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Veterinary Pathology Jan 2024Increased or constitutive activation of nuclear factor kappa B (NF-kB) is a feature of many chronic disease processes, including cancer. While NF-kB overactivation has...
Increased or constitutive activation of nuclear factor kappa B (NF-kB) is a feature of many chronic disease processes, including cancer. While NF-kB overactivation has been documented extensively in human oncology, there is a relative paucity of data documenting the same phenomenon in veterinary medicine. To assess NF-kB activity, antibodies to p65 and p100/p52, which are components of NF-kB heterodimers, were first validated for specificity and canine cross-reactivity via Western blot and labeling of immortalized cell pellets. Then, nuclear labeling for these antibodies was assessed via QuPath software in over 200 tumor tissue samples (10 hemangiosarcomas, 94 histiocytic sarcomas, 71 lymphomas, and 28 mast cell tumors) and compared to immunolabeling in appropriate normal tissue counterparts. Greater than 70% of spontaneous canine tumors evaluated in this study had more nuclear p65 and p100/p52 immunoreactivity than was observed in comparable normal cell populations. Specifically, 144/204 (70.58%) of tumors evaluated had positive p65 nuclear labeling and 179/195 (91.79%) had positive p100/p52 nuclear labeling. Surprisingly, greater nuclear p100/p52 reactivity was associated with a longer progression-free survival (PFS) and overall survival (OS) in canine lymphomas. These results provide support and preliminary data to investigate the role of NF-kB signaling in different types of canine cancer.
Topics: Animals; Dogs; Humans; NF-kappa B; Histiocytic Sarcoma; Hemangiosarcoma; Mast Cells; NF-kappa B p52 Subunit; Lymphoma; Dog Diseases
PubMed: 37357953
DOI: 10.1177/03009858231180484 -
Journal of the American Veterinary... Oct 2023To prospectively evaluate clinical outcomes using acellular fish skin grafts (FSGs) for the management of complete wound healing by secondary intention after wide...
OBJECTIVE
To prospectively evaluate clinical outcomes using acellular fish skin grafts (FSGs) for the management of complete wound healing by secondary intention after wide surgical excision of skin tumors in dogs.
ANIMALS
5 dogs undergoing wide surgical excision of skin tumors on the distal extremity.
CLINICAL PRESENTATION AND PROCEDURES
FSGs were applied to surgical wound beds following wide excision of the tumor. Bandages were changed weekly and additional grafts placed when integration of the previous graft was complete. The wounds were assessed for the following: dimensions, tissue health (color), time to complete epithelialization, complications, and tumor recurrence.
RESULTS
All masses were excised with 2-cm lateral margins and 1 fascial plane deep to the tumor. Tumor diagnoses included 3 mast cell tumors and 2 soft tissue sarcomas. Surgical wounds had a median area of 27.6 cm2 (range, 17.6 to 58.7 cm2). The median number of FSG applications was 5 (range, 4 to 9 applications). Complete epithelialization occurred within 7 to 9 weeks for uncomplicated wounds (3 of 5) and 12 to 15 weeks for complicated wounds (2 of 5) that sustained self-trauma. There were no adverse events related to the use of FSGs. Local recurrence was not seen over a follow-up period ranging from 239 to 856 days.
CLINICAL RELEVANCE
Wide surgical excision of distal extremity skin tumors, followed by repeated application of acellular FSGs, resulted in complete healing of all wounds with no adverse events. This treatment method does not require advanced reconstructive surgical skills and may be useful for the management of skin tumors on the distal extremities.
Topics: Dogs; Animals; Glomerulosclerosis, Focal Segmental; Neoplasm Recurrence, Local; Wound Healing; Skin Neoplasms; Sarcoma; Fishes; Skin Transplantation; Dog Diseases
PubMed: 37315939
DOI: 10.2460/javma.23.03.0157 -
Journal of the American Veterinary... Oct 2023To report to what degree narrative operative reports for soft tissue sarcoma (STS) and mast cell tumor (MCT) resections met a predetermined template made up of essential...
OBJECTIVE
To report to what degree narrative operative reports for soft tissue sarcoma (STS) and mast cell tumor (MCT) resections met a predetermined template made up of essential elements.
ANIMALS
197 consecutive client-owned animals between May 1, 2017, and August 1, 2022.
PROCEDURES
A consensus list of 9 elements made up the final synoptic operative report (SR) template. Consecutive narrative surgery reports (NRs) of dogs that underwent MCT or STS resection were then reviewed to determine how many of the SR elements were present in each NR. A score was then determined for each NR out of a maximum total of 9.
RESULTS
Overall, 197 reports (99 MCT and 98 STS) were included. The median score was 5 (56% of elements reported). No report had all 9 elements, and 1 report had none of the elements reported. When MCT and STS were analyzed independently, the median score was 6 (67% of elements reported) for MCT and 5 (56% of elements reported) for STS. There was a trend of more cases with MCT that had a preoperative diagnosis, intraoperative measurements of the tumor, and surgeon margins marked compared to dogs with STS. More dogs with STS had an estimated Enneking dose compared to dogs with MCT.
CLINICAL RELEVANCE
Our data show that essential elements of STS and MCT resection in dogs were inconsistently recorded and no case had all elements present. This mirrors data in people and presses the need for more standardization in reporting of cancer operations in veterinary medicine.
Topics: Dogs; Animals; Mast Cells; Dog Diseases; Sarcoma; Soft Tissue Neoplasms; Retrospective Studies
PubMed: 37290758
DOI: 10.2460/javma.23.03.0152 -
Journal of the American Veterinary... Sep 2023To determine the incidence of histologic grade shift (alteration of grade relative to the original tumor) in recurrent canine soft tissue sarcoma (STS) and mast cell...
OBJECTIVE
To determine the incidence of histologic grade shift (alteration of grade relative to the original tumor) in recurrent canine soft tissue sarcoma (STS) and mast cell tumor (MCT), and to determine the level of agreement between blinded pathologist review and original histology interpretation of STS and MCT grades.
ANIMALS
15 dogs with recurrent cutaneous/subcutaneous STS and 5 dogs with recurrent cutaneous MCT. All included dogs underwent excision of both the primary and recurrent tumors and had tumor samples available for review.
PROCEDURES
The medical records and histology database from a single institution were reviewed, and data were recorded and analyzed. A single board-certified veterinary pathologist performed blinded evaluation of all excisional tumor samples, including both primary and recurrent disease, and these were evaluated independently and in conjunction with initial pathologic diagnoses.
RESULTS
Based on single pathologist review, 7 of 15 (46.7%) dogs with recurrent STS had grade shift characterized by a higher or lower recurrent tumor grade in 4 of 7 and 3 of 7 cases, respectively, and 1 of 5 dogs with recurrent MCT had grade shift characterized by an increased grade of the recurrent tumor. Variability in reported grade between original histology report and pathologist review occurred for 13 of 30 (43.3%) STS excisional biopsy samples and 0 of 10 MCT excisional biopsy samples.
CLINICAL RELEVANCE
Grade shift has been reported in multiple tumor types in people and has the potential to alter prognosis and treatment recommendations. This is the first study to document this phenomenon in dogs. Additional large-scale studies are needed to determine factors associated with grade shift as well as prognostic significance of grade shift for recurrent canine STS and MCT.
Topics: Animals; Dogs; Female; Male; Dog Diseases; Incidence; Recurrence; Retrospective Studies; Soft Tissue Neoplasms; Sarcoma
PubMed: 37257826
DOI: 10.2460/javma.23.01.0050 -
American Journal of Clinical Pathology May 2023Sessions 8 and 9 of the 2021 Society for Hematopathology and the European Association for Haematopathology Workshop aimed to collect examples of transdifferentiation,...
OBJECTIVES
Sessions 8 and 9 of the 2021 Society for Hematopathology and the European Association for Haematopathology Workshop aimed to collect examples of transdifferentiation, lineage infidelity, progression, and transformation in precursor and mature T/natural killer (NK)-cell neoplasms.
METHODS
Twenty-eight cases were submitted and analyzed, with whole-exome sequencing and genome-wide RNA expression analysis performed in a subset of the cases.
RESULTS
In session 8, 7 T-lymphoblastic lymphoma/leukemia cases were received that showed transdifferentiation to clonally related mature myeloid hematopoietic neoplasms, including 6 histiocytic/dendritic cell lineage neoplasms and a mast cell sarcoma. Session 9 included 21 mature T-cell neoplasms that were grouped into 3 themes. The first one addressed phenotypic infidelity in mature T-cell lymphomas (TCLs) and included 8 TCLs expressing aberrant antigens, mimicking classic Hodgkin and non-Hodgkin B-cell lymphomas. The second theme addressed disease progression in TCL and included 5 cutaneous T-cell lymphoproliferative disorders and 2 T-cell large granular lymphocyte proliferations with subsequent progression to systemic TCL. The third theme included 6 patients with TCL with T-follicular helper phenotype, mainly angioimmunoblastic T-cell lymphoma, with concurrent/subsequent clonal hematopoiesis or myeloid neoplasms and/or subsequent/concomitant diffuse large B-cell lymphoma.
CONCLUSIONS
This cohort of cases allowed us to illustrate, discuss, and review current concepts of transdifferentiation, aberrant antigen expression, and progression in various T/NK-cell neoplasms.
PubMed: 37167533
DOI: 10.1093/ajcp/aqad045 -
Veterinary and Comparative Oncology Sep 2023In this study we undertook a comprehensive analysis of a Pet Tumour Registry of the Canary Archipelago (PTR-CA) in Spain to investigate the epidemiology of canine...
In this study we undertook a comprehensive analysis of a Pet Tumour Registry of the Canary Archipelago (PTR-CA) in Spain to investigate the epidemiology of canine cutaneous round cell tumours. From a database of 2526 tumours collected from 2003 to 2020, we conducted a longitudinal analysis of the main trends in diagnosis, age, multiplicity and anatomical distribution as well as a case-control study comparing these cases with the contemporaneous canine population of the Canary Archipelago to analyse breed distribution. In line with former studies, we found histiocytomas mostly affect young dogs (2, IQR 1-5) and mast cell tumours affect middle-to-old dogs (8, IQR 6-10) with grade 1 affecting at younger ages (6.5, IQR 6-8) than both grade 2 (8, IQR 6-10 years) and grade 3 (9, IQR 7-11). Histiocytomas and plasmacytomas showed a similar anatomical distribution appearing mainly on the face, head and neck regions while mast cell tumours occur mainly on limbs and trunk. Higher risk for mast cell tumours and histiocytomas were found for Bulldog-related breeds such as Boxer (OR = 23.61, CI95%: 19.12-29.15, OR = 10.17, CI95%: 6.60-15.67), Boston Terrier (OR 19.47, CI95%: 7.73-49.05, OR 32.61, CI95%: 11.81-90.07) and Pug (OR 8.10, CI95%: 5.92-11.07, OR 7.87, CI95%: 4.66-13.28) while Chihuahua dogs showed significantly less risk (OR 0.18, CI95%: 0.09-0.33, OR 0.41, CI95%: 0.21-0.78). Notably, the Canarian Mastiff, a local breed, had a low risk of suffering from a mast cell tumour which raises the question of whether this relates to a genetic peculiarity of this breed or some husbandry and environmental factor.
Topics: Dogs; Animals; Canaries; Case-Control Studies; Spain; Dog Diseases; Sarcoma; Histiocytoma; Skin Neoplasms
PubMed: 37143410
DOI: 10.1111/vco.12899 -
Blood Research Apr 2023Mastocytosis is a heterogeneous neoplasm characterized by accumulation of neoplastic mast cells in various organs. There are three main types: cutaneous mastocytosis... (Review)
Review
Mastocytosis is a heterogeneous neoplasm characterized by accumulation of neoplastic mast cells in various organs. There are three main types: cutaneous mastocytosis (CM), systemic mastocytosis (SM), and mast cell sarcoma. CM mainly affects children and is confined to the skin, whereas SM affects adults and is characterized by extracutaneous involvement, with or without cutaneous involvement. Most cases of SM have an indolent clinical course; however, some types of SM have aggressive behavior and a poor prognosis. Recent advances in the understanding of the molecular changes in SM have changed the diagnosis and treatment of aggressive and advanced SM subtypes. The International Consensus Classification and World Health Organization refined the diagnostic criteria and classification of SM as a result of accumulation of clinical experience and advances in molecular diagnostics. Somatic mutations in the gene, most frequently , are detected in 90% of patients with SM. Expression of CD30 and any mutation were introduced as minor diagnostic criteria after the introduction of highly sensitive screening methods. SM has a wide spectrum of clinical features, and only a few drugs are effective at treating advanced SM. Currently, the mainstay of SM treatment is limited to the management of chronic symptoms related to release of mast cell mediators. Small-molecule kinase inhibitors targeting the KIT-downstream and KIT-independent pathways were recently approved for treating advanced SM. I describe recent advances in diagnosis of SM, and review the currently available and emerging therapeutic options for SM management.
PubMed: 37105564
DOI: 10.5045/br.2023.2023024 -
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 -
Blood Mar 2023
Topics: Humans; Leukemia, Mast-Cell; Mast-Cell Sarcoma; Sarcoma; Lymphohistiocytosis, Hemophagocytic; Mast Cells
PubMed: 36929432
DOI: 10.1182/blood.2022018256 -
Frontiers in Veterinary Science 2023Plasmablastic lymphoma (PBL) is a rare form of lymphoma in people. PBL originates from plasmablasts and usually presents with swelling/mass in the mouth/neck. A...
Plasmablastic lymphoma (PBL) is a rare form of lymphoma in people. PBL originates from plasmablasts and usually presents with swelling/mass in the mouth/neck. A 7-year-old Mongrel dog was presented for a large oral and neck mass. Cytology and histopathology were suggestive of a round cell tumor that was suspected to be lymphoma. An immunohistochemical (IHC) stain panel showed positive for CD18, thus supporting the diagnosis of round cell tumor, but negative for T- and B-cell lymphomas, CD3, CD20, and PAX-5. Other markers including cytokeratin AE1/3 (for epithelial cell origin), CD31 (for endothelial cells), SOX10 (for melanoma), IBa-1 (for histiocytic sarcoma), and CD117 (for mast cell tumor) were all negative. MUM-1 (for plasma cell differentiation) was strongly positive and CD79a (B cell and plasma cells) was also scantly positive. Based on the histopathology and immunohistochemistry results in combination with the clinical presentation, a suspected diagnosis of PBL was made. As per available literature, this is perhaps the first highly suspected case of PBL in a dog.
PubMed: 36875999
DOI: 10.3389/fvets.2023.1100942