Diagnostic assessment of peritoneal fluid cytology in horses with abdominal neoplasia

Objective: To evaluate the diagnostic value of peritoneal fluid (PF) cytology for clinical diagnosis of abdominal neoplasia in horses. Material and methods: Ten horses with histopathologically confirmed abdominal neoplasia, in which a PF analysis was performed, were included in this retrospective study. PF was analyzed for total protein concentration and a nucleated cell count was performed. Using cytological criteria of malignancy, the PF samples were evaluated regarding their probability of malignancy. Results: Cytologic classification of cells according to criteria of malignancy allowed a positive cytologic diagnosis of neoplasia in 5 out of 10 peritoneal fluid samples. Malignant lymphoma was the most commonly diagnosed neoplasia (3/10) and could be identified by cytology in 2/3 cases. In 1/2 horses with plasma cell myeloma neoplastic cells were similarly found. Malignant melanoma (2/10) was diagnosed using cytology in one case (presence of melanin-containing cells). Cytological diagnosis of malignant neoplasia was established in the only horse with gastric squamous cell carcinoma, but the morphology of the identified tumour cells did not allow a specific diagnosis. Thus, a definitive diagnosis was achieved in 4/5 horses with proven abdominal neoplasia. The horses with adenocarcinoma (1/10) and haemangiosarcoma (1/10) had no evidence of neoplasia based on cytological findings. No relationship between total protein concentration or the nucleated cell count with the histolopathological diagnosis of abdominal neoplasia was found. Abnormal mitotic figures were considered of greater diagnostic value than the overall mitotic rate. Conclusion: The implementation of nuclear criteria of malignancy in the cytologic evaluation of PF samples allows the identification of neoplastic cells to an acceptable degree. For this purpose, the knowledge of the highly variable morphological features of mesothelial cells is essential. The absence of malignant cells does not rule out abdominal neoplasia. Clinical relevance: PF cytology should be considered as a valuable, minimally invasive, simple, and rapid diagnostic technique in horses with suspected abdominal neoplasia.     

Evaluation of progesterone and estrogen receptor expression in 15 meningiomas of dogs and cats

OBJECTIVE: To evaluate progesterone and estrogen receptor expression in meningiomas of the CNS in dogs and cats. ANIMAL: 8 dogs (1 of which was treated with gestrinone) and 5 cats with intracranial meningiomas and 2 dogs with spinal cord meningiomas; tissue samples were also obtained from 1 clinically normal dog and 1 clinically normal cat. PROCEDURE: Meningioma tissue was obtained during surgery or at necropsy; samples were processed for histologic classification and immunohistochemical evaluation of the proportion of tumor cells with progesterone and estrogen receptors. Correlation among receptor expression, tumor grade, and histologic subtypes was determined. RESULT: Several histologic subtypes of intracranial meningiomas were detected among tissue samples. In the cats, all intracranial meningiomas were benign. Progesterone receptor immunoreactivity was detected in 14 of 15 meningiomas. Progesterone receptor expression was identified in > 80% of cells in 8 intracranial meningiomas (4 dogs and 4 cats) and 2 spinal cord meningiomas. In samples of malignant transitional and granular cell meningiomas in dogs, progesterone receptors were detected in 32 and 4.8% of cells respectively. In 1 cat, 38% of tumor cells had progesterone receptors. In a dog treated with gestrinone, no progesterone receptors were detected in the intracranial meningioma. Estrogen receptors were only detected in the tumor of 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate a high proportion of progesterone receptors in cells of meningiomas of the CNS in dogs and cats. Antiprogesterone treatment may have a role in the treatment of unresectable or recurrent meningiomas in dogs and cats.     

Cytology of a mass on the meningeal surface of the left brain in a dog

An 11-year-old neutered male Labrador Retriever presented to Tufts University School of Veterinary Medicine for a 2-week history of seizures and altered behavior. Magnetic resonance imaging (MRI) revealed a homogeneously enhancing mass involving the surface of the left temporal, parietal, and occipital lobes of the brain, causing secondary hydrocephalus. Cytology samples obtained during rostrotentorial craniectomy contained abundant amorphous pink material suggestive of neuropil, scattered leukocytes, capillary fragments, large polyhedral nerve cell bodies, and other smaller cells with pale blue cytoplasm that occasionally were vacuolated and contained fine eosinophilic granules. The cytologic diagnosis was neoplasia, possibly meningioma. Ninety days after surgery the patient was euthanized after MRI results confirmed regrowth of the tumor. Histologic samples of the meningeal lesion collected at necropsy consisted of sheets and nests of loosely packed, large polygonal cells that compressed the brain parenchyma. The cytoplasm was eosinophilic and slightly granular, whereas nuclei were dense and eccentric. Neoplastic cells stained positive for S-100 protein, periodic acid-Schiff, and were partially diastase resistant. Vimentin staining was negative. Ubiquitin staining was light but diffusely positive. Ultrastructural features of the neoplastic cells included numerous secondary lysosomes and irregular pleomorphic nuclei. The final diagnosis was meningeal granular cell tumor. This case documents the cytologic and histologic features of an uncommon type of meningeal tumor.     

Fine needle aspiration cytology of pilomatricoma in three dogs

Background — Fine needle aspiration cytology is being used for the diagnosis of various neoplasms, but we are unaware of reports dealing with the cytologic features of canine pilomatricoma.
Objective — The purpose of this report was to describe the cytologic features of pilomatricoma in 3 dogs.
Methods — Fine-needle aspirates were obtained from cutaneous masses using a 25-ga needle. Smears were prepared and stained with May-Grünwald-Giemsa and hematoxylin and eosin. The cutaneous masses were excised and routinely processed for histologic examination.
Results — Cytologic features of all 3 tumors included high cellularity and numerous clusters of tightly arranged of basaloid cells with evenly distributed chromatin and small distinct nucleoli surrounding sheets of "ghost cells". Ghost cells were characterized by a central unstained zone corresponding to the site previously occupied by the nucleus. Amorphous keratinized material was observed in 1 tumor. Histopathologic findings confirmed the diagnosis of pilomatricoma in all 3 cases.
Conclusions — Basaloid cells in association with ghost cells are important cytopathologic criteria that may provide a definitive cytologic diagnosis of pilomatricoma in dogs, and may help avoid a false diagnosis of malignancy.     

Cytologically atypical anal sac adenocarcinoma in a dog

A 10-year-old intact female Shetland Sheepdog with tenesmus had a subcutaneous mass at the left ventral aspect of the anus. On cytologic examination, 2 types of cells were observed. Most of the cells were oval to polygonal and had elliptical or elongate nuclei and a moderate amount of pale to basophilic cytoplasm. The remaining cells had round to oval nuclei and pale to basophilic cytoplasm. Cells of both types were loosely adhered to each other and were arranged in rosette-like structures. Both neoplastic cell types had fine homogenous chromatin and either a small indistinct nucleolus or no visible nucleolus. Mild anisokaryosis and anisocytosis were observed. Histologically, the mass consists of glandular structures formed by cuboidal cells admixed with bundles of spindle cells. Eosinophilic PAS- and Alcian blue-positive secretory material was found in the center of some glandular structures. Both neoplastic cell types had positive staining with paradoxical concanavalin A and expressed cytokeratin, but not vimentin, S-100, α-smooth muscle actin, or desmin. Based on location and histologic and immunohistochemical features, the final diagnosis was adenocarcinoma of the apocrine gland of the anal sac, which should be included as a cytologic differential diagnosis when spindle cells and typical epithelial cells are observed in masses in the region of the anal sac of dogs.     

Canine angiosarcoma: cytologic, histologic, and immunohistochemical correlations

BACKGROUND: Angiosarcomas (AS) are malignant tumors that arise from vascular endothelial cells and are common in dogs. Histologically, AS are markedly heterogeneous neoplasms that make interpretation by cytology difficult. OBJECTIVE: Our objective was to evaluate the cytologic features of canine AS and look for additional diagnostic criteria. METHODS: Cytologic specimens from 19 histologically and immunohistochemically confirmed cases of canine AS were extensively reviewed for cytologic features. We compared cytologic, histopathologic, and immunohistochemical findings. RESULTS: Neoplastic cells in 14 cytology specimens had a high-grade sarcomatous appearance, whereas in 4 specimens the cells were extremely pleomorphic, ranging from sarcomatous to epithelioid. In the remaining case, the neoplastic cells were low grade, spindle shaped, and monomorphic. Other relevant cytologic findings were blood contamination (18/19 cases), cellular cohesiveness (16/19), punctate cytoplasmic vacuolation (19/19), background neutrophilia (11/19) and eosinophilia (5/19), erythrophagocytosis (8/19), extramedullary hematopoiesis (8/19), and apoptotic leukocytes (14/19). Vasoformative features (ie, pseudoacinar structures) were observed in 7 of 19 samples. Histologically, 16 neoplasms had a proliferative pattern typical of well-differentiated canine AS. Three tumors were atypical poorly differentiated AS; 2 of these had a striking epithelioid pattern and 1 was a poorly differentiated spindle cell tumor with focal vascular differentiation. Immunohistochemically, tumor cells in 16 cases were positive for both endothelial markers tested (Factor VIII-related antigen [FVIII-ra] and CD31 antigen), 2 were positive for CD31 only, and 1 was positive for FVIII-ra only. The epithelioid AS were negative for cytokeratins. CONCLUSIONS: The cytologic characteristics of canine AS are widely heterogeneous, but supplementary findings can provide clues that are useful for making a cytologic diagnosis. Histologic and immunohistochemical confirmation is nonetheless warranted in all cases.     

Spinal meningiomas in dogs: Description of 8 cases including a novel radiological and histopathological presentation

Clinical, imaging, and histological features of 8 canine spinal meningiomas, including a cervical cystic meningioma with imaging and intraoperative features of an arachnoid cyst, are described. All meningiomas were histologically classified and graded following the international World Health Organization human classification for tumors. Six meningiomas were located in the cervical spinal cord. Myelography showed intradural/ extramedullary lesions in 3/4 cases. Magnetic resonance imaging revealed hyperintense intradural/extramedullary masses on pre-contrast T1-weighted and T2-weighted images with homogeneous contrast enhancement in 7/8 cases. One dog had a cerebrospinal fluid-filled subarachnoid cavity dorsal to the cervical spinal cord. A spinal arachnoid cyst was diagnosed on imaging, but the histopathological study of the resected tissue revealed a grade I meningothelial cystic meningioma. There were no differences in outcome associated with tumor grade and surgical treatment (6/8). Cystic meningioma should be considered in the differential diagnosis of intraspinal cystic lesions, and biopsy is necessary for definitive diagnosis.     

Canine and feline intracranial meningiomas: an updated review

Meningiomas are the most common primary brain tumours in dogs and cats. There are several morphological phenotypes of this extra-axial neoplasm and they show predilections for certain anatomical locations. There have been a number of attempts to apply the current World Health Organization (WHO) classification for human meningiomas to dogs and cats and to obtain a universal classification scheme for domestic animals. Recently, certain enzymes involved in tumour growth have been recognised as biological markers and have been related to degrees of malignancy. The secondary effects of meningiomas have also been investigated, and vascular endothelial growth factor and peritumoural oedema have been reported to reduce survival rate. Breed and age predisposition are recognised in both dogs and cats and the presenting clinical signs are quite consistent. Magnetic resonance imaging and computed tomography are the techniques of choice for the presumptive diagnosis of meningiomas in domestic animals but advanced imaging techniques are constantly being developed and applied. Treatment methods for meningiomas involve a combination of de-bulking surgery, chemotherapy and radiotherapy, and detailed accounts of several treatment protocols have been reported.     

Expression of cell adhesion molecules and doublecortin in canine anaplastic meningiomas

Tumor cell invasion into the surrounding nervous tissue is one of the histologic hallmarks of anaplastic meningiomas. To identify other possible markers for aggression in canine meningiomas, the relationship between histologic features and the expression of molecules involved in cell adhesion, cell proliferation, and invasion was examined. Immunohistochemistry for epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), β-catenin, doublecortin (DCX), and Ki-67 was performed for 55 cases of canine meningioma. DCX was preferentially expressed in tumor cells invading the brain parenchyma (12 of 14 cases), suggesting its involvement in the invasion process. Regardless of the histologic type, E-cadherin and N-cadherin expression was observed in 31 of 55 and 44 of 55 cases, respectively. There was a significant positive correlation between DCX and N-cadherin expression and a significant negative correlation between E-cadherin and N-cadherin expression, suggesting that decreased E-cadherin and increased N-cadherin expression induce DCX expression. Typical membranous β-catenin expression was observed in 10 of 55 cases, whereas nuclear translocation was observed in 33 cases. Nuclear β-catenin expression was frequently found in anaplastic meningiomas (12 of 14 cases). The Ki-67 labeling indices were significantly higher in anaplastic meningiomas than in other types. These findings indicate that the expression of N-cadherin and DCX and the nuclear translocation of β-catenin are closely associated with the presence of invasion and anaplasia in canine meningiomas. Notably, granular cell meningiomas were negative for almost all the molecules examined, suggesting that they have a different tumor biology than other meningiomas.     

Cytologic evaluation of benign and malignant hemophagocytic disorders in canine bone marrow

Abstract: Canine hemophagocytic disorders were studied to better understand the cytologic features that differentiate benign and malignant disease. Of 286 canine clinical bone marrow reports evaluated retrospectively, 13 (4.5%) noted at least 3% hemophagocytic macrophages. Macrophages comprised between 6% and 44% of nucleated bone marrow cells. Clinical diagnoses for dogs with hemophagocytic disorders included malignant histiocytosis (n = 2), myelodysplastic syndromes (n = 4), round cell neoplasia (n = 2), immune-mediated disorders (n = 2), and idiopathic hemophagocytic syndrome (n = 3). Differentiation of benign and malignant forms of histiocytosis was problematic. Two dogs with a diagnosis of hemophagocytic syndrome had macrophages with atypical features similar to those described for malignant histiocytosis. Furthermore, only 2 of 11 dogs with presumably benign hemophagocytic disorders had exclusively mature macrophages in bone marrow. Other dogs had variable numbers of large reticular-type cells characterized by lacy chromatin, anisocytosis, anisokaryosis, and prominent and/or multiple nucleoli. On the basis of these results, cytomorphologic evaluation of bone marrow alone may not be adequate to consistently differentiate benign and malignant forms of hemophagocytic disorders.     

Magnetic resonance imaging and histological classification of intracranial meningiomas in 112 dogs

BACKGROUND: Intracranial meningiomas are the most common primary brain tumors in dogs. Classification of meningiomas by tumor grade and subtype has not been reported, and the value of magnetic resonance imaging (MRI) characteristics for predicting tumor subtype and grade has not been investigated. HYPOTHESIS: Canine intracranial meningiomas are a heterogenous group of tumors with differing histological subtypes and grades. Prediction of histopathological classification is possible based on MRI characteristics. ANIMALS: One hundred and twelve dogs with a histological diagnosis of intracranial meningioma. METHODS: Retrospective observational study. RESULTS: Meningiomas were overrepresented in the Golden Retriever and Boxer breeds with no sex predilection. The incidence of specific tumor grades was 56% benign (Grade I), 43% atypical (Grade II), and 1% malignant (Grade III). Grade I histological subtypes included meningothelial (43%), transitional (40%), microcystic (8%), psammomatous (6%), and angiomatous (3%). No statistically significant (P < .05) associations were found among tumor subtype or grade and any of the MRI features studied. CONCLUSIONS AND CLINICAL IMPORTANCE: Meningiomas in dogs differ from their counterparts in humans mainly in their higher incidence of atypical (Grade II) tumors observed. MRI characteristics do not allow for prediction of meningioma subtype or grade, emphasizing the necessity of histopathology for antemortem diagnosis. The higher incidence of atypical tumors in dogs may contribute to the poorer therapeutic response in dogs with meningiomas as compared with the response in humans with meningiomas.     

Canine orbital meningiomas: a review of 22 cases

Clinical and pathologic features of primary orbital meningiomas in the dog were reviewed. Twenty-two meningiomas, confined to the orbit, were identified from the Comparative Ophthalmic Pathology Laboratory of Wisconsin from 1981 to 1997. The dogs ranged in age from 3 to 17 years (mean = 9.2 years). The clinical presentation, reported in 20 cases, was indicative of a retrobulbar mass and included exophthalmos and orbital swelling (18/20), and papilledema or abnormalities of the posterior segment (7/20). Visual acuity was reported in 15 cases; of those, 12 dogs were blind in the affected eye. Follow-up information was obtained on 17 cases; six dogs developed local recurrence of the neoplasm. Two dogs with recurrent neoplasms simultaneously developed blindness in the opposite eye. Extension along the optic nerve to the optic chiasm was suspected. No metastasis was found at the time of the study. Enucleation with excisional biopsy was effective therapy to date in 11 cases (0.2–4.5 years follow-up time). All neoplasms were located within the vicinity of the optic nerve and, when sectioned through the optic nerve head, appeared to completely envelope the nerve. The neoplastic cells were arranged in tight whorls and bundles characteristic of meningiomas. Most tumors had islands of chondroid and osseous metaplasia (17/22). Ocular invasion was limited to small foci in the posterior choroid or optic nerve head of six dogs. Immunoperoxidase stains on 10 cases were positive for vimentin and S-100, but negative for cytokeratin. Electron microscopy revealed complex interdigitations between cell membranes and few desmosomal intercellular attachments. Primary orbital meningiomas have a characteristic histologic appearance and may recur locally after surgical excision.     

A multistep approach in the cytologic evaluation of liver biopsy samples of dogs with hepatic diseases

Cytologic criteria were evaluated for their diagnostic value in liver disease in dogs. Therefore, histopathologic and cytologic examination was performed on liver biopsy samples of 73 dogs with liver diseases and 28 healthy dogs. Logistic regression analysis was used to select the measured parameters to be included in a multistep approach. With the logistic regression method, different characteristic cytologic parameters could be defined for each histopathologic diagnosis. In malignant lymphoma of the liver, the presence of large numbers of lymphoblasts with a minimum of 5% of all cells was found. Clusters of epithelial cells with several cytologic characteristics of malignancy intermixed with normal hepatocytes were indicative of metastatic carcinoma or cholangiocellular carcinoma. Liver cells in hepatocellular carcinoma were characterized by a high nucleus/cytoplasm ratio, large cell diameters, increased numbers of nucleoli per nuclei, small numbers of cytoplasmic vacuoles, and frequently, small numbers of lymphocytes. Extrahepatic cholestasis was characterized by excessive extracellular bile pigment in the form of biliary casts, an increased number of nucleoli within hepatocytes, decreased hepatic cell size, and low numbers of lymphocytes. In destructive cholangiolitis, increased numbers of neutrophils and a small mean nuclear size within hepatocytes were seen. Acute and nonspecific reactive hepatitis are diagnosed based on the presence of moderate reactive nuclear patterns, including more pronounced chromatin, prominent nucleoli, increased numbers of inflammatory cells, excluding lymphocytes, and the absence of increased numbers of bile duct cell clusters. Increased number of mast cells also was indicative of nonspecific reactive hepatitis. Important cytologic criteria for the diagnosis of liver cirrhosis, in addition to chronic hepatitis, are intracellular bile accumulation and increased numbers of bile duct cell clusters. In summary, the stepwise approach based on logistic regression presented in this study might be helpful in the objective cytologic diagnosis of hepatic diseases.     

Basal cell tumor or cutaneous basilar epithelial neoplasm? Rethinking the cytologic diagnosis of basal cell tumors

A 1-cm-diameter, red, raised, cutaneous mass over the dorsal surface of the left third metacarpal of a 6-year-old neutered male yellow Labrador Retriever was aspirated. The aspirate contained cohesive clusters of cells, some containing cells with increased pleomorphism. Cellular debris (some keratinized), melanin, large numbers of macrophages, a few neutrophils, and fibroblasts were also observed. The cytologic interpretation was malignant neoplasia with histiocytic inflammation. Differentials included a carcinoma or, given the melanin pigment and variable morphology of the cells, possibly malignant melanoma. Histologically, the tumor was diagnosed as a basal cell epithelioma. Neoplasms that once were lumped into the broad histologic diagnosis of basal cell tumors have since been split into distinct entities, dependent on evidence of differentiation into epidermis, trichofollicular epithelium, or sweat or sebaceous glands. Although histologic reclassification has resulted in removal of most of these entities from the original basal cell tumor category, a cytologic diagnosis of basal cell tumor continues to be used to represent the large, heterogeneous group of epidermal, trichofollicular, and adnexal skin tumors with basal cell characteristics. The case in this report demonstrates the heterogeneity of neoplasms that may be diagnosed cytologically as basal cell tumors and supports the need for cytologic criteria and nomenclature that better reflect potential variation in tissue differentiation.     

Cytology in veterinary practice. A review of clinical cytology--body fluids, lymph nodes and skin neoplasms

A review over the most applicable areas of veterinary clinical cytology is given. The areas described are body fluids, lymph nodes and selected skin neoplasms. The review includes tables that survey general and specific cytologic criteria and is supplemented by photomicrographs. A classification of effusions according to cytologic criteria is discussed and there is a short discussion of 62 cases which also included histopathology.     

Clinical and pathologic features of canine ocular melanomas

Ocular melanomas in 40 dogs were reviewed and classified by site of origin and cytologic features. An apparent correlation existed between site, cytologic classification, and prognosis. Limbal melanomas and intraocular melanomas classified as spindle A or spindle B were less aggressive and had a more favorable prognosis than intraocular melanomas classified as a mixed-cell type or epithelioid.     

Cerebrospinal fluid from a 10-year-old dog with a single seizure episode

A cerebrospinal fluid sample collected from the cerebellomedullary cistern of a 10-year-old Shetland Sheepdog with a recent history of seizures was submitted for fluid analysis and cytologic examination. Key findings included a total nucleated cell count of 520/microL (reference interval 0-5 cells/microL), with a predominance of mononuclear cells, a protein concentration of 51.8 mg/dL (reference interval 0-35 mg/dL), and a glucose concentration of 44.7 mg/dL (reference interval 52-105 mg/dL). There was marked atypia of the mononuclear cells, with abundant eosinophilic cytoplasm, marked anisocytosis and anisokaryosis, occasional binucleated cells, mitotic figures, and rare erythrophagia. The cytologic interpretation was marked, monocytoid-rich, mixed cell pleocytosis with cellular atypia worrisome for neoplasia. In addition to histiocytic neoplasia, differentials included granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, and granulomatous inflammation. The dog did not respond to anti-inflammatory and anticonvulsive therapy. At necropsy, a mass involving the meninges and subtending the neuropil of the right temporal lobe of the cerebrum was found. Histologically, the mass was composed of large, bizarre histiocytic cells with multinucleated forms and numerous mitotic figures. Using immunochemistry on cytologic and histologic samples, the pleomorphic histiocytic cells were positive for CD1c, CD11ad, CD45, lysozyme, and vimentin, and were negative for CD3, CD4, CD79a, CD90, and pancytokeratin. These findings supported a diagnosis of primary CNS malignant histiocytosis of dendritic antigen-presenting cell (CD1c+) origin. To our knowledge, this is only the third reported case of primary CNS histiocytic sarcoma in dogs, and the first to demonstrate strong immunochemical evidence for dendritic antigen-presenting cell origin.     

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.