Journal of Pathology and Translational Medicine

Original Article

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea: Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho; J Pathol Transl Med. 2023;57(3):166-177. Published online May 10, 2023; DOI: https://doi.org/10.4132/jptm.2023.04.12

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Background
Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study.
Methods
Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53.
Results
CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history.
Conclusions
Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Citations

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Differenzierung von benignen und malignen Halszysten – eine diagnostische Herausforderung
Christina Sauter, Matthias Sand, Karim Plath, Michaela Maria Plath
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Daniela Messineo, Filippo Valentini, Giovanni Francesco Niccolini, Federica Zoccali, Francesca Ripari, Enrico Marotta, Marcello Caratozzolo, Pasquale Frisina
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Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy
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Cancer Immunology, Immunotherapy.2024;[Epub] CrossRef

Review

Neuropathologic features of central nervous system hemangioblastoma: Rebecca A. Yoda, Patrick J. Cimino; J Pathol Transl Med. 2022;56(3):115-125. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.04.13

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Abstract PDF

Hemangioblastoma is a benign, highly vascularized neoplasm of the central nervous system (CNS). This tumor is associated with loss of function of the VHL gene and demonstrates frequent occurrence in von Hippel-Lindau (VHL) disease. While this entity is designated CNS World Health Organization grade 1, due to its predilection for the cerebellum, brainstem, and spinal cord, it is still an important cause of morbidity and mortality in affected patients. Recognition and accurate diagnosis of hemangioblastoma is essential for the practice of surgical neuropathology. Other CNS neoplasms, including several tumors associated with VHL disease, may present as histologic mimics, making diagnosis challenging. We outline key clinical and radiologic features, pathophysiology, treatment modalities, and prognostic information for hemangioblastoma, and provide a thorough review of the gross, microscopic, immunophenotypic, and molecular features used to guide diagnosis.

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Ali Riazi, Yaser Emaeillou, Nima Najafi, Mohammad Hoseinimanesh, Mohammad Ibrahim Ashkaran, Donya Sheibani Tehrani
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François Fabi, Ève Chamberland, Myreille D’Astous, Karine Michaud, Martin Côté, Isabelle Thibault
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Case Study

Adrenal hemangioblastoma: Joo-Yeon Koo, Kyung-Hwa Lee, Joon Hyuk Choi, Ho Seok Chung, Chan Choi; J Pathol Transl Med. 2022;56(3):161-166. Published online February 28, 2022; DOI: https://doi.org/10.4132/jptm.2021.12.28

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Abstract PDF: Hemangioblastoma (HB) is a rare benign tumor that most commonly occurs in the cerebellum. HB is composed of neoplastic stromal cells and abundant small vessels. However, the exact origin of stromal cells is controversial. Extraneural HBs have been reported in a small series, and peripheral HBs arising in the adrenal gland are extremely rare. Herein, we report a case of sporadic adrenal HB in a 54-year-old woman. The tumor was a well-circumscribed, yellow mass measuring 4.2 cm in diameter. Histologically, the tumor was composed of small blood vessels and vacuolated stromal cells with clear cytoplasm. On immunohistochemical stain, the stromal cells were positive for S-100 protein, neuron-specific enolase, and synaptophysin. The tumor did not reveal mutation of VHL alleles. We herein present a case of HB of the adrenal gland and review of the literature.

Original Articles

Clinicopathological differences in radiation-induced organizing hematomas of the brain based on type of radiation treatment and primary lesions: Myung Sun Kim, Se Hoon Kim, Jong-Hee Chang, Mina Park, Yoon Jin Cha; J Pathol Transl Med. 2022;56(1):16-21. Published online October 15, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.30

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Abstract PDF

Background
Radiation-induced organizing hematoma (RIOH) is a sporadic form of cavernous hemangioma (CH) that occurs after cerebral radiation. RIOH lesions are distinct histologically from de novo CH; however, detailed research on this subject is lacking. In the present study, the clinical and histological features of RIOHs were evaluated based on causative lesions.
Methods
The present study included 37 RIOHs confirmed by surgical excision from January 2009, to May 2020, in Yonsei Severance Hospital. All cases were divided into subgroups based on type of radiation treatment (gamma knife surgery [GKS], n = 24 vs. conventional radiation therapy [RT], n = 13) and pathology of the original lesion (arteriovenous malformation, n = 14; glioma, n = 12; metastasis, n = 4; other tumors, n = 7). The clinicopathological results were compared between the groups.
Results
Clinical data of multiplicity, latency, and size and wall thickness of the original tumors and RIOHs were analyzed. The GKS group showed shorter latency (5.85 ± 4.06 years vs. 11.15 ± 8.27 years, p = .046) and thicker tumor wall (693.7 ± 565.7 μm vs. 406.9 ± 519.7 μm, p = .049) than the conventional RT group. Significant difference was not found based on original pathology.
Conclusions
RIOH is more likely to occur earlier with thick tumor wall in subjects who underwent GKS than in patients who underwent conventional RT. These results indicate the clinical course of RIOH differs based on type of treatment and might help determine the duration of follow-up.

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Hyoung Soo Choi, Chae-Yong Kim, Byung Se Choi, Seung Hyuck Jeon, In Ah Kim, Joo-Young Kim, Kyu Sang Lee, Gheeyoung Choe
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Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization: Hezhen Ren, Jennifer Pors, Christine Chow, Monica Ta, Simona Stolnicu, Robert Soslow, David Huntsman, Lynn Hoang; J Pathol Transl Med. 2020;54(6):480-488. Published online August 31, 2020; DOI: https://doi.org/10.4132/jptm.2020.07.18

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Abstract PDF

Background
The International Endocervical Adenocarcinoma Criteria and Classification (IECC) separated endocervical adenocarcinomas into human papillomavirus (HPV) associated (HPVA) and non–HPV-associated (NHPVA) categories by morphology alone. Our primary objective was to assess the accuracy of HPV prediction by the IECC system compared to p16 immunohistochemistry and HPV RNA in-situ hybridization (RISH). Our secondary goal was to directly compare p16 and HPV RISH concordance.
Methods
Cases were classified by IECC and stained for p16 and HPV RISH on tissue microarray, with discordant p16/HPV RISH cases re-stained on whole tissue sections. Remaining discordant cases (p16/HPV, IECC/p16, IECC/HPV discordances) were re-reviewed by the original pathologists (n = 3) and external expert pathologists (n = 2) blinded to the p16 and HPV RISH results. Final IECC diagnosis was assigned upon independent agreement between all reviewers.
Results
One hundred and eleven endocervical adenocarcinomas were classified originally into 94 HPVA and 17 NHPVA cases. p16 and HPV RISH was concordant in 108/111 cases (97%) independent of the IECC. HPV RISH and p16 was concordant with IECC in 103/111 (93%) and 106/111 (95%), respectively. After expert review, concordance improved to 107/111 (96%) for HPV RISH. After review of the eight discordant cases, one remained as HPVA, four were reclassified to NHPVA from HPVA, two were unclassifiable, and one possibly represented a mixed usual and gastric-type adenocarcinoma.
Conclusions
p16 and HPV RISH have excellent concordance in endocervical adenocarcinomas, and IECC can predict HPV status in most cases. Focal apical mitoses and apoptotic debris on original review led to the misclassification of several NHPVA as HPVA.

Citations

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Joint detection of multiple HPV-testing technologies and evaluation of clinicopathological characteristics discriminate between HPV-independent and low-copy HPV-associated cervical squamous cell carcinoma (CSCC) -an analysis of 3869 cases
Linghui Lu, Tianqi Liu, Shunni Wang, Jing Li, Feiran Zhang, Yan Ning, Yiqin Wang
Gynecologic Oncology.2023; 170: 59. CrossRef
Incidence and Clinicopathologic Characteristics of Human Papillomavirus–independent Invasive Squamous Cell Carcinomas of the Cervix
Simona Stolnicu, Douglas Allison, Aaron M. Praiss, Basile Tessier-Cloutier, Amir Momeni Boroujeni, Jessica Flynn, Alexia Iasonos, Rene Serrette, Lien Hoang, Andrei Patrichi, Cristina Terinte, Anna Pesci, Claudia Mateoiu, Ricardo R. Lastra, Takako Kiyokawa
American Journal of Surgical Pathology.2023; 47(12): 1376. CrossRef
Testing Algorithms for the Diagnosis of Malignant Glandular Tumors of the Uterine Cervix Histotyped per the International Endocervical Adenocarcinoma Criteria and Classification (IECC) System
Máire A. Duggan, Qiuli Duan, Ruth M. Pfeiffer, Mary Anne Brett, Sandra Lee, Mustapha Abubakar, Martin Köbel, Monica Rodriguez, Aylin Sar
Applied Immunohistochemistry & Molecular Morphology.2022; 30(2): 91. CrossRef
Local and Metastatic Relapses in a Young Woman with Papillary Squamous Cell Carcinoma of the Uterine Cervix
Ha Young Woo, Hyun-Soo Kim
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Pathology.2022; 54(5): 548. CrossRef
Reproducibility of Morphologic Parameters of the International Endocervical Adenocarcinoma Criteria and Classification System and Correlation With Clinicopathologic Parameters: A Multi-Institutional Study
Pinar Bulutay, Nihan Haberal, Özlem Özen, Özlem Erdem, Emine H. Zeren, İbrahim Kulac, Çagatay Taskiran, Dogan Vatansever, Ali Ayhan, Nilgün Kapucuoğlu
International Journal of Gynecological Pathology.2022; 41(5): 447. CrossRef
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Francesca Arezzo, Gennaro Cormio, Vera Loizzi, Gerardo Cazzato, Viviana Cataldo, Claudio Lombardi, Giuseppe Ingravallo, Leonardo Resta, Ettore Cicinelli
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International Endocervical Adenocarcinoma Criteria and Classification (IECC): An Independent Cohort With Clinical and Molecular Findings
Hezhen Ren, Noorah Almadani, Jennifer Pors, Samuel Leung, Julie Ho, Christine Chow, Monica Ta, Kay J. Park, Simona Stolnicu, Robert Soslow, David Huntsman, Blake C. Gilks, Lynn Hoang
International Journal of Gynecological Pathology.2021; 40(6): 533. CrossRef

Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas: Yuil Kim, Young-Hoon Joo, Min-Sik Kim, Youn Soo Lee; J Pathol Transl Med. 2020;54(5):411-418. Published online July 21, 2020; DOI: https://doi.org/10.4132/jptm.2020.06.22

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Abstract PDF

Background
High-risk (HR) human papillomavirus (HPV) is found in a subset of head and neck (HN) squamous cell carcinomas (SCCs). For oropharyngeal SCCs, HR HPV positivity is known to be associated with good prognosis, and a separate staging system for HPV-associated carcinomas using p16 immunohistochemistry (IHC) as a surrogate test has been adopted in the 8th American Joint Committee on Cancer staging system. We examined the HR HPV status and the genotype distribution in five HN subsites.
Methods
Formalin-fixed paraffin-embedded tissue sections were used for p16 IHC and DNA extraction. HPV DNA detection and genotyping were done employing either a DNA chip-based or real-time polymerase chain reaction–based method.
Results
During 2011–2019, a total of 466 SCCs were tested for HPV DNA with 34.1% positivity for HR HPV. Among HN subsites, the oropharynx showed the highest HR HPV prevalence (149/205, 75.1%), followed by the sinonasal tract (3/14, 21.4%), larynx (5/43, 11.6%), hypopharynx (1/38, 2.6%), and oral cavity (1/166, 0.6%). The most common HPV genotype was HPV16 (84.3%) followed by HPV35 (6.9%) and HPV33 (4.4%). Compared with HR HPV status, the sensitivity and specificity of p16 IHC were 98.6% and 94.3% for the oropharynx, and 99.2% and 93.8% for the tonsil, respectively.
Conclusions
Using a Korean dataset, we confirmed that HR HPV is most frequently detected in oropharyngeal SCCs. p16 positivity showed a good concordance with HR HPV DNA for oropharyngeal and especially tonsillar carcinomas. The use of p16 IHC may further be extended to predict HR HPV positivity in sinonasal tract SCCs.

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Gene variant profiles and tumor metabolic activity as measured by FOXM1 expression and glucose uptake in lung adenocarcinoma: Ashley Goodman, Waqas Mahmud, Lela Buckingham; J Pathol Transl Med. 2020;54(3):237-245. Published online March 4, 2020; DOI: https://doi.org/10.4132/jptm.2020.02.08

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Abstract PDF

Background
Cancer cells displaying aberrant metabolism switch energy production from oxidative phosphorylation to glycolysis. Measure of glucose standardized uptake value (SUV) by positron emission tomography (PET), used for staging of adenocarcinoma in high-risk patients, can reflect cellular use of the glycolysis pathway. The transcription factor, FOXM1 plays a role in regulation of glycolytic genes. Cancer cell transformation is driven by mutations in tumor suppressor genes such as TP53 and STK11 and oncogenes such as KRAS and EGFR. In this study, SUV and FOXM1 gene expression were compared in the background of selected cancer gene mutations.
Methods
Archival tumor tissue from cases of lung adenocarcinoma were analyzed. SUV was collected from patient records. FOXM1 gene expression was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Gene mutations were detected by allele-specific PCR and gene sequencing.
Results
SUV and FOXM1 gene expression patterns differed in the presence of single and coexisting gene mutations. Gene mutations affected SUV and FOXM1 differently. EGFR mutations were found in tumors with lower FOXM1 expression but did not affect SUV. Tumors with TP53 mutations had increased SUV (p = .029). FOXM1 expression was significantly higher in tumors with STK11 mutations alone (p < .001) and in combination with KRAS or TP53 mutations (p < .001 and p = .002, respectively).
Conclusions
Cancer gene mutations may affect tumor metabolic activity. These observations support consideration of tumor cell metabolic state in the presence of gene mutations for optimal prognosis and treatment strategy.

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Prognostic value of combining clinical factors, 18F-FDG PET-based intensity, volumetric features, and deep learning predictor in patients with EGFR-mutated lung adenocarcinoma undergoing targeted therapies: a cross-scanner and temporal validation study
Kun-Han Lue, Yu-Hung Chen, Sung-Chao Chu, Chih-Bin Lin, Tso-Fu Wang, Shu-Hsin Liu
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Case Study

Morphologic variant of follicular lymphoma reminiscent of hyaline-vascular Castleman disease: Jiwon Koh, Yoon Kyung Jeon; J Pathol Transl Med. 2020;54(3):253-257. Published online February 5, 2020; DOI: https://doi.org/10.4132/jptm.2019.12.17

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Abstract PDF

Follicular lymphoma (FL) with hyaline-vascular Castleman disease (FL-HVCD)-like features is a rare morphologic variant, with fewer than 20 cases in the literature. Herein, we report a case of FL-HVCD in a 37-year-old female who presented with isolated neck lymph node enlargement. The excised lymph node showed features reminiscent of HVCD, including regressed germinal centers (GCs) surrounded by onion skin-like mantle zones, lollipop lesions composed of hyalinized blood vessels penetrating into regressed GCs, and hyalinized interfollicular stroma. In addition, focal areas of abnormally conglomerated GCs composed of homogeneous, small centrocytes with strong BCL2, CD10, and BCL6 expression were observed, indicating partial involvement of the FL. Several other lymphoid follicles showed features of in situ follicular neoplasia. Based on the observations, a diagnosis of FL-HVCD was made. Although FLHVCD is very rare, the possibility of this variant should be considered in cases resembling CD. Identification of abnormal, neoplastic follicles and ancillary immunostaining are helpful for proper diagnosis.

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Unicentric Castleman Disease: Illustration of Its Morphologic Spectrum and Review of the Differential Diagnosis
Siba El Hussein, Andrew G. Evans, Hong Fang, Wei Wang, L. Jeffrey Medeiros
Archives of Pathology & Laboratory Medicine.2024; 148(1): 99. CrossRef
Finding a Needle in the Haystack
Hung-Yu Lin, Yi-Jen Peng, Yi-Ying Wu, Ping-Ying Chang
Journal of Medical Sciences.2023; 43(6): 292. CrossRef
Analysis of immunophenotypic features in hyaline vascular type Castleman disease
Yu Chang, Yu Ma, Chen Chang, Wensheng Li
Diagnostic Pathology.2023;[Epub] CrossRef
In‐situ follicular neoplasia: a clinicopathological spectrum
Gurdip S Tamber, Myriam Chévarie‐Davis, Margaret Warner, Chantal Séguin, Carole Caron, René P Michel
Histopathology.2021; 79(6): 1072. CrossRef

Original Articles

Colorectal epithelial neoplasm associated with gut-associated lymphoid tissue: Yo Han Jeon, Ji Hyun Ahn, Hee Kyung Chang; J Pathol Transl Med. 2020;54(2):135-145. Published online January 29, 2020; DOI: https://doi.org/10.4132/jptm.2019.11.06

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Abstract PDF

Background
Colorectal epithelial neoplasm extending into the submucosal gut-associated lymphoid tissue (GALT) can cause difficulties in the differential diagnosis. Regarding GALT-associated epithelial neoplasms, a few studies favor the term “GALT carcinoma” while other studies have mentioned the term “GALT-associated pseudoinvasion/epithelial misplacement (PEM)”.
Methods
The clinicopathologic characteristics of 11 cases of colorectal epithelial neoplasm associated with submucosal GALT diagnosed via endoscopic submucosal dissection were studied.
Results
Eight cases (72.7%) were in males. The median age was 59 years, and age ranged from 53 to 73. All cases had a submucosal tumor component more compatible with GALT-associated PEM. Eight cases (72.7%) were located in the right colon. Ten cases (90.9%) had a non-protruding endoscopic appearance. Nine cases (81.8%) showed continuity between the submucosal and surface adenomatous components. Nine cases showed (81.8%) focal defects or discontinuation of the muscularis mucosae adjacent to the submucosal GALT. No case showed hemosiderin deposits in the submucosa or desmoplastic reaction. No case showed single tumor cells or small clusters of tumor cells in the submucosal GALT. Seven cases (63.6%) showed goblet cells in the submucosa. No cases showed oncocytic columnar cells lining submucosal glands.
Conclusions
Our experience suggests that pathologists should be aware of the differential diagnosis of GALT-associated submucosal extension by colorectal adenomatous neoplasm. Further studies are needed to validate classification of GALT-associated epithelial neoplasms.

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Family adenomatous polyposis come across dome type adenocarcinoma: a case report and literature review
Ying-Ying Chang, Xiao-Long Zhang, Yao-Hui Wang, Ting-Sheng Ling
Diagnostic Pathology.2025;[Epub] CrossRef

Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution: Myunghee Kang, Seung Yeon Ha, Hyun Yee Cho, Dong Hae Chung, Na Rae Kim, Jungsuk An, Sangho Lee, Jae Yeon Seok, Juhyeon Jeong; J Pathol Transl Med. 2020;54(1):112-118. Published online January 15, 2020; DOI: https://doi.org/10.4132/jptm.2019.11.29

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Abstract PDF

Background
The decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution.
Methods
Patients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations.
Results
Sensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively).
Conclusions
Pap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

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Analysis of the molecular subtypes of preoperative core needle biopsy and surgical specimens in invasive breast cancer: Ye Sul Jeong, Jun Kang, Jieun Lee, Tae-Kyung Yoo, Sung Hun Kim, Ahwon Lee; J Pathol Transl Med. 2020;54(1):87-94. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.14

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Abstract PDF

Background
Accurate molecular classification of breast core needle biopsy (CNB) tissue is important for determining neoadjuvant systemic therapies for invasive breast cancer. The researchers aimed to evaluate the concordance rate (CR) of molecular subtypes between CNBs and surgical specimens.
Methods
This study was conducted with invasive breast cancer patients who underwent surgery after CNB at Seoul St. Mary’s Hospital between December 2014 and December 2017. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed using immunohistochemistry. ER and PR were evaluated by Allred score (0–8). HER2 was graded from 0 to +3, and all 2+ cases were reflex tested with silver in situ hybridization. The labeling index of Ki67 was counted by either manual scoring or digital image analysis. Molecular subtypes were classified using the above surrogate markers.
Results
In total, 629 patients were evaluated. The CRs of ER, PR, HER2, and Ki67 were 96.5% (kappa, 0.883; p<.001), 93.0% (kappa, 0.824; p<.001), 99.7% (kappa, 0.988; p<.001), and 78.7% (kappa, 0.577; p<.001), respectively. Digital image analysis of Ki67 in CNB showed better concordance with Ki67 in surgical specimens (CR, 82.3%; kappa, 0.639 for digital image analysis vs. CR, 76.2%; kappa, 0.534 for manual counting). The CRs of luminal A, luminal B, HER2, and triple negative types were 89.0%, 70.0%, 82.9%, and 77.2%, respectively.
Conclusions
CNB was reasonably accurate for determining ER, PR, HER2, Ki67, and molecular subtypes. Using digital image analysis for Ki67 in CNB produced more accurate molecular classifications.

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Pınar CELEPLİ, Pelin Seher ÖZTEKİN, Salih CELEPLİ, İrem BİGAT, Sema HÜCÜMENOĞLU
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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

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Abstract PDF Supplementary 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.

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Review

Current Status of and Perspectives on Cervical Cancer Screening in Korea: Sung-Chul Lim, Chong Woo Yoo; J Pathol Transl Med. 2019;53(4):210-216. Published online May 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.04.11

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Abstract PDF

Since the introduction of the Papanicolaou (Pap) smear system in 1943, cervicovaginal cytology has been used as a standard screening test for cervical cancer. The dissemination of this test contributed to reductions of the incidence and mortality of cervical cancer worldwide. In Korea, regular health check-ups for industrial workers and their family members were introduced in 1988 and were performed as part of the National Cancer Screening Program in 1999. As a result, the incidence of cervical cancer in Korea has been steadily decreasing. However, about 800 cases of cervical cancer-related deaths are reported each year due to false-negative test results. Hence, new screening methods have been proposed. Liquid-based cytology (LBC) was introduced in 1996 to overcome the limitations of conventional Pap smears. Since then, other LBC methods have been developed and utilized, including the human papilloma virus test—a method with higher sensitivity that requires fewer screenings. In this study, we review current issues and future perspectives related to cervical cancer screening in Korea.

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Case Study

Frozen Cytology of Meningeal Malignant Solitary Fibrous Tumor/Hemangiopericytoma: Myunghee Kang, Na Rae Kim, Dong Hae Chung, Gie-Taek Yie; J Pathol Transl Med. 2019;53(3):192-197. Published online April 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.03.20

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Abstract PDF

A 51-year-old woman presented with severe dizziness. The brain magnetic resonance image revealed a 5.5 cm multiloculated mass with a thick rim in the left temporal lobe. Cytological examination of frozen diagnosis of the mass showed hypercellular sheets of round and rhabdoid cells in a hemorrhagic background, and two mitotic figures were observed. Histologically, the excised dura-based mass consisted of predominantly round cells with small foci of rhabdoid tumor cells in a pseudoalveolar pattern in a hemorrhagic background, and the cells showed nuclear positivity for signal transducer and activator of transcription 6 as well as frequent mitosis. The mass was diagnosed as a grade 3 solitary fibrous tumor (SFT)/hemangiopericytoma (HPC). The cytological diagnosis of SFT/HPC is challenging because of the heterogeneous cytological findings, such as histological heterogeneity, and because there are no standardized cytological criteria for malignant SFT/HPC. Cytological findings, such as singly scattered small cells, hypercellularity, rare ropy collagen, and round and rhabdoid cells with pseudoalveolar pattern, may assist in the diagnosis of malignant SFT/HPC.

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Intraoperative frozen cytology of intraosseous cystic meningioma in the sphenoid bone
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Original Article

Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Coexpression Is an Independent Poor Prognostic Factor in Adenocarcinoma of the Lung: Yeon Bi Han, Hyun Jung Kwon, Soo Young Park, Eun-Sun Kim, Hyojin Kim, Jin-Haeng Chung; J Pathol Transl Med. 2019;53(2):86-93. Published online January 14, 2019; DOI: https://doi.org/10.4132/jptm.2018.12.26

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Abstract PDF

Background
Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression.
Methods
HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed.
Results
HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p = .033, p = .007, and p = .012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p < .001, p = .002, and p = .032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501).
Conclusions
Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression.

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Assessment of cancer cell‐expressed HLA class I molecules and their immunopathological implications
Terufumi Kubo, Shiori Asano, Kenta Sasaki, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Toshihiko Torigoe
HLA.2024;[Epub] CrossRef
Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis
Weiqiang Qiao, Zhiqiang Jia, Wanying Guo, Qipeng Liu, Xiao Guo, Miao Deng
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Ioannis M. Koukourakis, Alexandra Giatromanolaki, Achilleas Mitrakas, Michael I. Koukourakis
Cellular Immunology.2022; 373: 104495. CrossRef

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