Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis.

Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often affected is the skin. Mastocytosis is a relatively rare disorder that affects both sexes equally. It can occur at any age, although it tends to appear in the first decade of life, or later, between the second and fifth decades. Our understanding of the pathophysiology of mastocytosis has improved greatly in recent years, with the discovery that somatic c-kit mutations and aberrant immunophenotypic features have an important role. The clinical manifestations of mastocytosis are diverse, and skin lesions are the key to diagnosis in most patients.

Update on Mastocytosis (Part 2): Categories, Prognosis, and Treatment.

Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in different organs. The organ most often affected is the skin. The World Health Organization classifies cutaneous mastocytosis into mastocytoma, maculopapular cutaneous mastocytosis, and diffuse mastocytosis. The systemic variants in this classification are as follows: indolent systemic mastocytosis (SM), aggressive SM, SM with an associated clonal hematological non-mast cell lineage disease, mast cell leukemia, mast cell sarcoma, and extracutaneous mastocytoma. The two latest systemic variants are rare. Although the course of disease is unpredictable in children, lesions generally resolve by early adulthood. In adults, however, the disease tends to persist. The goal of treatment should be to control clinical manifestations caused by the release of mast cell mediators and, in more aggressive forms of the disease, to reduce mast cell burden.

[Cutaneous mastocytosis: A case report]. / Mastocitosis cutánea: reporte de un caso.

INTRODUCTION: Mastocytosis represents a group of diseases characterised by an excesive accumulation of mastocytes in one or multiple tissues. It can affect only the skin, or have a systemic involvement. It has a low prevalence, and the prognosis is benign in children. OBJECTIVE: To report a case of urticaria pigmentosa as a subtype of cutaneous mastocytosis, and present a literature review focused on clinical findings, diagnosis and initial basic management. CLINICAL CASE: A child of six months of age presenting with multiple blemishes and light brown papules located on the trunk, arms and legs. The symptoms were compatible with urticaria pigmentosa, and was confirmed by biopsy. Tests to rule out systemic involvement were requested. The patient was treated with general measures, education, and antihistamines, with favourable results. CONCLUSIONS: Cutaneous mastocytosis is a rare disease with a good prognosis. In childhood general measures and education are usually enough to obtain favourable results. Histamine H1 antagonists are the first line drug treatment.

Asociaciones infrecuentes de la cutis marmorata telangiectásica congénita: reporte de dos casos / Infrequent associations of cutis marmorata telangiectatica congenita: a two-case report

Introducción: La cutis marmorata telangiectásica congénita (CMTC) es una rara malformación capilar caracterizada por eritema reticular y violáceo persistente. Presentamos dos casos de CMTC. Observación clínica: Un varón de 13 meses presentaba una mácula violácea reticular en glúteo izquierdo y una pápula parduzca con signo de Darier en el maléolo interno del pie izquierdo, que fue biopsiada identificando > 15 mastocitos/campo, con lo cual se diagnosticó de CMTC y mastocitoma cutáneo solitario. El segundo caso, una recién nacida con una lesión característica de CMTC sin otras malformaciones al nacer, que durante el seguimiento desarrolló dos tumoraciones cutáneas compatibles con hemangiomas infantiles. Comentarios. La CMTC es una condición benigna, sin embargo, aproximadamente el 50% de los casos presentan anomalías asociadas. Ante la sospecha de CMTC se deben descartar malformaciones musculoesqueléticas, oftalmológicas y cutáneas. Hasta donde tenemos conocimiento, este es el primer reporte de CMTC asociada con mastocitoma y uno de los pocos con hemangioma infantil.(AU)

Introduction: Cutis marmorata telangiectatica congenita (CMTC) is a rare capillary malformation characterized by persistent reticular and violaceous erythema. We present two cases of CMTC. Clinical observation: The first case involved a 13-month-old male with a reticular violaceous macule on the left gluteal region and a brownish papule with Darier’s sign on the inner malleolus of the left foot, which was biopsied, revealing > 15 mast cells per field, leading to a diagnosis of CMTC and solitary cutaneous mastocytoma. The secondcase involved a newborn with a characteristic CMTC lesion without other malformations at birth, who subsequently developed two cutaneous tumors consistent with infantile hemangiomas during follow-up. Discussion. CMTC is a benign condition. However, approximately 50% of cases exhibit associated anomalies. When CMTC is suspected, musculoskeletal, ophthalmological, and cutaneous malformations should be ruled out. To the best of our knowledge, this is the first report of CMTC associated with mastocytoma and one of the few cases associated with infantile hemangioma.(AU)

Mastocitosis crónica. Presentación de un caso y revisión de la literatura

La mastocitosis cutánea crónica es una genodermatosis de etiología desconocida y que se encuentra dentro del grupo de enfermedades raras o poco frecuentes. Se caracterizan por el crecimiento y acumulación de causa desconocida de mastocitos en piel y otros órganos y se manifiesta como una urticaria pigmentosa. Se presenta el caso de un paciente de sexo masculino, con lesiones eritematopapulosas en región de las manos que fue extendiéndose a todo el cuerpo y cuero cabelludo que al desaparecer quedaban manchas hipercrómicas con signo de Darier positivo. Se confirmó el diagnóstico de urticaria pigmentosa mediante biopsia de la piel. Es una enfermedad rara con una baja incidencia, la forma cutánea tiene un pronóstico favorable, por lo que resulta de vital importancia conocer y diagnosticar de forma precoz esta entidad con un manejo multidisciplinario para prevenir las manifestaciones sistémicas que aparecen. Llevar un tratamiento sintomático permitirá una mejor calidad de vida en los infantes. Se presenta el caso porque al considerarse la mastocitosis una enfermedad rara la prevalencia e incidencia de estos casos es muy baja.

Chronic cutaneous mastocytosis is a genodermatosis of unknown etiology and that is within the group of rare or infrequent diseases. They are characterized by the growth and accumulation of mast cells in the skin and other organs of unknown cause and manifest as urticaria pigmentosa. The case of a male patient is presented, with erythematopapular lesions in the region of the hands that spread to the entire body and scalp that, when they disappeared, left hyperchromic spots with Darier's sign: positive. The diagnosis of urticaria pigmentosa was confirmed by skin biopsy. It is a rare disease with a low incidence, the cutaneous form has a favorable prognosis, so it is of vital importance to know and diagnose this entity early with a multidisciplinary management to prevent the systemic manifestations that appear. Taking a symptomatic treatment will allow a better quality of life in infants. The case is presented because mastocytosis is considered a rare disease, the prevalence and incidence of these cases is very low.

The value of molecular expression of KIT and KIT ligand analysed using real-time polymerase chain reaction and immunohistochemistry as a prognostic indicator for canine cutaneous mast cell tumours.

This study investigated the correlation between KIT gene expression determined by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) and the rate of tumour recurrence and tumour-related deaths in dogs affected with mast cell tumour (MCT). Kaplan-Meier curves were constructed to compare tumour recurrence and tumour-related death between patients. The log-rank test was used to check for significant differences between curves. KIT-I, KIT-II and KIT-III staining patterns were observed in 9 (11.11%), 50 (61.73%) and 22 (27.16%) tumours, respectively. Tumour recurrence rates and tumour-related deaths were not associated with KIT staining patterns (P = 0278, P > 0.05), KIT (P = 0.289, P > 0.05) or KIT ligand (P = 0.106, P > 0.05) gene expression. Despite the lack of association between KIT staining pattern and patient survival time, the results suggest a correlation between aberrant KIT localization and increased proliferative activity of MCTs. RT-PCR seems to be a sensible method for quantitative detection of KIT gene expression in canine MCT, although expressions levels are not correlated with prognosis.

Mastocitoma solitario ampollar / Solitary Blister Mastocytoma

La mastocitosis comprende un conjunto de desórdenes con expansión anormal y acumulación de mastocitos en diversos órganos incluida la piel, en la cual se describen distintas formas clínicas de presentación. El mastocitoma cutáneo solitario constituye el 10-15% de todas las mastocitosis. Presentamos el caso de un niño con mastocitoma cutáneo solitario ampollar, un cuadro infrecuente cuyo diagnóstico oportuno constituye un reto para pediatras y dermatólogos (AU)

Mastocytosis comprises a set of disorders with abnormal expansion and accumulation of mast cells in various organs including the skin, wich describes different form of clinical presentation. The solitary cutaneous mastocytoma constitutes 10-15 % of all mastocytosis. We present the case of a child with solitary blistering mastocytoma, an infrequent condition whose, timely diagnosis constitutes a challenge for pediatricians and dermatologists (AU)

Mastocitosis solitaria en pediatría. Presentación de un caso y revisión de la literatura / Solitary Mastocytoma in Pediatrics. Case Report and Literature Review

RESUMEN El mastocitoma es una genodermatosis de etiología desconocida, por lo que se incluye en el grupo de enfermedades raras o pocos frecuentes; aparece generalmente en la infancia o al momento de nacer. Se caracteriza por acumulación local o sistémica de células cebadas, lo que origina la aparición de lesiones cutáneas persistentes, pigmentadas y muy pruriginosas con compromiso exclusivo de la piel, se presenta generalmente como una lesión única en el cuello, el tronco, los brazos y las piernas. Las características típicas son las de un nódulo color marrón rojizo o amarillento, de consistencia gomosa, la superficie con aspecto de piel de naranja y signo de Darier. Se presenta el caso de un lactante de 4 meses de edad con un diagnóstico de mastocitoma solitario con signo de Darier. Se realiza este reporte por la baja frecuencia de esta patología en el Hospital Pediátrico Universitario Paquito González Cueto de Cienfuegos. Actualmente el paciente se mantiene con seguimiento por consulta de dermatología, con tratamiento antihistamínico y estabilizador de mastocitos.

ABSTRACT The mastocytoma is a genodermatosis of unknown etiology, so it is included in the group of rare or uncommon diseases; it usually appears in childhood or at birth. It is characterized by local or systemic accumulation of primed cells, which causes the appearance of persistent, pigmented and very itchy skin lesions with exclusive skin involvement, usually presents as a single lesion in the neck, trunk, arms and legs. Typical features are that of a reddish-brown or yellowish brown nodule, of gummy consistency, the surface looks like orange peel, and Darier's sign. The case of a 4-month-old infant with a diagnosis of solitary mastocytoma with Darier's sign is presented. This report is made due to the low frequency of this disease at the Paquito González Cueto de Cienfuegos University Pediatric Hospital. Currently the patient is monitored by dermatology specialists, with antihistamine treatment and mast cell stabilizer.

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.

Use of different fixation times and application of two immunohistochemical methods for detection of KIT and Ki67 proteins in canine cutaneous mast cell tumors / Utilização de diferentes tempos de fixação e métodos imuno-histoquímicos na detecção das proteínas KIT e Ki67 em mastocitomas cutâneos caninos

Due to the high prevalence of mast cell tumors (MCTs) in the diagnostic routine, several factors, especially prognostic, have been sought to determine the biological behavior of these neoplasms. Immunohistochemistry (IHC) is one of the main tools utilized to biologically differentiate more aggressive tumors from less aggressive ones. However, some immunostainings are influenced by formalin fixation, interfering with the results. This is both a retrospective and prospective study of MCTs diagnosed in laboratory routine. A total of 25 samples, without knowledge about fixation time, were analyzed in the retrospective study, whereas 12 samples, with known fixation times, were assessed in the prospective study. Two histologic grading systems (Patnaik and Kiupel), special staining of toluidine blue, and IHC for KIT and Ki67 proteins were applied in both studies. Additionally, two amplification systems (biotinylated and non-biotinylated) for Ki67 protein and counting of the argyrophilic nucleolar organizing regions (AgNOR method) were tested in the prospective study. In the retrospective study, greater agreement between the evaluating pathologists was observed when the Kiupel system was used. IHC staining for KIT protein was effective in both studies, regardless of fixation time. IHC staining for Ki67 protein was highly sensitive to formaldehyde, and staining failure was observed in 56% of the cases in the retrospective study. In the prospective study, samples fixed for longer than 24 hours showed a reduction in the number of stained cells (altering the determination of the cell growth fraction) or showed absence of IHC staining in both amplification systems. The use of the AgNOR method to evaluate the rate of cell proliferation may be an alternative when the fixation time of the neoplasm is unknown or longer than 24 hours.(AU)

Devido a alta prevalência dos mastocitomas cutâneos caninos (MCCs) na rotina diagnóstica, vários fatores, especialmente fatores prognósticos, têm sido buscados para auxiliar na determinação do comportamento biológico desse neoplasma. A imuno-histoquímica é uma das principais ferramentas empregadas para diferenciar tumores biologicamente mais agressivos de tumores menos agressivos. Entretanto, algumas imunomarcações sofrem influência pela fixação em formol, interferindo nos resultados. Este estudo compreendeu avaliar através de uma etapa retrospectiva e uma etapa prospectiva casos de MCCs diagnosticados na rotina laboratorial. Um total de 25 amostras, sem conhecimento do tempo de fixação, foi analisado no estudo retrospectivo e 12 amostras, com tempos de fixação conhecidos, no estudo prospectivo. Foram aplicados nos dois estudos, dois sistemas de graduação histológica (Patnaik e Kiupel), a coloração especial de azul de toluidina e a imuno-histoquímica para as proteínas KIT e Ki67. Adicionalmente, no estudo prospectivo, foram testados dois sistemas de amplificação (biotinilado e não biotinilado) para a proteína Ki67 e a técnica de AgNOR (contagem das regiões organizadoras nucleolares argirofílicas). Na etapa retrospectiva, observou-se uma maior concordância entre os patologistas avaliadores quando o sistema Kiupel foi utilizado. A imunomarcação para KIT se manteve eficaz em ambos os estudos, independentemente do tempo de fixação. A imunomarcação para o Ki67 mostrou-se altamente sensível ao tempo de fixação em formol, sendo observada falha na imunomarcação em 56% dos casos do estudo retrospectivo. No estudo prospectivo, constatou-se que amostras fixadas por mais de 24 horas em formol apresentaram redução na quantidade de células imunomarcadas (alterando a determinação da fração de crescimento celular) ou apresentaram ausência de imunomarcação em ambos os sistemas de amplificação. A utilização do método AgNOR, para avaliar a taxa de proliferação celular, pode ser uma alternativa quando o tempo de fixação do neoplasma for desconhecido ou superior a 24 horas.(AU)

Mastocitoma cutâneo canino: estudo retrospectivo dos casos atendidos pelo Serviço de Oncologia do Hospital Veterinário da FCAV-Unesp, Campus Jaboticabal, de 2005 a 2015 / Canine cutaneous mast cell tumors: retrospective study of cases attended by the oncology service at the Veterinary Hospital of FCAV-Unesp, Jaboticabal, from 2005 to 2015

Este estudo teve como objetivo analisar os casos de mastocitomas cutâneos em cães atendidos no Hospital Veterinário Governador Laudo Natel da Faculdade de Ciências Agrárias e Veterinárias (FCAV) Unesp Câmpus Jaboticabal, no período de 2005 a 2015, além de avaliar a ocorrência dessa neoplasia em relação à raça, sexo e idade; determinar as regiões corpóreas mais acometidas e as características neoplásicas observadas, assim como, os métodos de diagnóstico mais utilizados no setor, estabelecer os principais graus histológicos diagnosticados e os tratamentos preconizados, verificar alterações de tamanho em relação aos linfonodos, à taxa de recidiva, metástase e possíveis associações entre as variáveis consideradas. Foram avaliados 192 prontuários clínicos de pacientes e observou-se que os cães sem raça definida (SRD) (n=46, 23,96%) foram os mais acometidos, seguidos por cães da raça Boxer (n=40, 20,83%) e Pit bull (n=27, 14,06%). A maioria dos cães eram fêmeas (n=107, 55,7%), e com idade de 7 a 11 anos (n=120, 62,5%). Do total, 32 pacientes apresentaram (16,7%) tumores localizados em membro pélvico, seguidos por nódulos em membro torácico (10,4%, n=20). Sessenta e cinco animais possuíam nódulos ulcerados (33,9%), sendo 96 nódulos de consistência firme (50%). Setenta e seis animais apresentavam múltiplos nódulos (39,6%) e aqueles acima de três centímetros perfaziam 39,1% da amostra (n=75). O método mais utilizado para o diagnóstico foi a punção aspirativa por agulha fina associado à histopatologia (HT), totalizando 39,8% dos nódulos (n=66), seguido pela HT com 37,3% (n=62). Em relação às variáveis histológicas, 18 pacientes apresentaram grau I (11,8%), 112 com grau II (73,7%) e 22 com grau III (14,5%) de acordo com Patnaik et al. (1984). Segundo a classificação de Kiupel et al. (2011), 37 casos foram classificados como de alto grau (35,2%) e 68 como sendo de baixo grau (64,8%). Foi observada associação estatística quando se avaliou a presença de nódulos solitários/múltiplos e o grau histológico, segundo Patnaik et al. (1984) (p=0,008) e Kiupel et al. (2011) (p=0,004), sendo que nódulos com piores características prognósticas eram mais frequentes nos animais diagnosticados com múltiplos nódulos, independente da classificação histológica empregada. Também foi observada a associação entre a presença de nódulos múltiplos com estadio II ou IV (p<0,001) e com a presença de recidiva (p=0,001). Em relação à classificação histológica de Kiupel et al. (2011) foi possível observar associação estatística entre o grau histológico e o tamanho do tumor (p=0,001), a consistência (p=0,028) e a velocidade de crescimento do nódulo (p<0,001); aumento de linfonodo (p<0,001) e o tratamento empregado (p=0,002). Nódulos com tamanho superior a três centímetros (56,8%, n=21) e de crescimento rápido (52,9%, n=36%), eram mais frequentes nos tumores de alto grau. Aumento de linfonodo (80,6%, n=25) e tratamento quimioterápico (83,3%, n=5) também estavam associados a pacientes com alto grau histológico. Em relação à classificação de Patnaik et al. (1984), as variáveis raça e sexo diferiram proporcionalmente entre os grupos histológicos (p=0,008 e 0,040 respectivamente), sendo que o aumento do linfonodo e o crescimento rápido do tumor também tiveram associação com o grau histológico (p=0,002 e 0,001). Quase a metade dos pacientes (47,4%) foi submetidas ao tratamento cirúrgico e quimioterápico (n=91), sendo que em 31,3% (n=60) dos pacientes realizou-se apenas o procedimento cirúrgico. Sessenta e um animais (31,8%) apresentaram aumento de tamanho em linfonodos regionais (31,8%), sendo que 71,9% dos nódulos avaliados tiveram crescimento rápido. O tempo de evolução clínica do tumor foi menor ou igual a um ano, em 158 pacientes (82,3%), seguido por 25 pacientes (13%) com evolução de 1 a 2 anos. Foram observados 66 casos (40,5%) de recidiva e 16 (8,3%) de metástase à distância. Com este estudo, pode-se concluir que cães sem raça definida são os mais acometidos pelo mastocitoma cutâneo, na região de Jaboticabal, seguido por cães da raça Boxer, com idade variando entre 7 e 11 anos, não sendo observada predileção sexual; os nódulos encontrados eram predominantemente não ulcerados, solitários e menores que três centímetros; a maioria dos pacientes apresentou mastocitoma grau II, segundo Patnaik et al. (1984) e baixo grau segundo Kiupel et al. (2011); não se observou recidiva, em sua maioria, nem metástase em linfonodos e/ou a distância; o diagnóstico mais utilizado foi a punção aspirativa por agulha fina associada à histopatologia; a localização dos nódulos era mais prevalente nos membros pélvicos e torácicos, seguido por cabeça e pescoço. A consistência dos nódulos era de apresentação firme ou macia; e a metade dos pacientes foi submetida ao procedimento cirúrgico associado à quimioterapia antineoplásica.(AU)

This study analyzed the cases of cutaneous mastocytomas in dogs seen at the Governador Laudo Natel Veterinary Hospital of the College of Agrarian and Veterinary Sciences (FCAV), Unesp, in Jaboticabal, from 2005 to 2015. The objective was to determine the occurrence of this neoplasm regarding breed, sex, and age, the most affected body parts and observed neoplastic characteristics; the most widely used diagnosis methods, the main histological grades and recommended treatments, to evaluate size changes in relation to lymph nodes, recurrence rate, metastasis and to verify possible associations between the evaluated variables. The clinical files of 192 patients were evaluated. The most affected dogs were of mixed breed (n=46, 23.96%), followed by Boxer (n=40, 20.83%) and Pitbull (n=27, 14.06%). Most of the dogs were females (n=107, 55.7%), aged between 7 and 11 years old (n=120, 62.5%). Thirty-two patients had (16.7%) tumors located in the pelvic limb, followed by thoracic limbs (10.4% n=20). Sixty-five animals had ulcerated nodules (33.9%), of which 96 had firm consistency (50%). Seventy-six animals had multiple nodules (39.6%), and 39.1% of the sample (n=75) had nodules larger than three centimeters. The most used diagnosis method was fine needle aspiration together with histopathology (HT), totaling 39.8% of nodules (n=66), followed by HT in 37.3% of the patients (n=62). Regarding the histological variables, 18 patients had grade I (11.8%), 112 grade II (73.7%), and 22 grade III (14.5%) classified according to Patnaik et al. (1984). According to the classification of Kiupel et al. (2011) 37 cases were classified as high grade (35.2%) and 68 as low grade (64.8%). Statistical association was observed when the presence of solitary/multiple nodules and the histological grade were evaluated according to Patnaik et al. (1984) (P=0.008) and Kiupel et al. (2011) (P=0.004). The nodules with worse prognostic feature were more frequent in animals diagnosed with multiple nodules, regardless of the histological classification used. The presence of multiple nodules in stage II or IV (p<0.001) and recurrence of the disease (p=0.001) was also observed. Regarding the histological classification of Kiupel et al. (2011), there was a statistical association between histological grade and tumor size (p=0.001), consistency (p=0.028) and nodule growth rate (p<0.001), lymph node enlargement (p<0.001) and the treatment used (p=0.002). Nodules larger than three centimeters (56.8% n=21) and fast growing (52.9% n=36%) were more frequent in high-grade tumors. Lymph node enlargement (80.6% n=25) and chemotherapeutic treatment (83.3% n=5) were also associated with patients with this histological grade. According to the classification of Patnaik et al. (1984), breed and sex differed proportionally between the histological groups (p=0.008 and 0.040 respectively), and lymph node enlargement and rapid tumor growth were also associated with histological grade (p=0.002 and 0.001). Almost half of the patients (47.4%) underwent surgical and chemotherapeutic treatment (n=91) while only surgical procedure was performed in 31.3% (n=60) of the patients. Sixty-one animals (31.8%) had enlarged regional lymph nodes (31.8%), and 71.9% of the nodes evaluated had rapid growth. The clinical evolution time of the tumor was less than or equal to one year in 158 patients (82.3%), followed by 1 to 2 years in 25 patients (13%). There were 66 cases (40.5%) of recurrence and 16 (8.3%) of distant metastasis. With this study, it can be concluded that dogs with mixed breed are the most affected by cutaneous mastocytoma in Jaboticabal city, followed by Boxer dogs, with ages varying between 7 and 11 years, with no sexual predisposition observed. It was also concluded that nodules were predominantly non-ulcerated, solitary and smaller than 3 centimeters, that the majority of patients presented grade II mastocytoma according to Patnaik et al. (1984) and low grade according to Kiupel et al. (2011), not being observed in most of them recurrence, lymph node or distance metastasis. The most commonly used diagnosis was fine-needle aspiration associated with histopathology, and in relation to location, nodules were found predominantly in pelvic and thoracic limbs, followed by head and neck. The consistency of the nodules was both firm and soft, and half of the patients underwent the associated surgical procedure of antineoplastic chemotherapy.(AU)

Ancillary techniques on the evaluation of canine cutaneous mast cell tumors from Brazil / Técnicas auxiliares avaliação de mastocitomas cutâneos caninos do Brasil

ABSTRACT: The use of histologic classification by a 2-tier grading system only, immunohistochemistry (IHC) for KIT and Ki-67 and polymerase chain reaction (PCR) for internal tandem duplications (ITD) on exon 11 has improved the prognostication of canine cutaneous mast cell tumors (CCMTs) particularly in the United States. However, these techniques are not commonly used in most Brazilian laboratories. Likewise, no studies, to date, have investigated the occurrence of ITD in CCMTs from the country. Thus, this study tested the 2-tier grading system, the immunohistochemistry for KIT and Ki-67 and the PCR for exon 11 in a group of Brazilian CCMTs with the goal of investigating the applicability of these tests in a Brazilian laboratory. Of the 39 CCMTs, 69.2% (27/39) were identified as low-grade and 30.8% (12/39) as high-grade by a 2-tier grading system. All tumors had a KIT expression pattern II, and 30.6% (11/36) had a high growth fraction (Ki-67). PCR amplification was successful in four of the 11 tumors examined. Two of these (50%) were positive for ITD. This study highlights the importance of using auxiliary techniques in the CCMT evaluation, identifies limitations and confirms the applicability of these methods on a routine diagnostic basis in Brazil. Our results will help to improve the prognostication of CCMTs in Brazilian diagnostic laboratories, encouraging the use of supplementary methods.

RESUMO: O uso de classificação histológica por um novo sistema de graduação que utiliza apenas duas categorias, imuno-histoquímica (IHQ) para KIT e Ki-67 e reação de polimerase em cadeia (PCR) para mutações (duplicações internas) no éxon 11 tem melhorado a avaliação do prognóstico de mastocitomas cutâneos caninos (MCCs), particularmente nos Estados Unidos. No entanto, essas técnicas são ainda pouco utilizadas em laboratórios brasileiros e, até então, nenhum estudo investigou a prevalência de duplicações internas (DIs) em MCCs do país. Este estudo testou o novo sistema de graduação histológica de duas categorias, a imuno-histoquímica para KIT e Ki-67 e o PCR para exon 11 em um grupo de MCCs brasileiros, com o objetivo de investigar a aplicabilidade desses métodos em um laboratório brasileiro. De 39 MCCs, 69,2% foram identificados como sendo de baixo grau e 30,8% como de alto grau. Todos tiveram um padrão II de expressão de KIT, e 30,6% (11/36) tiveram uma alta contagem para Ki-67. A amplificação foi bem-sucedida em quatro dos 11 tumores examinados. Dois destes (50%) foram positivos para DIs. Este estudo ressaltou a importância do uso de técnicas auxiliares na avaliação de MCCs, identificou limitações e confirmou a aplicabilidade desses métodos em uma rotina de diagnósticos no Brasil. Esses resultados irão auxiliar na melhor avaliação prognóstica dos MCCs em laboratórios brasileiros, encorajando o uso de métodos suplementares neste processo.

Mastocitosis cutánea: reporte de un caso / Cutaneous mastocytosis: A case report

Introducción La mastocitosis representa un grupo de enfermedades caracterizadas por una acumulación excesiva de mastocitos en uno o múltiples tejidos. Puede limitarse a la piel o tener un compromiso sistémico, siendo de baja prevalencia y pronóstico benigno en la infancia. Objetivo Reportar un caso de urticaria pigmentosa como subtipo de mastocitosis cutánea y hacer una revisión bibliográfica enfocada en los hallazgos clínicos, el diagnóstico y el manejo inicial básico. Caso clínico Lactante de 6 meses de edad con múltiples máculas y pápulas de color café claro localizadas en el tronco, los brazos y las piernas, cuadro compatible con una urticaria pigmentosa, confirmada mediante biopsia. Se solicitaron exámenes para descartar compromiso sistémico. La paciente fue tratada con medidas generales, educación y antihistamínicos, con excelente evolución. Conclusiones La mastocitosis cutánea es una enfermedad poco común, de buen pronóstico. En la infancia generalmente bastan las medidas generales y educación para obtener resultados favorables. La terapia farmacológica de primera línea son los antagonistas H1.

Introduction Mastocytosis represents a group of diseases characterised by an excesive accumulation of mastocytes in one or multiple tissues. It can affect only the skin, or have a systemic involvement. It has a low prevalence, and the prognosis is benign in children. Objective To report a case of urticaria pigmentosa as a subtype of cutaneous mastocytosis, and present a literature review focused on clinical findings, diagnosis and initial basic management. Clinical case A child of six months of age presenting with multiple blemishes and light brown papules located on the trunk, arms and legs. The symptoms were compatible with urticaria pigmentosa, and was confirmed by biopsy. Tests to rule out systemic involvement were requested. The patient was treated with general measures, education, and antihistamines, with favourable results. Conclusions Cutaneous mastocytosis is a rare disease with a good prognosis. In childhood general measures and education are usually enough to obtain favourable results. Histamine H1 antagonists are the first line drug treatment.

Mastocitoma cutáneo solitario: A propósito de un caso / Solitary cutaneous mastocytosis: A case report

Se presenta una niña de 16 meses de edad, con una lesión de catorce meses de evolución que consistía en una única placa eritematosa, en forma de L, bien delimitada, localizada en la parte superior de la espalda. El signo de Darier fue positivo. La histopatología mostró edema intersticial y en la tinción con Giemsa, se observaron mastocitos. Se realizó el diagnóstico de un mastocitoma solitario. El mastocitoma solitario es una lesión tumoral benigna, que representa aproximadamente el 15% de la mastocitosis cutánea.

We report a 16 month years old female, with a 14 months history of a single erythematous, L shaped well-delimited plaque located on her upper back. Darier sign was positive. Histopathology revealed interstitial edema. The Giemsa staining showed mast cells. The diagnosis of a solitary mastocytoma was performed. Solitary mastocytoma is a benign tumoral lesion, that represents approximately 15% of cutaneous mastocytosis.

Mastocitoma cutáneo solitario: A propósito de un caso / Solitary cutaneous mastocytosis: A case report

Se presenta una niña de 16 meses de edad, con una lesión de catorce meses de evolución que consistía en una única placa eritematosa, en forma de L, bien delimitada, localizada en la parte superior de la espalda. El signo de Darier fue positivo. La histopatología mostró edema intersticial y en la tinción con Giemsa, se observaron mastocitos. Se realizó el diagnóstico de un mastocitoma solitario. El mastocitoma solitario es una lesión tumoral benigna, que representa aproximadamente el 15% de la mastocitosis cutánea.(AU)

We report a 16 month years old female, with a 14 months history of a single erythematous, L shaped well-delimited plaque located on her upper back. Darier sign was positive. Histopathology revealed interstitial edema. The Giemsa staining showed mast cells. The diagnosis of a solitary mastocytoma was performed. Solitary mastocytoma is a benign tumoral lesion, that represents approximately 15% of cutaneous mastocytosis.(AU)

Frequência de neoplasias cutâneas em cães atendidos no hospital veterinário da Universidade Federal de Uberlândia durante os anos 2000 a 2010 / Frequency of skin cancer in dogs treated at the Federal University of Uberlândia veterinary hospital from 2000 to 2010

Foram analisados os arquivos do laboratório de Patologia Animal do Hospital Veterinário da UFU de janeiro de 2000 a dezembro de 2010, selecionando protocolos referentes a biopsias cutâneas de cães coletando-se as seguintes informações: diagnóstico morfológico, localização anatômica, idade, sexo e raça dos cães, com o objetivo de realizar um estudo epidemiológico. Foram diagnosticados 549 tumores cutâneos em 543 cães, sendo que 281 cães eram machos e 247 fêmeas. Cães adultos e idosos foram os mais acometidos, assim como os cães sem raça definida, Poodle, Boxer, Pit Bull e Dashchund. Os tumores malignos prevaleceram com 65,39% dos casos, sendo os de origem epitelial os mais frequentes. O carcinoma de células escamosas foi a neoplasia predominante, seguido pelo mastocitoma e histiocitoma. Com relação á localização anatômica prevaleceu as regiões do abdômen (19,49%), cabeça (16,40%) e membros (15,30%). Não houve diferença na probabilidade de apresentar tumor cutâneo com relação ao sexo, porém considerando-se os tipos de tumores há maior probabilidade da população canina apresentar carcinoma de células escamosas e mastocitomas em detrimento dos outros tipos de tumores cutâneos.

We analyzed the archives of the Animal Pathology Laboratory of the Federal University of Uberlândia Veterinary Hospital from 2000 to 2010 with the aim of conducting an epidemiological study. Protocols for skin biopsies of dogs were selected and the following information was collected: morphological diagnosis, anatomical location, age, gender, and breed. Five hundred forty-nine skin tumors were diagnosed in 543 dogs, of which 281 were males and 247 were females. Adult and older dogs were the most affected, and mongrel dogs, Poodles, Boxers, Pit Bulls, and Dashchunds were the most frequent breeds. Malignant tumors were present in 65.39% dogs, and most tumors were derived from epithelial cells. Squamous cell carcinoma was the predominant neoplasia, followed by mast cell tumors and histiocytoma. With respect to the anatomic location, the abdomen (19.49%), head (16.40%), and limbs (15.30%) were the most frequently affected. Gender did not influence the probability of having a cutaneous tumor. With regard to tumor type, the canine population was more susceptible to squamous and mast cell tumors than to other skin tumors.

Análise de sobrevida e fatores prognósticos de cães com mastocitoma cutâneo / Survival analyses and prognostic markers in canine cutaneous mast cell tumors

O mastocitoma é a neoplasia cutânea maligna de maior frequência em cães. Apesar do estudo e do desenvolvimento de diversos marcadores prognósticos na tentativa de prever o comportamento biológico deste tipo de neoplasia, a graduação histológica continua sendo utilizada como principal delineador prognóstico para os animais acometidos, mesmo não conseguindo prever o comportamento de mastocitomas de diferenciação intermediária. Diferentes marcadores de proliferação e atividade celular vêm sendo testados com resultados promissores, entretanto, em sua maioria, demandam técnicas específicas de coloração e imuno-histoquímica que, ainda hoje, são de alto custo e muitas vezes não estão facilmente disponíveis. O índice mitótico é um método indireto de mensuração da atividade proliferativa celular, que pode ser contabilizado em uma lâmina comum de avaliação histológica e estudos vêm determinando-o como importante marcador prognóstico para o mastocitoma canino. Dada a recente publicação sugerindo nova graduação em dois graus (alto e baixo) e indisponibilidade das técnicas específicas utilizadas na determinação de outros fatores prognósticos, objetivou-se avaliar o poder prognóstico das diferentes classificações, associando-as à sobrevida destes animais e comparando com o índice mitótico. Apesar de isoladamente ambas as classificações histológicas apresentarem associação com a sobrevida (P<.001) dos animais acometidos, na análise multifatorial nenhuma foi significativamente associada com a sobrevida (P>0,05)...

Mast cell tumor (MCT) is the most common malignant cutaneous neoplasm in dogs. Even with several prognostic markers being studied, in attempt to previse the biological behavior of these tumors, the histological grading is still commonly used to predict behavior, however, it is not significant to predict intermediately differentiated MCT behavior. Different prognostic and cell proliferation markers are being tested with promising results however, the majority of then requires specific staining and immunohistochemical techniques that even nowadays are expensive and not suitable for all veterinarians. Mitotic index is an indirect measure of cell proliferation and it can be established in a common histological microscope slide, and studies indicate it as an important prognostic marker for MCT in dogs. Given the recent publication of the novel two-tier histologic grading system, this study objective to evaluate the prognostic value of the different grading systems associating with survival and compare it with the mitotic index. Even though both grading systems associate with survival in the univariable analyses (P<.001), at the multivariable analyses neither was associated with survival (P>0,05)...

Mastocitoma solitario: a propósito de un caso / Solitary mastocytoma: a propos of a case

El mastocitoma solitario es la segunda en frecuencia, de las variantes de las mastocitosis, caracterizada por una proliferación de los mastocitos tisulares que afecta únicamente a la piel, comúnmente congénita o de aparición en las primeras semanas de vida, con etiología aún desconocida y buen pronóstico, ya que tiene una resolución espontánea en la adolescencia. Presentamos el caso de un paciente quien desde su nacimiento, presentaba una placa en antebrazo derecho, con signo de Darier negativo y asintomatomática. Con los datos clínicos y los antecedentes personales se realiza biopsia de piel, mediante la que confirmamos el diagnóstico de mastocitoma solitario.

Solitary mastocytoma is the second most frequent disease within mastocytosis. It is characterized by a hyperplasia of the mastocitos tissue that affects only the skin. It is usually congenital though it can also appear in the first weeks of life, with unknown etiology; it has a good prognosis due to its spontaneous resolution in the adolescence. This paper presents case of a patient who, from birth, has had some plaque in his right forearm, with negative and asymptomatic Darier's sign. The skin biopsy has been performed with clinical data and personal history, thus confirming the diagnosis of solitary mastocytoma.

Mastocitoma solitario: a propósito de un caso / Solitary mastocytoma: a propos of a case

El mastocitoma solitario es la segunda en frecuencia, de las variantes de las mastocitosis, caracterizada por una proliferación de los mastocitos tisulares que afecta únicamente a la piel, comúnmente congénita o de aparición en las primeras semanas de vida, con etiología aún desconocida y buen pronóstico, ya que tiene una resolución espontánea en la adolescencia. Presentamos el caso de un paciente quien desde su nacimiento, presentaba una placa en antebrazo derecho, con signo de Darier negativo y asintomatomática. Con los datos clínicos y los antecedentes personales se realiza biopsia de piel, mediante la que confirmamos el diagnóstico de mastocitoma solitario.(AU)

Solitary mastocytoma is the second most frequent disease within mastocytosis. It is characterized by a hyperplasia of the mastocitos tissue that affects only the skin. It is usually congenital though it can also appear in the first weeks of life, with unknown etiology; it has a good prognosis due to its spontaneous resolution in the adolescence. This paper presents case of a patient who, from birth, has had some plaque in his right forearm, with negative and asymptomatic Dariers sign. The skin biopsy has been performed with clinical data and personal history, thus confirming the diagnosis of solitary mastocytoma.(AU)