Journal of Pathology and Translational Medicine

Review

A stepwise approach to fine needle aspiration cytology of lymph nodes: Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee; J Pathol Transl Med. 2023;57(4):196-207. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.12

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The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.

Citations

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Immunocytochemical markers, molecular testing and digital cytopathology for aspiration cytology of metastatic breast carcinoma
Joshua J. X. Li, Gary M. Tse
Cytopathology.2024; 35(2): 218. CrossRef
Response to comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee
Journal of Pathology and Translational Medicine.2024; 58(1): 43. CrossRef
Comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
Elisabetta Maffei, Valeria Ciliberti, Pio Zeppa, Alessandro Caputo
Journal of Pathology and Translational Medicine.2024; 58(1): 40. CrossRef

Original Articles

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea: Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho; J Pathol Transl Med. 2023;57(3):166-177. Published online May 10, 2023; DOI: https://doi.org/10.4132/jptm.2023.04.12

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Abstract PDF Supplementary Material

Background
Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study.
Methods
Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53.
Results
CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history.
Conclusions
Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

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Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy
Sangjoon Choi, Mofazzal Hossain, Hyun Lee, Jina Baek, Hye Seon Park, Chae-Lyul Lim, DoYeon Han, Taehyun Park, Jong Hyeok Kim, Gyungyub Gong, Mi-Na Kweon, Hee Jin Lee
Cancer Immunology, Immunotherapy.2024;[Epub] CrossRef

Correlation between myoferlin expression and lymph node metastasis in papillary thyroid carcinoma: Ji Min Na, Dong Chul Kim, Dae Hyun Song, Hyo Jung An, Hyun Min Koh, Jeong-Hee Lee, Jong Sil Lee, Jung Wook Yang, Min Hye Kim; J Pathol Transl Med. 2022;56(4):199-204. Published online May 11, 2022; DOI: https://doi.org/10.4132/jptm.2022.03.19

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Abstract PDF: Background
Myoferlin is a multifunctional protein expressed in various normal and cancer cells, with novel oncogenic roles being newly discovered. Recently, correlations have been found between myoferlin expression and unfavorable prognosis in various carcinomas. This study investigated the prognostic role of myoferlin expression in papillary thyroid carcinoma (PTC), specifically that associated with nodal metastasis.
Methods
We collected clinicopathological data and PTC tissues from 116 patients who had been admitted to Gyeongsang National University Hospital in 2010. Immunohistochemical analysis was performed on surgical specimen-derived tissue microarray blocks. Myoferlin expression was graded, and the relationship between expression level and pathological features of tumors based on the American Joint Committee on Cancer staging system was evaluated.
Results
Of the 116 patient samples, 100 cases exhibited positive myoferlin expression. Higher grade of myoferlin expression was correlated with lower T category group (p = .010). Presence of lymph node metastasis was determined to be significantly correlated with low-grade myoferlin expression (p = .019), with no significant difference between pN1a and pN1b tumors.
Conclusions
Our study revealed an adverse correlation between myoferlin expression and pathological features of PTC, evidence of the potential prognostic role of myoferlin in PTC lymph node metastasis.

Expression of prostate-specific membrane antigen in the neovasculature of primary tumors and lymph node metastasis of laryngeal squamous cell carcinomas: Gamze Erkılınç, Hasan Yasan, Yusuf Çağda Kumbul, Mehmet Emre Sivrice, Meltem Durgun; J Pathol Transl Med. 2022;56(3):134-143. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.02.22

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Abstract PDF

Background
Prostate-specific membrane antigen (PSMA) expression is encountered in tumor-associated neovascularization.
Methods
PSMA-antibody was applied to the paraffin blocks of 51 patients who were diagnosed with squamous cell carcinoma of the larynx and underwent laryngectomy and one who underwent lymph node dissection. The percentage of vascular expression in tumoral and extratumoral stroma and lymph nodes and intensity score in tumoral epithelium were evaluated and divided into groups according to the level of PSMA expression. Final PSMA expression was determined by multiplying intensity and percentage scores.
Results
The mean age was 61±10 years. Patients with perineural invasion, cartilage invasion, and local invasion exhibited higher PSMA expression scores. Age, tumor differentiation, tumor diameter, perineural invasion, tumor localization, capsular invasion, depth of invasion, surgical margin status, local invasion, nodal metastasis, TNM classification, and stage were similar in high and low PSMA expression groups. There was no PSMA expression in extratumoral vascular stroma. Significantly higher PSMA expression was observed in the vascular endothelium of metastatic lymph nodes compared with reactive lymph nodes. Patients with advanced-stage disease exhibited higher PSMA vascular expression scores compared to those with earlier stages (p<.001). PSMA expression was not correlated with overall survival, disease-specific survival, or disease-free survival (p>.05).
Conclusions
Our study suggests that higher PSMA expression is associated with cartilage invasion, local invasion, and advanced-stage of disease. PSMA expression can be utilized for detection of lymph node metastasis and has some predictive role in cases of neck metastasis.

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A Practical Guide to the Pearls and Pitfalls of PSMA PET Imaging
Andrew F. Voter, Rudolf A. Werner, Hatice Savas, Andrei Gafita, Ashley E. Ross, Michael A. Gorin, Lilja B. Solnes, Martin G. Pomper, Steven P. Rowe, Sara Sheikhbahaei
Seminars in Nuclear Medicine.2024; 54(1): 119. CrossRef
p53 and PTEN expression evaluation with molecular evident recent criteria in laryngeal carcinoma
Ayca Tan, Gorkem Eskiizmir, Ugur Kamiloglu, Sulen Sarioglu
Medicine.2023; 102(19): e33676. CrossRef
Diagnostic, Prognostic, and Therapeutic Role for Angiogenesis Markers in Head and Neck Squamous Cell Carcinoma: A Narrative Review
Lara Alessandrini, Laura Astolfi, Antonio Daloiso, Marta Sbaraglia, Tiziana Mondello, Elisabetta Zanoletti, Leonardo Franz, Gino Marioni
International Journal of Molecular Sciences.2023; 24(13): 10733. CrossRef

Causes of necrotic features in fine-needle aspirates from cervical lymph nodes: Young Jin Seo, Hyeongchan Shin, Hye Won Lee, Hye Ra Jung; J Pathol Transl Med. 2021;55(1):60-67. Published online November 27, 2020; DOI: https://doi.org/10.4132/jptm.2020.09.28

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Abstract PDF

Background
Lymph node fine-needle aspiration (LN FNA) cytology indicates necrosis in various diseases. Dominant necrotic features make the diagnosis of underlying conditions very difficult.
Methods
We retrospectively reviewed 460 patients who underwent cervical LN aspiration cytology that revealed necrotic findings at Keimyung University Dongsan Hospital in Daegu, Korea, from 2003–2017. Each specimen was evaluated and analyzed in association with the clinical findings, biopsy findings, and/or other ancillary tests, including acid-fast bacilli staining and molecular testing for Mycobacterium tuberculosis.
Results
When necrotic features were noted upon cervical LN FNA cytology, the most common pathologic LN FNA category was necrosis alone (31.5%). The second most common category was granulomatous inflammation (31.3%), followed by Kikuchi disease (20.0%) and malignant neoplasm (8.7%). In cases where the cervical LN FNA revealed necrosis alone, the most common final diagnosis was tuberculosis. In young patients, Kikuchi disease should be considered as one cervical LN FNA category, while metastatic carcinoma should be suspected in older patients.
Conclusions
Even when necrosis alone is observed in LN FNA cytology, it is important to determine the cause through further evaluation.

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The Potential Use of Peptides in the Fight against Chagas Disease and Leishmaniasis
Hayelom Berhe, Mahesh Kumar Cinthakunta Sridhar, Mulate Zerihun, Nir Qvit
Pharmaceutics.2024; 16(2): 227. CrossRef
Does the Necrotic Portion of Metastatic Lymphadenopathy from Squamous Cell Carcinoma Still Have Tumoral Oncologic Information? Differential Diagnosis of Benign Necrotic Lymphadenopathy Using microRNA
Eun Shin, Seung Hoon Han, Il-Seok Park, Jee Hye Wee, Joong Seob Lee, Heejin Kim
Biomedicines.2023; 11(9): 2407. CrossRef
Impact of HPV status in T1–2 oropharyngeal squamous cell carcinoma with bulky N3 nodes: a multicenter GETTEC study
Charles Hurel, Florent Carsuzaa, Julia Salleron, Philippe Gorphe, Christian Righini, Maximilien Rogé, Erwan de Mones, Sylvain Morinière, Sébastien Vergez, Juliette Thariat, Xavier Dufour
European Archives of Oto-Rhino-Laryngology.2023; 280(2): 847. CrossRef

Lymph node size and its association with nodal metastasis in ductal adenocarcinoma of the pancreas: Jaehoon Shin, Seungbeom Shin, Jae Hoon Lee, Ki Byung Song, Dae Wook Hwang, Hyoung Jung Kim, Jae Ho Byun, HyungJun Cho, Song Cheol Kim, Seung-Mo Hong; J Pathol Transl Med. 2020;54(5):387-395. Published online July 21, 2020; DOI: https://doi.org/10.4132/jptm.2020.06.23

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Abstract PDF

Background
Although lymph node metastasis is a poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC), our understanding of lymph node size in association with PDAC is limited. Increased nodal size in preoperative imaging has been used to detect node metastasis. We evaluated whether lymph node size can be used as a surrogate preoperative marker of lymph node metastasis.
Methods
We assessed nodal size and compared it to the nodal metastatic status of 200 patients with surgically resected PDAC. The size of all lymph nodes and metastatic nodal foci were measured along the long and short axis, and the relationships between nodal size and metastatic status were compared at six cutoff points.
Results
A total of 4,525 lymph nodes were examined, 9.1% of which were metastatic. The mean size of the metastatic nodes (long axis, 6.9±5.0 mm; short axis, 4.3±3.1 mm) was significantly larger than that of the non-metastatic nodes (long axis, 5.0±4.0 mm; short axis, 3.0±2.0 mm; all p<.001). Using a 10 mm cutoff, the sensitivity, specificity, positive predictive value, overall accuracy, and area under curve was 24.8%, 88.0%, 17.1%, 82.3%, and 0.60 for the long axis and 7.0%, 99.0%, 40.3%, 90.6%, and 0.61 for the short axis, respectively.
Conclusions
The metastatic nodes are larger than the non-metastatic nodes in PDAC patients. However, the difference in nodal size was too small to be identified with preoperative imaging. The performance of preoperative radiologic imaging to predict lymph nodal metastasis was not good. Therefore, nodal size cannot be used a surrogate preoperative marker of lymph node metastasis.

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Comparison of MRI and CT-based radiomics for preoperative prediction of lymph node metastasis in pancreatic ductal adenocarcinoma
Piaoe Zeng, Chao Qu, Jianfang Liu, Jingjing Cui, Xiaoming Liu, Dianrong Xiu, Huishu Yuan
Acta Radiologica.2023; 64(7): 2221. CrossRef
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Georgeann McGuinness, Jeffrey B. Alpert, Geraldine Brusca-Augello, Lea Azour, Jane P. Ko, Farah Tamizuddin, Elliott K. Gozansky, William H. Moore
Journal of Computer Assisted Tomography.2023; 47(1): 50. CrossRef
Predictive role of radiomics features extracted from preoperative cross-sectional imaging of pancreatic ductal adenocarcinoma in detecting lymph node metastasis: a systemic review and meta-analysis
Mohammad Mirza-Aghazadeh-Attari, Seyedeh Panid Madani, Haneyeh Shahbazian, Golnoosh Ansari, Alireza Mohseni, Ali Borhani, Shadi Afyouni, Ihab R. Kamel
Abdominal Radiology.2023; 48(8): 2570. CrossRef
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Kenichiro Uemura, Naru Kondo, Takeshi Sudo, Tatsuaki Sumiyoshi, Ryuta Shintakuya, Kenjiro Okada, Kenta Baba, Takumi Harada, Yoshiaki Murakami, Shinya Takahashi
Journal of Hepato-Biliary-Pancreatic Sciences.2023;[Epub] CrossRef
Regional lymph node metastasis detected on preoperative CT and/or FDG-PET may predict early recurrence of pancreatic adenocarcinoma after curative resection
Ja Kyung Yoon, Mi-Suk Park, Seung-Seob Kim, Kyunghwa Han, Hee Seung Lee, Seungmin Bang, Ho Kyoung Hwang, Sang Hyun Hwang, Mijin Yun, Myeong-Jin Kim
Scientific Reports.2022;[Epub] CrossRef
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Alessandro Coppola, Vincenzo La Vaccara, Tommaso Farolfi, Michele Fiore, Roberto Cammarata, Sara Ramella, Roberto Coppola, Damiano Caputo
Biomedicines.2022; 10(9): 2091. CrossRef
Evaluation of the 8th Edition AJCC Staging System for the Clinical Staging of Pancreatic Cancer
Huapyong Kang, Seung-seob Kim, Min Je Sung, Jung Hyun Jo, Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seung Woo Park, Si Young Song, Mi-Suk Park, Seungmin Bang
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Does direct invasion of peripancreatic lymph nodes impact survival in patients with pancreatic ductal adenocarcinoma? A retrospective dual-center study
Daisuke Hashimoto, Sohei Satoi, Mitsuaki Ishida, Kenji Nakagawa, Masaya Kotsuka, Tadataka Takagi, Hironori Ryota, Taichi Terai, Tatsuma Sakaguchi, Minako Nagai, So Yamaki, Takahiro Akahori, Tomohisa Yamamoto, Mitsugu Sekimoto, Masayuki Sho
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CA19.9 Serum Level Predicts Lymph-Nodes Status in Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Analysis
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Frontiers in Oncology.2021;[Epub] CrossRef

Prognostic Role of Metastatic Lymph Node Ratio in Papillary Thyroid Carcinoma: Jung-Soo Pyo, Jin Hee Sohn, Kyungseek Chang; J Pathol Transl Med. 2018;52(5):331-338. Published online August 30, 2018; DOI: https://doi.org/10.4132/jptm.2018.08.07

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Abstract PDF

Background
The aim of this study is to elucidate the clinicopathological significances, including the prognostic role, of metastatic lymph node ratio (mLNR) and tumor deposit diameter in papillary thyroid carcinoma (PTC) through a retrospective review and meta-analysis.
Methods
We categorized the cases into high (≥ 0.44) and low mLNR (< 0.44) and investigated the correlations with clinicopathological parameters in 64 PTCs with neck level VI lymph node (LN) metastasis. In addition, meta-analysis of seven eligible studies was used to investigate the correlation between mLNR and survival.
Results
Among 64 PTCs with neck level VI LN metastasis, high mLNR was found in 34 PTCs (53.1%). High mLNR was significantly correlated with macrometastasis (tumor deposit diameter ≥ 0.2 cm), extracapsular spread, and number of metastatic LNs. Based on linear regression test, mLNR was significantly increased by the largest LN size but not the largest metastatic LN (mLN) size. High mLNR was not correlated with nuclear factor κB or cyclin D1 immunohistochemical expression, Ki-67 labeling index, or other pathological parameters of primary tumor. Based on meta-analysis, high mLNR significantly correlated with worse disease-free survival at the 5-year and 10-year follow-up (hazard ratio [HR], 4.866; 95% confidence interval [CI], 3.527 to 6.714 and HR, 5.769; 95% CI, 2.951 to 11.275, respectively).
Conclusions
Our data showed that high mLNR significantly correlated with worse survival, macrometastasis, and extracapsular spread of mLNs. Further cumulative studies for more detailed criteria of mLNR are needed before application in daily practice.

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Thyroglobulin expression, Ki-67 index, and lymph node ratio in the prognostic assessment of papillary thyroid cancer
Helene Lindfors, Marie Karlsen, Ellinor Karlton, Jan Zedenius, Catharina Larsson, Catharina Ihre Lundgren, C. Christofer Juhlin, Ivan Shabo
Scientific Reports.2023;[Epub] CrossRef
Incidental Node Metastasis as an Independent Factor of Worse Disease-Free Survival in Patients with Papillary Thyroid Carcinoma
Renan Aguera Pinheiro, Ana Kober Leite, Beatriz Godoi Cavalheiro, Evandro Sobroza de Mello, Luiz Paulo Kowalski, Leandro Luongo Matos
Cancers.2023; 15(3): 943. CrossRef
A High-Quality Nomogram for Predicting Lung Metastasis in Newly Diagnosed Stage IV Thyroid Cancer: A Population-Based Study
WenYi Wang, JiaJing Liu, XiaoFan Xu, LiQun Huo, XuLin Wang, Jun Gu
Technology in Cancer Research & Treatment.2023; 22: 153303382311678. CrossRef
Lymph Node Ratio Predicts Recurrence in Patients with Papillary Thyroid Carcinoma with Low Lymph Node Yield
Il Ku Kang, Joonseon Park, Ja Seong Bae, Jeong Soo Kim, Kwangsoon Kim
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Superiority of metastatic lymph node ratio over number of node metastases and TNM/AJCC N classification in predicting cancer‐specific survival in medullary thyroid cancer
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Value of Combining Clinical Factors, Conventional Ultrasound, and Contrast-Enhanced Ultrasound Features in Preoperative Prediction of Central Lymph Node Metastases of Different Sized Papillary Thyroid Carcinomas
Yanfang Wang, Fang Nie, Guojuan Wang, Ting Liu, Tiantian Dong, Yamin Sun
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Atypical Histiocytoid Cells and Multinucleated Giant Cells in Fine-Needle Aspiration Cytology of the Thyroid Predict Lymph Node Metastasis of Papillary Thyroid Carcinoma
Ji Eun Choi, Ja Seong Bae, Dong-Jun Lim, So Lyung Jung, Chan Kwon Jung
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Patients Aged ≥55 Years With Stage T1-2N1M1 Differentiated Thyroid Cancer Should Be Downstaged in the Eighth Edition AJCC/TNM Cancer Staging System
Zeming Liu, Sichao Chen, Yihui Huang, Di Hu, Min Wang, Wei Wei, Chao Zhang, Wen Zeng, Liang Guo
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Case Study

Erdheim-Chester Disease Involving Lymph Nodes and Liver Clinically Mimicking Lymphoma: A Case Report: Yeoun Eun Sung, Yoon Seo Lee, Jieun Lee, Kyo Young Lee; J Pathol Transl Med. 2018;52(3):183-190. Published online December 27, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.16

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Abstract PDF

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis and multisystem disease. First described in 1930, there are no more than 750 cases reported. The etiology remains unknown, but a majority of cases of ECD and Langerhans cell histiocytosis were found to have clonal mutations involving genes of the mitogen-activated protein kinase pathway. We recently encountered a 53-year-old male patient with extensive ECD involving the systemic lymph nodes, pleura, liver, and long bones clinically mimicking malignant lymphoma. Biopsies were performed at multiple sites, including a pleural mass, an external iliac lymph node, bone marrow, and the liver. Based on histopathological and immunohistochemical findings of positivity for CD68 and negativity for CD1a and S-100, the patient was diagnosed with ECD. Interferon-α was administered as the first-line treatment, but the patient rapidly progressed to hepatic failure after 2 months of treatment. We report this rare case of ECD clinically mimicking malignant lymphoma and diagnosed by careful pathological review.

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Original Article

Programmed Death-Ligand 1 Expression and Its Correlation with Lymph Node Metastasis in Papillary Thyroid Carcinoma: Hyo Jung An, Gyung Hyuck Ko, Jeong-Hee Lee, Jong Sil Lee, Dong Chul Kim, Jung Wook Yang, Min Hye Kim, Jin Pyeong Kim, Eun Jung Jung, Dae Hyun Song; J Pathol Transl Med. 2018;52(1):9-13. Published online October 3, 2017; DOI: https://doi.org/10.4132/jptm.2017.07.26

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Abstract PDF

Background
The immunotherapeutic role of programmed death-ligand 1 (PD-L1) in life expectancy in many cancers has been highlighted. However, data regarding PD-L1 expression in papillary thyroid carcinoma (PTC) are limited. In this study, we describe the PD-L1 and programmed cell death protein 1 (PD-1) expressions in PTC and analyze their correlation with lymph node (LN) metastasis.
Methods
Clinicopathological data were obtained from 116 patients with PTC who were treated in Gyeongsang National University Hospital, Jinju, Korea in 2009. Tissue microarray blocks were made using representative paraffin blocks of classical PTCs excluding follicular variants. Two pathologists graded the proportion and intensity of PD-L1 and PD-1 expression in both tumor and inflammatory cells. According to their proportions, positive PTC cells were scored as negative (0%), grade 1 (1%–50%), and grade 2 (51%–100%). Similarly, positive inflammatory cells were graded as negative (0%), grade 1 (1%–10%), and grade 2 (11%–20%). The intensity of each protein expression was simplified as positive or negative.
Results
A statistically significant correlation exists between the proportions of PD-1 and PD-L1 expression both in papillary carcinoma (p=.001) and peritumoral lymphoid cells in the thyroid (p<.001). In addition, the proportion of PD-L1 expression in PTC cells was closely related to metastatic LNs (p=.036).
Conclusions
PD-L1 is a valuable predictive marker for LN metastasis in PTC. Immunomodulating therapies that inhibit PD-L1 might be an option for patients with LN metastasis.

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Vitor Barreto Santana, Vitória Machado Krüger, Maria Cristina Yunes Abrahão, Pietru Lentz Martins Cantú, Rosicler Luzia Brackmann, Gisele Moroni Pandolfi, Liane Scheffler Marisco, Gabriela Remonatto, Luciana Adolfo Ferreira, Marcia Silveira Graudenz
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Update regarding the role of PD-L1 in oncocytic thyroid lesions on cytological samples
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Analysis of anti‐apoptotic PVT1 oncogene and apoptosis‐related proteins (p53, Bcl2, PD‐1, and PD‐L1) expression in thyroid carcinoma
Afaf T. Ibrahiem, Amin K. Makhdoom, Khalid S. Alanazi, Abdulaziz M. Alanazi, Abdulaziz M. Mukhlef, Saad H. Elshafey, Eman A. Toraih, Manal S. Fawzy
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Wenyue Zhao, Lu Liu, Xuehao Li, Shun Xu
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Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas
Peter P. Issa, Mahmoud Omar, Yusef Buti, Chad P. Issa, Bert Chabot, Christopher J. Carnabatu, Ruhul Munshi, Mohammad Hussein, Mohamed Aboueisha, Mohamed Shama, Ralph L. Corsetti, Eman Toraih, Emad Kandil
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Rujia Qin, Chunyan Li, Xuemin Wang, Zhaoming Zhong, Chuanzheng Sun
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PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker
Marco Dell’Aquila, Alessia Granitto, Maurizio Martini, Sara Capodimonti, Alessandra Cocomazzi, Teresa Musarra, Vincenzo Fiorentino, Alfredo Pontecorvi, Celestino Pio Lombardi, Guido Fadda, Liron Pantanowitz, Luigi Maria Larocca, Esther Diana Rossi
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Programmed Death-Ligand 1 (PD-L1) Is a Potential Biomarker of Disease-Free Survival in Papillary Thyroid Carcinoma: a Systematic Review and Meta-Analysis of PD-L1 Immunoexpression in Follicular Epithelial Derived Thyroid Carcinoma
Ilaria Girolami, Liron Pantanowitz, Ozgur Mete, Matteo Brunelli, Stefano Marletta, Chiara Colato, Pierpaolo Trimboli, Anna Crescenzi, Massimo Bongiovanni, Mattia Barbareschi, Albino Eccher
Endocrine Pathology.2020; 31(3): 291. CrossRef
Regression of Papillary Thyroid Cancer during Nivolumab for Renal Cell Cancer
Andrea Palermo, Andrea Napolitano, Daria Maggi, Anda Mihaela Naciu, Gaia Tabacco, Silvia Manfrini, Anna Crescenzi, Chiara Taffon, Francesco Pantano, Bruno Vincenzi, Guiseppe Tonini, Daniele Santini
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A potential biomarker hsa-miR-200a-5p distinguishing between benign thyroid tumors with papillary hyperplasia and papillary thyroid carcinoma
Xian Wang, Shan Huang, Xiaocan Li, Dongrui Jiang, Hongzhen Yu, Qiang Wu, Chaobing Gao, Zhengsheng Wu, Yi-Hsien Hsieh
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Papillary Thyroid Carcinoma Emerging from Hashimoto Thyroiditis Demonstrates Increased PD-L1 Expression, Which Persists with Metastasis
Daniel Lubin, Ezra Baraban, Amanda Lisby, Sahar Jalali-Farahani, Paul Zhang, Virginia Livolsi
Endocrine Pathology.2018; 29(4): 317. CrossRef
Chemotherapeutic Treatments Increase PD-L1 Expression in Esophageal Squamous Cell Carcinoma through EGFR/ERK Activation
Hoi Yan Ng, Jian Li, Lihua Tao, Alfred King-Yin Lam, Kwok Wah Chan, Josephine Mun Yee Ko, Valen Zhuoyou Yu, Michael Wong, Benjamin Li, Maria Li Lung
Translational Oncology.2018; 11(6): 1323. CrossRef

Review

Sentinel Lymph Node in Breast Cancer: Review Article from a Pathologist’s Point of View: Sophia K. Apple; J Pathol Transl Med. 2016;50(2):83-95. Published online January 12, 2016; DOI: https://doi.org/10.4132/jptm.2015.11.23

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Abstract PDF

Breast cancer staging, in particular N-stage changed most significantly due to the advanced technique of sentinel lymph node biopsy two decades ago. Pathologists have more thoroughly examined and scrutinized sentinel lymph node and found increased number of small volume metastases. While pathologists use the strict criteria from the Tumor Lymph Node Metastasis (TNM) Classification, studies have shown poor reproducibility in the application of American Joint Committee on Cancer and International Union Against Cancer/TNM guidelines for sentinel lymph node classification in breast cancer. In this review article, a brief history of TNM with a focus on N-stage is described, followed by innate problems with the guidelines, and why pathologists may have difficulties in assessing lymph node metastases uniformly. Finally, clinical significance of isolated tumor cells, micrometastasis, and macrometastasis is described by reviewing historical retrospective data and significant prospective clinical trials.

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Brief Case Report

Peritoneal Carcinosarcoma and Ovarian Papillary Serous Carcinoma Are the Same Origin: Analysis of TP53 Mutation and Microsatellite Suggests a Monoclonal Origin: Chang Gok Woo, Dae Shik Suh, Joo Young Kim, Chang Ohk Sung, Jene Choi, Kyu-Rae Kim; Korean J Pathol. 2014;48(6):449-453. Published online December 31, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.6.449

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Original Articles

Extrapulmonary Lymphangioleiomyoma: Clinicopathological Analysis of 4 Cases: Dae Hyun Song, In Ho Choi, Sang Yun Ha, Kang Min Han, Jae Jun Lee, Min Eui Hong, Yoon-La Choi, Kee-Taek Jang, Sang Yong Song, Chin A Yi, Joungho Han; Korean J Pathol. 2014;48(3):188-192. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.188

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Abstract PDF

Background

Lymphangioleiomyomatosis (LAM) is a slowly progressive neoplastic disease that predominantly affects females. Usually, LAM affects the lung; it can also affect extrapulmonary sites, such as the mediastinum, the retroperitoneum, or the lymph nodes, although these locations are rare. A localized form of LAM can manifest as extrapulmonary lesions; this form is referred to as extrapulmonary lymphangioleiomyoma (E-LAM). Due to the rare occurrence of E-LAM and its variable, atypical location, E-LAM is often difficult to diagnose. Herein, we report the clinicopathological information from four E-LAM cases, and also review previous articles investigating this disease.

Methods

Four patients with E-LAM were identified at the Samsung Medical Center (Seoul, Korea) from 1995 to 2012. All E-LAM lesions underwent surgical excision.

Results

All patients were females within the age range of 43 to 47 years. Two patients had para-aortic retroperitoneal masses, while the other two patients had pelvic lesions; two out of the four patients also had accompanying pulmonary LAM. In addition, no patient displayed any evidence of tuberous sclerosis. Histologically, two patients exhibited nuclear atypism with cytologic degeneration.

Conclusions

E-LAM should be considered in the differential diagnosis of patients presenting with pelvic or para-aortic masses. We also conclude that further clinical and pathological evaluation is needed in patients with E-LAM and nuclear atypism.

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Lymphangioleiomyomatosis with Tuberous Sclerosis Complex—A Case Study
Aleksandra Marciniak, Jolanta Nawrocka-Rutkowska, Agnieszka Brodowska, Andrzej Starczewski, Iwona Szydłowska
Journal of Personalized Medicine.2023; 13(11): 1598. CrossRef
A case of lymphangioleiomyomatosis with endometrial cancer diagnosed by retroperitoneoscopic para-aortic lymph node dissection
Aiko Ogasawara, Shogo Yamaguchi, Hiroaki Inui, Mieko Hanaoka, Daisuke Shintani, Sho Sato, Masanori Yasuda, Akira Yabuno
JAPANESE JOURNAL OF GYNECOLOGIC AND OBSTETRIC ENDOSCOPY.2022; 38(1): 158. CrossRef
Primary retroperitoneal PEComa: an incidental finding
Bárbara Monteiro Marinho, António Gâmboa Canha, Donzília Sousa Silva, José Davide Pinto Silva
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Imaging Findings of Thoracic Lymphatic Abnormalities
Jingshuo (Derek) Sun, Thomas Shum, Fardad Behzadi, Mark M. Hammer
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Extrapulmonary uterine lymphangioleiomyomatosis (LAM) and dysfunctional uterine bleeding: the first presentation of LAM in a tuberous sclerosis complex patient
Lucy Grant, Saliya Chipwete, San Soo Hoo, Anjali Bhatnagar
BMJ Case Reports.2019; 12(2): e226358. CrossRef
Summary of the Japanese Respiratory Society statement for the treatment of lung cancer with comorbid interstitial pneumonia
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Respiratory Investigation.2019; 57(6): 512. CrossRef
Incidental lymphangioleiomyomatosis in the lymph nodes of gynecologic surgical specimens
Ikumi Kuno, Hiroshi Yoshida, Hanako Shimizu, Takashi Uehara, Masaya Uno, Mitsuya Ishikawa, Tomoyasu Kato
European Journal of Obstetrics & Gynecology and Reproductive Biology.2018; 231: 93. CrossRef
Solitary extrapulmonary lymphangioleiomyomatosis of the liver: A case report and literature review
Weiwei Fu, Yujun Li, Hong Li, Ping Yang, Xiaoming Xing
Experimental and Therapeutic Medicine.2016; 12(3): 1499. CrossRef
Incidental Pelvic and Para-aortic Lymph Node Lymphangioleiomyomatosis Detected During Surgical Staging of Pelvic Cancer in Women Without Symptomatic Pulmonary Lymphangioleiomyomatosis or Tuberous Sclerosis Complex
Joseph T. Rabban, Brandie Firetag, Ankur R. Sangoi, Miriam D. Post, Charles J. Zaloudek
American Journal of Surgical Pathology.2015; 39(8): 1015. CrossRef

Tumor Sprouting in Papillary Thyroid Carcinoma Is Correlated with Lymph Node Metastasis and Recurrence: Eunjung Lee, Wonkyung Jung, Jeong-Soo Woo, Jae Bok Lee, Bong Kyung Shin, Han Kyeom Kim, Aeree Kim, Baek-hui Kim; Korean J Pathol. 2014;48(2):117-125. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.117

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Abstract PDF

Background

Identification of poor prognostic factors in papillary thyroid carcinoma (PTC) patients is important for the patients' care and follow-up. We can sometimes see small tumor clusters without desmoplasia and no evidence of lymphatic emboli around the main tumor mass of PTC. We termed this form of tumor clustering, 'tumor sprouting,' and determined whether these tumors correlate with lymphovascular invasion, lymph node metastasis, and recurrence.

Methods

We analyzed a total of 204 cases of papillary thyroid macrocarcinoma. Number, size and distance from the main tumor of the tumor sprouting were observed and analyzed with clinicopathologic characteristics.

Results

Tumor sprouting was observed in 101 patients. Presence of tumor sprouting was significantly associated with positive resection margin (p=.002), lymphovascular invasion (p=.001), lymph node metastasis (p<.001), and recurrence (p=.004). Univariate analysis of recurrence-free survival revealed that tumor multiplicity (p=.037), positive resection margin (p=.007), lymphovascular invasion (p=.004), lymph node metastasis (p<.001), and tumor sprouting (p=.004) were poor prognostic factors. In multivariate analysis, positive resection margin was an independent poor prognostic factor of recurrence.

Conclusions

In conclusion, tumor sprouting is significantly correlated with lymph node metastasis and recurrence. Evaluation of tumor sprouting in PTC patients could be helpful in predicting tumor recurrence or lymph node metastasis.

Citations

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Significance of Lymphovascular Invasion as a Prognostic Factor in Patients with Papillary Thyroid Cancer: a Systematic Review and Meta-Analysis
Ho-Ryun Won, Bon Seok Koo
International Journal of Thyroidology.2023; 16(2): 157. CrossRef
Peripheral Versus Intraparenchymal Papillary Thyroid Microcarcinoma: Different Morphologies and PD-L1 Expression
Bozidar Kovacevic, Dragana Vucevic, Snezana Cerovic, Catarina Eloy
Head and Neck Pathology.2022; 16(1): 200. CrossRef
Lymphovascular invasion and risk of recurrence in papillary thyroid carcinoma
Katy Wagner, Earl Abraham, Bryan Tran, David Roshan, James Wykes, Peter Campbell, Ardalan Ebrahimi
ANZ Journal of Surgery.2020; 90(9): 1727. CrossRef
The Predictors of Multicentricity in Well-Differentiated Thyroid Cancer
Mohamed Hegazi, Waleed El Nahas, Mohamed Elmetwally, Amr Hassan, Waleed Gado , Islam Abdou, Ahmed Senbel, Mohamed Samir Abou-Sheishaa
Journal of Analytical Oncology.2018; 7(4): 65. CrossRef
Prognostic impact of vascular invasion in differentiated thyroid carcinoma: a systematic review and meta-analysis
Huy Gia Vuong, Tetsuo Kondo, Uyen N P Duong, Thong Quang Pham, Naoki Oishi, Kunio Mochizuki, Tadao Nakazawa, Lewis Hassell, Ryohei Katoh
European Journal of Endocrinology.2017; 177(2): 207. CrossRef
Detection of Tumor Multifocality Is Important for Prediction of Tumor Recurrence in Papillary Thyroid Microcarcinoma: A Retrospective Study and Meta-Analysis
Jung-Soo Pyo, Jin Hee Sohn, Guhyun Kang
Journal of Pathology and Translational Medicine.2016; 50(4): 278. CrossRef

Case Study

Peritoneal and Nodal Gliomatosis with Endometriosis, Accompanied with Ovarian Immature Teratoma: A Case Study and Literature Review: Na Rae Kim, Soyi Lim, Juhyeon Jeong, Hyun Yee Cho; Korean J Pathol. 2013;47(6):587-591. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.587

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Abstract PDF

Gliomatosis peritonei (GP) indicates the peritoneal implantation of mature neuroglial tissue and is usually accompanied by ovarian mature or immature teratoma. Here, we report a case of ovarian immature teratoma associated with gliomatosis involving the peritoneum, lymph nodes and Douglas' pouch, where gliomatosis coexisted with endometriosis. As far as we know, only seven cases of GP have been reported as coexisting with endometriosis. Eight cases with mature glial tissue in the lymph nodes, i.e., nodal gliomatosis, have been published either in association with GP or in its absence. Metaplasia of pluripotent coelomic stem cells has been suggested to be responsible for the pathogenesis of endometriosis and GP rather than implantation metastases of ovarian teratomatous tumor with varying maturation. This theory is also applied to GP independently of ovarian teratomatous tumors. To the best of our knowledge, nodal gliomatosis coexisting with GP and also involving endometriosis has not yet been reported.

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Ovarian Immature Teratoma With Nodal Gliomatosis: A Case Report and Literature Review
Marwa Alna’irat, W. Glenn McCluggage, Maysa Al-Hussaini
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Germ Cell Tumors of the Ovary: A Review
Preetha Ramalingam
Seminars in Diagnostic Pathology.2023; 40(1): 22. CrossRef
Immature Teratoma with Gliomatosis Peritonei Arising in a Young Girl: Report of a Rare Case and Review of Literature
Isheeta Ahuja, Ruchi Rathore, Neerja Bhatla, Sandeep R. Mathur
Indian Journal of Gynecologic Oncology.2023;[Epub] CrossRef
Growing Teratoma Syndrome with Synchronous Gliomatosis Peritonei during Chemotherapy in Ovarian Immature Teratoma: A Case Report and Literature Review
Sijian Li, Na Su, Congwei Jia, Xinyue Zhang, Min Yin, Jiaxin Yang
Current Oncology.2022; 29(9): 6364. CrossRef
Extratesticular gliomatosis peritonei after mesenteric teratoma: a case report and literature review
Jiaqiang Li, Shoulin Li, Dong Xiao, Jiaming Song, Jianxiong Mao, Jianchun Yin
Journal of International Medical Research.2021; 49(9): 030006052110470. CrossRef
Germ Cell Tumors of the Female Genital Tract
Elizabeth D. Euscher
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Gliomatosis peritonei: a series of eight cases and review of the literature
Dan Wang, Cong-wei Jia, Rui-e Feng, Hong-hui Shi, Juan Sun
Journal of Ovarian Research.2016;[Epub] CrossRef

Original Article

Histopathologic Predictors of Lymph Node Metastasis and Prognosis in Tonsillar Squamous Cell Carcinoma: Dong Jin Lee, Mi Jung Kwon, Eun Sook Nam, Ji Hyun Kwon, Jin Hwan Kim, Young-Soo Rho, Hyung Sik Shin, Seong Jin Cho; Korean J Pathol. 2013;47(3):203-210. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.203

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Abstract PDF

Background

Risk factors for lymph node metastasis in tonsillar squamous cell carcinoma (TSCC) need to be established to determine the degree of surgery required to achieve high curative rates. However, little is known currently about the histopathological features predicting prognosis, specifically in TSCC.

Methods

This study included 53 patients who underwent surgical resection with neck dissection. Clinicopathological factors investigated included age, gender, alcohol use, tobacco consumption, tumor stage, adjacent structure involvement, cell differentiation, squamous dysplasia, in situ carcinoma associated with primary invasive cancer, carcinoma in situ skip lesions, necrosis, invasive front, depth of invasion, and lymphatic, muscle, or perineural invasion.

Results

Contralateral cervical metastasis was associated with higher T stages and soft palate invasion. Lymphatic and muscle invasion were associated with ipsilateral cervical metastasis. Advanced T stage, invasion to the base of tongue, and skip lesions were associated with decreased disease-free survival. Advanced T stage and skip lesions were associated with worse overall survival.

Conclusions

Advanced T stage and soft palate invasion may predict a high risk of contralateral nodal metastasis. T stage and skip lesion are worse prognostic factors in TSCC and should be commented in pathology reports.

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Mi Jung Kwon, Young-Soo Rho, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe, Eun Soo Kim, Bumjung Park, Mineui Hong, Kyueng-Whan Min
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Guo-Jun Tong, Gui-Yang Zhang, Jian Liu, Zhao-Zheng Zheng, Yan Chen, Ping-Ping Niu, Xu-Ting Xu
World Journal of Clinical Oncology.2018; 9(7): 148. CrossRef
HIPK2 Overexpression and Its Prognostic Role in Human Papillomavirus-Positive Tonsillar Squamous Cell Carcinoma
Mi Jung Kwon, So Young Kang, Eun Sook Nam, Seong Jin Cho, Young-Soo Rho
BioMed Research International.2017; 2017: 1. CrossRef
Frequent hepatocyte growth factor overexpression and low frequency of c-Met gene amplification in human papillomavirus–negative tonsillar squamous cell carcinoma and their prognostic significances
Mi Jung Kwon, Dong Hoon Kim, Hye-Rim Park, Hyung Sik Shin, Ji Hyun Kwon, Dong Jin Lee, Jin Hwan Kim, Seong Jin Cho, Eun Sook Nam
Human Pathology.2014; 45(7): 1327. CrossRef
CT and MR imaging findings of palatal tumors
Hiroki Kato, Masayuki Kanematsu, Hiroki Makita, Keizo Kato, Daijiro Hatakeyama, Toshiyuki Shibata, Keisuke Mizuta, Mitsuhiro Aoki
European Journal of Radiology.2014; 83(3): e137. CrossRef

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