Journal of Pathology and Translational Medicine

Original Articles

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification: Hye Ju Kang, Sun Young Kwon, Ahrong Kim, Woo Gyeong Kim, Eun Kyung Kim, Ae Ree Kim, Chungyeul Kim, Soo Kee Min, So Young Park, Sun Hee Sung, Hye Kyoung Yoon, Ahwon Lee, Ji Shin Lee, Hyang Im Lee, Ho Chang Lee, Sung Chul Lim, Sun Young Jun, Min Jung Jung, Chang Won Jung, Soo Youn Cho, Eun Yoon Cho, Hye Jeong Choi, So Yeon Park, Jee Yeon Kim, In Ae Park, Youngmee Kwon; J Pathol Transl Med. 2021;55(6):380-387. Published online October 6, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.29

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Background
Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification.
Methods
Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier).
Results
On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems.
Conclusions
Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Citations

Citations to this article as recorded by

Invasive papillary carcinoma of the breast
Shijing Wang, Qingfu Zhang, Xiaoyun Mao
Frontiers in Oncology.2024;[Epub] CrossRef
Recommendations for Performance Evaluation of Machine Learning in Pathology: A Concept Paper From the College of American Pathologists
Matthew G. Hanna, Niels H. Olson, Mark Zarella, Rajesh C. Dash, Markus D. Herrmann, Larissa V. Furtado, Michelle N. Stram, Patricia M. Raciti, Lewis Hassell, Alex Mays, Liron Pantanowitz, Joseph S. Sirintrapun, Savitri Krishnamurthy, Anil Parwani, Giovann
Archives of Pathology & Laboratory Medicine.2024; 148(10): e335. CrossRef
Encapsulated papillary carcinoma of the breast: A single institution experience
Liang Xu, Qixin Mao, Qiuming Liu, Yufeng Gao, Lihua Luo, Chungen Guo, Wei Qu, Ningning Yan, Yali Cao
Oncology Letters.2023;[Epub] CrossRef
High-risk and selected benign breast lesions diagnosed on core needle biopsy: Evidence for and against immediate surgical excision
Aparna Harbhajanka, Hannah L. Gilmore, Benjamin C. Calhoun
Modern Pathology.2022; 35(11): 1500. 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

Citations to this article as recorded by

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
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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
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Case Report

Large-Cell Acanthoma: A case report.: Yu Hoon Kim, Seong Jin Cho, Ae ree Kim, Nam Hee Won, Kye Yong Song; Korean J Pathol. 1996;30(2):161-163.

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Abstract PDF: Large-cell acanthoma is a generally hyperkeratotic, sharply demarcated patch on sun-exposed skin with the outstanding pathologic feature being composed of large, relatively uniform keratinocytes. We describe a case of large-cell acanthoma that involved the skin of the nasal bridge. Patient was a 56-year-old women with a tannish brown patch, 2 cm in size and of 5 years' duration. Controversial issues about nosologic entity of large cell acanthoma are discussed.

Original Article

The p53 Mutation and DNA Ploidy in Human Metastatic Breast Cancer.: Seong Jin Cho, Ae Ree Kim, Nam Hee Won; Korean J Pathol. 1997;31(2):135-144.

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Abstract PDF: The p53 gene, one of the tumor suppressor genes, is believed to play an important role through mutation and overexpression in the progression of various human malignant tumors. To compare the p53 mutation status between the primary and metastatic lesions of breast cancers and to investigate the mutational pattern of p53, immunohistochemistry (IHC) and polymerase chain reaction and single strand conformational polymorphism (PCR-SSCP) were performed in 25 cases of breast cancers with paraffin embedded tissue. Mutant protein products or point mutation were detected through IHC or PCR-SSCP method. And flow cytometrical (FCM) analysis were performed in the same paraffin blocks to correlate the DNA ploidy and p53 mutation. The following results are summarized. 1. The detection of the p53 gene mutation and overexpression of the p53 protein were measured in 40% and 48%, respectively, in 25 primary tumors, either or both methods was detected in 64%. 2. A concordance rate of the p53 protein expression between the primary and metastatic lesions of 25 breast cancers was 100%, but the concordance rate of the p53 gene mutation was 72%. 3. The correlation between the p53 mutation and the DNA aneuploidy was not statistically significant (p=0.38) 4. A p53 mutation by IHC or PCR-SSCP was more frequently detected in grade III breast cancers than in grade I or II. 5. Among 5 to 9 exons of the p53 gene, exon 7 was the most frequent mutation spot in this study. 6. Additional mutation of the p53 gene was developed in the three metastatic lesions. With the above results it is suggested that the p53 protein overexpression by immunohistochemistry is not correlated with the p53 mutation by PCR-SSCP. The p53 mutation pattern between the primary and metastatic lesions are not idenitical and an additional point mutation can occur in the metastatic lesion. The DNA aneuploidy is more frequently detected in the cases with the p53 protein overexpression than in the p53 protein negative, but it is not statistically significant.

Case Report

Acute Interstitial Pneumonia (Hamman-Rich Syndrome): An Autopsy Case.: Han Kyeom Kim, Ae Ree Kim, Min Ji Jeoung, Won Hee Seo, Jee yeoun Lee, Su Hyun Park; Korean J Pathol. 1997;31(4):366-374.

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Abstract PDF: Acute interstitial pneumonia is a fulminant disease of unknown etiology that usually occurs in a previously healthy person and produces the histologic findings of the organizing phase of diffuse alveolar damage. We experienced an autopsy case of acute interstitial pneumonia of unknown etiology. The patient was a 48 year old man who had been healthy and had not been exposed to organic dusts or other toxic materials. The chief complaints represented were dyspnea and a dry cough for several weeks before hospitalization, and the chest radiographs showed bilateral interstitial infiltrates. Patchy consolidation of air space was also identified and ground-glass attenuation similar to those described in ARDS was detected on high-resolution computed tomography. Steroid pulse therapy, mechanical ventilation, and antibiotics for superimposed bacterial infection were performed, but the symptoms did not improve and the patient died of generalized respiratory insufficiency and severe hypoxemia 2 1/2 months after hospitalization. At autopsy the macroscopic and microscopic findings were confined mainly to the lungs. On the whole, both lungs were firm in consistency and the external surface showed a cobblestone appearance. The cut surface showed almost complete replacement of the normal lung parenchyma with gray to yellow fibrous tissue with a little residual functional area remaining. The pathology of both open lung biopsy and autopsy tissue showed marked hyperplasia of type II pneumocytes, hyaline membrane formation, thickening of the alveolar wall due to extensive fibroblast proliferation, and relatively abundant young collagen deposition in the interstitium. An immunohistochemical stain for cytokeratin revealed epithelial hyperplasia and showed that the alveolar spaces were markedly shrunken by fibrous tissue.

Original Article

Expression of bcl-2 Protein in Colorectal Adenoma and Adenocarcinoma and its Relationship with p53 and Apoptosis.: Ae Ree Kim, Seong Jin Cho, Nam Hee Won, Yang Seok Chae; Korean J Pathol. 1997;31(5):417-426.

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Abstract PDF: Either increased cellular proliferation or decreased death might result in an expansion of their numbers in the oncogenic process. Cellular apoptosis represents an autonomous suicide pathway that helps to restrict the cell number. However bcl-2 and mutant p53 inhibit programmed cell death. To determine whether the bcl-2 gene is activated during colorectal tumorigenesis and whether it has any relationship with p53 and apoptosis, we studied the expression of bcl-2 and p53 in the normal colonic mucosa, in the adenomatous polyps and in the adenocarcinomas using the immunohistochemical method. Also we evaluated the status of apoptosis using the in situ end labeling method. The bcl-2 immunoreactivity was restricted to the basal epithelial cells of all normal colonic mucosa and they were expressed in all adenomas and 86% of adenocarcinomas, especially in the superficial lesion of some tumors. Mutations of p53 were not found in the normal colonic mucosa, but they were present in dysplastic cells of adenomas (52%) and in cancer cells of the adenocarcinomas (47%). Apoptosis was confined to the tips of the normal colonic mucosa. It was more easily detected in the p53-positive adenomas than in the p53-negative adenomas (p=0.010). In the adenocarcinomas, the findings of apoptotic process are not related with p53 mutation (p=0.3) and bcl-2 expression (p=0.187). p53 and bcl-2 are probably one step of several apoptotic processes in the adenocarcinomas.

Case Report

Spontaneous Pneumothorax as a Complication of Pulmonary Metastasis of Osteosarcoma A case report.: Min Kyung Kim, Bong Kyung Shin, Wha Eun Oh, Ae Ree Kim, Nam Hee Won, Jong Sang Choi; Korean J Pathol. 1999;33(4):281-284.

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Abstract PDF: Spontaneous pneumothorax is a known, but relatively rare complication of pulmonary metastases of sarcoma. A 19-year-old man was presented with chest pain and dyspnea for three days and was diagnosed as left pneumothorax. After bleb resection, microscopic examination revealed metastatic osteosarcoma forming subpleural fistula and dystrophic calcification. Four years ago, he had had limb salvage operation and chemotherapy for osteosarcoma of left femur. After two and a half years he had a bleb resection for right pneumothorax without any evidence of metastasis. Six months later, he was found to have a 4x3cm sized lung mass in the right lower lobe. After lobectomy, he was diagnosed as pulmonary metastasis of osteosarcoma. Pneumothorax is the common complication of metastatic osteosarcoma to the lung and it may be presented before the pulmonary metastasis is clinically evident. It is important to recognize a pneumothorax of the patients with osteosarcoma as a possible sign of metastases.

Original Article

Mast Cells in 10-Dimethyl-1,2 Benzanthracene (DMBA)-Induced Rat Mammary Carcinomas: Relationship with Matrix Metallproteinase (MMP)-2 and MMP-9 Expression.: Hyun Ho Lee, Ae Ree Kim, Bum Woo Yeom, Insun Kim; Korean J Pathol. 2001;35(4):306-313.

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Abstract PDF: BACKGROUND
It has been suggested that mast cells are involved in the tumor growth and progression by production of a variety of enzymes and growth factors. They were studied in the 10-dimethyl-1,2 benzanthracene (DMBA)-induced rat mammary tumors, and evaluated in relation with the production of tryptase, chymase, and matrix metalloproteinase (MMP)-2 and MMP-9.
METHODS
Preneoplastic and neoplastic breast tissues of Sprague-Dawley female rats were obtained every week after DMBA treatment for 12 weeks. Toluidine blue stain was used for the identification of mast cells. Mast cell tryptase was studied by immunohistochemistry, and chymase by esterase stain. MMP-2 and MMP-9 were measured by Western blotting.
RESULTS
The numbers of mast cells in breast cancers were higher than in preneoplastic tissues, and there was a positive correlation between the numbers of tryptase-positive cells and the tumor size. MMP-9 quantity was correlated with the numbers of toluidine blue and chymase positive cells, but not with tryptase-positive cells and tumor size. Both active and inactive forms of MMP-2 and MMP-9 were identified in zymogram.
CONCLUSIONS
The mast cells are increased in the DMBA-induced breast cancers, and their tryptase and chymase may play a role in tumor progression with or without participation of MMP-2 and MMP-9.

Case Reports

Follicular Lymphoma with Monoclonal Plasma Cell Differentiation: A Case Report.: Hyun chul Kim, Young Seok Lee, Jung woo Choi, Ae ree Kim, Bom Woo Yeom, Han kyeom Kim, In sun Kim; Korean J Pathol. 2006;40(2):151-155.

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Abstract PDF: We present a case of recurrent follicular lymphoma with an extensive plasma cell component involving infra-auricular lymph nodes in a 64 year-old woman. Immunohistochemical staining showed a strongly positive reaction of the follicles with CD20, bcl-2, bcl-6, CD10 and CD21 on the first biopsy specimen. The intrafollicular and interfollicular plasma cells showed monoclonality for IgG heavy chain and lambda light chain. The histological and immunohistochemical findings in the recurrent tumor were identical with those of the original. Discussion is focused on the importance of the differential diagnosis between reactive lymphoid hyperplasia and other lymphomas having plasmacytic differentiation.

Pulmonary Alveolar Proteinosis accompanied by Osseous Metaplasia: A case report.: Ae Ree Kim, Hyun I Cho, Han Kyeom Kim, Jong Sang Choi, In Sun Kim; Korean J Pathol. 1994;28(5):547-549.

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Abstract PDF: The authors experienced a case of pulmonary alveolar proteinosis. A 58-year-old woman presented with 6 months duration of cough sputum and multiple patch mottled densities in both lung fields. Major histologic finding was filling of the alveoli by Periodic-Acid-Schiff-positive proteinaceous material with maintenance of normal alveolar architecture. Osseous metaplasia was seen in the alveolar space, focally. Ultrastructural study revealed numerous lamellar bodies in alveolar spaces. The immunohistochemical study using antibody to surfactant apoprotein revealed positive reaction in proteinaceous material.

Original Article

Assessment of DNA Ploidy, Estrogen and Progesterone Recetor Status and Her-2/neu Oneoprotein Expression in Breast Carcinoma by Image Analysis.: Ae Ree Kim, In Sun Kim, Kap No Lee; Korean J Pathol. 1994;28(3):246-259.

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Abstract: In 41 cases of breast cancers, the aneuploidy measured by Image Analyzer was compared with that of flow cytometric analysis, and estrogen and progesterone receptor(ER/PR) and Her-2/neu oncoprotein were immunohistochemically stained and measured by Image Analyzer. In ER/PR, the positive nuclear area(PNA, %) was measured, and in Her-2/neu, the content of oncoprotein was expressed as pg/cell. To assess the usefulness of these parameters as a prognostic factor, the author evaluated the results in relation with tumor size, nuclear grade and lymph node metastasis. The obtained results are summarized as follows: 1) The detection rate (90%) of aneuploidy by image analysis was higher than that (70%) of flow cytometric analysis. The concordance rate of both method was 80%. 2) The positivity of ER was 73% and PR was 34%, and the high PNA of ER and PR was related with high nuclear grade. There was an inverse correlation of the ER PNA with tumor size and PR PNA with negative lymph node. 3) Her-2/neu oncoprotein overexpression was found in only 2 cases and another two showed borderline overexpression. All four cases had DNA tetraploidy. From the above results, it was concluded that the image analyzer could be used in DNA analysis and in quantitation of immunostained ER/PR and Her-2/neu oncoprotein, providing the important information in the management of the breast cancer patients.

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