Journal of Pathology and Translational Medicine

Case Study

Metastatic choroidal melanoma in the breast: a case report and review of the literature: Loay Abudalu, Vinisha Malhotra, Nabila Nasir, Sami Titi; J Pathol Transl Med. 2023;57(4):238-241. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.07

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Abstract PDF: The breast is an unusual site for metastases, accounting for less than 2% of malignant breast lesions but include those from malignant melanomas, carcinomas, sarcomas, and lymphomas from various organs. We diagnosed a very rare case of metastatic choroidal melanoma for a 67-year-old female who presented with a right breast lump and who had been previously diagnosed with choroidal melanoma-monosomy 3 in 2017. To the best of our knowledge, only five such cases have been published so far, with one in a male patient.

Original Articles

A clinicopathologic and immunohistochemical study of primary and secondary breast angiosarcoma: Evi Abada, Hyejeong Jang, Seongho Kim, Rouba Ali-Fehmi, Sudeshna Bandyopadhyay; J Pathol Transl Med. 2022;56(6):342-353. Published online October 27, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.31

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Background
We aimed to study the clinicopathologic and immunohistochemical (IHC) (CD117, c-Myc, and p53) characteristics, and overall survival of primary and secondary breast angiosarcoma (BAS).
Methods
This was a retrospective study of BAS cases diagnosed between 1997 and 2020 at our institution. Hematoxylin and eosin-stained slides were reviewed for tumor morphology, margin status, and lymph node metastasis. CD117, p53, D2-40, CD31, and c-Myc IHC stains were performed on 11 viable tissue blocks. Additional clinical information was obtained from the electronic medical records.
Results
Seventeen patients with BAS were identified. Of these, five (29%) were primary and 12 (71%) were secondary BAS, respectively. The median age at diagnosis for primary BAS was 36 years. The median age at diagnosis for secondary BAS was 67 years. The median time to secondary BAS development following radiotherapy was 6.5 years (range, 2 to 12 years). There was no significant difference between primary and secondary BAS in several histopathologic parameters examined, including histologic grade, necrosis, mitotic count, lymph node metastasis, and positive tumor margins. There was also no difference in CD117, p53, D2-40, CD31, and c-Myc expression by IHC between primary and secondary BAS. During a median followup of 21 months, primary BAS had two (40%) reported deaths and secondary BAS had three (25%) reported deaths. However, this difference in survival between both groups was not statistically significant (hazard ratio, 0.51; 95% confidence interval, 0.09 to 3.28; p = .450).
Conclusions
BAS is a rare and aggressive disease. No histologic, IHC (CD117, c-Myc, and p53), or survival differences were identified between primary and secondary BAS in this study.

Citations

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Primary ovarian angiosarcoma: Two case reports and review of literature
Ying Zhou, Yi-Wen Sun, Xiao-Yang Liu, Dan-Hua Shen
World Journal of Clinical Cases.2023; 11(21): 5122. CrossRef

Fatty acid synthetase expression in triple-negative breast cancer: Jin Hee Park, Hye Seung Han, So Dug Lim, Wook Youn Kim, Kyoung Sik Park, Young Bum Yoo, Seung Eun Lee, Wan-Seop Kim; J Pathol Transl Med. 2022;56(2):73-80. Published online January 21, 2022; DOI: https://doi.org/10.4132/jptm.2021.10.27

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Abstract PDF

Background
Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism–related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC.
Methods
Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0–1+ FASN staining were grouped as low-grade FASN and patients with 2–3+ FASN staining as high-grade FASN.
Results
FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups.
Conclusions
We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.

Citations

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NFYA promotes malignant behavior of triple-negative breast cancer in mice through the regulation of lipid metabolism
Nobuhiro Okada, Chihiro Ueki, Masahiro Shimazaki, Goki Tsujimoto, Susumu Kohno, Hayato Muranaka, Kiyotsugu Yoshikawa, Chiaki Takahashi
Communications Biology.2023;[Epub] CrossRef
Role of EGFR and FASN in breast cancer progression
Suchi Chaturvedi, Mainak Biswas, Sushabhan Sadhukhan, Avinash Sonawane
Journal of Cell Communication and Signaling.2023; 17(4): 1249. CrossRef
Bioinformatics Method Was Used to Analyze the Highly Expressed Gene FAM83A of Breast Cancer in Young Women
Yongzhe Tang, Hao Wang, Qi He, Yuanyuan Chen, Jie Wang, Fahd Abd Algalil
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NCAPH promotes proliferation as well as motility of breast cancer cells by activating the PI3K/AKT pathway
Ting Zhang, Peng Li, Wanying Guo, Qipeng Liu, Weiqiang Qiao, Miao Deng
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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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Abstract PDF Supplementary Material

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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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

Potential of AKT2 expression as a predictor of lymph-node metastasis in invasive breast carcinoma of no special type: Primariadewi Rustamadji, Elvan Wiyarta, Kristina Anna Bethania, Kusmardi Kusmardi; J Pathol Transl Med. 2021;55(4):271-278. Published online June 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.04.26

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Abstract PDF

Background
Invasive breast carcinoma of no special type (IBC-NST) is the most common type of breast cancer and mainly causes regional lymph-node metastasis (LNM). We investigated the potential for AKT2 expression as a predictive biomarker for LNM in IBC-NST.
Methods
Forty-eight paraffin blocks containing IBC-NST primary tumors were divided into two groups based on presence or absence of LNM. Age, tumor grade, tumor size, lymphovascular invasion (LVI), and AKT expression were assessed. AKT2 expression was assessed based on immunohistochemical staining, while other data were collected from archives.
Results
Multiple logistic regression results showed that AKT2 expression and LVI were significantly associated with LNM (odds ratio [OR], 5.32; 95% confidence interval [CI], 1.42 to 19.93 and OR, 4.46; 95% CI, 1.17 to 16.97, respectively). AKT2 expression was able to discriminate against LNM (area under the receiver operating characteristic, 0.799 ± 0.063; 95% CI, 0.676 to 0.921) at an H-score cutoff of 104.62 (83.3% sensitivity, 62.5% specificity).
Conclusions
AKT2 expression has potential as a predictor of LNM in IBC-NST. The H-score cutoff for AKT2 expression can be used as a classification guide in future studies.

Citations

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Exploring the Expression of Survivin on Neoadjuvant Chemotherapy in Invasive Breast Carcinoma
Primariadewi Rustamadji, Elvan Wiyarta, Ineke Anggreani
Open Access Macedonian Journal of Medical Sciences.2022; 10(B): 1440. CrossRef
Effect of Omega-3-Rich Fish Oil on TNF-  Expression in Mice's Colonic Tissue Induced with Azoxymethane (AOM) and Dextran Sodium Sulphate (DSS)
Elvan Wiyarta, Kusmardi Kusmardi, Yurnadi Hanafi Midoen
Research Journal of Pharmacy and Technology.2022; : 3179. CrossRef
The potential of lunasin extract for the prevention of breast cancer progression by upregulating E-Cadherin and inhibiting ICAM-1
Kusmardi Kusmardi, Elvan Wiyarta, Numlil Khaira Rusdi, Andi Muh. Maulana, Ari Estuningtyas, Hadi Sunaryo
F1000Research.2021; 10: 902. CrossRef
CD44 Variant Exon 6 Isoform Expression as a Potential Predictor of Lymph Node Metastasis in Invasive Breast Carcinoma of No Special Type
Primariadewi Rustamadji, Elvan Wiyarta, Kristina A. Bethania, Rakesh Sathish Nair
International Journal of Breast Cancer.2021; 2021: 1. CrossRef

Review

Standardized pathology report for breast cancer: Soo Youn Cho, So Yeon Park, Young Kyung Bae, Jee Yeon Kim, Eun Kyung Kim, Woo Gyeong Kim, Youngmee Kwon, Ahwon Lee, Hee Jin Lee, Ji Shin Lee, Jee Young Park, Gyungyub Gong, Hye Kyoung Yoon; J Pathol Transl Med. 2021;55(1):1-15. Published online January 11, 2021; DOI: https://doi.org/10.4132/jptm.2020.11.20

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Abstract PDF Supplementary Material

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of ‘standard data elements,’ ‘conditional data elements,’ and a biomarker report form. The ‘standard data elements’ consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the ‘conditional data elements.’ In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.

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Residual pure intralymphatic carcinoma component only (lymphovascular tumor emboli without invasive carcinoma) after neoadjuvant chemotherapy is associated with poor outcome: Not pathologic complete response
Hyunwoo Lee, Yunjeong Jang, Yoon Ah Cho, Eun Yoon Cho
Human Pathology.2024; 145: 1. CrossRef
Sentinel lymph node biopsy in patients with ductal carcinomain situ: systematic review and meta-analysis
Matthew G. Davey, Colm O’Flaherty, Eoin F. Cleere, Aoife Nohilly, James Phelan, Evan Ronane, Aoife J. Lowery, Michael J. Kerin
BJS Open.2022;[Epub] CrossRef

Original Article

Automated immunohistochemical assessment ability to evaluate estrogen and progesterone receptor status compared with quantitative reverse transcription-polymerase chain reaction in breast carcinoma patients: Taesung Jeon, Aeree Kim, Chungyeul Kim; J Pathol Transl Med. 2021;55(1):33-42. Published online December 3, 2020; DOI: https://doi.org/10.4132/jptm.2020.09.29

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Abstract PDF

Background
This study aimed to investigate the capability of an automated immunohistochemical (IHC) evaluation of hormonal receptor status in breast cancer patients compared to a well-validated quantitative reverse transcription–polymerase chain reaction (RT-qPCR) method.
Methods
This study included 93 invasive breast carcinoma cases that had both standard IHC assay and Oncotype Dx assay results. The same paraffin blocks on which Oncotype Dx assay had been performed were selected. Estrogen receptor (ER) and progesterone receptor (PR) receptor status were evaluated through IHC stains using SP1 monoclonal antibody for ER, and 1E2 monoclonal antibody for PR. All ER and PR immunostained slides were scanned, and invasive tumor areas were marked. Using the QuantCenter image analyzer provided by 3DHISTECH, IHC staining of hormone receptors was measured and converted to histochemical scores (H scores). Pearson correlation coefficients were calculated between Oncotype Dx hormone receptor scores and H scores, and between Oncotype Dx scores and Allred scores.
Results
H scores measured by an automated imaging system showed high concordance with RT-qPCR scores. ER concordance was 98.9% (92/93), and PR concordance was 91.4% (85/93). The correlation magnitude between automated H scores and RT-qPCR scores was high and comparable to those of Allred scores (for ER, 0.51 vs. 0.37 [p=.121], for PR, 0.70 vs. 0.72 [p=.39]).
Conclusions
Automated H scores showed a high concordance with quantitative mRNA expression levels measured by RT-qPCR.

Citations

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Vision Transformers for Breast Cancer Human Epidermal Growth Factor Receptor 2 Expression Staging without Immunohistochemical Staining
Gelan Ayana, Eonjin Lee, Se-woon Choe
The American Journal of Pathology.2024; 194(3): 402. CrossRef
Marker assessments in ER‐positive breast cancers: old markers, new applications?
Joshua J X Li, Gary M Tse
Histopathology.2023; 82(2): 218. CrossRef
The Story of the Magee Equations: The Ultimate in Applied Immunohistochemistry
Rohit Bhargava, David J. Dabbs
Applied Immunohistochemistry & Molecular Morphology.2023; 31(7): 490. CrossRef
Dose-Dependent Relationship between Protection of Thioacetamide-Induced Acute Liver Injury and Hyperammonemia and Concentration of Lactobacillus salivarius Li01 in Mice
Pengcheng Lou, Yangfan Shen, Aoxiang Zhuge, Longxian Lv, Xueling Zhu, Yin Yuan, Liya Yang, Kaicen Wang, Bo Li, Lanjuan Li, Joanna B. Goldberg
Microbiology Spectrum.2021;[Epub] CrossRef

Reviews

Imaging features of breast cancer molecular subtypes: state of the art: Nariya Cho; J Pathol Transl Med. 2021;55(1):16-25. Published online November 9, 2020; DOI: https://doi.org/10.4132/jptm.2020.09.03

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Abstract PDF

Characterization of breast cancer molecular subtypes has been the standard of care for breast cancer management. We aimed to provide a review of imaging features of breast cancer molecular subtypes for the field of precision medicine. We also provide an update on the recent progress in precision medicine for breast cancer, implications for imaging, and recent observations in longitudinal functional imaging with radiomics.

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Association of clinicopathologic and molecular factors with the occurrence of positive margins in breast cancer
Anupama Praveen Kumar, Diego Vicente, Jianfang Liu, Praveen-Kumar Raj-Kumar, Brenda Deyarmin, Xiaoying Lin, Craig D. Shriver, Hai Hu
Breast Cancer Research and Treatment.2024; 204(1): 15. CrossRef
The effect of data resampling methods in radiomics
Aydin Demircioğlu
Scientific Reports.2024;[Epub] CrossRef
Treated Primary Cutaneous Malignant Melanoma With Later Metastasis Found in Clinical Presentation of Left Axilla Lymphadenopathy: A Case Report
Brigitte L Cochran, Sara Eliseo, Austin Vaughn, Tamryn L Van Der Horn, Enzo Ferrara, Jamie Edwards
Cureus.2024;[Epub] CrossRef
Histogram analysis of multi-model high-resolution diffusion-weighted MRI in breast cancer: correlations with molecular prognostic factors and subtypes
Yanjin Qin, Feng Wu, Qilan Hu, Litong He, Min Huo, Caili Tang, Jingru Yi, Huiting Zhang, Ting Yin, Tao Ai
Frontiers in Oncology.2023;[Epub] CrossRef
ASO Author Reflections: Sequence of Treatment in Clinically Node-Negative T1 Triple-Negative Breast Cancer
Kai Huang, James W. Jakub, Sarah A. McLaughlin
Annals of Surgical Oncology.2023; 30(13): 8455. CrossRef
Circulating non-coding RNAs as a diagnostic and management biomarker for breast cancer: current insights
Hamed Hosseinalizadeh, Mehrdad Mahmoodpour, Ammar Ebrahimi
Molecular Biology Reports.2022; 49(1): 705. CrossRef
MRI as a biomarker for breast cancer diagnosis and prognosis
Francesca Galati, Veronica Rizzo, Rubina Manuela Trimboli, Endi Kripa, Roberto Maroncelli, Federica Pediconi
BJR|Open.2022;[Epub] CrossRef
Multiparametric MRI Features of Breast Cancer Molecular Subtypes
Madalina Szep, Roxana Pintican, Bianca Boca, Andra Perja, Magdalena Duma, Diana Feier, Bogdan Fetica, Dan Eniu, Sorin Marian Dudea, Angelica Chiorean
Medicina.2022; 58(12): 1716. CrossRef
Circulating tumor cells as prognostic biomarkers in breast cancer: current status and future prospects
Evagelia Chantzara, Nikolaos Xenidis, Galatea Kallergi, Vassilis Georgoulias, Athanasios Kotsakis
Expert Review of Molecular Diagnostics.2021; 21(10): 1037. CrossRef

Clinicopathological characteristics of BRCA-associated breast cancer in Asian patients: Eun-Kyu Kim, So Yeon Park, Sung-Won Kim; J Pathol Transl Med. 2020;54(4):265-275. Published online May 14, 2020; DOI: https://doi.org/10.4132/jptm.2020.04.07

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Abstract PDF

BRCA1/2 germline mutations account for the majority of hereditary breast cancers. Since the identification of the BRCA genes, several attempts have been made to define the clinicopathological characteristics of BRCA-associated breast cancer in comparison with sporadic breast cancer. Asians constitute 60% of the world population, and although the incidence of breast cancer in Asia remains low compared to the West, breast cancer is the most prevalent female cancer in the region. The epidemiological aspects of breast cancer are different between Asians and Caucasians. Asian patients present with breast cancer at a younger age than Western patients. The contributions of BRCA1/2 mutations to breast cancer incidence are expected to differ between Asians and Caucasians, and the different genetic backgrounds among races are likely to influence the breast cancer phenotypes. However, most large-scale studies on the clinicopathological characteristics of BRCA-associated breast cancer have been on Western patients, while studies on Asian populations were small and sporadic. In this review, we provide an overview of the clinical and pathological characteristics of BRCA-associated breast cancer, incorporating findings on Asian patients.

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Songporn Oranratnachai, Watchalawalee Yamkaew, Atchara Tunteeratum, Thongchai Sukarayothin, Nareenart Iemwimangsa, Ravat Panvichien
Cancer Reports.2023;[Epub] CrossRef
Prognostic and predictive biomarkers with therapeutic targets in breast cancer: A 2022 update on current developments, evidence, and recommendations
Clement Chung, Vanessa T.Y. Yeung, Kenneth C.W. Wong
Journal of Oncology Pharmacy Practice.2023; 29(6): 1343. CrossRef
Mutations of TP53 and genes related to homologous recombination repair in breast cancer with germline BRCA1/2 mutations
Jinyong Kim, Kyeonghun Jeong, Hyeji Jun, Kwangsoo Kim, Jeong Mo Bae, Myung Geun Song, Hanbaek Yi, Songyi Park, Go-un Woo, Dae-Won Lee, Tae-Yong Kim, Kyung-Hun Lee, Seock-Ah Im
Human Genomics.2023;[Epub] CrossRef
BRCA 1–2 Incidence in Synchronous and Metachronous Breast Cancer: a Tertiary Center Study
Ahmet Dağ, Bilal Arslan, Erkan Güler, Serdar Mermer
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Habitat Analysis of Breast Cancer-Enhanced MRI Reflects BRCA1 Mutation Determined by Immunohistochemistry
Tianming Du, Haidong Zhao, Chen Li
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Prevalence and Factors Associated with BRCA1/2 Gene Mutation in Chinese Populations with Breast Cancer
Guoding Huang, Hongquan Lu, Qizhu Chen, Xinting Huang
International Journal of General Medicine.2022; Volume 15: 6783. CrossRef
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Xiaojing Liu, Jing Yue, Ruqiya Pervaiz, Hanwang Zhang, Lan Wang
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Francesco Dondi, Domenico Albano, Pietro Bellini, Luca Camoni, Giorgio Treglia, Francesco Bertagna
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The clinical and diagnostic characteristics of BRCA-associated breast cancer
M.A. Golotyuk, A.A. Berezhnoy, N.V. Kazantseva, A.V. Dorofeev, S.A. Shevchenko, I.V. Borzunov, N.I. Rozhkova
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Original Articles

Clinicopathologic characteristics of HER2-positive pure mucinous carcinoma of the breast: Yunjeong Jang, Hera Jung, Han-Na Kim, Youjeong Seo, Emad Alsharif, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Yeon Hee Park, Eun Yoon Cho, Soo Youn Cho; J Pathol Transl Med. 2020;54(1):95-102. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.24

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Abstract PDF

Background
Pure mucinous carcinoma (PMC) is a rare type of breast cancer, estimated to represent 2% of invasive breast cancer. PMC is typically positive for estrogen receptors (ER) and progesterone receptors (PR) and negative for human epidermal growth factor receptor 2 (HER2). The clinicopathologic characteristics of HER2-positive PMC have not been investigated.
Methods
Pathology archives were searched for PMC diagnosed from January 1999 to April 2018. Clinicopathologic data and microscopic findings were reviewed and compared between HER2-positive PMC and HER2-negative PMC. We also analyzed the differences in disease-free survival (DFS) and overall survival according to clinicopathologic parameters including HER2 status in overall PMC cases.
Results
There were 21 HER2-positive cases (4.8%) in 438 PMCs. The average tumor size of HER2-positive PMC was 32.21 mm (± 26.55). Lymph node metastasis was present in seven cases. Compared to HER2-negative PMC, HER2-positive PMC presented with a more advanced T category (p < .001), more frequent lymph node metastasis (p = .009), and a higher nuclear and histologic grade (p < .001). Microscopically, signet ring cells were frequently observed in HER2-positive PMC (p < .001), whereas a micropapillary pattern was more frequent in HER2-negative PMC (p = .012). HER2-positive PMC was more frequently negative for ER (33.3% vs. 1.2%) and PR (28.6% vs. 7.2%) than HER2-negative PMC and showed a high Ki-67 labeling index. During follow-up, distant metastasis and recurrence developed in three HER2-positive PMC patients. Multivariate analysis revealed that only HER2-positivity and lymph node status were significantly associated with DFS.
Conclusions
Our results suggest that HER2-positive PMC is a more aggressive subgroup of PMC. HER2 positivity should be considered for adequate management of PMC.

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Yurimi Lee, Kiyong Na, Ha Young Woo, Hyun-Soo Kim
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Ivana Mijatov, Aleksandra Fejsa Levakov, Aleksandar Spasić, Jelena Nikolić, Saša Mijatov
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Jihee Sohn, Yurimi Lee, Hyun-Soo Kim
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Dinesh Chandra Doval, Rupal Tripathi, Sunil Pasricha, Pankaj Goyal, Chaturbhuj Agrawal, Anurag Mehta
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A.M. González Aranda, E. Martínez Gómez, A. Santana Costa, F. Arnanz Velasco, M.H. González de Diego, A. Zapico Goñi
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Analysis of the molecular subtypes of preoperative core needle biopsy and surgical specimens in invasive breast cancer: Ye Sul Jeong, Jun Kang, Jieun Lee, Tae-Kyung Yoo, Sung Hun Kim, Ahwon Lee; J Pathol Transl Med. 2020;54(1):87-94. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.14

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Abstract PDF

Background
Accurate molecular classification of breast core needle biopsy (CNB) tissue is important for determining neoadjuvant systemic therapies for invasive breast cancer. The researchers aimed to evaluate the concordance rate (CR) of molecular subtypes between CNBs and surgical specimens.
Methods
This study was conducted with invasive breast cancer patients who underwent surgery after CNB at Seoul St. Mary’s Hospital between December 2014 and December 2017. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed using immunohistochemistry. ER and PR were evaluated by Allred score (0–8). HER2 was graded from 0 to +3, and all 2+ cases were reflex tested with silver in situ hybridization. The labeling index of Ki67 was counted by either manual scoring or digital image analysis. Molecular subtypes were classified using the above surrogate markers.
Results
In total, 629 patients were evaluated. The CRs of ER, PR, HER2, and Ki67 were 96.5% (kappa, 0.883; p<.001), 93.0% (kappa, 0.824; p<.001), 99.7% (kappa, 0.988; p<.001), and 78.7% (kappa, 0.577; p<.001), respectively. Digital image analysis of Ki67 in CNB showed better concordance with Ki67 in surgical specimens (CR, 82.3%; kappa, 0.639 for digital image analysis vs. CR, 76.2%; kappa, 0.534 for manual counting). The CRs of luminal A, luminal B, HER2, and triple negative types were 89.0%, 70.0%, 82.9%, and 77.2%, respectively.
Conclusions
CNB was reasonably accurate for determining ER, PR, HER2, Ki67, and molecular subtypes. Using digital image analysis for Ki67 in CNB produced more accurate molecular classifications.

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Review

HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation: Soomin Ahn, Ji Won Woo, Kyoungyul Lee, So Yeon Park; J Pathol Transl Med. 2020;54(1):34-44. Published online November 6, 2019; DOI: https://doi.org/10.4132/jptm.2019.11.03

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Abstract PDF

Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification is found in about 20% of invasive breast cancers. It is a sole predictive marker for treatment benefits from HER2 targeted therapy and thus, HER2 testing is a routine practice for newly diagnosed breast cancer in pathology. Currently, HER2 immunohistochemistry (IHC) is used for a screening test, and in situ hybridization is used as a confirmation test for HER2 IHC equivocal cases. Since the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines on HER2 testing was first released in 2007, it has been updated to provide clear instructions for HER2 testing and accurate determination of HER2 status in breast cancer. During HER2 interpretation, some pitfalls such as intratumoral HER2 heterogeneity and increase in chromosome enumeration probe 17 signals may lead to inaccurate assessment of HER2 status. Moreover, HER2 status can be altered after neoadjuvant chemotherapy or during metastatic progression, due to biologic or methodologic issues. This review addresses recent updates of ASCO/CAP guidelines and factors complicating in the interpretation of HER2 status in breast cancers.

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Original Articles

Primary Rhabdomyosarcoma of the Breast: Study of Three Cases at One Institution with a Review of Primary Breast Sarcomas: Junyoung Shin, Hee Jeong Kim, Dae-Yeon Kim, Gyungyub Gong, Kyung-Ja Cho; J Pathol Transl Med. 2019;53(5):308-316. Published online August 2, 2019; DOI: https://doi.org/10.4132/jptm.2019.07.22

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Abstract PDF

Background
Primary breast sarcoma (PBS) is rare, comprising approximately 1% of breast malignancies. Rhabdomyosarcoma (RMS) accounts for an extremely small proportion of PBSs, often leading to delayed histologic confirmation.
Methods
Upon reviewing Asan Medical Center’s pathology database between 2000 and 2018, 41 PBS cases were retrieved, including three cases of primary RMS of the breast. Their clinicopathological features were analyzed, and the literature related to PBS and primary RMS of the breast was reviewed.
Results
We identified three primary breast RMS cases from our institution database, comprising 7.3% of PBS: one case each of spindle cell/sclerosing RMS (ssRMS), alveolar RMS (aRMS), and embryonal RMS (eRMS). All cases involved adolescents or young adults (14, 16, and 25 years, respectively) who underwent mastectomy or radiotherapy and were confirmed using immunohistochemical testing for myogenin, desmin, and myogenic differentiation. The ssRMS patient experienced recurrence at the operation site 4 months post-surgery despite undergoing concurrent chemoradiotherapy. The aRMS patient had multiple metastases at diagnosis and showed FAX3-FOXO1 fusion transcripts; she died 22 months after the diagnosis. The eRMS patient had enlarged axillary lymph nodes; post-radiotherapy, the lesion recurred as multiple metastases to the bone and lung. She died 18 months post-diagnosis.
Conclusions
Our experience on RMS cases suggests that spindle cell or small round cell malignancy in breasts of young female should raise suspicion for the possibility of primary or secondary RMS. To our knowledge, this is the second report of primary breast ssRMS and it may help clinicians who encounter this rare disease in the future.

Citations

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Primary breast rhabdomyosarcoma in a 17-year-old girl
Laxmi Singotia, V.S. Haritha
Journal of Cancer Research and Therapeutics.2023; 19(7): 2070. CrossRef
High-Grade Spindle Cell Lesions of the Breast
Esther Yoon, Qingqing Ding, Kelly Hunt, Aysegul Sahin
Surgical Pathology Clinics.2022; 15(1): 77. CrossRef
Primary Small Cell Malignancies of the Breast: Are They Rare Malignancies?
Kemal Behzatoğlu, Fernando Schmitt
Acta Cytologica.2022; 66(4): 347. CrossRef
Recurrent malignant phyllodes tumor of the breast: An extremely rare case of recurrence with only rhabdomyosarcoma components
Jia Han, Shuice Liu, Akihoro Shioya, Motona Kumagai, Emi Morioka, Miki Noguchi, Masafumi Inokuchi, Sohsuke Yamada
SAGE Open Medical Case Reports.2022; 10: 2050313X2211166. CrossRef
Primary rhabdomyosarcoma: An extremely rare and aggressive variant of male breast cancer
Cătălin Bogdan Satală, Ioan Jung, Tivadar Jr Bara, Patricia Simu, Iunius Simu, Madalina Vlad, Rita Szodorai, Simona Gurzu
World Journal of Clinical Cases.2020; 8(19): 4466. CrossRef

Association between p53 Expression and Amount of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Miseon Lee, In Ah Park, Sun-Hee Heo, Young-Ae Kim, Gyungyub Gong, Hee Jin Lee; J Pathol Transl Med. 2019;53(3):180-187. Published online March 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.08

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196 Download
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Abstract PDF

Background
Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC.
Methods
In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression.
Results
No, low, and high p53 expression was identified in 44.1% (n = 299), 20.1% (n = 136), and 35.8% (n = 243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p < .001), high TIL levels (p = .009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p = .013; XBP1, p = .007), compared to patients with low p53 expression. There was no significant difference in disease-free (p = .406) or overall survival rates (p = .444) among the three p53 expression groups.
Conclusions
High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.

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Sotiris Loizides, Anastasia Constantinidou
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Koen Brummel, Anneke L. Eerkens, Marco de Bruyn, Hans W. Nijman
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Updated Austrian treatment algorithm for metastatic triple-negative breast cancer
Rupert Bartsch, Gabriel Rinnerthaler, Edgar Petru, Daniel Egle, Michael Gnant, Marija Balic, Thamer Sliwa, Christian Singer
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Dihydroartemisinin-Transferrin Adducts Enhance TRAIL-Induced Apoptosis in Triple-Negative Breast Cancer in a P53-Independent and ROS-Dependent Manner
Xinyu Zhou, Abel Soto-Gamez, Fleur Nijdam, Rita Setroikromo, Wim J. Quax
Frontiers in Oncology.2022;[Epub] CrossRef
New Challenges in the Differential Diagnosis of High-Grade Triple-Negative Breast Cancer and Serous Carcinoma
Andrii Puzyrenko, Chandler S Cortina, Julie M Jorns
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Prognostic analysis of cuproptosis-related gene in triple-negative breast cancer
Shengnan Sha, Luyi Si, Xinrui Wu, Yuanbiao Chen, Hui Xiong, Ying Xu, Wangrui Liu, Haijun Mei, Tao Wang, Mei Li
Frontiers in Immunology.2022;[Epub] CrossRef
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Ai-Yan Xing, Long Liu, Ke Liang, Bin Wang
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Crosstalk between Immune Checkpoint Modulators, Metabolic Reprogramming and Cellular Plasticity in Triple-Negative Breast Cancer
Arpita Poddar, Sushma R. Rao, Prashanth Prithviraj, George Kannourakis, Aparna Jayachandran
Current Oncology.2022; 29(10): 6847. CrossRef
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Natsuki Furukawa, Vered Stearns, Cesar A. Santa-Maria, Aleksander S. Popel
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Hiu Yee Kwan, Qinghua Xu, Ruihong Gong, Zhaoxiang Bian, Chih-Chang Chu
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Transcriptomic Properties of HER2+ Ductal Carcinoma In Situ of the Breast Associate with Absence of Immune Cells
Marie Colombe Agahozo, Marcel Smid, Ronald van Marion, Dora Hammerl, Thierry P. P. van den Bosch, Mieke A. M. Timmermans, Chayenne J. Heijerman, Pieter J. Westenend, Reno Debets, John W. M. Martens, Carolien H. M. van Deurzen
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The Research Progress on the Prognostic Value of the Common Hematological Parameters in Peripheral Venous Blood in Breast Cancer

Li Chen, Xiangyi Kong, Chengrui Yan, Yi Fang, Jing Wang
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Biomolecular Factors Represented by Bcl-2, p53, and Tumor-Infiltrating Lymphocytes Predict Response for Adjuvant Anthracycline Chemotherapy in Patients with Early Triple-Negative Breast Cancer

Xenia Elena Bacinschi, Anca Zgura, Inga Safta, Rodica Anghel
Cancer Management and Research.2020; Volume 12: 11965. CrossRef

Uterine Malignant Mixed Müllerian Tumors Following Treatment with Selective Estrogen Receptor Modulators in Patients with Breast Cancer: A Report of 13 Cases and Their Clinicopathologic Characteristics: Byung-Kwan Jeong, Chang O. Sung, Kyu-Rae Kim; J Pathol Transl Med. 2019;53(1):31-39. Published online December 18, 2018; DOI: https://doi.org/10.4132/jptm.2018.11.16

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96 Download
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Abstract PDF

Background
Breast cancer treatment with selective estrogen receptor modulators (SERMs) increasesthe incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologiccharacteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discusspossible pathogenetic mechanisms.
Methods
Among 28,104 patients with breast cancer, clinicopathologicfeatures and incidence of uMMMT were compared between patients who underwentSERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period,incidence, dose, and duration of SERM treatment, as well as overall survival rate, were comparedfor patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMTvs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathologicalfindings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ,progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT.
Results
The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold).All patients with SERM were postmenopausal and received daily 20–40 mg SERM. CumulativeSERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologicfeatures, such as International Federation of Gynecology and Obstetrics stage andoverall survival, were not significantly different between patients with S-uMMMT and NS-uMMMTor between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available forimmunostaining exhibited strong overexpression/null expression of p53 protein and significantlyincreased ERβ expression in carcinomatous and sarcomatous components.
Conclusions
SERMtherapy seemingly increases risk of S-uMMMT development; however, clinicopathologic featureswere similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expressionmight be involved in the etiology of S-uMMMT.

Citations

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Leskela, Pérez-Mies, Rosa-Rosa, Cristobal, Biscuola, Palacios-Berraquero, Ong, Guia, Palacios
Cancers.2019; 11(7): 964. CrossRef

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