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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 Internal Medicine 2014Mutation analysis of proto-oncogene c-kit (c-kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including...
BACKGROUND
Mutation analysis of proto-oncogene c-kit (c-kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including those with metastatic disease. Testing is usually performed on primary tumors, assuming that c-kit mutation status does not change in metastasis.
HYPOTHESIS/OBJECTIVES
To give an insight into the mutational processes and to make a recommendation on the use of c-kit mutational analysis in the clinical setting.
ANIMALS
Twenty-one client-owned dogs with metastatic MCT.
METHODS
Dogs undergoing resection or biopsy for both primary and matched metastatic MCT were prospectively enrolled. Total RNA or DNA was extracted from primary MCT and corresponding metastases. Exons 8, 9, and 11 were amplified by PCR and sequenced. Genetic features between primary MCT and metastases were compared. Their correlation with clinicopathologic features was investigated.
RESULTS
Concordance (mutated or wild-type) of mutational status, evaluable in 21 primary and matched metastatic (20 nodal and 1 splenic) MCTs, was 100%. Three new c-kit mutations were identified. No significant correlation was detected between c-kit mutation and clinicopathologic features.
CONCLUSIONS AND CLINICAL IMPORTANCE
Proto-oncogene c-kit mutational status is conserved between any primary and its matched secondary tumor, suggesting that both can be used for c-kit mutational testing. Targeted therapies might be also used to treat metastatic disease.
Topics: Animals; Dog Diseases; Dogs; Exons; Female; Genetic Testing; Genotyping Techniques; Male; Mast-Cell Sarcoma; Mastocytoma; Mutation; Proto-Oncogene Proteins c-kit
PubMed: 24372836
DOI: 10.1111/jvim.12266 -
Journal of the American Veterinary... Jan 2008To determine response rate and reduction in tumor burden and effect of dose on tumor response in dogs treated with neoadjuvant prednisone for cutaneous mast cell tumors...
OBJECTIVE
To determine response rate and reduction in tumor burden and effect of dose on tumor response in dogs treated with neoadjuvant prednisone for cutaneous mast cell tumors (MCTs).
DESIGN
Combined prospective clinical study and retrospective case series.
ANIMALS
49 dogs with MCT.
PROCEDURES
Medical records were retrospectively reviewed for dogs with primary untreated cutaneous MCT managed with neoadjuvant prednisone administration and surgery. Tumor characteristics and response to treatment were recorded. A subset of dogs assigned to low-dose (LD) treatment with neoadjuvant prednisone (1.0 mg/kg [0.45 mg/lb], PO, q 24 h) or high-dose (HD) treatment (2.2 mg/kg [1.0 mg/lb], PO, q 24 h) was used to determine the effects of dose.
RESULTS
The overall objective response rate was 70% for dogs treated with neoadjuvant prednisone; prednisone dose was not significantly associated with response. Prospectively, the median sum maximal diameter (MaxD) reduction was 45.2%, and reduction in tumor volume was 80.6%. In both treatment groups, the mean percentage MaxD reduction and tumor volume reduction were significant. The difference in response between the LD and HD groups was not significant. The LD group had mean MaxD and tumor volume reductions of 35.4% and 52.5%, respectively, compared with mean reductions of 48.8% in MaxD and 78% in tumor volume in the HD group.
CONCLUSIONS AND CLINICAL RELEVANCE
Treatment with neoadjuvant prednisone appears to be useful for inducing reduction of MCTs and may facilitate resection when adequate surgical margins cannot be confidently attained because of mass location or size or both.
Topics: Animals; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Disease-Free Survival; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Female; Male; Mast-Cell Sarcoma; Neoplasm Recurrence, Local; Neoplasm Staging; Prednisone; Prospective Studies; Random Allocation; Retrospective Studies; Skin Neoplasms; Treatment Outcome
PubMed: 18167109
DOI: 10.2460/javma.232.1.53 -
Journal of Veterinary Internal Medicine 2010The presence of drug residues in blood samples can represent an occupational hazard. However, studies on cytotoxic drug residues in serum of dogs are lacking in...
BACKGROUND
The presence of drug residues in blood samples can represent an occupational hazard. However, studies on cytotoxic drug residues in serum of dogs are lacking in veterinary oncology.
OBJECTIVE
To evaluate possible occupational hazards associated with handling of blood samples from dogs receiving oncolytic drugs 7 days after treatment.
ANIMALS
Twenty-seven client-owned dogs treated for lymphoma or mast cell tumors with vincristine, vinblastine, cyclophosphamide, or doxorubicin.
METHODS
Prospective, observational study. Serum samples were either taken 7 days after administration of vincristine, cyclophosphamide, doxorubicin (lymphoma), and vinblastine (mast cell tumor), or 1-2 days after the last concurrent oral administration of cyclophosphamide (mast cell tumor). Additionally, serum was collected within 5 minutes of treatment. Measurement of drug residues in serum was performed by liquid chromatography tandem mass spectrometry (LC/MS/MS).
RESULTS
In 33 samples collected within 5 minute of treatment, the median serum concentrations were vincristine: 37 microg/L (range: 11-87 microg/L), vinblastine: 13 microg/L (range: 13-35 microg/L), cyclophosphamide: 2,484 microg/L (range: 1,209-2,778 microg/L), doxorubicin: 404 microg/L (range: 234-528 microg/L). In 81 serum samples collected 7 days after treatment vinblastine (7 microg/L) was detected in 1 sample, and cyclophosphamide (7 and 9 microg/L) in 2 samples collected 1-2 days after oral administration of cyclophosphamide. Medications were not detected in any of the other samples.
CONCLUSIONS AND CLINICAL IMPORTANCE
Handling of blood samples from dogs receiving oncolytic chemotherapy 7 days after treatment with vincristine, vinblastine, cyclophosphamide, and doxorubicin should not present a health hazard.
Topics: Animals; Antineoplastic Agents; Dog Diseases; Dogs; Drug Residues; Lymphoma; Mast-Cell Sarcoma; Medical Laboratory Personnel; Occupational Exposure; Prospective Studies; Risk Factors; Veterinarians
PubMed: 20102504
DOI: 10.1111/j.1939-1676.2009.0469.x -
Veterinary Sciences Mar 2023The histopathological diagnosis of canine splenic mass lesions is crucial for prognostication. However, thus far, no study has been conducted on the histopathology of...
The histopathological diagnosis of canine splenic mass lesions is crucial for prognostication. However, thus far, no study has been conducted on the histopathology of canine splenic mass lesions in Republic of Korea. Herein, the prevalence of splenic diseases was analyzed in 137 canine splenic mass lesions via histopathological diagnosis, and the microscopic pattern associated with each disorder was described. Immunohistochemistry was performed for CD31, CD3, PAX5, Iba1, and C-kit for a more accurate diagnosis of splenic tumors. The proportion of non-neoplastic disorders, including nodular hyperplasia (48.2%, n = 66) and hematoma (24.1%, n = 33), was 72.3%. Splenic tumors, including splenic hemangiosarcoma (10.2%, n = 14), splenic lymphoma (nodular and diffuse types, 8.0%, n = 11), splenic stromal sarcoma (7.3%, n = 10), myelolipoma (1.5%, n = 2), and mast cell tumors (0.7%, n = 1), accounted for 27.7% of cases. The results of this study will aid veterinary clinicians in communication with pet owners about prognoses, recommendations for splenectomy, and subsequent histopathological diagnoses. This study will facilitate further investigations with more detailed comparisons of splenic mass lesions between small- and large-breed dogs.
PubMed: 37104402
DOI: 10.3390/vetsci10040247 -
Journal of Veterinary Internal Medicine 2000Presence of matrix metalloproteinases has been associated with tumor invasion and metastasis in human neoplasia. The presence of matrix metalloproteinase 2 and matrix...
Presence of matrix metalloproteinases has been associated with tumor invasion and metastasis in human neoplasia. The presence of matrix metalloproteinase 2 and matrix metalloproteinase 9 was determined in canine mast cell tumor tissue and normal stromal tissue from 24 dogs with spontaneously occurring cutaneous mast cell tumors. Seventeen of the mast cell tumors were of histologic grade 2, and 7 were of histologic grade 3. Gelatin zymography and computer assisted densitometry image analysis were used to quantify matrix metalloproteinase concentration. Bands from canine tissues migrated in the same location as human proenzyme and active enzyme matrix metalloproteinase 2 and matrix metalloproteinase 9 standards. A semiquantitative value for each patient sample was obtained by comparing the optical assessment density of each unknown band to the optical density of the human standard. The presence of matrix metalloproteinase 2 and matrix metalloproteinase 9 in histologic grade 2 mast cell tumors and histologic grade 3 mast cell tumors was compared, as was presence of matrix metalloproteinases in tumor and stromal tissue. There was dramatically more proenzyme matrix metalloproteinase 9 activity in histologic grade 3 mast cell tumors when compared to grade 2 tumors (P = .03). There was also dramatically more active enzyme matrix metalloproteinase 2 and active enzyme matrix metalloproteinase 9 activity in tumor tissue compared to stromal tissue (P = .02, P < .0001). This study demonstrates that the proenzyme and active enzyme forms of matrix metalloproteinase 2 and matrix metalloproteinase 9 are present in canine mast cell tumors. This appears to be related to the degree of histologic malignancy, although histologic grade 1 tumors were not evaluated.
Topics: Animals; Dog Diseases; Dogs; Electrophoresis, Agar Gel; Image Processing, Computer-Assisted; Mast-Cell Sarcoma; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Skin Neoplasms; Statistics, Nonparametric
PubMed: 11110378
DOI: 10.1892/0891-6640(2000)014<0583:iommic>2.3.co;2 -
The Journal of Experimental Medicine Nov 1985We characterize the natural killer (NK) cell colony-inhibiting activity (CIA) produced in supernatants from cultures of human peripheral blood lymphocytes (PBL) with...
Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor. Relationship with tumor necrosis factor and synergism with immune interferon.
We characterize the natural killer (NK) cell colony-inhibiting activity (CIA) produced in supernatants from cultures of human peripheral blood lymphocytes (PBL) with NK-sensitive target cell lines, and study its relationship with NK cell-derived cytotoxic factor (NKCF). Using monoclonal antibodies (mAb) specific for NK cells or other lymphocyte populations, we unambiguously identify NK cells as the only PBL subset able to produce both NKCF and NK-CIA. We present functional and biochemical data suggesting that NKCF and NK-CIA represent the same molecule: (a) a highly significant positive correlation exists between the quantity of NKCF and NK-CIA in supernatants independently produced by different PBL subsets; (b) both NK-CIA and NKCF are induced by culture of PBL with NK-sensitive, but not with NK-insensitive cell lines, and with HLA-DR+ bone marrow cells; (c) both NKCF and NK-CIA are absorbed on the same cell lines or bone marrow cell types; (d) the two activities coelute in the same gel filtration fractions; (e) D-mannose-6-phosphate blocks both NKCF and NK-CIA activity, and prevents their absorption by K562 cells; and (f) both NKCF and NK-CIA activity are lost after 2 d at 37 degrees C. The NK-CIA-containing preparations are devoid of antiviral activity, and antiinterferon (anti-IFN) antibodies do not block the inhibitor activity of NK-CIA. The effect of NK-CIA on day 14 (early) colony-forming units of granulocytes and macrophages (CFU-GM) is synergistic with that of IFN-gamma, and this synergy is also evident on day 7 (late) CFU-GM growth. A combination of NK-CIA and IFN-gamma suppresses late CFU-GM, at concentrations of the two lymphokines that are completely ineffective when used independently. No synergy between NK-CIA and IFN-alpha or -beta was observed, due to a direct inhibitory effect of these two IFN types on late CFU-GM. Antibodies specific for tumor necrosis factor (TNF), but not those specific for lymphotoxins, inhibit both NK-CIA and NKCF activity in the NK cell-derived supernatant. Recombinant TNF, in the range of concentrations corresponding to that of the cytotoxic activity on L-929 cells present in supernatants, mediated both NKCF and NK-CIA activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Bone Marrow; Bone Marrow Cells; Burkitt Lymphoma; Cell Line; Cells, Cultured; Colony-Forming Units Assay; Cytotoxicity, Immunologic; Drug Synergism; Glycoproteins; Growth Inhibitors; Humans; Interferon-gamma; Killer Cells, Natural; Leukemia, Myeloid; Lymphocytes; Lymphokines; Mast-Cell Sarcoma; Mice; Tumor Necrosis Factor-alpha
PubMed: 3932579
DOI: 10.1084/jem.162.5.1512 -
Medicine May 2018Mastocytosis is a rare disease characterized by clonal neoplastic proliferation of mast cells (MCs). It ranges from skin lesions as cutaneous mastocytosis (CM) which may... (Observational Study)
Observational Study
Mastocytosis is a rare disease characterized by clonal neoplastic proliferation of mast cells (MCs). It ranges from skin lesions as cutaneous mastocytosis (CM) which may spontaneously regress to highly aggressive neoplasms with multiorgan involvement corresponding to some aggressive systemic mastocytosis (ASM), mast cell leukemia (MCL), and/or mast cell sarcoma (MCS).There is increasing evidence of CD30 expression in neoplastic MCs of the bone marrow. This expression has been described almost exclusively in aggressive forms of systemic mastocytosis (SM).The aim of the present study is to evaluate CD30 expression both in cutaneous and systemic forms of mastocytosis. Forty-two mastocytosis cases were reviewed, including cutaneous (n = 29) and systemic (n = 13) forms to assess the prevalence of CD30 expression. Thirty-nine out of 42 (92.8%) cases were CD30 positive. In cases of CM, 28/29 (96.5%) cases were CD30 positive, 11/13 cases of SM (84.6%) were positive for CD30. MCs in normal skin biopsies and in urticaria lesions were CD30-negative. This study found that CD30 is also frequently expressed in CM as well as in systemic forms. This finding is a major departure from the prevailing concept that CD30 expression is often related to aggressive systemic forms of mastocytosis.
Topics: Adolescent; Adult; Aged; Biopsy; Child; Child, Preschool; Diagnosis, Differential; Humans; Immunohistochemistry; Ki-1 Antigen; Mast Cells; Mastocytosis; Middle Aged; Mutation; Prevalence; Proto-Oncogene Proteins c-kit; Retrospective Studies; Skin
PubMed: 29794740
DOI: 10.1097/MD.0000000000010642 -
Immunology Oct 1975Both phagocytic and non-phagocytic effector cells were able to kill rabbit antibody-coated chicken erythrocytes (CRBC) while only non-phagocytic effector cells were...
Characteristics of the effector cells mediating cytotoxicity against antibody-coated target cells. I. Phagocytic and non-phagocytic effector cell activity against erythrocyte and tumour target cells in a 51Cr release cytotoxicity assay and [125I]IUdR growth inhibition assay.
Both phagocytic and non-phagocytic effector cells were able to kill rabbit antibody-coated chicken erythrocytes (CRBC) while only non-phagocytic effector cells were active against alloantibody-coated SL2 lymphoma. In addition to the variation in susceptibility of erythrocyte and tumour target cells to various effector cell populations, it was found that different tumour cells can vary markedly in their ability to be killed by non-immune spleen cells in the presence of antibody. It is postulated that both the type of antibody and certain characteristics of the cell membrane are important in determining whether target cells are susceptible to antibody-dependent cell-mediated cytotoxicity detected by the 51Cr release assay. It was also demonstrated that alloantibody-coated P-815-Y mastocytoma, which showed very little evidence of cytotoxicity in the 51Cr release assay, was markedly inhibited in its ability to incorporate [125I]IUdR after incubation with antiserum and non-immune spleen cells. This growth inhibition in the absence of cytotoxicity, or cytostasis, is discussed in relation to the potential mechanisms of target cell damage, and in the light of recent observations (Plata, Gomard, LeClerc and Levy, 1974; Newlands and Roitt, 1975) that cytotoxicity and growth inhibition assays detect different effector cell populations in tumour-bearing animals.
Topics: Animals; Cell Membrane; Cells, Cultured; Chickens; Cytotoxicity Tests, Immunologic; Erythrocytes; Idoxuridine; Immunity, Cellular; Isoantibodies; Lymphoma; Mast-Cell Sarcoma; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Neoplasms, Experimental; Phagocytosis; Pinocytosis; Rabbits; Spleen
PubMed: 810417
DOI: No ID Found -
BMC Veterinary Research Jan 2020Traditionally, wide lateral surgical margins of 3 cm and one fascial plane deep have been recommended for resection of canine cutaneous mast cell tumor (MCT). Several...
BACKGROUND
Traditionally, wide lateral surgical margins of 3 cm and one fascial plane deep have been recommended for resection of canine cutaneous mast cell tumor (MCT). Several studies have been published assessing surgical margins of less than this traditional recommendation. The objective of this systematic review was to determine if resection MCT with lateral surgical margins < 3 cm results in low rates of incomplete resection and local tumor recurrence. Systematic searches of digital bibliographic databases were performed with two authors (AR & LES) screening abstracts to identify relevant scientific articles. Studies regarding surgical treatment of dogs with cutaneous MCT were reviewed. Data abstraction was performed and the quality of individual studies and the strength of the body of evidence for utilization of surgical margins < 3 cm for removal of MCTs was assessed.
RESULTS
From the initial 78 citations identified through the database searches, four articles were retained for data abstraction after both relevance screenings were performed. Two studies were retrospective observational studies, one was a prospective case series and one was a prospective clinical trial. Assessment of the quality level of the body of evidence identified using the GRADE system was low. Excision of MCT at 2 cm and 3 cm was associated with comparably low rates of incomplete excision and recurrence.
CONCLUSIONS
Despite the low quality of the overall body of evidence, a recommendation can be made that resection of canine cutaneous MCTs (< 4 cm) of Patnaik grade I and II with 2 cm lateral margins and 1 fascial plane deep results in low rates of incomplete excision and local tumor recurrence.
Topics: Animals; Dog Diseases; Dogs; Margins of Excision; Mast-Cell Sarcoma; Neoplasm Recurrence, Local; Skin Neoplasms; Treatment Outcome
PubMed: 31906934
DOI: 10.1186/s12917-019-2227-8