Journal of Pathology and Translational Medicine

Case Studies

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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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
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Hepatoid thymic carcinoma: a case report of a rare subtype of thymic carcinoma: Ji-Seon Jeong, Hyo Jeong Kang, Uiree Jo, Min Jeong Song, Soon Yeol Nam, Joon Seon Song; J Pathol Transl Med. 2021;55(3):230-234. Published online April 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.03.10

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Abstract PDF

Hepatoid thymic carcinoma is an extremely rare subtype of primary thymus tumor resembling “pure” hepatoid adenocarcinomas with hepatocyte paraffin 1 (Hep-Par-1) expression. A 53-year-old man presented with voice change and a neck mass. Multiple masses involving the thyroid, cervical and mediastinal lymph nodes, and lung were detected on computed tomography. Papillary thyroid carcinoma was confirmed by biopsy, and the patient underwent neoadjuvant chemoradiation therapy. However, the anterior mediastinal mass was enlarged after the treatment whereas the multiple masses in the thyroid and neck decreased in size. Microscopically, polygonal tumor cells formed solid sheets or trabeculae resembling hepatocytes and infiltrated remnant thymus. The tumor cells showed immunopositivity for cytokeratin 7, cytokeratin 19, and Hep-Par-1 and negativity for α-fetoprotein. Possibilities of germ cell tumor, squamous cell carcinoma, and metastasis of thyroid papillary carcinoma were excluded by immunohistochemistry. This report on the new subtype of thymic carcinoma is the third in English literature thus far.

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Hepatoid tumors of the gastrointestinal/pancreatobiliary district: morphology, immunohistochemistry, and molecular profiles
Paola Mattiolo, Aldo Scarpa, Claudio Luchini
Human Pathology.2023; 132: 169. CrossRef

Review

Standardized Pathology Report for Colorectal Cancer, 2nd Edition: Baek-hui Kim, Joon Mee Kim, Gyeong Hoon Kang, Hee Jin Chang, Dong Wook Kang, Jung Ho Kim, Jeong Mo Bae, An Na Seo, Ho Sung Park, Yun Kyung Kang, Kyung-Hwa Lee, Mee Yon Cho, In-Gu Do, Hye Seung Lee, Hee Kyung Chang, Do Youn Park, Hyo Jeong Kang, Jin Hee Sohn, Mee Soo Chang, Eun Sun Jung, So-Young Jin, Eunsil Yu, Hye Seung Han, Youn Wha Kim; J Pathol Transl Med. 2020;54(1):1-19. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.28

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The first edition of the ‘Standardized Pathology Report for Colorectal Cancer,’ which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of “standard data elements” and “conditional data elements.” Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as “standard data elements,” while other prognostic factors and factors related to adjuvant therapy are classified as “conditional data elements” so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.

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Original Articles

Progressive Familial Intrahepatic Cholestasis in Korea: A Clinicopathological Study of Five Patients: Hyo Jeong Kang, Soon Auck Hong, Seak Hee Oh, Kyung Mo Kim, Han-Wook Yoo, Gu-Hwan Kim, Eunsil Yu; J Pathol Transl Med. 2019;53(4):253-260. Published online May 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.05.03

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Abstract PDF

Background
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive liver diseases that present as neonatal cholestasis. Little is known of this disease in Korea.
Methods
The records of five patients histologically diagnosed with PFIC, one with PFIC1 and four with PFIC2, by liver biopsy or transplant were reviewed, and ATP8B1 and ABCB11 mutation status was analyzed by direct DNA sequencing. Clinicopathological characteristics were correlated with genetic mutations.
Results
The first symptom in all patients was jaundice. Histologically, lobular cholestasis with bile plugs was the main finding in all patients, whereas diffuse or periportal cholestasis was identified only in patients with PFIC2. Giant cells and ballooning of hepatocytes were observed in three and three patients with PFIC2, respectively, but not in the patient with PFIC1. Immunostaining showed total loss of bile salt export pump in two patients with PFIC2 and focal loss in two. Lobular and portal based fibrosis were more advanced in PFIC2 than in PFIC1. ATP8B1 and ABCB11 mutations were identified in one PFIC1 and two PFIC2 patients, respectively. One PFIC1 and three PFIC2 patients underwent liver transplantation (LT). At age 7 months, one PFIC2 patient was diagnosed with concurrent hepatocellular carcinoma and infantile hemangioma in an explanted liver. The patient with PFIC1 developed steatohepatitis after LT. One patient showed recurrence of PFIC2 after 10 years and underwent LT.
Conclusions
PFIC is not rare in patients with neonatal cholestasis of unknown origin. Proper clinicopathologic correlation and genetic testing can enable early detection and management.

Citations

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Progressive Familial Intrahepatic Cholestasis: A Descriptive Study in a Tertiary Care Center
Fahad I. Alsohaibani, Musthafa C. Peedikayil, Abdulaziz F. Alfadley, Mohamed K. Aboueissa, Faisal A. Abaalkhail, Saleh A. Alqahtani, Dirk Uhlmann
International Journal of Hepatology.2023; 2023: 1. CrossRef
Next-generation sequencing panel test results in pediatric patients with progressive familial intrahepatic cholestasis: a single-center experience
Ali TOPAK
The European Research Journal.2023; 9(6): 1438. CrossRef
Progressive Familial Intrahepatic Cholestasis: A Study in Children From a Liver Transplant Center in India
Sagar Mehta, Karunesh Kumar, Ravi Bhardwaj, Smita Malhotra, Neerav Goyal, Anupam Sibal
Journal of Clinical and Experimental Hepatology.2022; 12(2): 454. CrossRef
Liver transplantation in pediatric patients with progressive familial intrahepatic cholestasis: Single center experience of seven cases
Jung-Man Namgoong, Shin Hwang, Hyunhee Kwon, Suhyeon Ha, Kyung Mo Kim, Seak Hee Oh, Seung-Mo Hong
Annals of Hepato-Biliary-Pancreatic Surgery.2022; 26(1): 69. CrossRef
Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review
Christos D. Kakos, Ioannis A. Ziogas, Charikleia D. Demiri, Stepan M. Esagian, Konstantinos P. Economopoulos, Dimitrios Moris, Georgios Tsoulfas, Sophoclis P. Alexopoulos
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Morphology of transplanted liver in recurrent progressive familial intrahepatic cholestasis type 2
I. M. Iljinsky, N. P. Mozheiko, O. M. Tsirulnikova
Russian Journal of Transplantology and Artificial Organs.2021; 22(4): 192. CrossRef

Guanabenz Acetate Induces Endoplasmic Reticulum Stress–Related Cell Death in Hepatocellular Carcinoma Cells: Hyo Jeong Kang, Hyang Sook Seol, Sang Eun Lee, Young-Ah Suh, Jihun Kim, Se Jin Jang, Eunsil Yu; J Pathol Transl Med. 2019;53(2):94-103. Published online January 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.01.14

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Abstract PDF Supplementary Material

Background
Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients.
Methods
Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting.
Results
Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest.
Conclusions
Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.

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Caleb L. Lines, Morgan J. McGrath, Tanis Dorwart, Crystal S. Conn
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Case Study

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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Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
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Bilateral Diffuse Nodular Pulmonary Ossification Mimicking Metastatic Disease in a Patient with Fibrolamellar Hepatocellular Carcinoma
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Hepatocellular carcinoma arising from hepatic adenoma in a young woman
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Brief Case Report

Adenocarcinoma Arising in Gastric Duplication Cyst: Hyo Jeong Kang, Se Jin Jang, Young Soo Park; Korean J Pathol. 2014;48(2):159-161. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.159

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Original Article

Idiopathic Duct Centric Pancreatitis in Korea: A Clinicopathological Study of 14 Cases.: Hyo Jeong Kang, Tae Jun Song, Eunsil Yu, Jihun Kim; Korean J Pathol. 2011;45(5):491-497.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.491

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Abstract PDF: BACKGROUND
Idiopathic duct centric pancreatitis (IDCP) is a subtype of autoimmune pancreatitis (AIP) that is histologically characterized by granulocytic epithelial lesion and scarce IgG4-positive cells. This subtype of AIP has not been documented in Asian countries.
METHODS
We reviewed 38 histologically confirmed AIP cases and classified them into lymphoplasmacytic sclerosing pancreatitis (LPSP) and IDCP. Then, clinicopathological characteristics were compared between LPSP and IDCP.
RESULTS
Fourteen cases (36.8%) were IDCP. IDCP affected younger patients more than LPSP. IDCP was associated with ulcerative colitis in 35.7% of cases, whereas LPSP was associated with IgG4-related sclerosing diseases such as cholangitis, retroperitoneal fibrosis or sialadenitis in 41.7% of cases. IDCP was microscopically characterized by neutrophilic ductoacinitis with occasional granulocytic epithelial lesions, whereas LPSP was characterized by storiform inflammatory cell-rich fibrosis and obliterative phlebitis. IgG4-positive cells were not detected in any IDCP case but more than 20 IgG4-positive cells per high-power-field were invariably detected in LPSP cases. All patients with IDCP responded dramatically to steroids without recurrence, whereas 33.3% of patients with LPSP developed recurrences.
CONCLUSIONS
IDCP is clinicopathologically distinct from LPSP and can be diagnosed when neutrophilic ductoacinitis or granulocytic epithelial lesions are observed in a pancreatic biopsy under the appropriate clinical setting.

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