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Volume 51(2); March 2017
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Review
Molecular Testing for Gastrointestinal Cancer
Hye Seung Lee, Woo Ho Kim, Yoonjin Kwak, Jiwon Koh, Jeong Mo Bae, Kyoung-Mee Kim, Mee Soo Chang, Hye Seung Han, Joon Mee Kim, Hwal Woong Kim, Hee Kyung Chang, Young Hee Choi, Ji Y. Park, Mi Jin Gu, Min Jin Lhee, Jung Yeon Kim, Hee Sung Kim, Mee-Yon Cho
J Pathol Transl Med. 2017;51(2):103-121.   Published online February 19, 2017
DOI: https://doi.org/10.4132/jptm.2017.01.24
  • 15,882 View
  • 854 Download
  • 40 Citations
AbstractAbstract PDF
With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.
Original Articles
Mesothelin Expression in Gastric Adenocarcinoma and Its Relation to Clinical Outcomes
Song-Hee Han, Mee Joo, Hanseong Kim, Sunhee Chang
J Pathol Transl Med. 2017;51(2):122-128.   Published online February 15, 2017
DOI: https://doi.org/10.4132/jptm.2016.11.18
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  • 12 Citations
AbstractAbstract PDF
Background
Although surgical resection with chemotherapy is considered effective for patients with advanced gastric cancer, it remains the third leading cause of cancer-related death in South Korea. Several studies have reported that mesothelial markers including mesothelin, calretinin, and Wilms tumor protein 1 (WT1) were positive in variable carcinomas, associated with prognosis, and were evaluated as potential markers for targeted therapy. The aim of this study was to assess the immunohistochemical expression of mesothelial markers (mesothelin, calretinin, and WT1) in gastric adenocarcinoma and their relations to clinocopathological features and prognosis. Methods: We evaluated calretinin, WT1, and mesothelin expression by immunohistochemical staining in 117 gastric adenocarcinomas. Results: Mesothelin was positively stained in 30 cases (25.6%). Mesothelin expression was related to increased depth of invasion (p = .002), lymph node metastasis (p = .013), and presence of lymphovascular (p = .015) and perineural invasion (p = .004). Patients with mesothelin expression had significantly worse disease-free survival rate compared with that of nonmesothelin expression group (p = .024). Univariate analysis showed that mesothelin expression is related to short-term survival. None of the 117 gastric adenocarcinomas stained for calretinin or WT1. Conclusions: Mesothelin expression was associated with poor prognosis. Our results suggest that mesothelin-targeted therapy should be considered as an important therapeutic alternative for gastric adenocarcinoma patients with mesothelin expression.
Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry
Jiyoon Jung, Youngjin Kang, Yoo Jin Lee, Eojin Kim, Bokyung Ahn, Eunjung Lee, Joo Young Kim, Jeong Hyeon Lee, Youngseok Lee, Chul Hwan Kim, Yang-Seok Chae
J Pathol Transl Med. 2017;51(2):129-136.   Published online February 14, 2017
DOI: https://doi.org/10.4132/jptm.2016.12.09
  • 7,840 View
  • 292 Download
  • 20 Citations
AbstractAbstract PDF
Background
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses. Methods: In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. Results: Based on IHC, 7/61 primary tumors (11.4%) showed deficient MMR systems, while 13/61 secondary tumors (21.3%) showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. Conclusions: Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61). These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.
Current Status of Pathologic Examinations in Korea, 2011–2015, Based on the Health Insurance Review and Assessment Service Dataset
Sun-ju Byeon
J Pathol Transl Med. 2017;51(2):137-147.   Published online February 22, 2017
DOI: https://doi.org/10.4132/jptm.2016.12.30
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  • 1 Citations
AbstractAbstract PDFSupplementary Material
Background
Pathologic examinations play an important role in medical services. Until recently, the overall status of pathologic examinations in Korea has not been identified. I conducted a nationwide survey of pathologic examination status using the insurance reimbursements (IRs) dataset from the Health Insurance Review and Assessment Service (HIRA). The aims of this study were to estimate current pathologic examination status in Korea and to provide information for future resource arrangement in the pathology area. Methods: I asked HIRA to provide data on IR requests, including pathologic examinations from 2011 to 2015. Pathologic examination status was investigated according to the following categories: annual statistics, requesting department, type of medical institution, administrative district, and location at which pathologic examinations were performed. Results: Histologic mapping, immunohistochemistry, and cervicovaginal examinations have increased in the last 5 years. Internal medicine, general surgery, obstetrics/gynecology, and urology were the most common medical departments requesting pathologic examinations. The majority of pathologic examinations were frequently performed in tertiary hospitals. About 60.3% of pathologic examinations were requested in medical institutions located in Seoul, Gyeonggi-do, and Busan. More than half of the biopsies and aspiration cytologic examinations were performed using outside services. The mean period between IR requests and 99 percentile IR request completion inspections was 6.2 months. Conclusions: This survey was based on the HIRA dataset, which is one of the largest medical datasets in Korea. The trends of some pathologic examinations were reflected in the policies and needs for detailed diagnosis. The numbers and proportions of pathologic examinations were correlated with the population and medical institutions of the area, as well as patient preference. These data will be helpful for future resource arrangement in the pathology area.
Higher Expression of Toll-like Receptors 3, 7, 8, and 9 in Pityriasis Rosea
Mostafa Abou El-Ela, Mohamed El-Komy, Rania Abdel Hay, Rehab Hegazy, Amin Sharobim, Laila Rashed, Khalda Amr
J Pathol Transl Med. 2017;51(2):148-151.   Published online February 13, 2017
DOI: https://doi.org/10.4132/jptm.2016.09.09
  • 5,485 View
  • 96 Download
  • 2 Citations
AbstractAbstract PDF
Background
Pityriasis rosea (PR) is a common papulosquamous skin disease in which an infective agent may be implicated. Toll-like receptors (TLRs) play an important role in immune responses and in the pathophysiology of inflammatory skin diseases. Our aim was to determine the possible roles of TLRs 3, 7, 8, and 9 in the pathogenesis of PR. Methods: Twenty-four PR patients and 24 healthy individuals (as controls) were included in this case control study. All recruits were subjected to routine laboratory investigations. Biopsies were obtained from one active PR lesion and from healthy skin of controls for the detection of TLR 3, 7, 8, and 9 gene expression using real-time polymerase chain reaction. Results: This study included 24 patients (8 females and 16 males) with active PR lesions, with a mean age of 28.62 years. Twenty four healthy age- and sex-matched individuals were included as controls (8 females and 16 males, with a mean age of 30.83 years). The results of the routine laboratory tests revealed no significant differences between both groups. Significantly elevated expression of all studied TLRs were detected in PR patients relative to healthy controls (p < .001). Conclusions: TLRs 3, 7, 8, and 9 might be involved in the pathogenesis of PR.
GLUT1 as a Prognostic Factor for Classical Hodgkin’s Lymphoma: Correlation with PD-L1 and PD-L2 Expression
Young Wha Koh, Jae-Ho Han, Seong Yong Park, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh
J Pathol Transl Med. 2017;51(2):152-158.   Published online February 21, 2017
DOI: https://doi.org/10.4132/jptm.2016.11.03
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  • 14 Citations
AbstractAbstract PDF
Background
Glucose transporter type 1 (GLUT1) expression is linked to glucose metabolism and tissue hypoxia. A recent study reported that GLUT1 was significantly associated with programmed death ligand 1 (PD-L1) as a therapeutic target in relapsed or refractory classical Hodgkin’s lymphoma (cHL). The purpose of this study was to measure the expression of GLUT1 and assess its prognostic significance and potential relationships with PD-L1, programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expressions in cHL. Methods: Diagnostic tissues from 125 patients with cHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine were evaluated retrospectively via immunohistochemical analysis of GLUT1, PD-L1, PD-L2, and PD-1 expression. Results: The median follow-up time was 4.83 years (range, 0.08 to 17.33 years). GLUT1, PD-L1, PD-L2, and PD-1 were expressed in 44.8%, 63.2%, 9.6%, and 13.6% of the specimens, respectively. Positive correlations were found between GLUT1 and PD-L1 expression (p = .004) and between GLUT1 and PD-L2 expression (p = .031). GLUT1 expression in Hodgkin/Reed-Sternberg (HRS) cells was not associated with overall survival or event-free survival (EFS) in the entire cohort (p = .299 and p = .143, respectively). A subgroup analysis according to the Ann Arbor stage illustrated that GLUT1 expression in HRS cells was associated with better EFS in advanced-stage disease (p = .029). A multivariate analysis identified GLUT1 as a marginally significant prognostic factor for EFS (p = .068). Conclusions: This study suggests that GLUT1 expression is associated with better clinical outcomes in advanced-stage cHL and is significantly associated with PD-L1 and PD-L2 expressions.
Case Studies
A Pyloric Gland-Phenotype Ovarian Mucinous Tumor Resembling Lobular Endocervical Glandular Hyperplasia in a Patient with Peutz-Jeghers Syndrome
Eun Na Kim, Gu-Hwan Kim, Jiyoon Kim, In Ah Park, Jin Ho Shin, Yun Chai, Kyu-Rae Kim
J Pathol Transl Med. 2017;51(2):159-164.   Published online August 22, 2016
DOI: https://doi.org/10.4132/jptm.2016.07.01
  • 6,613 View
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  • 3 Citations
AbstractAbstract PDF
We describe an ovarian mucinous neoplasm that histologically resembles lobular endocervical glandular hyperplasia (LEGH) containing pyloric gland type mucin in a patient with Peutz-Jeghers syndrome (PJS). Although ovarian mucinous tumors rarely occur in PJS patients, their pyloric gland phenotype has not been clearly determined. The histopathologic features of the ovarian mucinous tumor were reminiscent of LEGH. The cytoplasmic mucin was stained with periodic acid-Schiff reaction after diastase treatment but was negative for Alcian blue pH 2.5, suggesting the presence of neutral mucin. Immunohistochemically, the epithelium expressed various gastric markers, including MUC6, HIK1083, and carbonic anhydrase-IX. Multiple ligation-dependent probe amplification detected a germline heterozygous deletion mutation at exons 1–7 of the STK11 gene (c.1-?_920+?del) in peripheral blood leukocytes and mosaic loss of heterozygosity in ovarian tumor tissue. Considering that LEGH and/or gastric-type cervical adenocarcinoma can be found in patients with PJS carrying germline and/or somatic STK11 mutations, our case indicates that STK11 mutations have an important role in the proliferation of pyloric-phenotype mucinous epithelium at various anatomical locations.
Thymoma and Synchronous Primary Mediastinal Seminomas with Florid Follicular Lymphoid Hyperplasia in the Anterior Mediastinum: A Case Report and Review of the Literature
Hyang-im Lee, In-seok Jang, Kyung Nyeo Jeon, Gyung Hyuck Ko, Jong Sil Lee, Dong Chul Kim, Dae Hyun Song, Jeong-Hee Lee
J Pathol Transl Med. 2017;51(2):165-170.   Published online February 2, 2017
DOI: https://doi.org/10.4132/jptm.2016.08.24
  • 7,519 View
  • 131 Download
  • 1 Citations
AbstractAbstract PDF
Thymoma is the most common neoplasm of the anterior mediastinum and has malignant potential. Germ cell tumors (GCTs) found in the anterior mediastinum are usually benign, and malignant GCTs, such as seminomas, are rare. Histologically, mediastinal seminoma is indistinguishable from testicular seminoma except for site-associated morphological features such as lymphoid follicular hyperplasia. Therefore, excluding metastasis is very important. Recently, we treated a young adult patient with multiple thymic masses that occurred simultaneously. The patient underwent a thymectomy for the removal of the mediastinal masses, one of which was diagnosed as type B2 invasive thymoma, and two of which were diagnosed as primary mediastinal seminomas with massive follicular hyperplasia. The patient received adjuvant chemotherapy after surgical resection. To our knowledge, this is the first description of a thymoma and a mediastinal seminoma occurring simultaneously in the thymus. We present this case along with a literature review.
Malignant Solitary Fibrous Tumor with Heterologous Rhabdomyosarcomatous Differentiation: A Case Report
Jeong-Hwa Kwon, Joon Seon Song, Hye Won Jung, Jong-Seok Lee, Kyung-Ja Cho
J Pathol Transl Med. 2017;51(2):171-175.   Published online February 3, 2017
DOI: https://doi.org/10.4132/jptm.2016.08.29
  • 6,265 View
  • 109 Download
  • 2 Citations
AbstractAbstract PDF
Malignant solitary fibrous tumor (MSFT) is a well-described entity, from which heterologous differentiation is extremely rare. We encountered a case of MSFT with rhabdomyosarcomatous differentiation in a 56-year-old man. This patient presented with a large mass in his posterior thigh. He had been treated with chemoradiation for sarcoma involving the cervical spine, right femoral head, and both lungs 6 months earlier. A wide excision was performed. The mass measured 10.6 cm and showed a fish-flesh cut surface with necrotic foci. Microscopically, the tumor showed heterogeneous cellularity with a hemangiopericytic vascular pattern. A hypercellular area showed spindle cells or epithelioid cells with high mitotic activity (63/10 high-power fields) and immunoreactivity for CD34 and CD99. A hypocellular area and a cystic area showed pleomorphic rhabdoid cells with immunoreactivity for desmin and myogenin. This is a report of a rare case of MSFT with rhabdomyosarcomatous differentiation and presents new histologic features of MSFT.
Mucinous Carcinoma with Extensive Signet Ring Cell Differentiation: A Case Report
Hye Min Kim, Eun Kyung Kim, Ja Seung Koo
J Pathol Transl Med. 2017;51(2):176-179.   Published online December 5, 2016
DOI: https://doi.org/10.4132/jptm.2016.08.17
  • 8,220 View
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  • 3 Citations
AbstractAbstract PDF
Breast cancers that present with mucin include mucinous carcinoma and carcinoma with signet ring cell differentiation. The former shows extracellular mucin and the latter shows abundant intracellular mucin. Here, we report a case of breast cancer showing both extracellular mucin and extensive signet ring cell differentiation due to abundant intracellular mucin. Unlike mucinous carcinoma, this case had the features of high-grade nuclear pleomorphism, high mitotic index, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor-2 positivity, and ductal type with positivity for E-cadherin. In a case with signet ring cell differentiation, differential diagnosis with metastatic signet ring cell carcinoma of the stomach and colon is essential. In this case, the presence of accompanied ductal carcinoma in situ component and mammaglobin and gross cystic disease fluid protein-15 positivity were findings that suggested the breast as the origin.
Mucinous Cystadenoma of the Testis: A Case Report with Immunohistochemical Findings
Gilhyang Kim, Dohee Kwon, Hee Young Na, Sehui Kim, Kyung Chul Moon
J Pathol Transl Med. 2017;51(2):180-184.   Published online February 13, 2017
DOI: https://doi.org/10.4132/jptm.2016.08.30
  • 6,360 View
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  • 4 Citations
AbstractAbstract PDF
Mucinous cystadenoma of the testis is a very rare tumor. Herein, we report a case of mucinous cystadenoma arising in the testis of a 61-year-old man, along with a literature review. Computed tomography showed a 2.5-cm-sized poorly enhancing cystic mass. Grossly, the tumor was a unilocular cystic mass filled with mucinous material and confined to the testicular parenchyma. Histologically, the cyst had a fibrotic wall lined by mucinous columnar epithelium without atypia. Immunohistochemical staining was positive for cytokeratin 20 and CDX2, as well as focally positive for cytokeratin 7. The pathologic diagnosis was mucinous cystadenoma.
Brief Case Reports
Heterotopic Ossification in the Gallbladder
Jihyun Ahn, Sunyoung Kim, Kangseung Kim, Seogjoon Kim
J Pathol Transl Med. 2017;51(2):185-186.   Published online June 6, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.10
  • 6,538 View
  • 92 Download
  • 2 Citations
PDF
Mucosal Schwann Cell Hamartoma in Colorectal Mucosa: A Rare Benign Lesion That Resembles Gastrointestinal Neuroma
Jiheun Han, Yosep Chong, Tae-Jung Kim, Eun Jung Lee, Chang Suk Kang
J Pathol Transl Med. 2017;51(2):187-189.   Published online August 25, 2016
DOI: https://doi.org/10.4132/jptm.2016.07.02
  • 8,694 View
  • 185 Download
  • 10 Citations
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JPTM : Journal of Pathology and Translational Medicine