Journal of Pathology and Translational Medicine

Original Articles

Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists: Jiwon Koh, Ha Young Park, Jeong Mo Bae, Jun Kang, Uiju Cho, Seung Eun Lee, Haeyoun Kang, Min Eui Hong, Jae Kyung Won, Youn-La Choi, Wan-Seop Kim, Ahwon Lee; J Pathol Transl Med. 2023;57(5):265-272. Published online September 15, 2023; DOI: https://doi.org/10.4132/jptm.2023.08.26

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Abstract PDF: Background
The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education.
Methods
The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education.
Results
The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: ‘NGS library preparation and quality control’ (score increased from 51.8 to 68.8), ‘NGS interpretation of variants and reference database’ (score increased from 54.1 to 68.0), and ‘whole genome, whole exome, and targeted gene sequencing’ (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated.
Conclusions
Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.

Single-center study on clinicopathological and typical molecular pathologic features of metastatic brain tumor: Su Hwa Kim, Young Suk Lee, Sung Hak Lee, Yeoun Eun Sung, Ahwon Lee, Jun Kang, Jae-Sung Park, Sin Soo Jeun, Youn Soo Lee; J Pathol Transl Med. 2023;57(4):217-231. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.10

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Abstract PDF: Background
The metastatic brain tumor is the most common brain tumor. The aim of this study was to demonstrate the clinicopathological and molecular pathologic features of brain metastases (BM).
Methods
A total of 269 patients were diagnosed with BM through surgical resection at Seoul St. Mary’s Hospital from January 2010 to March 2020. We reviewed the clinicopathological features and molecular status of primary and metastatic brain tissues using immunohistochemistry and molecular pathology results.
Results
Among 269 patients, 139 males and 130 females were included. The median age of primary tumor was 58 years (range, 13 to 87 years) and 86 patients (32.0%) had BM at initial presentation. Median BM free interval was 28.0 months (range, 1 to 286 months). The most frequent primary site was lung 46.5% (125/269), and followed by breast 15.6% (42/269), colorectum 10.0% (27/269). Epidermal growth factor receptor (EGFR) mutation was found in 50.8% (32/63) and 58.0% (40/69) of lung primary and BM, respectively. In both breast primary and breast cancer with BM, luminal B was the most frequent subtype at 37.9% (11/29) and 42.9% (18/42), respectively, followed by human epidermal growth factor receptor 2 with 31.0% (9/29) and 33.3% (14/42). Triple-negative was 20.7% (6/29) and 16.7% (7/42), and luminal A was 10.3% (3/29) and 7.1% (3/42) of breast primary and BM, respectively. In colorectal primary and colorectal cancer with BM, KRAS mutation was found in 76.9% (10/13) and 66.7% (2/3), respectively.
Conclusions
We report the clinicopathological and molecular pathologic features of BM that can provide useful information for understanding the pathogenesis of metastasis and for clinical trials based on the tumor’s molecular pathology.

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.

Citations

Citations to this article as recorded by

Concordance of immunohistochemistry for predictive and prognostic factors in breast cancer between biopsy and surgical excision: a single-centre experience and review of the literature
Chiara Rossi, Sara Fraticelli, Marianna Fanizza, Alberta Ferrari, Elisa Ferraris, Alessia Messina, Angelica Della Valle, Chiara Annunziata Pasqualina Anghelone, Angioletta Lasagna, Gianpiero Rizzo, Lorenzo Perrone, Maria Grazia Sommaruga, Giulia Meloni, S
Breast Cancer Research and Treatment.2023; 198(3): 573. CrossRef
Single-center study on clinicopathological and typical molecular pathologic features of metastatic brain tumor
Su Hwa Kim, Young Suk Lee, Sung Hak Lee, Yeoun Eun Sung, Ahwon Lee, Jun Kang, Jae-Sung Park, Sin Soo Jeun, Youn Soo Lee
Journal of Pathology and Translational Medicine.2023; 57(4): 217. CrossRef
The Role of Diffusion-Weighted Imaging Based on Maximum-Intensity Projection in Young Patients with Marked Background Parenchymal Enhancement on Contrast-Enhanced Breast MRI
Ga-Eun Park, Bong-Joo Kang, Sung-hun Kim, Na-Young Jung
Life.2023; 13(8): 1744. CrossRef
Concordance between core needle biopsy and surgical excision specimens for Ki‐67 in breast cancer – a systematic review of the literature
Jahnavi Kalvala, Ruth M Parks, Andrew R Green, Kwok‐Leung Cheung
Histopathology.2022; 80(3): 468. CrossRef
İnvaziv Meme Kanserinde Preoperatif Kor İğne Biyopsi ile Postoperatif Cerrahi Spesmenler Arasında ER, PR, HER2 ve Ki67 Açısından Karşılaştırma
Pınar CELEPLİ, Pelin Seher ÖZTEKİN, Salih CELEPLİ, İrem BİGAT, Sema HÜCÜMENOĞLU
Akdeniz Medical Journal.2022; : 179. CrossRef
Concordance of breast cancer biomarker testing in core needle biopsy and surgical specimens: A single institution experience
Jessica A. Slostad, Nicole K. Yun, Aimee E. Schad, Surbhi Warrior, Louis F. Fogg, Ruta Rao
Cancer Medicine.2022; 11(24): 4954. CrossRef
N-Cadherin Distinguishes Intrahepatic Cholangiocarcinoma from Liver Metastases of Ductal Adenocarcinoma of the Pancreas
Tiemo S. Gerber, Benjamin Goeppert, Anne Hausen, Hagen R. Witzel, Fabian Bartsch, Mario Schindeldecker, Lisa-Katharina Gröger, Dirk A. Ridder, Oscar Cahyadi, Irene Esposito, Matthias M. Gaida, Peter Schirmacher, Peter R. Galle, Hauke Lang, Wilfried Roth,
Cancers.2022; 14(13): 3091. CrossRef
Association of Ki-67 Change Pattern After Core Needle Biopsy and Prognosis in HR+/HER2− Early Breast Cancer Patients
Shuai Li, Xiaosong Chen, Kunwei Shen
Frontiers in Surgery.2022;[Epub] CrossRef
MRI Features for Prediction Malignant Intra-Mammary Lymph Nodes: Correlations with Mammography and Ultrasound
Meejung Kim, Bong Joo Kang, Ga Eun Park
Investigative Magnetic Resonance Imaging.2022; 26(2): 135. CrossRef
A single centre experience in Turkey for comparison between core needle biopsy and surgical specimen evaluation results for HER2, SISH, estrogen receptors and progesterone receptors in breast cancer patients
Hatice Karaman, Fatma Senel, Arzu Tasdemir, Ipek Özer, Merve Dogan
Journal of Cancer Research and Therapeutics.2022; 18(6): 1789. CrossRef
Meme kanseri trucut ve rezeksiyon materyallerinde yeni moleküler sınıflama, tanı ve hormon reseptörlerinin durumu tutarlı mı?
Yeliz ARMAN KARAKAYA, Sevda YILMAZ, Hande KARABAŞ
Pamukkale Medical Journal.2021;[Epub] CrossRef
What shear wave elastography parameter best differentiates breast cancer and predicts its histologic aggressiveness?
Hyunjin Kim, Jeongmin Lee, Bong Joo Kang, Sung Hun Kim
Ultrasonography.2021; 40(2): 265. CrossRef
Risk-based decision-making in the treatment of HER2-positive early breast cancer: Recommendations based on the current state of knowledge
Christian Jackisch, Patricia Cortazar, Charles E. Geyer, Luca Gianni, Joseph Gligorov, Zuzana Machackova, Edith A. Perez, Andreas Schneeweiss, Sara M. Tolaney, Michael Untch, Andrew Wardley, Martine Piccart
Cancer Treatment Reviews.2021; 99: 102229. CrossRef
Factors influencing agreement of breast cancer luminal molecular subtype by Ki67 labeling index between core needle biopsy and surgical resection specimens
Kristina A. Tendl-Schulz, Fabian Rössler, Philipp Wimmer, Ulrike M. Heber, Martina Mittlböck, Nicolas Kozakowski, Katja Pinker, Rupert Bartsch, Peter Dubsky, Florian Fitzal, Martin Filipits, Fanny Carolina Eckel, Eva-Maria Langthaler, Günther Steger, Mich
Virchows Archiv.2020; 477(4): 545. CrossRef

The Ratio of Atypical Ductal Hyperplasia Foci to Core Numbers in Needle Biopsy: A Practical Index Predicting Breast Cancer in Subsequent Excision: Jeong-Ju Lee, Hee Jin Lee, Jun Kang, Jeong-Hyeon Jo, Gyungyub Gong; Korean J Pathol. 2012;46(1):15-21. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.15

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Abstract PDF

Background

Although core needle biopsy (CNB) is considered to be the standard technique for histological diagnosis of breast lesions, it is less reliable for diagnosing atypical ductal hyperplasia (ADH). We therefore assessed the characteristics of CNB-diagnosed ADH that are more likely to be associated with more advanced lesions on subsequent surgical excision.

Methods

We retrospectively examined 239 consecutive CNBs, 127 of which were diagnosed as ADH following surgical excision, performed at Asan Medical Center between 1995 and 2010. Archival slides were analyzed for the number of cores per specimen, the number of ADH foci, and the ratio of ADH foci to number of cores (FC ratio).

Results

We found that ADH foci in 3 or more cores (p=0.003) and the presence of ADH in 3 or more foci (p=0.002) were correlated with malignancy following excision lesion. Moreover, an FC>1.1 was significantly associated with malignancy in the subsequent excision (p=0.000).

Conclusions

Including the number of ADH foci, the number of cores involved according to ADH, FC ratio, and histologic type in a pathology report of CNB may help in making clinical decisions about surgical excision.

Citations

Citations to this article as recorded by

Active Surveillance for Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ
Rachel Miceli, Cecilia L Mercado, Osvaldo Hernandez, Chloe Chhor
Journal of Breast Imaging.2023; 5(4): 396. CrossRef

Histologic Parameters Predicting Survival of Patients with Multiple Non-small Cell Lung Cancers.: Joo Young Kim, Hee Jin Lee, Jun Kang, Se Jin Jang; Korean J Pathol. 2011;45(5):506-515.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.506

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Abstract PDF: BACKGROUND
In multiple lung cancers (MLCs), distinction between intrapulmonary metastases and multiple primary tumors is important for staging and prognosis. In this study, we have investigated histopathologic prognostic factors of patients with MLCs.
METHODS
Histologic subtype, size differences, lobar location, lymphovascular invasion (LVI), size of the largest tumor, nodal status, number of tumors, morphology of tumor periphery, and immunohistochemical profiles using eight antibodies, were analyzed in 65 patients with MLCs.
RESULTS
There was no significant difference in the survivals of patients with multiple primary tumors and intrapulmonary metastases, as determined by the Martini-Melamed criteria (p=0.654). Risk grouping by four histologic parameters, LVI, margin morphology, size differences, and lobar locations of paired tumors were prognostic. The patients with one or two of aforementioned parameters had significantly longer survival than those with three or four parameters (p=0.017). In patients with largest mass (< or =5 cm), the risk grouping was found to be an independent prognostic factor (p=0.022). However, differences in immunohistochemical staining were not related to patients' survival.
CONCLUSIONS
A risk grouping of MLC patients by using combinations of histologic parameters can be a useful tool in evaluating the survival of patients with MLCs, and may indicate clonal relationship between multiple tumors.

The Clinicopathological Parameters for Making the Differential Diagnosis of Neonatal Cholestasis.: Heejin Lee, Jun Kang, Kyung Mo Kim, Joo Young Jang, Se Jin Jang, Eunsil Yu; Korean J Pathol. 2009;43(1):43-47.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.43

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5 Crossref

Abstract PDF

BACKGROUND
The diseases that cause neonatal cholestasis display several overlapping clinical feature. Making the differential diagnosis using liver biopsy specimens from infants with neonatal cholestasis is important for delivering the proper treatment.
METHODS
We assessed the clinical manifestations, laboratory data, and histopathologic features of the pretreatment liver biopsy specimens from patients suffering with biliary atresia (n=66), intrahepatic bile duct paucity (n=15), and neonatal hepatitis (n=21).
RESULTS
The gender distribution was nearly equal for the patients with biliary atresia and intrahepatic bile duct paucity, whereas males predominated for the cases of neonatal hepatitis. Only the gamma-glutamyl transferase level differed significantly amongst the groups. The diagnostic features for making the differential diagnosis of bile duct lesions included marked bile ductular proliferation, severe fibrosis, and bile duct loss. The difference of the average percentage of portal tracts with bile duct loss was statistically significant between the patients with intrahepatic bile duct paucity (73.9%) and those patients with neonatal hepatitis (39.1%) (p<0.001).
CONCLUSIONS
Bile ductular proliferation, bile duct loss, and advanced fibrosis are useful for the differential diagnosis of neonatal cholestasis. Moreover, stricter diagnostic criteria for bile duct loss (more than 2/3 of bile ducts) should be applied for the definitive diagnosis of intrahepatic bile duct paucity, because bile duct loss also frequently occurs in infants suffering with neonatal hepatitis.

Citations

Citations to this article as recorded by

False-negative Hepatobiliary Scintigraphy for Biliary Atresia
Hyunji Kim, Sujin Park, Sejin Ha, Jae Seung Kim, Dae Yeon Kim, Minyoung Oh
Nuclear Medicine and Molecular Imaging.2019; 53(5): 356. CrossRef
Morphometric assessment of liver fibrosis may enhance early diagnosis of biliary atresia
Ahmed F. Abdalla, Abeer Fathy, Khaled R. Zalata, Ahmed Megahed, Ahmed Abo-Alyazeed, Mohammed Ezz El regal
World Journal of Pediatrics.2013; 9(4): 330. CrossRef
Differential hepatic expression of CD56 can discriminate biliary atresia from other neonatal cholestatic disorders
Mostafa Mohamed Sira, Mohamed Abdel-Salam El-Guindi, Magdy Anwar Saber, Nermin Ahmad Ehsan, Marwa Sabry Rizk
European Journal of Gastroenterology & Hepatology.2012; 24(10): 1227. CrossRef
Biliary Atresia: A Multidisciplinary Approach to Diagnosis and Management
Roger Klein Moreira, Rodrigo Cabral, Robert A. Cowles, Steven J. Lobritto
Archives of Pathology & Laboratory Medicine.2012; 136(7): 746. CrossRef
Tentative Proposal of Optimal Timing of Kasai Operation for Biliary Atresia Based on Fibroscan Results
Hwa Young Lee, Young A Park, Seok Joo Han, Hong Koh
Korean Journal of Pediatric Gastroenterology and Nutrition.2011; 14(1): 74. CrossRef

Case Reports

Nasal Chondromesenchymal Hamartoma: A Case Report.: Jun Kang, Young Ok Hong, Geung Hwan Ahn, Young Min Kim, Hee Jeong Cha, Hye Jeong Choi; Korean J Pathol. 2007;41(4):258-262.

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Abstract PDF: We report a case of nasal chondromesenchymal hamartoma. A 14-year-old boy presented with a 5 cm sized mass in the left maxillary sinus, facial swelling and a loose tooth. A subtotal left maxillectomy with a bone graft was performed. The excised mass was composed of partly encapsulated, solid and cystic fragments of soft tissues. The mass contained chondroid and myxoid areas consisting of mesenchymal tissues including hyaline cartilage, osteoid and spindle cells in various proportions. The hyaline cartilage component was the most prominent. The spindle cell component had a fibrous matrix with variable myxoid or sclerotic changes. Thick hyalinized eosinophilic osteoid-like trabeculae were focally present. Immunohistochemically, all the mesenchymal cells tested positive for vimentin. The chondrocytes tested positive for the S-100 protein, and the spindle cell component showed focal immunoreactivity for smooth muscle actin and desmin. However, the cells were negative to pan-cytokeratin and p63.

Intraneural Perineurioma in the Tongue: A Case Report.: Jun Kang, Shin Kwang Khang, Jene Choi, Jeong Won Kim, Eul Ju Seo, Bu kyu Lee, Eunsil Yu; Korean J Pathol. 2007;41(1):51-54.

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Abstract PDF: We report a case of an intraneural perineurioma that developed in an unusual location, the tongue. A 16-year-old male presented with a 1 cm sized protruding submucosal mass in his tongue without any sensory or motor signs or symptoms. The mass was excised. The mucosa was intact, with an ill-defined firm mass measuring 1.0 x 0.8 x 0.6 cm in the submucosa and muscle. The cut surface of the mass was pinkish gray and fibrotic. Microscopically, the mass contained tortuous and thickened peripheral nerve bundles in the submucosa, showing onion bulb like structures. The onion bulb like structures consisted of centrally located S-100 protein positive Schwann cells surrounded by Glut-1 positive perineurial cells. The FISH study did not reveal any genetic aberrations in chromosome 22.

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