Journal of Pathology and Translational Medicine

Original Article

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

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Invasive papillary carcinoma of the breast
Shijing Wang, Qingfu Zhang, Xiaoyun Mao
Frontiers in Oncology.2024;[Epub] 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

Case Study

Malignant rhabdoid tumor of the kidney in an adult with loss of INI1 expression and mutation in the SMARCB1 gene: Eunkyung Han, Jiyoon Kim, Min Jung Jung, Susie Chin, Sang Wook Lee, Ahrim Moon; J Pathol Transl Med. 2021;55(2):145-153. Published online March 9, 2021; DOI: https://doi.org/10.4132/jptm.2021.01.26

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Abstract PDF

A 57-year-old man with left flank pain was referred to our institute. Computed tomography scans revealed two enhancing masses in the left kidney. The clinical diagnosis was renal cell carcinoma (RCC). He underwent a radical nephrectomy with an adrenalectomy. Two well-circumscribed solid masses in the hilum and the lower pole (4.5 × 3.5 cm and 7.0 × 4.1 cm) were present. Poorly cohesive uniform round to polygonal epithelioid cells making solid sheets accounted for most of the tumor area. The initial diagnosis was RCC, undifferentiated with rhabdoid features. As the tumor showed loss of INI1 expression and a mutation in the SMARCB1 gene on chromosome 22, the revised diagnosis was a malignant rhabdoid tumor (MRT) of the kidney. To date, only a few cases of renal MRT in adults have been reported. To the best of our knowledge, this is the first report of MRT in the native kidney of an adult demonstrating a SMARCB1 gene mutation, a hallmark of MRT.

Citations

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Supratentorial ATRT in a young Infant: Expanding the diagnostic spectrum beyond medulloblastoma
Ali Msheik, Mohamad Aoun, Youssef Fares
Interdisciplinary Neurosurgery.2024; 35: 101857. CrossRef
Malignant rhabdoid tumor of kidney in an adult patient with positive family history of rhabdoid tumor: A case report and review of literature
Farhood Khaleghi mehr, Nasrollah Abian, Mandana Rahimi, Yasaman Moradi
International Journal of Surgery Case Reports.2023; 113: 109053. CrossRef

Original Articles

Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma: Young Chan Wi, Ahrim Moon, Min Jung Jung, Yeseul Kim, Seong Sik Bang, Kiseok Jang, Seung Sam Paik, Su-Jin Shin; J Pathol Transl Med. 2018;52(6):378-385. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.21

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Abstract PDF

Background
BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients.
Methods
BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative.
Results
Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC.
Conclusions
Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC.

Citations

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Immune regulation and prognosis indicating ability of a newly constructed multi-genes containing signature in clear cell renal cell carcinoma
Ziwei Gui, Juan Du, Nan Wu, Ningning Shen, Zhiqing Yang, Huijun Yang, Xuzhi Wang, Na Zhao, Zixin Zeng, Rong Wei, Wenxia Ma, Chen Wang
BMC Cancer.2023;[Epub] CrossRef
Radiogenomic Associations Clear Cell Renal Cell Carcinoma: An Exploratory Study
Derek H Liu, Komal A Dani, Sharath S Reddy, Xiaomeng Lei, Natalie L Demirjian, Darryl H Hwang, Bino A Varghese, Suhn Kyong Rhie, Felix Y. Yap, David I. Quinn, Imran Siddiqi, Manju Aron, Ulka Vaishampayan, Haris Zahoor, Steven Y Cen, Inderbir S Gill, Vinay
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Immunohistochemistry for the diagnosis of renal epithelial neoplasms
Mahmut Akgul, Sean R Williamson
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BRCA1-Associated Protein 1 (BAP-1) as a Prognostic and Predictive Biomarker in Clear Cell Renal Cell Carcinoma: A Systematic Review
Shuchi Gulati, Melissa Previtera, Primo N. Lara
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Renal Cell Carcinoma in End-Stage Renal Disease: A Review and Update
Ziad M. El-Zaatari, Luan D. Truong
Biomedicines.2022; 10(3): 657. CrossRef
CD117, BAP1, MTAP, and TdT Is a Useful Immunohistochemical Panel to Distinguish Thymoma from Thymic Carcinoma
Mounika Angirekula, Sindy Y Chang, Sarah M. Jenkins, Patricia T. Greipp, William R. Sukov, Randolph S. Marks, Kenneth R. Olivier, Stephen D. Cassivi, Anja C Roden
Cancers.2022; 14(9): 2299. CrossRef
BAP1 in cancer: epigenetic stability and genome integrity
Sabrina Caporali, Alessio Butera, Ivano Amelio
Discover Oncology.2022;[Epub] CrossRef
Bioinformatic analysis identifying FGF1 gene as a new prognostic indicator in clear cell Renal Cell Carcinoma
Xiaoqin Zhang, Ziyue Wang, Zixin Zeng, Ningning Shen, Bin Wang, Yaping Zhang, Honghong Shen, Wei Lu, Rong Wei, Wenxia Ma, Chen Wang
Cancer Cell International.2021;[Epub] CrossRef
Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis
Dengyong Xu, Yuzi Xu, Yiming Lv, Fei Wu, Yunlong Liu, Ming Zhu, Dake Chen, Bingjun Bai
BioMed Research International.2020; 2020: 1. CrossRef
Functional characterisation guides classification of novel BAP1 germline variants
Jing Han Hong, Siao Ting Chong, Po-Hsien Lee, Jing Tan, Hong Lee Heng, Nur Diana Binte Ishak, Sock Hoai Chan, Bin Tean Teh, Joanne Ngeow
npj Genomic Medicine.2020;[Epub] CrossRef
Tissue-Based Immunohistochemical Markers for Diagnosis and Classification of Renal Cell Carcinoma
Liang G Qu, Vaisnavi Thirugnanasundralingam, Damien Bolton, Antonio Finelli, Nathan Lawrentschuk
Société Internationale d’Urologie Journal.2020; 1(1): 68. CrossRef
Radiogenomics: bridging imaging and genomics
Zuhir Bodalal, Stefano Trebeschi, Thi Dan Linh Nguyen-Kim, Winnie Schats, Regina Beets-Tan
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The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence: Jee Soon Kim, Youn Soo Lee, Min Jung Jung, Yong Kil Hong; J Pathol Transl Med. 2016;50(6):419-425. Published online October 6, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.30

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Abstract PDF

Background
The 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence.
Methods
One hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence.
Results
Analysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01).
Conclusions
Based on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

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International Journal of Molecular Sciences.2023; 24(22): 16162. CrossRef
Ki-67/MIB-1 and Recurrence in Pituitary Adenoma
Kent Tadokoro, Colten Wolf, Joseph Toth, Cara Joyce, Meharvan Singh, Anand Germanwala, Chirag Patel
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Su Jung Kum, Hye Won Lee, Soon Gu Kim, Hyungsik Park, Ilseon Hwang, Sang Pyo Kim
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Anne-Laure Bernat, Pénélope Troude, Stefano Maria Priola, Ahmad Elsawy, Faisal Farrash, Ozgur Mete, Shereen Ezzat, Sylvia L. Asa, John De Almeida, Allan Vescan, Eric Monteiro, Joao Paulo Almeida, Gelareh Mohammed Zadeh, Fred Gentili
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Frontiers in Oncology.2021;[Epub] CrossRef
Comparative Proteomic Study Shows the Expression of Hint-1 in Pituitary Adenomas
Carolina Carrillo-Najar, Daniel Rembao-Bojórquez, Martha L. Tena-Suck, Sergio Zavala-Vega, Noemí Gelista-Herrera, Miguel A. Ramos-Peek, Juan L. Gómez-Amador, Febe Cazares-Raga, Fidel de la Cruz Hernández-Hernández, Alma Ortiz-Plata
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Ching-Chung Ko, Tai-Yuan Chen, Sher-Wei Lim, Yu-Ting Kuo, Te-Chang Wu, Jeon-Hor Chen
Journal of Neurosurgery.2020; 132(2): 351. CrossRef
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Marta Araujo-Castro, Víctor Rodríguez Berrocal, Eider Pascual-Corrales
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E. Guadagno, E. D’Avella, P. Cappabianca, A. Colao, M. Del Basso De Caro
Journal of Endocrinological Investigation.2020; 43(10): 1429. CrossRef
Study of Simple Immunohistochemical Cytocolorimetric Assay Application for More Accurate Assessment of Prognosis in Patients with Pituitary Adenomas
Pavel V. Nikitin, Marina V. Ryzhova, Lyudmila V. Shishkina, Svetlana V. Shugay, Irina V. Zubova
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Residual Tumor Confers a 10-Fold Increased Risk of Regrowth in Clinically Nonfunctioning Pituitary Tumors
Jelena Maletkovic, Asmaa Dabbagh, Dongyun Zhang, Abdul Zahid, Marvin Bergsneider, Marilene B Wang, Michael Linetsky, Noriko Salamon, William H Yong, Harry V Vinters, Anthony P Heaney
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Case Study

A Case of Metastatic Angiosarcoma Diagnosed by Liquid-Based Preparation: Peculiar Cytoplasmic Changes: Min Jung Jung, Young Ok Kim; Korean J Pathol. 2014;48(3):241-247. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.241

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Abstract PDF

Angiosarcoma with predominantly epithelioid features is a rare soft tissue neoplasm and the interpretation of its cytopathologic findings may be difficult. We report a case of metastatic angiosarcoma with predominantly epithelioid features diagnosed by liquid-based cytology. The cytopathologic findings in this case differed from those of the conventional preparation and we found a clean background, no hyperchromatic nuclei and several cytoplasmic changes, including intracytoplasmic vacuoles with peculiar shapes, juxtanuclear condensation and perinuclear clearing. Identification of these changes using liquid-based cytology supplemented with immunochemistry may be helpful in reaching a correct cytopathologic diagnosis.

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Radiation-associated Angiosarcoma Presenting as Massive Pleural Effusion
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Original Articles

Prognostic Significance of Absolute Lymphocyte Count/Absolute Monocyte Count Ratio at Diagnosis in Patients with Multiple Myeloma: Su-Jin Shin, Jin Roh, Misung Kim, Min Jung Jung, Young Wha Koh, Chan-Sik Park, Dok Hyun Yoon, Cheolwon Suh, Chan-Jeong Park, Hyun Sook Chi, Jooryung Huh; Korean J Pathol. 2013;47(6):526-533. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.526

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Abstract PDF

Background

Absolute lymphocyte count (ALC) in peripheral blood has recently been reported to be an independent prognostic factor in multiple myeloma (MM). Previous studies indicated that the absolute monocyte count (AMC) in peripheral blood reflects the state of the tumor microenvironment in lymphomas. Neither the utility of the AMC nor its relationship with ALC has been studied in MM.

Methods

The prognostic value of ALC, AMC, and the ALC/AMC ratio at the time of diagnosis was retrospectively examined in 189 patients with MM.

Results

On univariate analysis, low ALC (<1,400 cells/µL), high AMC (≥490 cells/µL), and low ALC/AMC ratio (<2.9) were correlated with worse overall survival (OS) (p=.002, p=.038, and p=.001, respectively). On multivariate analysis, the ALC/AMC ratio was an independent prognostic factor (p=.047), whereas ALC and AMC were no longer statistical significant. Low ALC, high AMC, and low ALC/AMC ratio were associated with poor prognostic factors such as high International Staging System stage, plasmablastic morphology, hypoalbuminemia, and high β2-microglobulin.

Conclusions

Univariate analysis demonstrated that changes in ALC, AMC, and the ALC/AMC ratio are associated with patient survival in MM. Multivariate analysis showed that, of these factors, the ALC/AMC ratio was an independent prognostic factor for OS.

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Rahul Banerjee, Kara I. Cicero, Sarah S. Lee, Andrew J. Cowan
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Normal Absolute Monocyte Count at the Time of Relapse is Associated with Improved Survival After First Salvage Therapy in Adult Patients with Early Relapsed B-Lineage Acute Lymphoblastic Leukemia

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Michael Stotz, Joanna Szkandera, Tatjana Stojakovic, Julia Seidel, Hellmut Samonigg, Peter Kornprat, Renate Schaberl-Moser, Fridericke Seggewies, Gerald Hoefler, Armin Gerger, Martin Pichler
Clinical Chemistry and Laboratory Medicine (CCLM).2015;[Epub] CrossRef

Finding and Characterizing Mammary Analogue Secretory Carcinoma of the Salivary Gland: Min Jung Jung, Joon Seon Song, Sang Yoon Kim, Soon Yuhl Nam, Jong-Lyel Roh, Seung-Ho Choi, Sung-Bae Kim, Kyung-Ja Cho; Korean J Pathol. 2013;47(1):36-43. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.36

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Abstract PDF

Background

A new tumor entity of the salivary glands, mammary analogue secretory carcinoma (MASC) with ETV6-NTRK3 translocation, has recently been proposed. MASC was originally diagnosed as adenocarcinoma, not otherwise specified (ANOS), or acinic cell carcinoma (AciCC) by the current World Health Organization classification. We aimed to identify MASC cases by molecular tests, and to characterize their clinical, histological, and immunohistochemical features.

Methods

Thirty cases of MASC candidates were selected after review of 196 salivary gland tumors, and subjected to break-apart ETV6 fluorescence in situ hybridization (FISH), and immunohistochemical study for S100 protein, gross cystic disease fluid protein 15, DOG1, estrogen receptor, and progesterone receptor.

Results

Valid FISH results were obtained in 23 cases, and 13 positive cases were retrieved. MASCs were histologically varied, and the most frequent features observed in 10 cases were low-grade papillary/cystic/glandular patterns, intraluminal secretory materials, ovoid/wrinkled nuclei, and relatively abundant granular eosinophilic cytoplasms, corresponding to papillary-cystic or follicular types of AciCC. All cases showed diffuse immunopositivity for S100 protein. Three cases developed recurrences, but all patients remained alive.

Conclusions

MASC could be a molecularly well-defined salivary gland neoplasm, encompassing some portions of AciCC and ANOS, but its histological spectrum and clinical implication require further investigation.

Citations

Citations to this article as recorded by

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Expression of Survivin in Non-Small Cell Lung Carcinoma: Relationship to Tumor Biology and Prognosis in Surgically Treated Patients.: Min Jung Jung, Bong Kwon Chun; Korean J Pathol. 2005;39(3):151-157.

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Abstract PDF: BACKGROUND
Survivin, a novel member of inhibitor-of-apoptosis, is undetectable in most terminally differentiated nonproliferative adult tissue, but is overexpressed in some human malignancies. The survivin gene expression is repressed by binding of wild-type p53 with the survivin promotor. In this study, we investigated the prevalence of survivin expression, its association with p53 overexpression and proliferative index, and clinicopathological significance in non-small cell lung carcinomas (NSCLC).
METHODS
Immunohistochemical stainings were performed in 59 cases of primary NSCLC for survivin, p53 and Ki-67. Correlations between the survivin expression, p53 overexpression and Ki-67 labeling index were analyzed.
RESULTS
Survivin expression was detected in 47 carcinomas (80%) with nuclear immunoreactivity (56%). Survivin nuclear immunoreactivity revealed significantly worse prognosis in NSCLC patients (p=0.003), and correlated with lymph node metastasis (p=0.014), lymphovascular invasion (p=0.032), p53 overexpression, and Ki-67 labeling index (KI 24.2 +/- 6.9, p=0.045). Survivin expression was not correlated with histological type and pT status.
CONCLUSIONS
High incidence of survivin overexpression in NSCLC suggests that survivin is involved in lung carcinogenesis, and nuclear expression of survivin can be used as a poor prognostic predictor in NSCLC patients. Expression of mutant p53 seems to be a possible mechanism of survivin up-regulation in NSCLC.

The Relationship between PTEN Tumor Suppressor Gene and Vascular Endothelial Growth Factor-Mediated Angiogenesis in Breast Cancer.: Jean Kyung Park, Min Jung Jung, Bong Kwon Chun, Bang Hur; Korean J Pathol. 2004;38(2):100-105.

1,678 View
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Abstract PDF: BACKGROUND
PTEN is a novel tumor suppressor gene located at chromosome 10q23.3. Loss of PTEN function has been implicated in the progression of several types of cancer. Angiogenesis is a critical factor in tumor growth and metastasis. We investigated PTEN expression in invasive breast cancers and described its role in the regulation of angiogenesis related to vascular endothelial growth factor (VEGF).
METHODS
Forty-five, surgically resected, formalin-fixed and paraffin embedded breast cancer tissue samples were analyzed for PTEN and VEGF expressions by immunohistochemistry and for microvessel density (MVD) by CD34 immunostaining.
RESULTS
Loss of PTEN expression was found in 35.6% (16/45) of the breast cancer tissues, all of which showed positive VEGF expression. Among 29 cases with normal PTEN expression, 15 (51.7%) were VEGF positive. MVD was significantly higher in tumors with a loss of PTEN expression than in those with normal PTEN expression.
CONCLUSION
A loss of PTEN expression might increase the VEGF-related angiogenesis in breast cancer. There was no correlation between PTEN expression and clinicopathologic parameters. Detection of the loss of PTEN expression may serve as a useful biologic marker for progression in invasive breast cancer.

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