Síndrome paraneoplásica gastrintestinal e relação com o prognóstico em cães com mastocitoma cutâneo : estudo retrospectivo entre os anos de 2013 e 2020

As síndromes paraneoplásicas (SPN) são um grupo heterogêneo de alterações e sinais clínicos não associadas as ações invasivas das neoplasias e/ou suas metástases. Rotineiramente, as SPN comprometem a condição clínica do paciente, aumentam a morbidade e mortalidade, contribuindo para um pior prognóstico e menor expectativa de vida. Na espécie canina o mastocitoma é um tumor cutâneo, frequentemente, associado a ocorrência de SPN graves, sendo a ulceração gastroduodenal (UGD) a principal delas. A fisiopatogênia da UGD ainda não é bem elucidada, contudo é sugerida uma associação com valores séricos elevados de histamina. Informações sobre a real incidência de SPN na Medicina Veterinária ainda são inconsistentes e, em se tratando dos mastocitomas, desconhece-se outros estudos relacionando a ocorrência de sinais clínico, valores de histamina e lesões gastrintestinais macroscópicas e microscópicas com intervalo livre de doença (ILD) e sobrevida (SV) em cães. Assim sendo, esta tese foi dividida em dois capítulos. O primeiro deles, trata-se de uma revisão de literatura sobre o mastocitoma cutâneo canino e alguns de seus fatores prognósticos mais utilizados. O segundo capítulo trata-se de um artigo original retrospectivo, no qual buscou-se observar a ocorrência de SPN e sua relação com intervalo livre de doença e sobrevida, pela revisão de prontuários e acompanhamentos ao longo dos anos de 2013 a 2020. Para tal foram avaliados 41 prontuários e, após seleção, foram incluídos 38 cães com diagnóstico histológico de mastocitoma. Todos os cães passaram por avaliação clínica, endoscópica e dosagem de histamina plasmática no momento do diagnóstico. Foi considerada SPN a ocorrência de sinais clínicos GI e/ou presença de lesão GI na macroscopia e/ou microscopia. Devido à falta de um ponto de corte em relação aos níveis séricos de histamina, optou-se por estratificar aleatoriamente estes valores em três subcategorias, buscando relacionar estas categorias com o ILD e a SV. Foram observados sinais clínicos em 57,9% dos casos, 68,4% apresentavam lesão macroscópica GI e 42,1% lesão GI microscópica. A mediana do valor de histamina plasmática foi de 0,01ng/mL e, aproximadamente metade dos cães (52,6%) apresentaram valores inferiores ao valor da mediana. O intervalo livre de doença teve uma mediana de 18,1 meses. Com relação a SV, ao final do estudo (dez/2020), 71,1% dos cães vieram a óbito e 28,9% estão em seguimento. Neste grupo avaliado, a análise estatística não foi capaz de demonstrar relação entre a ocorrência de SPN e valores de histamina plasmática e as variáveis de tempo livre de doença e expectativa de vida, todavia não se descarta tal hipótese, pois acredita-se que o perfil da população que em sua maioria foi composta por casos leves da doença, possa ter contribuído para estes resultados.Paraneoplastic syndromes (PNS) are a heterogeneous group of alterations and clinical signs that are not associated with the invasive actions of the neoplasms and/or their metastases. Routinely, PNS can compromise the patient’s clinical conditions, increase the morbidity and mortality, consequently, contribute to a worse prognosis and a shorter life expectancy. In canine specie, mastocytoma is a cutaneous neoplasm, often associated with the occurrence of serious PNS with gastroduodenal ulceration being the main one. The physiopathogenesis of the gastroduodenal ulceration is still not well understood, however an association with elevated histamine values has been suggested. In Veterinary Medicine information on the real incidence of PNS is still inconsistent and in the case of mast cell tumors other studies relating the occurrence of clinical signs, plasma histamine values and macroscopic and/or microscopic gastrointestinal (GI) lesions with disease-free-interval and survival (SV) time are unknown. Therefore, this dissertation was divided into two chapters. The first one is a literature review on canine mast cell tumor and some of its most widely used prognostic factors. The second chapter is and original retrospective article in which we observed the occurrence of PNS and its relationship with disease-free-interval and survival time, by reviewing medical records and follow-up over the years 2013 to 2020. For this purpose, 41 records were evaluated and, after selection, 38 dogs with histological diagnosis of mast cell tumor were included. All dogs underwent clinical, endoscopic and plasma histamine measurements at the time of diagnosis. PNS was considered to be the occurrence of clinical GI signs and/or presence of lesions in macroscopy and/or microscopy. Due to the lack of a cutoff point for histamine serum values, it was decided to randomly stratify these values into three categories, seeking to relate these categories to DFI and SV. Clinical signs were observed in 57,9% of the cases, 68,4% had macroscopic GI lesions and 42,1% had microscopic GI lesions. The median plasma histamine value was 0,01ng/mL and approximately half of the dogs (52,6%) had values below the median value. The disease-free interval had a median of 18,1 months. Regarding SV, at the end of the study (Dec/2020), 71,1% of the dogs died and 28,9% are being followed up. In this evaluated group, the statistical analysis was not able to demonstrate a relationship between the occurrence of PNS and the histamine plasma values and the variables DFI and life expectancy, however this hypothesis is not discarded as it is believed that the profile of the population, in general mild cases of the disease, may have contributed to these results

Granulosa cell tumor associated with occult hyperadrenocorticism in a Yorkshire Terrier bitch

Background: Hyperadrenocorticism (HAC), is considered a set of symptoms due to excessive exposure to cortisol. Naturally occurring HAC is most often related to pituitary tumors (pituitary-dependent HAC - PDH). Occult HAC, is referred as a clinical picture highly consistent with HAC; however, routine screening tests are negative. In addition, one or more steroids are elevated following administration of adrenocorticotrophic hormone (ACTH). Ovarian granulosa cell tumors, can produce steroids leading to paraneoplastic syndromes. The objective of this study was to report an unpublished case of ovarian granulosa cell tumor associated with occult hyperadrenocorticism in a Yorkshire Terrier. Case: A 13-year-old intact female dog, Yorkshire Terrier, was brought for consultation with slight weight loss, polyuria, polydipsia, irregular estrous cycles, increased abdominal volume and thin coat. On physical examination the animal was gasping and presented severe periodontal disease, bulging abdomen, alopecia and skin hyperpigmentation. Complete blood count presented no changes; however, serum biochemistry evaluation highlighted hyperalbuminemia, hypertriglyceridemia, alkaline phosphatase increased activity, and urinary specific gravity and creatinine below reference values. On abdominal ultrasonography left adrenal gland measured 2.08 cm x 1.08 cm and the right adrenal gland measured 2.11 cm x 0.84 cm, indicating bilateral adrenomegaly compatible with PDH. In the hypogastric abdomen, a large heterogeneous hypoechogenic mass was also observed, with areas of cystic cavities, measuring 5.80 cm x 7.30 cm A low dose dexamethasone suppression test (LDDST) was performed, due to PDH suspicion. The test did not confirm HAC, suspecting, then, to be a case of occult/atypical HAC. Due to the strong clinical suspicion, and owner financial problems for further investigated occult HAC, trilostane treatment was initiated. Approximately one month after starting treatment, an ACTH stimulation test (AST) for cortisol and 17-hydroxyprogesterone (17-OHP) determination was performed, revealing high values for both hormones. Exploratory laparotomy was indicated due to the tumor image on hypogastric region visualized on abdominal ultrasonography. A cranial pole mass of the left ovary measuring 8.5 x 7.0 x 4.5 cm, of friable consistency and brownish color, was removed through ovariohysterectomy. A granulosa cell tumor on left ovary, as well as leiomyoma and cystic endometrial hyperplasia in the uterus, became clear through histopathological examination. Trilostane treatment was sustained after surgery. Few weeks later, the patient presented a clinical picture suggestive of hypoadrenocorticism, associated with a low sodium:potassium ratio (25:1), and AST results (basal and post-ACTH cortisol) below reference range, confirming Addisonian´ crises. The patient deceives within two days Discussion: Granulosa cell tumors can produce estrogen and progesterone, as well as other steroids, leading to paraneoplastic syndromes with peculiar clinical presentations. Steroids transport in plasma occurs via specific carrier proteins. Increased production of other steroid hormones may result in higher concentration of free cortisol, thus leading to clinical manifestations of hypercortisolism. As 17-OHP is one of the precursors in cortisol synthesis and has been shown elevated on AST, it can be assumed that altered steroid hormone levels due to the granulosa cell tumor interfered on cortisol biodisponibility, leading to HAC signs. Dexamethasone suppression test results indicated that pituitary-adrenal axis was responsive to negative feedback. The Addisonian crises after tumor removal indicate that the main source for systemic excessive cortisol effects was the eminent steroid secretion by the granulosa cell tumor

Granulosa Cell Tumor Associated with Occult Hyperadrenocorticism in a Yorkshire Terrier Bitch

Background: Hyperadrenocorticism (HAC), is considered a set of symptoms due to excessive exposure to cortisol. Naturally occurring HAC is most often related to pituitary tumors (pituitary-dependent HAC - PDH). Occult HAC, is referred as a clinical picture highly consistent with HAC; however, routine screening tests are negative. In addition, one or more steroids are elevated following administration of adrenocorticotrophic hormone (ACTH). Ovarian granulosa cell tumors, can produce steroids leading to paraneoplastic syndromes. The objective of this study was to report an unpublished case of ovarian granulosa cell tumor associated with occult hyperadrenocorticism in a Yorkshire Terrier.Case: A 13-year-old intact female dog, Yorkshire Terrier, was brought for consultation with slight weight loss, polyuria, polydipsia, irregular estrous cycles, increased abdominal volume and thin coat. On physical examination the animal was gasping and presented severe periodontal disease, bulging abdomen, alopecia and skin hyperpigmentation. Complete blood count presented no changes; however, serum biochemistry evaluation highlighted hyperalbuminemia, hypertriglyceridemia, alkaline phosphatase increased activity, and urinary specific gravity and creatinine below reference values. On abdominal ultrasonography left adrenal gland measured 2.08 cm x 1.08 cm and the right adrenal gland measured 2.11 cm x 0.84 cm, indicating bilateral adrenomegaly compatible with PDH. In the hypogastric abdomen, a large heterogeneous hypoechogenic mass was also observed, with areas of cystic cavities, measuring 5.80 cm x 7.30 cm. A low dose dexamethasone suppression test (LDDST) was performed, due to PDH suspicion. The test did not confirm HAC, suspecting, then, to be a case of occult/atypical HAC. Due to the strong clinical suspicion, and owner financial problems for further investigated occult HAC, trilostane treatment was initiated. Approximately one month after starting treatment, an ACTH stimulation test (AST) for cortisol and 17-hydroxyprogesterone (17-OHP) determination was performed, revealing high values for both hormones. Exploratory laparotomy was indicated due to the tumor image on hypogastric region visualized on abdominal ultrasonography. A cranial pole mass of the left ovary measuring 8.5 x 7.0 x 4.5 cm, of friable consistency and brownish color, was removed through ovariohysterectomy. A granulosa cell tumor on left ovary, as well as leiomyoma and cystic endometrial hyperplasia in the uterus, became clear through histopathological examination. Trilostane treatment was sustained after surgery. Few weeks later, the patient presented a clinical picture suggestive of hypoadrenocorticism, associated with a low sodium:potassium ratio (25:1), and AST results (basal and post-ACTH cortisol) below reference range, confirming Addisonian´ crises. The patient deceives within two days.Discussion: Granulosa cell tumors can produce estrogen and progesterone, as well as other steroids, leading to paraneoplastic syndromes with peculiar clinical presentations. Steroids transport in plasma occurs via specific carrier proteins. Increased production of other steroid hormones may result in higher concentration of free cortisol, thus leading to clinical manifestations of hypercortisolism. As 17-OHP is one of the precursors in cortisol synthesis and has been shown elevated on AST, it can be assumed that altered steroid hormone levels due to the granulosa cell tumor interfered on cortisol biodisponibility, leading to HAC signs. Dexamethasone suppression test results indicated that pituitary-adrenal axis was responsive to negative feedback. The Addisonian crises after tumor removal indicate that the main source for systemic excessive cortisol effects was the eminent steroid secretion by the granulosa cell tumor

Immune-Mediated Hemolytic Anemia in a Bitch Triggered by Drugs

Background: Immune-mediated hemolytic anemia (IMHA) is characterized by an autoimmune response with production of auto-antibodies and destruction of erythrocytes resulting in anemia. Primary IMHA is referred to a condition when the cause is unknown (idiopathic), whereas secondary IMHA involves changes in red blood cells caused by the action of drugs, neoplasms, or infectious diseases. The diagnosis can be made through changes in the blood count, usually of a regenerative character, Coombs test, and autoagglutination test. The present study aimed to report a case of drug-induced hemolytic anemia, with emphasis on the clinical signs, diagnostic methods, and treatment, in a female dog.Case: A 9-year-old mixed-breed bitch weighing 29.6 kg was referred to the Veterinary Medical Teaching Hospital (HCV-UFRGS) with a previous diagnosis of gallbladder mucocele that was unresponsive to clinical treatment. After laboratory tests, cholecystectomy was performed, and the procedure required conversion from laparoscopic to open cholecystectomy. Therapy included administration of amoxicillin, dipyrone, tramadol hydrochloride, and meloxicam. Three days after surgery, the dog presented with apathy, lethargy, hyporexia, and a pale and subicteric mucosa. The patient developed hypochromic macrocytic anemia with reticulocytosis, spherocytosis, anisocytosis, and leukocytosis with neutrophilia. The result of the autoagglutination test was positive, confirming the diagnosis. All medications were suspended, and immunosuppressive treatment with dexamethasone was included, with a subsequent switch to prednisolone. After 10 days of treatment, the patient experienced significant improvement, and therapy was discontinued.Discussion: Based on the patient's history, the cause of the IMHA was secondary to drug administration, and it is not possible to distinguish if it was due to one or a combination of drugs, as they were all started and stopped simultaneously. The patient had hypothyroidism, which may have contributed to the production of antibodies against TSH receptors, blocking the hormone's action, thereby causing tissue damage due to T cell-mediated cytotoxicity and the effect of cytokines. The pale and subicteric mucosa, apathy, weakness, lethargy, exercise intolerance, and dyspnea resulted from extravascular hemolysis and bilirubin released from erythrocyte rupture with a subsequent decrease in the number of red blood cells, leading to oxygen transport deficiency. The diagnosis is based on the blood count and results of autoagglutination supported by the response to immunosuppressive therapy. Anemia results in increased production and release of precursor cells from the bone marrow, accompanied by reticulocytosis and increased mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC). The treatment of IMHA consists of supportive care and immunosuppressive therapy with corticosteroids to ensure suppression of the immune system, preventing response against erythrocytes. Initially, tramadol hydrochloride, dipyrone, and amoxicillin with potassium clavulanate were suspended to interrupt the cause of IMHA, and administration of dexamethasone in an immunosuppressive dose was started. Therefore, it is important to include drug-induced IMHA in the differential diagnosis of patients who present with anemia after using medications. Early diagnosis, initiation of therapy, and adequate care were important factors for the recovery of the animal.Título: Anemia hemolítica imunomediada medicamentosa em uma cadelaKeywords: dog, hypochromic macrocytic anemia, erythrocyte, hemoglobin, spherocyte.Descritores: cão, anemia macrocítica hipocrômica, eritrócito, hemoglobina, esferócito.

Immune-mediated hemolytic anemia in a bitch triggered by drugs

Background: Immune-mediated hemolytic anemia (IMHA) is characterized by an autoimmune response with production of auto-antibodies and destruction of erythrocytes resulting in anemia. Primary IMHA is referred to a condition when the cause is unknown (idiopathic), whereas secondary IMHA involves changes in red blood cells caused by the action of drugs, neoplasms, or infectious diseases. The diagnosis can be made through changes in the blood count, usually of a regenerative character, Coombs test, and autoagglutination test. The present study aimed to report a case of drug-induced hemolytic anemia, with emphasis on the clinical signs, diagnostic methods, and treatment, in a female dog. Case: A 9-year-old mixed-breed bitch weighing 29.6 kg was referred to the Veterinary Medical Teaching Hospital (HCVUFRGS) with a previous diagnosis of gallbladder mucocele that was unresponsive to clinical treatment. After laboratory tests, cholecystectomy was performed, and the procedure required conversion from laparoscopic to open cholecystectomy. Therapy included administration of amoxicillin, dipyrone, tramadol hydrochloride, and meloxicam. Three days after surgery, the dog presented with apathy, lethargy, hyporexia, and a pale and subicteric mucosa. The patient developed hypochromic macrocytic anemia with reticulocytosis, spherocytosis, anisocytosis, and leukocytosis with neutrophilia. The result of the autoagglutination test was positive, confirming the diagnosis. All medications were suspended, and immunosuppressive treatment with dexamethasone was included, with a subsequent switch to prednisolone. After 10 days of treatment, the patient experienced significant improvement, and therapy was discontinued. Discussion: Based on the patient’s history, the cause of the IMHA was secondary to drug administration, and it is not possible to distinguish if it was due to one or a combination of drugs, as they were all started and stopped simultaneously. The patient had hypothyroidism, which may have contributed to the production of antibodies against TSH receptors, blocking the hormone’s action, thereby causing tissue damage due to T cell-mediated cytotoxicity and the effect of cytokines. The pale and subicteric mucosa, apathy, weakness, lethargy, exercise intolerance, and dyspnea resulted from extravascular hemolysis and bilirubin released from erythrocyte rupture with a subsequent decrease in the number of red blood cells, leading to oxygen transport deficiency. The diagnosis is based on the blood count and results of autoagglutination supported by the response to immunosuppressive therapy. Anemia results in increased production and release of precursor cells from the bone marrow, accompanied by reticulocytosis and increased mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC). The treatment of IMHA consists of supportive care and immunosuppressive therapy with corticosteroids to ensure suppression of the immune system, preventing response against erythrocytes. Initially, tramadol hydrochloride, dipyrone, and amoxicillin with potassium clavulanate were suspended to interrupt the cause of IMHA, and administration of dexamethasone in an immunosuppressive dose was started. Therefore, it is important to include drug-induced IMHA in the differential diagnosis of patients who present with anemia after using medications. Early diagnosis, initiation of therapy, and adequate care were important factors for the recovery of the animal

Anestesia local asociada a biopsias de piel en medicina veterinária : una revisión narrativa

Biópsias cutâneas, especialmente por punch, são amplamente utilizadas como ferramenta diagnóstica na dermatologia veterinária. Esse procedimento pode ser realizado com anestesia geral aliada ou não a anestesia local, e em alguns casos, com anestesia local isoladamente. A lidocaína é o anestésico local mais utilizado, devido a sua rápida ação, fácil acesso e relativo baixo custo. A anestesia infiltrativa é normalmente utilizada em procedimentos dermatológicos, mas anestesia regional e anestesia tópica também podem ser recomendadas em alguns casos. Efeitos adversos variam de incomuns a raros, e incluem reações locais, de lesões nervosas locais e hipersensibilidade ou dermatite de contato, e reações sistêmicas como anafilaxia, cardiotoxicidade e depressão do sistema nervoso central. Quando administrados na dose adequada para a espécie referida, com técnica padronizada e conhecimento anatômico, as reações adversas são extremamente raras. Anestésicos locais são de importância fundamental para a dermatologia veterinária, principalmente em biópsias de pele de cães e gatos. O objetivo desta revisão narrativa é explorar a estrutura e mecanismo de ação dos principais fármacos utilizados, técnicas de anestesia local, assim como possíveis efeitos adversos associados à utilização destes fármacos em cirurgias dermatológicas, com ênfase em biópsias cutâneas.Skin biopsies, especially by punch, are widely used as a diagnostic tool in veterinary dermatology. It can be performed in patients under general anesthesia combined or not with local anesthesia, and in some cases, with local anesthesia alone. Lidocaine is the most widely used local anesthetic due to its rapid onset of action, easy to access and relatively inexpensive cost. Infiltrative anesthesia is often used in dermatological procedures, but regional anesthesia and topical anesthesia may also be recommended in some cases. Adverse effects vary from uncommon to rare and include local reactions such as local nerve lesions and hypersensitivity or contact dermatitis, and systemic reactions namely anaphylaxis, cardiotoxicity, and central nervous system depression. When administered at the appropriate dose for the referred species, with standardized technique and anatomical knowledge, adverse reactions are extremely rare. Local anesthetics are of fundamental importance for veterinary dermatology, especially in skin biopsy of dogs and cats. The aim of this narrative review, is to explore the structure and mechanism of action of the main drugs used, local anesthesia techniques, as well as possible side effects associated with the use of these drugs in dermatological surgeries, with focus on skin biopsies.Las biopsias cutáneas, especialmente por punción, se utilizan ampliamente como herramienta de diagnóstico em Dermatología veterinaria. Este procedimiento puede ser realizado con anestesia general aliada o no a anestesia local, y en algunos casos, con anestesia local aisladamente. La lidocaína es el anestésico local más utilizado, debido a su rápida acción, fácil acceso y relativo bajo costo. La anestesia infiltrativa se usa típicamente en procedimientos dermatológicos, pero en algunos casos también se pueden recomendar anestesia regional y anestesia tópica. Los efectos adversos varían de inusuales a raros, e incluyen reacciones locales, desde lesiones nerviosas locales e hipersensibilidad o dermatitis de contacto, y reacciones sistémicas como anafilaxia, cardiotoxicidad y depresión del sistema nervioso central. Cuando se administran en la dosis adecuada para la especie referida, con técnica estandarizada y conocimiento anatómico, las reacciones adversas son extremadamente raras. Los Anestésicos locales son de importancia fundamental para la dermatología veterinaria, especialmente en biopsias de piel en perros y gatos. El objetivo de esta revisión narrativa es explorar la estructura y mecanismo de acción de los principales fármacos utilizados, las técnicas de anestesia local, así como los posibles efectos adversos asociados al uso de estos fármacos en cirugías dermatológicas, con foco en las biopsias de piel

Frequência e intensidade de lesões gastroduodenais em cães com mastocitoma cutâneo

A síndrome paraneoplásica é definida como um conjunto de sinais e sintomas que acontecem distantes do tumor primário e de suas metástases. Nos mastocitomas, os sinais sistêmicos mais comuns são os sinais gastrintestinais secundários à liberação de histamina, heparina e outras substâncias bioativas contidas no interior dos mastócitos neoplásicos. Em decorrência da ação sistêmica destas substâncias, a ulceração gastrintestinal é a principal síndrome paraneoplásica descrita. Assim, o presente trabalho avalia a ocorrência de lesões gastroduodenais em cães com mastocitoma cutâneo no momento do diagnóstico, correlacionando seu aparecimento com a apresentação clínica da doença, aparência macroscópica do tumor, diferentes marcadores prognósticos pré-estabelecidos pela literatura e valores plasmáticos de histamina. Para tal, foram utilizados 41 cães da rotina clinico/oncológica do Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul (HCV-UFRGS) com diagnóstico confirmado de mastocitoma cutâneo. Os animais foram avaliados clinicamente e, posteriormente, foram submetidos à cirurgia para exérese do tumor e exame endoscópico para avaliação do esôfago, estômago e porção proximal do duodeno. Todos os cães foram avaliados quanto a presença e a gravidade dos sinais clínicos, velocidade de crescimento tumoral, número e localização dos nódulos, tamanho tumoral, características macroscópicas do tumor, presença de metástase em linfonodo regional, classificação histopatológica, índice mitótico e valor de histamina plasmática, buscando-se estabelecer uma relação com o surgimento e a gravidade das lesões gástricas e duodenais. A análise macro e microscópica da mucosa gástrica e duodenal, não evidenciou lesões compatíveis com úlceração grave em nenhum dos cães avaliados. A ocorrência de sinais clínicos gastrintestinais foi observada em 41,5% dos casos e padrões inflamatórios, sugestivos de gastrite, foram evidenciados tanto no exame endoscópico quanto no exame histopatológico. Sendo assim, na população estudada, as lesões gastroduodenais observadas foram consideradas leves no momento do diagnóstico e não apresentaram relação estatística com as variáveis estudadas, sugerindo que a heterogenicidade da população possa ter contribuído para os resultados, ou ainda que outros fatores possam influenciar a degranulação dos mastócitos neoplásicos.Paraneoplastic syndrome is defined as a set of signs and symptoms that are not related to the local effect of the primary tumor or its metastases. Gastrointestinal ulceration is the most common sign attributed to mast cell tumor’s paraneoplastic syndrome in dogs. In mastocytoma, release of histamine, heparin, and other bioactive substances by the neoplastic mast cells can lead to increased systemic action of these substances and induce gastrointestinal disturbances. This study aimed to evaluate the occurrence of gastroduodenal lesions in dogs with cutaneous mast cell tumor at the time of diagnosis and correlate them to the clinical presentation of the disease, tumor’s macroscopic aspects, neoplasic prognostic markers, and plasmatic histamine values. We evaluated 41 dogs with cutaneous mast cell tumor diagnosed at the oncology service of the Veterinary Hospital of the Federal University of Rio Grande do Sul (UFRGS-HCV). After clinical examination, as the animals underwent surgery to remove the tumor and endoscopy to evaluate the esophagus, stomach and proximal duodenum was performed Presence and severity of clinical signs, neoplasms macroscopic characteristics, tumor size, number and location of neoplasic masses, tumor growth rate, presence of regional lymph node metastasis, histopathological classification, mitotic index, and plasmatic histamine concentration were determined and correlated with gastrodueodenal endoscopic findings. The macro and microscopic analyses of the gastric and duodenal mucosa showed no lesions compatible with ulceration in any of the pacients. The occurrence of gastrointestinal clinical signs was observed in 41.5% of cases and inflammatory patterns, suggestive of gastritis were evidenced in both endoscopic and histopathological examination; however, its correlation with the presence of mast cell tumor could not be established. Therefore, in this population, gastroduodenal lesions observed were considered mild at diagnosis and had no relation with the variables analyzed, suggesting that the heterogeneity of the population may have contributed to the results or that other factors may influence the degranulation of mast cells neoplastic

Frequência e intensidade de lesões gastroduodenais em cães com mastocitoma cutâneo

A síndrome paraneoplásica é definida como um conjunto de sinais e sintomas que acontecem distantes do tumor primário e de suas metástases. Nos mastocitomas, os sinais sistêmicos mais comuns são os sinais gastrintestinais secundários à liberação de histamina, heparina e outras substâncias bioativas contidas no interior dos mastócitos neoplásicos. Em decorrência da ação sistêmica destas substâncias, a ulceração gastrintestinal é a principal síndrome paraneoplásica descrita. Assim, o presente trabalho avalia a ocorrência de lesões gastroduodenais em cães com mastocitoma cutâneo no momento do diagnóstico, correlacionando seu aparecimento com a apresentação clínica da doença, aparência macroscópica do tumor, diferentes marcadores prognósticos pré-estabelecidos pela literatura e valores plasmáticos de histamina. Para tal, foram utilizados 41 cães da rotina clinico/oncológica do Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul (HCV-UFRGS) com diagnóstico confirmado de mastocitoma cutâneo. Os animais foram avaliados clinicamente e, posteriormente, foram submetidos à cirurgia para exérese do tumor e exame endoscópico para avaliação do esôfago, estômago e porção proximal do duodeno. Todos os cães foram avaliados quanto a presença e a gravidade dos sinais clínicos, velocidade de crescimento tumoral, número e localização dos nódulos, tamanho tumoral, características macroscópicas do tumor, presença de metástase em linfonodo regional, classificação histopatológica, índice mitótico e valor de histamina plasmática, buscando-se estabelecer uma relação com o surgimento e a gravidade das lesões gástricas e duodenais. A análise macro e microscópica da mucosa gástrica e duodenal, não evidenciou lesões compatíveis com úlceração grave em nenhum dos cães avaliados. A ocorrência de sinais clínicos gastrintestinais foi observada em 41,5% dos casos e padrões inflamatórios, sugestivos de gastrite, foram evidenciados tanto no exame endoscópico quanto no exame histopatológico. Sendo assim, na população estudada, as lesões gastroduodenais observadas foram consideradas leves no momento do diagnóstico e não apresentaram relação estatística com as variáveis estudadas, sugerindo que a heterogenicidade da população possa ter contribuído para os resultados, ou ainda que outros fatores possam influenciar a degranulação dos mastócitos neoplásicos.Paraneoplastic syndrome is defined as a set of signs and symptoms that are not related to the local effect of the primary tumor or its metastases. Gastrointestinal ulceration is the most common sign attributed to mast cell tumor’s paraneoplastic syndrome in dogs. In mastocytoma, release of histamine, heparin, and other bioactive substances by the neoplastic mast cells can lead to increased systemic action of these substances and induce gastrointestinal disturbances. This study aimed to evaluate the occurrence of gastroduodenal lesions in dogs with cutaneous mast cell tumor at the time of diagnosis and correlate them to the clinical presentation of the disease, tumor’s macroscopic aspects, neoplasic prognostic markers, and plasmatic histamine values. We evaluated 41 dogs with cutaneous mast cell tumor diagnosed at the oncology service of the Veterinary Hospital of the Federal University of Rio Grande do Sul (UFRGS-HCV). After clinical examination, as the animals underwent surgery to remove the tumor and endoscopy to evaluate the esophagus, stomach and proximal duodenum was performed Presence and severity of clinical signs, neoplasms macroscopic characteristics, tumor size, number and location of neoplasic masses, tumor growth rate, presence of regional lymph node metastasis, histopathological classification, mitotic index, and plasmatic histamine concentration were determined and correlated with gastrodueodenal endoscopic findings. The macro and microscopic analyses of the gastric and duodenal mucosa showed no lesions compatible with ulceration in any of the pacients. The occurrence of gastrointestinal clinical signs was observed in 41.5% of cases and inflammatory patterns, suggestive of gastritis were evidenced in both endoscopic and histopathological examination; however, its correlation with the presence of mast cell tumor could not be established. Therefore, in this population, gastroduodenal lesions observed were considered mild at diagnosis and had no relation with the variables analyzed, suggesting that the heterogeneity of the population may have contributed to the results or that other factors may influence the degranulation of mast cells neoplastic

Granulosa cell tumor associated with occult hyperadrenocorticism in a Yorkshire Terrier bitch

Background: Hyperadrenocorticism (HAC), is considered a set of symptoms due to excessive exposure to cortisol. Naturally occurring HAC is most often related to pituitary tumors (pituitary-dependent HAC - PDH). Occult HAC, is referred as a clinical picture highly consistent with HAC; however, routine screening tests are negative. In addition, one or more steroids are elevated following administration of adrenocorticotrophic hormone (ACTH). Ovarian granulosa cell tumors, can produce steroids leading to paraneoplastic syndromes. The objective of this study was to report an unpublished case of ovarian granulosa cell tumor associated with occult hyperadrenocorticism in a Yorkshire Terrier. Case: A 13-year-old intact female dog, Yorkshire Terrier, was brought for consultation with slight weight loss, polyuria, polydipsia, irregular estrous cycles, increased abdominal volume and thin coat. On physical examination the animal was gasping and presented severe periodontal disease, bulging abdomen, alopecia and skin hyperpigmentation. Complete blood count presented no changes; however, serum biochemistry evaluation highlighted hyperalbuminemia, hypertriglyceridemia, alkaline phosphatase increased activity, and urinary specific gravity and creatinine below reference values. On abdominal ultrasonography left adrenal gland measured 2.08 cm x 1.08 cm and the right adrenal gland measured 2.11 cm x 0.84 cm, indicating bilateral adrenomegaly compatible with PDH. In the hypogastric abdomen, a large heterogeneous hypoechogenic mass was also observed, with areas of cystic cavities, measuring 5.80 cm x 7.30 cm A low dose dexamethasone suppression test (LDDST) was performed, due to PDH suspicion. The test did not confirm HAC, suspecting, then, to be a case of occult/atypical HAC. Due to the strong clinical suspicion, and owner financial problems for further investigated occult HAC, trilostane treatment was initiated. Approximately one month after starting treatment, an ACTH stimulation test (AST) for cortisol and 17-hydroxyprogesterone (17-OHP) determination was performed, revealing high values for both hormones. Exploratory laparotomy was indicated due to the tumor image on hypogastric region visualized on abdominal ultrasonography. A cranial pole mass of the left ovary measuring 8.5 x 7.0 x 4.5 cm, of friable consistency and brownish color, was removed through ovariohysterectomy. A granulosa cell tumor on left ovary, as well as leiomyoma and cystic endometrial hyperplasia in the uterus, became clear through histopathological examination. Trilostane treatment was sustained after surgery. Few weeks later, the patient presented a clinical picture suggestive of hypoadrenocorticism, associated with a low sodium:potassium ratio (25:1), and AST results (basal and post-ACTH cortisol) below reference range, confirming Addisonian´ crises. The patient deceives within two days Discussion: Granulosa cell tumors can produce estrogen and progesterone, as well as other steroids, leading to paraneoplastic syndromes with peculiar clinical presentations. Steroids transport in plasma occurs via specific carrier proteins. Increased production of other steroid hormones may result in higher concentration of free cortisol, thus leading to clinical manifestations of hypercortisolism. As 17-OHP is one of the precursors in cortisol synthesis and has been shown elevated on AST, it can be assumed that altered steroid hormone levels due to the granulosa cell tumor interfered on cortisol biodisponibility, leading to HAC signs. Dexamethasone suppression test results indicated that pituitary-adrenal axis was responsive to negative feedback. The Addisonian crises after tumor removal indicate that the main source for systemic excessive cortisol effects was the eminent steroid secretion by the granulosa cell tumor