Early metastatic colorectal cancers show increased tissue expression of miR-17/92 cluster members in the invasive tumor front
Accurate prediction of regional lymph node metastases (LNM) in endoscopically resected pT1 colorectal cancer (CRC) is crucial in treatment stratification for subsequent radical surgery. Several miRNAs have been linked to CRC invasion and metastasis, including the oncogenic miR-17/92 cluster, and expression levels might have predictive value in the risk assessment of early metastatic progression in CRC. We performed global miRNA microarray using tissue samples from the invasive front of pT1 CRC and investigated associations of the miR-17/92 cluster and presence of LNM. (Source: Human Pathology)
Source: Human Pathology - June 11, 2018 Category: Pathology Authors: Rikke Karlin Jepsen, Guy Wayne Novotny, Louise Laurberg Klarskov, Claus Heiner Bang-Bertelsen, Ida Trondhjem Haakansson, Anker Hansen, Ib Jarle Christensen, Lene Buhl Riis Ass, Estrid H øgdall Tags: Original Contributions Source Type: research

Androgen receptor expression is a favorable prognostic factor in triple-negative breast cancers
Androgen receptor (AR) expression is an emerging prognostic marker that has been observed in 25% to 75% of triple negative breast cancers (TNBCs) that lack estrogen receptor, progesterone receptor and HER2 overexpression. TNBCs are treated with AR-targeted therapies and standardized evaluation of AR expression may help guide patient management. Basal-like TNBCs are a subgroup of TNBCs defined by positive immunoreactivity for CK5/6 or EGFR that carry a worse prognosis. However, it's unclear whether basal-like TNBCs have a different rate of AR positivity or if AR expression is predictive of disease free survival in this pati...
Source: Human Pathology - June 11, 2018 Category: Pathology Authors: Tao Zuo, Parker Wilson, Ali Fuat Cicek, Malini Harigopal Tags: Original contribution Source Type: research

The Impact of the effectiveness of GATA3 as a prognostic factor in breast cancer
The transcription factor GATA3 plays a significant role in mammary gland development and differentiation. We analyzed expression of GATA3 in breast cancer (BC) cell lines and clinical specimens from BC patients in Taiwan. Semi-quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR), quantitative real-time PCR carried out to determine the mRNA level of GATA3 from 241 pairs of matched tumor and adjacent normal tissues from anonymous female donors. GATA3 immunohistochemistry (IHC) staining and H-score were performed (n=25). (Source: Human Pathology)
Source: Human Pathology - June 11, 2018 Category: Pathology Authors: Fararjeh-Salah Abdul Fattah, Shih-Hsin Tu, Li-Ching Chen, Yun-Ru Liu, Yen-Kuang Lin, Hang-Lung Chang, Hui-Wen Chang, Chih-Hsiung Wu, Wendy-Hwang Verslues, Yuan-Soon Ho Tags: Original contribution Source Type: research

Desmoplastic non- infantile astrocytoma/Ganglioglioma: rare low-grade tumor with frequent BRAF V600E mutation
This study was carried out to evaluate the frequency of BRAF V600E mutation in DIA/DIG. All cases of DIA/DIGs diagnosed over 7years (2010–2016) were reviewed ret rospectively. The clinical, radiological and histopathological characteristics of these patients were evaluated along with immunohistochemical analysis for glial and neuronal markers. (Source: Human Pathology)
Source: Human Pathology - June 11, 2018 Category: Pathology Authors: Debajyoti Chatterjee, Chandni Garg, Navneet Singla, Bishan Dass Radotra Tags: Original contribution Source Type: research

Lymphomas with pseudo-double hit BCL6-MYC translocations due to t(3;8)(q27;q24) are associated with a germinal center immunophenotype, extranodal involvement, and frequent BCL2 translocations
High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, “double hit” or “triple hit” lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique “pseudo-double hit” BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization ( FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 inst...
Source: Human Pathology - June 11, 2018 Category: Pathology Authors: Steven M. Johnson, Jayadev Manikkam Umakanthan, Ji Yuan, Yuri Fedoriw, R. Gregory Bociek, Kathleen Kaiser-Rogers, Jennifer N. Sanmann, Nathan D. Montgomery Tags: Original contribution Source Type: research

FOXP3-positive T-cell lymphomas in non-HTLV1 carriers include ALK-negative anaplastic large cell lymphoma: expanding the Spectrum of T-cell lymphomas with regulatory phenotype
We report 6 cases of T-cell lymphomas with Treg phenotype based on diffuse positivity for FOXP3 in tumor cells. The patients showed a median age of 56years with a male predominance. Sites of disease included lymph nodes (4), skin (2), subcutaneous tissue (1) and bone marrow (1). All cases showed monomorphic large cells, some with Hodgkin-like or anaplastic cells. All cases expressed pan T cell markers and lacked cytotoxic markers; one case showed diffuse PD1 staining. (Source: Human Pathology)
Source: Human Pathology - June 10, 2018 Category: Pathology Authors: Cristiane R. Ferreira, Shuchun Zhao, Malaya K. Sahoo, Benjamin Pinsky, Jenna Weber, Luis A.P.C. Lage, Juliana Pereira, Maria C.N. Zerbini, Yasodha Natkunam Tags: Original Contributions Source Type: research

Myosin 5a regulates tumor migration and epithelial-mesenchymal transition in esophageal squamous cell carcinoma: utility as a prognostic factor
In this study, we confirmed the expression of myosin 5a in ESCC surgical specimens and cell lines, revealing its correlation with tumor invasion, migration, patient prognosis, and expression of EMT-related proteins. (Source: Human Pathology)
Source: Human Pathology - June 10, 2018 Category: Pathology Authors: Naomi Sato, Fumiyoshi Fujishima, Yasuhiro Nakamura, Yayoi Aoyama, Yoshiaki Onodera, Yohei Ozawa, Ken Ito, Hirotaka Ishida, Takashi Kamei, Mika Watanabe, Hironobu Sasano Tags: Original Contributions Source Type: research

Clinicopathological, Immunohistochemical and molecular correlation of neural crest transcription factor SOX10 expression in triple negative breast carcinoma
The transcription factor SOX10 mediates the differentiation of neural crest –derived cells, and SOX10 by immunohistochemistry(IHC) is used primarily for the diagnosis of melanoma. SOX10 expression has been previously documented in benign breast myoepithelial cells. However there is limited literature on its expression in triple negative breast carcinoma(TNBC). The aim was to study the clinical, pathologic and molecular profiles of SOX10+ tumors in TNBC. Tissue microarrays of TNBC were evaluated for SOX10 expression in 48cases. (Source: Human Pathology)
Source: Human Pathology - June 9, 2018 Category: Pathology Authors: Aparna Harbhajanka, Satyapal Chahar, Kristy Miskimen, Paula Silverman, Lyndsay Harris, Nicole Williams, Vinay Varadan, Hannah Gilmore Tags: Original contribution Source Type: research

Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate
In this study, we analyzed the expression of INSM in three high-throughput RNA sequencing data sets and performed INSM1 immunohistochemistry on a large series of prostatic SCCs and nonneuroendocrine prostate tissues. (Source: Human Pathology)
Source: Human Pathology - June 6, 2018 Category: Pathology Authors: Wei Xue, Zhixiang Xin, Yong Zhang, Zhou Jiang, Ling Zhao, Liancheng Fan, Yanqing Wang, Shaowei Xie, Xun Shangguan, Yinjie Zhu, Jiahua Pan, Qiang Liu, Yiran Huang, Baijun Dong Tags: Original Contributions Source Type: research

Evaluation of tumor-infiltrating lymphocytes using routine H & E slides predicts patient survival in resected non-small cell lung cancer
The presence of tumor-infiltrating lymphocytes (TILs) positively impacts the outcome of non-small cell lung cancer (NSCLC) patients. Most previous studies have assessed TILs using different immunohistochemical assays. The purpose of this study was to develop and validate a histopathological scoring model for the assessment of TILs in whole tissue hematoxylin and eosin (H&E)-stained section slides of NSCLC patients and to evaluate the model in an immunoscore setting. Therefore, TIL was evaluated manually on H&E slides from 537 surgical specimens of primary resected stage I-III NSCLC patients. (Source: Human Pathology)
Source: Human Pathology - June 6, 2018 Category: Pathology Authors: Mehrdad Rakaee, Thomas K. Kilvaer, Stig Manfred Dalen, Elin Richardsen, Erna-Elise Paulsen, Sigurd M. Hald, Samer Al-Saad, Sigve Andersen, Tom Donnem, Roy M. Bremnes, Lill-Tove Busund Tags: Original Contributions Source Type: research

In situ analysis of mTORC1/2 and cellular metabolism-related proteins in human Lymphangioleiomyomatosis
Lymphangioleiomyomatosis (LAM) is a rare progressive cystic lung disease with features of a low-grade neoplasm. It is primarily caused by mutations in TSC1 or TSC2 genes. Sirolimus, an inhibitor of mTOR complex 1 (mTORC1), slows down disease progression in some, but not all patients. Hitherto, other potential therapeutic targets such as mTOR complex 2 (mTORC2) and various metabolic pathways have not been investigated in human LAM tissues. The aim of this study was to assess activities of mTORC1, mTORC2 and various metabolic pathways in human LAM tissues through analysis of protein expression. (Source: Human Pathology)
Source: Human Pathology - June 6, 2018 Category: Pathology Authors: Ildiko Krencz, Anna Sebestyen, Judit Papay, Andras Jeney, Zoltan Hujber, Charles D. Burger, Cesar A. Keller, Andras Khoor Tags: Original Contributions Source Type: research

Evaluation of miRNAs expression in medullary thyroid carcinoma tissue samples: miR-34a and miR-144 as promising overexpressed markers in MTC
Medullary Thyroid Carcinoma (MTC) is a rare neoplasia derived from neural parafollicular C cells. MicroRNAs (miRNAs) are small regulatory RNAs with essential roles in the biology of cancers such as MTC and can be applied as diagnostic markers. According to previous studies, miR-144 and miR-34 and their two oncogenes target, mammalian target of rapamycin (mTOR) and AXL receptor tyrosine kinase (AXL), were selected for further investigations in our study. Thirty MTC samples as well as thirty adjacent normal thyroid tissues were applied in this study including 28 Formalin-Fixed Paraffin-Embedded (FFPE) and 2 fresh-frozen MTC ...
Source: Human Pathology - June 6, 2018 Category: Pathology Authors: Noushin Shabani, Javad Razaviyan, Mahdi Paryan, Seyed Mohammad Tavangar, Fereidoun Azizi, Samira Mohammadi-Yeganeh, Mehdi Hedayati Tags: Original Contributions Source Type: research

Epstein - Barr virus - associated lymphoid proliferations, a 2018 update
Epstein-Barr virus (EBV) has been linked to many human neoplasms including hematopoietic, epithelial, and mesenchymal tumors. Since our original review of EBV-associated lymphoproliferative disorders in 2007 (1), many advances and developments have been reported. In this review, we will examine the recent advances in EBV-associated lymphoid/ histiocytic proliferations, dividing them into reactive, B cell, T/NK cell, immunodeficiency-related, and histiocytic/dendritic cell proliferations. (Source: Human Pathology)
Source: Human Pathology - June 6, 2018 Category: Pathology Authors: Sherif A. Rezk, Xiaohui Zhao, Lawrence M. Weiss Tags: Perspectives in pathology Source Type: research

B7H4 is associated with stemness and cancer progression in esophageal squamous cell carcinoma
In this study, we have assessed the expression of B7H4 and cancer stemness proteins in 156 paraffin embedded ESCC tissue samples using immunohistochemistry as well as in ESCC cell lines using western blotting and immunofluorescence imaging. (Source: Human Pathology)
Source: Human Pathology - June 6, 2018 Category: Pathology Authors: Longzhen Piao, Zhaoting Yang, Jiajun Jin, Weidong Ni, Wenbo Qi, Yanhua Xuan Tags: Original Contributions Source Type: research

Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype
In this study, we focused on micropapillary urothelial carcinoma (MPUC), an aggressive, histomorphologically defined rare variant. Apart from genetic alterations shared with conventional UBC alterations of the HER2 gene have been reported in higher frequencies. However, only small cohorts of MPUCs have been analyzed and the real impact is still unclear. We collected a cohort of 94 MPUCs and immunohistochemically tested HER2, basal (CD44, CK5, EGFR, p63) and luminal (CD24, FOXA1, GATA3, CK20) markers to allocate MPUC to a molecular subtype. (Source: Human Pathology)
Source: Human Pathology - June 6, 2018 Category: Pathology Authors: Ulrike Zinnall, Veronika Weyerer, Eva Comp érat, Philippe Camparo, Nadine T. Gaisa, Ruth Knuechel-Clarke, Aurel Perren, Alessandro Lugli, Marieta Toma, Gustavo Baretton, Glen Kristiansen, Ralf M. Wirtz, Liang Cheng, Bernd Wullich, Robert Stoehr, Arndt Ha Tags: Original contribution Source Type: research

Eosinophilic solid and cystic renal cell carcinoma mimicking epithelioid Angiomyolipoma: series of 4 primary tumors and 2 metastases
Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel entity of rare tumors with rather unique morphology and immunohistochemical profile. Until recently these tumors were characterized by indolent behavior. Herein we describe a series of six primary and metastatic ESC-RCCs morphologically and immunophenotypically mimicking epithelioid angiomyolipoma (eAML). Retrospective review of unclassified RCCs with oncocytic phenotype yielded several candidate cases, 4 of which fulfilled diagnostic criteria after additional work-up. (Source: Human Pathology)
Source: Human Pathology - June 6, 2018 Category: Pathology Authors: Maria S Tretiakova Tags: Original contribution Source Type: research

TP53 mutations in peripheral mature T and NK cell lymphomas: a whole-exome sequencing study with correlation to p53 expression
In this study, fifty-seven formalin-fixed paraffin-embedded samples were collected for whole-exome sequencing and immunohistochemical study. Ten cases had TP53 mutation variant allele frequency (VAF) of more than 5%, predominantly in intestinal T-cell lymphoma (60%), peripheral T-cell lymphoma, not otherwise specified (22.2%), and extranodal nasal-type NK/T-cell lymphoma (21.7%). (Source: Human Pathology)
Source: Human Pathology - June 6, 2018 Category: Pathology Authors: Hui-Shan Huang, Chun-Kai Liao, Ting-Ting Liu, Huey-Ling You, Ming-Chung Wang, Wan-Ting Huang Tags: Original Contributions Source Type: research

DICER1 mutation-positive Giant Botryoid Fibroepithelial polyp of the urinary bladder mimicking embryonal rhabdomyosarcoma
Fibroepithelial polyps of the urinary tract are rare lesions. They occur mainly in the upper urinary tract of children. A high disease prevalence has been reported in families with pleuropulmonary blastoma. Here we present a case of a 46-year-old woman who presented with a giant botryoid fibroepithelial polyp of the urinary bladder. Histologically, the lesion showed prominent botryoid features with an embryonal rhabdomyosarcoma-like cambium layer lacking nuclear or cellular atypia. Immunohistochemical analysis ruled out rhabdomyoblastic differentiation. (Source: Human Pathology)
Source: Human Pathology - June 5, 2018 Category: Pathology Authors: Markus Eckstein, Abbas Agaimy, Joachim Woenckhaus, Alexander Winter, Iris Bittmann, Joerg Janzen, Simone Bertz, Florian Haller, Arndt Hartmann Tags: Case study Source Type: research

Tumor infiltrating lymphocyte volume is a better predictor of neoadjuvant therapy response and overall survival in triple negative invasive breast Cancer
Triple-negative breast cancer (TNBC) has an aggressive behavior, limited therapeutic options, and high mortality rate. Neoadjuvant chemotherapy (NACT) is a standard treatment for TNBC and patients with pathological complete response (pCR) have a favorable outcome. We conducted a comprehensive evaluation of cancer clinicopathologic parameters, and correlated these parameters with the pCR rate and the overall survival. Fifty-eight patients with TNBC of no special type who underwent breast biopsy, neoadjuvant therapy, and mastectomy in our institution during 2005 –2016 were included in this study. (Source: Human Pathology)
Source: Human Pathology - June 5, 2018 Category: Pathology Authors: Lin Zhang, Xiaohong I Wang, Songlin Zhang Tags: Original Contributions Source Type: research

Alanine-Glyoxylate Aminotransferase 1 (AGXT1) is a Novel Marker for Hepatocellular Carcinomas
Arginase-1 has been demonstrated as a marker for hepatocellular carcinoma with higher sensitivity and specificity than HepPar-1 and glypican-3. However, its sensitivity is diminished in moderately and poorly differentiated hepatocellular carcinomas. In current study, we evaluated the utility of AGXT1 as a diagnostic marker. Immunostains for AGXT1 and arginase-1 were performed in tissue microarrays of 139 hepatocellular carcinomas (HCCs) and 374 gastrointestinal and non-gastrointestinal carcinomas. (Source: Human Pathology)
Source: Human Pathology - June 5, 2018 Category: Pathology Authors: Chaohui Lisa Zhao, Yiang Hui, Li Juan Wang, Dongfang Yang, Evgeny Yakirevich, Shamlal Mangray, Chiung-Kuei Huang, Shaolei Lu Tags: Original Contributions Source Type: research

The phrase NIFTP accentuates, rather than resolves, the current issues with thyroid neoplasia classification —reply
Ricardo V. Lloyd MD, PhD rvlloyd@wisc.edu (Source: Human Pathology)
Source: Human Pathology - June 4, 2018 Category: Pathology Tags: Correspondence Source Type: research

The phrase NIFTP accentuates, rather than resolves, the current issues with thyroid neoplasia classification
Cheng Liu, BmedSci, MBBS, FRCPA john.liu@qimrberghofer.edu.au (Source: Human Pathology)
Source: Human Pathology - June 4, 2018 Category: Pathology Tags: Correspondence Source Type: research

Aberrant expression of stress-induced phosphoprotein 1 in colorectal cancer and its clinicopathologic significance
Stress-Inducible Phosphoprotein1 (STIP1) is an adaptor protein that bridges HSP70 and HSP90 folding and a secretory protein that regulates malignant tumor progression. The aim of the present study was to demonstrate the clinicopathological significance and prognostic role of STIP1 in colorectal cancer (CRC). We used data from The Cancer Genome Atlas (TCGA) to analyze STIP1 expression in CRC and utilized 8 pairs of fresh-frozen tissue samples to investigate STIP1 expression in CRC tissues and adjacent normal tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays. (Source: Human Pathology)
Source: Human Pathology - June 4, 2018 Category: Pathology Authors: Zhimei Zhang, Hui Ren, Liang Yang, Xinhua Zhang, Wei Liang, Hui Wu, Leilei Huang, Jihui Kang, Jianbo Xu, Ertao Zhai, Shirong Cai, Yulong He Tags: Original Contributions Source Type: research

Masthead
(Source: Human Pathology)
Source: Human Pathology - June 1, 2018 Category: Pathology Source Type: research

Table of Contents
(Source: Human Pathology)
Source: Human Pathology - June 1, 2018 Category: Pathology Source Type: research

Editorial Board
(Source: Human Pathology)
Source: Human Pathology - June 1, 2018 Category: Pathology Source Type: research

In This Issue
(Source: Human Pathology)
Source: Human Pathology - June 1, 2018 Category: Pathology Source Type: research

Frequent expression of somatostatin receptor 2a in olfactory neuroblastomas: a new and distinctive feature
Olfactory neuroblastoma (ONB) is a malignant neuroendocrine neoplasm with a usually slow course, but with considerable recurrence rate. Many neuroendocrine tumors have shown good response to the treatment with somatostatin analogues and somatostatin radioreceptor therapy. In ONBs, there are scarce data on somatostatin-based treatment and the cellular expression of somatostatin receptors (SSTR), the prerequisite for binding and effect of somatostatin on normal and tumor cells. The aim of our study was to investigate the immunohistochemical expression of somatostatin receptor (SSTR) 2A and 5 in a cohort of 40 ONBs. (Source: Human Pathology)
Source: Human Pathology - May 25, 2018 Category: Pathology Authors: Piotr Czapiewski, Micha ł Kunc, Adam Gorczyński, Johannes Haybaeck, Krzysztof Okoń, Joanna Reszec, Anna Lewczuk, Jaroslaw Dzierzanowski, Joanna Karczewska, Wojciech Biernat, Mario Turri-Zanoni, Paolo Castelnuovo, Cecilia Taverna, Alessandro Franchi, St Tags: Original Contributions Source Type: research

Initial diagnosis of insignificant Cancer, HGPIN, ASAP and negative have the same rate of upgrade to Gleason ≥7 on repeat prostate biopsy
Extended prostate needle core biopsies are standard of care for the diagnosis of prostatic carcinoma. Subsequent biopsies may be performed for a variety of indications. Knowledge of biopsy characteristics indicating risk for progression may have utility to guide therapeutic management. Prostate needle core biopsies performed between 2008 –2014 were reviewed. Patients with at least 1 subsequent biopsy were identified. Cases were categorized by worst initial diagnosis. Gleason ≤6 carcinoma was further classified as significant or insignificant with insignificant defined as: ≤2 cores with carcinoma, sites with &le...
Source: Human Pathology - May 24, 2018 Category: Pathology Authors: Saranya Prathibha, Kashika G. Goyal, Debra L. Zynger Tags: Original contribution Source Type: research

The diagnostic role of BAP1 in serous effusions
The aim of this study was to analyze the diagnostic role of BAP1 in effusion cytology. Effusions (n=258), consisting of 53 malignant mesotheliomas and 205 other cancers, the majority carcinomas (62 breast, 60 ovarian, 31 lung, 51 carcinomas of other origin, 1 melanoma), were analyzed for BAP1 expression using immunohistochemistry. BAP1 was lost in 46 (87%) mesotheliomas, compared to 4/205 (2%) loss in other cancers (P (Source: Human Pathology)
Source: Human Pathology - May 23, 2018 Category: Pathology Authors: Ben Davidson, Martin T ötsch, Jeremias Wohlschlaeger, Thomas Hager, Maurizio Pinamonti Tags: Original Contributions Source Type: research

TOX expression decreases with progression of colorectal cancers and is associated with CD4 T-cell density and Fusobacterium nucleatum infection
Fusobacterium nucleatum (F. nucleatum) in the tumor microenvironment plays an important role in the development of colorectal cancer (CRC). The underlying mechanism of action, however, remains to be elucidated. We evaluated the relation of F. nucleatum amount to thymocyte selection-associated high-mobility group box (TOX) protein expression and CD4+ T cell density in 138 human colorectal tissues. TOX expression and CD4+ T cell density in F. nucleatum negative tissues were significantly higher compared to those in F. (Source: Human Pathology)
Source: Human Pathology - May 21, 2018 Category: Pathology Authors: Ting Chen, Qing Li, Xiaoyan Zhang, Ran Long, Yaxin Wu, Jiao Wu, Xiangsheng Fu Tags: Original Contributions Source Type: research

Pathological significance and prognostic roles of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios in clear cell renal cell carcinoma
In this study, the clinical significance of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios were investigated in patients with clear cell RCC. The densities of CD57+, CD68+, and mast cells were evaluated by immunohistochemical techniques in 179 patients. (Source: Human Pathology)
Source: Human Pathology - May 19, 2018 Category: Pathology Authors: Hiromi Nakanishi, Yasuyoshi Miyata, Yasushi Mochizuki, Takuji Yasuda, Yuichiro Nakamura, Kyohei Araki, Yuji Sagara, Tomohiro Matsuo, Kojiro Ohba, Hideki Sakai Tags: Original Contributions Source Type: research

Clinicopathological characteristics of thyroid transcription factor 1-negative small cell lung cancers
This study aimed to elucidate the characteristics of TTF-1-negative SCLC. We studied the associations between the expression of TTF-1 and the clinicopathological factors associated with SCLC, including survival and expression of neuroendocrine markers (synaptophysin, chromogranin A, and CD56), neuroendocrine cell-specific transcription factors (achaete-scute homolog like 1 (ASCL1), BRN2), a proliferation marker (Ki-67 labeling index), and an oncogene (Nuclear Factor 1B (NF1B)). (Source: Human Pathology)
Source: Human Pathology - May 19, 2018 Category: Pathology Authors: Yuko Iida, Shinobu Masuda, Yoko Nakanishi, Tetsuo Shimizu, Haruna Nishimaki, Mai Takahashi, Mari Hikichi, Shuichiro Maruoka, Yasuhiro Gon, Noriaki Takahashi, Shu Hashimoto Tags: Original contribution Source Type: research

Budding and tumor infiltrating lymphocytes – combination of both parameters predicts survival in colorectal cancer and leads to new prognostic subgroups
Tumor budding is an independent prognostic factor in colorectal cancer (CRC) and has recently been well defined by the International Concensus Conference on Tumor Budding (ITBCC). Tumor infiltrating lymphocytes (TILs) are also an issue in different human cancers and correlate with prognosis in CRC.Here we evaluate the combination of budding and TILs in CRC with regard to prognosis.Hematoxylin and Eosin (H&E) stained slides of 501 CRC patients, diagnosed between 2005 and 2010 were reevaluated for tumor budding according to the ITBCC-criteria. (Source: Human Pathology)
Source: Human Pathology - May 19, 2018 Category: Pathology Authors: Corinna Lang-Schwarz, Balint Melcher, Franziska Haumaier, Klaus Lang-Schwarz, Thomas Rupprecht, Michael Vieth, William Sterlacci Tags: Original contribution Source Type: research

Clinicopathological analysis of immunohistochemical expression of retinoic acid-related orphan receptor- γt in peripheral T-cell lymphoma, not otherwise specified
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is cytologically and phenotypically heterogeneous. Retinoic acid-related orphan receptor- γt (RORγt) is a transcription factor that regulates the differentiation of naïve CD4+ helper T-cells to Th17 cells. In the present study, we immunohistochemically confirmed the expression of RORγt in PTCL-NOS. Pathological and clinical investigations were performed for 170 cases of PTCL-NOS. ROR γt-positive cases accounted for 17.6% (30/170) of the total cases and they showed a significantly higher frequency of CD8 positivity (P=.033), lower co...
Source: Human Pathology - May 15, 2018 Category: Pathology Authors: Eriko Yanagida, Hiroaki Miyoshi, Keisuke Kawamoto, Kazutaka Nakashima, Kotaro Matsuda, Kyohei Yamada, Reiji Muto, Koji Nagafuji, Masao Seto, Koichi Ohshima Tags: Original contribution Source Type: research

BAP1 loss is unusual in well-differentiated papillary mesothelioma and may predict development of malignant mesothelioma
Literature on BRCA1-associated protein 1 (BAP1) expression status in well-differentiated papillary mesothelioma (WDPM) is limited. In the present study, we examined the prevalence of BAP1 loss in WDPM by immunohistochemistry with clinical correlation, along with CDKN2A deletion status by fluorescence in situ hybridization (FISH). Eight patients diagnosed as WDPM were identified from the surgical pathology file. Adenomatoid tumors (n=8) and malignant mesothelioma (MM) (n=39) were included for comparison. (Source: Human Pathology)
Source: Human Pathology - May 12, 2018 Category: Pathology Authors: Hee Eun Lee, Julian R. Molina, William R. Sukov, Anja C. Roden, Eunhee S. Yi Tags: Original contribution Source Type: research

TPL2 expression is correlated with distant metastasis and poor prognosis in colorectal cancer
Tumor progression locus 2 (TPL2) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K). The present study aimed to elucidate the clinicopathological significance and prognostic role of TPL2 expression in colorectal cancer (CRC) through immunohistochemistry. In the present study, the correlations between TPL2 expression and clinicopathological parameters, including survival rate, were investigated using 262 archival paraffin-embedded CRC tissue samples. In addition, the correlation between TPL2 expression and tumor-infiltrating lymphocytes was evaluated using immunoscore. (Source: Human Pathology)
Source: Human Pathology - May 12, 2018 Category: Pathology Authors: Jung-Soo Pyo, Mee Ja Park, Chang-Nam Kim Tags: Original contribution Source Type: research

Prognostic factors in primary anorectal melanoma: a Clinicopathologic study of 60 cases in China
To investigate the clinicopathologic features and prognostic factors of primary anorectal melanoma, we described the clinical presentations, histopathology, and prognosis of 60 cases in China. Patients' age ranged from 17 to 86years with a female-to-male ratio of 2.33:1. The prevalent anatomic site of tumor was anorectum. The mean tumor thickness was 11.5mm and mean tumor size was 2.9cm. Abdominoperineal resection was performed on 38 (63.3%) patients, while wide local excision on 22 (36.7%) patients. (Source: Human Pathology)
Source: Human Pathology - May 12, 2018 Category: Pathology Authors: Min Ren, Yawen Lu, Jiaojie Lv, Xuxia Shen, Jincheng Kong, Bo Dai, Yunyi Kong Tags: Original Contributions Source Type: research

Small cell carcinoma of the urinary bladder: a Clinicopathologic and Immunohistochemical analysis of 81 cases
Small cell carcinoma (SmCC) of the bladder is a rare disease. We retrospectively studied a large series of bladder SmCC from a single institution. The patients included 69 men and 12 women with a mean age of 68years. Most bladder SmCC were presented at advanced stage with tumors invading the muscularis propria and beyond (n=77). SmCC was pure in 27 cases and mixed with other histologic types in 54 cases, including urothelial carcinoma (UC) (n=32), UC in situ (n=26), glandular (n=14), micropapillary (n=4), sarcomatoid (n=4), and squamous (n=3), and plasmacytoid (n=1) features. (Source: Human Pathology)
Source: Human Pathology - May 12, 2018 Category: Pathology Authors: Gang Wang, Li Xiao, Miao Zhang, Ashish M. Kamat, Arlene Siefker-Radtke, Colin P. Dinney, Bogdan Czerniak, Charles C. Guo Tags: Original Contributions Source Type: research

New insights into hypoxia-related mechanisms involved in different microvascular patterns of bronchopulmonary carcinoids and poorly differentiated neuroendocrine carcinomas. Role of ribonuclease T2 (RNASET2) and HIF-1 alpha
In this study, we investigated RNASET2 expression in well-differentiated and poorly differentiated neuroendocrine neoplasms of the lung (Lu-NENs), which are known to show clear-cut differences in morphology, biology and clinical behavior. (Source: Human Pathology)
Source: Human Pathology - May 12, 2018 Category: Pathology Authors: Silvia Uccella, Stefano La Rosa, Debora Scaldaferri, Laura Monti, Roberta Maragliano, Elisa Sorrenti, Marzia Gariboldi, Roberto Taramelli, Fausto Sessa, Francesco Acquati Tags: Original Contributions Source Type: research

Hepatic micrometastases are associated with poor prognosis in patients with liver metastases from neuroendocrine tumors of the digestive tract
Pathologic examination of hepatic metastasectomies from patients with metastatic small intestinal or pancreatic neuroendocrine tumor frequently reveals micrometastases undetectable by radiologic or macroscopic gross examination. This finding raises the possibility that undetectable micrometastases remain in these patients after metastasectomy. Here we examined liver resections for micrometastases and assessed their impact on prognosis. Hepatic metastasectomies from 65 patients with neuroendocrine tumor of the small intestine (N=43) or pancreas (N=22) were reviewed for the presence of micrometastases, which were defined as ...
Source: Human Pathology - May 12, 2018 Category: Pathology Authors: William E. Gibson, Raul S. Gonzalez, Justin M.M. Cates, Eric Liu, Chanjuan Shi Tags: Original contribution Source Type: research

Role of HNF1 β in the differential diagnosis from other germ cell tumors
Identification of the yolk sac tumor (YST) component in germ cell tumors (GCT) may prove challenging, and highly sensitive and specific immunohistochemical markers are still lacking. Preliminary data from the literature suggest that HNF1 β may represent a sensitive marker of YST. The specificity of HNF1β has not been addressed in GCT. A cohort of 49 YST specimens from 45 patients was designed, occurring either as pure tumors, or as a component of a mixed GCT. Immunohistochemistry was conducted on whole tumor sections using HNF1β. (Source: Human Pathology)
Source: Human Pathology - May 10, 2018 Category: Pathology Authors: Anne-Laure Rougemont, Jean-Christophe Tille Tags: Original Contributions Source Type: research

Determination of the mutational landscape in Taiwanese patients with papillary thyroid cancer by whole-exome sequencing
Among women in Taiwan, thyroid cancer is the fifth most common malignant neoplasia. However, genomic profiling of papillary thyroid cancer (PTC) cases from Taiwan has not been attempted previously. We used whole-exome sequencing to identify mutations in a cohort of 19 PTC patients. Sequencing was performed using the Illumina system; Sanger sequencing was used to validate all identified mutations. We identified new somatic mutations in APC, DICER1, LRRC8D and NDRG1. We also found somatic mutations in ARID5A, CREB3L2, MDM4, PPP2R5A and TFPT; mutations in these genes had been found previously in other tumors, but had not been...
Source: Human Pathology - May 9, 2018 Category: Pathology Authors: Chun-Chi Chang, Ya-Sian Chang, Hsi-Yuan Huang, Kun-Tu Yeh, Ta-Chih Liu, Jan-Gowth Chang Tags: Original contribution Source Type: research

Overexpression of MCM6 predicts poor survival in patients with glioma
Minichromosome maintenance proteins (MCMs) play an essential role in DNA replication and other cellular activities. However, their expression levels and clinical value in glioma are unclear. In the present study, we analyzed the relationship between MCM mRNA expression and clinical parameters in 325 gliomas, and found that MCM6 presented high expression and was associated with poor survival. Immunohistochemistry analysis of an independent dataset of 423 glioma tissues confirmed the overexpression of MCM6 protein, especially in glioblastomas (GBMs) with shorter overall survival (OS). (Source: Human Pathology)
Source: Human Pathology - May 9, 2018 Category: Pathology Authors: Hong-Qing Cai, Zhi-Jian Cheng, Hai-Peng Zhang, Peng-Fei Wang, Yu Zhang, Jia-Jie Hao, Ming-Rong Wang, Jing-Hai Wan Source Type: research

Evaluating agreement, histological features and relevance of separating pleomorphic and florid lobular carcinoma-in-situ subtypes
Morphological variants of lobular carcinoma in situ (LCIS) include classical- (CLCIS), pleomorphic- (PLCIS) and florid-type (FLCIS). Treatment guidelines suggest managing PLCIS and FLCIS like ductal carcinoma in situ (DCIS); therefore accurate identification of LCIS subtypes is critical. However significance of separating PLCIS from FLCIS is not clear. Also inter-observer agreement in identifying LCIS subtypes, using contemporary criteria, is not known. We aimed to evaluate inter-observer agreement amongst breast pathologists in diagnosing LCIS subtypes and use the agreement data to justify LCIS classification for manageme...
Source: Human Pathology - May 9, 2018 Category: Pathology Authors: Kamaljeet Singh, Cherie Paquette, Elizabeth T Kalife, Yihong Wang, Shamlal Mangray, M Ruhul Quddus MD MPhil, Margaret M. Steinhoff Tags: Original contribution Source Type: research

The implications of TrkA and MET aberrations in de novo salivary duct carcinoma
In this study, the recently identified receptor tyrosine kinases MET and tropomyosin-receptor kinase (Trk) were investigated as potential therapeutic targets. A total of 28 consecutive, surgically resected, de novo SDC cases were selected after evaluating histology and immunohistochemical expression of androgen receptor. (Source: Human Pathology)
Source: Human Pathology - May 9, 2018 Category: Pathology Authors: Hyang Joo Ryu, Yoon Woo Koh, Sun Och Yoon Tags: Original Contributions Source Type: research

Next-generation sequencing analysis for gastric adenocarcinoma with enteroblastic differentiation: emphasis on the relationship with hepatoid adenocarcinoma
In this study, we employed next-generation sequencing (NGS) to establish a molecular/clinicopathological concept of GAED and clarify whether these two tumors should be grouped together in one category. (Source: Human Pathology)
Source: Human Pathology - May 8, 2018 Category: Pathology Authors: Yoichi Akazawa, Tsuyoshi Saito, Takuo Hayashi, Yuka Yanai, Sho Tsuyama, Keisuke Akaike, Yoshiyuki Suehara, Fumiyuki Takahashi, Kazuya Takamochi, Hiroya Ueyama, Takashi Murakami, Sumio Watanabe, Akihito Nagahara, Takashi Yao Tags: Original contribution Source Type: research

Masthead
(Source: Human Pathology)
Source: Human Pathology - May 1, 2018 Category: Pathology Source Type: research

Table of Contents
(Source: Human Pathology)
Source: Human Pathology - May 1, 2018 Category: Pathology Source Type: research

Editorial Board
(Source: Human Pathology)
Source: Human Pathology - May 1, 2018 Category: Pathology Source Type: research