Presence of Gastrointestinal Paraneoplastic Syndrome at Diagnosis in Dogs With Cutaneous Mast Cell Tumors and Its Influence on Disease-Free Interval and Survival.

Paraneoplastic syndrome (PNS) is a combination of signs unrelated to the physical presence of a tumor and/or its metastases. Its presence may result in poorer clinical outcomes and prognosis. Gastrointestinal ulceration is a well-known PNS in animals with cutaneous MCT. This retrospective study analyzed the occurrence of gastrointestinal (GI) PNS at the time of diagnosis. Using medical records, we attempted to correlate the occurrence of these GI signs with clinical and histologic criteria, as well as to evaluate their influence on the disease-free interval (DFI) and survival (ST) over a 6-year follow-up period (2013-2020). The medical records of 41 dogs with a confirmed diagnosis of cutaneous MCT treated between 2013 and 2014 were included. All dogs underwent surgical biopsy or tumor excision, endoscopic and histologic examination to evaluate possible GI lesions. The presence and severity of GI signs were recorded. Clinical data such as the history of recurrence, number of tumors, tumor size, presence of ulceration, local pruritus, edema and erythema, histopathological classification, and mitotic index were extracted from medical records. Clinical signs relating to the GI system were observed in 41.5% of the dogs and were classified as mild in 94.1% at the time of diagnosis. Endoscopic examination of the upper digestive tract showed evidence of inflammation, but histologic examination of the mucosa showed no serious lesions in any case. There was no significant association between the occurrence of clinical GI signs and any of the variables studied. Follow-up issues meant that only 38 dogs were included for evaluation of the ST and 32 for DFI analysis. DFI was 25.1 months for dogs with GI signs and 14.8 months for dogs without GI signs. At the end of the study, 71.1% of patients had died. Survival time for dogs with GI signs was 54.9 months and 48 months for dogs without GI signs. Over the 6 years of the study, no differences were observed between the ST and the DFI, and the presence or absence of GI PNS at the time of diagnosis.

Markers for internal neoplasia in the horse.

The diagnosis of internal neoplasia in horses is challenging. Increased production of hormones physiologic for adult animals (e.g., adrenocorticotropin, norepinephrine, and erythropoietin) or typical for the foetal phase (alpha-fetoprotein, anti-Müllerian hormone, and parathyroid-hormone-related protein) might aid in tumour diagnostics. Thymidine kinase-1 and alkaline phosphatase are examples of intracellular enzymes, whose activity in the blood may increase in some neoplasia cases. Furthermore, inappropriate production of abnormal monoclonal or autologous antibodies can accompany lymphoma and multiple myeloma. Many of those tumour markers lead to clinical or laboratory changes, called paraneoplastic syndromes, such as hypercalcaemia and erythrocytosis. The interpretation of the results of the tumour marker measurements in horses is complicated due to many factors affecting the markers' concentration or activity (e.g., young age, pregnancy, and inflammation) and other diseases triggering the same changes. Moreover, the presence of paraneoplastic syndromes is inconsistent, which leads to low sensitivity of those substances as tumour markers. In conclusion, screening for neoplasia in horses is not recommended. The measurement of tumour markers should be performed only in risk groups with suspicious clinical or laboratory findings, and the results should be interpreted with caution. It is advisable to add inflammatory markers to the tumour profile or repeat the measurements.

Hypercalcemia of Malignancy in a Dog Diagnosed With Cholangiocellular Carcinoma.

A 4-year-old, neutered male Golden Retriever was presented with a 1-week history of weight loss, polyuria, and polydipsia. The diagnostic workup showed an increased ionized calcium concentration, mild increase in serum creatinine and urea concentration, and severe hyperlipasemia. A complete abdominal ultrasound revealed multiple hepatic nodules. A cytological diagnosis of malignant epithelial neoplasia, highly suggestive of bile duct adenocarcinoma was made. In order to confirm the presumptive diagnosis of hypercalcemia of malignancy due to the presence of a hepatic neoplasia, serum parathormone-related peptide concentration was measured, and the result revealed an increased concentration. The dog was hospitalized and received supportive treatments consisting of intravenous furosemide and fluid therapy. After ruling out lymphoma and hypoadrenocorticism, oral prednisone was initiated and ionized calcium concentration decreased gradually down to normal concentration after 7 days of hospitalization. Chemotherapy with intravenous epirubicin was initiated based on the cytological diagnosis. One month after diagnosis and due to the worsening of its clinical condition, the dog was humanely euthanized. Postmortem examination confirmed a cholangiocellular carcinoma. To our knowledge, this is the first report of malignant hypercalcemia associated with cholangiocellular carcinoma in a dog.

A previously undescribed cutaneous paraneoplastic syndrome in a cat with thymoma.

BACKGROUND: Exfoliative dermatitis is a well-recognized cutaneous paraneoplastic syndrome (PNS) associated with thymoma in cats, of which the clinical and histopathological presentation has been well-characterized. OBJECTIVES: To describe a novel clinical skin manifestation associated with thymoma in a cat. ANIMAL: A 14-year-old neutered female domestic short hair cat. METHODS AND MATERIALS: Physical, abdominal ultrasonographic, thoracic radiographic, ultrasonographic and computed tomographic examinations, histopathological assessment of the skin and mediastinal mass. RESULTS: The cat was presented with noninflammatory alopecia, with a dorsal multifocal distribution. Examination of the alopecic areas using a dermascope indicated an apparent lack of follicular ostia. Histopathological assessment of alopecic areas confirmed follicular and epidermal atrophy, trichilemmal keratinization and mild orthokeratotic hyperkeratosis. Diagnostic imaging revealed a mediastinal mass, which was surgically removed. Histopathological and immunohistopathological examination of the mass was consistent with a thymoma, associated with multiloculated cyst formation and multifocal cholesterol granulomas. Following surgery, hair re-growth was noted in the previously alopecic areas. The cat was euthanized 3.5 months later because of recurrent chylothorax suspected to be a postoperative complication. The alopecic lesions had improved markedly. CONCLUSIONS AND CLINICAL IMPORTANCE: Thymoma-associated PNS might not always manifest as an exfoliative dermatitis and should be considered in the differential diagnosis of multifocal noninflammatory alopecia.

Canine Clitoral Carcinoma: A Clinical, Cytologic, Histopathologic, Immunohistochemical, and Ultrastructural Study.

Vaginal and vulvar tumors are uncommon in dogs. Knowledge of canine primary clitoral neoplasia is restricted to a few case reports, and only carcinomas have been reported. Cytologic and histologic features reported in the literature seem to overlap with those of canine apocrine gland anal sac adenocarcinoma (AGASA). Clinical features also recall those of canine AGASA, such as locoregional metastases and hypercalcemia of malignancy (HM). In this study, 6 cases of primary canine clitoral carcinomas (CCCs), with and without HM, were investigated by means of cytology, histopathology, electron microscopy, and immunohistochemistry for neuroendocrine markers including chromogranin A (CGA), synaptophysin (SYN), neuron-specific enolase (NSE), and S-100. In all 6 tumors, cytologic findings were consistent with malignant epithelial neoplasia of apocrine gland origin. The tumors examined were classified into 3 different histological patterns representing different degrees of differentiation: tubular, solid, and rosette type. Both CGA and SYN were mildly expressed in 2 of 6 tumors, while NSE was consistently expressed in all 6 cases. None of the tumors were S-100 positive. Transmission electron microscopy revealed electron-dense cytoplasmic granules compatible with neuroendocrine granules in all 6 cases. CCCs presented clinicopathologic features resembling AGASAs with neuroendocrine characteristics, and 2 of 6 neoplasms were considered as carcinomas with neuroendocrine differentiation and were positive for 3 neuroendocrine markers. CCCs can often present with HM, and long-term outcome is likely poor. Our study concludes that CCC seems to be a rare tumor, but it might be underestimated because of the overlapping features with AGASA. Further studies should aim to define the true incidence of this disease.

Paraneoplastic hematological, biochemical, and hemostatic abnormalities in female dogs with mammary neoplasms / Anormalidades hematológicas, bioquímicas e hemostáticas de origem paraneoplásica em fêmeas caninas com neoplasia mamária

Paraneoplastic laboratory abnormalities are identified in several types of cancers in dogs and cats. In veterinary medicine, particularly in mammary cancer, there are few studies that correlate abnormal laboratory findings with tumor type and staging. The aim of this study was to evaluate hematological, biochemical, and hemostatic abnormalities and correlate them with mammary tumor staging in female dogs with mammary cancer. Blood samples from 24 female dogs were evaluated, and the hematological, biochemical, and hemostatic parameters were correlated with tumor staging obtained by physical examination, imaging exams, and histopathological surgical biopsies. The groups were organized according to tumor staging: group 1 (stages I and II), group 2 (stage III), and group 3 (stages IV and V). Anemia, neutrophilic leukocytosis, monocytosis, eosinophilia, thrombocytosis, hypoalbuminemia, hypocalcemia, hypoglycemia, and low blood urea were observed. The variables MCHC, TPP, and RDW were correlated with tumor staging with no clinical relevance. Thrombin time and fibrinogen were significant between the groups in the coagulation test, being associated with tumor staging. The findings suggest influence of the proinflammatory cytokines released during tumor growth.(AU)

Alterações laboratoriais de origem paraneoplásica são identificadas em diversos tipos de câncer de cães e gatos. Na medicina veterinária, existem poucos estudos que correlacionam os achados laboratoriais anormais com o tipo e estadiamento tumorais, principalmente em cadelas com neoplasia mamária. O objetivo deste estudo foi avaliar as alterações hematológicas, bioquímicas e hemostáticas em cadelas com neoplasia mamária e relacioná-las com o estadiamento tumoral. Foram coletadas amostras de sangue de 24 fêmeas caninas, e os parâmetros hematológicos, bioquímicos e hemostáticos obtidos foram relacionados com o estadiamento tumoral, realizado através do exame físico, exames de imagem e avaliação histopatológica após remoção cirúrgica. Os grupos foram organizados de acordo com o estadiamento tumoral em: Grupo 1 (estádios I e II), grupo 2 (estádio III) e grupo 3 (estádios IV e V). Observou-se anemia, leucocitose neutrofílica, monocitose, eosinofilia, trombocitose, hipoalbuminemia, hipocalcemia, hipoglicemia e diminuição de ureia sanguínea. As variáveis CHCM, PPT e RDW foram relacionadas com o estadiamento tumoral, porém sem relevância clínica. Nos testes de coagulação, o TT e o fibrinogênio apresentaram diferença significativa entre os grupos, sendo associado com estadiamento tumoral. Os resultados sugerem influência das citocinas pró-inflamatórias liberadas durante o crescimento do tumor.(AU)

Temporal deterioration of neurological symptoms and increase of serum acetylcholine receptor antibody levels after thymectomy: a case report of a cat with myasthenia gravis.

Neurological signs and serum acetylcholine receptor antibody (AChR-Ab) levels before and after thymectomy were monitored in a 6-year-old male cat with acquired Myasthenia Gravis (MG) as a paraneoplastic syndrome of thymoma. Soon after surgery, the neurological symptoms relapsed, and the cholinesterase inhibitor was administered to control them. The AChR-Ab levels increased postoperatively until 90 days after surgery. This is the first report on long term measurements of serum AChR-Ab levels in a cat with MG. Although thymectomy is valuable for the removal of thymoma, it may not resolve MG symptoms, neurological signs and serum AChR-Ab levels, without medication early after surgery. Also, this case report indicates that the AChR-Ab level might be a guide to detect a deterioration of MG symptoms.

Imaging diagnosis-hypoglycemia associated with cholangiocarcinoma and peritoneal carcinomatosis in a horse.

An 8-year-old Thoroughbred mare presented for decreased appetite, ataxia, and weakness. Abdominal ultrasound revealed a large volume of anechoic fluid along with multiple masses involving the spleen, liver, and diaphragm. Pleural fluid was identified via ultrasonography and thoracic radiography. Thoracic radiographs also identified pulmonary interstitial nodules, an undulant dorsal diaphragmatic margin and enlargement of tracheobronchial lymph nodes. Clinical signs of weakness and mild seizures were concurrent with hypoglycemic episodes. The final diagnosis was cholangiocarcinoma with extensive metastasis. Clinical signs of weakness, ataxia, and seizures were attributed to a paraneoplastic syndrome of tumor-associated hypoglycemia that has been infrequently reported in horses.

Paraneoplastic hypertrophic osteopathy in 30 dogs.

Paraneoplastic hypertrophic osteopathy (pHO) is known to occur in both canine and human cancer patients. While the pathology of pHO is well-described in the dog, very little information exists regarding the true clinical presentation of dogs affected with pHO. The primary objective of this study was to provide a more comprehensive clinical picture of pHO. To this end, we retrospectively identified 30 dogs and recorded data regarding presenting complaints and physical examination (PE) findings on the date of pHO diagnosis. As a secondary objective, any blood test results were also collected from the computerized records. The most common clinical signs included leg swelling, ocular discharge and/or episcleral injection, lameness, and lethargy. The most common haematological and serum biochemical abnormalities included anaemia, neutrophilia and elevated alkaline phosphatase. In addition to presenting a more detailed clinical description of pHO in the dog, these data support the previously described haematological, serum biochemical and PE abnormalities published in individual case reports.

Epidemiological, clinical and immunohistochemical aspects of canine lymphoma in the region of Porto Alegre, Brazil / Aspectos epidemiológicos, clínicos e imuno-histoquímicos do linfoma canino na região de Porto Alegre

This paper describes the epidemiological, clinical and immunohistochemical characteristics of canine lymphomas diagnosed in the region of Porto Alegre, Brazil. Thirty dogs were enrolled in the study; most of them were male (60 percent), mixed-breed (23 percent) and middle-aged or older. The majority (87 percent) of affected dogs showed the multicentric form. The B-cell phenotype was most frequently detected (62 percent); 37 percent of the animals were in clinical stage IV, and 83 percent were classified as sub-stage "b". Lymphadenopathy was observed in 67 percent of the cases, and dyspnea, prostration, decreased appetite and vomiting were the most common clinical signs encountered. Anemia was a frequently encountered laboratory alteration (57 percent), as were leukocytosis (40 percent), thrombocytopenia (33 percent), lymphopenia (30 percent), hyperglobulinemia (20 percent) and hypercalcemia (13 percent). The results of this study indicate that the clinical features of dogs with lymphoma in the region of Porto Alegre are similar to those observed worldwide.

Esse trabalho apresenta os achados epidemiológicos, clínicos e imuno-histoquímicos de linfomas caninos diagnosticados na região de Porto Alegre. Trinta cães foram incluídos no estudo; sendo principalmente machos (60 por cento), sem raça definida (23 por cento) e de meia-idade a idosos. A maioria (87 por cento) dos cães afetados apresentou a forma anatômica multicêntrica. O imunofenótipo B foi detectado com mais frequência (62 por cento); 37 por cento dos cães apresentavam estadiamento clínico IV e 83 por cento encontravam-se no subestádio "b". Linfadenopatia foi observada em 67 por cento dos casos; outros sinais clínicos comumente detectados foram dispneia, prostração, diminuição do apetite e vômitos. Anemia foi a alteração laboratorial mais frequente (57 por cento), seguida por leucocitose (40 por cento), trombocitopenia (33 por cento), linfopenia (30 por cento), hiperglobulinemia (20 por cento), hiperproteinemia (17 por cento) e hipercalcemia (13 por cento). Os resultados do presente estudo indicam que as características epidemiológicas e clínicas de cães com linfoma na região de Porto Alegre são semelhantes às observadas em todo o mundo.

Cutaneous paraneoplastic syndrome in a cat with thymoma.

Feline cutaneous paraneoplastic syndrome is a rare disorder associated mainly with pancreatic carcinoma and thymoma. In this report the authors describe the case of a 12-year-old cat with paraneoplastic exfoliative dermatitis associated with thymoma. Lateral radiographic examination of the chest showed a small subtle soft tissue density in the ventral part of the first and second intercostal space, which together with skin changes suggested thymoma. Because of pain associated with the skin condition, costs of treatment and the risk associated with surgical treatment, the owner chose euthanasia of the cat. Post-mortem examination revealed a tumour which was diagnosed as thymoma by histopathological examination.

Nodular dermatofibrosis in a German shepherd dog: case report.

An 7-year-old male German shepherd dog not neutered was attended presenting several cutaneous nodules ranging from 0.5-3 cm in diameter at least a one year history, located mainly in thoracic and pelvic limbs, with progressive weight loss over two months. Fine needle aspiration biopsy and pelvic and thoracic limbs nodules excision biopsy were performed. After histopathological diagnosis, nodular dermatofibrosis diagnosis was determined and abdominal ultrasound was performed for possible renal cysts evaluation. The animal received treatment to control secondary bacterial infection. It is necessary to carry out histopathological examination and ultraosund to identify possible renal cysts and for definitive diagnosis. There is no specific treatment for nodular dermatofibrosis.

Cutaneous manifestations of internal diseases.

One of the best-recognized cutaneous manifestations of internal disease includes the skin changes seen in endocrine diseases. Cutaneous manifestations of internal disease can also be seen with certain neoplastic processes. Metabolic disturbances in zinc, lipid metabolism, or increased amino acid catabolism can result in zinc-responsive dermatosis, cutaneous xanthomas, and superficial necrolytic dermatitis, respectively. Certain infectious diseases can result in skin lesions that may provide visual clues but also critical diagnostic information if the skin is biopsied and cultured. Recognizing those skin changes that are clinical markers for internal disease can expedite the diagnosis and timely management of several systemic diseases.

European consensus document on mast cell tumours in dogs and cats.

In preparing this document the Authors aimed to pool current information on canine and feline mast cell disease. The information was gathered from international studies and a emphasis was placed on material and opinion with a strong evidence base. We intend it to form the basis of our understanding in this disease at the current time and we anticipate that it will be particularly useful for the general practitioner. It should be emphasized that the authors are presenting this work from a European perspective.

Paraneoplastic syndrome in haemophagocytic histiocytic sarcoma in a dog.

A case of metastatic splenic haemophagocytic histiocytic sarcoma (HHS) in a 6-year-old neutered male flat-coated retriever is described. The main clinical findings were hypoalbuminaemia and regenerative anaemia. The diagnosis was based on histological features and expression of CD11d by the neoplastic cells. Tumour cells were shown to produce interleukin (IL)-6, to phagocytose erythrocytes and to take up albumin, as demonstrated by immunohistochemistry and ultrastructural examination. Quantitative polymerase chain reaction identified increased IL-6 gene expression in affected organs. These findings suggest that neoplastic cells are responsible for the clinical features of HHS, by removing erythrocytes and albumin from the blood and releasing cytokines, such as IL-6.

Paraneoplastic hypercalcemia.

Paraneoplastic syndromes (PNSs) are neoplasm-associated alterations in bodily structure or function or both that occur distant to the tumor. They are an extremely diverse group of clinical aberrations that are associated with the noninvasive actions of the tumor. In many situations, the PNS parallels the underlying malignancy, and therefore, successful treatment of the tumor leads to disappearance of the PNS. Alternatively, recurrence of the PNS after successful treatment signals recurrence of the tumor, and the return of the PNS often significantly precedes the detectable recurrence of the tumor. This is often the case with paraneoplastic hypercalcemia, often referred to as hypercalcemia of malignancy (HM). The most common cause of hypercalcemia in dogs is cancer. Neoplasia is diagnosed in approximately two-thirds of dogs with hypercalcemia vs. approximately one-third in cats. A variety of tumors have been associated with HM. Lymphoma is the most common cause of HM, and the most common anatomical site for dogs with lymphoma-associated HM is the cranial mediastinum. Other tumors associated with HM in dogs and cats include anal sac apocrine gland adenocarcinoma, thyroid carcinoma, multiple myeloma, bone tumors, thymoma, squamous cell carcinoma, mammary gland carcinoma/adenocarcinoma, melanoma, primary lung tumors, chronic lymphocytic leukemia, renal angiomyxoma, and parathyroid gland tumors. As HM is a potential medical emergency, the primary goal in cases of HM is the elucidation of the underlying cause and thereby instituting the appropriate specific therapy.