scholarly journals Micropapillary Carcinoma of the Bladder: Recent Advances

2019 ◽  
pp. 1-10
Author(s):  
Jim Hsu ◽  
Jae Y. Ro
Keyword(s):  
Urothelial Carcinoma ◽  
Molecular Mechanisms ◽  
Current Treatment ◽  
Invasive Micropapillary Carcinoma ◽  
Micropapillary Carcinoma ◽  
Treatment Protocols ◽  
Immunohistochemical Markers ◽  
Recent Advances ◽  
Carcinoma Of The Bladder

The 2016 WHO classification of tumors of the urothelial tract recently revised the classification of invasive urothelial carcinoma to include nested, microcystic, micropapillary, plasmacytoid, sarcomatoid, giant cell, and poorly differentiated variants, among others. In particular, invasive micropapillary carcinoma (IMPC) is now recognized as a distinct entity with aggressive features, including higher-stage disease, invasive features, and poorer response to intravesical chemotherapy. In this review, we highlight recent studies that further characterize the histopathology, immunohistochemistry, molecular mechanisms, and clinical implications of a diagnosis of IMPC. Because the correct morphologic diagnosis of IMPC is critical in terms of clinical management, we explore the diagnostic criteria of IMPC and differential diagnosis of urothelial IMPC from non-urothelial sites, highlighting studies that examine both traditional urothelial immunohistochemical markers as well as novel markers. We highlight recent advances in the molecular sub-categorization of IMPC, and review the differences compared to other forms of urothelial carcinoma. Optimal management of patients with IMPC is still unclear, although early cystectomy, regardless of pathologic stages, is recommended. We also highlight several studies that address the clinical challenges as well as current treatment protocols for IMPC.

scholarly journals How to use new biology to guide therapy in multiple myeloma

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 342-349 ◽  
Author(s):  
Gareth J. Morgan ◽  
Martin F. Kaiser
Keyword(s):  
Multiple Myeloma ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Survival Rates ◽  
Current Treatment ◽  
Next Generation ◽  
Molecular Subgroups ◽  
Treatment Protocols ◽  
Sequencing Technologies ◽  
A Genome

Abstract Recent advances in multiple myeloma (MM) therapy have led to significantly longer median survival rates and some patients being cured. At the same time, our understanding of MM biology and the molecular mechanisms driving the disease is constantly improving. Next-generation sequencing technologies now allow insights into the genetic aberrations in MM at a genome-wide scale and across different developmental stages in the course of an individual tumor. This improved knowledge about MM biology needs to be rapidly translated and transformed into diagnostic and therapeutic applications to finally achieve cure in a larger proportion of patients. As a part of these translational efforts, novel drugs that inhibit oncogenic proteins overexpressed in defined molecular subgroups of the disease, such as FGFR3 and MMSET in t(4;14) MM, are currently being developed. The potential of targeted next-generation diagnostic tests to rapidly identify clinically relevant molecular subgroups is being evaluated. The technical tools to detect and define tumor subclones may potentially become clinically relevant because intraclonal tumor heterogeneity has become apparent in many cancers. The emergence of different MM subclones under the selective pressure of treatment is important in MM, especially in the context of maintenance therapy and treatment for asymptomatic stages of the disease. Finally, novel diagnostic and therapeutic achievements have to be implemented into innovative clinical trial strategies with smaller trials for molecularly defined high-risk patients and large trials with a long follow-up for the patients most profiting from the current treatment protocols. These combined approaches will hopefully transform the current one-for-all care into a more tailored, individual therapeutic strategy for MM patients.

scholarly journals Recent advances in understanding of the pathogenesis of ANCA-associated vasculitis

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1113 ◽  
Author(s):  
Maria Prendecki ◽  
Charles D. Pusey
Keyword(s):  
Side Effects ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Systemic Autoimmune Diseases ◽  
Treatment Protocols ◽  
Recent Advances ◽  
Recent Developments ◽  
The Complement System ◽  
Made In

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are rare systemic autoimmune diseases characterised by inflammation of small blood vessels. Recent developments have been made in our understanding of the pathogenesis of these diseases, including the pathogenic role of ANCA, neutrophils and monocytes as mediators of injury, dysregulation of the complement system, and the role of T and B cells. Current treatment strategies for AAV are based on broad immunosuppression, which may have significant side effects. Advances in understanding of the pathogenesis of disease have led to the identification of new therapeutic targets which may lead to treatment protocols with less-toxic side effects. The aim of this review is to summarise current information and recent advances in understanding of the pathogenesis of AAV.

Detection, evaluation, and management of iron-restricted erythropoiesis

Blood ◽  
2010 ◽  
Vol 116 (23) ◽  
pp. 4754-4761 ◽  
Author(s):  
Lawrence Tim Goodnough ◽  
Elizabeta Nemeth ◽  
Tomas Ganz
Keyword(s):  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Intravenous Iron ◽  
Diagnostic Classification ◽  
Markers Of Inflammation ◽  
Recent Advances ◽  
Detection Evaluation

AbstractProgress in our understanding of iron-restricted erythropoiesis has been made possible by important advances in defining the molecular mechanisms of iron homeostasis. The detection and diagnostic classification of iron-restricted erythropoiesis can be a challenging process for the clinician. Newer assays for markers of inflammation may allow more targeted management of the anemia in these conditions. The availability of new intravenous iron preparations provides new options for the treatment of iron-restricted erythropoiesis. This review summarizes recent advances regarding the detection, evaluation, and management of iron-restricted erythropoiesis.

scholarly journals Recent advances in understanding the phenotypes of osteoarthritis

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 2091 ◽  
Author(s):  
Ali Mobasheri ◽  
Simo Saarakkala ◽  
Mikko Finnilä ◽  
Morten A. Karsdal ◽  
Anne-Christine Bay-Jensen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Precision Medicine ◽  
Biochemical Markers ◽  
Molecular Mechanisms ◽  
Review Article ◽  
Clinical Phenotypes ◽  
Recent Advances ◽  
The People ◽  
Molecular Phenotypes

Recent research in the field of osteoarthritis (OA) has focused on understanding the underlying molecular and clinical phenotypes of the disease. This narrative review article focuses on recent advances in our understanding of the phenotypes of OA and proposes that the disease represents a diversity of clinical phenotypes that are underpinned by a number of molecular mechanisms, which may be shared by several phenotypes and targeted more specifically for therapeutic purposes. The clinical phenotypes of OA supposedly have different underlying etiologies and pathogenic pathways and they progress at different rates. Large OA population cohorts consist of a majority of patients whose disease progresses slowly and a minority of individuals whose disease may progress faster. The ability to identify the people with relatively rapidly progressing OA can transform clinical trials and enhance their efficiency. The identification, characterization, and classification of molecular phenotypes of rapidly progressing OA, which represent patients who may benefit most from intervention, could potentially serve as the basis for precision medicine for this disabling condition. Imaging and biochemical markers (biomarkers) are important diagnostic and research tools that can assist with this challenge.

scholarly journals Sarcomatoid Urothelial Carcinoma of the Bladder: Analysis of 28 Cases With Emphasis on Clinicopathologic Features and Markers of Epithelial-to-Mesenchymal Transition

2016 ◽  
Vol 140 (6) ◽  
pp. 543-551 ◽  
Author(s):  
Joseph Sanfrancesco ◽  
Jesse K. McKenney ◽  
Mariah Z. Leivo ◽  
Sounak Gupta ◽  
Paul Elson ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Mesenchymal Transition ◽  
Immunohistochemical Markers ◽  
Not Otherwise Specified ◽  
Cytokeratin 5 ◽  
Aggressive Tumor ◽  
Carcinoma Of The Bladder

Context.—Sarcomatoid urothelial carcinoma (UCa) is a rare but aggressive variant of bladder cancer that can show diagnostic challenges even using ancillary techniques. Objective.—To examine immunohistochemical markers in the context of sarcomatoid UCa, including those associated with epithelial-to-mesenchymal transition. Design.—Twenty-eight cases of sarcomatoid UCa were rereviewed. Clinical outcomes were obtained through database search. Immunohistochemistry for clinical and epithelial-to-mesenchymal transition markers was performed. Results.—All patients had biopsy-proven invasive UCa; 61% (17 of 28) had sarcomatoid UCa at initial diagnosis. A recognizable epithelial component(s) was present in 17 lesions. The sarcomatoid component accounted for 65% of the lesion (average), with heterologous elements present in 3 of 28 cases (11%). The morphologic spectrum of the sarcomatoid element included spindled not otherwise specified, myxoid, pseudoangiosarcomatous, and malignant fibrous histiocytoma–like undifferentiated features. The sarcomatoid component was immunoreactive for pancytokeratin (22 of 26; 85%), p63 (20 of 26; 77%), cytokeratin 903 (17 of 26; 65%), cytokeratin 7 (16 of 26; 62%), GATA3 (16 of 26; 62%), and cytokeratin 5/6 (16 of 26; 62%). STAT-6, CD31, CD34, and HMB45 were all nonreactive, whereas smooth muscle actin often showed at least focal immunoreactivity (22 of 26; 85%). Epithelial-to-mesenchymal transition markers were frequently expressed, including vimentin (26 of 26; 100%), FoxC2 (26 of 26; 100%), SNAIL (23 of 26; 88.5%), and ZEB1 (18 of 26; 69.2%). Follow-up was available for 24 patients (median, 7 months). Sixteen of 28 patients (57%) died of disease (overall mean survival, 9.1 months). The presence of myxoid or chordoid features was associated with reduced survival (P < .05). Conclusions.—Sarcomatoid UCa is an aggressive form of UCa that frequently expresses epithelial-to-mesenchymal transition markers, suggesting a possible mechanism associated with aggressive tumor behavior.

scholarly journals Invasive Micropapillary Carcinoma of the Breast: An Update

2016 ◽  
Vol 140 (8) ◽  
pp. 799-805 ◽  
Author(s):  
Yi-Ling Yang ◽  
Bing-Bing Liu ◽  
Xinmin Zhang ◽  
Li Fu
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Immunohistochemical Analysis ◽  
Sialyl Lewis X ◽  
Invasive Micropapillary Carcinoma ◽  
Micropapillary Carcinoma ◽  
Genomic Aberration ◽  
Clinical Behavior ◽  
Molecular Alterations ◽  
Inside Out

Context.—Invasive micropapillary carcinoma (IMPC) is a distinct variant of mammary carcinoma in which tumor cells are arranged in morulelike clusters devoid of fibrovascular cores and situated within empty stromal spaces. Identification of IMPC can be achieved by the assessment of morphologic features in conjunction with the characteristic “inside-out” staining pattern of epithelial membrane antigen and sialyl Lewis X highlighted by immunohistochemical analysis. Although recognizing micropapillary architecture is often not challenging, the criteria for distinguishing between mixed and pure IMPC remain imprecise. Some mucin-producing carcinomas can also have micropapillary histology, but there is no consensus on whether these tumors are variants of IMPC or mucinous carcinomas. The molecular genetic studies demonstrate that IMPCs have distinct molecular genetic profiles, supporting the theory that they constitute distinct pathologic entities. However, genomic analyses have not identified any specific genomic aberration that may explain the distinctive morphology and clinical behavior of IMPC. Objective.—To provide an overview on the current concepts in the diagnosis and pathogenesis of IMPC of the breast, incorporating recent molecular genetic advances and prognosis-based reclassification. Data Sources.—PubMed search and the cited references were reviewed. Conclusions.—The recent evolution of prognosis-based reclassification and molecular genetic advances has enhanced our knowledge of the pathogenesis of IMPC of the breast. Additional studies might reveal consistent molecular alterations that underlie the formation of the inside-out growth pattern, and they might elucidate the molecular mechanisms responsible for the unfavorable clinical behavior of IMPC.

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