Mastocitoma felino. Reporte de caso / Feline mastocytoma. Case report

RESUMEN Los mastocitomas son tumores originarios de los mastocitos que usualmente afectan a los perros y los gatos. Pueden llegar a tener un comportamiento benigno, sin embargo, esto dependerá del grado de la neoplasia y su estadiaje. En felinos, clínicamente se han descrito dos patrones: visceral y cutáneo, de los cuales el cutáneo es el más frecuente, llegando a causar metástasis a órganos adyacentes e incluso afectar el bazo y/o intestino en estadios más diferenciados. Se presenta un caso de mastocitoma felino correspondiente a un ejemplar mestizo con cuadro clínico de inicio de más de dos meses de evolución, consistente en la aparición de una placa alopécica ulcerada y elevada en región interescapular, acompañada de prurito que presentó resolución espontánea. Mediante el curso clínico se imnunizó contra el virus de la rabia, posteriormente, se observó la aparición de una lesión nodular subcutánea de características inusuales de 2cm de diámetro. Acorde con el tiempo de evolución y el antecedente vacunal se decidió la realización de biopsia y resección quirúrgica. El reporte de la biopsia confirmó diagnóstico de mastocitoma grado histológico 3 de Patnaik, teniendo en cuenta las características histológicas, estructurales y su comportamiento clínico. Se realizó seguimiento del caso pasados ocho meses, donde se evidenció mejoría del cuadro clínico, sin aparición de nueva masa sugestiva de neoplasia, sin hallazgos de metástasis a otras estructuras, con cicatrización exitosa de herida quirúrgica y evolución satisfactoria.

ABSTRACT Mast cells are tumors originating from mast cells which usually affect cats and dogs. They may have benign behavior, however, this will depend on the degree of the neo-plasm and its staging. In cats, two patterns have been described clinically: visceral and cutaneous, of which the cutaneous form is the most frequent, reaching metastasis to adjacent organs and even affecting the spleen and / or intestine in more differentiated stages. A case of a mastocytoma is presented, a feline corresponding to a mongrel specimen with a clinical picture of onset of more than two months of evolution, consisting of the appearance of an allopecal plaque, ulcerated and elevated in the interscapular region, accompanied by pruritus that presented spontaneous resolution. Through the clinical course, he was immunized against the rabies virus, later the appearance of a nodular lesion of unusual subcutaneous characteristics, 2 cm in diameter, was observed. According to the evolution time and the vaccination history, it was decided to perform a biopsy and surgical resection. The biopsy report confirmed the diagnosis of Patnaik's histological grade 3 mastocytoma, taking into account the histological and structural characteristics and its clinical behavior. The case was followed up after eight months, where an improvement in the clinical picture was evident, without the appearance of a new mass suggestive of neoplasia, without metastatic findings to other structures, with successful healing of the surgical wound and satisfactory evolution.

Avaliação da proliferação celular como indicador prognóstico para mastocitomas cutâneos caninos / Evaluation of cellular proliferation as prognostic indicator for canine cutaneous mast cell tumors

Este estudo teve como objetivo avaliar o valor prognóstico de marcadores de proliferação celular em casos de mastocitomas cutâneos caninos. Vinte e três casos foram analisados quanto à expressão imuno-histoquímica de Ki67 e do Antígeno Nuclear de Proliferação Celular (PCNA), sendo subsequentemente acompanhados clinicamente. Observou-se que a expressão de Ki67 mantém relação negativa com a tradicional graduação histopatológica (p= 0,0418; p<0,05 entre os graus I e III), sendo um indicador confiável para o tempo de sobrevida pós-cirúrgica (p=0,0089). A imunoexpressão de PCNA, apesar de estar correlacionada à marcação por Ki67, não apresentou valores estatisticamente significantes na predição da mortalidade em função da doença e do tempo de sobrevida pós-cirúrgico. Os resultados obtidos confirmam que informações sobre a atividade proliferativa tumoral pela detecção imuno-histoquímica de Ki67 podem incrementar a classificação de mastocitomas cutâneos caninos quanto à malignidade.

This study evaluated the prognostic value of cell proliferation markers for canine cutaneous mast cell tumor cases. Twenty-three cases were analyzed with regard to immuno-histochemical expression of Ki67 and Proliferating Cell Nuclear Antigen (PCNA), and were clinically followed up. Ki67 expression was related to the traditional histopathological grading (p= 0.0418; p<0.05 between grades I and III), and was a reliable indicator of post-surgical survival (p=0.0089). PCNA immunoexpression did not show statistically significant values in the prediction of disease-related mortality and survival, although it is correlated to Ki67 expression. These results confirm that information about tumoral proliferative activity through Ki67 immunohistochemical detection can improve canine cutaneous mast cell tumor grading with regard to malignancy.

Ultra-estrutura dos mastócitos de diferentes tipos histológicos de mastocitoma em cäes / Mast cell ultrastructure in different types of canine mast cell tumor

Este trabalho teve por objetivo estudar as diferenças ultraestruturais de mastócitos neoplásicos de diferentes tipos histológicos de mastocitoma em cäes, usando microscopia eletrônica de transmissäo Os resultados mostraram que o núcleo e os grânulos citoplasmáticos säo as estruturas mais indicadas para se avaliar o grau de anaplasia celular e o estádio de indiferenciaçäo do tumor

Mastocitoma canino: aplicaçäo do escore de Patnaik et al. para o diagnóstico/prognóstico de rotina / Canine mastocytoma: application of Patnaik et al. escore for the routine diagnosis/prognosis

O diagnóstico clínico-laboratorial, diferencial dos mastocitomas com outras neoplasias do grupo de ®tumores de células redondas cutâneas do cäo¼ (histiocitoma cutâneo canino, tumor venéreo transmissível - extragenital, linfossarcoma cutâneo canino, plasmocitoma cutâneo canino - extramedular), assim como sua gradaçäo morfológica em graus crescentes (I, II e III) de malignidade, conforme proposta de Patnaik et al. (1984), säo importantes para efeitos prognósticos e terapêuticos. Foram estudadas 23 amostras de mastocitoma canino, a partir de peças cirúrgicas, necropsias e amostras de tecido/pele provindos de biópsia. Os resultados enquadrados (1 no grau I, 9 no grau II e 13 no grau III) foram discutidos e o escore empregado foi considerado de valor para a rotina de diagnóstico anatomopatológico em veterinária.

Damage induction by direct electric current in tumoural target cells.

Damage induction to tumour target cells (P815) by direct electric current (DC) was investigated. A 6 min treatment of P815 cells with DC generated decreased levels of cell viability and proliferation. The ultrastructural analysis of DC-treated cells revealed the presence of blebs, loss of cell surface filopodia, and ruptures in cell membrane. Mitochondrial alterations, swelling of cells, cytoplasmic matrix rarefaction, and cellular debri formation were also observed. The study shows that tumoural target cells can be damaged by direct electric current and this approach may provide means to understand the mechanism of tumour regression induced by electrochemical therapy.

Effect of cytokines on tumour cell-endothelial interactions.

The adherence of tumour cells to microvascular endothelium is believed to be a necessary step in their migration to sites of metastasis. It has been proposed that this process occurs when cell surface molecules on tumour cells bind to complementary sites on endothelial cells. The expression of these endothelial-derived cell adhesion molecules appears to be modulated by cytokines, a broad class of protein mediators which play important roles in immune and inflammatory reactions. It has been found by ourselves and others that exposure of endothelium to some cytokines augments the adhesion of inflammatory cells as well as tumour cells in in vitro assays. We used a murine model consisting of P815 mastocytoma cells and microvascular endothelium and found that pretreatment of endothelial monolayers with TNF-alpha, IL-1, LPS or PMA augmented the number of tumour cells that attach in a dose-dependent fashion. FACS analysis showed that the change in binding was due to an increase in the expression of VCAM-1 on the surface of the endothelial cell. Methylxanthines (caffeine and theophylline) as well as "classical" calcium-mobilizing agents (ionomycin and thapsigargin) inhibited the expression of VCAM-1 in MME. We also studied the possible mechanisms of TNF-alpha signal transduction in endothelial cells. We examined the involvement of protein kinases in the TNF-alpha effect. Although we found that inhibitors of PKC could inhibit the TNF-alpha effect, our studies suggest that the "classical" PKC pathway is not completely responsible for signaling since TNF-alpha did not cause translocation of PKC to the cell membrane and its effect could not be completely mimicked by PMA. We also studied the effect of TGF-beta on the binding of tumour cells to endothelium. Exposure of endothelium to TGF-beta led to the inhibition of both basal and TNF-alpha enhanced binding of P815 cells. Inhibitors of G-proteins do not abolish TGF-beta action, and PKC and PKA activators elicit an opposite effect. However, TGF-beta-mediated inhibition of both basal binding and TNF-alpha-enhanced P815 binding to endothelium is completely abolished in the presence of the protein phosphatase inhibitor okadaic acid suggesting that TGF-beta elicits its effect by stimulating protein phosphatase activity.

Immunoregulation by processed immunoglobulin on B-cells.

According to Jerne's network hypothesis, the unique amino acid sequences of Ig variable regions, that is, the idiotypic determinants can function in immunoregulatory mechanisms and cellular interactions. Indeed, Id-specific T-cells (mostly CD4+) have since been described, but the nature of Id-positive Ig on B-cells involved in recruiting T-cells is unclear. Studies from our ongoing investigation presented here clearly show that Id can evoke both CD4+ and CD8+ T cells, and exist not only as the integral components of a bona fide antigen-binding receptor Ig but also as distinct molecular entities in processed forms on the cell surface of B-lymphocytes. Using a B-cell hybridoma, 2C3, that expresses anti-hapten (phthalate) antibody receptors on the cell surface, we induced both Id-specific CD4+ and CD8+ T effector cells. The CD4+ T cells were suppressive and mediated generation of Id-loss 2C3 variants, whereas CD8+ T cells were highly cytotoxic and selectively eliminated 2C3 cells both in vitro and in vivo. These effector cells could be induced by cell membrane-associated Ig but not by its soluble form, secreted by 2C3 cells. Antibodies to MHC class I but not class II molecules were inhibitory to this induction. Furthermore, brefeldin A (BFA), an inhibitor of MHC class I mediated processing, blocked induction of CTL but had no effect on the expression of membrane Ig. Moreover, chloroquine, an inhibitor of class II-mediated processing, had no effect. A few reports have recently appeared indicating that an exogenous Ig can be processed by B-cells in the context of MHC class II proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Malignant systemic mastocytosis.

Malignant Systemic Mastocytosis is a very rare condition. Only about less than 40 well documented cases have been reported as per the available literature. The paper presents the case report of a 54 year old male patient who presented with huge hepatosplenomegaly and abdominal lymphadenopathy. Splenectomy specimen was 17 x 16 x 10 cm size with cut surface studded with numerous tiny 1-2 mm nodules. Histologic sections of spleen showed extensive mast cell (typical and atypical) infiltrates. Liver biopsy and abdominal lymphnode biopsy specimens and bone marrow smears also showed similar infiltration by mast cells. Special stains done for non-specific esterase and chloracetate esterase showed strong positivity for mast cells. The results of immunohistochemical and electron microscopic studies are also presented.

Influência do BCG no controle da imunodeficiência humoral induzida pelo mastocitoma P-815 / Influence of BCG in the control of humoral deficiency induced by mastocytoma P-815

O BCG, em soluçäo lipídica, injetado por via intravenosa, foi capaz de reverter a imunosupressäo humoral provocada pelo mastocitoma P-815, em camundongos singênicos DBA/2, aumentando tanto o número de células formadoras de placas hemolíticas quanto os títulos de anticorpos hemaglutinantes do soro. Näo foram encontradas diferenças significativas nos títulos de anticorpos hemaglutinantes da classe IgG. Nenhum efeito bloqueador pôde ser notado na progressäo normal do tumor