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Volume 53(1); January 2019
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Review
Artificial Intelligence in Pathology
Hye Yoon Chang, Chan Kwon Jung, Junwoo Isaac Woo, Sanghun Lee, Joonyoung Cho, Sun Woo Kim, Tae-Yeong Kwak
J Pathol Transl Med. 2019;53(1):1-12.   Published online December 28, 2018
DOI: https://doi.org/10.4132/jptm.2018.12.16
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  • 82 Citations
AbstractAbstract PDF
As in other domains, artificial intelligence is becoming increasingly important in medicine. In particular,deep learning-based pattern recognition methods can advance the field of pathology byincorporating clinical, radiologic, and genomic data to accurately diagnose diseases and predictpatient prognoses. In this review, we present an overview of artificial intelligence, the brief historyof artificial intelligence in the medical domain, recent advances in artificial intelligence applied topathology, and future prospects of pathology driven by artificial intelligence.

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Original Articles
Prognostic Role of S100A8 and S100A9 Protein Expressions in Non-small Cell Carcinoma of the Lung
Hyun Min Koh, Hyo Jung An, Gyung Hyuck Ko, Jeong Hee Lee, Jong Sil Lee, Dong Chul Kim, Jung Wook Yang, Min Hye Kim, Sung Hwan Kim, Kyung Nyeo Jeon, Gyeong-Won Lee, Se Min Jang, Dae Hyun Song
J Pathol Transl Med. 2019;53(1):13-22.   Published online November 26, 2018
DOI: https://doi.org/10.4132/jptm.2018.11.12
  • 5,836 View
  • 223 Download
  • 6 Citations
AbstractAbstract PDF
Background
S100A8 and S100A9 have been gaining recognition for modulating tumor growthand metastasis. This study aimed at evaluating the clinical significance of S100A8 and S100A9 innon-small cell lung cancer (NSCLC).
Methods
We analyzed the relationship between S100A8and S100A9 expressions, clinicopathological characteristics, and prognostic significance in tumorcells and peritumoral inflammatory cells.
Results
The positive staining of S100A8 in tumorcells was significantly increased in male (p < .001), smoker (p = .034), surgical method other thanlobectomy (p = .024), squamous cell carcinoma (SQCC) (p < .001) and higher TNM stage (p = .022)compared with female, non-smoker, lobectomy, adenocarcinoma (ADC), and lower stage. Theproportion of tumor cells stained for S100A8 was related to histologic type (p < .001) and patientsex (p = .027). The proportion of inflammatory cells stained for S100A8 was correlated with patientage (p = .022), whereas the proportion of inflammatory cells stained for S100A9 was correlatedwith patient sex (p < .001) and smoking history (p = .031). Moreover, positive staining in tumorcells, more than 50% of the tumor cells stained and less than 30% of the inflammatory cellsstained for S100A8 and S100A9 suggested a tendency towards increased survivability in SQCCbut towards decreased survivability in ADC.
Conclusions
S100A8 and S100A9 expressions might be potential prognostic markers in patients with NSCLC.

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  • Prognostic Role of S100A8 in Human Solid Cancers: A Systematic Review and Validation
    An Huang, Wei Fan, Jiacui Liu, Ben Huang, Qingyuan Cheng, Ping Wang, Yiping Duan, Tiantian Ma, Liangyue Chen, Yanping Wang, Mingxia Yu
    Frontiers in Oncology.2020;[Epub]     CrossRef
PLAG1, SOX10, and Myb Expression in Benign and Malignant Salivary Gland Neoplasms
Ji Hyun Lee, Hye Ju Kang, Chong Woo Yoo, Weon Seo Park, Jun Sun Ryu, Yuh-Seog Jung, Sung Weon Choi, Joo Yong Park, Nayoung Han
J Pathol Transl Med. 2019;53(1):23-30.   Published online November 14, 2018
DOI: https://doi.org/10.4132/jptm.2018.10.12
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AbstractAbstract PDF
Background
Recent findings in molecular pathology suggest that genetic translocation and/oroverexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. Weinvestigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues.
Methods
A total of 113 cases of surgically resected salivary gland neoplasms at the NationalCancer Center from January 2007 to March 2017 were identified. Immunohistochemical stainingof PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays.
Results
Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showednuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphicadenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary glandneoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissuesSOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expressionwas observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not inother benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors.Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%)malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and onemyoepithelial carcinoma with focal AdCC-like histology.
Conclusions
PLAG1 expression is specificto pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor,but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology isunclear in the surgical specimen.

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Uterine Malignant Mixed Müllerian Tumors Following Treatment with Selective Estrogen Receptor Modulators in Patients with Breast Cancer: A Report of 13 Cases and Their Clinicopathologic Characteristics
Byung-Kwan Jeong, Chang O. Sung, Kyu-Rae Kim
J Pathol Transl Med. 2019;53(1):31-39.   Published online December 18, 2018
DOI: https://doi.org/10.4132/jptm.2018.11.16
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AbstractAbstract PDF
Background
Breast cancer treatment with selective estrogen receptor modulators (SERMs) increasesthe incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologiccharacteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discusspossible pathogenetic mechanisms.
Methods
Among 28,104 patients with breast cancer, clinicopathologicfeatures and incidence of uMMMT were compared between patients who underwentSERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period,incidence, dose, and duration of SERM treatment, as well as overall survival rate, were comparedfor patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMTvs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathologicalfindings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ,progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT.
Results
The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold).All patients with SERM were postmenopausal and received daily 20–40 mg SERM. CumulativeSERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologicfeatures, such as International Federation of Gynecology and Obstetrics stage andoverall survival, were not significantly different between patients with S-uMMMT and NS-uMMMTor between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available forimmunostaining exhibited strong overexpression/null expression of p53 protein and significantlyincreased ERβ expression in carcinomatous and sarcomatous components.
Conclusions
SERMtherapy seemingly increases risk of S-uMMMT development; however, clinicopathologic featureswere similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expressionmight be involved in the etiology of S-uMMMT.

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    Leskela, Pérez-Mies, Rosa-Rosa, Cristobal, Biscuola, Palacios-Berraquero, Ong, Guia, Palacios
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Prognostic Impact of Fusobacterium nucleatum Depends on Combined Tumor Location and Microsatellite Instability Status in Stage II/III Colorectal Cancers Treated with Adjuvant Chemotherapy
Hyeon Jeong Oh, Jung Ho Kim, Jeong Mo Bae, Hyun Jung Kim, Nam-Yun Cho, Gyeong Hoon Kang
J Pathol Transl Med. 2019;53(1):40-49.   Published online December 26, 2018
DOI: https://doi.org/10.4132/jptm.2018.11.29
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  • 221 Download
  • 29 Citations
AbstractAbstract PDFSupplementary Material
Background
This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy.
Methods
F. nucleatumDNA was quantitatively measured in a total of 593 CRC tissues retrospectively collectedfrom surgically resected specimens of stage III or high-risk stage II CRC patients who had receivedcurative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOXor CAPOX). Each case was classified into one of the three categories: F. nucleatum–high, –low, or –negative.
Results
No significant differences in survival were observed between the F.nucleatum–high and –low/negative groups in the 593 CRCs (p = .671). Subgroup analyses accordingto tumor location demonstrated that disease-free survival was significantly better in F.nucleatum–high than in –low/negative patients with non-sigmoid colon cancer (including cecal,ascending, transverse, and descending colon cancers; n = 219; log-rank p = .026). In multivariateanalysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoidcolon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p = .043). Furthermore,the favorable prognostic effect of F. nucleatum–high was observed only in a non-microsatellite instability-high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p = 0.014), but not ina MSI-high subset (log-rank p = 0.844), suggesting that the combined status of tumor locationand MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treatedwith adjuvant chemotherapy.
Conclusions
Intratumoral F. nucleatum load is a potential prognosticfactor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treatedwith oxaliplatin-based adjuvant chemotherapy.

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Quilty Lesions in the Endomyocardial Biopsies after Heart Transplantation
Haeyon Cho, Jin-Oh Choi, Eun-Seok Jeon, Jung-Sun Kim
J Pathol Transl Med. 2019;53(1):50-56.   Published online December 26, 2018
DOI: https://doi.org/10.4132/jptm.2018.11.30
  • 5,050 View
  • 102 Download
  • 5 Citations
AbstractAbstract PDFSupplementary Material
Background
The aim of this study was to investigate the clinical significance of Quilty lesions in endomyocardial biopsies (EMBs) of cardiac transplantation patients.
Methods
A total of 1190EMBs from 117 cardiac transplantation patients were evaluated histologically for Quilty lesions,acute cellular rejection, and antibody-mediated rejection. Cardiac allograft vasculopathy wasdiagnosed by computed tomography coronary angiography. Clinical information, including thepatients’ survival was retrieved by a review of medical records.
Results
Eighty-eight patients(75.2%) were diagnosed with Quilty lesions, which were significantly associated with acute cellularrejection, but not with acute cellular rejection ≥ 2R or antibody-mediated rejection. In patientsdiagnosed with both Quilty lesions and acute cellular rejection, the time-to-onset of Quilty lesionsfrom transplantation was longer than that of acute cellular rejections. We found a significant associationbetween Quilty lesions and cardiac allograft vasculopathy. No significant relationship wasfound between Quilty lesions and the patients’ survival.
Conclusions
Quilty lesion may be an indicator of previous acute cellular rejection rather than a predictor for future acute cellular rejection.

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Case Studies
Primary Peripheral Gamma Delta T-Cell Lymphoma of the Central Nervous System: Report of a Case Involving the Intramedullary Spinal Cord and Presenting with Myelopathy
Jeemin Yim, Seung Geun Song, Sehui Kim, Jae Won Choi, Kyu-Chong Lee, Jeong Mo Bae, Yoon Kyung Jeon
J Pathol Transl Med. 2019;53(1):57-61.   Published online October 1, 2018
DOI: https://doi.org/10.4132/jptm.2018.08.21
  • 4,218 View
  • 144 Download
  • 2 Citations
AbstractAbstract PDF
Primary central nervous system lymphoma of T-cell origin (T-PCNSL) is rare, and its clinicopathological features remain unclear. Peripheral T-cell lymphoma of γδ T-cell origin is an aggressive lymphoma mainly involving extranodal sites. Here, we report a case of γδ T-PCNSL involving the intramedullary spinal cord and presenting with paraplegia. A 75-year-old Korean woman visited the hospital complaining of back pain and lower extremity weakness. Magnetic resonance imaging revealed multifocal enhancing intramedullary nodular lesions in the thoracic and lumbar spinal cord. An enhancing nodular lesion was observed in the periventricular white matter of the lateral ventricle in the brain. There were no other abnormalities in systemic organs or skin. Laminectomy and tumor removal were performed. The tumor consisted of monomorphic, medium-to-large atypical lymphocytes with pale-to-eosinophilic cytoplasm. Immunohistochemically, the tumor cells were CD3(+), TCRβF1(-), TCRγ(+), CD30(-), CD4(-), CD8(-), CD56(+), TIA1(+), granzyme B(+), and CD103(+). Epstein-Barr virus in situ was negative. This case represents a unique T-PCNSL of γδ T-cell origin involving the spinal cord.

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  • Clinicopathologic and Genetic Features of Primary T-cell Lymphomas of the Central Nervous System
    Jeemin Yim, Jiwon Koh, Sehui Kim, Seung Geun Song, Jeong Mo Bae, Hongseok Yun, Ji-Youn Sung, Tae Min Kim, Sung-Hye Park, Yoon Kyung Jeon
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TFE3-Expressing Perivascular Epithelioid Cell Tumor of the Breast
Hyunjin Kim, Jimin Kim, Se Kyung Lee, Eun Yoon Cho, Soo Youn Cho
J Pathol Transl Med. 2019;53(1):62-65.   Published online October 1, 2018
DOI: https://doi.org/10.4132/jptm.2018.08.30
  • 5,605 View
  • 138 Download
  • 8 Citations
AbstractAbstract PDF
Perivascular epithelioid cell tumor (PEComa) is a very rare mesenchymal tumor with a distinctive morphology and immunophenotype. PEComas usually harbor TSC2 alterations, although TFE3 translocations, which occur in MiT family translocation renal cell carcinoma and alveolar soft part sarcoma, are also possible. We recently experienced a case of PEComa with TFE3 expression arising in the breast. An 18-year-old female patient presented with a right breast mass. Histologically, the tumor consisted of epithelioid cells with alveolar structure and showed a diffuse strong expression of HMB45 and TFE3. TSC2 was preserved. Melan A and smooth muscle actin were negative. To our knowledge, this is the first Korean case of PEComa of the breast that intriguingly presented with TFE3 expression.

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Brief Case Report
Rare Manifestations of Churg-Strauss Syndrome with Mediastinal and Hilar Lymphadenopathies: Report of an Autopsy Case
Woo Cheal Cho, Bharat Ramlal, Mary Fiel-Gan, Xianyuan Song
J Pathol Transl Med. 2019;53(1):66-69.   Published online December 18, 2017
DOI: https://doi.org/10.4132/jptm.2017.12.13
  • 5,756 View
  • 140 Download
  • 1 Citations
PDF

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  • Radiological significance of mediastinal lymphadenopathy in eosinophilic granulomatosis with polyangiitis
    Hisashi Sasaki, Jun Miyata, Ryohei Suematsu, Yoshifumi Kimizuka, Yuji Fujikura, Yoshiko Kichikawa, Hiroaki Sugiura, Kenji Itoh, Akihiko Kawana
    Allergology International.2022; 71(4): 536.     CrossRef
Case Study
Cytopathologic Features of Secretory Carcinoma of Salivary Gland: Report of Two Cases
Young Ah Kim, Jae Won Joung, Sun-Jae Lee, Hoon-Kyu Oh, Chang Ho Cho, Woo Jung Sung
J Pathol Transl Med. 2019;53(1):70-74.   Published online December 28, 2018
DOI: https://doi.org/10.4132/jptm.2018.11.09
  • 4,700 View
  • 124 Download
  • 4 Citations
AbstractAbstract PDF
Secretory carcinoma of the salivary gland (SC) is a newly introduced rare salivary gland tumor that shares histological, immunohistochemical, and genetic characteristics with secretory carcinoma of the breast. Here, we report the cytologic features of two cases of SC confirmed by surgical resection. In these two cases, SC was incidentally detected in a 64-year-old female and a 56-yearold male. Fine needle aspiration cytology revealed nests of tumor cells with a papillary or glandular structure floating in mucinous secretions. The tumor cells demonstrated uniform, round, smooth nuclear contours and distinct nucleoli. Multiple characteristic cytoplasmic vacuoles were revealed. Singly scattered tumor cells frequently showed variable sized cytoplasmic vacuoles. The cytopathologic diagnosis of SC should be considered when characteristic cytological findings are revealed. Further immunohistochemistry and gene analyses are helpful to diagnose SC.

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    Head & Neck.2022; 44(3): 792.     CrossRef
  • A systematic review of secretory carcinoma of the salivary gland: where are we?
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    Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.2021; 132(4): e143.     CrossRef
  • Clinical characteristics of acinic cell carcinoma and secretory carcinoma of the parotid gland
    Tetsuya Terada, Ryo Kawata, Keiki Noro, Masaaki Higashino, Shuji Nishikawa, Shin-ichi Haginomori, Yoshitaka Kurisu, Hiroko Kuwabara, Yoshinobu Hirose
    European Archives of Oto-Rhino-Laryngology.2019; 276(12): 3461.     CrossRef

JPTM : Journal of Pathology and Translational Medicine