese Patients with Advanced Lung Adenocarcinoma Harboring an Anaplastic Lymphoma Kinase Rearrangement
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Oncology Research and Treatment.2017; 40(1-2): 27. CrossRef
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Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases
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APMIS.2016; 124(10): 832. CrossRef

Brief Case Report

Primary Extraskeletal Mesenchymal Chondrosarcoma of the Anterior Mediastinum: Sang Seok Jeong, Phil Jo Choi, Dong Won Kim, Choonhee Son, Mee Sook Roh; Korean J Pathol. 2013;47(5):492-494. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.492

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Mesenchymal Tumors of the Mediastinum: An Update on Diagnostic Approach
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A chondrosarcoma in the anterior mediastinum mimicking a thymoma
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Original Articles

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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Abstract 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.

Citations

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Koilocytic changes are not elicited by human papillomavirus genotypes with higher oncogenic potential
Mitsuaki Okodo, Kaori Okayama, Koji Teruya, Hirokazu Kimura, Natsumi Noji, Yasuyoshi Ishii, Masahiko Fujii, Mizue Oda, Toshiyuki Sasagawa
Journal of Medical Virology.2020; 92(12): 3766. CrossRef
Analysis of Sequence Variation and Risk Association of Human Papillomavirus 52 Variants Circulating in Korea
Youn Jin Choi, Eun Young Ki, Chuqing Zhang, Wendy C. S. Ho, Sung-Jong Lee, Min Jin Jeong, Paul K. S. Chan, Jong Sup Park, Xuefeng Liu
PLOS ONE.2016; 11(12): e0168178. CrossRef
Uncommon and Rare Human Papillomavirus Genotypes Relating to Cervical Carcinomas
Na Rae Kim, Myunghee Kang, Soon Pyo Lee, Hyunchul Kim, Jungsuk An, Dong Hae Chung, Seung Yeon Ha, Hyun Yee Cho
Korean Journal of Pathology.2014; 48(1): 43. CrossRef
Distribution of Human Papillomavirus 52 and 58 Genotypes, and Their Expression of p16 and p53 in Cervical Neoplasia
Tae Eun Kim, Hwal Woong Kim, Kyung Eun Lee
Korean Journal of Pathology.2014; 48(1): 24. CrossRef

Prevalence and Genotype Distribution of Cervical Human Papillomavirus DNA in Korean Women: A Multicenter Study.: Sung Ran Hong, In Sun Kim, Dong Won Kim, Mi Jin Kim, Ae Ree Kim, Young Ok Kim, Hye Sun Kim, Seo Hee Rha, Gyeong Sin Park, Yong Koo Park, Yong Wook Park, Ho Sung Park, Kwang Sun Suh, Jin Hee Sohn, Mi Kyung Shin, Hoon Kyu Oh, Ki Jung Yun, Hye Kyoung Yoon, Shi Nae Lee, Ah Won Lee, Hyo Jin Lee, Hyun Yee Cho, Chan Choi, Woon Won Jung; Korean J Pathol. 2009;43(4):342-350.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.342

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Abstract PDF

Background
DNA prevalence and type distribution of human papillomavirus (HPV) varies geographically. We investigated HPV prevalence and type distribution in Korean women using the MyHPV DNA chip testing. Methods: A total of 2,368 women from five regions of the country underwent Pap smear examination and MyHPV chip testing. Results: Overall HPV positivity was 15.8% and 78.4% in women with normal and abnormal cytology, respectively. High-risk HPV infection was strongly correlated with cytological atypia. In women with abnormal cytology, the five most common HPV types were 16, 58, 18, 52, and 56/53, and HPV16 was significantly the most common type in most geographical regions. After HPV16, HPV58, and 52 were the next most frequently detected types. Women with normal cytology, in contrast, showed heterogeneity in HPV type distribution. High-grade intraepithelial lesions infected with HPV16, 18, 31 or 45 are more likely to progress to carcinoma. Conclusions: The HPV chip test can provide useful data regarding HPV positivity and type. The most common HPV type in Korean women with abnormal cytology is HPV16, with HPV58 and 52 being frequently present. Our data may have important implications for vaccination programs and the development of cervical screening.

Citations

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HPV genotyping by L1 amplicon sequencing of archived invasive cervical cancer samples: a pilot study
Charles D. Warden, Preetam Cholli, Hanjun Qin, Chao Guo, Yafan Wang, Chetan Kancharla, Angelique M. Russell, Sylvana Salvatierra, Lorraine Z. Mutsvunguma, Kerin K. Higa, Xiwei Wu, Sharon Wilczynski, Raju Pillai, Javier Gordon Ogembo
Infectious Agents and Cancer.2022;[Epub] CrossRef
Enhanced disease progression due to persistent HPV-16/58 infections in Korean women: a systematic review and the Korea HPV cohort study
Jaehyun Seong, Sangmi Ryou, JeongGyu Lee, Myeongsu Yoo, Sooyoung Hur, Byeong-Sun Choi
Virology Journal.2021;[Epub] CrossRef
Comparison of FFPE histological versus LBP cytological samples for HPV detection and typing in cervical cancer
Geehyuk Kim, Hyemi Cho, Dongsup Lee, Sunyoung Park, Jiyoung Lee, Hye-young Wang, Sunghyun Kim, Kwang Hwa Park, Hyeyoung Lee
Experimental and Molecular Pathology.2017; 102(2): 321. CrossRef
Distribution of Oncogenic Human Papillomavirus Genotypes at High Grade Cervical Lesions above CIN 2 Grade with Histological Diagnosis
Geehyuk Kim, Sungyoung Park, Hye-young Wang, Sunghyun Kim, Sangjung Park, Kwangmin Yu, Boohyung Lee, Seung-Ju Ahn, Eun-Joong Kim, Dongsup Lee
Biomedical Science Letters.2016; 22(2): 37. CrossRef
Human Papillomavirus Prevalence and Genotype Distribution in Normal and ASCUS Specimens: Comparison of a Reverse Blot Hybridization Assay with a DNA Chip Test
Sunghyun Kim, In-soo Lee, Dongsup Lee
Biomedical Science Letters.2015; 21(1): 32. CrossRef
Genotype Analysis of Human Papilloma Virus Infection in Accordance with Cytological Diagnoses
Mi-Suk Park, Hyun-Wook Cho, Jin-Gak Kim, Nan-Young Bae, Dong-Sun Oh, Ho-Hyun Park
Korean Journal of Clinical Laboratory Science.2015; 47(1): 39. CrossRef
Comparison of the Cobas 4800 HPV and HPV 9G DNA Chip Tests for Detection of High-Risk Human Papillomavirus in Cervical Specimens of Women with Consecutive Positive HPV Tests But Negative Pap Smears
Sun-Young Jun, Eun Su Park, Jiyoung Kim, Jun Kang, Jae Jun Lee, Yoonjin Bae, Sang-Il Kim, Lee-So Maeng, Magdalena Grce
PLOS ONE.2015; 10(10): e0140336. CrossRef
Uncommon and Rare Human Papillomavirus Genotypes Relating to Cervical Carcinomas
Na Rae Kim, Myunghee Kang, Soon Pyo Lee, Hyunchul Kim, Jungsuk An, Dong Hae Chung, Seung Yeon Ha, Hyun Yee Cho
Korean Journal of Pathology.2014; 48(1): 43. CrossRef
Evaluation of Human Papillomavirus Genotyping from Formalin-fixed Paraffin-embedded Specimens in Cervical Cancers
Hyunwoo Jin
Journal of Life Science.2014; 24(9): 1025. CrossRef
Comparative Evaluation of the HPV28 Detection and HPV DNA Chip Test for Detecting and Genotyping Human Papillomaviruses
Eunsim Shin, Heojin Bae, Wan-Keun Song, Sun-Kyung Jung, Yoo-Sung Hwang
Laboratory Medicine Online.2013; 3(4): 234. CrossRef
Significance of HPV-58 Infection in Women Who Are HPV-Positive, Cytology-Negative and Living in a Country with a High Prevalence of HPV-58 Infection
Joon Seon Song, Eun Ju Kim, Jene Choi, Gyungyub Gong, Chang Ohk Sung, Robert D. Burk
PLoS ONE.2013; 8(3): e58678. CrossRef
REBA HPV‐ID® for efficient genotyping of human papillomavirus in clinical samples from Korean patients
Sunghyun Kim, Dongsup Lee, Sangjung Park, Tae Ue Kim, Bo‐Young Jeon, Kwang Hwa Park, Hyeyoung Lee
Journal of Medical Virology.2012; 84(8): 1248. CrossRef
Dynamin 2 expression as a biomarker in grading of cervical intraepithelial neoplasia
Yoo-Young Lee, Sang Yong Song, In-Gu Do, Tae-Joong Kim, Byoung-Gie Kim, Jeong-Won Lee, Duk-Soo Bae
European Journal of Obstetrics & Gynecology and Reproductive Biology.2012; 164(2): 180. CrossRef
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
The Korean Journal of Pathology.2011; 45(6): 612. CrossRef
Human Papillomavirus Prevalence in Gangwon Province Using Reverse Blot Hybridization Assay
Dongsup Lee, Sunghyun Kim, Sangjung Park, Hyunwoo Jin, Tae Ue Kim, Kwang Hwa Park, Hyeyoung Lee
The Korean Journal of Pathology.2011; 45(4): 348. CrossRef
Pediatric vulvar squamous cell carcinoma in a liver transplantation recipient: a case report
Na-Rae Kim, Soyi Lim, Hyun Yee Cho
Journal of Gynecologic Oncology.2011; 22(3): 207. CrossRef

Diagnostic Accuracy of Cervicovaginal Cytology in the Detection of Squamous Epithelial Lesions of the Uterine Cervix; Cytologic/Histologic Correlation of 481 Cases.: So Young Jin, Sang Mo Park, Mee Sun Kim, Yoon Mi Jeen, Dong Won Kim, Dong Wha Lee; J Pathol Transl Med. 2008;19(2):111-118.; DOI: https://doi.org/10.3338/kjc.2008.19.2.111

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Abstract PDF

BACKGROUND
Cervicovaginal cytology is a screening test of uterine cervical cancer. The sensitivity of cervicovaginal cytology is less than 50%, but studies of cytologic/histologic correlation are limited. We analyzed the diagnostic accuracy of cervicovaginal cytology in the detection of the squamous epithelial lesions of the uterine cervix and investigate the cause of diagnostic discordance. MATERIALS AND METHODS: We collected a total of 481 sets of cervicovaginal cytology and biopsies over 5 years. The cytologic diagnoses were categorized based on The Bethesda System and the histologic diagnoses were classified as negative, flat condyloma, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, or squamous cell carcinoma. Cytohistologic discrepancies were reviewed.
RESULTS
The concordance rate between the cytological and the histological diagnosis was 79.0%. The sensitivity and specificity of cervicovaginal cytology were 80.6% and 92.6%, respectively. Its positive predictive value and negative predictive value were 93.7% and 77.7%, respectively. The false negative rate was 19.4%. Among 54 false negative cytology cases, they were confirmed by histology as 50 flat condylomas, 2 CIN I, 1 CIN III, and 1 squamous cell carcinoma. The causes of false negative cytology were sampling errors in 75.6% and interpretation errors in 24.4%. The false positive rate was 7.4%. Among 15 false positive cytology cases, they were confirmed by histology as 12 atypical squamous cells of undetermined significance (ASCUS) and 3 low grade squamous intraepithelial lesions (LSIL). The cause of error was interpretation error in all cases. The overall diagnostic accuracy of cervicovaginal cytology was 85.7%.
CONCLUSIONS
Cervicovaginal cytology shows high overall diagnostic accuracy and is a useful primary screen of uterine cervical cancer.

Citations

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Overall accuracy of cervical cytology and clinicopathological significance of LSIL cells in ASC‐H cytology
S. H. Kim, J. M. Lee, H. G. Yun, U. S. Park, S. U. Hwang, J.‐S. Pyo, J. H. Sohn
Cytopathology.2017; 28(1): 16. CrossRef
Correlation Analysis Between Cervicovaginal Cytologic and Histopathologic Diagnoses in Cervical Squamous Cell Neoplasm
Kyoung Bun Lee, Woon Sun Park, Jin Hee Sohn, Min Kyung Kim, Dong Hoon Kim, Hee Sung Kim, Seoung Wan Chae, Sung Hee Kang, Young Hye Cho, Hee Dae Pak, Sun Hee Kim
The Korean Journal of Pathology.2009; 43(2): 157. CrossRef

Fine Needle Aspiration Cytology of the Salivary Gland: An analysis of 221 cases .: Ayoung Park, Hee Kyoung Kim, Dong Won Kim, So Young Jin, Dong Wha Lee; J Pathol Transl Med. 1999;10(2):133-143.

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Abstract PDF: Fine needle aspiration cytology of the salivary lesions was performed on 221 patients at Soonchunhyang University Hospital for 10 years. Of 221 aspirates, 6 aspirates(2.7%) were inadequate, 116 cases(52.5%) were non-neoplastic lesions, 76(34.4%) cases were benign neoplasms and 23 cases(10.4%) were malignant neoplasms. The cytologic diagnoses could be correlated with histologic findings in 58 cases. FNAC correctly discriminated between neoplastic and nonneoplastic lesions in fifty-seven lesions and failed in a case, and overall accuracy, sensitivity, and specificity were 98.3%, 98.0%, and 100.0%. FNAC correctly discriminated malignant neoplasms from benign neoplastic/non- neoplastic lesions in fifty-three cases and failed in five cases, and overall accuracy, sensitivity, and specificity were 91.3%, 72.7%, and 95.7%. Among three false negative cases, two mucoepidermoid carcinomas were misdiagnosed as mucocele and benign neoplasm, and an acinic cell carcinoma were misdiagnosed as Warthin's tumor. Two false positive cases were a Warthin's tumor misdiagnosed as squamous cell carcinoma and a pleomorphic adenoma misinterpretated as suggestive of malignancy. In conclusion, diagnostic accuracy of FNAC of salivary lesions is high, and the possibilities of low grade mucoepidermoid carcinoma and acinic cell carcinoma should be considered on hypocellular smears with mucoid or fluidy background.

A Multiinstitutional Consensus Study on the Pathologic Diagnosis of Endometrial Hyperplasia and Carcinoma.: Kwang Sun Suh, Insun Kim, Moon Hyang Park, Geung Hwan Ahn, Jin Hee Sohn, In Ae Park, Hye Kyoung Yoon, Kyu Rae Kim, Hee Jung An, Dong Won Kim, Mi Jin Kim, Hee Jae Joo, Eun Kyung Kim, Young Hee Choi, Chong Woo Yoo, Kyung Un Choi, Sang Yeop Yi, Hye Sun Kim, Sung Ran Hong, Hee Jeong Lee, Sun Lee; Korean J Pathol. 2008;42(2):87-93.

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Abstract PDF: BACKGROUND
The purpose of this study was to examine the reproducibility of both the diagnosis of endometrial hyperplasia (EH) or adenocarcinoma, and the histologic grading (HG) of endometrioid adenocarcinoma (EC).
METHODS
Ninety-three cases of EH or adenocarcinomas were reviewed independently by 21 pathologists of the Gynecologic Pathology Study Group. A consensus diagnosis was defined as agreement among more than two thirds of the 21 pathologists.
RESULTS
There was no agreement on the diagnosis in 13 cases (14.0%). According to the consensus review, six of the 11 EH cases (54.5%) were diagnosed as EH, 48 of the 57 EC cases (84.2%) were EC, and 5 of the 6 serous carcinomas (SC) (83.3%) were SC. There was no consensus for the 6 atypical EH (AEH) cases. On the HG of EC, there was no agreement in 2 cases (3.5%). According to the consensus review, 30 of the 33 G1 cases (90.9%) were G1, 11 of the 18 G2 cases (61.1%) were G2, and 4 of the 4 G3 cases (100.0%) were G3.
CONCLUSIONS
The consensus study showed high agreement for both EC and SC, but there was no consensus for AEH. The reproducibility for the HG of G2 was poor. We suggest that simplification of the classification of EH and a two-tiered grading system for EC will be necessary.

A study of diagnostic value on fine needle aspiration cytology of the breast masses.: Dong Won Kim, Dong Wha Lee; J Pathol Transl Med. 1993;4(1):1-8.

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Abstract PDF: No abstract available.

Case Report

Fine Needle Aspiration Cytology of Solid Papillary Carcinoma of the Breast: Report of a case associated with mucinous carcinoma.: Hee Kyung Kim, Dong Won Kim, So Young Jin, Dong Wha Lee; J Pathol Transl Med. 2001;12(2):127-130.

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Abstract PDF: Solid papillary carcinoma of the breast is a distinctive form of intraductal papillary carcinoma frequently associated with both mucinous carcinoma and infiltrating ductal carcinoma, not otherwise specific. To our knowledge, this case is the first description of the cytologic aspects of solid papillary carcinoma of the breast in the Korean literature. We experienced a case of solid papillary carcinoma of the right breast diagnosed by fine needle aspiration cytology(FNAC) in a 70-year-old female. FNAC from the right breast showed high cellularity consisting of mostly tight clusters of tumor cells and a few scattered tumor cells. The nuclei were monotonously round to oval in shape with inconspicuous nucleoli. The cytoplasm was abundant and finely granular. Scant amount of mucinous material was present on the background. The diagnosis was confirmed histologically and immunohistochemically.

Original Article

Ki-67 Labelling Index and Bax Expression According to the Capsular Invasion in the Follicular Neoplasms of the Thyroid.: Hee Kyung Kim, Dong Wha Lee, So Young Jin, Dong Won Kim; Korean J Pathol. 2001;35(6):531-535.

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Abstract: BACKGROUND
There have been a few studies concerning the differential diagnosis between follicular adenomas and minimally invasive follicular carcinomas, but it is difficult to exclude the possibility of minute capsular and/or vascular invasion throughout the capsular areas as a whole.
METHODS
We examined the diagnostic usefulness of Ki-67 labelling index and bax expression for the differential diagnosis of follicular adenomas and minimally invasive follicular carcinomas.
RESULTS
The result of immunohistochemical staining with Ki-67 and bax antibodies were analyzed in 58 cases of follicular neoplasms from 1996 to 1999. Of 58 cases, 35 were follicular adenomas and 23 were minimally invasive follicular carcinomas. The Ki-67 labelling index was significantly higher in minimally invasive follicular carcinoma of the thyroid (Ki-67 labelling index, 1.62+/-0.35%) than follicular adenoma (0.46+/-0.21%) (P<0.05). Of the follicular adenomas, Ki-67 labelling index of the tumor with 5 cm or more in diameter was 0.38+/-0.13%, while that of the tumor with less than 5 cm was 0.51+/-0.24%. Of the minimally invasive follicular carcinoma, Ki-67 labelling index of the tumor with 5 cm more was 1.30+/-0.07%, while that of the tumor with less than 5 cm was 1.65+/-0.37%. Diffuse bax expression was seen in 27 of 35 cases of follicular adenomas and 2 of 23 cases of minimally invasive follicular carcinoma (P<0.05).
CONCLUSIONS
Our findings suggest Ki-67 labelling index and the degree of bax expression are useful markers for the differential diagnosis between the follicular adenoma and the minimally invasive follicular carcinoma of the thyroid.

Case Report

Fine Needle Aspiration Cytology of Mucoepidermoid Carcinoma of the Peripheral Lung: A Case Report.: Min Sung Choi, So Young Jin, Dong Won Kim, Dong Wha Lee; J Pathol Transl Med. 2005;16(1):36-40.

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Abstract PDF: The mucoepidermoid carcinoma is a rare tumor in the lung for less than 1% of all pulmonary neoplasm. It is mostly presented as a solitary pulmonary nodule at a large bronchial tree on bronchoscope. But more peripheral located tumor that not accessible to the bronchoscope are rarely reported on literature. The cytologic findings of these tumors are discribed as a mixture of squamous cells, mucous cells, and intermediate cells with overlapped cellular clusters. We experienced a case of peripheral mucoepidermoid carcinoma of lung diagnosed by fine needle aspiration cytology. The smear showed many cellular clusters on mucoid background. They consisted of many intermediate cells with occasional mucus-secreting cells, but malignant squamous cells were not present.

Original Articles

A Cytopathologic Analysis of Percutaneous Transthoracic Needle Aspiration Cytology of the Lung: A Six-year Correlation Study in 322 Cases.: Sook Kim, Dong Won Kim, So Young Jin, Dong Wha Lee; J Pathol Transl Med. 1995;6(2):140-147.

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Abstract PDF: In a six-year period (from May 1988 to April 1994), fine needle aspiration cytology (FNAC) of 322 pulmonary lesions from 296 patients were performed at Soonchunhyang University Hospital. Of these 322, malignancy was diagnosed cytologically in 139 (43.2%), suspicious malignancy in 7 (2.2%), negative in 164 (50.8%), and insufficient material in 12 (3.8%). Malignant lesion consisted of 54 cases of adenocarcinoma, 50 cases of squamous cell carcinoma, 18 cases of small cell carcinoma. They were verified by histologic confirmation in 70 cases. There were 2 (0.6%) false positive cases due to florid bronchoalveolar hyperplasia and atypical bronchial epithelial cells associated with granulomatous lesion. Overall accuracy rate was 90%, the sensitivity 84.3% and the specificity 94.7%.

Utility of Bile Duct Brush Cytology in Pancreaticobiliary Diseases: Prospective Comparative Study of Conventional Smear and MonoPrep2(TM) Liquid Based Cytology.: So Young Jin, Dong Wha Lee, Mee Sun Kim, Young Deok Cho, Young Koog Cheon, Min Sung Choi, Dong Won Kim; J Pathol Transl Med. 2006;17(1):38-45.

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Abstract PDF: Bile duct brush cytology has been employed as a diagnostic tool for the evaluation of pancreatic and biliary tract strictures. The specificity of this method is high however, its sensitivity is quite low. A recent study employing liquid based cytology (LBC) reported results comparable to those achieved via conventional cytology. Therefore, we have attempted to prospectively evaluate the diagnostic utility of bile duct brush cytology in pancreaticobiliary diseases. A total of 46 cases with bile duct stricture were enrolled including 11 cases of benign stricture, 29 cases of bile duct carcinoma, 3 cases of gallbladder cancer, and 3 cases of pancreatic cancer. Both conventional smear and LBC using MonoPrep2(TM) system were conducted in each case. The cytological diagnosis of each case was classed into the following categories; benign, suspicious for malignancy, and malignancy. The diagnostic accuracy of both cytologic methods was investigated. LBC evidenced a high rate of material insufficiency (13/46), which was attributed to low cellularity. The kappa index of both cytological methods was 0.508. Cytological and tissue diagnoses were correlated in 25 cases conducted from biopsy or operation. The sensitivity, specificity, positive predictive value, and negative predictive value were 41.2% (7/17), 100% (8/8), 100% (7/7), and 44.4% (10/18) in conventional smear; 58.8% (10/17), 87.5% (7/8), 90.9% (10/11), and 50.0% (7/14) in LBC; and 94.1% (16/17), 87.5% (7/8), 94.1% (16/17), and 87.5% (7/8) in any one of both cytological methods, respectively. Based on these results, the sensitivity of LBC was found to be superior to that of conventional smear and we were able to obtain higher positive predictive value upto 94.1% by simultaneously conducting both cytologic methods.

Alterations of 9p21-22 Region Encoding Genes in Primary Glioblastomas.: Hong Jik Doh, Seong Il Suh, Dong Won Kim, Il Man Kim, Man Bin Yim, Eun Ik Son, Kun Young Kwon, Sang Sook Lee, Sang Pyo Kim; Korean J Pathol. 2002;36(6):394-399.

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Abstract PDF: BACKGROUND
Glioblastomas are one of the most common and aggressive malignant glial tumors occuring in the central nervous system. This study analyzed the status of p15INK4b, p14ARF, p16INK4a, MTAP, IFNA, and IFNB genes in 36 primary glioblastomas to investigate whether the inactivation of these genes participate in primary glioblastoma tumorigenesis.
METHODS
We used polymerase chain reaction, polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) analysis, and methylation-specific PCR.
RESULTS
Homozygous deletions at the p16INK4a gene were detected in 11 cases (30.5%) of 36 primary glioblastomas, and the promoter hypermethylation was found in 3 cases (8.3%) of 36 primary glioblastomas. In mutational analysis for the p16INK4a gene by PCR/SSCP, there was no abnormal mobility-shifted band in 36 cases of primary glioblastomas. The overall frequency of p16INK4a alterations including homozygous deletion and promoter hypermethylation in 36 primary glioblastomas was 38.8% (14 of 36). Deletions of p15INK4b were noted in 4 cases (11.1%), whereas deletions of the p14ARF and MTAP genes were detected in 1 case of 36 cases of primary glioblastomas. But deletions of the INFA and B genes were not found.
CONCLUSIONS
These results suggest that alterations of the p16INK4a gene can be important mechanisms of the tumorigenesis of primary glioblastomas, and the p16INK4a gene is inactivated by mechanisms including homozygous deletion and promoter hypermethylation.

Case Reports

Adenoid Basal Carcinoma Associated with Invasive Squamous Cell Carcinoma of Uterine Cervix: A case report.: Hyun Jung Kim, Dong Won Kim, So Young Jin, Dong Wha Lee; Korean J Pathol. 1996;30(8):739-741.

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Abstract PDF: Adenoid basal carcinoma of the uterine cervix is a rare neoplasm that accounts for less than 1% of cervical adenocarcinomas. Though it has been confused with adenoid cystic carcinoma, it is now distinctly recognized by better prognosis and different histologic and immunohistochemical findings. We have experienced a case of adenoid basal carcinoma associated with invasive squamous cell carcinoma of the uterine cervix in a 52-year-old woman. The tumor was composed of small, round to oval nests of basaloid cells with peripheral palisading. Some of the nests showed central cystic spaces, or cribriform pattern, and central squamous differentiation with cytological atypia. Invasive squamous cell carcinoma was located adjacent to the adenoid basal carcinoma without any transition between these two lesions. Immunohistochemically, the tumor cells disclosed positive staining for cytokeratin, but negative reaction for CEA, EMA, and S-100 protein.

Malignant Mixed Mesodermal Tumors of Ovary: 3 cases report.: Dong Won Kim, Tae Jung Kwon, Dong Wha Lee; Korean J Pathol. 1988;22(2):169-179.

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Abstract PDF: Malignant mixed mesodermal tumor (MMMT) of the ovary is endometrioid tumor containing epithelial and mesenchymal components. The mesenchymal component may be homologous, in which case the term carcinosarcoma is often used, or heterologous, containing cartilage, striated muscle, osteoid, bone, or fat, or combination of these elements. MMMT usually afflicts the postmenopausal woman and occurs more often in the nulliparous female. The disease is usually advanced (stage III) when diagnosed. Cliniopathologic data were presented for 3 cases of MMMT of the ovary with review of literatures. Clinical history substantiated previous reports in postmenopausal women wit this tumor. Symptoms were the same as for ovarian malignancy in general. All the patients presented wit stage II disease, according to the International Federation fo Gynecology and Obstetrics (FIGO) classification. Two patients died of tumor 4 and 10 months after operation, respectively. One patient had been alive at 2 months after operation. None of 3 cases demonstrate evidence of endometriosis in the remaining ovaries. Microscopically, periodic acid-Schiff (PAS)-positive, diastase-resistant hyaline droplets were found frequently in undifferentiated mesenchymal stroma and epithelial structures. The clinical significance and origin of the hyaline droplets in MMMT should be further explored.

Original Article

Diagnostic Usefulness of Fine Needle Aspiration Cytology on Lymphadenopathy: An analysis of 1,216 Cases .: Dong Won Kim, So Young Jin, Dong Wha Lee, Chan Soo Lee; J Pathol Transl Med. 1997;8(1):11-19.

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Abstract PDF: Clinical lymphadenopathies are subjected to fine needle aspiration cytology(FNAC) for diagnosing not only benign lesions but also malignant ones, as the first diagnostic procedure. While the diagnostic reliability in metastatic carcinoma is high, it is difficult to differentiate malignant lymphoma from reactive conditions. We evaluated the diagnostic reliability of FNAC in lymphadenopathy, and discuss the diagnostic limitation and its place in clinical practice in this study. Over 8 years from January 1988, FNAC of 1,216 lymphadenopathies were analyzed and among them 170 cases were compared with histopathology. The results are as follows. 1. Of all the cases, 890 cases(73.2%) were diagnosed cytologically as benign, 312 cases(25.7%) as malignant, and 14 cases(1.1%) as unsatisfactory material. Reactive hyperplasia was diagnosed in 585 cases(65.7%) of the benign lesions, and among the malignant diseases, metastatic carcinoma was diagnosed in 248 cases(79.5%), and malignant lymphoma in 62 cases(19.9%). 2. The overall diagnostic accuracy was 89.2%, and no false positive case and 9 false negative results were observed among 170 cases which were proven by histopathology. Six cases of sampling error of false negative diagnoses included 3 of metastatic carcinomas and 3 of malignant lymphomas. The causes were difference between aspiration and biopsy site, poor fixation, or scanty cellularity with bloody smear. All 3 cases of misinterpretation error were malignant lymphomas, one of mixed type on biopsy which was diagnosed as reactive hyperplasia cytologically. In summary, FNAC technique is thought to be useful in the initial diagnosis of lymphadenopathies as well as in the follow-up of patients with known malignancy. Although the results of malignant lymphoma was less accurate than other malignant lesions, the application of strict cytologic criteria or lymphoid marker studies of aspiration material will reduce the false negative rate.

Case Report

A Case of Desmoplastic Fibroma of the Mandible.: Dong Won Kim, Tae Jung Kwon, Dong Wha Lee; Korean J Pathol. 1988;22(3):340-347.

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Abstract PDF: A case of desmoplastic fibroma of mandible in a 18 years old woman is presented. She had complained progressive swelling of right mandible for 4 years. Radiographically, a multilocular radiolucent of right hemimandibulectomy showed multinodular external surface without cortical destruction. Cut surfaces revealed grayish white, fibrous homogeneous appearance with firm consistency, sparing head portion. The maximum diameter of the tumor was 13 cm. Microscopically, the tumor was composed of interlacing bundles of monomorphic spindle-shaped cells with abundant intercellular collagen. Ultrastructurally, most tumor cells were fibroblastic-like cells with abundant RER and cytoplasmic fibrils, but a few disclosed transition to myofibroblasts. However, no fully developed myofibroblasts were seen.

Original Article

Plasminogen Activator Inhibitor-1, c-erbB2, and p53 Protein Overexpression and Prognosis in Gastric Adenocarcinoma.: Ayoung Park, So Young Jin, Dong Won Kim, Dong Wha Lee; Korean J Pathol. 2000;34(8):559-566.

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Abstract PDF: Despite its fall in incidence, gastric adenocarcinoma remains a common disease with dismal prognosis worldwide. A better understanding of its tumorigenesis and biologic properties of tumor cells related to invasion and metastasis is crucial to improving diagnosis and treatment. Conflicting results concerning the relationships between overexpression of PAI-1, c-erbB2, and p53 protein and biologic behavior of gastric carcinoma have been noted. The aim of this study was to evaluate the value of overexpression of PAI-1, c-erbB2, and p53 protein as prognostic factors in gastric adenocarcinoma. Overexpression of PAI-1, c-erbB2, and p53 protein by immunohistochemistry was correlated with variable clinicopathological parameters and patients' survival in 80 cases of gastric adenocarcinoma. Overall PAI-1 expression rate was 63.7% (51/80) and higher in advanced cancer (p=0.0003) and nodal metastasis (p=0.003) groups. Overall c-erbB2 expression rate was 43.8% (35/80) and higher in antral (p=0.03), differentiated (p=0.001), intestinal (p=0.0007), and expanding (0.03) groups. The p53 protein overexpression was 37.5% (30/80) and higher in early cancer (p=0.02), differentiated (p=0.006) and intestinal groups (p=0.009). Patients with PAI-1, c-erbB2, and p53 protein positive tumors tended to have poorer survival rates than patients with PAI-1, c-erbB2, and p53 protein negative tumors, but the difference was not statistically significant (p=0.25, 0.37, 0.52). Our data indicated that PAI-1 overexpression is one of the poor prognostic factors in gastric adenocarcinoma and c-erbB2 and p53 protein seem to be involved in the early stage of carcinogenesis of intestinal type-gastric adenocarcinoma.

Case Report

Fine Needle Aspiration Cytology of Salivary Duct Carcinoma: A Case Report.: A Young Park, Hyun Jung Kim, Dong Won Kim, Dong Wha Lee; J Pathol Transl Med. 1997;8(2):143-149.

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Abstract PDF: PURPOSE: To investigate renal toxicity of high-dose intravenous immunoglobulin(IVIG) in children with Kawasaki disease and idiopathic thrombocytopenic purpura. METHODS: 23 children with Kawasaki disease and 7 children with idiopathic thrombocytopenic purpura who were treated with high-dose IVIG(2 g/kg) were evaluated for the change of urine output, blood urea nitrogen(BUN), serum creatinine(Scr), creatinine clearance(Ccr), tubular reabsorption of phosphorus(TRP), fractional excretion of sodium(FENa), 24hour urine b2-microg1obuin/creatinine(b2MG/cr) ratio and urine microalbumin/creatinine(MA/cr) ratio at post-IVIG 1 and 3 day. RESULTS: There was no significant change of urine output, BUN, Scr, Ccr, TRP, 24hour urine b2MG/cr and MA/cr ratio after high-dose IVIG treatment. Transient increase of FENa at post-IVIG 1 day was the only significant change.
CONCLUSION
There was no significant renal toxicity of high-dose IVIG in children with Kawasaki disease and idiopathic thrombocytopenic purpura who had normal renal function.

Original Article

Fine Needle Aspiration Cytology of Matrix Producing Carcinoma of the Breast.: Hyun Jung Kim, Ayoung Park, Dong Won Kim, Dong Wha Lee, Kui Hyang Kwon; J Pathol Transl Med. 1997;8(2):174-178.

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Abstract PDF: Matrix producing carcinoma of the breast is a variant of heterologous metaplastic carcinoma which is defined as "overt carcinoma with direct transition to a cartilagenous and/or osseous stromal matrix without an intervening spindle cell zone or osteoclastic cells". This tumor is very rare, occuring in less than 0.2% of total breast carcinoma, but the prognosis is better than other metaplastic carcinoma. We experienced a case of fine needle aspiration(FNA) cytologic finding of matrix producing carcinoma of the breast. A 75-year old woman, who presented a right huge breast mass(9x8cm) during 10months, was examined. Mammography reveals right lateral mass with even density without calcification. Breast ultrasonography shows multifocal hypoechogenic cystic change in the huge mass, suggesting resolving hematoma or carcinoma or sarcoma with necrosis. On cytologic finding of FNA, myxoid matrix was the dominant feature and the rest of the material was composed of scanty isolated atypical cells with large irregular nuclei. The histologic finding was moderately differentiated adenocarcinoma with abundant cartilagenous matrix and focal squamous metaplasia.

Case Report

A Case of Gastric Inverted Hyperplastic Polyp Associated with Gastritis Cystica Profunda and Early Gastric Carcinoma.: Min Sung Choi, So Young Jin, Dong Won Kim, Dong Wha Lee, Sang Mo Park; Korean J Pathol. 2007;41(1):55-58.

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Abstract PDF: A gastric inverted hyperplastic polyp is characterized by downward growth of the hyperplastic mucosal components into the submucosa. Lesions are composed of hyperplastic foveolar-type glands, and sometimes coexist with gastritis cystica profunda (GCP). Adenocarcinoma frequen- tly can coexist, but the relationship is not clear. A 71-year-old male was admitted to hospital because of dyspepsia for one month. He underwent a wedge resection of the stomach, after endoscopic biopsies. The gross finding showed a slightly elevated papillary lesion with central depression. Microscopically, the elevated lesion was composed of hyperplastic fundic glands and foveolar cells, and the central depressed lesion showed a nodular inverted proliferation of normal appearing gastric epithelium and glands in the submucosa. An additional proximal gastrectomy specimen exhibited marked GCP and a minute adenocarcinoma at the proximal margin with p53 protein overexpression.

Original Article

Expression of MMP-2, MT1-MMP, and TIMP-2 mRNA in Breast Carcinomas.: Dong Won Kim, So Young Jin, Dong Wha Lee; Korean J Pathol. 2003;37(6):400-406.

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Abstract PDF: BACKGROUND
The activation of proMMP-2 is induced by membrane type 1-matrix metalloproteinase (MT1-MMP), but inhibited by tissue inhibitors of matrix metalloproteinase type 2 (TIMP-2). This study was carried out to establish the pattern of mRNA expression of MMP-2, MT1-MMP, and TIMP-2 in breast carcinomas.
METHODS
Seventy-nine cases of invasive ductal carcinoma, 10 of ductal carcinoma in situ, and 10 of fibrocystic disease as a control were analysed for the expression of MMP-2, MT1-MMP, and TIMP-2 mRNA, using in situ hybridization. Correlations of the results with the clinical stage, tumor size, nodal status, and nuclear grade were analysed.
RESULTS
The expression rates of MMP-2, MT1-MMP, and TIMP-2 mRNA in invasive ductal carcinoma were 68%, 73%, and 56%, respectively. They were localized to both stromal and tumor cells, but mainly in the latter. The MMP-2 mRNA expression was significantly correlated with the clinical stage (p < 0.05), while the expression of TIMP-2 mRNA was inversely correlated with clinical stage and tumor size(p < 0.05). Significant positive correlations between MMP-2 and MT1-MMP expressions, along with inverse relationships between MMP-2 and TIMP-2, and between TIMP-2 and MT1-MMP, were also found. CONCLUSIONS: MMP-2 and TIMP-2 mRNA expressions might be useful as one of a range of prognostic parameters in breast carcinoma patients.

Case Reports

A Sertoli-Leydig Cell Tumor in a Patient with Complete Androgen Insensitivity Syndrome: A Case Report.: Min Sung Choi, Dong Won Kim, So Young Jin, Sang Mo Park, Dong Wha Lee; Korean J Pathol. 2007;41(1):59-62.

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Abstract PDF: Complete androgen insensitivity syndrome (CAIS) is a rare disorder sometimes referred to as male pseudohermaphroditism. This syndrome is characterized by a 46,XY karyotype with internal bilateral testes, female external genitalia, absence or scantiness of pubic and axillary hair and normal breast development. A variety of gonadal tumors can develop in individuals with CAIS. A 57-year-old patient was admitted to urology with intermittent gross hematuria for one month. CT revealed a left ureteric mass, measuring 2.5 x 2 cm. Ureteroscopic biopsy was performed and the result was a diagnosis of high grade urothelial carcinoma. The patient underwent laparotomy which revealed slightly enlarged gonads in the pelvic cavity. However, a uterus and fallopian tubes were not identified. Left nephroureterectomy and bilateral gonadectomy were performed. The right gonad measured 3.9 x 2.5 x 2 cm and the cut surface showed a well circumscribed, firm, brownish gray colored 2 x 1.8 cm sized nodule. Microscopically, this nodule consisted of uniform and solid tubules containing immature Sertoli cells and Leydig cells which were both positive for alpha-inhibin. The left gonad measured 3.5 x 2 x 1.9 cm and showed atrophic testicular tissue.

Pneumocystis carinii Pneumonia Presented as Diffuse Alveolar Damage: Report of a case.: Sook Kim, Jeong Ja Kwak, Dong Won Kim, So Young Jin, Dong Wha Lee; Korean J Pathol. 1996;30(12):1155-1158.

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Abstract PDF: Pneumocystis carinii is the most common cause of diffuse pulmonary infiltrates in the immunocompromised patients. Microscopically, Pneumocystis carinii pneumonia(PCP) shows characteristic frothy intraalveolar exudate and interstitial lymphocytic and plasma cell infiltrate. However, sometimes the only histologic finding of PCP on routine hematoxylin-eosin stain is that of diffuse alveolar damage(DAD), when we can miss the diagnosis without aid of special stains. We report a case of Pneumocystis carinii pneumonia presenting as DAD in a 50-year old man after chemotherapy due to malignant lymphoma. Open lung biopsy specimen reveals the early stage of DAD without any characteristic findings, such as foamy exudate. However many cysts of Pneumocystis carinii were found on Gomori's methenamine silver(GMS) stain. Therefore, GMS stain should be routinely performed on all biopsy specimens obtained from immunocompromised patients.

Fine Needle Aspiration Cytology of Myositis Ossificans: A Case Report.: Dong Won Kim, Dong Wha Lee; J Pathol Transl Med. 1998;9(1):123-128.

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Abstract PDF: The aspiration cytologic finding of myositis ossificans is not well documented but similar to that seen in nodular fasciitis except less cellularity. Myositis ossificans is a reactive condition that is sometimes mistaken microscopically for extraosseous osteosarcoma. Cytologically, myositis ossificans may be distinguished from extraosseous osteosarcoma by the presence of uniform benign stromal cells composed of mature fibroblasts and osteoclastic giant cells. However, the differential diagnosis may be difficult in the early stage of this reactive and proliferative process. We recently experienced a case of myositis ossificans. The patient was a 67-year-old woman with painful swelling of the left index finger for one month. Simple x-ray finding showed a soft tissue mass with calcific center at middle phalanx of the left hand. Fine needle aspiration cytology revealed a few individual or clusters of spindle cells in dense eosinophilic stroma with osteoclastic giant cells. The spindle cells were uniform, smooth-bordered, and oval nuclei with single small inconspicuous nucleoli, and elongated cytoplasm. The scattered individual cells had eccentric nuclei with one or two nucleoli and abundant, basophilic cytoplasm.

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