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Volume 53(2); March 2019
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Original Articles
Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer
Hong Sik Park, Uiju Cho, So Young Im, Chang Young Yoo, Ji Han Jung, Young Jin Suh, Hyun Joo Choi
J Pathol Transl Med. 2019;53(2):75-85.   Published online November 14, 2018
DOI: https://doi.org/10.4132/jptm.2018.10.11
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  • 14 Citations
AbstractAbstract PDF
Background
Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear.
Methods
We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed.
Results
Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort.
Conclusions
Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.
Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Coexpression Is an Independent Poor Prognostic Factor in Adenocarcinoma of the Lung
Yeon Bi Han, Hyun Jung Kwon, Soo Young Park, Eun-Sun Kim, Hyojin Kim, Jin-Haeng Chung
J Pathol Transl Med. 2019;53(2):86-93.   Published online January 14, 2019
DOI: https://doi.org/10.4132/jptm.2018.12.26
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  • 1 Citations
AbstractAbstract PDF
Background
Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression.
Methods
HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed.
Results
HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p = .033, p = .007, and p = .012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p < .001, p = .002, and p = .032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501).
Conclusions
Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression.
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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  • 6 Citations
AbstractAbstract PDFSupplementary 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.
Intraoperative Frozen Cytology of Central Nervous System Neoplasms: An Ancillary Tool for Frozen Diagnosis
Myunghee Kang, Dong Hae Chung, Na Rae Kim, Hyun Yee Cho, Seung Yeon Ha, Sangho Lee, Jungsuk An, Jae Yeon Seok, Gie-Taek Yie, Chan Jong Yoo, Sang Gu Lee, Eun Young Kim, Woo Kyung Kim, Seong Son, Sun Jin Sym, Dong Bok Shin, Hee Young Hwang, Eung Yeop Kim, Kyu Chan Lee
J Pathol Transl Med. 2019;53(2):104-111.   Published online January 14, 2019
DOI: https://doi.org/10.4132/jptm.2018.11.10
  • 7,545 View
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  • 4 Citations
AbstractAbstract PDF
Background
Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms.
Methods
Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated.
Results
Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency.
Conclusions
Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.
Case Studies
Squamous Cell Carcinoma of the Extrahepatic Common Hepatic Duct
Myunghee Kang, Na Rae Kim, Dong Hae Chung, Hyun Yee Cho, Yeon Ho Park
J Pathol Transl Med. 2019;53(2):112-118.   Published online October 1, 2018
DOI: https://doi.org/10.4132/jptm.2018.09.03
  • 5,246 View
  • 149 Download
  • 7 Citations
AbstractAbstract PDF
We report a rare case of hilar squamous cell carcinoma. A 62-year-old Korean woman complaining of nausea was referred to our hospital. Her biliary computed tomography revealed a 28 mm-sized protruding solid mass in the proximal common bile duct. The patient underwent left hemihepatectomy with S1 segmentectomy and segmental excision of the common bile duct. Microscopically, the tumor was a moderately differentiated squamous cell carcinoma of the extrahepatic bile duct, without any component of adenocarcinoma or metaplastic portion in the biliary epithelium. Immunohistochemically, the tumor was positive for cytokeratin (CK) 5/6, CK19, p40, and p63. Squamous cell carcinoma of the extrahepatic bile duct is rare. To date, only 24 cases of biliary squamous cell carcinomas have been reported. Here, we provide a clinicopathologic review of previously reported extrahepatic bile duct squamous cell carcinomas.
Primary Malignant Melanoma of the Breast: A Report of Two Cases
Jiwon Koh, Jihyeon Lee, So Youn Jung, Han Sung Kang, Tak Yun, Youngmee Kwon
J Pathol Transl Med. 2019;53(2):119-124.   Published online November 26, 2018
DOI: https://doi.org/10.4132/jptm.2018.10.18
  • 5,309 View
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  • 3 Citations
AbstractAbstract PDFSupplementary Material
Primary malignant melanoma of the breast (PMMB) is a rare tumor with only a few case reports available in the literature. We report two cases of PMMB, one derived from the breast parenchyma and the other from the breast skin. The first case consisted of atypical epithelioid cells without overt melanocytic differentiation like melanin pigments. The tumor cells showed diffuse positivity for S100 protein, tyrosinase, and BRAF V600E. However, the tumor cells were negative for cytokeratin, epithelial membrane antigen, and HMB-45. The second case showed atypical melanocytic proliferation with heavy melanin pigmentation. The tumor cells were positive for S100 protein, HMB-45, tyrosinase, and BRAF V600E. These two cases represent two distinct presentations of PMMB in terms of skin involvement, melanin pigmentation, and HMB-45 positivity. Although PMMB is very rare, the possibility of this entity should be considered in malignant epithelioid neoplasms in the breast parenchyma.
Coexisting Mucinous Cystic Neoplasm of the Pancreas and Type 1 Autoimmune Pancreatitis
Mee-Jeong Kim, Tae Jun Song, Hyoung Jung Kim, Song-Cheol Kim, Myung-Hwan Kim, Seung-Mo Hong
J Pathol Transl Med. 2019;53(2):125-128.   Published online November 14, 2018
DOI: https://doi.org/10.4132/jptm.2018.10.25
  • 5,645 View
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  • 3 Citations
AbstractAbstract PDF
Type 1 autoimmune pancreatitis (AIP1) is an IgG4-related systemic disease that mimics tumors. We report a rare case of AIP1 accompanied by mucinous cystic neoplasm (MCN). A pancreatic lesion was incidentally detected in a woman in her 60s. After 6 years of follow-up, the lesion abruptly increased in size. Computed tomography showed a 3.5 cm unilocular cyst in the tail of the pancreas and distal pancreatectomy was performed. On microscopic examination, the cyst was lined by mucinous and non-mucinous epithelial cells with mild cytologic atypia. The surrounding stroma comprised ovarian-type spindle cells with progesterone receptor positivity. The pericystic pancreas exhibited multifocal lymphoid follicles, lymphoplasmacytic infiltrations, obliterative phlebitis, and storiform fibrosis. IgG4-positive plasma cell infiltration (215 cells high-power field) and the IgG4/IgG ratio (57%) were increased. Cases of MCN coexisting with AIP1 are extremely rare; only two such cases have been reported in the English-language literature. This third case featured low-grade MCN with AIP1.
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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  • 2 Citations
AbstractAbstract 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.
Encapsulated Papillary Thyroid Tumor with Delicate Nuclear Changes and a KRAS Mutation as a Possible Novel Subtype of Borderline Tumor
Kenji Ohba, Norisato Mitsutake, Michiko Matsuse, Tatiana Rogounovitch, Nobuhiko Nishino, Yutaka Oki, Yoshie Goto, Kennichi Kakudo
J Pathol Transl Med. 2019;53(2):136-141.   Published online January 14, 2019
DOI: https://doi.org/10.4132/jptm.2018.12.07
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  • 5 Citations
AbstractAbstract PDF
Although papillary thyroid carcinoma (PTC)–type nuclear changes are the most reliable morphological feature in the diagnosis of PTC, the nuclear assessment used to identify these changes is highly subjective. Here, we report a noninvasive encapsulated thyroid tumor with a papillary growth pattern measuring 23 mm at its largest diameter with a nuclear score of 2 in a 26-year-old man. After undergoing left lobectomy, the patient was diagnosed with an encapsulated PTC. However, a second opinion consultation suggested an alternative diagnosis of follicular adenoma with papillary hyperplasia. When providing a third opinion, we identified a low MIB-1 labeling index and a heterozygous point mutation in the KRAS gene but not the BRAF gene. We speculated that this case is an example of a novel borderline tumor with a papillary structure. Introduction of the new terminology “noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS)” without the word “cancer” might relieve the psychological burden of patients in a way similar to the phrase “noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).”
Brief Case Reports
Crystal-Storing Histiocytosis with Plasma Cell Neoplasm in the Setting of Chronic Carbamazepine Exposure
Woo Cheal Cho, Safina Hafeez, Peter Shen
J Pathol Transl Med. 2019;53(2):142-144.   Published online June 7, 2018
DOI: https://doi.org/10.4132/jptm.2018.05.25
  • 3,347 View
  • 132 Download
  • 2 Citations
PDF
Wharton Jelly Hair in a Case of Umbilical Cord Stricture and Fetal Death
Eun Na Kim, Jae-Yoon Shim, Chong Jai Kim
J Pathol Transl Med. 2019;53(2):145-147.   Published online November 14, 2018
DOI: https://doi.org/10.4132/jptm.2018.10.24
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Metastatic Insulinoma Presenting as a Liver Cyst
Hua Li, Tony El Jabbour, Ankesh Nigam, Hwajeong Lee
J Pathol Transl Med. 2019;53(2):148-151.   Published online January 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.01.15
Correction in: J Pathol Transl Med 2019;53(6):415
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JPTM : Journal of Pathology and Translational Medicine