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Volume 52(1); January 2018
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Review
Extracellular Vesicles and the Promise of Continuous Liquid Biopsies
Don Armstrong, Derek E. Wildman
J Pathol Transl Med. 2018;52(1):1-8.   Published online January 15, 2018
DOI: https://doi.org/10.4132/jptm.2017.05.21
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  • 50 Citations
AbstractAbstract PDF
The rapid and accurate diagnosis of patients with minimally invasive procedures was once only found in science fiction. However, the discovery of extracellular vesicles (EVs) and their near ubiquity in body fluids, coupled with the advent of inexpensive next generation sequencing techniques and EV purification protocols, promises to make science fiction a reality. Purifying and sequencing the RNA content of EV from routine blood draws and urine samples are likely to enable pathologists and physicians to diagnose and track the progress of diseases in many inaccessible tissues in the near future. Here we present the evolutionary background of EV, summarize the biology of EV formation and cargo selection, and discuss the current barriers to making continuous liquid biopsies through the use of EV a science reality.
Original Articles
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
  • 7,077 View
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  • 10 Citations
AbstractAbstract 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.
The Significance of TROP2 Expression in Predicting BRAF Mutations in Papillary Thyroid Carcinoma
Joon Seog Kong, Hyeon Jin Kim, Min-Jung Kim, Areumnuri Kim, Dalnim Lee, Kanghee Han, Sunhoo Park, Jae Soo Koh, Jae Kyung Myung
J Pathol Transl Med. 2018;52(1):14-20.   Published online December 11, 2017
DOI: https://doi.org/10.4132/jptm.2017.10.17
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  • 7 Citations
AbstractAbstract PDF
Background
Trophoblast antigen 2 (TROP2) is a human trophoblast cell-surface glycoprotein that is overexpressed in several types of epithelial cancers, and is suggested to be associated with an unfavorable prognosis. BRAF mutations are the most common genetic alteration in papillary thyroid carcinoma (PTC). We evaluated the correlation between TROP2 expression and BRAF mutation in PTC.
Methods
First, we carried out pyrosequencing for BRAF mutations and immunohistochemistry for TROP2 expression with a tissue microarray consisting of 52 PTC cases. Membranous staining in at least 5% of tumor cells was designated as positive staining and we analyzed the relationship between TROP2 expression and diverse clinicopathological factors, including BRAF mutation. Second, we tested TROP2 mRNA expression in three thyroid cancer cell lines with BRAF mutations (BCPAP, SNU790, and 8505C) and a normal thyroid cell line. Additionally, we checked TROP2 protein levels in a normal thyroid cell line after introduction of the BRAF V600E mutation.
Results
In this study, 21 of 26 cases with BRAF mutation showed TROP2 immunoreactivity, whereas all 26 cases without BRAF mutation showed no immunoreactivity for TROP2 with a statistically significant difference (p<.001). Upregulation of TROP2 mRNA was observed in all three thyroid cancer cell lines, but not in the normal thyroid cell line. Interestingly, however, the TROP2 expression was increased in the normal thyroid cell line after introduction of the BRAF V600E mutation.
Conclusions
Based on these results, we concluded that TROP2 expression is significantly associated with BRAF mutation and that TROP2 immunohistochemistry could be used for predicting BRAF mutations or diagnosing papillary thyroid carcinoma.
Comparison of the Classical Method and SEE-FIM Protocol in Detecting Microscopic Lesions in Fallopian Tubes with Gynecological Lesions
Nermin Koc, Selçuk Ayas, Sevcan Arzu Arinkan
J Pathol Transl Med. 2018;52(1):21-27.   Published online August 19, 2016
DOI: https://doi.org/10.4132/jptm.2016.06.17
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  • 15 Citations
AbstractAbstract PDF
Background
The objective of this study was to compare the classical method and Sectioning and Extensively Examining the Fimbriated End Protocol (SEE-FIM) in detecting microscopic lesions in fallopian tubes with gynecological lesions. Methods: From a total of 1,118 cases, 582 with various parts of both fallopian tubes sampled in three-ring-shape sections and 536 sampled with the SEE-FIM protocol were included in this study. Pathological findings of cases with endometrial carcinoma, non-uterine pelvic malignant tumor, ovarian borderline tumors, premalignancy, and benign lesions were compared. Results: We detected two tubal infiltrative carcinomas among 40 uterine endometrioid adenocarcinomas, 15 serous tubal intraepithelial carcinomas in 39 non-uterine pelvic serous high-grade carcinoma cases, seven papillary tubal hyperplasias in 13 serous borderline tumor cases, and 11 endometriotic foci and four adenomatoid tumors among all cases sampled with the SEE-FIM protocol. Using the classical method, we detected only one serous tubal intraepithelial carcinoma in 113 non-uterine pelvic serous high-grade carcinoma cases and two papillary tubal hyperplasia cases in 31 serous borderline tumors. We did not identify additional findings in 185 uterine endometrioid carcinoma cases, and neither endometriotic focus nor adenomatoid tumor was shown in other lesions by the classical method. Conclusions: Benign, premalignant, and malignant lesions can possibly be missed using the classical method. The SEE-FIM protocol should be considered especially in cases of endometrial carcinoma, nonuterine pelvic serous cancers, or serous borderline ovarian tumors. For other lesions, at least a detailed examination of the fimbrial end should be undertaken.
Reclassification of Mixed Oligoastrocytic Tumors Using a Genetically Integrated Diagnostic Approach
Seong-Ik Kim, Yujin Lee, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Sung-Hye Park
J Pathol Transl Med. 2018;52(1):28-36.   Published online September 29, 2017
DOI: https://doi.org/10.4132/jptm.2017.09.25
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  • 2 Citations
AbstractAbstract PDF
Background
Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients.
Methods
Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups.
Results
We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p<.001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old).
Conclusions
Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods.
The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma
Yumin Chung, Young Chan Wi, Yeseul Kim, Seong Sik Bang, Jung-Ho Yang, Kiseok Jang, Kyueng-Whan Min, Seung Sam Paik
J Pathol Transl Med. 2018;52(1):37-44.   Published online October 23, 2017
DOI: https://doi.org/10.4132/jptm.2017.10.20
  • 9,035 View
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  • 8 Citations
AbstractAbstract PDFSupplementary Material
Background
Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma.
Methods
Combined expression patterns based on Smad4+/– and PTEN+/– status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed.
Results
Smad4–/PTEN– status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4–/PTEN– and Smad4+/PTEN+ groups were compared, Smad4–/PTEN– status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4–/PTEN+ or Smad4+/PTEN–, and Smad4–/PTEN–) (all p<.05).
Conclusions
Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.
Importance of Individual Ghost Cells in Fine-Needle Aspiration Cytology Diagnosis of Pilomatricoma
Kanghee Han, Hwa-Jeong Ha, Joon Seog Kong, Jae Kyung Myung, Sunhoo Park, Jung-Soon Kim, Myung-Soon Shin, Hye Sil Seol, Jae Soo Koh, Seung-Sook Lee
J Pathol Transl Med. 2018;52(1):45-50.   Published online January 15, 2018
DOI: https://doi.org/10.4132/jptm.2017.10.18
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  • 1 Citations
AbstractAbstract PDF
Background
Although histological diagnosis of pilomatricoma is not difficult because of its unique histological features, cytological diagnosis through fine-needle aspiration cytology (FNAC) is often problematic due to misdiagnoses as malignancy.
Methods
We reviewed the cytological features of 14 cases of histologically-proven pilomatricoma from Korea Cancer Center Hospital, with a discussion on the diagnostic pitfalls of FNAC.
Results
Among 14 cases of pilomatricoma, 10 (71.4%) were correctly diagnosed through FNAC, and two (14.3%) were misdiagnosed as carcinoma. Cytologically, all cases had easily recognizable clusters of basaloid cells and foreign body-type multinucleated cells. Although ghost cells were also found in all cases, some were inconspicuous and hardly recognizable due to their small numbers.
Conclusions
An accurate diagnosis of pilomatricoma in FNAC is feasible with consideration of clinical information and close examination of ghost cells.
Case Studies
An Autopsy Case of Epstein-Barr Virus–Associated Diffuse Large B-Cell Lymphoma of the Central Nervous System in an Immunocompromised Host
Sun-Young Park, Seong Ik Kim, Hannah Kim, Yoojin Lee, Sung-Hye Park
J Pathol Transl Med. 2018;52(1):51-55.   Published online August 4, 2017
DOI: https://doi.org/10.4132/jptm.2017.01.23
  • 5,666 View
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  • 1 Citations
AbstractAbstract PDF
Lymphomas arising in the central nervous system (CNS) of immunocompromised hosts are most commonly non-Hodgkin’s lymphomas and are highly associated with Epstein-Barr virus (EBV). Here we report an autopsy case of EBV-associated CNS diffuse large B-cell lymphoma (DLBCL) in a host suffering from systemic lupus erythematosus who underwent immunosuppressive therapy. After autopsy, EBV-associated CNS DLBCL as well as pulmonary mixed aspergillosis and Pneumocystis jirovecii pneumonia were added to the cause of clinical manifestations of complicated pneumonia and cerebral hemorrhage in this immunocompromised patient. In conclusion, complex disease processes were revealed by autopsy in this case, indicating that the clinicopathological correlations observed through autopsy can improve our understanding of disease progression and contribute to the management of similar patients in the future.
Colloid Carcinoma of the Uterine Cervix and Its Immunohistochemical Analysis: A Case Report
Nermin Koc, Sevcan Arzu Arinkan, Nurver Ozel Ozbay, Selcuk Selcuk
J Pathol Transl Med. 2018;52(1):56-60.   Published online January 15, 2018
DOI: https://doi.org/10.4132/jptm.2017.04.08
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AbstractAbstract PDF
Colloid carcinoma, which is a very rare tumor of the uterine cervix, is composed of an excessive amount of mucus and a relative paucity of tumoral glandular cells within them. Herein, we report a rare case of colloid carcinoma of the cervix with adenocarcinoma in situ (AIS), intestinal and usual types, and endocervical adenocarcinoma (usual type) components. We also discuss the morphological and immunohistochemical characteristics of this tumor. A 51-year-old woman was referred to our outpatient clinic with the symptom of genital bleeding lasting for 5 months. She had a cervix surrounded by an irregular tumor with a diameter of 5 cm. The colloid carcinoma cells were positive for MUC2, MUC5AC, and cytokeratin (CK) 7, focal positive for CDX2, and negative for MUC6 and CK20. Also, the intestinal type AIS showed a similar staining pattern. Colloid carcinoma cells producing mucin showed an intestinal phenotype and AIS. The intestinal type can be considered as a precursor lesion of colloid carcinoma.
Liquid-Based Cytology of the Cerebrospinal Fluid in a Case of Cryptococcal Meningitis
Jiwoon Choi, Se Hoon Kim
J Pathol Transl Med. 2018;52(1):61-63.   Published online October 26, 2017
DOI: https://doi.org/10.4132/jptm.2017.06.13
  • 5,513 View
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  • 4 Citations
AbstractAbstract PDF
Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF) cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4–11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small.
Brief Case Reports
Hyalinizing Cholecystitis and Associated Carcinoma: A Case Report
Youngjin Kang, Yang-Seok Chae, Chul Hwan Kim, Youngseok Lee, Dong-Sik Kim, Young-Dong Yu, Joo Young Kim
J Pathol Transl Med. 2018;52(1):64-66.   Published online April 4, 2017
DOI: https://doi.org/10.4132/jptm.2016.11.04
  • 6,996 View
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  • 4 Citations
PDF
An Extremely Rare Case of Back and Hip Pain due to the Metastasis of Late Recurrent Myxopapillary Ependymoma to the Inguinal Lymph Node
Suheyla Ekemen, Ozlem Yapicier, Hatice Deniz Boler, Umit Ince
J Pathol Transl Med. 2018;52(1):67-70.   Published online November 23, 2017
DOI: https://doi.org/10.4132/jptm.2017.11.09
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JPTM : Journal of Pathology and Translational Medicine