Publications by authors named "Joseph Rohr"

19 Publications

  • Page 1 of 1

Some Pleomorphic Adenomas of the Breast Share PLAG1 Rearrangements with the Analogous Tumor of the Salivary Glands.

Histopathology 2021 Jul 22. Epub 2021 Jul 22.

Department of Pathology, the Basic Medicine Science and the First Affiliated Hospital of the Air Force Military Medical University, Xi'an, Shaan Xi Province, 710032, China.

Aims: Pleomorphic adenoma (PA) of the breast, and especially its malignant transformation, is extremely rare and represents a diagnostic pitfall. Molecular alterations in this entity have not been investigated. We aimed to examine the clinicopathologic features of our breast PAs and perform molecular analysis.

Methods: Seven cases of breast PA including two cases of carcinoma ex PA were analyzed. PLAG1 and HMGA2 gene rearrangements were assayed by FISH and RNA-Seq, respectively. RT-PCR and Sanger sequencing were used to verify RNA sequencing results.

Results: All seven cases of breast PA occurred in women. The histological features were similar to the analogous tumor in salivary glands, including a dual epithelial-myoepithelial component and negativity of ER, PR, and HER2 by immunohistochemistry. Of the two cases with carcinoma ex PA, one demonstrated minimal invasion and one was extensively invasive. PLAG1 rearrangements were identified in two cases (28.6%), but no rearrangements of HMG2A were found. A novel fusion product in PAs, TRPS1-PLAG1, was identified in one case. No patients had recurrence or metastasis with a follow-up period of 6 to 158 months.

Conclusions: Breast PA is rare, but it is an important differential diagnosis of breast pathology with the potential to develop carcinoma ex PA. We reported a novel TRPS1-PLAG1 fusion gene in breast PA.
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http://dx.doi.org/10.1111/his.14461DOI Listing
July 2021

Partial recapitulation of fetal thymic T-cell constitution postnatally in a patient with cartilage hair hypoplasia-anauxetic dysplasia spectrum disorder: A case report.

Cytometry B Clin Cytom 2021 May 6. Epub 2021 May 6.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.

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http://dx.doi.org/10.1002/cyto.b.22009DOI Listing
May 2021

p63 expression is associated with high histological grade, aberrant p53 expression and TP53 mutation in HER2-positive breast carcinoma.

J Clin Pathol 2020 Sep 1. Epub 2020 Sep 1.

Department of Pathology, The Basic Medicine Science and the First Affiliated Hospital of the Air Force Military Medical University, Xi'an, China.

Aim: p63, a member of the p53 family, is a myoepithelial cell marker usually expressed in metaplastic breast carcinoma and its expression suggests a myoepithelial phenotype. However, its expression and association with clinicopathological features of human epidermal growth factor receptor 2 (HER 2)-positive breast carcinoma is poorly investigated.

Materials And Methods: Sixty-seven patients with oestrogen receptor-negative and progesterone receptor-negative, HER2-positive breast carcinoma who received anti-HER2-based neoadjuvant±adjuvant therapy was retrospectively analysed.

Results: Twenty cases were p63-positive and 47 cases were p63-negative. The clinicopathological features and tumour responses after neoadjuvant therapy and outcomes were analysed. Among HER2-positive tumours, expression of p63 was significantly associated with younger age (42.5 vs 55.9; p=0.010). Expression of p63 was also significantly associated with histological grade 3 (11/20 (55%) vs 11/47 (23.4%); p=0.012) and negatively associated with grade 2 (9/20 (45%) vs 36/47 (76.6%); p=0.012). Intriguingly, p63-positive breast carcinomas showed significant aberrant p53 expression by immunohistochemistry (16/18 (88.9%) vs 29/47 (61.7%); p=0.03) and of mutation by Sanger sequencing (15/16 (93.8%) vs 12/22 (54.5%); p=0.009). No significant difference in tumour response after anti-HER2 neoadjuvant therapy nor in survival were found between p63-positive and p63-negative breast carcinomas.

Conclusion: Expression of p63 in HER2-positive breast carcinoma is significantly associated with younger age, poor differentiation, high histological grade and aberrant expression of p53 and of mutation. HER2-positive breast carcinoma with a myoepithelial immunophenotype shows distinctive clinicopathological features representing a distinct subtype of HER2-positive breast carcinoma. Further, these findings suggest an interaction between p63 and mutant p53 in the tumorigenesis of HER2-positive breast carcinomas.
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http://dx.doi.org/10.1136/jclinpath-2020-206643DOI Listing
September 2020

Progress in triple negative breast carcinoma pathophysiology: Potential therapeutic targets.

Pathol Res Pract 2020 Apr 13;216(4):152874. Epub 2020 Feb 13.

State Key Laboratory of Tumor Biology, Department of Pathology, Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi Province,710032, China. Electronic address:

Triple-negative breast carcinoma (TNBC) is a subtype of breast carcinoma defined by negativity for estrogen receptor (ER) or progesterone receptor (PR) by immunohistochemical analysis and negativity for human epidermal growth factor receptor (Her2) by immunohistochemistry or in situ hybridization. TNBC is clinically marked by its high aggressiveness, particularly poor outcomes including a low survival rate, and the lack of specific and effective treatments. Therefore, new potential targets for the treatment of TNBC must be identified. This review summarizes recent evidence supporting novel targets and possible therapeutic regimens in the treatment of TNBC.
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http://dx.doi.org/10.1016/j.prp.2020.152874DOI Listing
April 2020

Hb Gibbon [β124(H2)Pro→Thr (: c.373C>A, p.P125T)], an Asymptomatic Novel Hemoglobin Variant Detected by Newborn Screening.

Hemoglobin 2019 May 6;43(3):207-209. Epub 2019 Aug 6.

Department of Pediatrics, Children's Hospital and Medical Center, University of Nebraska Medical Center , Omaha , NE , USA.

We describe here a previously unreported hemoglobin (Hb) variant, Hb Gibbon [β124(H2)Pro→Thr (: c.373C>A, p.P125T)] detected by newborn Hb screening in a term male with no family history for hemoglobinopathy or other screening abnormalities. This missense mutation produces a β-globin chain variant that was detected by high performance liquid chromatography (HPLC) methods, but is silent by capillary electrophoresis (CE). DNA sequencing studies revealed that his father was also a heterozygote for this mutation. Neither has abnormalities on complete blood count (CBC) or any symptomatology.
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http://dx.doi.org/10.1080/03630269.2019.1634591DOI Listing
May 2019

Utilization of Health Care Resources by the Amish of a Rural County in Nebraska.

J Community Health 2019 12;44(6):1090-1097

Department of Family Medicine, University of Nebraska Medical Center, 983075 Nebraska Medical Center, Omaha, NE, 68198, USA.

The medical needs of the New Order Amish (NOA) remain poorly understood. The NOA community in Pawnee County, Nebraska was founded in 2011 by members from across the Midwest. Understanding what this community wants from their medical providers informs how rural hospitals may best serve the needs of growing NOA populations. To address this, the current utilization of the closest healthcare resource to community were assessed. Medical records data for Amish patients were obtained at Pawnee County Memorial Hospital and Rural Health Clinic from 2011 to 2016. Subjective data were obtained by surveys and interviews administered to Amish in Pawnee County. The 422 complete interactions in the medical record covered most primary care complaints. The fifteen survey respondents valued direct interaction with providers and expressed concerns about cost, emergencies, and access to obstetric practice. Surprisingly, though surveys indicated minimal use of health establishments for many common health complaints, medical records indicated frequent doctor visits for myriad reasons. Naturalistic books were the most utilized source of health information. The NOA utilize formal medicine, but may feel excluded in medical decision-making. They desire better access to obstetric care and culturally sensitive medical practice. Providers should ensure appropriate communication to increase healthcare-related comfort of this underserved population.
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http://dx.doi.org/10.1007/s10900-019-00696-9DOI Listing
December 2019

First report of Sarcina ventriculi in a pyloric and duodenal brushing specimen.

Cytopathology 2019 09 26;30(5):563-564. Epub 2019 Jun 26.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.

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http://dx.doi.org/10.1111/cyt.12735DOI Listing
September 2019

Clinicopathological features of primary diffuse large B-cell lymphoma of the central nervous system - strong EZH2 expression implying diagnostic and therapeutic implication.

APMIS 2016 Dec 2;124(12):1054-1062. Epub 2016 Nov 2.

State Key Laboratory of Tumor Biology, Department of Pathology, Xi Jing Hospital, The Fourth Military Medical University, Xi'an, Shaan Xi Province, China.

Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare entity which is difficult to diagnose and treat. The histone methyltransferase EZH2 was reported to be involved in the tumorigenesis of systemic DLBCL but has not been implicated in primary CNS DLBCL. The clinicopathological features of 33 cases of primary CNS DLBCL and expression of EZH2 and Y641 mutation were assessed. The tumor cells of the majority cases resembled centroblasts, and intriguingly, three cases of rare anaplastic variant were observed. Immunophenotypically, 25/33 (75.8%) cases were non-germinal center B-cell-like type. Several cases (10/33; 30.3%) co-expressed BCL2 and MYC, 6/33 (18.2%) expressed both BCL6 and MYC, and 5/33 (15.2%) expressed BCL2, BCL6, and MYC. MYC expression alone and BCL2/MYC co-expression were associated with poor prognosis. EZH2 was strongly expressed in all 33 cases independent of Y641 mutation and was significantly associated with the tumor proliferative index Ki67. However, no association was found between the level of EZH2 expression and outcomes of patients. In summary, the clinicopathological features including three rare anaplastic variant of primary CNS DLBCL are described. Strong expression of EZH2 in all the primary CNS DLBCL and association with high proliferative index provides further information for treatment and diagnosis of this distinctive entity.
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http://dx.doi.org/10.1111/apm.12623DOI Listing
December 2016

Comment on: Frequent CTLA4-CD28 gene fusion in diverse types of T-cell lymphoma, by Yoo et al.

Haematologica 2016 06 31;101(6):e269-70. Epub 2016 May 31.

Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA

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http://dx.doi.org/10.3324/haematol.2016.147074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013938PMC
June 2016

Teaching High School Students About Pathology:  Development of a Secondary School-Focused Enrichment Course in Pathology and Physiology.

Am J Clin Pathol 2016 May 26;145(5):617-21. Epub 2016 Feb 26.

From the Department of Pathology and Microbiology.

Objectives: Although pathology is a central discipline in medicine, many do not understand the role of pathologists and laboratory professionals. While there are efforts to educate the public, few focus on precollege students.

Methods: To define a curriculum exposing high school students to major concepts in health and disease, while introducing them to professions that employ this knowledge. A semester-long class was designed to meet for 2-hour sessions semiweekly. Each session included a lecture given by a pathologist followed by group activities including hands-on gross or virtual laboratory experiences and clinical simulations. Content included epidemiology, biostatistics, and the critical evaluation of health-related articles in the popular press. Students were evaluated by examination, group assignments, and a capstone research project presentation.

Results: Over 4 years (2011-2014), 114 of 122 students completed the course with a "B" or better. By course conclusion, students could articulate the link between tissue changes and clinical phenotypes. Surveys showed that 90% of students found the course appropriately challenging, 98% found the class appropriate for their learning style, and the teaching methods and course content received 99% approval.

Conclusions: We present a pathology course geared toward high school students that taught the foundations of human disease that allowed students to fully understand and engage in the material. Students felt that the knowledge earned was valuable and helped them to understand human health as well as inform their future career choices. This course could serve as a model for public outreach programs and for secondary and postsecondary educators.
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http://dx.doi.org/10.1093/ajcp/aqw011DOI Listing
May 2016

EZH2 overexpression in different immunophenotypes of breast carcinoma and association with clinicopathologic features.

Diagn Pathol 2016 Apr 26;11:41. Epub 2016 Apr 26.

Department of Pathology, Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi Province, 710032, China.

Background: Enhancer of zest homolog 2 (EZH2), a histone 3 methyltransferase, is associated with aggressive behavior of many tumors and is a promising target of molecular therapy.

Methods: To better elucidate the relevance of EZH2 in breast cancer subtypes, we evaluated EZH2 expression in 226 invasive breast carcinomas with four distinct immunophenotypes and in association with clinicopathological features.

Results: Of these cases, 138 (61.1 %) were defined as EZH2-overexpressing with a multiplicative score > 3. EZH2 expression was inversely related to the status of ER and PR (Chi-square, p < 0.001), and it was significantly associated with HER2 positivity, high proliferative index, and high histologic grade (Chi-square, p < 0.05). ER-positive breast carcinoma with low proliferative index (Ki67 < 14 %) showed the lowest expression and triple-negative breast carcinoma showed the highest overexpression of EZH2, 18.5 % (10/54) versus 90.9 % (50/55) (Chi-square, p < 0.001). Intriguingly, 88 % (44/50) cases of grade 3 triple-negative breast carcinoma showed uniformly strong EZH2 expression with a multiplicative score of 9. The percentage of EZH2 overexpression in ER-positive breast carcinoma with a high proliferative index or HER2-positive cases were 61.2 and 74 %, respectively. Furthermore, EZH2 expression was significantly elevated in high-grade DCIS compared to benign lesions (90 % versus 0, p < 0.001). However, there is no association between EZH2 expression and the status of histone 3 lysine 27 trimethylation or other clinicopathologic features.

Conclusion: In summary, triple-negative breast carcinoma showed the highest overexpression of EZH2. EZH2 overexpression is associated aggressive pathologic features including high nuclear grade, high proliferative index, and positivity of HER2 of breast carcinoma.
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http://dx.doi.org/10.1186/s13000-016-0491-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845361PMC
April 2016

Solid papillary carcinoma of the breast: A special entity needs to be distinguished from conventional invasive carcinoma avoiding over-treatment.

Breast 2016 Apr 29;26:67-72. Epub 2016 Jan 29.

Department of Pathology, Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi Province, 710032, China. Electronic address:

Introduction: Solid papillary carcinoma of the breast, a newly-defined entity, is poorly recognized, and its nature and management is still debated.

Material And Methods: Eleven cases of pure solid papillary breast carcinoma in our archive and 253 cases reported in previous literature were retrospectively analyzed for their clinicopathological features and outcomes.

Results: The eleven cases occurred in elderly females. Grossly, all tumors were well-circumscribed and typically composed of solid papillary nodules. The tumor cells were bland-looking with low-grade atypia and mitoses < 5/10HPF. Immunophenotypically, all eleven cases showed positivity for ER and PR, negativity for CK5/6 and HER2, and a low proliferative index of Ki67. Five cases showed scattered positivity for myoepithelial marker p63, and four cases were positive for CK5/6 and CD10 around the nodules, whereas the other cases were completely negative for all myoepithelial markers. Five cases expressed the neuroendocrine marker synaptophysin, and six cases expressed chromogranin. In nine cases, mastectomy and axillary lymph nodes excision were performed, and only one showed micrometastasis in an axillary lymph node. There was no local recurrence or distant metastasis or breast carcinoma related-death during the follow-up periods of 50 months. Out of 253 solid papillary breast carcinomas reported in literature, the percentage of axillary lymph node metastasis was 4/136 (3%), with rare local recurrences and distant metastasis; only three patients died of breast carcinoma.

Conclusion: Solid papillary carcinoma of the breast is a rare entity with distinctive clinicopathological features and excellent prognosis and should be distinguished from conventional breast carcinoma to avoid over-treatment.
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http://dx.doi.org/10.1016/j.breast.2015.12.015DOI Listing
April 2016

A clinicopathologic study of paragangliomas of the urinary bladder: can the clinical behavior of the tumor be predicted?

Histol Histopathol 2016 Jul 10;31(7):785-91. Epub 2016 Mar 10.

Department of Pathology, Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi Province, China.

Lymphovascular invasion (LVI) is an independent predictor of metastatic lymph node disease in penile carcinoma and is one factor used to guide clinical management. The presence of LVI with and without the use of the endothelial immunohistochemical (IHC) markers, ERG and CD31, was retrospectively assessed in 46 penectomy cases containing invasive penile carcinoma (43 squamous cell carcinoma and 3 non-squamous cell carcinoma). Concordance for the detection of LVI between the original report, upon pathology review, and with the use of IHC was determined and histologic pitfalls were identified. For penile squamous cell carcinoma, LVI was diagnosed in 27.9% of tumors in the original reports, 16.3% upon pathology review, and in 16.3% with use of ERG and CD31. Concordance of LVI identification in the original report compared to IHC was 74.4% while concordance of review compared to IHC was 95.3%. Using IHC data as the reference, false positive LVI diagnoses were more common in the original report than false negatives. Histologic mimickers of LVI including involvement of the penile corpora cavernosum or spongiosum vasculature, seromucinous colonization, and a nested pattern of tumor invasion were identified. We demonstrated that it was not uncommon for LVI in penile carcinoma to be overdiagnosed or underdiagnosed. The use of endothelial IHC markers, such as ERG or CD31, or additional pathology consultation is recommended for penectomy cases in which LVI is difficult to histologically discern.
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http://dx.doi.org/10.14670/HH-11-751DOI Listing
July 2016

Genomic signatures in B-cell lymphoma: How can these improve precision in diagnosis and inform prognosis?

Blood Rev 2016 Mar 18;30(2):73-88. Epub 2015 Aug 18.

Department of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE, USA.

Current genomic technologies have immensely improved disease classification and prognostication of major subtypes of B-cell lymphomas. This novel genetic information has not only aided in diagnosis, but has also revealed a landscape of critical molecular events that determine the biological and clinical behavior of a lymphoma. In this review, we summarized the genetic characteristics of major subtypes of B-cell lymphomas, including diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt lymphoma (BL), and mantle cell lymphoma (MCL). We illustrated how genomic profiling had identified molecular subgroups in DLBCL with varied clinical outcomes, and how a subset of genes defined prognosis in MCL and aided in BL diagnoses. We also highlighted some Phase II/III clinical trials using new therapeutic agents to determine clinical efficacy in novel molecular subgroups with distinct gene expression patterns. We believe that refinement of genomic signatures will require more intensive efforts from the biomedical research community to improve targeted therapy designs and bring a substantial change in the treatment decisions. In the next era of genomic medicine, we anticipate that a clinically and biologically relevant molecular profile of each tumor will be obtained at diagnosis to guide therapy.
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http://dx.doi.org/10.1016/j.blre.2015.08.002DOI Listing
March 2016

Genomic signatures in T-cell lymphoma: How can these improve precision in diagnosis and inform prognosis?

Blood Rev 2016 Mar 18;30(2):89-100. Epub 2015 Aug 18.

Department of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE, USA.

The novel genetic information gained from genome-wide high throughput techniques has greatly improved our understanding of peripheral T-cell lymphoma (PTCL). PTCL consists of numerous distinct entities and is currently diagnosed using a combination of clinical and morphologic features and immunophenotyping together with limited molecular assays leading to an often fragmented, complicated diagnostic system. The diagnosis of many cases is challenging even for expert hematopathologists and more than a third of the cases cannot be further classified and thus put into the PTCL-NOS category. Gene expression profiling (GEP) has significantly improved the molecular classification of PTCLs and identified robust molecular signatures for common nodal subtypes of PTCL including angioimmunoblastic T-cell lymphoma (AITL), anaplastic T-cell lymphoma (ALCL), adult T-cell leukemia/lymphoma (ATLL) and extra-nodal NK/T cell lymphoma (ENKTL). These studies also led to identification of novel molecular subtypes with distinct prognosis, that otherwise could not be identified by conventional methods. Integration of massive sequencing strategies and gene expression has characterized driver genetic alterations in common subtypes like AITL, ALCL, ENKTL and other PTCLs. These studies have identified oncogenic pathways and genes affected in specific disease subtypes that can be potentially targeted by specific therapies. Novel treatment options with FDA approved drugs directed towards mutant IDH2, the NF-κB, JAK/STAT, or mTOR pathways illustrate the usefulness of genome-wide techniques to identify targets for therapy. In this review, we highlight recent advances in the molecular diagnosis and prognosis of PTCL using these genome-wide techniques.
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http://dx.doi.org/10.1016/j.blre.2015.08.003DOI Listing
March 2016

IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma.

Blood 2015 Oct 12;126(15):1741-52. Epub 2015 Aug 12.

Department of Pathology, City of Hope National Medical Center, Duarte, CA;

Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of peripheral T-cell lymphoma (PTCL) with a poor prognosis. We performed targeted resequencing on 92 cases of PTCL and identified frequent mutations affecting RHOA, TET2, DNMT3A, and isocitrate dehydrogenase 2 (IDH2). Although IDH2 mutations are largely confined to AITL, mutations of the other 3 can be found in other types of PTCL, although at lower frequencies. These findings indicate a key role of epigenetic regulation in the pathogenesis of AITL. However, the epigenetic alterations induced by these mutations and their role in AITL pathogenesis are still largely unknown. We correlated mutational status with gene expression and global DNA methylation changes in AITL. Strikingly, AITL cases with IDH2(R172) mutations demonstrated a distinct gene expression signature characterized by downregulation of genes associated with TH1 differentiation (eg, STAT1 and IFNG) and a striking enrichment of an interleukin 12-induced gene signature. Ectopic expression of IDH2(R172K) in the Jurkat cell line and CD4(+) T cells led to markedly increased levels of 2-hydroxyglutarate, histone-3 lysine methylation, and 5-methylcytosine and a decrease of 5-hydroxymethylcytosine. Correspondingly, clinical samples with IDH2 mutations displayed a prominent increase in H3K27me3 and DNA hypermethylation of gene promoters. Integrative analysis of gene expression and promoter methylation revealed recurrently hypermethylated genes involved in T-cell receptor signaling and T-cell differentiation that likely contribute to lymphomagenesis in AITL.
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http://dx.doi.org/10.1182/blood-2015-05-644591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600014PMC
October 2015

Global microRNA expression profiling uncovers molecular markers for classification and prognosis in aggressive B-cell lymphoma.

Blood 2015 Feb 10;125(7):1137-45. Epub 2014 Dec 10.

Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;

We studied the global microRNA (miRNA) expression in diffuse large B-cell lymphoma (DLBCL; n = 79), Burkitt lymphoma (BL; n = 36), primary mediastinal B-cell lymphoma (PMBL; n = 12), B-cell lines (n = 11), and normal subsets of naïve B cells, centroblasts (CBs), and peripheral blood B cells along with their corresponding gene expression profiles (GEPs). The normal B-cell subsets have well-defined miRNA signatures. The CB miRNA signature was significantly associated with germinal center B-cell (GCB)-DLBCL compared with activated B-cell (ABC)-DLBCL (P = .002). We identified a 27-miRNA signature that included v-myc avian myelomatosis viral oncogene homolog (MYC) targets and enabled the differentiation of BL from DLBCL, a distinction comparable with the "gold standard" GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, including GCB-DLBCL, activated B-cell (ABC)-DLBCL, and PMBL. Interestingly, most of the unclassifiable-DLBCL by GEP showed a strong similarity to the ABC-DLBCL by miRNA expression profiling. Consistent results for BL and DLBCL subgroup classification were observed in formalin-fixed, paraffin-embedded tissue, making such tests practical for clinical use. We also identified predictive miRNA biomarker signatures in DLBCL, including high expression of miR-155, which is significantly associated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment failure. This finding was further supported by the observation that high expression of miR-155 sensitizes cells to v-akt murine thymoma viral oncogene homolog-1 inhibitors in vitro, suggesting a novel treatment option for resistant DLBCL.
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http://dx.doi.org/10.1182/blood-2014-04-566778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326773PMC
February 2015

Erdheim-Chester disease involving the breast--a rare but important differential diagnosis.

Hum Pathol 2015 Jan 18;46(1):159-64. Epub 2014 Oct 18.

Department of Pathology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shan Xi Province, 710032, China. Electronic address:

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by multisystem infiltration by foamy histiocytes surrounded by fibrosis. ECD often involves the long bones, skin, and retroperitoneum, whereas breast involvement is very rare with only 6 reported cases in English literature. We report a case of ECD presenting within the right breast as a clinically malignant tumor, in addition to bilateral sclerotic lesions of the femurs, bilateral soft tissue masses of the cerebellum, and multiple subcutaneous nodules on the abdominal wall in a 61-year-old woman. Histologically, there was a prominent infiltrate of foamy histiocytes with scattered Touton-type giant cells, lymphocytes, and plasma cells. The foamy histiocytes were arranged in small clusters or scattered singly in the background of fibrosis. However, in some areas, there was a prominent proliferation of fibrosis with scant cellular infiltrate including histiocytes. The diagnosis of ECD was made by characteristic histopathologic features in addition to clinical-radiographic features and the typical immunoprofile (positive for cluster of differentiation 68 [CD68], CD163, and p16; negative for CD1a and S-100). Although rare, ECD must be considered in the differential diagnosis of clinically malignant tumor of the breast. To our knowledge, this is the second case of ECD involving the breast in which a valine 600 glutamic acid mutation was detected, which probably represents a clonal disorder of non-Langerhans cells.
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http://dx.doi.org/10.1016/j.humpath.2014.10.005DOI Listing
January 2015

Tissue interaction is required for glenoid fossa development during temporomandibular joint formation.

Dev Dyn 2011 Nov 26;240(11):2466-73. Epub 2011 Sep 26.

Department of Operative Dentistry and Endodontics, College of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, P R China.

The mammalian temporomandibular joint (TMJ) develops from two distinct mesenchymal condensations that grow toward each other and ossify through different mechanisms, with the glenoid fossa undergoing intramembranous ossification while the condyle being endochondral in origin. In this study, we used various genetically modified mouse models to investigate tissue interaction between the condyle and glenoid fossa during TMJ formation in mice. We report that either absence or dislocation of the condyle results in an arrested glenoid fossa development. In both cases, glenoid fossa development was initiated, but failed to sustain, and became regressed subsequently. However, condyle development appears to be independent upon the presence of the forming glenoid fossa. In addition, we show that substitution of condyle by Meckel's cartilage is able to sustain glenoid fossa development. These observations suggest that proper signals from the developing condyle or Meckel's cartilage are required to sustain the glenoid fossa development.
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http://dx.doi.org/10.1002/dvdy.22748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197963PMC
November 2011
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