Clinical,cytologic, and histologic features of a mammary micropapillary carcinoma in a dog

Mammary invasive micropapillary carcinoma is a rare variant of mammary carcinoma that was recently recognized in dogs. The cytologic features and biologic behavior of such neoplasms in dogs have not yet been widely discussed in the veterinary literature. We report the clinical, cytologic, and histologic features of a canine micropapillary carcinoma in a 13‐year‐old female mongrel dog. The mammary region presented with extreme local pain, severe edema and erythema, and multifocal epidermal ulceration, which is typical for an inflammatory mammary carcinoma. Fine‐needle aspirates were highly cellular and consisted of individual cells and papillary cell clusters with characteristics of malignant epithelial cells. Histologic examination revealed neoplastic cells arranged in small papillae without fibrovascular cores, sometimes inside clear lymphatic spaces, indicating lymphovascular invasion. Regional lymph node evaluation revealed metastatic cells. Due to deteriorating clinical condition the dog was euthanatized 5 months after mastectomy. At necropsy, metastatic neoplastic mammary cells were found in popliteal and mediastinal lymph nodes, the right femoral biceps muscle, liver, heart, lungs, and urinary bladder.     

A statistical assessment of the biological relationship between simultaneous canine mammary tumours

Simultaneous canine mammary tumours (CMTs) are frequently reported in the literature, but few studies have addressed their biological relationship in detail or performed statistical assessments. In this study, 269 canine mammary gland tumours from 216 dogs were categorized using an extended histopathological classification, where semiquantitative and binomial scales enumerated morphological parameters of the tumours. The classification facilitated a statistical study of the biological relationship between simultaneous within‐dog tumours. Seventy‐seven percent of the dogs had single tumours and 23% had simultaneous tumours. Sixty‐one percent of the neoplasias were benign, with complex adenoma as the most frequent diagnosis and 39% were malignant, with complex carcinoma as the most common malignancy. Simultaneous tumours within dogs more often had equal diagnoses and neoplastic level (benign or malignant) than would be expected by chance alone, as compared with random pairs of single tumours from different dogs. This statistically supported finding indicated the presence of a biological relationship between simultaneous tumours.     

一例犬乳腺导管乳头状癌的诊断与治疗

犬乳腺导管乳头状癌是犬乳腺肿瘤的一种,为恶性肿瘤,多发于中老年未绝育母犬。临床症状为乳腺出现肿块,大小不等,生长快速,肿瘤可以在一个或多个腺体中发展。在晚期转移的情况下,癌变会扩散到淋巴结,肺,结肠,肾脏,有时还会扩散到骨骼,及早施行手术通常预后良好。本文对一例8岁母犬的乳腺导管内乳头状癌病例的临床诊断与手术治疗情况作详细介绍,以期为犬乳腺肿瘤的临床诊治提供参考。     

Cytologic examination of fine‐needle aspirates from mammary gland tumors in the dog: diagnostic accuracy with comparison to histopathology and association with postoperative outcome

Background: Mammary tumors are the most common neoplasms in female dogs. Malignant tumors may carry a poor prognosis and necessitate surgery. Few data are available on the value of cytologic examination as a diagnostic or prognostic tool for mammary tumors in dogs. Objectives: The objectives of this study were to determine whether cytologic findings in fine‐needle aspirate specimens of canine mammary tumors correlate with histopathologic results and whether the cytologic diagnosis is associated with postoperative outcome. Methods: In this prospective study, fine‐needle aspirate samples were obtained from 50 mammary tumors in 50 dogs. Results of cytologic and histopathologic examination were compared, using the histologic diagnosis as the reference method. Kaplan–Meier log rank analysis was used to evaluate univariate association of the cytologic diagnosis with duration of survival, local control, and metastasis‐free interval. Results: Adequate cytologic samples were obtained in 43/50 (86%) cases. The cytologic diagnosis correlated with the histologic diagnosis for benign and malignant tumors in 40/43 (93%) and 35/43 (81%) cases, respectively. Cytologic examination had a sensitivity of 88% and a specificity of 96% for the diagnosis of malignancy. The cytologic diagnosis had significant univariate association with duration of survival (P=.016), recurrence‐free interval (P=.003), and metastasis‐free interval (P=.014). Conclusions: Cytologic examination of mammary tumors in the dog has satisfactory accuracy, sensitivity, and specificity for the diagnosis of malignancy and is associated with postoperative outcome. Further studies on the diagnostic accuracy of cytology as well as multivariate analysis of its preoperative prognostic value in mammary tumors in the dog are warranted.     

Immunocytochemical study of Ki-67 as a prognostic marker in canine mammary neoplasia

Background: Canine mammary tumors are challenging for clinicians and pathologists because of complex histologic classification, low specificity of cytologic diagnosis, and unpredictable biological behavior. In histologic specimens, expression of tumor proliferation marker Ki‐67, a nuclear nonhistone protein, has been shown to have prognostic value for canine mammary tumors and to correlate with malignancy and low survival rates. Objective: The objective of this study was to measure the proliferation index of canine mammary tumors by immunochemical detection of Ki‐67 in cytologic specimens and to determine its relationship to clinical and pathologic variables and patient outcome. Methods: Spontaneous mammary tumors from 31 female dogs were surgically excised. Imprint specimens for cytologic evaluation were wet‐fixed in ethanol; histologic specimens were prepared routinely. Immunostaining was performed with the PH 177 monoclonal antibody against Ki‐67; proliferation index was graded from negative to +++. Dogs were followed for 18 months. Multivariate logistic regression analysis was used to determine correlations between immunocytochemical results, tumor and clinical variables, and patient outcome. Results: Ki‐67 proliferation indices in cytologic specimens were significantly lower for nonmalignant tumors than for malignant tumors. High index values of Ki‐67 were positively correlated with metastasis, death from neoplasia, low disease‐free survival rates, and low overall survival rate. With the exception of 4 specimens for which cellularity was insufficient, positive expression of Ki‐67 in cytologic specimens correlated with that of histologic specimens. Conclusions: The prognostic value of the Ki‐67 index in canine mammary tumors by using wet‐fixed cytology imprint specimens was similar to that observed previously for histologic specimens. Immunocytochemical detection of Ki‐67 could improve the accuracy and value of cytology by providing safe and rapid information about malignancy and patient outcome.     

Mastitis caused by Mycobacterium kansasii infection in a dog

A 2‐year, 7‐month‐old female Chihuahua was admitted for a mammary mass measuring one cm in diameter. The dog had a history of demodicosis for 4 months and showed signs of pseudopregnancy at the time of the visit. Cytologic examination of an aspirate of the mass revealed a large number of macrophages containing nonstaining bacterial rods, which were acid‐fast in a Ziehl–Neelsen stain, suggesting mycobacterial infection. Histologic examination of the mass revealed a pyogranulomatous mastitis characterized by an infiltration with macrophages containing acid‐fast bacteria. Mycobacterium kansasii was subsequently cultured and identified by PCR. Surgical excision of the mass resulted in the growth of other dermal masses, but antimycobacterial treatment with rifampin and clarithromycin resolved these masses within 1 month. Three months after discontinuation of the treatment, similar organisms were found in aspirates of the enlarged bilateral inguinal lymph nodes by cytologic examination. Despite antimycobacterial treatment for another 4 months, there was no improvement and demodicosis also recurred. The dog eventually died of lymphoma 5 months after the relapse of mycobacterial infection. Although M kansasii is considered an important pathogen for pulmonary and cutaneous disease in people, there is only one report in a dog with an infection in a pleural effusion. As both adult‐onset demodicosis in dogs as well as mycobacterial infection in people have been associated with T‐lymphocyte deficiency, the M kansasii infection in this dog may have been associated with a condition of immune compromise.     

Carcinocythemia: First report in a cat and literature review

A 6‐year‐old female neutered European Shorthair cat was presented with a 2‐day history of lethargy and hyporexia. On physical examination, the cat was slightly depressed and had a 2.5 cm nodule in the left 3^rd mammary gland. The hemogram revealed mild leukocytosis with mature neutrophilia and moderate thrombocytopenia. On blood smear evaluation, rare pleomorphic cells, possibly of epithelial origin, were observed mainly at the feathered edge. The animal died about 12 hours after presentation, and a necropsy was performed. On histopathology, the mammary nodule was diagnosed as a tubulopapillary adenocarcinoma with vascular invasion and widespread metastases. Immunocytochemical tests for cytokeratins (AE1/AE3) confirmed the epithelial phenotype of the neoplastic cells observed on the blood smear. The present report describes a feline mammary carcinoma with widespread metastases and the presence of malignant epithelial cells in the peripheral blood referred to as carcinocythemia. This condition has been previously described in people and dogs. To the author's knowledge, this is the first reported case of feline carcinocythemia. As in other species, the phenomenon was associated with a terminal phase of systemic malignancy.     

Identification of microfilaria in a mammary mass aspirate from a female dog

A filarial nematode larva (microfilaria) was found in an aspirate of a mammary mass from a dog imported to Saskatchewan from Myanmar. This was an unusual location for a microfilaria and numerous filarial nematodes infecting dogs in Asia had to be considered. This report describes the laboratory diagnosis of canine heartworm disease in this dog.     

Neoplastic pleocytosis in a dog with metastatic mammary carcinoma and meningeal carcinomatosis

Abstract: A 12‐year‐old female spayed Labrador Retriever was presented with a history of seizures and abnormal vocalization. Approximately 1 year before presentation, multiple mammary cysts had been surgically excised. A mammary mass was noted on physical examination, and 2 separate parenchymal brain lesions were found on imaging studies. Cerebrospinal fluid (CSF) collected from the cisterna magna was analyzed, and abnormalities included moderate pleocytosis with atypical discrete round cells that occasionally formed loose clusters. The dog was euthanized, and on necropsy a primary solid mammary carcinoma was identified as well as multiple metastatic foci in the brain with diffuse meningeal involvement. The cells in the CSF had a morphologic appearance similar to the cells in the primary mammary tumor and in the metastatic tumors in the brain. On immunostaining, cells from the primary mammary tumor, the brain tumors, and the CSF expressed cytokeratin. The CSF cells did not express CD18, CD3, or CD79a. A final diagnosis of mammary carcinoma with brain metastasis and meningeal carcinomatosis was made.     

Mammary carcinoma arising in an adenoma in a ewe

A large, firm, multi-cystic mammary gland mass grew slowly over 4 y in a 12-y-old, female Finn–Shetland cross sheep. A diagnosis of epithelial malignancy was suspected following fine-needle aspiration cytology at 30 mo after initial observation. The sheep was euthanized when the flock was downsized 18 mo later. A field postmortem examination revealed a large mammary mass, but an absence of metastases to internal organs. Imprint cytology of the mammary tissue supported a benign proliferative process. Histologically, mammary tissue was obliterated by cystic, tubular, and papillary adenomatous arrangements of mammary epithelium, with an anaplastic component, consistent with mammary carcinoma arising in an adenoma. IHC showed strong nuclear positivity to the antibody against progesterone receptor and minimal positivity to the antibody against estrogen receptor alpha expression. Intrinsic subtyping for basal or luminal epithelial origin was attempted through adaptation of companion animal IHC classification panels; high- and low-molecular-weight cytokeratins (CK5, CK8, CK18) failed to stain, but p63 expression for basal epithelium was positive.     

Cytomorphologic differentiation of benign and malignant mammary tumors in fine needle aspirate specimens from irradiated female Sprague–Dawley rats

Background: Fine needle aspiration (FNA) offers a rapid and minimally invasive means to distinguish malignant from benign neoplasms. However, few studies have been published regarding the cytopathology of mammary tumors in rats despite widespread use of the rat model for breast cancer formation and inhibition.
Objective: The purpose of this study was to determine the diagnostic accuracy of FNA cytology and to develop distinguishing cytologic criteria for the diagnosis of radiation-induced benign and malignant mammary tumors in rats.
Methods: In a study of radiation-induced mammary carcinogenesis, 100 Sprague–Dawley rats with cutaneous masses were randomly chosen for FNA. The aspirates were smeared, fixed, and stained with a modified Papanicolaou procedure for diagnostic evaluation. Cytologic and histologic diagnoses (benign vs malignant) were compared, and diagnostic accuracy was calculated using the histologic diagnosis as the criterion standard. FNA smears were scored semiquantitatively on a scale of 1–4 for cellularity, atypia, nuclear size, chromatin pattern, nuclear membrane thickness, nucleoli, and mitoses. The background was evaluated for necrosis, hemorrhage, inflammation, and mucosecretory material. Cytomorphologic features were compared statistically between benign and malignant tumors, based on the histologic diagnosis.
Results: The sensitivity of FNA was 92.3% and specificity was 89.4% for the detection of malignancy. However, 14% of specimens, all fibroadenomas by histology, had insufficient cells for cytologic evaluation, for an overall accuracy rate of 78.0%. Malignant tumors had significantly higher scores for all cytomorphologic features, and were significantly more likely to contain cell clusters and necrotic debris.
Conclusions: FNA is an accurate method for differentiating benign and malignant rat mammary tumors.     

Clinocopathologic and Immunohistochemical Findings of Multiple Genital Leiomyomas and Mammary Adenocarcinomas in a Bitch

A 13‐year‐old female Pointer dog was presented for evaluation of mammary tumours and bloody vaginal discharge at the Veterinary Teaching Hospital of Mehmet Akif Ersoy University, Faculty of Veterinary Medicine. On the history, owner complained of mammary tumours and bloody vaginal discharge. Three mammary tumours and lymphadenopathy at the mammary lymph nodes were observed at the clinical examination. A big, firm, palpable mass was found in the abdominal cavity. Vaginal cytology revealed numerous pleomorphic and anaplastic cells. Abdominal ultrasonography demonstrated a large mid‐abdominal mass at the distal part of the left uterine horn. Also multiple masses in the cervix and vagina were found. Because of the poor prognosis and the desire of the owner, the bitch was killed. At the necropsy numerous masses were seen at the vagina and cervix and one big mass seen at the left cornu uteri. Histopathological diagnosis was leiomyoma. Multiple metastases of mammary tumours were seen at the lungs. Histopathologically, mammary tumours were diagnosed as complex type tubulopapillary adenocarcinoma. The objectives of this study were to measure the proliferation indices in canine complex type mammary adenocarcinoma and genital leiomyomas using immunohistochemical detection of Ki‐67 and proliferating cell nuclear antigen to determine the relationship of these antigens to clinical and pathologic variables; and to examine the immunoreactivity of these tumours with different markers. Pan‐cytokeratin and S100 were negative, desmin and glial fibriler acidic protein were slight positive and the other markers (carsinoembryogenic antigen, proliferating cell nuclear antigen, vimentin, smooth muscle actin, p53, fibronectin, Ki67) were found strong positive at the genital tumours. Only desmin were negative; the other markers were strong positive at the mammary tumours.     

Abdominal CT evaluation of the liver and spleen for staging mast cell tumors in dogs yields nonspecific results

Canine mast cell tumor staging is commonly performed using abdominal ultrasonography and fine‐needle aspiration cytology of masses, lymph nodes, and hepatic and splenic parenchyma. Computed tomography is used for abdominal, thoracic, or whole body imaging in staging mast cell tumors in the authors’ institution enabling evaluation of multiple body areas in one examination. The aim of this study was to compare the CT examinations acquired for staging of mast cell disease to their subsequent liver and spleen cytology findings. Medical records of dogs with primary mast cell tumors that underwent abdominal CT and concurrent liver and spleen aspirates were reviewed. The CT examinations were evaluated for attenuation, size, and margination of the liver and spleen. The relationship between CT findings and cytology results was analyzed. Forty‐nine dogs matched the inclusion criteria: five of forty‐nine dogs with cutaneous mast cell tumors were positive for metastasis from liver and/or spleen aspirates. Of the five dogs with cytological evidence of liver or spleen metastasis, four had normal CT liver attenuation and size, one dog had concurrent primary hepatocellular neoplasia, four dogs had abnormal splenic parenchyma (two nodular and two diffuse heterogeneity), and one dog had a normal attenuation of the spleen. In four dogs, the spleen was subjectively enlarged. Computed tomographic evaluation of the liver showed no consistent pattern associated with mast cell metastasis and did not predict cytology results. Multifocal splenic hypoattenuating lesions more commonly coincided with mast cell metastasis. Sampling of the liver and spleen remains to be considered in the absence of abnormal CT findings for full staging.     

Serum neopterin levels in female dogs with malignant mammary tumours

In this study, we have determined serum neopterin levels in female dogs with primary malignant mammary tumours. The study involved 50 female dogs which had a malignant mammary tumours removed surgically (32 animals with carcinoma, 12 animals with sarcoma and 6 animals with carcinosarcoma) and 10 clinically healthy female dogs. Serum neopterin levels were determined using a commercial ELISA kit. The mean neopterin levels were lower in the malignant tumour groups than in healthy animals but differences were statistically significant only in carcinoma and sarcoma groups. The decrease of neopterin levels in animals with malignant mammary tumours may suggest their decreased cellular immunity. Moreover, it might indicate that decreased activity of cellular mechanisms of the anti‐neoplastic response is one of the factors associated with the development and course of malignant mammary tumours in female dogs; however, further studies are necessary.     

A case of hypercalcemia in a heifer presumably due to mammary carcinoma bovine hypercalcemia of malignancy

Mammary carcinoma is rare in cattle with only a handful of cases found in the literature, and none have reported an associated hypercalcemia. An 8‐year‐old Holstein‐Friesian heifer was presented to the Purdue University Veterinary Teaching Hospital's Large Animal Hospital with a 3‐month history of lethargy. Laboratory abnormalities included ionized hypercalcemia and hypophosphatemia (2.28 mmol/L and 1.8 mg/dL, respectively). Physical examination revealed a mammary mass that was cytologically described as a suspected mammary carcinoma, which was later confirmed by histologic evaluation. On surgical removal of the mass, calcium initially decreased rapidly, and within a few days was within the RI, further supporting a diagnosis of hypercalcemia of malignancy in a heifer. However, attempts to confirm this using hormone profiles (parathyroid hormone [PTH], parathyroid hormone‐related protein [PTHrp], and calcitriol) were inconclusive due to the lack of validated assays and RIs for cattle. Immunohistochemical staining for PTHrP showed scattered cytoplasmic staining among the neoplastic cells, suggesting PTHrP production by these cells.     

Description of the use of contrast‐enhanced ultrasonography in four dogs with pancreatic tumours

Canine pancreatic tumours are rare compared to human medicine and the detection and differentiation of pancreatic neoplasia is challenging with B‐mode ultrasonography, which often leads to late clinical diagnosis and poor prognosis. This case report describes the findings of contrast‐enhanced ultrasonography in four dogs with pancreatic adenocarcinoma or insulinoma. B‐mode ultrasonography of the pancreas revealed a hypoechoic nodule in three dogs and heterogenous tissue in one dog. Contrast‐enhanced ultrasonography was able to differentiate between two tumour types: adenocarcinomas showed hypoechoic and hypovascular lesions, whereas insulinomas showed uniformly hypervascular lesions. Contrast‐enhanced ultrasonography findings were confirmed by cytology and/or histopathology. The results demonstrated that contrast‐enhanced ultrasonography was able to establish different enhancement patterns between exocrine (adenocarcinoma) and endocrine (insulinoma) tumours in dogs .     

IMAGING DIAGNOSIS—ENDOMETRIAL MINERALIZATION IN A DOG

A 9‐year‐old intact female mixed breed dog was presented for mammary gland tumor surgery, and preoperative radiographs showed a tubular soft tissue opacity mass with multifocal mineralization in the caudoventral abdominal cavity. Subsequent ultrasonography demonstrated uterine dilation with echogenic fluid and endometrial acoustic shadowing consistent with mineralization. Resection of mammary gland tumors and ovariohysterectomy were performed. Pyometra was diagnosed on cytologic examination of uterine fluid. Histopathology of the uterine tissue confirmed a diagnosis of cystic endometrial hyperplasia with uterine mineralization.     

Loss of p27 expression in canine mammary tumors and their metastases

The p27 gene is a member of the cyclin-dependent kinase inhibitors, which arrest G1- to S-phase transition of the cell cycle. We have previously shown a significant reduction of p27 mRNA expression level in laser-microdissected mammary carcinomas and their lymph node metastases when compared to non-neoplastic mammary gland of the same dog. Here, p27 expression was analyzed on the protein level in non-neoplastic mammary gland, primary mammary carcinomas, their lymph node metastases and intravascular tumor cells of 49 dogs, adenomas of 49 dogs and non-neoplastic mammary gland of 98 dogs by immunohistochemistry. A significantly (p ? 0.05) decreased percentage of p27 positive tissue samples was found when normal gland was compared with adenomas, carcinomas and lymph node metastases. Specifically, 91% of normal gland epithelium displayed nuclear p27 expression. In contrast, only 22% of the adenomas, 20% of carcinomas, 12% of lymph node metastases and 32% of intravascular tumor cells had p27 reactivity. Cell cycle control by p27 is therefore lost in the majority of canine mammary tumors. The lack of significant differences between benign and malignant mammary tumors indicates that decreased p27 expression is an early step in carcinogenesis of canine mammary tumors and hinders the use of p27 as a marker of malignancy for this tumor type.     

Osseous metaplasia within a canine insulinoma

An 11‐year‐old male castrated mixed‐breed dog was presented for exercise intolerance, tetraparesis, and persistent hypoglycemia. Abdominal ultrasound examination revealed 2 nodules within the right limb of the pancreas. Cytology from one nodule was consistent with a carcinoma of neuroendocrine origin, with a primary differential diagnosis of insulinoma. Histologic evaluation and immunohistochemistry for synaptophysin and insulin confirmed the diagnosis of insulinoma. Additionally, there was a solitary nodule of mineralized compact bone composing approximately 60% of the mass. To the authors' knowledge, this is the first report of osseous metaplasia within an insulinoma (islet cell carcinoma).