Subcutaneous seeding following surgical excision of an intracranial meningioma in a cat.

Traditionally patient owners express their concerns that surgical or diagnostic procedures on a tumor may induce metastasis. In pets, this has been documented in only very rare occasions, e. g. needle path metastases after diagnostic fine needle biopsies of urinary bladder or prostatic tumors. Here, we describe a case of subcutaneous seeding of a feline intracranial grade 1 meningioma 6 months after surgical resection. A 10-year-old male neutered domestic shorthaired cat with typical neurological signs was diagnosed with an extra-axial contrast enhancing mass in the dorsal frontotemporal lobes using magnetic resonance imaging (MRI). Transfronto-parietal bone craniotomy was performed and the 24 × 19 × 22 mm large tumor was largely removed. Tumor recurrence after 12 months resulted in a second surgical tumor removal. In addition, 2 subcutaneous masses of 10 × 4 × 4 mm in size were removed at the site of the original surgical site which were fully separated from the recurring meningeal tumor by the intact frontal bone. Histology and immunohistochemistry suggested the same tumor growth in all 4 masses. Most likely the tumor seeding had been caused during the first surgery. After all, the risk of surgical seeding of a benign tumor seems very low.

Genome-wide association analysis of canine T zone lymphoma identifies link to hypothyroidism and a shared association with mast-cell tumors.

BACKGROUND: T zone lymphoma (TZL), a histologic variant of peripheral T cell lymphoma, represents about 12% of all canine lymphomas. Golden Retrievers appear predisposed, representing over 40% of TZL cases. Prior research found that asymptomatic aged Golden Retrievers frequently have populations of T zone-like cells (phenotypically identical to TZL) of undetermined significance (TZUS), potentially representing a pre-clinical state. These findings suggest a genetic risk factor for this disease and caused us to investigate potential genes of interest using a genome-wide association study of privately-owned U.S. Golden Retrievers. RESULTS: Dogs were categorized as TZL (n = 95), TZUS (n = 142), or control (n = 101) using flow cytometry and genotyped using the Illumina CanineHD BeadChip. Using a mixed linear model adjusting for population stratification, we found association with genome-wide significance in regions on chromosomes 8 and 14. The chromosome 14 peak included four SNPs (Odds Ratio = 1.18-1.19, p = .3 × 10- 5-5.1 × 10- 5) near three hyaluronidase genes (SPAM1, HYAL4, and HYALP1). Targeted resequencing of this region using a custom sequence capture array identified missense mutations in all three genes; the variant in SPAM1 was predicted to be damaging. These mutations were also associated with risk for mast cell tumors among Golden Retrievers in an unrelated study. The chromosome 8 peak contained 7 SNPs (Odds Ratio = 1.24-1.42, p = 2.7 × 10- 7-7.5 × 10- 5) near genes involved in thyroid hormone regulation (DIO2 and TSHR). A prior study from our laboratory found hypothyroidism is inversely associated with TZL risk. No coding mutations were found with targeted resequencing but identified variants may play a regulatory role for all or some of the genes. CONCLUSIONS: The pathogenesis of canine TZL may be related to hyaluronan breakdown and subsequent production of pro-inflammatory and pro-oncogenic byproducts. The association on chromosome 8 may indicate thyroid hormone is involved in TZL development, consistent with findings from a previous study evaluating epidemiologic risk factors for TZL. Future work is needed to elucidate these mechanisms.

Implementation of various approaches to study the prevalence, incidence and progression of disseminated neoplasia in mussel stocks.

Marine mussel production is of substantial economic interest in numerous coastal areas worldwide, making crucial the study of pathologies that affect them. Disseminated neoplasia (DN) has recently been suggested to be linked to blue mussel, Mytilus edulis, mortality outbreaks observed in France since 2014, although the evidence remains indirect. In order to improve DN detection and monitoring, we compared the sensitivity of four diagnostic tools, namely haemocytology, histology, flow cytometry, and genetics. Haemocytological examination gave the best results in sensitivity and had the advantage of being non-invasive, allowing disease progression to be followed in affected mussels. Using this approach, we showed that DN progression is usually slow, and we provide evidence of remission events. We observed a high diversity of forms and mitotic features of neoplastic cells located in the vesicular connective tissue but rarely in the haemolymph. Circulating cells occur as four main types but are homogenous in morphology and DNA content within a single individual. Polyploidy proved very high, from 8 N to 18 N. Genetic analysis of haemolymph DNA showed that a Mytilus trossulus genetic signal was associated with almost all the DN cases here diagnosed by haemocytological examination, regardless of the DN type. This result corroborates DN is a transmissible cancer that first originated in a M. trossulus host and subsequently crossed into M. edulis. No pre-neoplastic conditions were detectable. The prevalence of the disease was quite low, which, together with the low morbidity observed in the lab, suggest DN is unlikely to be the direct cause of mortality outbreaks in France.

Clinical response of masitinib mesylate in the treatment of canine macroscopic mast cell tumours.

OBJECTIVES: To retrospectively evaluate the clinical response and toxicity associated with masitinib mesylate (Masivet®) treatment of macroscopic mast cell tumours in the dog. METHODS: Retrospective review of medical records of 39 dogs that had undergone treatment with masitinib for macroscopic mast cell tumours. Patient signalment, tumour location, tumour grade, tumour stage, previous treatments, concurrent medications, dose of masitinib, side effects, response, time to tumour progression, survival time and cause of death were documented. Response was assessed according to RECIST criteria. RESULTS: Clinical response was observed in 32 (82·1%) dogs receiving masitinib, with 15 dogs (38·5%) exhibiting a complete response and 17 dogs (43·6%) achieving a partial response. The median time to progression was 79 days (range: 14 to 667 days). Adverse effects were seen in 25 dogs (64·1%) with serum alanine aminotransferase elevation (n=9; 23·1%) and vomiting (n=6; 15·4%) being most common. Median survival time following initiation of masitinib was 159 days (range: 14 to 1339). CLINICAL SIGNIFICANCE: Masitinib appears to be a well-tolerated and effective drug against macroscopic mast cell tumours.

Murine xenograft model demonstrates significant radio-sensitising effect of liposomal doxorubicin in a combination therapy for Feline Injection Site Sarcoma.

Therapy of cats suffering from feline injection site sarcomas (FISS) is still a challenging problem, as the recurrence rate after surgery is up to 70%. Four FISS-derived primary tumour cell lines and corresponding xenograft tumour mouse models were established to evaluate the efficacy of a concomitant chemo-/radiation therapy with doxorubicin. In vitro, strongly depending upon the timing of administration, pre-treatment with 0.25 µmol doxorubicin resulted in a significant enhancement of radiation-induced (3.5 Gy) tumour cell death. This result was confirmed in vivo, where only the combined chemo-/radiation therapy resulted in a significant reduction in tumour growth compared to the respective mono-therapies with either doxorubicin or radiation. These results support the use of the concomitant chemo-/radiation therapy for adjuvant treatment of FISS, particularly in advanced or recurrent disease where surgery alone is no longer feasible.

In vitro efficacy of doxorubicin and etoposide against a feline injection site sarcoma cell line.

Feline injection site sarcoma (ISS) is a locally invasive tumor, in which surgical treatment is frequently combined with radiation or chemotherapy to improve tumor control. The focus of this study was to evaluate the cytotoxic effects of doxorubicin or etoposide on a feline injection site sarcoma cell line (JB) and to assess the impact of combining these drugs on cell death and cell cycle. Both single agent and combination drug administration increased cell death and significantly reduced the number of viable cells. Cells in G0/G1 were significantly reduced while the G2/M fraction was significantly increased following treatment. Collectively, combining doxorubicin and etoposide at the lower EC yielded comparable results to the EC50 of either drug alone in degree of cytotoxicity, level of apoptosis, and % of cells in G2/M. The results of this study indicate that doxorubicin and etoposide alone and in combination differentially alter ISS cell viability and cycle.

Metastatic angioinvasive lymphoma (lymphomatoid granulomatosis) in a cat.

A subcutaneous mass removed from the right rear leg of a 17-year-old, spayed, female Domestic Shorthair cat was characterized histopathologically by granulomatous inflammation, sheets of large atypical lymphoid cells, and necrosis. The walls of the small and medium caliber blood vessels were invaded transmurally by atypical lymphoid cells. A diagnosis of angioinvasive lymphoma (AIL), or lymphomatoid granulomatosis, was made based on histopathologic findings. The cat was euthanized 2 months later because of recurrence of the mass and elevated serum alanine aminotransferase activity, and a necropsy was performed. The histopathologic lesion of AIL was seen in the skin and subcutis of the right rear leg, and neoplastic cell infiltrates were seen in adjacent skeletal muscle, right superficial inguinal lymph node, liver, and spleen. By immunohistochemistry, variable numbers of neoplastic cells expressed B-lymphocyte antigen 36 (BLA36) or cluster of differentiation (CD)3 markers, indicative of B- and T-cell lineages, respectively. Neoplastic cells were uniformly positive for vimentin and uniformly negative for cytokeratins and myeloid/histiocytic antigen. Although the cat had received a Rabies virus vaccine subcutaneously in the right rear leg 6 months earlier, the AIL lesion was not typical of vaccine-induced sarcomas. The AIL in this cat was unusual because the extrapulmonary metastases involved the skin and subcutis.

The diagnosis and prognosis of synovial tumors in dogs: 35 cases.

Although synovial cell sarcoma is reported to be the most common neoplasm of the canine synovium, this retrospective study of 35 canine synovial tumors found that the majority were of histiocytic origin. Five (14.3%) synovial cell sarcomas were identified by positive immunohistochemical staining with antibodies to cytokeratin. Eighteen (51.4%) histiocytic sarcomas were identified by cell morphology and immunohistochemical staining with antibodies to CD18. Six (17.1%) synovial myxomas were identified by histologic pattern. The remaining six (17.1%) synovial tumors represented a variety of sarcomas, including two malignant fibrous histiocytomas (actin positive), one fibrosarcoma, one chondrosarcoma, and two undifferentiated sarcomas. Rottweilers were overrepresented in the histiocytic sarcoma category and Doberman Pinschers were overrepresented in the synovial myxoma category. The average survival time was 31.8 months for dogs with synovial cell sarcoma, 5.3 months for dogs with histiocytic sarcoma, 30.7 months for dogs with synovial myxoma, and 3.5 months for dogs with other sarcomas. Among the dogs with follow-up information available, metastatic disease was detected in 25% of dogs with synovial cell sarcoma, in 91% of dogs with histiocytic sarcoma, in none of the dogs with synovial myxoma, and in 100% of dogs with other sarcomas. Immunohistochemical staining for cytokeratin, CD18, and smooth muscle actin is recommended to make the diagnosis and thereby predict the behavior of synovial tumors in dogs.

Growth and metastasis of two canine mast cell tumors in SCID mice.

Intermediately differentiated mast cell tumors in two dogs were subcutaneously xenotransplanted into severe combined immunodeficiency (SCID) mice. Both tumors primarily grew and were serially transplantable in SCID mice. The histological features of the xenografts were similar to those of original tumors in dogs. Both of these subcutaneous tumors were judged as connective tissue mast cells by toluidine blue stain. One of the two xenografts metastasized to the tracheobronchial lymph nodes, omentum, mesentery, subpleural region and retroperitoneum of the SCID mouse. These canine mast cell tumor xenografts in SCID mice may be valuable tools for investigating the growth and metastatic behaviors of the tumor.

Morphogenesis of compound melanosomes in melanoma cells of a gray horse.

A thoroughbred horse, gelding, gray color, aged 19 years old had cutaneous melanomas from the root to the middle of the tail, and throughout the connective tissues of the whole body. Histologically, the tumors were diagnosed as mature melanotic melanomas characteristically deposited with abundant melanin pigment. Examined with an electron microscope, melanosomes were electron opaque without internal structure (stage IV), or as mature granular and lamellar types. Most of them were fused with each other, and formed compound melanosomes, which was similar to internal melanin aggregates in shape. The internal melanin aggregates gradually disintegrated, and compound melanosomes grew spherical. The compound melanosomes changed into autophagosomes.

Equine connective tissue tumors contain unintegrated bovine papilloma virus DNA.

Bovine papilloma virus (BPV) appears to be the etiological agent of common equine connective tissue tumors. We investigated the physical state of the viral DNA within such tumors and found no indication for integration into the host genome. The BPV genomes were present as free circular episomes. Two equine sarcoids were shown to contain multiple copies of free circular BPV type 1 (BPV-1) DNA. When the tumors were digested with several single-cut restriction enzymes, there were only form III BPV-1 DNA sequences could be revealed. One of the sarcoids contained, apart from wild-type BPV-1 DNA, a class of smaller BPV-1 circular DNA molecules bearing a deletion of approximately 9% of the BPV-1 genome. This deletion is located in the physical map between the relative units 0 and 0.32.

Tumours of the soft (mesenchymal) tissues.

This is a classification of tumours of fibrous tissue, fat, muscle, blood and lymph vessels, and mast cells, irrespective of the region of the body in which they arise. Tumours of fibrous tissue are divided into fibroma, fibrosarcoma (including "canine haemangiopericytoma"), other sarcomas, equine sarcoid, and various tumour-like lesions. The histological appearance of the tumours is described and illustrated with photographs.