Journal of Pathology and Translational Medicine

Case Study

Hepatic small vessel neoplasm: not totally benign, not yet malignant: Madison Miranda, David Howell, Tony El Jabbour; J Pathol Transl Med. 2023;57(5):273-277. Published online August 24, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.19

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Abstract PDF: Hepatic small vessel neoplasm (HSVN) is a rare vascular tumor with few reports in the literature. While imaging findings may show characteristic enhancement patterns, limited available literature may not reveal the full potential for image-based diagnosis. Histologically, HSVN mimics other entities, though certain morphologic and immunohistochemical findings provide clues for diagnosis. However, HSVN still provides diagnostic challenges, especially on core biopsies with limited material for morphologic and molecular evaluation. While current recommendations are surgical resection and close observation, the long-term course of the tumor is unknown. We report a case of HSVN in a liver with additional feature of organized lymphoid aggregates necessitating additional hematopathology consultation and workup to rule out concurrent entities.

Review

A review of liver fibrosis and cirrhosis regression: Michael J. Lee; J Pathol Transl Med. 2023;57(4):189-195. Published online June 20, 2023; DOI: https://doi.org/10.4132/jptm.2023.05.24

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Cirrhosis has traditionally been considered an irreversible process of end-stage liver disease. With new treatments for chronic liver disease, there is regression of fibrosis and cirrhosis, improvement in clinical parameters (i.e. liver function and hemodynamic markers, hepatic venous pressure gradient), and survival rates, demonstrating that fibrosis and fibrolysis are a dynamic process moving in two directions. Microscopically, hepatocytes push into thinning fibrous septa with eventual perforation leaving behind delicate periportal spikes in the portal tracts and loss of portal veins. Obliterated portal veins during progressive fibrosis and cirrhosis due to parenchymal extinction, vascular remodeling and thrombosis often leave behind a bile duct and hepatic artery within the portal tract. Traditional staging classification systems focused on a linear, progressive process; however, the Beijing classification system incorporates both the bidirectional nature for the progression and regression of fibrosis. However, even with regression, vascular lesions/remodeling, parenchymal extinction and a cumulative mutational burden place patients at an increased risk for developing hepatocellular carcinoma and should continue to undergo active clinical surveillance. It is more appropriate to consider cirrhosis as another stage in the evolution of chronic liver disease as a bidirectional process rather than an end-stage, irreversible state.

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Vasudevan Sekar, Venkateish VP, Vani Vijay, Annapoorna BR, Nivya Vijayan, Madan Kumar Perumal
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Cells.2023; 12(17): 2127. CrossRef

Case Studies

Hepatic carcinoma expressing inhibin: case report of a proposed novel entity and review of the literature: Antonia Syrnioti, Evangelia Athanasiou, Prodromos Hytiroglou; J Pathol Transl Med. 2022;56(4):225-230. Published online June 15, 2022; DOI: https://doi.org/10.4132/jptm.2022.04.07

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Abstract PDF: Hepatic carcinoma expressing inhibin is a recently described neoplasm with varied architecture, including trabecular, pseudoglandular, follicular/microcystic, organoid, solid and tubular patterns of growth. We report a case of hepatic carcinoma expressing inhibin that occurred in a 47-year-old woman presenting with epigastric and back pain. The tumor was located in the left hepatic lobe and measured 12 cm in diameter. On immunohistochemical stains, the neoplastic cells were positive for inhibin, as well as cytokeratins 7, 8/18 and 19. There was mild focal expression of synaptophysin, and lack of expression of hepatocytic markers. The histogenesis of hepatic carcinoma expressing inhibin is presently uncertain. From a practical point of view, this neoplasm can potentially cause diagnostic pitfalls by simulating other primary or metastatic tumors, such as hepatocellular carcinoma, cholangiocarcinoma, neuroendocrine tumors, and follicular carcinoma of thyroid gland. Performing inhibin immunostain could assist in the differential diagnosis of liver tumors with unusual histologic features.

Primary hepatic mixed germ cell tumor in an adult: Hyun-Jung Sung, Jihun Kim, Kyu-rae Kim, Shinkyo Yoon, Jae Hoon Lee, Hyo Jeong Kang; J Pathol Transl Med. 2021;55(5):355-359. Published online August 3, 2021; DOI: https://doi.org/10.4132/jptm.2021.06.16

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Abstract PDF

Primary hepatic mixed germ cell tumor (GCT) is very rare, and less than 10 cases have been reported. We report a case of mixed GCT composed of a choriocarcinoma and yolk sac tumor, which occurred in the liver of a 40-year-old woman. A large mass was detected by computed tomography solely in the liver. Serum β-human chorionic gonadotropin (hCG) was highly elevated, otherwise, other serum tumor markers were slightly elevated or within normal limits. For hepatic choriocarcinoma, neoadjuvant chemotherapy was administered, followed by right lobectomy. Histologic features of the resected tumor revealed characteristic choriocarcinoma features with diffuse positivity for hCG in the syncytiotrophoblasts and diffuse positivity for α-fetoprotein and Sal-like protein 4 in the yolk sac tumor components. Primary malignant GCT in the liver is associated with a poor prognosis and requires specific treatment. Therefore, GCT should be considered during a differential diagnosis of a rapidly growing mass in the liver.

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Testicular Seminoma in Prostate: Case Report and Review of Literature
Peter Lesko, Jana Obertova, Karol Kajo, Katarina Rejlekova, Zuzana Orszaghova, Viera Lehotska, Martina Ondrusova, Michal Chovanec, Dalibor Ondrus, Michal Mego
Clinical Genitourinary Cancer.2024; 22(2): 210. CrossRef

Primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: Soyeon Choi, Ji Hye Kim, Kyungbin Kim, Misung Kim, Hye Jeong Choi, Young Min Kim, Jae Hee Suh, Min Jung Seo, Hee Jeong Cha; J Pathol Transl Med. 2020;54(4):340-345. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.18

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Abstract PDF

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), is one of the specific type of low-grade B-cell lymphoma not infrequently found worldwide. It typically involves mucosal sites such as stomach and conjunctiva; however, primary hepatic MALT lymphoma has been extremely rarely reported. We describe a case of hepatic MALT lymphoma in a 70-year-old male patient who underwent left hepatectomy due to the incidentally detected liver masses at a medical checkup. The resected specimen revealed multinodular masses consisting of small-to-intermediate-sized lymphoid cells with serpentine pattern and focal lymphoepithelial lesions. The tumor cells were diffusely positive for CD20 and Bcl-2 but negative for CD3, CD10, CD5, CD23, CD43, and cyclinD1. The Ki-67 labeling index was 10% and immunoglobulin heavy chain gene rearrangement study confirmed monoclonal proliferation. In this paper, we discuss several unique clinicopathologic characteristics which will be helpful to the differential diagnosis of hepatic MALT lymphoma.

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Primary hepatic mucosa-associated lymphoid tissue lymphoma: a case report and literature review
Tao He, Jieyu Zou
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“Speckled Enhancement” on Gd-EOB-DTPA Enhanced MR Imaging of Primary Hepatic Mucosa-associated Lymphoid Tissue Lymphoma
Ryota Hyodo, Yasuo Takehara, Ayumi Nishida, Masaya Matsushima, Shinji Naganawa
Magnetic Resonance in Medical Sciences.2023; 22(3): 273. CrossRef
Primary hepatic extranodal marginal zone B-cell mucosa-associated lymphoid tissue lymphoma treated by laparoscopic partial hepatectomy: a case report
Keisuke Okura, Satoru Seo, Hironori Shimizu, Hiroto Nishino, Tomoaki Yoh, Ken Fukumitsu, Takamichi Ishii, Koichiro Hata, Hironori Haga, Etsuro Hatano
Surgical Case Reports.2023;[Epub] CrossRef
Incidental Findings in Pediatric Patients: How to Manage Liver Incidentaloma in Pediatric Patients
Andrius Cekuolis, Dagmar Schreiber-Dietrich, Rasa Augustinienė, Heike Taut, Judy Squires, Edda L. Chaves, Yi Dong, Christoph F. Dietrich
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Wing Yu Lau, Kit‐Man Ho, Fiona Ka‐Man Chan, Shi Lam, Kai‐Chi Cheng
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18F-FDG Versus 68Ga-FAPI PET/CT in Visualizing Primary Hepatic Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
Yizhen Pang, Long Zhao, Qihang Shang, Tinghua Meng, Haojun Chen
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Primary hepatopancreatobiliary lymphoma: Pathogenesis, diagnosis, and management
Qianwen Wang, Kangze Wu, Xuzhao Zhang, Yang Liu, Zhouyi Sun, Shumei Wei, Bo Zhang
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Original Article

A scoring system for the diagnosis of non-alcoholic steatohepatitis from liver biopsy: Kyoungbun Lee, Eun Sun Jung, Eunsil Yu, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Woo Sung Moon, Jin Sook Jeong, Cheol Keun Park, Jae-Bok Park, Dae Young Kang, Jin Hee Sohn, So-Young Jin; J Pathol Transl Med. 2020;54(3):228-236. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.07

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Abstract PDF

Background
Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis.
Methods
Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses (‘not-NASH,’ ‘borderline,’ and ‘NASH’) of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system.
Results
Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52–0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH.
Conclusions
A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

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Debi Swertfeger, Ahlee Kim, Hannah Sexmith, Maria E. Moreno‐Fernandez, W. Sean Davidson, Michael Helmrath, Todd Jenkins, Tsuyoshi Okura, Esmond Geh, Stavra A. Xanthakos, Sara Szabo, Takahisa Nakamura, Senad Divanovic, Amy Sanghavi Shah
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Immunobiotic Bacteria Attenuate Hepatic Fibrosis through the Modulation of Gut Microbiota and the Activation of Aryl‐Hydrocarbon Receptors Pathway in Non‐Alcoholic Steatohepatitis Mice
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Lipid nanoparticle-mediated hepatocyte delivery of siRNA and silibinin in metabolic dysfunction-associated steatotic liver disease
Yifu Lyu, Xiuyi Yang, Lei Yang, Jinyu Dai, Huanyu Qin, Yunuo Zhou, Yunan Huang, Yanmei Wang, Di Wu, Qindai Shuai, Qilong Li, Xiaofei Xin, Lifang Yin
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Changes in indications for outpatient percutaneous liver biopsy over 5 years: from hepatitis C to fatty liver disease
Marlone Cunha-Silva, Luíza D. Torres, Mariana F. Fernandes, Tirzah de M. Lopes Secundo, Marina C.G. Moreira, Ademar Yamanaka, Leonardo T. Monici, Larissa B. Eloy da Costa, Daniel F. Mazo, Tiago Sevá-Pereira
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Case Studies

Adrenal Cortical Neoplasm with Uncertain Malignant Potential Arising in the Heterotopic Adrenal Cortex in the Liver of a Patient with Beckwith-Wiedemann Syndrome: Eun Na Kim, Dong Eun Song, Hee Mang Yoon, Beom Hee Lee, Chong Jai Kim; J Pathol Transl Med. 2019;53(2):129-135. Published online November 26, 2018; DOI: https://doi.org/10.4132/jptm.2018.11.13

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Abstract PDF

Patients with Beckwith-Wiedemann syndrome (BWS) are predisposed to developing embryonal tumors, with hepatoblastoma being the most common type. Our patient showed hemihypertrophy, macroglossia, and paternal uniparental disomy in chromosome 11 and was diagnosed with BWS. When the patient was 9 months old, a 2.5×1.5 cm oval hypoechoic exophytic mass was detected in the inferior tip of his right liver. Preoperative imaging identified it as hepatoblastoma; however, histologic, immunohistochemistry, and electron microscopic findings were compatible with adrenal cortical neoplasm with uncertain malignant potential. The origin of the adrenal tissue seemed to be heterotopic. Here, we describe for the first time an adrenal cortical neoplasm with uncertain malignant potential arising in the heterotopic adrenal cortex located in the liver of a patient with BWS.

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Functional adrenocortical carcinoma with adrenohepatic fusion: A case report
Pastor Escárcega-Fujigaki, Guillermo Hernández-Peredo Rezk, José de Jesús Loeza- Oliva, Anallely Luna-Hernández, Bethsaida Natali Arreguín-Cortés, Rafael López-Cruz
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Beckwith–Wiedemann syndrome: Clinical, histopathological and molecular study of two Tunisian patients and review of literature
Hela Sassi, Yasmina Elaribi, Houweyda Jilani, Imen Rejeb, Syrine Hizem, Molka Sebai, Nadia Kasdallah, Habib Bouthour, Samia Hannachi, Jasmin Beygo, Ali Saad, Karin Buiting, Dorra H’mida Ben‐Brahim, Lamia BenJemaa
Molecular Genetics & Genomic Medicine.2021;[Epub] CrossRef
Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment
Emilia Modolo Pinto, Carlos Rodriguez-Galindo, Catherine G. Lam, Robert E. Ruiz, Gerard P. Zambetti, Raul C. Ribeiro
Frontiers in Endocrinology.2021;[Epub] CrossRef

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.

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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
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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
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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
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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
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Hepatocellular Carcinoma Arising in a Huge Hepatocellular Adenoma with Bone Marrow Metaplasia: Hyo Jeong Kang, Hui Jeong Jeong, So-Woon Kim, Eunsil Yu, Young-Joo Lee, So Yeon Kim, Jihun Kim; J Pathol Transl Med. 2018;52(4):226-231. Published online December 27, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.12

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Abstract PDF

Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner.

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Hirotsugu Noguchi, Michiyo Higashi, Ryo Desaki, Takashi Tasaki, Mari Kirishima, Ikumi Kitazono, Kazuhiro Tabata, Akihide Tanimoto
International Journal of Surgical Pathology.2022; 30(3): 339. CrossRef
Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
Wenhua Shao, Orgil Jargalsaikhan, Mayuko Ichimura-Shimizu, Qinyi Cai, Hirohisa Ogawa, Yuko Miyakami, Kengo Atsumi, Mitsuru Tomita, Mitsuko Sutoh, Shunji Toyohara, Ryoji Hokao, Yasusei Kudo, Takeshi Oya, Koichi Tsuneyama
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Juan Putra, Linda D. Ferrell, Annette S.H. Gouw, Valerie Paradis, Arvind Rishi, Christine Sempoux, Charles Balabaud, Swan N. Thung, Paulette Bioulac-Sage
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Hepatocellular carcinoma arising from hepatic adenoma in a young woman
Haythem Yacoub, Hela Kchir, Dhouha Cherif, Hajer Hassine, Slim Haouet, Asma Ayari, Habiba Mizouni, Saber Mannai, Mohamed Tahar Khalfallah, Nadia Maamouri
Clinical Case Reports.2020; 8(9): 1659. CrossRef
Metanephric adenoma with osseous metaplasia and bone marrow elements
Alessandro Pietro Aldera, Jeff John, Dharshnee Chetty, Dhirendra Govender
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Erdheim-Chester Disease Involving Lymph Nodes and Liver Clinically Mimicking Lymphoma: A Case Report: Yeoun Eun Sung, Yoon Seo Lee, Jieun Lee, Kyo Young Lee; J Pathol Transl Med. 2018;52(3):183-190. Published online December 27, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.16

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Abstract PDF

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis and multisystem disease. First described in 1930, there are no more than 750 cases reported. The etiology remains unknown, but a majority of cases of ECD and Langerhans cell histiocytosis were found to have clonal mutations involving genes of the mitogen-activated protein kinase pathway. We recently encountered a 53-year-old male patient with extensive ECD involving the systemic lymph nodes, pleura, liver, and long bones clinically mimicking malignant lymphoma. Biopsies were performed at multiple sites, including a pleural mass, an external iliac lymph node, bone marrow, and the liver. Based on histopathological and immunohistochemical findings of positivity for CD68 and negativity for CD1a and S-100, the patient was diagnosed with ECD. Interferon-α was administered as the first-line treatment, but the patient rapidly progressed to hepatic failure after 2 months of treatment. We report this rare case of ECD clinically mimicking malignant lymphoma and diagnosed by careful pathological review.

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Original Articles

Prognosis of Hepatocellular Carcinoma after Liver Transplantation: Comparative Analysis with Partial Hepatectomy: Kyuho Lee, Kyoung-Bun Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang; J Pathol Transl Med. 2017;51(1):79-86. Published online December 25, 2016; DOI: https://doi.org/10.4132/jptm.2016.10.13

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Background
Liver transplantation (LT) is the treatment of choice for hepatocellular carcinoma (HCC). The aim of this study was to investigate the recurrence rate of HCC after LT and prognostic factors for recurrence by comparing LT with non-transplanted resection. Methods: The participants were 338 patients who underwent LT between 1996 and 2012 at Seoul National University Hospital (LT group) and 520 HCC patients who underwent partial hepatectomy between 1995 and 2006 (control group, non-LT group). Results: In the LT group, 68 of 338 patients (19.8%) showed relapse, and the recurrence rate was lower than that in the non-LT group (64.9%, 357/520, p < .001). Stratification analysis by American Joint Committee on Cancer (AJCC) stage showed that the stage I-II LT group had a lower recurrence rate than the non-LT group. Univariate comparative analysis demonstrated that multiplicity of tumor, tumor size, gross type, Edmondson- Steiner (ES) nuclear grade, extent of tumor, angioinvasion, AJCC stage, Milan criteria, University of California at San Francisco criteria on explant pathology (all p < .001), positive expression of cytokeratin 19 (p = .002), and preoperative α-fetoprotein (AFP) (p < .001) were predictors of tumor recurrence. In multivariate analysis, LT, preoperative AFP, multiplicity of tumor, extent of tumor, size of tumor, and ES nuclear grade were independent prognostic factors. Conclusions: LT might have a protective effect against the late recurrence of stage I-II HCC compared to non-LT, and the prognostic factors for recurrence were similar to previously well-known prognostic factors for HCC.

Citations

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Related Factors of Hepatocellular Carcinoma Recurrence Associated With Hyperglycemia After Liver Transplantation
Yujian Zheng, Qing Cai, Lishan Peng, Shibo Sun, Shaoping Wang, Jie Zhou
Transplantation Proceedings.2021; 53(1): 177. CrossRef
Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma
A.T. Akcam, A.G. Saritas, A. Ulku, A. Rencuzogullari
Transplantation Proceedings.2019; 51(4): 1147. CrossRef
Clustering Asian Countries According to the Trend of liver cancer Mortality Rates: an Application of Growth Mixture Models
Maryam Salari, Anoshirvan Kazemnejad, Farid Zayeri
Iranian Red Crescent Medical Journal.2017;[Epub] CrossRef

Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma: Kijong Yi, Hyunsung Kim, Yumin Chung, Hyein Ahn, Jongmin Sim, Young Chan Wi, Ju Yeon Pyo, Young-Soo Song, Seung Sam Paik, Young-Ha Oh; J Pathol Transl Med. 2016;50(5):327-336. Published online August 31, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.22

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Abstract PDF

Background
Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown.
Methods
Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between E-cadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated.
Results
E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient’s survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (> 40%) were independent prognostic factors for shorter overall survival.
Conclusions
Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.

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The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach
Mahdieh Razmi, Fatemeh Tajik, Farideh Hashemi, Ayna Yazdanpanah, Fatemeh Hashemi-Niasari, Adeleh Divsalar
Journal of Gastrointestinal Cancer.2024; 55(2): 599. CrossRef
Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma
Ruizhi Wang, Yichao Zhu, Hao Zhong, Xinyue Gao, Qiang Sun, Meifang He
Frontiers in Oncology.2022;[Epub] CrossRef
Dysregulated paired related homeobox 1 impacts on hepatocellular carcinoma phenotypes
Weronika Piorońska, Zeribe Chike Nwosu, Mei Han, Michael Büttner, Matthias Philip Ebert, Steven Dooley, Christoph Meyer
BMC Cancer.2021;[Epub] CrossRef

Interobserver Agreement on Pathologic Features of Liver Biopsy Tissue in Patients with Nonalcoholic Fatty Liver Disease: Eun Sun Jung, Kyoungbun Lee, Eunsil Yu, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Woo Sung Moon, Jin Sook Jeong, Cheol Keun Park, Jae-Bok Park, Dae Young Kang, Jin Hee Sohn, So-Young Jin; J Pathol Transl Med. 2016;50(3):190-196. Published online April 18, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.01

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Abstract PDF

Background
The histomorphologic criteria for the pathological features of liver tissue from patients with non-alcoholic fatty liver disease (NAFLD) remain subjective, causing confusion among pathologists and clinicians. In this report, we studied interobserver agreement of NAFLD pathologic features and analyzed causes of disagreement.
Methods
Thirty-one cases of clinicopathologically diagnosed NAFLD from 10 hospitals were selected. One hematoxylin and eosin and one Masson’s trichrome-stained virtual slide from each case were blindly reviewed with regard to 12 histological parameters by 13 pathologists in a gastrointestinal study group of the Korean Society of Pathologists. After the first review, we analyzed the causes of disagreement and defined detailed morphological criteria. The glass slides from each case were reviewed a second time after a consensus meeting. The degree of interobserver agreement was determined by multi-rater kappa statistics.
Results
Kappa values of the first review ranged from 0.0091–0.7618. Acidophilic bodies (k = 0.7618) and portal inflammation (k = 0.5914) showed high levels of agreement, whereas microgranuloma (k = 0.0984) and microvesicular fatty change (k = 0.0091) showed low levels of agreement. After the second review, the kappa values of the four major pathological features increased from 0.3830 to 0.5638 for steatosis grade, from 0.1398 to 0.2815 for lobular inflammation, from 0.1923 to 0.3362 for ballooning degeneration, and from 0.3303 to 0.4664 for fibrosis.
Conclusions
More detailed histomorphological criteria must be defined for correct diagnosis and high interobserver agreement of NAFLD.

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Review

Idiopathic Noncirrhotic Portal Hypertension: An Appraisal: Hwajeong Lee, Aseeb Ur Rehman, M. Isabel Fiel; J Pathol Transl Med. 2016;50(1):17-25. Published online November 11, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.23

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Abstract PDF

Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity.

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Original Article

Mdm2 and p53 Expression in Radiation-Induced Sarcomas of the Head and Neck: Comparison with De Novo Sarcomas: Min Jeong Song, Joon Seon Song, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Sung Bae Kim, Sang-wook Lee, Kyung-Ja Cho; Korean J Pathol. 2014;48(5):346-350. Published online October 27, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.5.346

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Abstract PDF

Background: The pathogenesis of radiation-induced sarcomas (RISs) is not well known. In RIS, TP53 mutations are frequent, but little is known about Mdm2-p53 interaction, which is a recent therapeutic target of sarcomas. Methods: We studied the immunohistochemical expression of Mdm2 and p53 of 8 RISs. The intervals between radiation therapy and diagnosis of secondary sarcomas ranged from 3 to 17 years. Results: Mdm2 expression was more common in de novo sarcomas than RISs (75% vs 37.5%), and p53 expression was more common in RISs than in de novo cases (75% vs 37.5%). While half of the RISs were Mdm2(–)/p53(+), none of de novo cases showed such combination; while half of de novo sarcomas were Mdm2(+)/p53(–), which are a candidate group of Mdm2 inhibitors, only 1 RIS showed such a combination. Variable immunoprofiles observed in both groups did not correlate with tumor types, except that all of 2 myxofibrosarcomas were Mdm2(+)/p53(+). Conclusions: In conclusion, we speculated that both radiation- induced and de novo sarcomagenesis are not due to a unique genetic mechanism. Mdm2- expression without p53 overexpression in 1 case of RIS decreases the future possibility of applying Mdm2 inhibitors on a subset of these difficult tumors.

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Radiation-Induced Sarcomas of the Head and Neck: A Systematic Review
Andrés Coca-Pelaz, Antti A. Mäkitie, Primož Strojan, June Corry, Avraham Eisbruch, Jonathan J. Beitler, Sandra Nuyts, Robert Smee, Johannes A. Langendijk, William M. Mendenhall, Cesare Piazza, Alessandra Rinaldo, Alfio Ferlito
Advances in Therapy.2021; 38(1): 90. CrossRef
Genomic Characterization of Radiation-Induced Intracranial Undifferentiated Pleomorphic Sarcoma
Christopher S. Hong, Edwin Partovi, James Clune, Anita Huttner, Henry S. Park, Sacit Bulent Omay, Balraj Mittal
Case Reports in Genetics.2021; 2021: 1. CrossRef
Radiation-Induced Sarcoma of the Head and Neck: A Review of the Literature
Lorenzo Giannini, Fabiola Incandela, Marco Fiore, Alessandro Gronchi, Silvia Stacchiotti, Claudia Sangalli, Cesare Piazza
Frontiers in Oncology.2018;[Epub] CrossRef

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