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BMC Veterinary Research Aug 2022Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes...
BACKGROUND
Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes that are composed of DNA wrapped around a histone core made of four duplicate histone proteins forming an octamer. The nucleosome compartment is a relatively uninvestigated area of circulating tumor biomarkers in dogs. The objectives of this study were to quantify and better characterize nucleosome concentrations in 528 dogs with various common malignancies and compare them to 134 healthy dogs.
RESULTS
The sensitivity of increased circulating nucleosome concentrations for the detection of cancer in all dogs was 49.8% with a specificity of 97% with an area under the curve of 68.74%. The top 4 malignancies detected by the test included lymphoma, hemangiosarcoma, histiocytic sarcoma and malignant melanoma. The malignancies least likely to be detected were soft tissue sarcomas, osteosarcoma and mast cell tumors.
CONCLUSIONS
A variety of tumor types may cause increased nucleosome concentrations in dogs. Tumors of hematopoietic origin are most likely to cause elevations and local tumors such as soft tissue sarcomas are least likely to cause elevations in plasma nucleosome concentrations.
Topics: Animals; Bone Neoplasms; Dog Diseases; Dogs; Histones; Nucleosomes; Sarcoma
PubMed: 36045415
DOI: 10.1186/s12917-022-03429-8 -
International Journal of Hyperthermia :... 2022To investigate the safety, feasibility, and outcomes of High-Intensity Focused Ultrasound (HIFU) for the treatment of solid tumors in a spontaneous canine cancer model.
PURPOSE
To investigate the safety, feasibility, and outcomes of High-Intensity Focused Ultrasound (HIFU) for the treatment of solid tumors in a spontaneous canine cancer model.
METHODS
Dogs diagnosed with subcutaneous solid tumors were recruited, staged and pretreatment biopsies were obtained. A single HIFU treatment was delivered to result in partial tumor ablation using a commercially available HIFU unit. Tumors were resected 3-6 days post HIFU and samples obtained for histopathology and immunohistochemistry. Total RNA was isolated from paired pre and post treated FFPE tumor samples, and quantitative gene expression analysis was performed using the nCounter Canine IO Panel.
RESULTS
A total of 20 dogs diagnosed with solid tumors were recruited and treated in the study. Tumors treated included Soft Tissue Sarcoma ( = 15), Mast Cell Tumor ( = 3), Osteosarcoma ( = 1), and Thyroid Carcinoma ( = 1). HIFU was well tolerated with only 1 dog experiencing a clinically significant adverse event. Pathology confirmed the presence of complete tissue ablation at the HIFU targeted site and immunohistochemistry indicated immune cell infiltration at the treated/untreated tumor border. Quantitative gene expression analysis indicated that 28 genes associated with T-cell activation were differentially expressed post-HIFU.
CONCLUSIONS
HIFU appears to be safe and feasible for the treatment of subcutaneous canine solid tumors, resulting in ablation of the targeted tissue. HIFU induced immunostimulatory changes, highlighting the canine cancer patient as an attractive model for studying the effects of focal ablation therapies on the tumor microenvironment.
Topics: Animals; Dogs; High-Intensity Focused Ultrasound Ablation; Pilot Projects; Sarcoma; Tumor Microenvironment
PubMed: 35848421
DOI: 10.1080/02656736.2022.2097323 -
Veterinary Surgery : VS Oct 2022To describe the frequency of incomplete histological margins following planned narrow excision (PNE) of mast cell tumors (MCTs) and soft tissue sarcomas (STSs), and to...
Incomplete histological margins following planned narrow excision of canine appendicular soft tissue sarcomas and mast cell tumors, using the residual tumor classification scheme.
OBJECTIVE
To describe the frequency of incomplete histological margins following planned narrow excision (PNE) of mast cell tumors (MCTs) and soft tissue sarcomas (STSs), and to assess the residual tumor classification (R) scheme for reporting histological margins in clinical cases.
STUDY DESIGN
Retrospective clinical study.
SAMPLE POPULATION
Forty-four client-owned dogs with 47 masses.
METHODS
Medical records of dogs undergoing planned narrow excision of STSs and MCTs were reviewed (2016-2019). Histologic specimens were reviewed by a single pathologist and assigned R scoring (histologically incomplete/R1 margins defined as "tumor on ink").
RESULTS
Six out of 23 (26%) MCT PNEs and 10/42 (42%) of STS PNEs resulted in R1 margins. R1 margins were more likely when performing PNE with 6-10 mm lateral measured surgical margins (LMSMs) versus 0-5 mm LMSM for MCTs (1/14 vs 5/9), but not STSs (3/7 vs 7/17) (P = .049). The R scheme resulted in higher retrospective percentage agreement in histological reporting than defining incomplete histological margin as tumor cells within ≤1 mm of the margin (83% vs 68% agreement). Complications occurred in 12/47 surgeries, with none requiring additional surgery. Tumors recurred in 3/18 (17%) STSs and 2/18 (11%) MCTs.
CONCLUSION
Fewer R1 margins were obtained when PNE with LMSM of 6-10 mm was performed for mast cell tumors. The use of the R scheme increased agreement in histopathological margin assessment.
CLINICAL SIGNIFICANCE
Planned narrow excision is a viable technique for histopathological diagnosis of appendicular soft tissue sarcomas and mast cell tumors for limb salvage.
Topics: Animals; Dog Diseases; Dogs; Margins of Excision; Mast Cells; Neoplasm Recurrence, Local; Neoplasm, Residual; Retrospective Studies; Sarcoma; Seizures; Skin Neoplasms; Soft Tissue Neoplasms
PubMed: 35830150
DOI: 10.1111/vsu.13852 -
Cancers Jun 2022As in humans, cancer is one of the leading causes of companion animal mortality. Up to 30% of all canine and feline neoplasms appear on the skin or directly under it....
As in humans, cancer is one of the leading causes of companion animal mortality. Up to 30% of all canine and feline neoplasms appear on the skin or directly under it. There are only a few available studies that have investigated pet tumors by biophotonics techniques. In this study, we acquired 1115 optical coherence tomography (OCT) images of canine and feline skin, lipomas, soft tissue sarcomas, and mast cell tumors ex vivo, which were subsequently used for automated machine vision analysis. The OCT images were analyzed using a scanning window with a size of 53 × 53 μm. The distributions of the standard deviation, mean, range, and coefficient of variation values were acquired for each image. These distributions were characterized by their mean, standard deviation, and median values, resulting in 12 parameters in total. Additionally, 1002 Raman spectral measurements were made on the same samples, and features were generated by integrating the intensity of the most prominent peaks. Linear discriminant analysis (LDA) was used for sample classification, and sensitivities/specificities were acquired by leave-one-out cross-validation. Three datasets were analyzed-OCT, Raman, and combined. The combined OCT and Raman data enabled the best sample differentiation with the sensitivities of 0.968, 1, and 0.939 and specificities of 0.956, 1, and 0.977 for skin, lipomas, and malignant tumors, respectively. Based on these results, we concluded that the proposed multimodal approach, combining Raman and OCT data, can accurately distinguish between malignant and benign tissues.
PubMed: 35740486
DOI: 10.3390/cancers14122820 -
Journal of Clinical Medicine Jun 2022Mastocytosis, a heterogeneous mastcell disease, include three different entities: cutaneous mastocytosis, systemic mastocytosis (SM) and mast-cell sarcoma. Tryptase... (Review)
Review
Mastocytosis, a heterogeneous mastcell disease, include three different entities: cutaneous mastocytosis, systemic mastocytosis (SM) and mast-cell sarcoma. Tryptase levels can differentiate cutaneous mastocytosis from SM. In mastocytosis, quick onset drug hypersensitivity reactions (DHRs) that are facilitated by mastcell mediators, are investigated in adults. Due to the limited number of children with mastcell disease and increased serum tryptase levels, the role of drugs in this age group is less studied. In this review, we critically assessed relevant papers related with immediate DHRs in children with mastocytosis and discuss practical issues of the management. In childhood mastocytosis, anaphylaxis is frequently idiopathic, and elevated level of basal tryptase, and high burden of disease may increase the risk. Among drugs, antibiotics, NSAIDs and opioids can potentially induce anaphylaxis, anyway avoidance should be recommended only in case of previous reactions. Moreover, vaccinations are not contraindicated in patients with mastocytosis. The risk of severe systemic reactions after drugs intake seems to be extremely low and in general lower in children than in adults. Anyway, studies on this topic especially focusing on children, are missing to state final recommendations.
PubMed: 35683540
DOI: 10.3390/jcm11113153 -
Human Pathology Aug 2022Systemic mastocytosis (SM) is a myeloid neoplasm characterized by abnormal growth and accumulation of neoplastic mast cells in at least one extracutaneous site. Clinical...
Systemic mastocytosis (SM) is a myeloid neoplasm characterized by abnormal growth and accumulation of neoplastic mast cells in at least one extracutaneous site. Clinical presentation and course are variable, most patients are developing an indolent disease and some, an aggressive/leukemic form. Because of its rarity, most physicians are unfamiliar with this disease and do not readily diagnose it. In the present retrospective study, the authors describe 12 patients diagnosed with mast cell neoplasm. Cases were selected from three institutions from Campinas and São Paulo City, Brazil. Morphological features and diagnostic pitfalls are emphasized. Patients' age ranged from 15 to 81 years (mean 51.6 years). Male and female were affected similarly (1:1). Ten patients were classified as aggressive SM, one patient as SM with an associated acute promyelocytic leukemia with t(15;17), and one patient with mast cell sarcoma. The most common clinical findings included anemia (9 patients), thrombocytopenia (3 patients), and skin lesions (3 patients). Bone marrow was involved in 11 patients at diagnosis, followed by skin (5 patients). Five morphological patterns were present: mast cell aggregates (5), plasmacytoid (4), monocytoid (2), spindle cell (2), and epithelioid/pleomorphic (1); two patients showed two histological patterns. In all cases, neoplastic cells were positive for CD117/C-KIT. C-KIT D816V mutation was present in four patients, C-KIT K509I in two, and del(7q22) in one; in five cases no mutational status was available. Despite limited resources, basically morphology and a restricted immunohistochemical panel, it is possible to diagnose mast cell neoplasm. Of note, the pathologist should recognize the different morphological variants of the disease and include adequate markers when requesting immunohistochemical studies.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brazil; Female; Humans; Male; Mast Cells; Mastocytosis, Systemic; Middle Aged; Myeloproliferative Disorders; Proto-Oncogene Proteins c-kit; Retrospective Studies; Young Adult
PubMed: 35550832
DOI: 10.1016/j.humpath.2022.05.007 -
Novel prognostic biomarkers, METTL14 and YTHDF2, associated with RNA methylation in Ewing's sarcoma.Scientific Reports Apr 2022Ewing's sarcoma has a poor prognosis and high metastasis rate; thus, it is critical to explore prognostic biomarkers of m6A-related genes. Two datasets were downloaded...
Ewing's sarcoma has a poor prognosis and high metastasis rate; thus, it is critical to explore prognostic biomarkers of m6A-related genes. Two datasets were downloaded from the Gene Expression Omnibus database, m6A-related genes were extracted, and prognostic models were constructed using the least absolute shrinkage and selection operator and multivariate COX regression analyses. Immune cell composition and drug sensitivity analyses were performed, and our analysis was validated using laboratory methods of immunohistochemical specific staining and qRT-PCR. Ewing's sarcoma prognostic model demonstrated that the survival rate of cases in the high-risk group was much lower than that of the low-risk group. Naïve B cells, macrophages M0, macrophages M1, and resting mast cells are closely associated with Ewing's sarcoma. METTL14 and YTHDF2 are strongly associated with multiple drug sensitivity. Immunohistochemical specific staining revealed higher expression of both METTL14 and YTHDF2 in Ewing's sarcoma than in the paraneoplastic tissues. The results of qRT-PCR showed that METTL14 expression was significantly higher in both ES cell lines than in the control cell line. The prognostic model constructed using m6A-related genes METTL14 and TYHDF2, can be a potential prognostic biomarker for Ewing's sarcoma, with the survival rate of cases in the high-risk group being much lower than that of the low-risk group.
Topics: Biomarkers; Humans; Methylation; Methyltransferases; Neuroectodermal Tumors, Primitive, Peripheral; Prognosis; RNA; RNA-Binding Proteins; Sarcoma, Ewing; Transcription Factors
PubMed: 35487915
DOI: 10.1038/s41598-022-06744-0 -
PloS One 2022Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived...
Clinical validation of a next-generation sequencing-based multi-cancer early detection "liquid biopsy" blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study.
Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here. In total, 1,358 cancer-diagnosed and presumably cancer-free dogs were enrolled in the study, representing the range of breeds, weights, ages, and cancer types seen in routine clinical practice; 1,100 subjects met inclusion criteria for analysis and were used in the validation of the test. Overall, the liquid biopsy test demonstrated a 54.7% (95% CI: 49.3-60.0%) sensitivity and a 98.5% (95% CI: 97.0-99.3%) specificity. For three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85.4% (95% CI: 78.4-90.9%); and for eight of the most common canine cancers (lymphoma, hemangiosarcoma, osteosarcoma, soft tissue sarcoma, mast cell tumor, mammary gland carcinoma, anal sac adenocarcinoma, malignant melanoma), the detection rate was 61.9% (95% CI: 55.3-68.1%). The test detected cancer signal in patients representing 30 distinct cancer types and provided a Cancer Signal Origin prediction for a subset of patients with hematological malignancies. Furthermore, the test accurately detected cancer signal in four presumably cancer-free subjects before the onset of clinical signs, further supporting the utility of liquid biopsy as an early detection test. Taken together, these findings demonstrate that NGS-based liquid biopsy can offer a novel option for noninvasive multi-cancer detection in dogs.
Topics: Animals; Biomarkers, Tumor; Dogs; Early Detection of Cancer; Hemangiosarcoma; Hematologic Tests; High-Throughput Nucleotide Sequencing; Humans; Liquid Biopsy; Osteosarcoma
PubMed: 35471999
DOI: 10.1371/journal.pone.0266623 -
Animals : An Open Access Journal From... Apr 2022Since small mammals are gaining popularity as pets in Poland, the number of tumour samples submitted for histopathological examination is quite high. This study was a...
Since small mammals are gaining popularity as pets in Poland, the number of tumour samples submitted for histopathological examination is quite high. This study was a retrospective analysis of cutaneous and subcutaneous tumours in small pet mammals submitted for histopathology in 2014-2021. The analysis included 256 tumours sampled from 103 guinea pigs, 53 rats, 43 pet rabbits, 21 ferrets, 17 hamsters, 8 degus, 5 African pygmy hedgehogs, 3 Mongolian gerbils and 3 chinchillas. Tumours were diagnosed based on routine histopathology, with additional immunohistochemistry when necessary. The results of this study revealed that the vast majority of cutaneous tumours in guinea pigs were benign, with a predominance of lipoma. Adnexal tumours constituted a significant percentage of cutaneous tumours in guinea pigs (24.3%, with the most common being trichofolliculoma), pet rabbits (46.5%, with the most common being trichoblastoma), ferrets (33.3%, mostly derived from sebaceous glands), hamsters (52.9%, with the most common being trichoepithelioma) and gerbils (66.7%, scent gland epithelioma). Soft tissue sarcomas were a predominant group of tumours in rats (52.8%, with the most common being fibrosarcoma), African pygmy hedgehogs (100%), degus (87.5%) and chinchillas (66.7%). Melanocytic tumours were only sporadically seen in small mammal pets. Mast cell tumours were diagnosed only in ferrets, while epitheliotropic T-cell lymphoma was diagnosed only in a hamster and a degu. In summary, malignant tumours constitute a significant percentage of cutaneous tumours in many species of small mammal pets. Therefore, each cutaneous tumour should be sampled for further cytologic or histopathologic diagnosis.
PubMed: 35454212
DOI: 10.3390/ani12080965 -
The Journal of Allergy and Clinical... Aug 2022Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology... (Review)
Review
Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma. In most patients with SM, somatic mutations in KIT are detected. Patients with indolent SM have a normal to near-normal life expectancy, whereas patients with advanced SM, including aggressive SM and MC leukemia, have a poor prognosis. In those with advanced SM, multiple somatic mutations and an associated hematologic neoplasm may be detected. Mediator-related symptoms can occur in any type of mastocytosis. Symptoms may be mild, severe, or even life-threatening. In patients with severe acute symptoms, an MC activation syndrome may be diagnosed. In these patients, relevant comorbidities include IgE-dependent and IgE-independent allergies. Management of patients with SM is an emerging challenge in daily practice and requires in-depth knowledge and a multidisciplinary and personalized approach with selection of appropriate procedures and interventions. In this article, we review the current knowledge on SM and MC activation syndrome, with emphasis on multidisciplinary aspects in diagnosis and patient-specific management. In addition, we provide a user's guide for application of markers, algorithms, prognostic scores, and treatments for use in daily practice.
Topics: Humans; Immunoglobulin E; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Proto-Oncogene Proteins c-kit; Tryptases
PubMed: 35342031
DOI: 10.1016/j.jaip.2022.03.007