Review on Canine Oral Melanoma: An Undervalued Authentic Genetic Model of Human Oral Melanoma?

Oral melanoma (OM) is a highly aggressive tumor of the oral cavity in humans and dogs. Here we review the phenotypic similarities between the disease in these 2 species as the basis for the view that canine OM is a good model for the corresponding human disease. Utility of the "canine model" has likely been hindered by a paucity of information about the extent of the molecular genetic similarities between human and canine OMs. Current knowledge of the somatic alterations that underpin human tumorigenesis and metastatic progression is relatively limited, primarily due to the rarity of the disease in humans and consequent lack of opportunity for large-scale molecular analysis. The molecular genetic comparisons between human and canine OMs that have been completed indicate some overlap between the somatic mutation profiles of canine OMs and a subset of human OMs. However, further comparative studies featuring, in particular, larger numbers of human OMs are required to provide substantive evidence that canine OMs share mechanisms of tumorigenesis with at least a subset of human OMs. Future molecular genetic investigations of both human and canine OMs should investigate how primary tumors develop a metastatic gene expression signature and the genetic and epigenetic alterations specific to metastatic sites. Such studies may identify genetic alterations and pathways specific to the metastatic disease which could be targetable by new drugs.

Feline ventral abdominal wall angiosarcoma: haemangiosarcoma or lymphangiosarcoma? Clinical and pathological characteristics in nine cases.

OBJECTIVES: Angiosarcomas are rare malignant mesenchymal neoplasms of endothelial cell origin with a predilection to the ventral abdominal wall in cats. Larger case series describing this entity are lacking. METHODS: Two referral centre laboratory databases were searched for angiosarcoma of the ventral abdominal wall. Nine cases with a histological diagnosis were included. Immunohistochemistry (factor VIII and PROX-1 antibodies) was used to phenotype them as haemangiosarcoma or lymphangiosarcoma. RESULTS: All cats presented with a ventral abdominal mass, five of which were producing a serosanguinous discharge. Eight underwent tumour staging and pulmonary metastases were suspected in one cat (but not histologically confirmed). With histopathology alone, a diagnosis of angiosarcoma and lymphangiosarcoma was made in four and five cases, respectively. After immunohistochemistry, five cases had a haemangiosarcoma phenotype and four had a lymphangiosarcoma phenotype, including two cases of lymphangiosarcoma that were reclassified as hemangiosarcoma. Eight cats received treatment (either surgery with or without adjuvant therapies or medical management alone). Six cats were euthanased due to local disease progression. The median survival time for haemangiosarcoma was 166 days (range 137-381), and for lymphangiosarcoma it was 197 days (range 67-208). Two cats with haemangiosarcoma remained alive for a follow-up period of 329 and 580 days, respectively. CONCLUSIONS AND RELEVANCE: Feline ventral abdominal angiosarcomas are rare locally aggressive neoplasms. While histology often provides a diagnosis of angiosarcoma, immunohistochemistry is ultimately required to differentiate between haemangiosarcoma and lymphangiosarcoma phenotypes. Further studies are required to evaluate whether the different phenotypes have an impact on treatment response and outcome.

Mastocytosis in the skin in dogs: A multicentric case series.

Canine cutaneous mastocytosis (CM) is rare in contrast to canine mast cell tumours. In humans, CM commonly affects children and is usually indolent with possible spontaneous resolution. Systemic mastocytosis (SM) with bone marrow involvement typically affects adults, can have a poor outcome, and often includes skin lesions. 'Mastocytosis in the skin' (MIS) is the preferred term of skin lesions, if bone marrow evaluations are not available, which is often the cases in dogs. In human SM and CM, KIT mutations are often detected. The veterinary literature suggests clinical resemblances between human and canine MIS, but data is limited, and KIT mutations are rarely assessed. This retrospective study describes clinicopathological findings, treatment and outcome of 11 dogs with suspected MIS. Dogs with multiple mast cell tumours were excluded. Histopathology reports (n = 5) or slides (n = 6) were reviewed. KIT mutation analysis including exons 8, 9, 11, 14 and 17 were analysed in eight dogs. Median age at diagnosis was 4 years (range, 1-12). Typical clinical signs included multifocal to generalised nodules and papules. Histologically, skin lesions were characterised by dermal infiltration of well-differentiated mast cells. KIT mutations were detected in 3/8 dogs (exon 9: n = 2; exon 11: n = 1). One dog had mastocytaemia suggesting possible SM. Glucocorticoids were mostly successful with lesion improvement in all treated dogs (n = 8). This cohort highlights resemblances between human and canine MIS. Further studies are required to confirm these findings and establish diagnostic criteria for CM and MIS associated with SM in dogs.

Clinical presentation, treatment and outcome in 23 cats with laryngeal or tracheal lymphoma.

OBJECTIVES: Feline primary laryngeal or tracheal lymphoma (PLTL) is an uncommon extranodal presentation. Information on long-term survival is scarce, although some small case series describe this being achieved with multiagent protocols; an accurate outcome for cats with PLTL is yet to be determined. The aim of this study was to gather information on the clinical presentation, response to treatment and outcome in a large case series of feline PLTL. METHODS: This retrospective multicentre study included cats with a cytological or histopathological confirmation of PLTL. Histopathology samples, when available, were reassessed for grade and immunophenotype. Clinical (age, signalment, retroviral status, presence of anaemia, clinical signs, location and therapy type) and outcome (response, progression-free survival [PFS] and overall survival [OS]) variables were recorded. Survival analyses to assess the impact of variables on PFS and OS were performed. RESULTS: Twenty-three cases were included; cats had a median age of 11 years (range 2-16) and the male:female ratio was 3.6:1. Common clinical signs at presentation included increased respiratory effort (74%) and abnormal upper respiratory tract sounds (48%). Immunophenotyping was performed in 48% of cases and all were B cell. Debulking surgery was performed in 26% of cases. All cats received chemotherapy, COP (cyclophosphamide, vincristine and prednisolone; 39%), CHOP (cyclophosphamide, vincristine, doxorubicin and prednisolone; 44%) and other protocols (17%); 35% had a partial response and 65% a complete response. Median PFS and OS were 909 days (range 23-1484) and 909 days (range 23-2423), respectively. Complete response was associated with longer PFS (P <0.001) and OS (P = 0.012). Pretreatment with steroids was associated with longer OS (P = 0.003). No other variable was found to be significant. CONCLUSIONS AND RELEVANCE: PLTL in cats is mostly of a B-cell phenotype, could be of a low-to-medium grade, and may respond to surgical and medical treatment with a longer survival time than has previously been reported.

Retrospective Study of T Cell Leukaemia (Large Granular Lymphocyte Variant) in Dogs Associated with Suspected Immune-Mediated Cytopaenia(s) in the Absence of Peripheral Lymphocytosis.

Canine chronic large granular lymphocyte (LGL) leukaemia is commonly characterised by moderate to marked lymphocytosis but not neutropaenia. In humans, LGL leukaemia is often associated with autoimmune disorders, including immune-mediated cytopaenias (mainly neutropaenia). This presentation is rare in dogs. The aim of this retrospective study was to describe the clinical characteristics, treatments, and outcomes of dogs with chronic LGL leukaemia with suspected immune-mediated cytopaenia. Six dogs with a median age of 4.5 years (range 2-8 years) were included in the study. The most common presenting signs were pyrexia and lethargy. All dogs had severe neutropaenia (median neutrophil count 0.07 × 109/L), three had thrombocytopaenia (median platelet count 66 × 109/L), and one had anaemia (HCT 0.32 L/L). In all dogs, bone marrow cytology revealed infiltration of granular T lymphocytes; PARR analysis confirmed clonality in four, and bone marrow flow cytometry identified CD3+ CD8+ neoplastic cells in two cases. All patients received systemic chemotherapy, and the cytopaenias resolved after 1-19 weeks. Two dogs were euthanised 133 and 322 days after diagnosis, two were lost to follow-up after 224 and 357 days, and two were alive at 546 and 721 days. A subset of LGL leukaemia in dogs is associated with immune-mediated cytopaenia and has a unique clinical presentation.

Strontium 90 plesiotherapy for the treatment of eyelid squamous cell carcinoma in eight cats.

OBJECTIVES: Squamous cell carcinoma (SCC) is the most common eyelid tumour in cats. The main treatment is extensive surgery and the cosmetic outcome can be worrisome for some owners. Strontium 90 (ST-90) plesiotherapy is a therapeutic modality used for superficial tumours, including SCC. The aim of this study was to describe the use and response of feline eyelid SCC to ST-90 plesiotherapy either as single treatment or as adjuvant therapy following surgery. METHODS: A referral centre clinical database was searched for all cats diagnosed with SCC located on an eyelid. Cats treated with ST-90 plesiotherapy were included. The response to treatment was evaluated visually every 4-6 weeks until complete healing and based on response evaluation criteria in solid tumours (RECIST). Descriptive statistics of the survival were applied to the data collected. RESULTS: Eight cats treated between 2014 and 2017 met the inclusion criteria. The median age was 10.8 years. In six cases, ST-90 was used as the only treatment modality, while in two cats it was used as an adjuvant to surgery. Four cats received a single protocol and four a hypofractionated protocol. In the six cats in which ST-90 was used as the primary treatment, the response was 100%. Four cats died at a median time of 9 months (3-17 months) after ST-90 due to causes unrelated to SCC. Of the remaining four cats, three had no signs of recurrence at a median time of 34 months and one was lost to follow-up at 17 months with no signs of recurrence. CONCLUSIONS AND RELEVANCE: This small study showed that ST-90 can be used for treatment of eyelid SCC with good therapeutic and cosmetic outcomes.

Prognostic factors for dogs with mammary inflammatory carcinoma: 43 cases (2003-2008).

OBJECTIVE: To describe clinical characteristics, treatment, and outcome of dogs with inflammatory carcinoma (IC) and identify patient-, tumor-, and treatment-related factors associated with overall survival time. DESIGN: Retrospective case series. ANIMALS: 43 client-owned dogs. PROCEDURES: Records of dogs with a clinical diagnosis of IC that had histologic evidence of dermal lymphatic invasion were reviewed. Data on clinical staging, treatment, toxicoses, response, and survival time were retrieved. Results-26 (60%) dogs had primary IC and 17 (40%) had secondary IC. Thirty-five (81%) dogs had distant metastases and 2 (5%) had local metastases at the time of initial examination. Six of 29 (21%) dogs had a coagulopathy. Sixteen (37%) dogs did not receive specific treatment for IC, 24 (56%) received medical treatment only, 2 (5%) underwent surgical excision and received medical treatment, and 1 (2%) underwent surgical excision only. Forty-one (95%) dogs had progressive disease, and 2 (5%) had stable disease. Mean survival time for all dogs was 60 days (range, 1 to 300 days). Dogs with a coagulopathy survived a significantly shorter time than did dogs without a coagulopathy (odds ratio, 0.28), and dogs that received medical treatment survived significantly longer than dogs that did not (odds ratio, 2.54). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that mammary IC is a biologically aggressive condition in dogs associated with a guarded prognosis. In addition, results suggested that medical treatment may improve outcome, thereby supporting its use in dogs with IC.

Response, disease-free interval and overall survival of cats with nasal planum squamous cell carcinoma treated with a fractionated vs a single-dose protocol of strontium plesiotherapy.

OBJECTIVES: The main aim of the study was to establish response, disease-free interval (DFI) and overall survival of cats with nasal planum squamous cell carcinoma (SCC) treated with Sr90 plesiotherapy. A secondary aim was to determine whether a fractionated protocol is more effective than a single-dose protocol in terms of response, DFI and overall survival. The third aim was to evaluate whether we can identify prognostic factors that influence overall survival. METHODS: This was a retrospective study that included cats with a diagnosis of nasal planum SCC treated with Sr90 plesiotherapy at a single institution. RESULTS: Seventy-four cats were included in the study. Thirty-two were treated with a fractionated protocol and 42 with a single-dose treatment. Sr90 plesiotherapy was able to induce complete response in 74% of cats with nasal planum SCC. The median DFI was 780 days (95% confidence interval [CI] 383-1177), with 17% of cats experiencing local recurrence. The overall survival for all cats was 1039 days (95% CI 55-1528). The DFI of cats treated with the fractionated Sr90 was significantly longer compared with the single-dose treatment, whereas response and overall survival were not statistically different. Other prognostic factors that influenced the overall survival were early-stage disease, absence of concurrent problems and complete response to the treatment. Acute and long-term toxicity associated with the treatment were minimal and the aesthetic outcome was pleasing in almost all cases. CONCLUSIONS AND RELEVANCE: Strontium plesiotherapy is a safe and effective treatment of nasal planum SCC in cats.

Immunohistochemical diagnosis of canine ovarian epithelial and granulosa cell tumors.

In humans and canines, the morphology of granulosa cell tumors is extremely variable and causes diagnostic difficulties. In human pathology, immunohistochemistry has been widely used for the diagnosis of granulosa cell tumors, whereas, limited studies are present in canine species. The aim of this study was to investigate the expression of cytokeratins, vimentin, and inhibin-alpha in canine normal ovaries, epithelial ovarian tumors, and granulosa cell tumors to establish an immunohistochemical panel for the differential diagnosis of ovarian tumors. Formalin-fixed, paraffin-embedded tissue sections from 4 normal ovaries, 8 granulosa cell tumors, and 6 epithelial ovarian tumors (2 adenomas and 4 adenocarcinomas) sections were obtained and stained with hematoxylin and eosin and immunohistochemically for cytokeratin AE1/AE3, cytokeratin 7, vimentin, and inhibin-alpha. In normal ovaries, cytokeratin 7, cytokeratin AE1/AE3, and vimentin were expressed in the surface epithelium. Granulosa cells were negative for cytokeratin 7 and displayed variable expression of vimentin, cytokeratin AE1/AE3, and inhibin-alpha toward follicular maturation. Granulosa cell tumors were negative for cytokeratin 7 and positive for inhibin-alpha. Conversely, ovarian epithelial cells tumors were positive for cytokeratin 7 and negative for inhibin-alpha. Both granulosa and epithelial cell tumors displayed variable expression of vimentin. Cytokeratin AE1/AE3 was expressed by all epithelial-derived tumors and 6 of 8 granulosa cell tumors. The results of this study suggest that useful immunohistochemical markers to distinguish epithelial ovarian tumors from granulosa cell tumors are cytokeratin 7 and inhibin-alpha.