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Veterinary Surgery : VS Feb 2021To identify which classification systems have been used for tumor margin reporting and to determine whether factors (publication year, tumor type, and specialty of the...
OBJECTIVE
To identify which classification systems have been used for tumor margin reporting and to determine whether factors (publication year, tumor type, and specialty of the contributing authors) influenced trends in margin reporting within literature describing canine soft tissue sarcoma (STS) and cutaneous mast cell tumors (MCT).
STUDY DESIGN
Systematic literature review.
METHODS
Eligible articles were identified through electronic database searches performed for STS and MCT. Data abstracted from relevant studies included publication year, author list, specialty of contributing authors, criteria used to report the planned surgical margins, and the status of histologic margins. Categorization of papers was based on the classification systems used to report surgical and histologic tumor margins.
RESULTS
Fifty-three articles were included, 11 on STS, 37 on MCT, and five that included both tumor types. Criteria for classifying the planned surgical margins were described in only 50.9% of studies. Articles that listed a veterinary surgeon as a contributing author (P = .01) and STS articles compared to MCT papers (P = .01) were more likely to report surgical margins. Most (56.6%) studies reported the status of histologic margins dichotomously as "complete" or "incomplete." Although a previously published consensus statement recommended that quantitative criteria be used to report histologic margins, only 7.5% of articles used quantitative methods.
CONCLUSION
Classification systems used for reporting tumor margins were highly variable among studies.
CLINICAL SIGNIFICANCE
The findings of this review provide evidence that a standardized classification system for reporting surgical and histologic tumor margins is required in veterinary medicine. A universal system may support more consistent reporting of neoplastic biopsy specimens and allow for more meaningful comparisons across research studies.
Topics: Animals; Dog Diseases; Dogs; Margins of Excision; Sarcoma; Soft Tissue Neoplasms
PubMed: 33331059
DOI: 10.1111/vsu.13539 -
Medicine Dec 2020Systemic mastocytosis is a rare disease due to mast cell accumulation in various extracutaneous sites. Systemic mastocytosis with an associated clonal hematologic non-MC...
INTRODUCTION
Systemic mastocytosis is a rare disease due to mast cell accumulation in various extracutaneous sites. Systemic mastocytosis with an associated clonal hematologic non-MC lineage disease is the second most common subtype of systemic mastocytosis. The most common mutation associated with both systemic mastocytosis and myeloid sarcoma is mutation in Kit. Here, we identified the novel KIT D816V and ARID1A G1254S mutations co-occurring in systemic mastocytosis with myeloid sarcoma.
PATIENT CONCERNS
A 33-year old male patient presented multiple skin lesions for 10 years. Symptoms accelerated in 2017 with decreased body weight. Physical examination revealed enlarged lymph nodes in his neck, axilla and inguinal region; conjunctival hemorrhage; gingival hyperplasia. Skin biopsy showed mast cell infiltration. Flow cytometry detected CD2, CD25 and CD117 positive cells in lymph nodes. Codon 816 KIT mutation D816V and codon 1245 ARID1A mutation G1254S were found in peripheral blood. MPO, CD117, CD68 positive cells in lymph nodes indicated co-existing myeloid sarcoma.
DIAGNOSIS
Systemic mastocytosis with an associated clonal hematologic non-MC lineage disease of myeloid sarcoma INTERVENTIONS:: Cytarabine and daunorubicin for myeloid sarcoma and dasatinib for systemic mastocytosis were initiated. Anti-histamine and anti-leukotrienes therapy were used to prevent NSAIDs-induced shock. Platelets were infused to treat bone marrow suppression.
OUTCOMES
Patient was discharged after recovered from bone marrow suppression. Dasatinib continued on outpatient.
CONCLUSION
This is the first case of patient with systemic mastocytosis and myeloid sarcoma simultaneously presenting extensive skin involvements. Mutations of Kit and Arid1a emphasis the importance to notice possibility of various tumors occurring in patients with multiple mutations. In addition, cysteine-leukotrienes-receptor antagonists should always be used to prevent anaphylactic shock due to mast cell activation.
Topics: Adult; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; CD2 Antigens; Cytarabine; DNA-Binding Proteins; Dasatinib; Daunorubicin; Drug Therapy, Combination; Histamine Antagonists; Humans; Interleukin-2 Receptor alpha Subunit; Leukotriene Antagonists; Lymph Nodes; Male; Mastocytosis, Systemic; Mutation; Platelet Transfusion; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit; Sarcoma, Myeloid; Skin; Transcription Factors; Treatment Outcome
PubMed: 33327223
DOI: 10.1097/MD.0000000000021948 -
Journal of Veterinary Medical Education Dec 2021Tumors of the skin and subcutaneous tissues are commonly encountered in primary care practice. The most common of these tumors are mast cell tumors and soft tissue...
Tumors of the skin and subcutaneous tissues are commonly encountered in primary care practice. The most common of these tumors are mast cell tumors and soft tissue sarcomas, for which the primary treatment is most often surgical excision. Understanding surgical margins, particularly the deep fascial plane, can be difficult for veterinary students. Current techniques to teach these concepts typically rely on cadaver-based laboratories, which require simulated tumors to improve the realism of the laboratory. Tumors can be difficult to replicate in cadaver laboratories; thus a new technique for a simulated tumor was developed. A gelatin-based simulated tumor was injected into the subcutaneous space in two different sites in canine cadavers. Students then practiced incisional biopsy and wide excision of a subcutaneous mass. Students were able to appropriately perform both techniques using the simulated tumors. When the deep margin was not clean on the wide excision, students were able to understand the error by identifying the simulated tumor, reinforcing the concept of obtaining an appropriate deep fascial plane. In summary, this gelatin-based simulated tumor technique was cost-effective, easy to perform, and effective for the teaching laboratory.
Topics: Animals; Biopsy; Dermatologic Surgical Procedures; Dog Diseases; Dogs; Education, Veterinary; Humans; Sarcoma; Skin; Students; Surgical Oncology
PubMed: 33226896
DOI: 10.3138/jvme-2020-0028 -
Life Sciences Jan 2021RNA regulatory genes were closely associated with tumorigenesis and prognosis in multiple tumors. Copy number variation (CNV) is a frequent characteristic in soft tissue...
AIMS
RNA regulatory genes were closely associated with tumorigenesis and prognosis in multiple tumors. Copy number variation (CNV) is a frequent characteristic in soft tissue sarcomas (STS). However, little is known regarding their possible roles in STS.
MAIN METHODS
RNA sequence profiles and CNV data of 255 STS patients were downloaded from the Cancer Genome Atlas (TCGA). The correlation analysis involved CNVs of RNA regulatory genes, patient survival, immune infiltration, and DNA methylation. Drug sensitivity (IC50) was analyzed and validated by MTT assays in STS cell lines.
KEY FINDINGS
CNV events were frequently observed in all kinds (m6A, m5C, ac4C, m1A, m3C, m6Am, m7G, and Ψ) of RNA regulatory genes. Diploid copy number (CN) of METTL4 was associated with better overall survival (OS) in STS and the subtypes (leiomyosarcoma, LMS; dedifferentiated liposarcoma, DDLPS). In STS and LMS, diploid CN of METTL4 was significantly associated with higher infiltration fraction of resting mast cells. In STS and DDLPS, diploid CN of METTL4 possessed lower methylation level in CpG site of cg12105018, which represented better OS. Besides, sensitive drugs for STS cell lines were analyzed according to lower IC50 for the loss CN of METTL4. Temozolomide and Olaparib were identified. Further validation by MTT assays demonstrated that GCT was the most sensitive cell line to both Temozolomide and Olaparib.
SIGNIFICANCE
CNV of METTL4 could be a prognostic biomarker for STS by potentially influencing mast cell infiltration and DNA methylation. Besides, STS with loss CN of METTL4 would be sensitive to Temozolomide and Olaparib.
Topics: DNA; DNA Copy Number Variations; DNA Methylation; Databases, Genetic; Female; Genes, Regulator; Humans; Male; Methyltransferases; Prognosis; RNA; Regulatory Sequences, Ribonucleic Acid; Sarcoma
PubMed: 33166590
DOI: 10.1016/j.lfs.2020.118734 -
Canadian Journal of Veterinary Research... Oct 2020Immunohistochemistry has been used extensively to evaluate protein expression in clinical and research settings. However, immunohistochemistry is not always successful...
Immunohistochemistry has been used extensively to evaluate protein expression in clinical and research settings. However, immunohistochemistry is not always successful in veterinary medicine due to the lack of reliable antibody options, poor tissue preservation, labor-intensive staining, and antigen-retrieval optimization processes. RNAscope hybridization (ISH) is a powerful technology that uses a specific sequence probe to identify targeted mRNA. In this study, we demonstrate RNAscope ISH in 4 common canine malignancies, which are traditionally diagnosed by histopathology and immunohistochemistry. Probes were designed for commonly targeted mRNA markers of neoplastic tumors; these included c-kit in mast cell tumor, microphthalmia-associated transcription factor in malignant melanoma, ionized calcium-binding adapter molecule-1 in histiocytic sarcoma, and alkaline phosphatase in osteosarcoma. A strong staining signal was obtained by these 4 targets in each canine malignancy. These results support the use of RNAscope ISH for definitive diagnosis in canine malignancies.
Topics: Animals; Dog Diseases; Dogs; Immunohistochemistry; In Situ Hybridization; Neoplasms; RNA, Messenger
PubMed: 33012982
DOI: No ID Found -
Journal of Cancer Research and Clinical... Jan 2021Ewing sarcoma (ES) is one of the most common malignant bone tumors in children and adolescents. The immune microenvironment plays an important role in the development of...
PURPOSE
Ewing sarcoma (ES) is one of the most common malignant bone tumors in children and adolescents. The immune microenvironment plays an important role in the development of ES. Here, we developed an optimal signature for determining ES patient prognosis based on immune-related genes (IRGs).
METHODS
We analyzed the ES gene expression profile dataset, GSE17679, from the GEO database and extracted differential expressed IRGs (DEIRGs). Then, we conducted functional correlation and protein-protein interaction (PPI) analyses of the DEIRGs and used the machine learning algorithm-iterative Lasso Cox regression analysis to build an optimal DEIRG signature. In addition, we applied ES samples from the ICGC database to test the optimal gene signature. We performed univariate and multivariate Cox regressions on clinicopathological characteristics and optimal gene signature to evaluate whether signature is an important prognostic factor. Finally, we calculated the infiltration of 24 immune cells in ES using the ssGSEA algorithm, and analyzed the correlation between the DEIRGs in the optimal gene signature and immune cells.
RESULTS
A total of 249 DEIRGs were screened and an 11-gene signature with the strongest correlation with patient prognoses was analyzed using a machine learning algorithm. The 11-gene signature also had a high prognostic value in the ES external verification set. Univariate and multivariate Cox regression analyses showed that 11-gene signature is an independent prognostic factor. We found that macrophages and cytotoxic, CD8 T, NK, mast, B, NK CD56bright, TEM, TCM, and Th2 cells were significantly related to patient prognoses; the infiltration of cytotoxic and CD8 T cells in ES was significantly different. By correlating prognostic biomarkers with immune cell infiltration, we found that FABP4 and macrophages, and NDRG1 and Th2 cells had the strongest correlation.
CONCLUSION
Overall, the IRG-related 11-gene signature can be used as a reliable ES prognostic biomarker and can provide guidance for personalized ES therapy.
Topics: Adolescent; Biomarkers, Tumor; Bone Neoplasms; Female; Follow-Up Studies; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Lymphocytes, Tumor-Infiltrating; Machine Learning; Male; Prognosis; Sarcoma, Ewing; Survival Rate; Tumor Microenvironment
PubMed: 32968877
DOI: 10.1007/s00432-020-03396-3 -
The Veterinary Record Oct 2020
Topics: Animals; Antineoplastic Agents; Dog Diseases; Dogs; Injections; Mast-Cell Sarcoma; Skin Neoplasms
PubMed: 32747483
DOI: 10.1136/vr.m3070 -
The Journal of Infectious Diseases Jan 2021It has been demonstrated that activated mast cells (MCs) are enriched in Kaposi sarcoma (KS) tumors and contribute to the inflammatory microenvironment. Mechanisms...
It has been demonstrated that activated mast cells (MCs) are enriched in Kaposi sarcoma (KS) tumors and contribute to the inflammatory microenvironment. Mechanisms driving MC activation, however, are incompletely understood. We sought to understand whether immunoglobulin E (IgE), a potent activator of MCs, was associated with KS incidence and severity. In a cross-sectional study of untreated human immunodeficiency virus (HIV)-infected adults with or without KS in Uganda, we found that patients with KS had higher plasma IgE levels than those without KS. After adjustment for age, sex, CD4+ T-cell count, and HIV RNA levels, there was a dose-response relationship between plasma IgE levels and the presence and severity of KS. Higher eosinophil counts were also associated with IgE levels, and plasma interleukin 33 concentrations were higher in individuals with KS. These findings suggest that IgE-driven atopic inflammation may contribute the pathogenesis of KS. Therapies targeting IgE-mediated MC activation thus might represent a novel approach for treatment or prevention of KS.
Topics: Adult; CD4 Lymphocyte Count; Case-Control Studies; Cross-Sectional Studies; Female; HIV Infections; Humans; Immunoglobulin E; Interleukin-33; Male; Sarcoma, Kaposi; Severity of Illness Index; Uganda
PubMed: 32561934
DOI: 10.1093/infdis/jiaa340 -
Genes May 2020The tumor microenvironment plays important roles in cancer biology, but genetic backgrounds of mouse models can complicate interpretation of tumor phenotypes. A deeper...
The tumor microenvironment plays important roles in cancer biology, but genetic backgrounds of mouse models can complicate interpretation of tumor phenotypes. A deeper understanding of strain-dependent influences on the tumor microenvironment of genetically-identical tumors is critical to exploring genotype-phenotype relationships, but these interactions can be difficult to identify using traditional Cre/loxP approaches. Here, we use somatic CRISPR/Cas9 tumorigenesis approaches to determine the impact of mouse background on the biology of genetically-identical malignant peripheral nerve sheath tumors (MPNSTs) in four commonly-used inbred strains. To our knowledge, this is the first study to systematically evaluate the impact of host strain on CRISPR/Cas9-generated mouse models. Our data identify multiple strain-dependent phenotypes, including changes in tumor onset and the immune microenvironment. While BALB/c mice develop MPNSTs earlier than other strains, similar tumor onset is observed in C57BL/6, 129X1 and 129/SvJae mice. Indel pattern analysis demonstrates that indel frequency, type and size are similar across all genetic backgrounds. Gene expression and IHC analysis identify multiple strain-dependent differences in CD4+ T cell infiltration and myeloid cell populations, including M2 macrophages and mast cells. These data highlight important strain-specific phenotypes of genomically-matched MPNSTs that have implications for the design of future studies using similar gene editing approaches.
Topics: Animals; CD4-Positive T-Lymphocytes; CRISPR-Cas Systems; Carcinogenesis; Disease Models, Animal; Gene Editing; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Humans; Mice; Mice, Inbred BALB C; Neurofibrosarcoma; Tumor Microenvironment
PubMed: 32456131
DOI: 10.3390/genes11050583 -
Veterinary Sciences Apr 2020Tumors of mesenchymal origin are rarely reported in the pancreas. Therefore, this study characterized 17 feline non-epithelial pancreatic tumors, including clinical...
Tumors of mesenchymal origin are rarely reported in the pancreas. Therefore, this study characterized 17 feline non-epithelial pancreatic tumors, including clinical data, histopathology, and immunohistochemistry. Seventeen feline pancreatic tissue samples were investigated histopathologically and immunohistochemically. Selected pancreatic and inflammatory serum parameters, e.g., feline pancreatic lipase immunoreactivity (fPLI), 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase and serum amyloid A (SAA), were recorded, when available. The neoplasms were characterized as round (n = 13) or spindle (n = 4) cell tumors. Round cell tumors included 12 lymphomas and one mast cell tumor in ectopic splenic tissue within the pancreas. Lymphomas were of T-cell (n = 9) or B-cell (n = 3) origin. These cats showed leukocytosis (3/3) and increased fPLI (5/5), DGGR lipase (3/5) and SAA (4/5) values. Spindle cell tumors included two hemangiosarcomas, one pleomorphic sarcoma and one fibrosarcoma. The cat with pleomorphic sarcoma showed increased SAA value. Overall survival time was two weeks to seven months. These are the first descriptions of a pancreatic pleomorphic sarcoma and a mast cell tumor in accessory spleens within feline pancreas. Although rare, pancreatic tumors should be considered in cats presenting with clinical signs and clinical pathology changes of pancreatitis. Only histopathology can certainly distinguish solitary pancreatitis from a neoplasm with inflammation.
PubMed: 32349235
DOI: 10.3390/vetsci7020055