Pathology Commons^™

Primary Sclerosing Epithelioid Fibrosarcoma Of Kidney With Variant Histomorphologic Features: Report Of 2 Cases And Review Of The Literature., Dilek Ertoy Baydar, Kemal Kosemehmetoglu, Oguz Aydin, Julia A. Bridge, Berrin Buyukeren, Fazil Tuncay Aki

Journal Articles: Pathology and Microbiology

The authors present two cases of primary sclerosing epithelioid fibrosarcoma (SEF) of the kidney. Both patients had a mass in the upper part of the left kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were solid masses both measuring 7.5 cm in the greatest diameter. Histologically, one of the lesions exhibited a predominantly lobular growth of round or oval small uniform epithelioid cells in variable cellularity. Circular zones of crowded tumor cells alternating with hypocellular collagenous tissue in a concentric fashion around entrapped native renal tubules were distinctive. The second case was distinctive with significant cytological atypia in …

Clinical And Biochemical Function Of Polymorphic Nr0b1 Ggaa-Microsatellites In Ewing Sarcoma: A Report From The Children's Oncology Group., Michael J. Monument, Kirsten M. Johnson, Elizabeth Mcilvaine, Lisa Abegglen, W. Scott Watkins, Lynn B. Jorde, Richard B. Womer, Natalie Beeler, Laura Monovich, Elizabeth R. Lawlor, Julia A. Bridge, Joshua D. Schiffman, Mark D Krailo, R. Lor Randall, Stephen L. Lessnick

Journal Articles: Pathology and Microbiology

BACKGROUND: The genetics involved in Ewing sarcoma susceptibility and prognosis are poorly understood. EWS/FLI and related EWS/ETS chimeras upregulate numerous gene targets via promoter-based GGAA-microsatellite response elements. These microsatellites are highly polymorphic in humans, and preliminary evidence suggests EWS/FLI-mediated gene expression is highly dependent on the number of GGAA motifs within the microsatellite.

OBJECTIVES: Here we sought to examine the polymorphic spectrum of a GGAA-microsatellite within the NR0B1 promoter (a critical EWS/FLI target) in primary Ewing sarcoma tumors, and characterize how this polymorphism influences gene expression and clinical outcomes.

RESULTS: A complex, bimodal pattern of EWS/FLI-mediated gene expression was observed …

Evidence For Aberrant Astrocyte Hemichannel Activity In Juvenile Neuronal Ceroid Lipofuscinosis (Jncl)., Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian

Journal Articles: Pathology and Microbiology

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have …

Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to …

Response Of An Aggressive Periosteal Aneurysmal Bone Cyst (Abc) Of The Radius To Denosumab Therapy., Chantal Pauli, Bruno Fuchs, Christian Pfirrmann, Julia A. Bridge, Silvia Hofer, Beata Bode

Journal Articles: Pathology and Microbiology

Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease. Under the influence of this RANKL inhibitor, the tumor showed a marked reduction of the content of the osteoclastic giant cells and an extensive metaplastic osteoid production leading to the …

Il-1ri (Interleukin-1 Receptor Type I) Signalling Is Essential For Host Defence And Hemichannel Activity During Acute Central Nervous System Bacterial Infection., Juan Xiong, Maria Burkovetskaya, Nikolay Karpuk, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a common aetiological agent of bacterial brain abscesses. We have previously established that a considerable IL-1 (interleukin-1) response is elicited immediately following S. aureus infection, where the cytokine can exert pleiotropic effects on glial activation and blood-brain barrier permeability. To assess the combined actions of IL-1α and IL-1β during CNS (central nervous system) infection, host defence responses were evaluated in IL-1RI (IL-1 receptor type I) KO (knockout) animals. IL-1RI KO mice were exquisitely sensitive to intracerebral S. aureus infection, as demonstrated by enhanced mortality rates and bacterial burdens within the first 24 h following pathogen exposure compared …

Sox11 Expression Is Highly Specific For Mantle Cell Lymphoma And Identifies The Cyclin D1-Negative Subtype., Ana Mozos, Cristina Royo, Elena Hartmann, Daphne De Jong, Cristina Baró, Alexandra Valera, Kai Fu, Dennis D. Weisenburger, Jan Delabie, Shih-Sung Chuang, Elaine S. Jaffe, Carmen Ruiz-Marcellan, Sandeep Dave, Lisa Rimsza, Rita Braziel, Randy D. Gascoyne, Francisco Solé, Armando López-Guillermo, Dolors Colomer, Louis M. Staudt, Andreas Rosenwald, German Ott, Pedro Jares, Elias Campo

Journal Articles: Pathology and Microbiology

BACKGROUND: Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma. The aim of this study was to determine whether this gene is expressed in cyclin D1-negative mantle cell lymphoma and whether its detection may be useful to identify these tumors.

DESIGN AND METHODS: The microarray database of 238 mature B-cell neoplasms was re-examined. SOX11 protein expression was investigated immunohistochemically in 12 cases of cyclin …

Molecular Diagnosis Of Burkitt's Lymphoma., Sandeep S. Dave, Kai Fu, George W. Wright, Lloyd T. Lam, Philip Kluin, Evert-Jan Boerma, Timothy Greiner, Dennis D. Weisenburger, Andreas Rosenwald, German Ott, Hans-Konrad Müller-Hermelink, Randy D. Gascoyne, Jan Delabie, Lisa M. Rimsza, Rita M. Braziel, Thomas M. Grogan, Elias Campo, Elaine S. Jaffe, Bhavana J. Dave, Warren Sanger, M Bast, Julie M. Vose, James O. Armitage, Joseph M. Connors, Erlend B. Smeland, Stein Kvaloy, Harald Holte, Richard I. Fisher, Thomas P. Miller, Emilio Montserrat, Wyndham H. Wilson, Manisha Bahl, Hong Zhao, Liming Yang, John Powell, Richard Simon, Wing C. Chan, Louis M. Staudt

Journal Articles: Pathology and Microbiology

BACKGROUND: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.

METHODS: Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation.

RESULTS: A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt's lymphoma. Burkitt's lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target …

Analysis Of The Effects Of Overexpression Of Metallothionein-I In Transgenic Mice On The Reproductive Toxicology Of Cadmium., T Dalton, Kai Fu, G C Enders, R D Palmiter, G K Andrews

Journal Articles: Pathology and Microbiology

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. …