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Volume 53(6); November 2019
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Original Articles
Interobserver Reproducibility of PD-L1 Biomarker in Non-small Cell Lung Cancer: A Multi-Institutional Study by 27 Pathologists
Sunhee Chang, Hyung Kyu Park, Yoon-La Choi, Se Jin Jang
J Pathol Transl Med. 2019;53(6):347-353.   Published online October 28, 2019
DOI: https://doi.org/10.4132/jptm.2019.09.29
  • 4,266 View
  • 178 Download
  • 16 Citations
AbstractAbstract PDF
Background
Assessment of programmed cell death-ligand 1 (PD-L1) immunohistochemical staining is used for treatment decisions in non-small cell lung cancer (NSCLC) regarding use of PD-L1/programmed cell death protein 1 (PD-1) immunotherapy. The reliability of the PD-L1 22C3 pharmDx assay is critical in guiding clinical practice. The Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists investigated the interobserver reproducibility of PD-L1 staining with 22C3 pharmDx in NSCLC samples.
Methods
Twenty-seven pathologists individually assessed the tumor proportion score (TPS) for 107 NSCLC samples. Each case was divided into three levels based on TPS: <1%, 1%–49%, and ≥50%.
Results
The intraclass correlation coefficient for TPS was 0.902±0.058. Weighted κ coefficient for 3-step assessment was 0.748±0.093. The κ coefficients for 1% and 50% cut-offs were 0.633 and 0.834, respectively. There was a significant association between interobserver reproducibility and experience (formal PD-L1 training, more experience for PD-L1 assessment, and longer practice duration on surgical pathology), histologic subtype, and specimen type.
Conclusions
Our results indicate that PD-L1 immunohistochemical staining provides a reproducible basis for decisions on anti–PD-1 therapy in NSCLC.
MicroRNA-374a Expression as a Prognostic Biomarker in Lung Adenocarcinoma
Yeseul Kim, Jongmin Sim, Hyunsung Kim, Seong Sik Bang, Seungyun Jee, Sungeon Park, Kiseok Jang
J Pathol Transl Med. 2019;53(6):354-360.   Published online October 24, 2019
DOI: https://doi.org/10.4132/jptm.2019.10.01
  • 3,571 View
  • 117 Download
  • 2 Citations
AbstractAbstract PDF
Background
Lung cancer is the most common cause of cancer-related death, and adenocarcinoma is the most common histologic subtype. MicroRNA is a small non-coding RNA that inhibits multiple target gene expression at the post-transcriptional level and is commonly dysregulated in malignant tumors. The purpose of this study was to analyze the expression of microRNA-374a (miR-374a) in lung adenocarcinoma and correlate its expression with various clinicopathological characteristics.
Methods
The expression level of miR-374a was measured in 111 formalin-fixed paraffin-embedded lung adenocarcinoma tissues using reverse transcription-quantitative polymerase chain reaction assays. The correlation between miR-374a expression and clinicopathological parameters, including clinical outcome, was further analyzed.
Results
High miR-374 expression was correlated with advanced pT category (chi-square test, p=.004) and pleural invasion (chi-square test, p=.034). Survival analysis revealed that patients with high miR-374a expression had significantly shorter disease-free survival relative to those with low miR-374a expression (log-rank test, p=.032).
Conclusions
miR-374a expression may serve as a potential prognostic biomarker for predicting recurrence in early stage lung adenocarcinoma after curative surgery.
Molecular and Clinicopathological Features of Gastrointestinal Stromal Tumors in Vietnamese Patients
Quoc Dat Ngo, Quoc Thang Pham, Dang Anh Thu Phan, Anh Vu Hoang, Thi Ngoc Ha Hua, Sao Trung Nguyen
J Pathol Transl Med. 2019;53(6):361-368.   Published online September 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.08.27
  • 4,306 View
  • 141 Download
  • 2 Citations
AbstractAbstract PDFSupplementary Material
Background
Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. Management of GIST patients is currently based on clinicopathological features and associated genetic changes. However, the detailed characteristics and molecular genetic features of GISTs have not yet been described in the Vietnamese population.
Methods
We first identified 155 patients with primary GIST who underwent surgery with primary curative intent between 2011 and 2014 at University Medical Center at Ho Chi Minh City, Vietnam. We evaluated the clinicopathological features and immunohistochemical reactivity to p53 and Ki-67 in these patients. Additionally, KIT genotyping was performed in 100 cases.
Results
The largest proportion of GISTs was classified as high-risk (43.2%). Of the 155 GISTs, 52 (33.5%) were positive for Ki-67, and 58 (37.4%) were positive for p53. The expression of Ki-67 and p53 were correlated with mitotic rate, tumor size, risk assessment, and tumor stage. Out of 100 GIST cases, KIT mutation was found in 68%, of which 62 (91.2%) were found in exon 11, two (2.9%) in exon 9, and four (5.8%) in exon 17. No mutation in exon 13 was identified. Additionally, KIT mutations did not correlate with any clinicopathological features.
Conclusions
The expression of Ki-67 and p53 were associated with high-risk tumors. Mutations in exon 11 were the most commonly found, followed by exon 17 and exon 9. Additionally, KIT mutation status was not correlated with any recognized clinicopathological features.
Comparison of Squamous Cell Carcinoma of the Tongue between Young and Old Patients
Gyuheon Choi, Joon Seon Song, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Jong-Lyel Roh, Bu-Kyu Lee, Kyung-Ja Cho
J Pathol Transl Med. 2019;53(6):369-377.   Published online October 11, 2019
DOI: https://doi.org/10.4132/jptm.2019.09.16
  • 4,359 View
  • 155 Download
  • 6 Citations
AbstractAbstract PDFSupplementary Material
Background
The worldwide incidence of squamous cell carcinoma of the tongue (SCCOT) in young patients has been increasing. We investigated clinicopathologic features of this unique population and compared them with those of SCCOT in the elderly to delineate its pathogenesis.
Methods
We compared clinicopathological parameters between patients under and over 45 years old. Immunohistochemical assays of estrogen receptor, progesterone receptor, androgen receptor, p53, p16, mdm2, cyclin D1, and glutathione S-transferase P1 were also compared between them.
Results
Among 189 cases, 51 patients (27.0%) were under 45 years of age. A higher proportion of women was seen in the young group, but was not statistically significant. Smoking and drinking behaviors between age groups were similar. Histopathological and immunohistochemical analysis showed no significant difference by age and sex other than higher histologic grades observed in young patients.
Conclusions
SCCOT in young adults has similar clinicopathological features to that in the elderly, suggesting that both progress via similar pathogenetic pathways.
A Multi-institutional Study of Prevalence and Clinicopathologic Features of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) in Korea
Ja Yeong Seo, Ji Hyun Park, Ju Yeon Pyo, Yoon Jin Cha, Chan Kwon Jung, Dong Eun Song, Jeong Ja Kwak, So Yeon Park, Hee Young Na, Jang-Hee Kim, Jae Yeon Seok, Hee Sung Kim, Soon Won Hong
J Pathol Transl Med. 2019;53(6):378-385.   Published online October 21, 2019
DOI: https://doi.org/10.4132/jptm.2019.09.18
  • 4,773 View
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  • 6 Citations
AbstractAbstract PDF
Background
In the present multi-institutional study, the prevalence and clinicopathologic characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were evaluated among Korean patients who underwent thyroidectomy for papillary thyroid carcinoma (PTC).
Methods
Data from 18,819 patients with PTC from eight university hospitals between January 2012 and February 2018 were retrospectively evaluated. Pathology reports of all PTCs and slides of potential NIFTP cases were reviewed. The strict criterion of no papillae was applied for the diagnosis of NIFTP. Due to assumptions regarding misclassification of NIFTP as non-PTC tumors, the lower boundary of NIFTP prevalence among PTCs was estimated. Mutational analysis for BRAF and three RAS isoforms was performed in 27 randomly selected NIFTP cases.
Results
The prevalence of NIFTP was 1.3% (238/18,819) of all PTCs when the same histologic criteria were applied for NIFTP regardless of the tumor size but decreased to 0.8% (152/18,819) when tumors ≥1 cm in size were included. The mean follow-up was 37.7 months and no patient with NIFTP had evidence of lymph node metastasis, distant metastasis, or disease recurrence during the follow-up period. A difference in prevalence of NIFTP before and after NIFTP introduction was not observed. BRAFV600E mutation was not found in NIFTP. The mutation rate for the three RAS genes was 55.6% (15/27).
Conclusions
The low prevalence and indolent clinical outcome of NIFTP in Korea was confirmed using the largest number of cases to date. The introduction of NIFTP may have a small overall impact in Korean practice.
Clinical Utility of a Fully Automated Microsatellite Instability Test with Minimal Hands-on Time
Miseon Lee, Sung-Min Chun, Chang Ohk Sung, Sun Y. Kim, Tae W. Kim, Se Jin Jang, Jihun Kim
J Pathol Transl Med. 2019;53(6):386-392.   Published online October 11, 2019
DOI: https://doi.org/10.4132/jptm.2019.09.25
  • 5,173 View
  • 203 Download
  • 12 Citations
AbstractAbstract PDFSupplementary Material
Background
Microsatellite instability (MSI) analysis is becoming increasingly important in many types of tumor including colorectal cancer (CRC). The commonly used MSI tests are either time-consuming or labor-intensive. A fully automated MSI test, the Idylla MSI assay, has recently been introduced. However, its diagnostic performance has not been extensively validated in clinical CRC samples.
Methods
We evaluated 133 samples whose MSI status had been rigorously validated by standard polymerase chain reaction (PCR), clinical nextgeneration sequencing (NGS) cancer panel test, or both. We evaluated the diagnostic performance of the Idylla MSI assay in terms of sensitivity, specificity, and positive and negative predictive values, as well as various sample requirements, such as minimum tumor purity and the quality of paraffin blocks.
Results
Compared with the gold standard results confirmed through both PCR MSI test and NGS, the Idylla MSI assay showed 99.05% accuracy (104/105), 100% sensitivity (11/11), 98.94% specificity (93/94), 91.67% positive predictive value (11/12), and 100% negative predictive value (93/93). In addition, the Idylla MSI assay did not require macro-dissection in most samples and reliably detected MSI-high in samples with approximately 10% tumor purity. The total turnaround time was about 150 minutes and the hands-on time was less than 2 minutes.
Conclusions
The Idylla MSI assay shows good diagnostic performance that is sufficient for its implementation in the clinic to determine the MSI status of at least the CRC samples. In addition, the fully automated procedure requires only a few slices of formalin-fixed paraffin-embedded tissue and might greatly save time and labor.
Cytomorphological Features of Hyperchromatic Crowded Groups in Liquid-Based Cervicovaginal Cytology: A Single Institutional Experience
Youngeun Lee, Cheol Lee, In Ae Park, Hyoung Jin An, Haeryoung Kim
J Pathol Transl Med. 2019;53(6):393-398.   Published online September 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.08.14
  • 5,778 View
  • 165 Download
  • 2 Citations
AbstractAbstract PDF
Background
Hyperchromatic crowed groups (HCGs) are defined as three-dimensional aggregates of crowded cells with hyperchromatic nuclei, and are frequently encountered in cervicovaginal liquid-based cytology (LBC). Here, we aimed to examine the prevalence of HCGs in cervicovaginal LBC and the cytomorphological characteristics of various epithelial cell clusters presenting as HCGs.
Methods
We first examined the prevalence of HCGs in a “routine cohort” of LBC cytology (n=331), consisting of all cervicovaginal LBCs accessioned over 3 days from outpatient clinics (n=179) and the screening population (n=152). Then we examined a second “high-grade epithelial cell abnormalities (H-ECA) cohort” (n=69) of LBCs diagnosed as high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma (SCC), or adenocarcinoma during 1 year.
Results
HCGs was observed in 34.4% of the routine cohort and were significantly more frequent in the epithelial cell abnormality category compared to the non-neoplastic category (p=.003). The majority of HCGs represented atrophy (70%). Of the 69 histologically confirmed H-ECA cases, all contained HCGs. The majority of cases were HSIL (62%), followed by SCC (16%). Individually scattered neoplastic cells outside the HCGs were significantly more frequent in SCCs compared to glandular neoplasia (p=.002). Despite the obscuring thick nature of the HCGs, examining the edges and the different focal planes of the HCGs and the background were helpful in defining the nature of the HCGs.
Conclusions
HCGs were frequently observed in cervicovaginal LBC and were mostly non-neoplastic; however, neoplastic HCGs were mostly high-grade lesions. Being aware of the cytomorphological features of different HCGs is important in order to avoid potential false-negative cytology interpretation.
Case Study
Concurrent Anti-glomerular Basement Membrane Nephritis and IgA Nephropathy
Kwang-Sun Suh, Song-Yi Choi, Go Eun Bae, Dae Eun Choi, Min-kyung Yeo
J Pathol Transl Med. 2019;53(6):399-402.   Published online September 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.08.05
  • 3,787 View
  • 148 Download
  • 4 Citations
AbstractAbstract PDFSupplementary Material
Anti–glomerular basement membrane (GBM) nephritis is characterized by circulating anti-GBM antibodies and crescentic glomerulonephritis (GN) with deposition of IgG along the GBM. In a limited number of cases, glomerular immune complexes have been identified in anti-GBM nephritis. A 38-year-old female presented azotemia, hematuria, and proteinuria without any pulmonary symptoms. A renal biopsy showed crescentic GN with linear IgG deposition along the GBM and mesangial IgA deposition. The patient was diagnosed as concurrent anti-GBM nephritis and IgA nephropathy. Therapies with pulse methylprednisolone and cyclophosphamide administration were effective. Concurrent cases of both anti-GBM nephritis and IgA nephropathy are rare among cases of anti-GBM diseases with deposition of immune complexes. This rare case of concurrent anti-GBM nephritis and IgA nephropathy with literature review is noteworthy.
Brief Case Reports
Adenocarcinoma Arising in an Ectopic Hamartomatous Thymoma with HER2 Overexpression
Harim Oh, Eojin Kim, Bokyung Ahn, Jeong Hyeon Lee, Youngseok Lee, Yang Seok Chae, Chul Hwan Kim, Yoo Jin Lee
J Pathol Transl Med. 2019;53(6):403-406.   Published online August 19, 2019
DOI: https://doi.org/10.4132/jptm.2019.06.23
  • 2,999 View
  • 92 Download
  • 1 Citations
PDF
Peritoneal Fluid Cytology of Disseminated Large Cell Neuroendocrine Carcinoma Combined with Endometrioid Adenocarcinoma of the Endometrium
Yong-Moon Lee, Min-Kyung Yeo, Song-Yi Choi, Kyung-Hee Kim, Kwang-Sun Suh
J Pathol Transl Med. 2019;53(6):407-410.   Published online September 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.07.29
  • 3,241 View
  • 72 Download
PDF
Letters to the Editor
Comment on “Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis”
Bolin Wang, Yan Huang
J Pathol Transl Med. 2019;53(6):411-411.   Published online November 1, 2019
DOI: https://doi.org/10.4132/jptm.2019.09.26
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  • 63 Download
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Response to Comment on “Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis”
Jung-Soo Pyo, Nae Yu Kim, Won Jin Cho
J Pathol Transl Med. 2019;53(6):412-414.   Published online November 1, 2019
DOI: https://doi.org/10.4132/jptm.2019.09.27
  • 3,101 View
  • 54 Download
PDF
Corrigendum
Correction of Ethics Statement: Metastatic Insulinoma Presenting as a Liver Cyst
Hua Li, Tony El Jabbour, Ankesh Nigam, Hwajeong Lee
J Pathol Transl Med. 2019;53(6):415-415.   Published online November 5, 2019
DOI: https://doi.org/10.4132/jptm.2019.08.12
Corrects: J Pathol Transl Med 2019;53(2):148
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JPTM : Journal of Pathology and Translational Medicine