Journal of Pathology and Translational Medicine

Volume 49(5); September 2015

Reviews

Current Issues and Clinical Evidence in Tumor-Infiltrating Lymphocytes in Breast Cancer: Sung Gwe Ahn, Joon Jeong, SoonWon Hong, Woo Hee Jung; J Pathol Transl Med. 2015;49(5):355-363. Published online August 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.29

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With the advance in personalized therapeutic strategies in patients with breast cancer, there is an increasing need for biomarker-guided therapy. Although the immunogenicity of breast cancer has not been strongly considered in research or practice, tumor-infiltrating lymphocytes (TILs) are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value and the potential for predictive value, particularly in triple-negative and human epidermal growth factor receptor 2–positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy. To date, no standardized methodology for measuring TILs has been established. In this article, we review current issues and clinical evidence for the use of TILs in breast cancer.

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The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression in triple negative breast cancer (TNBC)
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Cytology Specimen Management, Triage and Standardized Reporting of Fine Needle Aspiration Biopsies of the Pancreas: Won Jae Yoon, Martha Bishop Pitman; J Pathol Transl Med. 2015;49(5):364-372. Published online August 10, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.19

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Abstract PDF

The recent advances in pancreas cytology specimen sampling methods have enabled a specific cytologic diagnosis in most cases. Proper triage and processing of the cytologic specimen is pivotal in making a diagnosis due to the need for ancillary testing in addition to cytological evaluation, which is especially true in the diagnosis of pancreatic cysts. Newly proposed terminology for pancreaticobiliary cytology offers a standardized language for reporting that aims to improve communication among patient caregivers and provide for increased flexibility in patient management. This review focuses on these updates in pancreas cytology for the optimal evaluation of solid and cystic lesions of the pancreas.

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It is necessary to exam bottom and top slide smears of EUS-FNA for pancreatic cancer
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Original Articles

SALL4 Expression in Hepatocellular Carcinomas Is Associated with EpCAM-Positivity and a Poor Prognosis: Hyunjin Park, Hyejung Lee, An Na Seo, Jai Young Cho, Young Rok Choi, Yoo-Seok Yoon, Ho-Seong Han, Young Nyun Park, Haeryoung Kim; J Pathol Transl Med. 2015;49(5):373-381. Published online August 10, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.09

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Abstract PDF

Background
There is increasing interest in hepatocellular carcinomas (HCC) expressing “stemness”-related markers, as they have been associated with aggressive behavior and poor prognosis. In this study, we investigated the usefulness of Sal-like protein 4 (SALL4), a recently proposed candidate marker of “stemness.” Methods: Immunohistochemical stains were performed for SALL4, K19, and epithelial cellular adhesion molecule (EpCAM) on tissue microarrays constructed from 190 surgically resected HCCs, and the results were correlated with the clinicopathological features and patient survival data. Results: Nuclear SALL4 expression was observed in 39/190 HCCs (20.5%), while K19 and EpCAM were expressed in 30 (15.9%) and 92 (48.7%) HCCs, respectively. The nuclear expression was generally weak, punctate or clumped. SALL4 expression was significantly associated with a poor overall survival compared to SALL4-negative HCCs (p = .014) compared to SALL4-negative HCCs. On multivariate analysis adjusted for tumor size, multiplicity, vascular invasion, and pathological tumor stage, SALL4 remained as a significant independent predictor of decreased overall survival (p= .004). SALL4 expression was positively correlated with EpCAM expression (p = .013) but not with K19 expression. HCCs that expressed both SALL4 and EpCAM were associated with significantly decreased overall survival, compared to those cases which were negative for both of these markers (p = .031). Conclusions: Although SALL4 expression was not significantly correlated with other clinicopathological parameters suggestive of tumor aggressiveness, SALL4 expression was an independent predictor of poor overall survival in human HCCs, and was also positively correlated with EpCAM expression.

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Cytoplasmic SALL4-A isoform expression as a diagnostic marker of less aggressive tumor behavior in gastric cancer
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World Journal of Surgical Oncology.2025;[Epub] CrossRef
Stemness markers in hepatocellular carcinoma of Eastern vs. Western population: Etiology matters?
Caecilia HC Sukowati, Korri El-Khobar, Chyntia Olivia Maurine Jasirwan, Juferdy Kurniawan, Rino Alvani Gani
Annals of Hepatology.2024; 29(1): 101153. CrossRef
Research progress and prospects of AFP-positive gastric cancer
Long Zhao, Changjiang Yang, Yilin Lin, Shan Wang, Yingjiang Ye, Zhanlong Shen
Foregut Surgery.2022; 2(1): 29. CrossRef
SALL4 and microRNA: The Role of Let-7
Jun Liu, Madeline A. Sauer, Shaza G. Hussein, Junyu Yang, Daniel G. Tenen, Li Chai
Genes.2021; 12(9): 1301. CrossRef
Hepatoid Teratoma, Hepatoid Yolk Sac Tumor, and Hepatocellular Carcinoma
Khaleel I. Al-Obaidy, Sean R. Williamson, Nathan Shelman, Muhammad T. Idrees, Thomas M. Ulbright
American Journal of Surgical Pathology.2021; 45(1): 127. CrossRef
Targeting an Inducible SALL4-Mediated Cancer Vulnerability with Sequential Therapy
Junyu Yang, Chong Gao, Miao Liu, Yao-Chung Liu, Junsu Kwon, Jun Qi, Xi Tian, Alicia Stein, Yanjing V. Liu, Nikki R. Kong, Yue Wu, Shenyi Yin, Jianzhong Xi, Zhiyuan Chen, Kalpana Kumari, Hannan Wong, Hongbo Luo, Leslie E. Silberstein, Julie A.I. Thoms, Ash
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Lipoprotein‐Like Nanoparticle Carrying Small Interfering RNA Against Spalt‐Like Transcription Factor 4 Effectively Targets Hepatocellular Carcinoma Cells and Decreases Tumor Burden
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Hepatoid adenocarcinoma of the stomach: a unique subgroup with distinct clinicopathological and molecular features
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Gynecologic Serous Carcinoma: An Immunohistochemical Analysis of Malignant Body Fluid Specimens
Shuyue Ren, William Klump
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The Pluripotency Network in Colorectal Cancer Pathogenesis and Prognosis: an Update
Ioannis A Voutsadakis
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Cancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies
Nuozhou Wang, Shanshan Wang, Ming-Yue Li, Bao-guang Hu, Li-ping Liu, Sheng-li Yang, Shucai Yang, Zhongqin Gong, Paul B. S. Lai, George G. Chen
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Higher expression of SALL4 predicts poor cancer prognosis: A meta-analysis
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Lorenzo Nicolè, Tiziana Sanavia, Nicola Veronese, Rocco Cappellesso, Claudio Luchini, Paolo Dabrilli, Ambrogio Fassina
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A New Cell Block Method for Multiple Immunohistochemical Analysis of Circulating Tumor Cells in Patients with Liver Cancer
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MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression
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Membranous Insulin-like Growth Factor-1 Receptor (IGF1R) Expression Is Predictive of Poor Prognosis in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma: Eunhyang Park, Soo Young Park, Hyojin Kim, Ping-Li Sun, Yan Jin, Suk Ki Cho, Kwhanmien Kim, Choon-Taek Lee, Jin-Haeng Chung; J Pathol Transl Med. 2015;49(5):382-388. Published online August 4, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.10

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Abstract PDF

Background
Insulin-like growth factor-1 receptor (IGF1R) is a membrane receptor-type tyrosine kinase that has attracted considerable attention as a potential therapeutic target, although its clinical significance in non-small cell lung cancer (NSCLC) is controversial. This study aimed to clarify the clinical significance of IGF1R expression in human NSCLC. Methods: IGF1R protein expression was evaluated using immunohistochemistry in 372 patients with NSCLC who underwent curative surgical resection (146 squamous cell carcinomas [SqCCs] and 226 adenocarcinomas [ADCs]). We then analyzed correlations between expression of IGF1R and clinicopathological and molecular features and prognostic significance. Results: Membranous and cytoplasmic IGF1R expression were significantly higher in SqCCs than in ADCs. In patients with SqCC, membranous IGF1R expression was associated with absence of vascular, lymphatic, and perineural invasion; lower stage; and better progression-free survival (PFS) (hazard ratio [HR], 0.586; p = .040). In patients with ADC, IGF1R expression did not have a significant prognostic value; however, in the subgroup of epidermal growth factor receptor (EGFR)-mutant ADC, membranous IGF1R expression was associated with lymphatic and perineural invasion, solid predominant histology, and higher cancer stage and was significantly associated with worse PFS (HR, 2.582; p = .009). Conclusions: Lung ADC and SqCC showed distinct IGF1R expression profiles that demonstrated prognostic significance. High membranous IGF1R expression was predictive of poor PFS in EGFR-mutant lung ADC, while it was predictive of better PFS in SqCC. These findings will help improve study design for subsequent investigations and select patients for future anti-IGF1R therapy.

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Yu-Hua Xu, Jian-Ren Tu, Tian-Tian Zhao, Shi-Guang Xie, Sheng-Bo Tang
International Journal of Oncology.2018;[Epub] CrossRef
IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights
Heming Li, Izhar Singh Batth, Xiujuan Qu, Ling Xu, Na Song, Ruoyu Wang, Yunpeng Liu
Molecular Cancer.2017;[Epub] CrossRef
Insulin-like growth factor 1 receptor expression in advanced non-small-cell lung cancer and its impact on overall survival
Mojca Humar, Izidor Kern, Gregor Vlacic, Vedran Hadzic, Tanja Cufer
Radiology and Oncology.2017; 51(2): 195. CrossRef
IGF1R depletion facilitates MET-amplification as mechanism of acquired resistance to erlotinib in HCC827 NSCLC cells
Dianna Hussmann, Anne Tranberg Madsen, Kristine Raaby Jakobsen, Yonglun Luo, Boe Sandahl Sorensen, Anders Lade Nielsen
Oncotarget.2017; 8(20): 33300. CrossRef
Upregulated Neuro-oncological Ventral Antigen 1 (NOVA1) Expression Is Specific to Mature and Immature T- and NK-Cell Lymphomas
Eun Kyung Kim, Sun Och Yoon, Soo Hee Kim, Woo Ick Yang, Yoon Ah Cho, Soo Jeong Kim
Journal of Pathology and Translational Medicine.2016; 50(2): 104. CrossRef
The Clinical Significance of the Insulin-Like Growth Factor-1 Receptor Polymorphism in Non-Small-Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation
Tu-Chen Liu, Ming-Ju Hsieh, Ming-Che Liu, Whei-Ling Chiang, Thomas Tsao, Shun-Fa Yang
International Journal of Molecular Sciences.2016; 17(5): 763. CrossRef

Parafibromin Staining Characteristics in Urothelial Carcinomas and Relationship with Prognostic Parameters: Serap Karaarslan, Banu Yaman, Hakan Ozturk, Banu Sarsik Kumbaraci; J Pathol Transl Med. 2015;49(5):389-395. Published online September 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.08.10

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Background
Parafibromin is a recently defined tumor suppressor gene. The aim of our study was to determine the relationships of parafibromin expression in urothelial carcinomas (UCs) with prognostic parameters and to evaluate the use of parafibromin as a potential marker of UC. Methods: Parafibromin expression was assessed in 49 UC specimens using immunohistochemistry. The correlations between parafibromin expression and clinical and pathologic parameters were investigated. Results: Of the patients, 42 (85.7%) were male, and the mean age was 69.6 ± 8.2 years (range, 54 to 88 years). Morphologically, the UCs were divided into two groups: papillary (n = 27) and non-papillary (n = 22). There were seven low-grade (14.3%) and 42 high-grade (85.7%) tumors. Parafibromin was negative in 13 tumors (26.5%), partially positive in 19 tumors (38.8%), and positive in 17 tumors (34.7%). Parafibromin expression was more negative in UCs from upper urinary locations (n=17) and with muscularis propria invasion (n=28), which was statistically significant (p = .009 and p = .007, respectively). There was no statistically significant relationship between parafibromin expression and gender, age, tumor grade, survival, or disease-free survival. Conclusions: We found that UC cases with parafibromin positivity had less of a tendency to show muscularis propria invasion and were more commonly located in the lower urinary system. These results need to be confirmed with studies based on larger case series.

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The roles of the tumor suppressor parafibromin in cancer
Hua-chuan Zheng, Hang Xue, Cong-yu Zhang
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
Prognostic role of parafibromin staining and CDC73 mutation in patients with parathyroid carcinoma: A systematic review and meta‐analysis based on individual patient data
Ruizhe Zhu, Zixing Wang, Ya Hu
Clinical Endocrinology.2020; 92(4): 295. CrossRef
Thein vitroandin vivoeffects of nuclear and cytosolic parafibromin expression on the aggressive phenotypes of colorectal cancer cells: a search of potential gene therapy target
Hua-chuan Zheng, Jia-jie Liu, Jing Li, Ji-cheng Wu, Lei Yang, Gui-feng Zhao, Xin Zhao, Hua-mao Jiang, Ke-qiang Huang, Zhi-jie Li
Oncotarget.2017; 8(14): 23603. CrossRef
The clinicopathological and prognostic significances of CDC73 expression in cancers: a bioinformatics analysis
Hua-Chuan Zheng, Bao-Cheng Gong, Shuang Zhao
Oncotarget.2017; 8(56): 95270. CrossRef
Significance of Parafibromin Expression in Laryngeal Squamous Cell Carcinomas
Inju Cho, Mija Lee, Sharon Lim, Ran Hong
Journal of Pathology and Translational Medicine.2016; 50(4): 264. CrossRef

Comparison of Cytologic Characteristics between Adenoid Cystic Carcinoma and Adenoid Basal Carcinoma in the Uterine Cervix: Juhyeon Jeong, Seung Yeon Ha, Hyun Yee Cho, Dong Hae Chung, Jungsuk An; J Pathol Transl Med. 2015;49(5):396-402. Published online August 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.08

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Abstract PDF

Background
Adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) are rare in the uterine cervix. ACC is more aggressive than ABC, thus accurate differential diagnosis is important. In this study, we identified cytologic features useful in distinguishing these two tumors for diagnosis. Methods: Three cases of ACC and five cases of ABC were selected for this study. Cervicovaginal smear slides were reviewed retrospectively, and the area, circumference, major axis, and minor axis of nuclei were measured using an image analyzer. Results: ACC displayed three-dimensional clusters with a small acini pattern. ABC displayed peripheral palisading without an acini pattern. The nuclei of ACC were more irregular and angulated than those of ABC, and the former showed a coarsely granular chromatin pattern. The nucleic area, circumference, major axis, and minor axis were 18.556±8.665 µm², 23.320±11.412 µm, 5.664±1.537 µm, and 4.127±1.107 µm in ACC and 11.017±4.440 µm², 15.920±5.664 µm, 4.612±1.025 µm, and 3.088±0.762 µm in the cases of ABC. All measured values showed statistically significant difference (p < .001). Conclusions: Although the nuclei of both of these tumor types were oval shaped, inferred from the ratio of minor axis to major axis (0.728 in ACC and 0.669 in ABC), the area of nuclei was approximately 1.7 times larger in ACC than in ABC. Distinguishing nucleic features, including area, morphology, and chromatin pattern, may be helpful in making a correct diagnosis.

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Adenoid basal carcinoma of the uterine cervix
Anas Mohamed, Tesfalem Korga, Ahlam Ali, Javier Laurini
International Journal of Gynecological Cancer.2025; : 101873. CrossRef
Adenoid Basal Carcinoma of the Uterine Cervix: A Case Report
Tatsuya Kanuma, Keiko Kigure, Tosio Nishimura, Yuji Ibuki, Shigeru Tsuchida, Harumi Kamiyama, Misa Iijima, Kazuto Nakamura
The KITAKANTO Medical Journal.2016; 66(1): 11. CrossRef

Case Studies

Paediatric Primary Pachymeningeal Xanthogranuloma with Scattered Foci Displaying Reticulohistiocytoma-like Features: Miguel Fdo. Salazar, María del Rocío Estrada Hernández, Erick Gómez Apo, Laura G. Chávez Macías, Carlos Alfonso Rodríguez Álvarez; J Pathol Transl Med. 2015;49(5):403-408. Published online June 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.05.28

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We report a unique case of a 4-year-old girl with an intriguing fibrohistiocytic tumour. Magnetic resonance imaging scans showed a dural mass of variegated intensity compressing the left occipital pole and apparently extending toward the superior sagittal sinus. Grossly, the cut surface of the surgical specimen was yellow, pale, and soft with reddish kernel-like crusts. Histologically, the yellow areas resembled cholesterol granulomas with widespread coagulative necrosis, cholesterol clefts, powdery calcification, foreign body-type giant cells, and foamy macrophages, while the scattered red spots contained numerous multinucleated giant cells of foreign-body and Touton types, the former with amphophilic to slightly eosinophilic cytoplasm. Immunoperoxidase reactions confirmed the expression of histiocytic markers and vimentin. As far as we know, no tumour displaying these peculiar morphological features has yet been described.

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Reticulohistiocytoses: a revision of the full spectrum
A. Bonometti, E. Berti
Journal of the European Academy of Dermatology and Venereology.2020; 34(8): 1684. CrossRef

Human Herpesvirus 8-Negative and Epstein-Barr Virus-Positive Effusion-Based Lymphoma in a Patient with Human Immunodeficiency Virus: Jung-Woo Choi, Younghye Kim, Ju-Han Lee, Young-Sik Kim; J Pathol Transl Med. 2015;49(5):409-412. Published online June 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.06.03

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Abstract PDF

A 39-year-old man infected with human immunodeficiency virus (HIV) was admitted to our hospital because of sudden onset of chest pain. Chest radiography revealed pneumothorax of the right lung. Computed tomographic scans disclosed a 5.8-cm-sized emphysematous bulla in the right middle lobe of the lung. Histologically, the wedge-resected lung showed medium to large atypical cells within the bullous cavity of the Pneumocystis jirovecii pneumonia, without solid mass formation. These atypical cells were confirmed to be large B-cell lymphoma, Epstein-Barr virus–positive and human herpesvirus 8–negative. Therefore, this case was not diagnosed as primary effusion lymphoma, but effusion-based lymphoma arising in an emphysematous cavity of an HIV-infected patient. This type of effusion-based lymphoma has never been reported, and, although rare, it should be noted in order to clinically diagnose this lymphoma.

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Primary Effusion Lymphoma: A Timely Review on the Association with HIV, HHV8, and EBV
Chih-Yi Liu, Bo-Jung Chen, Shih-Sung Chuang
Diagnostics.2022; 12(3): 713. CrossRef
Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics
Savanah D. Gisriel, Ji Yuan, Ryan C. Braunberger, Danielle L.V. Maracaja, Xueyan Chen, Xiaojun Wu, Jenna McCracken, Mingyi Chen, Yi Xie, Laura E. Brown, Peng Li, Yi Zhou, Tarsheen Sethi, Austin McHenry, Ronald G. Hauser, Nathan Paulson, Haiming Tang, Eric
Modern Pathology.2022; 35(10): 1411. CrossRef
Age and CD20 Expression Are Significant Prognostic Factors in Human Herpes Virus-8-negative Effusion-based Lymphoma
Tomomi Kubota, Yosuke Sasaki, Eisuke Shiozawa, Masafumi Takimoto, Tsunekazu Hishima, Ja-Mun Chong
American Journal of Surgical Pathology.2018; 42(12): 1607. CrossRef

Oncocytic Renal Cell Carcinoma with Tubulopapillary Growth Having a Fat Component: Na Rae Kim, Hyun Yee Cho; J Pathol Transl Med. 2015;49(5):413-417. Published online July 30, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.01

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We report a rare case of oncocytic renal cell carcinoma (RCC) with tubulopapillary growth in the background of tuberculous end-stage kidney disease. Histology of the renal mass consisted of oncocytic cells forming solid, thin tubules and rare papillae. The tumor had abundant eosinophilic oncocytic cells containing occasional cytoplasmic Mallory body–like hyaline globules and a tiny focus of clear cells with intervening mature fat. Both the oncocytic cells and clear cells were immunoreactive for a-methylacyl-CoA racemase, vimentin, pancytokeratin, and CD10, and negative for transcription factor E3, CD15, human melanoma black 45, and c-kit. Mallory body–like hyaline globules were positive for CAM 5.2 and periodic acid–Schiff with or without diastase. Ultrastructurally, the tumor cells had abundant cytoplasmic mitochondria. The present case is a rare case of oncocytic RCC with tubulopapillary growth pattern. The case is unique in that the tumor was mixed with fat component, which is not common in RCC and thus can lead to misdiagnosis.

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Oncocytic papillary renal cell carcinoma (OPRCC): 2 case report and literature review
Yanchen Wang, Lihui Guan, Yaming Liu, Yuxuan Liu, Xiaoyan Guo, Yaofei Sun
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Brief Case Reports

Multifocal Polypoid Endometriosis Mimicking Malignancy in a Young Woman with a History of Hormonal Treatment: Ji-Young Kim, Tae-Jong Song, Hye-Kyung Choi, Jeong Yun Shim; J Pathol Transl Med. 2015;49(5):418-420. Published online June 9, 2015; DOI: https://doi.org/10.4132/jptm.2015.05.12

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Fertility preservation of polypoid endometriosis: Case series and literature review
Sayuri Miyoshi, Ken Yamaguchi, Yoshitsugu Chigusa, Masumi Sunada, Koji Yamanoi, Akihito Horie, Junzo Hamanishi, Eiji Kondoh, Masaki Mandai
Journal of Obstetrics and Gynaecology Research.2022; 48(2): 502. CrossRef
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Hiroyuki Yazawa, Riho Yazawa, Kaoru Fukuda, Miki Ohara
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Polypoid endometriosis: a mimic of malignancy
Soleen Ghafoor, Yulia Lakhman, Kay J. Park, Iva Petkovska
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Gastric Langerhans Cell Histiocytosis: Case Report and Review of the Literature: So Jung Lee, Chung Su Hwang, Gi Young Huh, Chang Hun Lee, Do Youn Park; J Pathol Transl Med. 2015;49(5):421-423. Published online June 9, 2015; DOI: https://doi.org/10.4132/jptm.2015.05.19

10,055 View
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Jianmin Zhao, Yanlei Li, Yanlin Zhang, Xue Mei, Wei Liu, Yinghong Li
Journal of Hematopathology.2024; 17(2): 63. CrossRef
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The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2024; 24(2): 175. CrossRef
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Langerhans Cell Histiocytosis with the Synchronous Invasion of Stomach and Colon in an Adult Patient: A Case Report
Seong Je Kim, Se In Hah, Ji Yoon Kwak, Jung Woo Choi, Hyun Chin Cho, Chang Yoon Ha, Woon Tae Jung, Ok Jae Lee, Chang Min Lee
The Korean Journal of Gastroenterology.2022; 80(3): 149. CrossRef
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Li Wang, Fang Yang, Yong Ding, Lixia Lu, Haili Li, Yangyang Cui, Lu Lu, Xiaohan Shen, Rong Ge
Journal of Clinical Laboratory Analysis.2022;[Epub] CrossRef
Upper Gastrointestinal Langerhans Cell Histiocytosis: A Report of 2 Adult Cases and a Literature Review
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