Journal of Pathology and Translational Medicine

Review

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists: Soomin Ahn, Yoonjin Kwak, Gui Young Kwon, Kyoung-Mee Kim, Moonsik Kim, Hyunki Kim, Young Soo Park, Hyeon Jeong Oh, Kyoungyul Lee, Sung Hak Lee, Hye Seung Lee; J Pathol Transl Med. 2024;58(3):103-116. Published online April 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.15

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Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2–negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti–programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

Citations

Citations to this article as recorded by

Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIG
F. Lordick, M.E. Mauer, G. Stocker, C.A. Cella, I. Ben-Aharon, G. Piessen, L. Wyrwicz, G. Al-Haidari, T. Fleitas-Kanonnikoff, V. Boige, R. Lordick Obermannová, U.M. Martens, C. Gomez-Martin, P. Thuss-Patience, V. Arrazubi, A. Avallone, K.K. Shiu, P. Artru
Annals of Oncology.2024;[Epub] CrossRef
PD-L1 thresholds predict efficacy of immune checkpoint inhibition in first-line treatment of advanced gastroesophageal adenocarcinoma. A systematic review and meta-analysis of seven phase III randomized trials
V. Formica, C. Morelli, L. Fornaro, S. Riondino, M. Rofei, E. Fontana, E.C. Smyth, M. Roselli, H.-T. Arkenau
ESMO Open.2024; 9(11): 103967. CrossRef

Case Study

Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature: Hyun Jung Kwon, Ji-Won Kim, Haeryoung Kim, YoungRok Choi, Soomin Ahn; J Pathol Transl Med. 2018;52(4):232-237. Published online May 25, 2018; DOI: https://doi.org/10.4132/jptm.2018.05.17

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Abstract PDF

Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC.

Citations

Citations to this article as recorded by

Case report: mixed large-cell neuroendocrine and hepatocellular carcinoma of the liver
Xin Gao, Heng Wang, Zheyu Niu, Meng Liu, Xiaohan Kong, Hongrui Sun, Chaoqun Ma, Huaqiang Zhu, Jun Lu, Xu Zhou
Frontiers in Oncology.2024;[Epub] CrossRef
Mixed glandular neuroendocrine carcinoma of the endometrium with hypercalcemic crisis
Mei Luo, Xiaoxia Yu, Zhongpei Chen, Zhenhan Li
The American Journal of the Medical Sciences.2024;[Epub] CrossRef
Mixed Primary Hepatocellular Carcinoma and Hepatic Neuroendocrine Carcinoma: Case Report and Literature Review
Woo Young Shin, Keon Young Lee, Kyeong Deok Kim
Medicina.2023; 59(2): 418. CrossRef
Comparison of Metastatic Patterns Among Neuroendocrine Tumors, Neuroendocrine Carcinomas, and Nonneuroendocrine Carcinomas of Various Primary Organs
Hyung Kyu Park, Ghee Young Kwon
Journal of Korean Medical Science.2023;[Epub] CrossRef
Immunohistochemical characterization of a steroid-secreting oncocytic adrenal carcinoma responsible for paraneoplastic hyperparathyroidism
Magalie Haissaguerre, Estelle Louiset, Christofer C Juhlin, Adam Stenman, Christophe Laurent, Hélène Trouette, Hervé Lefebvre, Antoine Tabarin
European Journal of Endocrinology.2023; 188(4): K11. CrossRef
Neuroendocrine neoplasms of the biliary tree, liver and pancreas: a pathological approach
Claudio Luchini, Giuseppe Pelosi, Aldo Scarpa, Paola Mattiolo, Deborah Marchiori, Roberta Maragliano, Fausto Sessa, Silvia Uccella
Pathologica.2021; 113(1): 28. CrossRef
Contrast-Enhanced Ultrasound Findings of Hepatocellular Carcinoma With Neuroendocrine Carcinoma: A Case Report
Hong Wang, Dan Yang, Zhenru Wu, Yan Luo, Wenwu Ling
Frontiers in Medicine.2021;[Epub] CrossRef
Combined primary hepatic neuroendocrine carcinoma and hepatocellular carcinoma: case report and literature review
Akira Nakano, Kenichi Hirabayashi, Hiroshi Yamamuro, Taro Mashiko, Yoshihito Masuoka, Seiichiro Yamamoto, Soji Ozawa, Toshio Nakagohri
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Hsuan Yeh, Chung-Cheng Chiang, Tzung-Hai Yen
World Journal of Gastroenterology.2021; 27(26): 4104. CrossRef
Severe hypercalcaemia from ectopic intact parathyroid hormone secretion treated with continuous renal replacement therapy in a patient with two malignancies
Nathaniel Hocker, Maria Story, Alysa Lerud, Sarat Kuppachi
BMJ Case Reports.2021; 14(6): e242172. CrossRef
Parathyroid Carcinoma and Ectopic Secretion of Parathyroid hormone
Filomena Cetani, Elena Pardi, Claudio Marcocci
Endocrinology and Metabolism Clinics of North America.2021; 50(4): 683. CrossRef
Primary hepatic neuroendocrine cancer coexisted with hepatocellular carcinoma: a case report
Chikara Ebisutani, Seitetsu Yoon, Toshiki Hyodo, Takafumi Watanabe, Hirofumi Okada, Yutaka Shirakawa, Yoshio Sakamoto, Shigeya Hirohata
Kanzo.2020; 61(3): 122. CrossRef
Two-in-one: A pooled analysis of primary hepatic neuroendocrine carcinoma combined/collided with hepatocellular carcinoma
Jia-Xi Mao, Fei Teng, Ke-Yan Sun, Cong Liu, Guo-Shan Ding, Wen-Yuan Guo
Hepatobiliary & Pancreatic Diseases International.2020; 19(4): 399. CrossRef
Primary hepatic neuroendocrine carcinoma coexisting with distal cholangiocarcinoma
Qi Xin, Rong Lv, Cheng Lou, Zhe Ma, Gui-Qiu Liu, Qin Zhang, Hai-Bo Yu, Chuan-Shan Zhang
Medicine.2020; 99(26): e20854. CrossRef
Mixed hepatocellular carcinoma-neuroendocrine carcinoma—A diagnostic and therapeutic challenge
Nusrat Jahan, Irfan Warraich, Edwin Onkendi, Sanjay Awasthi
Current Problems in Cancer: Case Reports.2020; 1: 100020. CrossRef

Case Report

Combined Epithelial-Myoepithelial Carcinoma and Basal Cell Adenocarcinoma of the Parotid Gland: A case report.: Young Kyung Bae, Dong Sug Kim, Jang Soo Suh, Jae Yun Ro; Korean J Pathol. 1999;33(6):453-456.

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Abstract PDF: Epithelial-myoepithelial carcinoma and basal cell adenocarcinoma are uncommon, low-grade malignant epithelial neoplasms of salivary gland. They occur predominantly in the parotid glands with frequent recurrences and occasional distant metastases. We report an unusual case of combined epithelial-myoepithelial carcinoma and basal cell adenocarcinoma within the same mass of the parotid gland in a 32-year-old woman. To the best of our knowledge, this is the first such a combined carcinoma case.

Original Article

Combined Hepatocellular-Cholangiocarcinoma: Analysis of 8 cases with special reference to their growth patterns.: Yong Il Kim, Geun Kook Lee, Woo Ho Kim, Eun Sil Yu, Ghee Young Choe; Korean J Pathol. 1992;26(3):229-241.

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Abstract PDF: Eight cases of combine hepatocellular-cholangiocarcinoma(HCC-CC) of the liver were analysed along with their growth patterns and histologic subtypes to draw a possible implication in understanding of their histogenesis. The relative incidence of combined HCC-CC among the surgically resected primary carcinomas of the liver(485 cases) was 1.6%. The combination patterns varied and were classified as follows; the multinodular tumor, each consisting of HCC or CC element(type 1) was found in 1 case, the single tumor mass with two distinct compartments of HCC and CC(type 2) in 3, and the single tumor with random mixture of two elements(type 3) comprised the remaining 4 cases. Of the 7 cases of single tumor mass(type 2 and 3) HCC and CC comprised the major component in 5 and 2 cases, respectively. The histologic features of both HCC and CC elements were not different from those of isolated HCC and CC, except for two of CC element in type 3 which disclosed the intermediated differentiation or socalled cholangiolocellular carcinoma in part. We conclude that there is no significant difference in the relative incidence of combined HCC-CC among primary carcinomas of the liver and their subtypes compared to that in other countries, regardless of high incidence of both HCC and CC in Korea. Also, we discussed a possible histogenisis along a hypothesis that some of the combined HCC-CC be the consequence of interposition of different cell type from a new subclone into the growth of an initial single cell type of primary carcinoma of the liver.

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