Journal of Pathology and Translational Medicine

Case Study

Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder: Jiyoon Jung, Yang-Seok Chae, Chul Hwan Kim, Youngseok Lee, Jeong Hyeon Lee, Dong-Sik Kim, Young-Dong Yu, Joo Young Kim; J Pathol Transl Med. 2018;52(2):121-125. Published online October 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.08.20

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Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.

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Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?
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Original Article

Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients: Sung Joo Kim, Soyeon An, Jae Hoon Lee, Joo Young Kim, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong; J Pathol Transl Med. 2017;51(4):388-395. Published online June 8, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.19

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Abstract PDF

Background
Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients.
Methods
To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival.
Results
PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses.
Conclusions
Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

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Brief Case Report

Hyalinizing Cholecystitis and Associated Carcinoma: A Case Report: Youngjin Kang, Yang-Seok Chae, Chul Hwan Kim, Youngseok Lee, Dong-Sik Kim, Young-Dong Yu, Joo Young Kim; J Pathol Transl Med. 2018;52(1):64-66. Published online April 4, 2017; DOI: https://doi.org/10.4132/jptm.2016.11.04

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Original Articles

Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry: Jiyoon Jung, Youngjin Kang, Yoo Jin Lee, Eojin Kim, Bokyung Ahn, Eunjung Lee, Joo Young Kim, Jeong Hyeon Lee, Youngseok Lee, Chul Hwan Kim, Yang-Seok Chae; J Pathol Transl Med. 2017;51(2):129-136. Published online February 14, 2017; DOI: https://doi.org/10.4132/jptm.2016.12.09

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Abstract PDF

Background
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses. Methods: In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. Results: Based on IHC, 7/61 primary tumors (11.4%) showed deficient MMR systems, while 13/61 secondary tumors (21.3%) showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. Conclusions: Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61). These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.

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Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors: Eun-Mi Son, Joo Young Kim, Soyeon An, Ki-Byung Song, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong; J Pathol Transl Med. 2015;49(1):30-36. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.23

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Abstract PDF

Background
Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients. Methods: To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors. Results: Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses. Conclusions: CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.

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Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients
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Brief Case Report

Peritoneal Carcinosarcoma and Ovarian Papillary Serous Carcinoma Are the Same Origin: Analysis of TP53 Mutation and Microsatellite Suggests a Monoclonal Origin: Chang Gok Woo, Dae Shik Suh, Joo Young Kim, Chang Ohk Sung, Jene Choi, Kyu-Rae Kim; Korean J Pathol. 2014;48(6):449-453. Published online December 31, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.6.449

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A successfully treated primary peritoneal carcinosarcoma and serous carcinoma of stage IIIC rescued from hypovolemic shock due to tumor rupture
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Taiwanese Journal of Obstetrics and Gynecology.2019; 58(2): 296. CrossRef
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Sharlene Helene C. See, Amir Behdad, Kruti P. Maniar, Luis Z. Blanco
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Case Reports

Clinicopathologic Analysis of the Liver Explant with Severe Hepatitis A Virus Infection.: Joo Young Kim, Sung Gyu Lee, Shin Hwang, Ji Hoon Kim, Se Jin Jang, Eunsil Yu; Korean J Pathol. 2011;45:S48-S52.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S48

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Abstract PDF: The incidence of severe hepatitis A virus (HAV) infection has been increasing. However, clinicopathologic features of severe HAV infection that lead to liver transplantation (LT) have not been reported in Korea. We retrieved 16 LT cases with HAV infection during the last 3 years at Asan Medical Center, Seoul, Korea. Fifteen cases progressed to hepatic encephalopathy. Thirteen cases survived with or without complications, and three patients died of sepsis. The explanted liver showed massive or zonal necrosis with moderate to severe cholestasis. The zonal distribution of necrosis was frequently associated with endothelialitis of portal and/or central veins. Degenerative changes of hepatocytes were various in degree and distribution. Viral inclusions were suspected in two cases. Although HAV infection is usually confirmed by serological tests, significant venulitis of central and/or portal veins and viral inclusions, which are rarely observed, can suggest an HAV infection as a cause of massive hepatic necrosis of unknown mechanism.

IgG4-Related Sclerosing Sialadenitis: Report of Three Cases.: Ji Seon Bae, Joo Young Kim, Sang Hak Han, Seung Ho Choi, Kyung Ja Cho; Korean J Pathol. 2011;45:S36-S40.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S36

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Chronic sclerosing sialadenitis, Mikulicz disease or Kuttner tumor has been recently recognized as a spectrum of IgG4-related sclerosing disease. IgG4-related disease is characterized by a high serum IgG4 level and tissue infiltration of IgG4-positive plasmacytes. We report three cases of chronic sclerosing sialadenitis with variably associated systemic involvement. All patients presented with a submandibular mass or swelling, and all the resected submandibular glands showed diffuse lymphocytic infiltration, lymphoid follicles, and septal fibrosis. Two of the specimens revealed numerous IgG-positive plasma cells, most of which were IgG4-positive on immunohistochemical staining. One of them was associated with dacryoadenitis and hypophysitis. The other patient had ureterorenal lesions. Immunohistochemical study was unavailable in remaining one case, but the histologic features along with elevated IgG level and associated pancreatitis supported the diagnosis. All patients received steroid therapy postoperatively and are doing well. Salivary gland involvement in IgG4-related fibrosclerosis should be recognized in systemic medical pathology.

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A Case of Immunoglobulin G4-Related Sialadenitis and Dacryoadenitis
Kyoung Kyu Lee, Hun Po Cho, Young Min Lee, Jun Ho Park
Korean Journal of Otorhinolaryngology-Head and Neck Surgery.2013; 56(7): 444. CrossRef

Original Article

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.

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