Journal of Pathology and Translational Medicine

Volume 50(1); January 2016

Reviews

Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives: Yoon Young Choi, Sung Hoon Noh, Jae-Ho Cheong; J Pathol Transl Med. 2016;50(1):1-9. Published online October 26, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.10

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Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus–positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

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Ménétrier’s Disease: Its Mimickers and Pathogenesis: Won Jae Huh, Robert J. Coffey, Mary Kay Washington; J Pathol Transl Med. 2016;50(1):10-16. Published online December 18, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.15

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Abstract PDF

Ménétrier’s disease is a rare protein-losing hypertrophic gastropathy. Histologically, it can be mistaken for other disorders showing hypertrophic gastropathy. The pathogenesis of Ménétrier’s disease is not fully understood; however, it appears that the epidermal growth factor receptor (EGFR) ligand, transforming growth factor alpha, contributes to the pathogenesis of this disorder. In this review, we will discuss disease entities that can mimic Ménétrier’s disease and the role of EGFR signaling in Ménétrier’s disease.

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Idiopathic Noncirrhotic Portal Hypertension: An Appraisal: Hwajeong Lee, Aseeb Ur Rehman, M. Isabel Fiel; J Pathol Transl Med. 2016;50(1):17-25. Published online November 11, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.23

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Abstract PDF

Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity.

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Overview of IgG4-Related Tubulointerstitial Nephritis and Its Mimickers: Hyeon Joo Jeong, Su-Jin Shin, Beom Jin Lim; J Pathol Transl Med. 2016;50(1):26-36. Published online December 14, 2015; DOI: https://doi.org/10.4132/jptm.2015.11.09

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Abstract PDF

Tubulointerstitial nephritis (TIN) is the most common form of renal involvement in IgG4-related disease. It is characterized by a dominant infiltrate of IgG4-positive plasma cells in the interstitium and storiform fibrosis. Demonstration of IgG4-positive plasma cells is essential for diagnosis, but the number of IgG4-positive cells and the ratio of IgG4-positive/IgG-positive plasma cells may vary from case to case and depending on the methods of tissue sampling even in the same case. IgG4-positive plasma cells can be seen in TIN associated with systemic lupus erythematosus, Sjögren syndrome, or anti-neutrophil cytoplasmic antibody–associated vasculitis, which further add diagnostic confusion and difficulties. To have a more clear view of IgG4-TIN and to delineate differential points from other TIN with IgG4-positive plasma cell infiltrates, clinical and histological features of IgG4-TIN and its mimickers were reviewed. In the rear part, cases suggesting overlap of IgG4-TIN and its mimickers and glomerulonephritis associated with IgG4-TIN were briefly described.

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IgG4-related kidney disease: Clinicopathologic features, differential diagnosis, and mimics
Sarwat I. Gilani, Alessia Buglioni, Lynn D. Cornell
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Original Articles

Review of Medical Advisory Services by the Korean Society of Pathologists from 2003 to 2014: Min Hye Jang, Geon Kook Lee, Han Seong Kim, Wan Seop Kim; J Pathol Transl Med. 2016;50(1):37-44. Published online November 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.18

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Abstract PDF Supplementary Material: Background
Since 2003, the Korean Society of Pathologists (KSP) has been officially providing medical advisory services (MAS). We reviewed the cases submitted to the KSP between 2003 and 2014. Methods: In total, 1,950 cases were submitted, most by private health insurance companies. The main purposes of the consultations were to clarify the initial diagnoses and to assign a proper disease classification code. We comprehensively reviewed 1,803 consultation cases with detailed information. Results: In spite of some fluctuations, the number of submitted cases has been significantly increasing over the 12 study years. The colon and rectum (40.3%), urinary bladder (14.2%), and stomach (6.9%) were the three most common tissues of origin. The most common diagnoses for each of the three tissues of origin were neuroendocrine tumor (50.7%), non-invasive papillary urothelial carcinoma (70.7%), and adenocarcinoma (36.2%). Regardless of the tissue of origin, neuroendocrine tumor of the digestive system was the most common diagnosis (419 of 1,803). Conclusions: In the current study, we found that pathologic consultations associated with private health insurance accounted for a large proportion of the MAS. Coding of the biologic behavior of diseases was the main issue of the consultations. In spite of the effort of the KSP to set proper guidelines for coding and classification of tumors, this review revealed that problems still exist and will continue to be an important issue.

Eosinophils in Colorectal Neoplasms Associated with Expression of CCL11 and CCL24: Hyuck Cho, Sung-Jig Lim, Kyu Yeoun Won, Go Eun Bae, Gou Young Kim, Ji Won Min, Byeong-joo Noh; J Pathol Transl Med. 2016;50(1):45-51. Published online December 14, 2015; DOI: https://doi.org/10.4132/jptm.2015.10.16

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Abstract PDF

Background
A decrease in the number of tissue eosinophils is known to reflect the malignancy potential of neoplastic lesions and even prognosis. Increased levels of the chemokines CCL11 and CCL24 in serum and tissue are also known to have diagnostic value as serum tumor markers or prognostic factors. The aim of this study was to evaluate the correlation between the degree of tissue eosinophilia and the expression of these chemokines in the glandular and stromal cells of colorectal neoplastic lesions ranging from benign to malignant tumors. Methods: We counted the number of infiltrating eosinophils in neoplastic lesion tissue and we evaluated the expression of CCL11 and CCL24 in glandular cells and stromal cells by immunohistochemical staining. Results: The results showed that the number of eosinophils decreased significantly and the expression of CCL11 and CCL24 in glandular cells decreased with tumor progression, whereas the stromal expression of CCL11 and CCL24 appeared to increase. Conclusions: The discrepancy in CCL11 and CCL24 expression between glandular cells and stromal cells might shed light on how colorectal cancer evades the immune system, which would enable further development of immunotherapies that target these chemokines. Further research on eosinophil biology and the expression pattern of chemokines in tumor cells is needed.

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Immunohistochemical Expression and Clinical Significance of Suggested Stem Cell Markers in Hepatocellular Carcinoma: Jong Jin Sung, Sang Jae Noh, Jun Sang Bae, Ho Sung Park, Kyu Yun Jang, Myoung Ja Chung, Woo Sung Moon; J Pathol Transl Med. 2016;50(1):52-57. Published online November 18, 2015; DOI: https://doi.org/10.4132/jptm.2015.10.09

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Abstract PDF

Background
Increasing evidence has shown that tumor initiation and growth are nourished by a small subpopulation of cancer stem cells (CSCs) within the tumor mass. CSCs are posited to be responsible for tumor maintenance, growth, distant metastasis, and relapse after curative operation. We examined the expression of CSC markers in paraffin-embedded tissue sections of hepatocellular carcinoma (HCC) and correlated the results with clinicopathologic characteristics. Methods: Immunohistochemical staining for the markers believed to be expressed in the CSCs, including epithelial cell adhesion molecule (EpCAM), keratin 19 (K19), CD133, and CD56, was performed in 82 HCC specimens. Results: EpCAM expression was observed in 56% of the HCCs (46/82) and K19 in 6% (5/82). EpCAM expression in HCC significantly correlated with elevated α-fetoprotein level, microvessel invasion of tumor cells, and high histologic grade. In addition, Ep- CAM expression significantly correlated with K19 expression. The overall survival and relapsefree survival rates in patients with EpCAM-expressing HCC were relatively lower than those in patients with EpCAM-negative HCC. All but two of the 82 HCCs were negative for CD133 and CD56, respectively. Conclusions: Our results suggest that HCCs expressing EpCAM are associated with unfavorable prognostic factors and have a more aggressive clinical course than those not expressing EpCAM. Further, the expression of either CD133 or CD56 in paraffin-embedded HCC tissues appears to be rare.

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Recent Progress in Systemic Therapy for Advanced Hepatocellular Carcinoma
Narayanan Sadagopan, Aiwu Ruth He
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Clinicopathological and prognostic value of epithelial cell adhesion molecule in solid tumours: a meta-analysis
Peiwen Ding, Panyu Chen, Jiqi Ouyang, Qiang Li, Shijie Li
Frontiers in Oncology.2023;[Epub] CrossRef
PD-L1 Downregulation and DNA Methylation Inhibition for Molecular Therapy against Cancer Stem Cells in Hepatocellular Carcinoma
Caecilia Sukowati, Loraine Kay D. Cabral, Beatrice Anfuso, Francesco Dituri, Roberto Negro, Gianluigi Giannelli, Claudio Tiribelli
International Journal of Molecular Sciences.2023; 24(17): 13357. CrossRef
EpCAM, Ki67, and ESM1 Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation
Aiat Shaban Hemida, Doha Maher Taie, Moshira Mohamed Abd El-Wahed, Mohammed Ibrahim Shabaan, Mona Saeed Tantawy, Nermine Ahmed Ehsan
Applied Immunohistochemistry & Molecular Morphology.2023; 31(9): 596. CrossRef
The clinical, prognostic and therapeutic significance of liver cancer stem cells and their markers
Izabela Zarębska, Arkadiusz Gzil, Justyna Durślewicz, Damian Jaworski, Paulina Antosik, Navid Ahmadi, Marta Smolińska-Świtała, Dariusz Grzanka, Łukasz Szylberg
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Detection of oncogenic mutations in paired circulating tumor DNA and circulating tumor cells in patients with hepatocellular carcinoma
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Translational Oncology.2021; 14(7): 101073. CrossRef
Hepatocellular Carcinoma Score and Subclassification Into Aggressive Subtypes Using Immunohistochemical Expression of p53, β-Catenin, CD133, and Ki-67
Asmaa G. Abdou, Nanis S. Holah, Dina S. Elazab, Walaa G. El-Gendy, Mohammed T. Badr, Dalia R. Al-Sharaky
Applied Immunohistochemistry & Molecular Morphology.2021; 29(1): 20. CrossRef
The prognostic significance of neuroendocrine markers and somatostatin receptor 2 in hepatocellular carcinoma
Keigo Murakami, Hiroyuki Kumata, Shigehito Miyagi, Takashi Kamei, Hironobu Sasano
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Hend Ibrahim Shousha, Rabab Fouad, Tamer Mahmoud Elbaz, Dina Sabry, Mohamed Mahmoud Nabeel, Ahmed Hosni Abdelmaksoud, Aisha Mahmoud Elsharkawy, Zeinab Abdellatif Soliman, Ghada Habib, Ashraf Omar Abdelaziz
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Napabucasin Reduces Cancer Stem Cell Characteristics in Hepatocellular Carcinoma
Ya Li, Qiuju Han, Huajun Zhao, Quanjuan Guo, Jian Zhang
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The mRNA Distribution of Cancer Stem Cell Marker CD90/Thy-1 Is Comparable in Hepatocellular Carcinoma of Eastern and Western Populations
An B. Luong, Huy Q. Do, Paola Tarchi, Deborah Bonazza, Cristina Bottin, Loraine Kay D. Cabral, Long D. C. Tran, Thao P. T. Doan, Lory S. Crocè, Hoa L. T. Pham, Claudio Tiribelli, Caecilia H. C. Sukowati
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Histological architectural classification determines recurrence pattern and prognosis after curative hepatectomy in patients with hepatocellular carcinoma
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Chih‑Jan Ko, Chia‑Jung Li, Meng‑Yu Wu, Pei‑Yi Chu
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Evaluation of the VE1 Antibody in Thyroid Cytology Using Ex Vivo Papillary Thyroid Carcinoma Specimens: Yon Hee Kim, Hyunee Yim, Yong-Hee Lee, Jae Ho Han, Kyi Beom Lee, Jeonghun Lee, Euy Young Soh, Seon-Yong Jeong, Jang-Hee Kim; J Pathol Transl Med. 2016;50(1):58-66. Published online December 14, 2015; DOI: https://doi.org/10.4132/jptm.2015.10.10

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Abstract PDF

Background
Recently, VE1, a monoclonal antibody against the BRAFV600E mutant protein, has been investigated in terms of its detection of the BRAFV600E mutation. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in thyroid cytology samples is rarely performed, and its diagnostic value in cytology has not been well established. In present study, we explored VE1 immunoexpression in cytology samples from ex vivo papillary thyroid carcinoma specimens in order to minimize limitations of low cellularity and sampling/targeting errors originated from thyroid fineneedle aspiration and compared our results with those obtained using the corresponding papillary thyroid carcinoma tissues. Methods: The VE1 antibody was evaluated in 21 cases of thyroid cytology obtained directly from ex vivo thyroid specimens. VE1 immunostaining was performed using liquid-based cytology, and the results were compared with those obtained using the corresponding tissues. Results: Of 21 cases, 19 classic papillary thyroid carcinomas had BRAFV600E mutations, whereas two follicular variants expressed wild-type BRAF. VE1 immunoexpression varied according to specimen type. In detection of the BRAFV600E mutation, VE1 immunostaining of the surgical specimen exhibited 100% sensitivity and 100% specificity, whereas VE1 immunostaining of the cytology specimen exhibited only 94.7% sensitivity and 0% specificity. Conclusions: Our data suggest that VE1 immunostaining of a cytology specimen is less specific than that of a surgical specimen for detection of the BRAFV600E mutation, and that VE1 immunostaining of a cytology specimen should be further evaluated and optimized for clinical use.

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Journal of Pathology and Translational Medicine.2017; 51(6): 521. CrossRef
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Case Studies

IgG4-Related Disease Presented as a Mural Mass in the Stomach: Chang Gok Woo, Jeong Hwan Yook, Ah Young Kim, Jihun Kim; J Pathol Transl Med. 2016;50(1):67-70. Published online September 30, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.28

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Abstract PDF

Isolated gastric IgG4-related disease (IgG4-RD) is a very rare tumefactive inflammatory condition, with only a few cases reported to date. A 48-year-old woman was incidentally found to have a subepithelial tumor in the stomach. Given a presumptive diagnosis of gastrointestinal stromal tumor or neuroendocrine tumor, she underwent wedge resection. The lesion was vaguely nodular and mainly involved the submucosa and proper muscle layer. Microscopically, all classical features of type I autoimmune pancreatitis including lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and numerous IgG4-positive plasma cells were seen. She had no evidence of IgG4-RD in other organs. Although very rare, IgG4-RD should be considered one of the differential diagnoses in the setting of gastric wall thickening or subepithelial mass-like lesion. Deep biopsy with awareness of this entity might avoid unnecessary surgical intervention.

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Gastric-Type Extremely Well-Differentiated Adenocarcinoma of the Stomach: A Challenge for Preoperative Diagnosis: Mee Joo, Song Hee Han; J Pathol Transl Med. 2016;50(1):71-74. Published online September 30, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.14

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Gastric-type extremely well-differentiated adenocarcinoma (EWDA) is a rare type of gastric adenocarcinoma characterized by infiltration of well-formed mucinous glands with little or no nuclear atypia, which resemble foveolar epithelium or pyloric glands. Because of its high degree of differentiation, preoperative biopsy diagnosis of gastric-type EWDA is very difficult. We encountered a case of gastric-type EWDA, manifesting as a Borrmann type 4 lesion, in a 47-year-old man. Despite four repeated biopsies, the preoperative biopsy diagnosis was not conclusive due to the scarcity of diagnostic tumor cells and lack of knowledge regarding the unusual histologic findings of gastric-type EWDA. We herein describe the histologic findings of gastric-type EWDA in detail, with the aim of facilitating a preoperative biopsy diagnosis and understanding of this rare type of gastric adenocarcinoma.

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