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Human Pathology

Babar Bashir, Dante J Merlino, Jeffrey A Rappaport, Esteban Gnass, Juan P Palazzo, Ying Feng, Eric R Fearon, Adam E Snook, Scott A Waldman
Colorectal cancers (CRCs) initiate through distinct mutations, including in APC pathway components leading to tubular adenomas (TAs); in BRAF, with epigenetic silencing of CDX2, leading to serrated adenomas (SAs); and in the DNA mismatch repair machinery driving microsatellite instability (MSI). Transformation through the APC pathway involves loss of the hormone GUCA2A that silences the tumor suppressing receptor GUCY2C. Indeed, oral hormone replacement is an emerging strategy to reactivate GUCY2C and prevent CRC initiation and progression...
February 1, 2019: Human Pathology
Yin P Hung, Gary M Hunninghake, Ezra R Miller, Rachel Putman, Mizuki Nishino, Tetsuro Araki, Hiroto Hatabu, Lynette M Sholl, Marina Vivero
The prevalence of incidental non-neoplastic lung disease in patients undergoing resection for mass lesions is unknown. We determined the prevalence and characteristics of parenchymal findings in patients with lung nodules, aiming to increase awareness of findings that could potentially impact patient management. 397 patients with benign or malignant mass lesions with available pre-surgical chest computed tomography scans resected between January 2001 and July 2015 were included. Retrospective histologic assessment of parenchymal abnormalities in at least one section of grossly normal lung was performed for each case by two pulmonary pathologists and correlated with original pathology reports, clinical history, and radiologic findings...
January 15, 2019: Human Pathology
Klaus Jürgen Schmitz, Matthias Losch, Abbas Agaimy
Myositis ossificans (MO) is an uncommon myofibroblastic proliferation that may closely mimic sarcoma. A 33-year old woman presented with a 2cm breast mass. A core needle biopsy showed highly cellular spindle cell proliferations with atypia and high proliferation activity. Focal areas of immature osteoid-like matrix were seen. After immunohistochemical analysis, a diagnosis of metaplastic breast cancer was made. Due to the proximity of the tumor to the rib, resection of the tumor including partial resection of the rib was carried out...
January 11, 2019: Human Pathology
Weiwei Shen, Na Niu, Barrett Lawson, Lisha Qi, Jing Zhang, Ting Li, Helong Zhang, Jinsong Liu
Ovarian cancer (OC) is the main cause of gynecological cancer-associated mortality. Improving the diagnosis is important for guiding clinical treatment. The present study aimed to investigate the relationship between expression of GATA6, a stem cell factor, and its prognosis in OC. In total, 521 OC cases were included. Immunohistochemistry analysis demonstrated that GATA6 was expressed in both high grade serous carcinoma as well as non-serous tumors. High grade serous carcinoma showed a higher percentage of GATA6 positive staining...
January 8, 2019: Human Pathology
Yanjun Hou, Hiroaki Nitta, Anil V Parwani, Zaibo Li
Triple-negative and HER2-positive breast cancers (BCs) are more aggressive than hormone receptor-positive/HER2-negative BCs and show higher levels of tumor infiltrating lymphocytes (TILs) and PD-L1 expression. Recently, US Food and Drug Administration approved anti-PD-L1 immunotherapy for solid tumors with deficient mismatch repair (MMR). In this study, we aimed to examine the prevalence of deficient MMR and its association with checkpoint immune markers in BCs. Immunohistochemistries (IHCs) with anti-MMR proteins (MLH1, PMS2, MSH2 and MSH6) and multiplex IHCs with anti-PD-L1, anti-CD8 or anti-CD163 were performed on tissue microarrays (TMAs) with 101 triple negative BCs (TNBC) and 197 HER2-positive BCs...
January 8, 2019: Human Pathology
Markku Miettinen, Anna Felisiak-Golabek, Alejandro Luiña Contreras, John Glod, Rosandra N Kaplan, J Keith Killian, Jerzy Lasota
Many sarcomas contain gene fusions that can be pathogenetic mechanisms and diagnostic markers. In this article we review selected fusion sarcomas and techniques for their detection. CIC-DUX4 fusion sarcoma is a round-cell tumor now considered an entity separate from Ewing sarcoma with a more aggressive clinical course, occurrence in older age, and predilection to soft tissues. It is composed of larger cells than Ewing sarcoma and often has prominent necrosis. Nuclear DUX4 expression is a promising immuno-histochemical marker...
January 8, 2019: Human Pathology
Jamie Lombardo, Devin Broadwater, Ryan Collins, Katherine Cebe, Robert Brady, Stephen Harrison
Mast cells are present throughout the body in low numbers. We know their role in immediate hypersensitivity and the subsequent tissue damage due to release of cytokines, vasoactive amines, and lipid mediators when mast cells are activated. Recent research has found that there is an association between an increased concentration of mast cells in the liver and the severity of hepatic fibrosis in animal models. We currently don't understand the role of mast cells in the liver with regard to fibrosis. This retrospective review study investigated whether there is a correlation between stages of fibrosis and mast cell concentrations...
December 28, 2018: Human Pathology
Mami Hatano, Hidenori Ojima, Yohei Masugi, Hanako Tsujikawa, Nobuyoshi Hiraoka, Yae Kanai, Kazuaki Shimada, Masahiro Shinoda, Michiie Sakamoto
We investigated the clinicopathological and molecular characteristics of scirrhous hepatocellular carcinoma (HCC) to elucidate its uniqueness. Samples from 120 resected HCC cases underwent immunohistochemical analysis. Tumor area containing fibrous stroma and the percentage of steatotic cells within the tumor were evaluated. In our previous report, tumors were immunohistochemically subclassified as biliary/stem cell markers-positive (B/S) (cytokeratin 19 and/or sal-like protein 4 and/or epithelial cell adhesion molecule positive), Wnt/beta-catenin signaling-related markers-positive (W/B) (beta-catenin and/or glutamine synthetase positive), or all markers negative (-/-) groups...
December 28, 2018: Human Pathology
Leonardo Boiocchi, Robert P Hasserjian, Olga Pozdnyakova, Waihay J Wong, Jochen K Lennerz, Long Phi Le, Dora Dias-Santagata, Anthony J Iafrate, Gabriela S Hobbs, Valentina Nardi
The introduction of next-generation sequencing has broadened the genetic landscape of myeloproliferative neoplasms (MPNs) beyond JAK2, MPL and CALR. However, the biological role and clinical impact of most other mutations is not well defined. We interrogated 101 genes in 143 BCR-ABL1-negative MPNs in chronic phase from two large institutions. We detected SF3B1 mutations in 15 cases (10%) and set to investigate the clinical, morphologic and molecular features of SF3B1 mutated (SF3B1+) MPNs in comparison to SF3B1 wild-type (SF3B1-) cases and to identify distinctive features with myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), which can show partial clinical and morphological overlap with MPNs...
December 27, 2018: Human Pathology
Gehad Youssef, Cheryl Gillett, Dyanne Rampling, Tasnim Chagtai, Alex Virasami, Jack Barton, Darren Edwards, Neil Sebire, John Anderson, Ximena Montano
The tumor suppressor TP53, promotes nerve growth factor receptor (NTRK1) Y674/Y675-phosphorylation (NTRK1-pY674/pY675), via repression of the NTRK1-phosphatase PTPN6, in a ligand independent manner, resulting in suppression of breast-cancer cell proliferation. Moreover, NTRK1-pY674/pY675 together with low levels of PTPN6 and TP53 expression is associated with favorable disease-free survival of breast-cancer patients. We determined whether in neuroblastoma this protein expression pattern impacts on relapse-free-survival (RFS)...
December 27, 2018: Human Pathology
Samantha N McNulty, Catherine E Cottrell, Katinka A Vigh-Conrad, Jamal H Carter, Jonathan W Heusel, George Ansstas, Sonika Dahiya
Glioblastoma is the most common primary malignancy of the adult central nervous system. Gliomagenesis involves a complex range of alterations, including sequence changes, copy number variations (CNVs), and epigenetic modifications, that have clinical implications for disease classification and prognosis. Thus, multiple testing modalities are required to support a complete diagnostic workup. The goal of this study was to streamline the multipart workflow by predicting both sequence changes and CNVs (specifically EGFR-amplifications) from a single NGS test...
December 27, 2018: Human Pathology
Dan Guo, Xiaoxiao Zhao, Anqi Wang, Qiu Xie, Xixia Xu, Jian Sun
The immunosuppressive effect of the programmed death (PD)-1/PD-L1 pathway plays an important role in the treatment of a variety of tumors, such as lung and breast cancer, but there is little literature about PD-1/PD-L1 in pheochromocytomas/paragangliomas (PCC/PGLs). We explored the relationship of PD-L1 and malignant behavior in 77 cases of PCC/PGL using immunohistochemistry (IHC) to assess protein expression and RNAscope to detect mRNA expression in 20 cases. The IHC data showed that 59.74% of the PCC/PGLs expressed PD-L1, and the extent of expression was highly correlated with Ki-67 (P = ...
December 27, 2018: Human Pathology
Xin Xiong, Fang Liu, Weilin Zhao, Xinhua Ji, Weigang Chen, Hong Zou, Feng Li
Primary cytomegalovirus (CMV) infection is rare in immunocompetent hosts and generally asymptomatic. CMV infective gastritis in patients without immunosuppression is very unusual. A 44-year-old man presented with complaints of intermittent epigastric pain. He had no history of organ transplantation, human immunodeficiency virus (HIV) infection, or immunosuppression of any type. Upper gastrointestinal endoscopy revealed ulcers in the gastric antrum and uplift of the gastric body. Computed Tomography (CT) scan showed obvious thickening of the gastric wall and enlargement of retroperitoneal lymph nodes, suggesting malignancy...
December 22, 2018: Human Pathology
Michael D Carter, Alison B Durham, Jayson R Miedema, Paul W Harms, May P Chan, Rajiv M Patel, Lori Lowe, Douglas R Fullen, Alexandra C Hristov, Min Wang, Aleodor A Andea
Melanocytic lesions with borderline features are diagnostically challenging. Single nucleotide polymorphism (SNP) arrays, which detect genomic copy number alterations (CNAs), can be helpful in distinguishing between nevi and melanoma. Fluorescence in situ hybridization (FISH) has been used as a more rapid, less expensive alternative to SNP array, employing a panel of probes that are often gained or lost in melanoma. We used SNP array data from 63 borderline cutaneous melanocytic lesions and 44 definitive melanomas to predict the performance of FISH testing...
December 18, 2018: Human Pathology
Dirschmid Klaus, Sterlacci William, Wöll Ewald, Tschann Peter, Rhomberg Michaela, Offner Felix
Extramural venous invasion (EMVI) is prognostic for colorectal cancer, however veins are only detected partially by normal perpendicular preparation. Therefore reported findings are conflicting and standardization is required. 239 resection specimens were examined by tangential preparation of the extramural veins at the invasive tumor front. Average follow up was 39months. The relationship of EMVI to metachronous hematogenic metastasis (MHM) was evaluated. With this method, a high prevalence of EMVI beginning in stage II is apparent...
December 17, 2018: Human Pathology
Jennifer S Ko, Loren E Clarke, Eugen C Minca, Krystal Brown, Darl D Flake, Steven D Billings
A 23-gene expression signature was recently developed as an adjunct to histopathology to differentiate melanocytic nevi from melanoma. The current study correlated the gene expression signature scores to actual clinical outcomes in cases from the first validation study. RNA was extracted from 127 archival formalin-fixed paraffin-embedded tissue sections of melanocytic lesions. Gene expression was measured using quantitative reverse transcription polymerase chain reaction and a weighting algorithm was used to generate a numeric score...
December 16, 2018: Human Pathology
Euno Choi, Seonk-Ik Kim, Jae-Kyung Won, Chun Kee Chung, Seung Ki Kim, Seung-Hong Choi, Seongmin Choi, Bome Han, Bokyung Ahn, I M Sun-Wha, Sung-Hye Park
Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a recently recognized rare neuronal tumor, and its pathogenesis is unclear. We analyzed 7 cases of histologically typical MVNT: six were adults [mean age: 43.0years (range: 23-56)] and one was a child (10-year-old). The most common symptoms were seizures (n=4) and headache (n=2). The tumors were supratentorial (temporal=5 and frontal lobes=2) in origin as reported. Vacuolated tumor cells were robustly positive for alpha-INA and Olig2 and at least partly positive for synaptophysin and MAP2, but negative for Neu-N...
December 11, 2018: Human Pathology
Caroline Talsma Simon, Stephanie L Skala, Alon Z Weizer, Sapan N Ambani, Arul M Chinnaiyan, Ganesh Palapattu, Khaled Hafez, Martin J Magers, Samuel D Kaffenberger, Daniel E Spratt, Jeffrey S Montgomery, Todd M Morgan, Aaron M Udager, Madelyn Lew, Rohit Mehra
5% of urothelial carcinoma occurs in the upper urinary tract (UUT), a challenging location to biopsy. We aim to evaluate concordance between biopsy, cytology, and resection specimens in a large upper tract urothelial carcinoma (UTUC) cohort.117 UTUC resections with UUT biopsy and/or cytology specimens from 2000-2016 were retrieved; pathologic material was re-reviewed, evaluated for concordance, and correlated with clinical information. 14% pre-operative biopsies, including 8 from renal pelvis and 6 from ureter, lacked neoplastic diagnoses...
December 8, 2018: Human Pathology
Jie Yu, Yi Zheng, Xue Ping Han, Hao Peng, Li Juan Pang, Feng Li, Yunzhao Chen, Xiaobin Cui
Esophageal squamous cell carcinoma (ESCC) is a highly invasive disease with a poor long-term survival rate. Although there has been progress in understanding the pathogenesis of ESCC, there are currently no molecular biomarkers that are used in routine clinical practices to determine prognosis. Therefore, the aim of this study was to determine a small immunohistochemical (IHC) panel that could predict the prognosis of patients with ESCC. Phospholipase C epsilon-1 (PLCE1), IKKα, IKBα, p65, and p53 were highly expressed in ESCC tissues...
December 8, 2018: Human Pathology
Jing Zhai, Gabriel Giannini, Mark D Ewalt, Elizabeth Y Zhang, Marta Invernizzi, Joyce Niland, Lily L Lai
Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer with variable morphology. MBC is more often triple negative (ER-, PR-, HER2-) and is associated with poorer clinical outcome when compared to infiltrating ductal carcinoma. The purpose of our study is to identify molecular alterations in MBC using next generation sequencing (NGS) which may aid chemotherapy selection and use of targeted therapy. A cohort of 18 patients with MBC yielded adequate DNA from microdissected formalin fixed and paraffin embedded (FFPE) tumor blocks...
December 8, 2018: Human Pathology
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