Bone marrow bi-hypoplasia in a dog with a sertoli cell tumor / Hipoplasia dupla de medula óssea em um cão com tumor de células de sertoli

A 20-year-old unneutered male poodle presented prostration, apathy, staggering gait, lack of appetite and tick infestation. The dog was diagnosed with a Sertoli cell tumor in an undescended testicle by cytological, histopathological and immunohistochemical tests. Pancytopenia with moderate nonregenerative anemia, leukopenia and severe thrombocytopenia were detected in the complete blood count. Cytological and histopathological evaluation of the bone marrow revealed a cellularity of 30%, with erythroid (59%), lymphoid (40%) and mast cells (1%), and an absence of granulocytic, monocytic and megakaryocytic lineage cells. In post-mortem examinations, changes related to hemostatic disorders were found. The absence of microorganisms in molecular tests and an estrogen serum concentration over reference values confirmed hyperestrogenism as a possible cause of pancytopenia. The literature describes a Sertoli cell tumor hyperestrogenism that induced pancytopenia, along with bone marrow hypoplasia of all hematopoietic lineages. In contrast, in the present case, the erythroid precursor cells were preserved in the bone marrow, although there were no reticulocytes circulating in the blood. This case, therefore, should be considered in future investigations of pancytopenia induced by Sertoli cell tumor hyperestrogenism.(AU)

Um cão Poodle, macho, de 20 anos, não castrado, apresentou prostração, apatia, andar cambaleante, falta de apetite e infestação por carrapatos. Nesse animal, foi diagnosticado tumor de células de Sertoli em um testículo não descendente, utilizando-se citologia, histopatologia e imuno-histoquímica. Pancitopenia com anemia moderada não regenerativa, leucopenia e trombocitopenia intensas foram detectadas no hemograma. Na avaliação citológica e histopatológica da medula óssea, havia celularidade de 30%, constituída pelas linhagens eritroide (59%) e linfoide (40%) e por mastócitos (1%), com ausência de células das linhagens granulocítica, monocítica e megacariocítica. Em exames post mortem, mudanças relacionadas à hemostasia foram encontradas. A ausência de micro-organismos nos testes moleculares e a concentração sérica de estrogênio acima dos valores de referência confirmaram hiperestrogenismo como a possível causa da pancitopenia. A literatura descreve hiperestrogenismo em tumores de células de Sertoli induzindo pancitopenia associada com hipoplasia da medula óssea de todas as linhagens hematopoiéticas. Em contraste, no presente caso, as células precursoras eritróides estavam preservadas na medula óssea, embora não houvesse reticulócitos no sangue. Assim, o relato apresentado deve ser considerado em futuras investigações de pancitopenia induzida por hiperestrogenismo em tumor de células de Sertoli.(AU)

Glycogen-rich clear cell carcinoma of the feline mammary gland: case report / Carcinoma de células claras rico em glicogênio da glândula mamária felina: relato de caso

The aim of this report is to describe the first histopathological, immunohistochemical, and clinical characteristics of a feline glycogen-rich clear cell carcinoma (GRCCC). A Persian queen was admitted with mammary gland tumors and underwent radical unilateral mastectomy. Overall survival was considered 33 days and death was due to clinical evolution of the disease. Microscopic evaluation demonstrated epithelial cells arranged in a predominantly solid pattern, tumor cells presented an ample, granular, and foamy clear cytoplasm, and moderate cellular pleomorfism. The presence of cytoplasmatic glycogen was confirmed through diastase digestion followed by PAS staining. Histopathological and histochemical findings lead to the diagnosis of GRCCC with regional metastases.(AU)

O objetivo deste relato de caso é descrever as características clínicas, histopatológicas e imuno-histoquímicas do primeiro carcinoma mamário de células claras rico em glicogênio em felino. Uma gata persa foi atendida com tumores na glândula mamária e foi submetida à mastectomia radical unilateral. A sobrevida livre de doença foi considerada 33 dias, e o óbito foi devido à evolução da doença. A avaliação microscópica demonstrou células epiteliais arranjadas em um padrão predominantemente sólido, as células tumorais apresentaram um citoplasma claro, amplo, granular e espumoso e pleomorfismo celular moderado. A presença do glicogênio citoplasmático foi confirmada pela digestão pela diástase, seguida da coloração de PAS. Achados histopatológicos e histoquímicos levaram ao diagnóstico de carcinoma de células claras rico em glicogênio felino com metástase regional.(AU)

HER-2, EGFR, Cox-2 and Ki67 expression in lymph node metastasis of canine mammary carcinomas: Association with clinical-pathological parameters and overall survival.

Studies about canine mammary tumors based on single molecular markers probably cannot accurately account for the heterogeneity of this disease, and the investigation of multiple molecular alterations in primary tumors and their metastases, in conjunction, has assumed great importance for the understanding of mammary tumor progression. In the present study, we selected 54 primary mammary carcinomas with lymph node metastasis (T1,2,3N1M0), 29 primary mammary carcinomas without metastasis (T1,2,3N0M0), and 25 canine lymph nodes metastasis to evaluate the immunohistochemical expression of HER-2, EGFR, Cox-2 and Ki67 and its association with clinical-pathological parameters and overall survival. Our results found a concordance between the expression of HER-2 (K coefficient: 0.250), Cox-2 (K coefficient: 0.571), and Ki67 (K coefficient: 0.397) and a discordance between EGFR expression (K coefficient: -0.195) in primary mammary carcinomas and paired lymph node metastasis. Furthermore, a high Ki67 index (>24%), large tumor size and the presence of angiolymphatic invasion in canine primary mammary carcinoma with lymph node metastasis plus the presence of extracapsular extension in lymph nodes metastasis were also related to worse prognoses and shorter overall survival (P<0.05). In conclusion, our study demonstrates that primary mammary carcinomas with high expression of HER-2, Cox-2 and Ki67 also show high expression of these markers in paired lymph node metastasis. Moreover, the expression of these molecular markers in lymph nodes metastasis did not demonstrate a prognostic relevance.

The Relationship Between E-Cadherin and its Transcriptional Repressors in Spontaneously Arising Canine Invasive Micropapillary Mammary Carcinoma.

E-cadherin downregulation is related to metastatic behaviour and a poor prognosis in cancer. It might be induced by transcriptional repression mediated by the transcription factors SNAIL, ZEB1, ZEB2 and TWIST. Here, we investigated E-cadherin expression and its relationship to those transcriptional repressors (i.e. SNAIL, ZEB1, ZEB2 and TWIST) in the progression from carcinoma 'in situ' to invasion to lymph node metastasis in spontaneously arising canine invasive micropapillary carcinoma (IMPC). E-cadherin expression decreased from carcinoma in situ to invasive progression and was likely to increase with lymph node metastasis. Expression of SNAIL decreased from carcinoma in situ to invasive areas and from invasive areas to lymph nodes. Metastatic lymph nodes had higher expression of ZEB1 than carcinoma in situ and invasive areas. ZEB2 expression was observed in 52%, 38% and 33% of carcinoma in situ areas, invasive areas and lymph node metastases, respectively. TWIST expression was observed in 52%, 38% and 33% of carcinoma in situ areas, invasive areas and lymph node metastases, respectively. In invasive areas, E-cadherin downregulation correlated significantly with SNAIL and TWIST upregulation. Additionally, in infiltrating components of IMPCs, E-cadherin(-)SNAIL(+) neoplastic epithelial cells were observed by immunofluorescence. Taken together, canine mammary IMPCs had a loss of E-cadherin from carcinoma in situ to invasive areas, which appears to be induced by the transcription factor SNAIL. In lymph node metastasis, ZEB1 appears to not exert E-cadherin transcriptional repression activity.

ZEB2 and ZEB1 expression in a spontaneous canine model of invasive micropapillary carcinoma of the mammary gland.

ZEB1 and ZEB2 have been recently related to cancer prognosis. We investigated their expression and its association with clinicopathological parameters and overall survival in invasive micropapillary carcinoma (IMPC), which is a metastasising neoplasm of the canine mammary gland. Immunohistochemical evaluation showed nuclear and cytoplasmic staining for ZEB2 and nuclear staining for ZEB1. 'In situ' areas presented higher positivity for cytoplasmic ZEB2 than invasive areas of IMPC did (p = 0.03). ZEB1 positivity was associated with a low histological grade (p = 0.01). A shorter overall survival rate was observed in IMPCs that were positive for cytoplasmic ZEB2 (p = 0.04). Antibodies specificity in canine species was confirmed by western blot. Our results indicated that cytoplasmic ZEB2 appears to be an important factor in the early stages of malignancy and predicts a poor overall survival rate for IMPC in this canine mammary cancer model. ZEB1 downregulation appears to be associated with the dedifferentiation process of IMPC.

Metastatic well differentiated squamous cell carcinoma in the prepuce of a dog: a report of clinicopathological, immunophenotypic and therapeutic approach / Carcinoma de células escamosas bem diferenciado metastático no prepúcio de cão: relato da abordagem clinicopatológica, imunofenotípica e terapêutica

This report describes a case of a well differentiated squamous cell carcinoma (SCC) of the foreskin of a dog, with metastasis in the regional lymph node. A six-year-old male intact Pit Bull dog presented a preputial ulcerated lesion with an evolution time of one year and enlarged left inguinal lymph node. Surgical resection of the preputial lesion and inguinal lymph nodes was made. The diagnosis of a well differentiated SCC was made following histopathological analysis and immunohistochemistry technique was used to confirm lymph node metastasis and to determine the histological features of the tumor. Here we demonstrated that immunohistochemistry can be an important complementary diagnostic tool to assess the prognostic features of SCC and to determine the treatment of choice. Also, the combination of COX-2 selective inhibitors in adjuvant therapy is presented as an effective alternative treatment for metastatic SCC in dogs...

Este relato descreve um caso de carcinoma de células escamosas (CCE) bem diferenciado no prepúcio de um cão, que apresentou metástase para o linfonodo regional. Um cão macho inteiro, de seis anos de idade, da raça Pit Bull, apresentou lesão ulcerada na região prepucial, com evolução de um ano, e linfonodo inguinal esquerdo aumentado, e foi submetido à exérese cirúrgica. O diagnóstico de CCE bem diferenciado foi obtido após avaliação histopatológica, e a técnica de imuno-histoquímica foi realizada para confirmação de metástase em linfonodo e para determinação das características imunofenotípicas do tumor. No estádio avançado da doença (T3N2M0) e com positividade para COX-2, foi proposta a utilização de quimioterapia adjuvante com carboplatina combinada com inibidor seletivo de COX-2. Neste estudo, demonstrou-se que a técnica de imuno-histoquímica pode ser uma importante ferramenta diagnóstica para determinar o prognóstico e o tratamento de escolha do CCE. Adicionalmente, a associação de carboplatina com inibidores seletivos de COX-2 é apresentada como uma efetiva alternativa de tratamento de CCE metastáticos caninos...

Clinical and pathological aspects of multicentric hemangiosarcoma in a Pinscher dog / Sinais neurológicos multifocais devido ao hemangiossarcoma multicêntrico em um cão Pinscher: aspectos clínicos e patológicos

A 3-year-old female Pinscher dog was presented with a history of lameness and pain in hind limbs for one week which acutely progressed to non-ambulatory paraparesis. The dog had been apathetic and anorexic during the six days prior to presentation. The neurological findings were compatible with upper motor neuron signs to the left hind limb due to a spinal cord compressive mass on the twelfth thoracic vertebral body. On the other hand, signs of lower motor neurons to the right hind limb were due to a mass with a pathological fracture in the right proximal femur, compressing the sciatic nerve. A histopathological analysis of all organs revealedthe proliferation of endothelial cells showingin filtrative growth and organization into vascular structures with a solid pattern. In addition, immunohistochemycal analysis revealed low proliferation index and citoplasmatic positivity for CD-31, confirming the vascular nature of the neoplasm. Clinical, histopathological and immunophenotipical findings were consistent with hemangiosarcoma.

Uma cadela Pinscher de três anos de idade foi atendida em Hospital Veterinário Escola com histórico de dor nos membros pélvicos com progressão aguda para paraparesia não ambulatória. O animal estava apático e anoréxico há seis dias. Os achados neurológicos foram compatíveis com sinais de lesão de neurônios motores superiores para o membro pélvico esquerdo devido a uma massa no 12º corpo vertebral comprimindo a medula espinhal. Por outro lado, foram observados sinais de lesão de neurônios motores inferiores para o membro pélvico direito devido a uma fratura patológica no colo proximal do fêmur direito que comprimiu o nervo isquiático. Análises histopatológicas de todos os órgãos revelaram proliferação de células endoteliais com crescimento infiltrativo e organização sólida em estruturas vasculares. Adicionalmente, a análise imuno-histoquímica revelou baixa proliferação e marcação citoplasmática positiva para CD-31, confirmando a natureza vascular da neoplasia. Os achados clínicos, histopatológicos e imuno-histoquímicos foram consistentes com hemangiossarcoma.

Histopathological and immunohistochemical assessment of invasive micropapillary mammary carcinoma in dogs: a retrospective study.

Invasive micropapillary carcinoma (IMPC) of the mammary gland, despite its rare occurrence in humans and dogs, is an important neoplasm due to its aggressive behaviour. The aim of this study was to evaluate the clinicopathological and immunophenotypical characteristics of IMPC and to determine the overall survival of dogs with this tumour. Of the selected cases, the majority had >3 cm neoplasms (15/19, 78.95%) and lymph node metastases (16/16, 100%), but only two cases (2/9, 22.2%) had distant metastases. The IMPCs were classified as either pure (15/22, 68.18%) or mixed (7/22, 31.82%) types. There was a predominance of moderate histological grade tumours (16 grade II) and the average overall survival was 120 days. Positive immunohistochemical staining for epithelial membrane antigen and negative staining for CD-31, p63 and cytokeratin (CK) AE1AE3 in cystic formations confirmed the micropapillary nature of these neoplasms. A proportion of cases exhibited positive epithelial staining for p63 (4/20, 20%) and CK34ßE12 (20/22, 90.9%). Most cases were positive for oestrogen (19/20, 95%) and progesterone (19/20, 95%) receptors, but lacked HER-2 (16/22, 72.72%) and epidermal growth factor receptor (15/22, 68.18%) over-expression. The mean proliferation index was 14.8%. The findings demonstrate that, similar to humans, canine IMPCs behave aggressively with high rates of metastasis to regional lymph nodes and short overall survival times.

Tubulopapillary carcinoma of the mammary gland in a maned wolf (Chrysocyon brachyurus): histopathological and immunophenotypical analysis / Carcinoma túbulo-papilar da glândula mamária em lobo guará fêmea (Chrysocyon brachyurus): análise histopatológica e imunofenotípica

A maned female wolf (Chrysocyon brachyurus) showed nodules in the inguinal and left abdominal cranial mammary glands. The mammary gland was surgically excised, and microscopic analysis revealed epithelial cell proliferation in a tubular and papillary pattern; delicate fibrovascular stalks presenting numerous layers of moderately pleomorfic epithelial cells were observed. This histologic appearance was compatible with a diagnosis of mammary tubulopapillary carcinoma. The immunohistochemical profile revealed nuclear positivity for estrogen (70 percent) and progesterone (at least 90 percent of the neoplastic cells). The myoepithelium-associated with neoplastic cells lacked integrity, as evidenced by failed smooth muscle alpha actin reactivity in microinvasive areas. A low proliferation index was observed (3.4 percent). To the authors' knowledge, the present case represents the first finding of female tubulopapillary carcinoma in a mammary gland in this species.

Um lobo guará fêmea (Chrysocyon brachyurus) apresentou nódulos nas mamas inguinal e abdominal cranial esquerda. As glândulas mamárias foram cirurgicamente excisadas, e na análise microscópica revelaram proliferação de células epiteliais em arranjo tubular e papilar com tecido conjuntivo de sustentação delicado e formação múltiplas camadas de células epiteliais moderadamente pleomórficas. Os achados histopatológicos foram compatíveis com carcinoma túbulo-papilar da glândula mamária. O estudo do perfil imuno-histoquímico mostrou positividade nuclear para estrógeno (70 por cento) e progesterona (em pelo menos 90 por cento das células). Observou-se perda da integridade da camada mioepitelial, adjacente a proliferação epitelial, evidenciada pela perda de reatividade para alfa actina de músculo liso em áreas de microinvasão. Índice de proliferação celular baixo foi observado (3,4 por cento). O presente relato representa a primeira descrição de um carcinoma túbulo-papilar da glândula mamária em uma fêmea desta espécie.

Cistoadenocarcinoma simulando hemangiossarcoma de glândula salivar em cão: relato de caso / Cystadenocarcinoma simulating hemangiosarcoma of the salivary gland in dog: case report

Cystadenocarcinoma is regarded as a rare adenocarcinoma variant in animals. This work reports the case of an 8-year-old female Poodle dog with salivary gland cystadenocarcinoma with morphological characteristics similar to a hemangiosarcoma. Histopathological analysis showed a tumor mass with cystic formations containing a large amount of red blood cells. In order to distinguish these two entities, periodic acid Schiff (PAS) staining and immunohistochemical analysis were carried out with the use of cytokeratin AE1/AE3 (CK) and CD31-specific antibodies. Neoplastic cells were PAS-negative, CK-positive and CD31-negative confirming their epithelial origin. Based on the findings, the diagnosis of high grade cystadenocarcinoma was established.

O cistoadenocarcinoma é considerado uma variante do adenocarcinoma de rara ocorrência em animais. Este trabalho relata um caso de cadela Poodle de oito anos, portadora de cistoadenocarcinoma de glândula salivar com características morfológicas semelhantes a de hemangiossarcoma. Na análise histopatológica observou-se uma massa tumoral com formações císticas contendo grande quantidade de hemácias. Para a diferenciação entre as duas entidades realizou-se coloração pelo ácido periódico de Schiff (PAS) e análise imuno-histoquímica com a utilização de anticorpos para citoqueratina AE1/AE3 (CK) e CD31. As células neoplásicas apresentaram-se PAS negativas, CK positivas e CD31 negativas demonstrando a origem epitelial. Com base nos achados firmou-se o diagnóstico de cistoadenocarcinoma de alto grau.