Primary peritoneal Epithelioid mesothelioma of clear cell type with a novel VHL gene mutation: a case report
Clear cell variant of epithelioid mesothelioma is an extremely rare tumor with only isolated cases reported so far in the peritoneum. Here, we report a case of peritoneal epithelioid mesothelioma, clear cell variant, in a 63-year-old female patient with a novel VHL gene mutation and an unusual indolent clinical course. The patient, who has no clinical history of asbestos exposure, presented with a 27.2 cm upper abdominal mass and a 5.5 cm liver lesion. Retrospective review of the patient's abdominal CT scan 4 years ago showed two small abdominal lesions that were felt clinically to represent hemangiomas. (Source: Human Pathology)
Source: Human Pathology - August 14, 2018 Category: Pathology Authors: Alexandria Smith-Hannah, Rana Naous Tags: Case study Source Type: research

Pseudo –“solid pseudopapillary neoplasms” of the testis: in reality Sertoli cell tumors
We read with interest and concern two reports published in Human Pathology [1,2] concerning testicular neoplasms that were felt to be “testicular analogues” of the well-known “solid pseudopapillary neoplasm” (SPN) of the pancreas, albeit in one of the 2 papers the authors preferred to designate the tumors as primary signet ring stromal tumors of the testis [1]. Although we acknowledge that the pseudopapillae in the SPNs ma y be limited in amount, their apparent absence, according to the descriptions of the microscopic findings in all of the 14 tumors in these 2 reports, struck us as unusual for a tu...
Source: Human Pathology - August 12, 2018 Category: Pathology Authors: Thomas M. Ulbright, Robert H. Young Tags: Correspondence Source Type: research

Tumor necrosis factor α-induced protein 8 expression as a predictor of prognosis and resistance in patients with advanced ovarian cancer treated with neoadjuvant chemotherapy
We explored the correlation of tumor necrosis factor α-induced protein 8 (TNFAIP8) with platinum resistance in ovarian cancers (OCs) treated with neoadjuvant chemotherapy (NACT). We observed a significant trend of decreased TNFAIP8 expression after NACT (P=.042), and the extent of decreased TNFAIP8 expression following NACT was positively associated with response to NACT (P=.013). Interestingly, in patients treated with NACT, the extent of decreased TNFAIP8 expression following NACT in tumor (change in immunohistochemistry [ΔIHC] score≤−1 vs. (Source: Human Pathology)
Source: Human Pathology - August 11, 2018 Category: Pathology Authors: Jing Wang, Hongyu Gao, Guohui Liu, Lina Gu, Chang Yang, Fengmin Zhang, Tianbo Liu Tags: Original contribution Source Type: research

EGFR gene copy number decreases during anti-EGFR antibody therapy in colorectal cancer
Epidermal growth factor receptor (EGFR) gene copy number (GCN) increase is associated with a favourable anti-EGFR antibody treatment response in RAS wild-type metastatic colorectal cancer. However, there are limited comparative data regarding the EGFR GCN in primary colorectal cancer tumours and corresponding metastases or the effect of anti-EGFR antibody treatment on EGFR GCN in recurrent disease. Additionally, little is known about the potential EGFR GCN changes during anti-EGFR therapy in comparison to other treatment regimens. (Source: Human Pathology)
Source: Human Pathology - August 7, 2018 Category: Pathology Authors: Eva-Maria Birkman, Tuulia Avoranta, Annika Ålgars, Eija Korkeila, Minnamaija Lintunen, Laura Lahtinen, Teijo Kuopio, Raija Ristamäki, Olli Carpén, Jari Sundström Tags: Original contribution Source Type: research

So-called “non-classic” ciliated Muconodular papillary tumors: a comprehensive comparison of the Clinicopathological and molecular features with classic ciliated Muconodular papillary tumors
Ciliated muconodular papillary tumors (CMPTs) are characterized by tripartite cellular components of ciliated columnar cells, mucinous cells, and basal cells with predominantly papillary architecture. Some peripheral lung nodules may not demonstrate papillary architecture and tripartite cells that show bronchiolar differentiation; these nodules are termed “CMPTs with non-classic morphology” by some authors. To validate the rationality of “non-classic” CMPTs and to analyze the clinicopathological features of CMPTs, we enrolled 21 cases of lung nodules, comprising classic CMPTs (n=11) and so-called &l...
Source: Human Pathology - August 6, 2018 Category: Pathology Authors: Qiang Zheng, Rongkui Luo, Yan Jin, Xuxia Shen, Ling Shan, Lei Shen, Yingyong Hou, Yuan Li Tags: Original contribution Source Type: research

Chronic lymphocytic leukemia with proliferation centers in bone marrow is associated with younger age at initial presentation, complex karyotype and TP53 disruption
The presence of expanded proliferation centers (PCs) in lymph nodes involved by chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has been associated with adverse clinical outcomes, but the frequency and significance of PCs in bone marrow (BM) remains unclear. The study group included 36 patients with BM involvement by CLL in which PCs were present. We compared this group with 110 randomly selected BM samples involved by CLL without morphologically discernable PCs. Patients with PCs in BM were younger (median age, 53years [range,18 –71] versus 58years [range, 31–82]; P=.007), more frequently exp...
Source: Human Pathology - August 6, 2018 Category: Pathology Authors: Sofia Garces, Joseph D. Khoury, Rashmi Kanagal-Shamanna, Alireza Salem, Sa A. Wang, Chi Young Ok, Shimin Hu, Keyur P. Patel, Mark J. Routbort, Rajyalakshmi Luthra, Guilin Tang, Ellen J. Schlette, Carlos E. Bueso-Ramos, L. Jeffrey Medeiros, Sanam Loghavi Tags: Original contribution Source Type: research

The correlation of NLRC3 expression to the progression and prognosis of hepatocellular carcinoma
NLRC3 is a member of the NLR (nucleotide-binding domain and leucine-rich repeat) family protein that plays a role in inflammation and immunity. Although chronic inflammation has been identified as a hallmark of cancer, whether NLRC3 expression correlated to the development and prognosis of hepatocellular carcinoma (HCC) is unclear. In the present study, we first used Oncomine and OncoLnc database to determine the clinical significance of NLRC3 in HCC. Then we performed quantitative real-time polymerase chain reaction (qRT-PCR), western-blot and immunohistochemical staining (IHC), and analyzed the correlation between NLRC3 ...
Source: Human Pathology - August 3, 2018 Category: Pathology Authors: Ying-Yu Ma, Guo-Hai Zhang, Jingjing Li, Shi-Bing Wang, Zhi-Ming Hu, Cheng-Wu Zhang, Erguang Li Tags: Original contribution Source Type: research

ATRX loss is an independent predictor of poor survival in pancreatic neuroendocrine tumours
Pancreatic neuroendocrine tumours (PanNETs) are rare neoplasms accounting for 1-2% of all pancreatic tumours. The biological behaviour of PanNETs is heterogeneous and unpredictable, adding to the difficulties of clinical management. The DAXX (death domain associated protein) and ATRX (alpha-thalassemia/mental retardation syndrome X-linked) genes encode proteins involved in SWI/SNF-like chromatin remodelling. Somatic inactivating mutations in DAXX and ATRX are frequent in PanNETs, mutually exclusive, and associated with telomere dysfunction resulting in genomic instability and alternate lengthening of telomeres. (Source: Human Pathology)
Source: Human Pathology - August 3, 2018 Category: Pathology Authors: Angela Chou, Malinda Itchins, Philip R de Reuver, Jennifer Arena BSc, Adele Clarkson BSc, Amy Sheen BSc, Loretta Sioson BSc, Veronica Cheung MChD, Aurel Perren, Christopher Nahm, Anubhav Mittal, Jaswinder S Samra, Marina Pajic, Anthony J Gill Tags: Original contribution Source Type: research

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

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

Editorial board
(Source: Human Pathology)
Source: Human Pathology - August 1, 2018 Category: Pathology Source Type: research

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

Reproducibility of PD-L1 immunohistochemistry interpretation across various types of genitourinary and head/neck carcinomas, antibody clones, and tissue types
Programmed death-ligand 1 (PD-L1) expression by tumor cells is a mechanism for downregulation of antitumor T cell responses and is a target for immunotherapy in various cancers. PD-L1 status as a predictor of treatment response has led to the development of multiple platforms with different reference cutoffs. We studied 128 cases of genitourinary and head/neck carcinomas, aiming to assess the frequency of PD-L1 positivity, interobserver reliability of PD-L1 interpretation and the concordance of PD-L1 scoring between small samples from tissue microarray (TMA) and whole sections (WS) using SP263 and SP142 clones. (Source: Human Pathology)
Source: Human Pathology - August 1, 2018 Category: Pathology Authors: Chiyun Wang, Elan Hahn, Elzbieta Slodkowska, Antoine Eskander, Danny Enepekides, Kevin Higgins, Danny Vesprini, Stanley K. Liu, Michelle R. Downes, Bin Xu Tags: Original Contributions Source Type: research

Concordance levels of PD-L1 expression by immunohistochemistry, mRNA in situ hybridization, and outcome in lung carcinomas
Targeted inhibition of programmed cell death-1 (PD-1) and its ligand (PD-L1) has emerged as first-line therapy for advanced non-small cell lung cancer. While patients with high PD-L1 expression have improved outcomes with anti-PD-1/PD-L1 directed therapies, use as a predictive biomarker is complicated by robust responses in some patients with low-level expression. Furthermore, reported PD-L1 levels in lung cancers vary widely and discrepancies exist with different antibodies. PD-L1 expression was thus compared by immunohistochemistry (IHC) versus RNA in situ hybridization (ISH) in 112 lung cancers by tissue microarray: 51 ...
Source: Human Pathology - August 1, 2018 Category: Pathology Authors: Joseph D. Coppock, Ashley K. Volaric, Anne M. Mills, Alejandro A. Gru Tags: Original Contributions Source Type: research

Anaplastic thyroid carcinoma: an epidemiologic, histologic, immunohistochemical and molecular single institution study
Anaplastic thyroid carcinoma (ATC) is a highly aggressive form of thyroid cancer. A single institution thyroid cancer cohort of ATC was identified within the last ten years at our institution. Retrospective analysis revealed that the frequency of ATC was 0.5% (11/2106 thyroid carcinomas). The average age at diagnosis of ATC was 74 years, and the female to male ratio was 1.2:1. ATC presented as a rapidly enlarging neck mass involving predominantly the left thyroid lobe (7/11, 64%). Cervical adenopathy was present in 7/11 (64%) of cases. (Source: Human Pathology)
Source: Human Pathology - August 1, 2018 Category: Pathology Authors: Audrey Deeken-Draisey, Guang-Yu Yang, Juehua Gao, Borislav A. Alexie Tags: Original Contributions Source Type: research

Strong SOX10 expression in HPV-related multiphenotypic sinonasal carcinoma: report of six new cases validated by high-risk HPV mRNA in situ hybridization test
HPV-related multiphenotypic sinonasal carcinoma (HMSC) is associated with high-risk human papillomavirus (HR-HPV) infection. Using HR-HPV mRNA in situ hybridization (ISH), we reported six new HMSC cases and compared their histopathology with that of sinonasal adenoid cystic carcinoma (ACC). Using p16 immunohistochemistry (IHC) and HR-HPV ISH, we retrospectively identified six HMSC cases. All HMSC cases were positive for HR-HPV mRNA ISH and p16 IHC. Two HMSC cases had overlying atypical squamous epithelium and one also had invasive squamous cell carcinoma (SCC). (Source: Human Pathology)
Source: Human Pathology - July 30, 2018 Category: Pathology Authors: Min-Shu Hsieh, Yi-Hsuan Lee, Ying-Tai Jin, Wen-Chih Huang Tags: Original Contributions Source Type: research

Epithelial-to-mesenchymal transition related transcription factors are upregulated in ependymomas and correlate with a poor prognosis
Epithelial-to-mesenchymal transition (EMT) plays an important role in invasion and metastasis of various cancers including gliomas. EMT has also been linked to cancer stem cells and resistance to chemotherapy. An initial in-silico data mining in a published ependymoma (EPN) patient series (GSE21687) revealed upregulation of EMT-Transcription factors (EMT-TFs) in tumor samples. Further, quantitative real-time polymerase chain reaction (q-RT-PCR) based gene expression analysis of EMT-TFs in 96 EPNs showed significant up-regulation of SNAI1, SNAI2, ZEB1, and TWIST1 as compared to normal brain, associated with upregulation of ...
Source: Human Pathology - July 29, 2018 Category: Pathology Authors: Prit Benny Malgulwar, Aruna Nambirajan, Pankaj Pathak, Madhu Rajeshwari, Vaishali Suri, Chitra Sarkar, Manmohan Singh, Mehar Chand Sharma Tags: Original contribution Source Type: research

Protein expression of the transcription factors DMRT1, TCLF5, and OCT4 in selected germ cell neoplasms of the testis
In the present study, we investigated protein expression of the transcription factors mammalian doublesex and mab-3 related transcription factor 1 (DMRT1), basic helix –loop–helix transcription factor-like 5 (TCLF5), and octamer-binding transcription factor 4 (OCT4) in normal human spermatogenesis, testicular mixed germ cell-sex cord stromal tumor (MGC-SCST), spermatocytic tumor, and seminoma. In normal human spermatogenesis, DMRT1 is expressed in the nuclei o f spermatogonia, but not in those of more mature germ cells. (Source: Human Pathology)
Source: Human Pathology - July 29, 2018 Category: Pathology Authors: Lawrence M. Roth, Michal Michal, Michael Michal, Liang Cheng Tags: Original contribution Source Type: research

Histopathologic findings in lung biopsies from patients with primary biliary cholangitis
Primary biliary cholangitis (PBC) is a progressive autoimmune disease of the liver causing destruction of intrahepatic bile ducts, associated with lymphocytic and granulomatous inflammation. PBC has been associated with many extrahepatic manifestations including interstitial lung disease. However, comprehensive pulmonary histopathology in PBC has not been well documented. Sixteen PBC patients who underwent lung biopsies were identified from surgical pathology files in three institutions. Histopathologic review was performed. (Source: Human Pathology)
Source: Human Pathology - July 29, 2018 Category: Pathology Authors: Hee Eun Lee, Andrew Churg, Jay H. Ryu, Ana Maria Bilawich, Brandon T. Larsen, Henry D. Tazelaar, Eunhee S. Yi Tags: Original contribution Source Type: research

Immunohistochemical profiles of different subsets of Merkel cell carcinoma
The objectives of the current study were (1) to examine the immunohistochemical profile of different subsets of MCC to determine whether predictable subset-specific patterns exist and (2) to establish whether shared immunophenotypic patterns might reveal links between individual subsets, as demonstrated previously at a genetic level. In 52 cases of MCC, stratified by viral status and morphology, we studied 5 markers commonly used in the diagnostic evaluation of these tumors (CK20, CK7, chromogranin, neurofilament and TTF-1). (Source: Human Pathology)
Source: Human Pathology - July 29, 2018 Category: Pathology Authors: Sylvia Pasternak, Michael D Carter, Thai Yen Ly, Steve Doucette, Noreen M. Walsh Tags: Original Contributions Source Type: research

Can tumor-associated macrophages in ductal carcinoma in situ (DCIS) on biopsy predict invasive carcinoma on excision?
Recent trials have explored surveillance of ductal carcinoma in situ (DCIS) without complete excision but it is difficult to fully exclude an associated, un-sampled invasive focus. Tumor microenvironment, including tumor-associated macrophages, may play a role in the transition from in situ to invasive carcinoma and the presence of CD163 positive cells with DCIS has been associated with increased risk of progression to invasive carcinoma. We aimed to evaluate the role of DCIS-associated CD163 positive cells on biopsy in predicting associated invasion on excision. (Source: Human Pathology)
Source: Human Pathology - July 29, 2018 Category: Pathology Authors: Deepthi Hoskoppal, Emily S Reisenbichler Tags: Original contribution Source Type: research

Ectopic expression of band 3 anion transport protein in colorectal cancer revealed in an autoimmune hemolytic anemia patient
Cancer patients occasionally have anemia with high mean corpuscular volume in addition to iron deficiency anemia. Secondary autoimmune hemolytic anemia (AIHA) following cancer is also observed with low frequency. To date, no causal mechanisms for these disease states have been reported. Here, we present the case of an 80-year-old woman with AIHA that was resistant to prednisolone. Further examinations revealed primary adenocarcinoma of the sigmoid colon and primary squamous cell carcinoma in the right lung. (Source: Human Pathology)
Source: Human Pathology - July 28, 2018 Category: Pathology Authors: Shinichiro Kawamoto, Toyomi Kamesaki, MT Ryota Masutani, Akihito Kitao, Kazuo Hatanaka, Masami Imakita, Toshiharu Tamaki, Takayuki Takubo Tags: Case study Source Type: research

The theranostic target prostate-specific membrane antigen is expressed in medullary thyroid Cancer
Medullary thyroid cancer (MTC) accounts for 4% of all thyroid cancers and originates from the parafollicular C-cells. Prostate-Specific Membrane Antigen (PSMA) is known for its expression in the epithelium of prostate cancer and has been demonstrated to be useful both for therapeutic and diagnostic purposes as a so-called theranostic target. As PSMA is also expressed in the neovasculature of other solid tumor types, our aim was to assess PSMA expression and its prognostic role in MTC. Tissues from patients that underwent surgery for MTC between 1988 and 2014 in five tertiary referral centers in The Netherlands were include...
Source: Human Pathology - July 25, 2018 Category: Pathology Authors: Lutske Lodewijk, Stefan M. Willems, Koen M.A. Dreijerink, Bart de Keizer, Paul J. van Diest, Abbey Schepers, Hans Morreau, Han J. Bonenkamp, Ilse A.C.H. Van Engen – van Grunsven, Schelto Kruijff, Bettien M. van Hemel, Thera P. Links, Els Nieveen van Dij Tags: Original contribution Source Type: research

Parafollicular lymphoid tissue in follicular lymphoma: nodal versus extranodal
To the Editor: (Source: Human Pathology)
Source: Human Pathology - July 24, 2018 Category: Pathology Authors: Howe J. Ree, Young-Hyeh Ko, Seok Woo Yang, Boram Lee Tags: Correspondence Source Type: research

Benign vascular tumors, cysts and pseudocysts of the adrenal gland: a contemporary multi-institutional clinicopathologic analysis of 55 cases
Benign adrenal vascular tumors, cysts and pseudocysts are a heterogeneous group of relatively uncommon entities that may pose diagnostic challenges radiologically and pathologically. However, there are only a few small cases series, systematically characterizing the clinicopathologic features of these lesions. We identified 55 cases of benign adrenal vascular tumors, cysts and pseudocysts (23 pseudocysts, 17 hemangiomas, 8 lymphangiomas, 6 angiomatous endothelial cysts and 1 arteriovenous malformation) from a multi-institutional Urologic Pathology database between 2000 –2017, and retrospectively analyzed their clinic...
Source: Human Pathology - July 21, 2018 Category: Pathology Authors: Wei Zheng, Kar-Ming Fung, Liang Cheng, Adeboye O. Osunkoya Tags: Original contribution Source Type: research

Histological features of autoimmune hepatitis: a critical appraisal
We speculate that the ‘typical’ histological features (lymphoplasmacytic interface hepatitis, emperipolesis and hepatocyte rosettes) of autoimmune hepatitis (AIH) are related to severity of hepatitis rather than etiology. We critically appraised various histologic features of AIH and compared them to cases of chronic hepatitis with similar inflammatory grade and fibrosis stage. Fifty one patients with clinically confirmed AIH were identified at our institution, of which 43 biopsies (from 42 patients) were taken prior to initiation of therapy and formed the study group. (Source: Human Pathology)
Source: Human Pathology - July 21, 2018 Category: Pathology Authors: Ananta Gurung, David N Assis, Thomas McCarty, Kisha A Mitchell, James L Boyer, Dhanpat Jain Tags: Original contribution Source Type: research

Distribution of dysplasia and cancer in the gallbladder: an analysis from a high cancer-risk population
Gallbladder dysplasia can progress to cancer and may be associated with increased cancer risk at other biliary tract sites. Thus, its accurate identification is relevant both for etiologic understanding and for clinical purposes. Data on the frequency and distribution of gallbladder dysplasia are lacking due to limited gallbladder sampling and inability to visualize dysplasia grossly. An expert pathology group used consensus criteria to review 140 totally sampled consecutive cholecystectomy specimens from Chilean women. (Source: Human Pathology)
Source: Human Pathology - July 21, 2018 Category: Pathology Authors: Jill Koshiol, Enrique Bellolio, Carolina Vivallo, Paz Cook, Juan Carlos Roa, Emma E. McGee, Hector Losada, Alison L. Van Dyke, Vanessa Van De Wyngard, Rodrigo Prado, Miguel Villaseca, Pia Riquelme, Johanna Acevedo, Vanessa Olivo, Karen Pettit, Allan Hilde Tags: Original contribution Source Type: research

Testicular germ cell tumors: revisiting a series in light of the new WHO classification and AJCC staging systems, focusing on challenges for pathologists
Testicular germ cell tumors (TGCTs) are strikingly heterogeneous, reflecting a complex tumor model, posing serious challenges for pathologists. Accurate classification and staging, according to most recent systems, is fundamental. We aimed to revise a series of consecutively diagnosed TGCTs (2005 –2016) in light of the new World Health Organization (WHO) classification and American Joint Committee on Cancer (AJCC) staging systems, discussing dilemmas imposed to pathologists. All 164 patients' clinical files/histological slides were reviewed. (Source: Human Pathology)
Source: Human Pathology - July 21, 2018 Category: Pathology Authors: Jo ão Lobo, Ana Laura Costa, Bárbara Vilela-Salgueiro, Ângelo Rodrigues, Rita Guimarães, Mariana Cantante, Paula Lopes, Luís Antunes, Carmen Jerónimo, Rui Henrique Tags: Original contribution Source Type: research

Genotype-phenotype correlation of patients with tuberous sclerosis complex-associated renal angiomyolipoma: a descriptive study
TSC2 gene mutation was repeatedly reported associated with a more severe phenotype in patients of tuberous sclerosis complex (TSC). Our current study aims to further explore whether there is such a correlation in patients with TSC-associated renal angiomyolipoma (TSC-RAML). TSC1/TSC2 gene mutation was screened by high throughput sequencing in 25 TSC-RAML patients from two medical centers. Clinical data were also carefully collected. Linear-regression analysis and student t-test were conducted by IBM SPSS Statistics Version 21.0 to analyze the genotypic-phenotypic relationship. (Source: Human Pathology)
Source: Human Pathology - July 21, 2018 Category: Pathology Authors: Shuqiang Li, Yushi Zhang, Zhiyong Wang, Yanfeng Yang, Wansheng Gao, Dongsheng Li, Jinxing Wei Tags: Original contribution Source Type: research

Prognostic and predictive values of immune infiltrate in patients with head and neck squamous cell carcinoma
This study sought to determine whether the in situ tumor-infiltrating immune lymphocytes, as a novel companion to the Immunoscore analysis, could be a promising, valuable prognostic and predictive marker in patients with head and neck squamous cell carcinoma (HNSCC). Total (CD3+) and cytotoxic (CD8+) T lymphocytes were assessed using immunohistochemistry in tumor nests and stroma obtained from patient surgical specimens. The “Immunoscore” methodology has been defined to quantify the amount of in situ immune infiltrate (from I0 to I4). (Source: Human Pathology)
Source: Human Pathology - July 20, 2018 Category: Pathology Authors: Xue-Mei Zhang, Ling-Jun Song, Juan Shen, Hao Yue, Ya-Qin Han, Chen-Ling Yang, Shi-Yun Liu, Jia-Wen Deng, Yue Jiang, Guo-Hui Fu, Wei-Wei Shen Tags: Original contribution Source Type: research

Identification of LETM1 as a marker of cancer stem-like cells and predictor of poor prognosis in esophageal squamous cell carcinoma
This study discusses the expression of LETM1 in esophageal squamous carcinoma (ESCC) and its association with cancer stem-like cells (CSC). We used immunohistochemistry in 166 ESCC tissue samples, as well as western blot, and immunofluorescent methods in ESCC cell lines to study the role of LETM1 and its association with CSC in ESCC. The expression of LETM1 was significantly higher in ESCC, and it was closely related to the primary tumor (pT) stage and clinical stage. (Source: Human Pathology)
Source: Human Pathology - July 18, 2018 Category: Pathology Authors: Zhaoting Yang, Weidong Ni, Chunai Cui, Wenbo Qi, Longzhen Piao, Yanhua Xuan Tags: Original Contributions Source Type: research

IMP3 as a prognostic biomarker in patients with malignant peritoneal mesothelioma
Malignant peritoneal mesothelioma (MPeM) is an incurable cancer with poor prognosis and several biomarkers have been suggested for screening of MPeM. The aim of our study was to evaluate the prognostic significanceas of IMP3 and Fli-1 in MPeM. Diagnostic biopsies of 44 MPeM patients were centrally collected and were immunohistochemically analyzed for expression of IMP3, Fli-1, and Ki-67. Labelling was assessed by two pathologists. Complete clinical information and follow up were obtained from patients' records. (Source: Human Pathology)
Source: Human Pathology - July 18, 2018 Category: Pathology Authors: S Hui, Z Guo-qi, G Xiao-Zhong, L Chun-Rong, L Yu-Fei, Y Dong-Liang Tags: Original Contributions Source Type: research

TFE3 is a diagnostic marker for solid pseudopapillary neoplasms of the pancreas
Aberrant Wnt signaling is a hallmark of solid pseudopapillary neoplasms of the pancreas (SPN). Transcription factor E3 (TFE3) plays a critical role in activation and regulation of the Wnt pathway, and is predicted to be a candidate gene implicated in SPN by gene regulatory network analysis. The aim of this study was to evaluate TFE3 as a marker for SPN. Paraffin embedded tissues of SPN (n = 75) and other primary pancreatic tumors were analyzed, including pancreatic neuroendocrine tumors (PanNET) (n = 17), pancreatic ductal adenocarcinomas (PDAC) (n = 14), pancreatic neuroendocrine carcinomas (PanNEC) (n = 4) and acinar cel...
Source: Human Pathology - July 18, 2018 Category: Pathology Authors: Yina Jiang, Juan Xie, Bo Wang, Yudong Mu, Peijun Liu Tags: Original contribution Source Type: research

PD-1, PD-L1 and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implications
Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has striking genetic similarity to PDAC but a significantly improved overall survival. We hypothesize that this difference could be due to the immune response to the tumor, and as such, we investigated the expression of PD-1, PD-L1 and CD163 in a series of UCOGC. To this aim, 27 pancreatic UCOGCs (11 pure and 16 PDAC-associated), 5 extra-pancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas (ACs) were immunostained using antibodies against PD-1, PD-L1 and CD163. (So...
Source: Human Pathology - July 18, 2018 Category: Pathology Authors: Claudio Luchini, Jerome Cros, Antonio Pea, Camilla Pilati, Nicola Veronese, Borislav Rusev, Paola Capelli, Andrea Mafficini, Alessia Nottegar, Lodewijk A.A. Brosens, Micha ël Noë, G. Johan A. Offerhaus, Peter Chianchiano, Giulio Riva, Paola Piccoli, Cla Tags: Original contribution Source Type: research

Histomorphometric Evaluation of the Ki-67 Proliferation Rate and CD34 Microvascular and D2-40 Lymphovascular Densities Drives the Pulmonary Typical Carcinoid Outcome
In this study, we sought to validate the importance of Ki-67 and study the relationships between Ki-67 and other stromal biomarkers of vascular density. We examined Ki-67, CD34 and D2-40 in tumor tissues from 128 patients with surgically excised typical carcinoid of the lung. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for cellular proliferation (Ki-67), microvascular density (CD34-MVD) and lymphovascular density (D2-40-LVD). (Source: Human Pathology)
Source: Human Pathology - July 18, 2018 Category: Pathology Authors: Alyne Fonseca de Vilhena, Jo ão Carlos das Neves Pereira, Edwin Roger Parra, Marcelo Luiz Balancin, Alexandre A'b Saber, Vanessa Martins, Cecilia Farhat, Marcelo Militao Abrantes, Jose Ribas Milanez de Campos, Miguel Lia Tedde, Teresa Takagaki, Vera Luiz Tags: Original contribution Source Type: research

Role of complement system in patients with biopsy-proven IgG4 related kidney disease
Hypocomplementaemia has been frequently reported in IgG4 related kidney disease (IgG4-RKD). However, studies on the role of complement system in IgG4-RKD are lacking. A total of 40429 renal biopsies from January 2010 to January 2018 were re-examined in the present study, and 17 patients were confirmed to meet the criteria of IgG4-RKD. According to the serum C3 levels, they were divided into two groups: the low C3 group (C3 (Source: Human Pathology)
Source: Human Pathology - July 18, 2018 Category: Pathology Authors: Rong Wang, Dafeng He, Lili Zhao, Shaoshan Liang, Dandan Liang, Feng Xu, Mingchao Zhang, Xiaodong Zhu, Huiping Chen, Honglang Xie, Caihong Zeng, Zheng Tang, Zhihong Liu Tags: Original Contributions Source Type: research

Immunohistochemical characteristics of Renomedullary interstitial cell tumor: a study of 41 tumors with emphasis on differential diagnosis of mesenchymal neoplasms
Renomedullary interstitial cell tumors (RMICT) are almost always incidentally identified either at autopsy or resection of the kidney for other reasons. However, rare cases have been reported which are large, resulting in a clinical mass. The immunohistochemical phenotype of usual, incidental RMICT using modern soft tissue tumor markers in is largely unknown, however, providing little information to aid in classification of larger or atypical tumors. We retrieved 41 RMICTs from 36 patients, and studied pathologic characteristics including morphology, immunohistochemistry (S100, keratin AE1/AE3, smooth muscle actin, desmin,...
Source: Human Pathology - July 18, 2018 Category: Pathology Authors: Zhichun Lu, Khaleel Al-Obaidy, Liang Cheng, Kyle D Perry, David J Grignon, Sean R Williamson Tags: Original Contributions Source Type: research

Metastatic breast Cancer simulating well-differentiated neuroendocrine neoplasms of visceral organs
A series of metastatic breast carcinoma (MBC) mimicking visceral well-differentiated neuroendocrine neoplasms has not previously been reported. We identified five consultation cases originally submitted as neuroendocrine neoplasms in females but which were found to be MBC on subsequent review. All 5 neoplasms demonstrated nested architecture and relatively uniform nuclei. Four patients had a known history of breast cancer (remote in 3 and concurrent in 1), but the metastases (3 liver, 1 lung) labeled for chromogranin and/or synaptophysin, prompting misdiagnosis as neuroendocrine neoplasm. (Source: Human Pathology)
Source: Human Pathology - July 18, 2018 Category: Pathology Authors: Jeffrey Cloutier, Elizabeth D. Thompson, Ashley Cimino-Mathews, Lisa M. Rooper, Andres Matoso, Pedram Argani Tags: Original Contributions Source Type: research

Roles of human epidermal growth factor receptor family in pulmonary lymphangioleiomyomatosis
Lymphangioleiomyomatosis (LAM) is a rare and refractory disease that affects women of reproductive age. Several target therapies are used to manage LAM but no curative modes of treatment have been reported yet. Therefore, in this study, we focused on targeting human epidermal growth factor receptor (HER) family proteins as a treatment strategy for LAM. In antibody array analysis, HER signaling was detected in the proteins extracted from LAM tissues. We then evaluated the expression of HER family members in 34 pulmonary LAM specimens using both immunohistochemistry and quantitative reverse transcription polymerase chain rea...
Source: Human Pathology - July 17, 2018 Category: Pathology Authors: Kazuma Kobayashi, Yasuhiro Miki, Ryoko Saito, Koko Adachi, Kuniaki Seyama, Yoshinori Okada, Hironobu Sasano Tags: Original contribution Source Type: research

Tumor-infiltrating lymphocytes associate with outcome in non-endemic nasopharyngeal carcinoma: a multicenter study
The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been studied recently in many cancers. For the first time in a non-endemic region, we have evaluated the prognostic value of TILs in a whole population-based nationwide cohort of nasopharyngeal carcinoma (NPC) in Finland. A total of 115 cases from Finnish hospitals were included. TILs were analyzed using hematoxylin and eosin stained slides according to the criteria of the International Immuno-Oncology Biomarker Working Group. (Source: Human Pathology)
Source: Human Pathology - July 17, 2018 Category: Pathology Authors: Alhadi Almangush, Miia Ruuskanen, Jaana Hagstr öm, Pasi Hirvikoski, Satu Tommola, Veli-Matti Kosma, Pentti Nieminen, Antti Mäkitie, Ilmo Leivo Tags: Original Contributions Source Type: research

The clinical significance of PINX1 expression in papillary thyroid carcinoma
PIN2/TERF1 interacting telomerase inhibitor 1 (PINX1) is a telomerase inhibitor located on human chromosome 8p23, and also act as a tumor suppressor in several types of cancers, including breast, gastric, ovarian and bladder cancer; However, the role of PINX1 expression in papillary thyroid carcinoma (PTC) has not been defined. Therefore, we investigated the role of PINX1 expression in PTC by analyzing the correlation between PINX1 expression and various clinicopathological factors. Immunohistochemistry for PINX1 was performed using a tissue microarray of samples taken from the 160 patients with PTC. (Source: Human Pathology)
Source: Human Pathology - July 16, 2018 Category: Pathology Authors: JiHoon Kang, Kanghee Han, Hyeon Jin Kim, Ju Hui Park, Jun Suk Kong, Sunhoo Park, Jae Kyung Myung Tags: Original Contributions Source Type: research

TPL2, a therapeutic potential target for cancer
Dear Editor, (Source: Human Pathology)
Source: Human Pathology - July 6, 2018 Category: Pathology Authors: Qianqian Wang, Hongfeng Dai Tags: Correspondence Source Type: research

Immune checkpoint blockade as a potential therapeutic strategy for undifferentiated malignancies
Undifferentiated malignancies (UMs) encompass a diverse set of aggressive tumors that pose not only a diagnostic challenge but also a challenge for clinical management. Most tumors in this category are currently treated empirically with nonspecific chemotherapeutic agents that yield extremely poor clinical responses. Given that UMs are inherently genetically unstable neoplasms with the potential for immune dysregulation and increased neoantigen production, they are likely to be particularly amenable to immune checkpoint inhibitors, which target programmed cell death protein 1 (PD-1) or its ligands, PD-L1 and PD-L2, to prom...
Source: Human Pathology - July 6, 2018 Category: Pathology Authors: Kelly A. Devereaux, Vivek Charu, Shuchun Zhao, Gregory W. Charville, Charles D. Bangs, Matt van de Rijn, Athena M. Cherry, Yasodha Natkunam Tags: Original contribution Source Type: research

Telocytes as possible precursors of PDGFRA-mutant gastrointestinal mesenchymal tumors —reply
We are pleased that Ricci et al. have provided supporting evidence for our hypothesis that the telocyte, the only CD34- and PDGFRA-positive cell of the stomach and intestines [1], is the cell of origin of inflammatory fibroid polyps (IFPs). IFPs arising sporadically or syndromically predominantly have a gain-of-function mutation within the PDGFRA gene and are CD34 and PDGFRA positive. (Source: Human Pathology)
Source: Human Pathology - July 5, 2018 Category: Pathology Authors: Paul Manley, Jagdeep S Walia, Richard Kirsch, Robert Riddell Tags: Correspondence Source Type: research

Telocytes as possible precursors of PDGFRA-mutant gastrointestinal mesenchymal tumors
(See Fig..) (Source: Human Pathology)
Source: Human Pathology - July 5, 2018 Category: Pathology Authors: Maria C. Giustiniani, Paola Lanza, Riccardo Ricci Tags: Correspondence Source Type: research

Diagnostic criterion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): absence of papillae
Pedro Weslley Rosario MD pedrowsrosario@gmail.com (Source: Human Pathology)
Source: Human Pathology - July 5, 2018 Category: Pathology Tags: Correspondence Source Type: research

Co-expression of CDX2 and CK20 in hepatocellular carcinoma, an exceedingly rare co-incidence with potential diagnostic pitfall - reply
Dear Editor, (Source: Human Pathology)
Source: Human Pathology - July 4, 2018 Category: Pathology Authors: Vishal S. Chandan, Sejal S. Shah, Michael S. Torbenson, Tsung-Teh Wu Tags: Correspondence Source Type: research

Clonality assessment of multifocal lung adenocarcinoma by pathology evaluation and molecular analysis
The aim of this study was to explore morphologic and molecular features distinguishing between multifocal lung adenocarcinoma (MLA) and intrapulmonary metastases (IM). Sixteen patients with MLAs, a total of 34 tumors, were reviewed. Four approaches were used: (1) array-comparative genomic hybridization (CGH) as a standard clonality assessment; (2) EGFR and KRAS mutational profiles as a supplementary method; (3) comprehensive histologic assessment (CHA) was method I in pathology evaluation; (4) CHA combined with lepidic (scaling) component analysis was method II. (Source: Human Pathology)
Source: Human Pathology - July 3, 2018 Category: Pathology Authors: Wei Sun, Lin Feng, Xin Yang, Lin Li, Yu Liu, Ning Lv, Dongmei Lin Tags: Original Contributions Source Type: research

Targeted gene sequencing of lynch syndrome-related and sporadic endometrial carcinomas
About one third of endometrial carcinomas (ECs), mainly of endometrioid histology, harbor the mismatch repair (MMR) defects and microsatellite instability (MSI). Among these, ECs arising in women with Lynch Syndrome (LS) account for a large proportion. To date, no somatic genetic analyses have been published comparing LS-ECs with sporadic ECs. In this work, we examined the mutational profiles of a well-characterized series of sporadic and LS-related ECs, performing exonic targeted sequencing of 16 genes mainly involved in MSI ECs. (Source: Human Pathology)
Source: Human Pathology - July 3, 2018 Category: Pathology Authors: Laura Libera, Ilaria Craparotta, Nora Sahnane, Anna Maria Chiaravalli, Laura Mannarino, Roberta Cerutti, Cristina Riva, Sergio Marchini, Daniela Furlan Tags: Declarations of interest: none Source Type: research

Neuropilin-1 (NRP-1) upregulated by IL-6/STAT3 signalling contributes to invasion in pancreatic neuroendocrine neoplasms
In this study, the expression of NRP-1 in pNEN tissue samples and pNEN cell line BON1 was analysed by Western blot, polymerase chain reaction (PCR) and immunocytochemistry upon exposure to interleukin-6 (IL-6). (Source: Human Pathology)
Source: Human Pathology - July 3, 2018 Category: Pathology Authors: Yongchao Yang, Linfei Yang, Yixiong Li Tags: Original Contributions Source Type: research