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Volume 52(2); March 2018
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Original Articles
Protein Phosphatase Magnesium-Dependent 1δ (PPM1D) Expression as a Prognostic Marker in Adult Supratentorial Diffuse Astrocytic and Oligodendroglial Tumors
Hui Jeong Jeong, Chang Gok Woo, Bora Lee, Shin Kwang Khang, Soo Jeong Nam, Jene Choi
J Pathol Transl Med. 2018;52(2):71-78.   Published online October 18, 2017
DOI: https://doi.org/10.4132/jptm.2017.10.21
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  • 1 Citations
AbstractAbstract PDFSupplementary Material
Background
Protein phosphatase magnesium-dependent 1δ (PPM1D) is a p53-induced serine/ threonine phosphatase, which is overexpressed in various human cancers. A recent study reported that a mutation in the PPM1D gene is associated with poor prognosis in brainstem gliomas. In this study, we evaluated the utility of PPM1D as a prognostic biomarker of adult supratentorial diffuse astrocytic and oligodendroglial tumors.
Methods
To investigate PPM1D protein expression, mRNA expression, and copy number changes, immunohistochemistry, RNAscope in situ hybridization, and fluorescence in situ hybridization were performed in 84 adult supratentorial diffuse gliomas. We further analyzed clinical characteristics and overall survival (OS) according to PPM1D protein expression, and examined its correlation with other glioma biomarkers such as isocitrate dehydrogenase (IDH) mutation, and p53 expression.
Results
Forty-six cases (54.8%) were PPM1D-positive. PPM1D expression levels were significantly correlated with PPM1D transcript levels (p= .035), but marginally with PPM1D gene amplification (p=.079). Patients with high-grade gliomas showed a higher frequency of PPM1D expression than those with low-grade gliomas (p <.001). Multivariate analysis demonstrated that PPM1D expression (hazard ratio [HR], 2.58; p=.032), age over 60 years (HR, 2.55; p=.018), and IDH1 mutation (HR, 0.18; p=.002) were significantly independent prognostic factors; p53 expression had no prognostic significance (p=.986). The patients with tumor expressing PPM1D showed a shorter OS (p=.003). Moreover, patients with tumor harboring wild-type IDH1 and PPM1D expression had the worst OS (p<.001).
Conclusions
Our data suggest that a subset of gliomas express PPM1D; PPM1D expression is a significant marker of poor prognosis in adult supratentorial diffuse astrocytic and oligodendroglial tumors.
Extramural Perineural Invasion in pT3 and pT4 Gastric Carcinomas
Alejandro España-Ferrufino, Leonardo S. Lino-Silva, Rosa A. Salcedo-Hernández
J Pathol Transl Med. 2018;52(2):79-84.   Published online November 9, 2017
DOI: https://doi.org/10.4132/jptm.2017.11.01
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  • 126 Download
  • 5 Citations
AbstractAbstract PDF
Background
Perineural invasion (PNI) is widely studied in malignant tumors, and its prognostic significance is well demonstrated. Most studies have focused on evaluating the mural PNI (mPNI); however, extramural PNI (ePNI) may influence the prognosis in gastric cancer. We evaluated the prognostic value of ePNI compared with mPNI in gastric cancer in this observational comparative cross-sectional study.
Methods
Seventy-three pT3 and pT4 gastric carcinomas with PNI were evaluated. Forty-eight (65.7%) were in the mPNI group and the remaining in the ePNI group.
Results
Clinicopathologic characteristics between the two groups were similar, except for the outcomes. The 5-year disease-specific survival (DSS) rate was 64% for the mPNI group and 50% for the ePNI group (p=.039), a difference that did not remain significant in multivariate analysis. The only independent adverse prognostic factor in multivariate analysis was the presence of lymph node metastasis (hazard ratio, 1.757; 95% confidence interval, 1.082 to 2.854; p=.023).
Conclusions
We demonstrated the prognostic effect of ePNI for DSS in surgically resected pT3–pT4 gastric cancer patients. ePNI could be considered in the staging and prognostic systems of gastric cancer to stratify patients with a high risk of recurrence.
The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma
Yangkyu Lee, Hyunjin Park, Hyejung Lee, Jai Young Cho, Yoo-Seok Yoon, Young-Rok Choi, Ho-Seong Han, Eun Sun Jang, Jin-Wook Kim, Sook-Hyang Jeong, Soomin Ahn, Haeryoung Kim
J Pathol Transl Med. 2018;52(2):85-92.   Published online November 24, 2017
DOI: https://doi.org/10.4132/jptm.2017.11.13
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  • 14 Citations
AbstractAbstract PDF
Background
We aimed to determine the clinicopathological significance of the gross classification of hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association (KLCA) guidelines.
Methods
A retrospective analysis was performed on 242 cases of consecutively resected solitary primary HCC between 2003 and 2012 at Seoul National University Bundang Hospital. The gross classification (vaguely nodular [VN], expanding nodular [EN], multinodular confluent [MC], nodular with perinodular extension [NP], and infiltrative [INF]) was reviewed for all cases, and were correlated with various clinicopathological features and the expression status of “stemness”-related (cytokeratin 19 [CK19], epithelial cell adhesion molecule [EpCAM]), and epithelial-mesenchymal transition (EMT)–related (urokinase plasminogen activator receptor [uPAR] and Ezrin) markers.
Results
Significant differences were seen in overall survival (p=.015) and disease-free survival (p = .034) according to the gross classification; INF type showed the worst prognosis while VN and EN types were more favorable. When the gross types were simplified into two groups, type 2 HCCs (MC/NP/INF) were more frequently larger and poorly differentiated, and showed more frequent microvascular and portal venous invasion, intratumoral fibrous stroma and higher pT stages compared to type 1 HCCs (EN/VN) (p<.05, all). CK19, EpCAM, uPAR, and ezrin expression was more frequently seen in type 2 HCCs (p<.05, all). Gross classification was an independent predictor of both overall and disease-free survival by multivariate analysis (overall survival: p=.030; hazard ratio, 4.118; 95% confidence interval, 1.142 to 14.844; disease-free survival: p=.016; hazard ratio, 1.617; 95% confidence interval, 1.092 to 2.394).
Conclusions
The gross classification of HCC had significant prognostic value and type 2 HCCs were associated with clinicopathological features of aggressive behavior, increased expression of “stemness”- and EMT-related markers, and decreased survival.
Myoferlin Expression and Its Correlation with FIGO Histologic Grading in Early-Stage Endometrioid Carcinoma
Min Hye Kim, Dae Hyun Song, Gyung Hyuck Ko, Jeong Hee Lee, Dong Chul Kim, Jung Wook Yang, Hyang Im Lee, Hyo Jung An, Jong Sil Lee
J Pathol Transl Med. 2018;52(2):93-97.   Published online March 14, 2018
DOI: https://doi.org/10.4132/jptm.2017.11.29
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  • 108 Download
  • 7 Citations
AbstractAbstract PDF
Background
For endometrioid carcinoma patients, International Federation of Gynecologists and Obstetricians (FIGO) histologic grading is very important for identifying the appropriate treatment method. However, the interobserver discrepancy with this three-tiered grading system is a serious potential problem. In this study, we used immunohistochemistry to analyze the relationship between FIGO histologic grading score and myoferlin expression.
Methods
We studied the endometrioid carcinoma tissues of 60 patients from Gyeongsang National University Hospital between January 2002 and December 2009. Immunohistochemical analysis of myoferlin was performed on tissue microarray blocks from surgical specimens.
Results
Myoferlin expression was observed in 58 of 60 patients. Moderate and strong myoferlin expression was observed in low-grade endometrioid carcinoma, while there was a tendency toward loss of myoferlin expression in high-grade endometrioid carcinoma (p<.001).
Conclusions
Our study revealed that myoferlin loss is significantly correlated with high FIGO grade of endometrioid carcinoma.
Prognostic Utility of Histological Growth Patterns of Colorectal Lung Oligometastasis
Son Jae Yeong, Min Gyoung Pak, Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh
J Pathol Transl Med. 2018;52(2):98-104.   Published online February 12, 2018
DOI: https://doi.org/10.4132/jptm.2017.12.27
  • 4,659 View
  • 115 Download
  • 2 Citations
AbstractAbstract PDF
Background
Patients with resectable colorectal lung oligometastasis (CLOM) demonstrate a heterogeneous oncological outcome. However, the parameters for predicting tumor aggressiveness have not yet been fully investigated in CLOM. This study was performed to determine the prognostic value of histological growth patterns in patients who underwent surgery for CLOM.
Methods
The study included 92 patients who were diagnosed with CLOM among the first resection cases. CLOMs grow according to three histological patterns: aerogenous, pushing, and desmoplastic patterns. The growth patterns were evaluated on archival hematoxylin and eosin–stained tissue sections.
Results
The aerogenous pattern was found in 29.4% (n=27) of patients, the pushing pattern in 34.7% (n=32), the desmoplastic pattern in 6.5% (n=6), and a mix of two growth patterns in 29.4% (n=27). The size of the aerogenous pattern was significantly smaller than that of metastases with other patterns (p=.033). Kaplan-Meier analysis demonstrated that patients showing an aerogenous pattern appeared to have a poorer prognosis, which was calculated from the time of diagnosis of the CLOM (p=.044). The 5-year survival rate from the diagnosis of colorectal cancer tended to be lower in patients with an aerogenous pattern than in those who had a non-aerogenous pattern; however, the difference was marginally significant (p=.051). In the multivariate Cox analysis, the aerogenous pattern appeared as an independent predictor of poor overall survival (hazard ratio, 3.122; 95% confidence interval, 1.196 to 8.145; p=.020).
Conclusions
These results suggest that the growth patterns may play a part as a histology-based prognostic parameter for patients with CLOM.
Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma
Jisup Kim, Beom Jin Lim, Soon Won Hong, Ju Yeon Pyo
J Pathol Transl Med. 2018;52(2):105-109.   Published online February 12, 2018
DOI: https://doi.org/10.4132/jptm.2017.12.26
  • 5,634 View
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  • 2 Citations
AbstractAbstract PDF
Background
Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation.
Methods
Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations.
Results
WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology.
Conclusions
The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.
Cytological Features That Differentiate Follicular Neoplasm from Mimicking Lesions
Kanghee Han, Hwa-Jeong Ha, Joon Seog Kong, Jung-Soon Kim, Jae Kyung Myung, Jae Soo Koh, Sunhoo Park, Myung-Soon Shin, Woo-Tack Song, Hye Sil Seol, Seung-Sook Lee
J Pathol Transl Med. 2018;52(2):110-120.   Published online January 29, 2018
DOI: https://doi.org/10.4132/jptm.2018.01.17
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  • 3 Citations
AbstractAbstract PDF
Background
It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions. The aim of this study was to identify the cytological features that differentiate FNs from mimicking lesions.
Methods
We included the cytological slides from 116 cases of thyroid FN diagnosed on FNAC, and included their subsequent histological diagnoses. We evaluated the cytological architectural pattern and nuclear features of the lesions according to their histological groups.
Results
The final histological diagnoses of the 116 cases varied, and included 51 FNs (44%), 47 papillary thyroid carcinomas (40%) including follicular variant, and seventeen cellular nodular hyperplasias (15%). Regardless of the final histological diagnosis, microfollicular pattern was observed in most cases. On the other hand, trabecular pattern was identified in 34% of FNs, but not in any other lesions. Additionally, elongated nuclei and ground glass chromatin were found in only some papillary thyroid carcinomas.
Conclusions
This study shows that the trabecular pattern is a representative cytological feature of FNs that can be used to distinguish FNs from mimicking lesions. In addition, nuclear shape and chromatin pattern can be used to further confirm the diagnosis of FNs from mimicking lesions through FNAC.
Case Studies
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
  • 5,530 View
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  • 5 Citations
AbstractAbstract PDF
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.
Multiple Neuroendocrine Tumors in Stomach and Duodenum in a Multiple Endocrine Neoplasia Type 1 Patient
Bohyun Kim, Han-Kwang Yang, Woo Ho Kim
J Pathol Transl Med. 2018;52(2):126-129.   Published online December 21, 2017
DOI: https://doi.org/10.4132/jptm.2017.09.16
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  • 1 Citations
AbstractAbstract PDF
A 67-year-old woman with a history of subtotal parathyroidectomy, distal pancreatectomy, and total splenectomy 23 years prior underwent surgical gastric resection for neuroendocrine tumors of the stomach and duodenum. Meticulous examination of the entire stomach and duodenum revealed multiple scattered, minute neuroendocrine tumors. To the best of our knowledge, this is the first case report of a patient diagnosed with gastroduodenal neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN 1) in whom complete histologic mapping of the whole gastrectomy specimen was performed. The presence of MEN 1–associated neuroendocrine tumors in the stomach is very rare, but should be considered in patients diagnosed with MEN 1 who present with a new tumor in the stomach.
Brief Case Reports
Osteosarcomatous Differentiation in Rebiopsy Specimens of Pulmonary Adenocarcinoma with EGFR-TKI Resistance
Hyein Ahn, Hyun Jung Kwon, Eunhyang Park, Hyojin Kim, Jin-Haeng Chung
J Pathol Transl Med. 2018;52(2):130-132.   Published online April 4, 2017
DOI: https://doi.org/10.4132/jptm.2016.11.17
  • 4,576 View
  • 120 Download
  • 1 Citations
PDF
Denosumab-Treated Giant Cell Tumor of the Bone Mimicking Low-Grade Central Osteosarcoma
Chang-Che Wu, Pin-Pen Hsieh
J Pathol Transl Med. 2018;52(2):133-135.   Published online February 12, 2018
DOI: https://doi.org/10.4132/jptm.2016.12.21
  • 5,866 View
  • 176 Download
  • 5 Citations
PDF
Case Study
Fine-Needle Aspiration Cytology of Carcinosarcoma in the Salivary Gland: An Extremely Rare Case Report
Hyo Jung An, Hye Jin Baek, Jin Pyeong Kim, Min Hye Kim, Dae Hyun Song
J Pathol Transl Med. 2017;52(2):136-139.   Published online December 28, 2017
DOI: https://doi.org/10.4132/jptm.2017.07.27
  • 4,637 View
  • 107 Download
  • 1 Citations
AbstractAbstract PDF
Carcinosarcoma of the salivary gland is an extremely rare tumor that is composed of both malignant epithelial and mesenchymal components. Diagnosing carcinosarcoma with fine-needle aspiration cytology is challenging because of its overlapping cytomorphologic characteristics with other high-grade malignant salivary gland tumors. Among the many features, including pleomorphic oncocytoid epithelial components, necrotic background, and mitoses, recognizing the singly scattered atypical spindle cells is most essential in carcinosarcoma. We present a case of a 66-year-old male patient with characteristic features of carcinosarcoma, who was successfully treated by wide local excision and subsequent radiation therapy.

JPTM : Journal of Pathology and Translational Medicine