Pigmented Epithelioid Melanocytomas and Their Mimics; Focus on Their Novel Molecular Findings

Pigmented epithelioid melanocytoma (PEM) is a unique tumor with significantly pigmented appearance and indolent behavior; however, it can demonstrate cytological atypia and metastasize to local lymph nodes. Clinical and histomorphological overlap between PEM and its lower or higher-grade mimics can make it difficult to distinguish in certain cases. Genomic, transcriptomic and epigenetic data indicate that PEMs are molecularly distinct entities from other melanocytic neoplasms and melanomas. In addition, methylation studies are emerging as a tool that can be useful in difficult cases. In this review, we focus on the clinical, histopathologic and recent insights in the molecular features of pigmented epithelioid melanocytic melanocytomas and their mimics. We also present a challenging case that was resolved using methylation analysis providing a proof of concept for using epigenetic studies for similar challenging cases.

Download Full-text

60 Facilitating discussions of difficult cases at lung cancer MDTs – can the SUV of the primary tumour and lymph nodes be of any help?

Lung Cancer ◽

10.1016/s0169-5002(13)70060-6 ◽

2013 ◽

Vol 79 ◽

pp. S20-S21

Author(s):

M. Evison ◽

P. Crosbie ◽

J. Martin ◽

P. Barber ◽

R. Booton

Keyword(s):

Lung Cancer ◽

Lymph Nodes ◽

Primary Tumour ◽

Difficult Cases ◽

Facilitating Discussions

Download Full-text

Evaluation of a pre-harvest bacteriophage therapy for control of Salmonella within bovine peripheral lymph nodes

Journal of Food Protection ◽

10.4315/jfp-21-292 ◽

2021 ◽

Author(s):

L. R. Wottlin ◽

Tom Edrington ◽

T. R. Brown ◽

C. A. Zook ◽

A. Sulakvelidze ◽

...

Keyword(s):

Lymph Nodes ◽

Post Mortem ◽

Proof Of Concept ◽

Bacteriophage Therapy ◽

Transmission Electron ◽

Peripheral Lymph ◽

Final Study ◽

Phage Cocktail ◽

The Right ◽

Phage Treatment

A series of proof of concept studies were developed to determine if a commercial bacteriophage (phage) cocktail could be utilized for the mitigation of Salmonella in bovine peripheral lymph nodes (LN). The first objective sought to determine if exogenous phage could be isolated from the LN following administration. If successful, the second objective sought to determine if once in the LN, could the phage effectively reduce Salmonella . Salmonella Montevideo was inoculated intradermally in multiple sites and administrations, later followed by delivery of the phage cocktail subcutaneously in two injections around each of the right and left prescapular and subiliac LN. At the conclusion of each study, animals were euthanized and the popliteal and above LN examined. The first study was successful, in that transmission electron microscopy revealed the presence of phage in the LN of the treated cattle, that were identical to the strains in the cocktail. Concentrations of phage were increased ( P < 0.01) in the pre-scapular and subiliac LN in the phage-treated versus control cattle. Subsequent studies modified the protocols to increase Salmonella and phage concentrations within the LN. Overall concentrations of Salmonella were increased in the LN compared to the first study and phage treatment decreased ( P < 0.01) Salmonella in the some of the LN. Phage concentrations were numerically ( P = 0.12), but not statistically, increased in the treated cattle. The final study was modified, hypothesizing that a 48h post-mortem period prior to LN removal would facilitate phage/ Salmonella interaction, however, there were no differences ( P > 0.10) in Salmonella concentrations among treatments. Results demonstrated that Salmonella- specific phages administered to live cattle can translocate to the LN, however once in the LN they had limited to no effect on Salmonella within these nodes.

Download Full-text

Plasmablastic Lymphoma of the Cervical Lymph Nodes in a Human Immunodeficiency Virus–Negative Patient: A Case Report and Review of the Literature

Archives of Pathology & Laboratory Medicine ◽

10.5858/2004-128-581-plotcl ◽

2004 ◽

Vol 128 (5) ◽

pp. 581-584 ◽

Cited By ~ 1

Author(s):

Fan Lin ◽

Kai Zhang ◽

Albert T. Quiery ◽

Jeffrey Prichard ◽

Conrad Schuerch

Keyword(s):

Human Immunodeficiency Virus ◽

Lymph Nodes ◽

Large Cell ◽

Needle Aspiration ◽

Plasmablastic Lymphoma ◽

Chain Gene ◽

Cervical Lymph Nodes ◽

Light Chain Gene ◽

Molecular Features ◽

Immunodeficiency Virus

Abstract We report a case of plasmablastic lymphoma presenting in cervical lymph nodes in an 82-year-old, human immunodeficiency virus–negative man. Cytologic and histologic examinations demonstrated a large cell lymphoma with plasmacytic differentiation. The tumor cells were positive for CD138, CD38, epithelial membrane antigen, CD30, and lysozyme, but lacked expression of leukocyte common antigen, T-cell, and B-cell markers. Abundant Epstein-Barr virus–encoded RNA transcripts were identified by in situ hybridization. A monoclonal rearrangement of κ-light- chain gene was demonstrated. The cytologic, histologic, immunohistochemical, and molecular features of plasmablastic lymphoma are reviewed. The potential diagnostic pitfalls and differential diagnoses, especially in a fine-needle aspiration specimen, are addressed.

Download Full-text

MALT lymphoma of the colon: a clinicopathological review

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-206377 ◽

2020 ◽

Vol 73 (7) ◽

pp. 378-383 ◽

Cited By ~ 3

Author(s):

Norris Hollie ◽

Saja Asakrah

Keyword(s):

Malt Lymphoma ◽

Lymphoid Tissue ◽

Marginal Zone ◽

Cell Lymphoma ◽

Polypoid Lesion ◽

B Cell Lymphoma ◽

Marginal Zone Lymphoma ◽

Histological Evaluation ◽

Molecular Features ◽

Difficult Cases

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) occurs in approximately 9% of non-Hodgkin B cell lymphoma. However, it occurs only rarely within the colon. The presentation is often asymptomatic, and can have multiple endoscopic appearances, including a single or multinodular polypoid lesion. Furthermore, small biopsies can make histological evaluation challenging. The 2016 WHO classification update includes many molecular features of entities and expands the differential diagnosis of lymphoid lesions of the colon. In addition to immunohistochemistry, molecular methods may be tempting to use for small difficult cases. Furthermore, treatment approaches are varied for this entity, and not well studied. Therefore, an updated review on MALT lymphoma of the colon is needed.

Download Full-text

Telepathological evaluation of paediatric histological specimens in support of a hospital in Tanzania

African Health Sciences ◽

10.4314/ahs.v20i3.37 ◽

2020 ◽

Vol 20 (3) ◽

pp. 1313-1321

Author(s):

Hans-Ullrich Voelker ◽

Laura Poetzl ◽

Annette Strehl ◽

Hans-Konrad Mueller-Hermelink ◽

Ansgar Stuefe ◽

...

Keyword(s):

Soft Tissue ◽

Lymph Nodes ◽

Low Income ◽

Medical Diagnostics ◽

Benign Tumors ◽

Malignant Diseases ◽

Benign Diseases ◽

Low Income Country ◽

Histological Images ◽

Difficult Cases

Background/Objective: In a project of telepathology (TP) between German pathologists and a hospital in Tanzania, trained technical assistants have uploaded digital histological images onto the internet-based platform ipath. The diagnoses from 486 paediatric specimens were analysed. Methods: The investigation included diagnoses, either primarily done via TP or secondarily after a further workup of the paraffin-embedded tissue, which was sent to Germany for cases which could not be solved via TP. In the latter, the initial TP-diagnoses were compared with the results after re-evaluation. Results: The median age was 11 years. The cohort comprised 390 benign diseases (80.2%) and 96 malignant diseases (19.8%). For benign diseases, the most frequent anatomic sites were lymph nodes, skin, and soft tissue, breast, and head&- neck. Frequent diagnoses were non-specific inflammations and benign tumors. In malignant diseases, the most sites were lymph nodes, skin, soft tissue, head&neck, and ovary and the most frequent diseases sarcomas and lymphomas. The paraffin embedded tissue of 179 cases (36.3%) was shipped to Germany. With the concordance analysis, we could discover the man- datory necessity for the possibility of second opinion in difficult cases. Conclusion: An exclusively TP-support cannot meet all requirements of modern medical diagnostics. The education of local pathologists is imperative. Keywords: Telepathology; low income country; ipath; paediatric.

Download Full-text

Metabolomics Identifies Perturbations in Human Disorders of Propionate Metabolism

Clinical Chemistry ◽

10.1373/clinchem.2007.089011 ◽

2007 ◽

Vol 53 (12) ◽

pp. 2169-2176 ◽

Cited By ~ 114

Author(s):

William R Wikoff ◽

Jon A Gangoiti ◽

Bruce A Barshop ◽

Gary Siuzdak

Keyword(s):

Clinical Chemistry ◽

Propionic Acidemia ◽

Disease Diagnosis ◽

Metabolic Effects ◽

P Value ◽

Proof Of Concept ◽

Healthy Individuals ◽

Molecular Features ◽

Human Disorders ◽

Screening Platform

Abstract Background: We applied untargeted mass spectrometry-based metabolomics to the diseases methylmalonic acidemia (MMA) and propionic acidemia (PA). Methods: We used a screening platform that used untargeted, mass-based metabolomics of methanol-extracted plasma to find significantly different molecular features in human plasma samples from MMA and PA patients and from healthy individuals. Capillary reverse phase liquid chromatography (4 μL/min) was interfaced to a TOF mass spectrometer, and data were processed using nonlinear alignment software (XCMS) and an online database (METLIN) to find and identify metabolites differentially regulated in disease. Results: Of the approximately 3500 features measured, propionyl carnitine was easily identified as the best biomarker of disease (P value 1.3 × 10−18), demonstrating the proof-of-concept use of untargeted metabolomics in clinical chemistry discovery. Five additional acylcarnitine metabolites showed significant differentiation between plasma from patients and healthy individuals, and γ-butyrobetaine was highly increased in a subset of patients. Two acylcarnitine metabolites and numerous unidentified species differentiate MMA and PA. Many metabolites that do not appear in any public database, and that remain unidentified, varied significantly between normal, MMA, and PA, underscoring the complex downstream metabolic effects resulting from the defect in a single enzyme. Conclusions: This proof-of-concept study demonstrates that metabolomics can expand the range of metabolites associated with human disease and shows that this method may be useful for disease diagnosis and patient clinical evaluation.

Download Full-text

Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study

Scientific Reports ◽

10.1038/s41598-020-73014-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Chloé Albert Vega ◽

Guy Oriol ◽

François Bartolo ◽

Jonathan Lopez ◽

Alexandre Pachot ◽

...

Keyword(s):

Septic Shock ◽

Immune Response ◽

Nosocomial Infections ◽

Added Value ◽

Functional Assay ◽

Proof Of Concept ◽

Concept Study ◽

The Third ◽

Molecular Features ◽

Therapeutic Decisions

Abstract The complexity of sepsis pathophysiology hinders patient management and therapeutic decisions. In this proof-of-concept study we characterised the underlying host immune response alterations using a standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock patients, ex vivo LPS and SEB stimulations modulated, respectively, 5.3% (1/19) and 57.1% (12/21) of the pathways modulated in healthy volunteers (HV), highlighting deeper alterations induced by LPS than by SEB. SEB-based clustering, identified 3 severity-based groups of septic patients significantly different regarding mHLA-DR expression and TNFα level post-LPS, as well as 28-day mortality, and nosocomial infections. Combining the results from two independent cohorts gathering 20 HV and 60 patients, 1 cluster grouped all HV with 12% of patients. The second cluster grouped 42% of patients and contained all non-survivors. The third cluster grouped 46% of patients, including 78% of those with nosocomial infections. The molecular features of these clusters indicated a distinctive contribution of previously described genes defining a “healthy-immune response” and a “sepsis-related host response”. The third cluster was characterised by potential immune recovery that underlines the possible added value of SEB-based IFA to capture the sepsis immune response and contribute to personalised management.

Download Full-text

Multi-layered network-based pathway activity inference using directed random walks: application to predicting clinical outcomes in urologic cancer

10.1101/2020.07.22.163949 ◽

2020 ◽

Author(s):

So Yeon Kim ◽

Eun Kyung Choe ◽

Manu Shivakumar ◽

Dokyoon Kim ◽

Kyung-Ah Sohn

Keyword(s):

Integrative Approach ◽

Proof Of Concept ◽

R Software ◽

Pathway Activity ◽

Source Codes ◽

Prognostic Features ◽

Molecular Features ◽

Urologic Cancer ◽

Inference Methods ◽

Urologic Cancers

AbstractMotivationTo better understand the molecular features of cancers, a comprehensive analysis using multi-omics data has been conducted. Additionally, a pathway activity inference method has been developed to facilitate the integrative effects of multiple genes. In this respect, we have recently proposed a novel integrative pathway activity inference approach, iDRW, and demonstrated the effectiveness of the method with respect to dichotomizing two survival groups. However, there were several limitations, such as a lack of generality. In this study, we designed a directed gene-gene graph using pathway information by assigning interactions between genes in multiple layers of networks.ResultsAs a proof-of-concept study, it was evaluated using three genomic profiles of urologic cancer patients. The proposed integrative approach achieved improved outcome prediction performances compared with a single genomic profile alone and other existing pathway activity inference methods. The integrative approach also identified common/cancer-specific candidate driver pathways as predictive prognostic features in urologic cancers. Furthermore, it provides better biological insights into the prioritized pathways and genes in an integrated view using a multi-layered gene-gene network. Our framework is not specifically designed for urologic cancers and can be generally applicable for various datasets.AvailabilityiDRW is implemented as the R software package. The source codes are available at https://github.com/sykim122/iDRW.

Download Full-text

hcapca: Automated Hierarchical Clustering and Principal Component Analysis of Large Metabolomic Datasets in R

Metabolites ◽

10.3390/metabo10070297 ◽

2020 ◽

Vol 10 (7) ◽

pp. 297 ◽

Cited By ~ 3

Author(s):

Shaurya Chanana ◽

Chris S. Thomas ◽

Fan Zhang ◽

Scott R. Rajski ◽

Tim S. Bugni

Keyword(s):

Anticancer Agent ◽

Marine Invertebrate ◽

Principal Component ◽

Large Datasets ◽

Proof Of Concept ◽

Associated Bacteria ◽

New Approach ◽

Biological Assays ◽

The Past ◽

Molecular Features

Microbial natural product discovery programs face two main challenges today: rapidly prioritizing strains for discovering new molecules and avoiding the rediscovery of already known molecules. Typically, these problems have been tackled using biological assays to identify promising strains and techniques that model variance in a dataset such as PCA to highlight novel chemistry. While these tools have shown successful outcomes in the past, datasets are becoming much larger and require a new approach. Since PCA models are dependent on the members of the group being modeled, large datasets with many members make it difficult to accurately model the variance in the data. Our tool, hcapca, first groups strains based on the similarity of their chemical composition, and then applies PCA to the smaller sub-groups yielding more robust PCA models. This allows for scalable chemical comparisons among hundreds of strains with thousands of molecular features. As a proof of concept, we applied our open-source tool to a dataset with 1046 LCMS profiles of marine invertebrate associated bacteria and discovered three new analogs of an established anticancer agent from one promising strain.

Download Full-text