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.     

Cytologic–histologic concordance in the diagnosis of neoplasia in canine and feline lymph nodes: a retrospective study of 367 cases

Lymph nodes are frequently sampled in dogs and cats for the diagnosis of primary and metastatic neoplasia. We determined the accuracy of cytologic diagnosis in lymph nodes using histology as the gold standard. Lymph node reports (2001–2011) were retrospectively evaluated and diagnoses were categorized as neoplastic or non‐neoplastic. Lymph nodes from 296 dogs and 71 cats included 157 (42.7%) non‐neoplastic lesions, 62 (16.9%) lymphomas and 148 (40.3%) metastatic neoplasms. Cytology had a sensitivity of 66.6% [95% confidence interval (CI) 60.0–72.8%], specificity of 91.5% (CI 86.3–95.2%), and accuracy of 77.2% (CI 72.6–81.3%) for neoplasia. Likelihood of malignancy with a positive cytologic diagnosis of neoplasia was 93.0%. High proportions of false‐negative results were found in mesenteric T‐cell lymphoma (22/35, 63%, mainly cats), metastatic sarcoma (8/14, 57%) and metastatic mast cell tumour (15/48, 31%, mainly dogs). Factors contributing to discrepancies included well‐differentiated lymphocyte morphology, focal distribution of metastases and poorly defined criteria for metastatic mast cell tumours.     

Multiple joint metastasis of a transitional cell carcinoma in a dog

An 8‐year‐old castrated male hound mix was referred to the Purdue University Veterinary Teaching Hospital for severe lameness, pollakiuria, and dyschezia. On presentation, the dog was nonweight bearing on the right rear limb and the right carpus was diffusely swollen. Synovial fluid analysis from the right carpus revealed a population of epithelial cells displaying marked anisocytosis, anisokaryosis, multinucleation, and prominent, variably sized nucleoli. A metastatic carcinoma with presumed prostatic or urothelial origin was diagnosed based on cytomorphology. Subsequent cytologic evaluation of peripheral lymph nodes revealed the presence of a similar neoplastic population. The dog was euthanized and synovial fluid from both stifle joints, as well as impression smears of the prostate gland, were collected. Carcinoma cells were identified in each stifle joint and in the prostate gland. Immunocytochemistry was performed on synovial fluid smears from 2 of the joints (right stifle and right carpus) and on impression smears of the prostate gland. The neoplastic population in the joints and prostate gland showed strong immunoreactivity to uroplakin III, a urothelial marker, indicating metastasis of a transitional cell carcinoma to multiple joints. In addition, evidence for epithelial to mesenchymal transition was identified using cytokeratin, an epithelial marker, and vimentin, a mesenchymal marker. A necropsy was performed and histopathology confirmed the presence of metastatic transitional cell carcinoma in various tissues. This case illustrates the importance of considering metastatic disease when a patient is presented with severe lameness and joint pain, and the clinical utility of synovial fluid cytology for diagnosis of metastasis in these cases.     

B‐cell lymphoma with Mott cell differentiation in a cat

A 12‐year‐old, male castrated Domestic Shorthair cat was presented to Animal Medical Center of Gifu Univeristy with anorexia and vomiting. Physical examination revealed an enlarged left tonsil and right mandibular lymph node (approximately 2–3× the normal size), and a submucosal mass on the right side of the epiglottis (1.5 × 2.0 cm). On computed tomography images, an enlarged left tonsil, and enlarged right mandibular, right pharyngeal, and left and right cervical lymph nodes were observed. Cytologic examination of smears of tonsil and lymph nodes revealed numerous medium‐ to large‐sized neoplastic lymphoid cells, approximately half of which contained one or several light‐blue homogenous globoid cytoplasmic inclusions (5–10 μm), which stained magenta with periodic acid–Schiff (PAS) stain. Histopathologic examination of the left tonsil revealed diffuse proliferation of medium‐ to large‐sized neoplastic lymphoid cells effacing the original lymphoid architecture. Half of the cells contained one or several eosinophilic globoid cytoplasmic inclusions, which stained magenta with PAS and showed positive immunohistochemical reactions for immunoglobulin M (IgM) and λ light chain. Neoplastic lymphoid cells were also CD20⁺, Pax5⁺, and MUM1⁺, and CD3^?. Thus, the neoplastic lymphoid cells expressed a B‐cell immunophenotype, and the globoid cytoplasmic inclusions represented an aberrant IgM λ light chain accumulation, similar to Russell bodies. B‐cell lymphoma with Mott cell differentiation was diagnosed based on cytologic, histopathologic, and immunohistochemical features. This is the first report of B‐cell lymphoma with Mott cell differentiation in a cat.     

Mast cell tumor in the nasal cavity of a dog

An 11-year-old male Shetland sheepdog displayed epistaxis and nasal discharge from the left nasal foramen. Cytological examination of a smear sample obtained by rhinotomy revealed neoplastic mast cells in the nasal cavity, a definitive diagnostic sign of mast cell tumor. The case was treated by surgery combined with radiotherapy and chemotherapy. Eighteen days after the last treatment, marked enlargement of the mandibular lymph nodes and facial edema developed, and the dog was euthanized at the owner's request. At necropsy, metastatic proliferation of mast cells was confirmed in the lymph nodes and liver, but no neoplastic mast cells were observed in the nasal cavity.     

Metastatic balloon cell melanoma in a dog

Background: Balloon cell melanoma is a rare variant of amelanotic melanoma that is difficult to differentiate from sebaceous cell carcinoma, liposarcoma, and other clear cell neoplasms without immunohistochemistry or ultrastructural evidence of melanin or melanosomes. Objective: The purpose of this report was to describe the clinical, cytologic, histologic, immunohistochemical, and ultrastructural findings in a dog with metastatic balloon cell melanoma. Methods: A 6‐year‐old female Golden Retriever was evaluated for a white, flocculent infiltrate in the anterior chamber of the left eye and an enlarged left prescapular lymph node. Cytologic evaluation of the eye and lymph node were performed following aqueocentesis and fine‐needle aspiration, respectively. The affected lymph node was examined histologically and stained for cytokeratin, vimentin, S‐100, and Melan A. Following euthanasia a necropsy was performed and samples of the affected lymph node were examined by electron microscopy. Results: Cytologic examination of the lymph node and aqueocentesis sample revealed round neoplastic cells that had abundant clear vacuolated cytoplasm. A tentative diagnosis of metastatic sebaceous cell carcinoma or clear cell neoplasm was made. Histologically, the affected lymph node had similar polygonal clear cells arranged in sheets and packets divided by delicate fibrovascular stroma. Immunohistochemical staining of the cells was negative for cytokeratin but positive for vimentin, weakly positive for S‐100, and strongly positive for Melan A. At necropsy, metastatic lesions were identified in the diaphragm, heart, lung, kidneys, left eye, prescapular and sublumbar lymph nodes, and multiple skin sites. Ultrastructural examination of neoplastic lymph nodes revealed many membrane‐bound vacuoles, myelinlike figures, and rare melanosomes. Conclusion: Immunohistochemical staining and ultrastructural features of the neoplastic cells supported a diagnosis of metastatic balloon cell melanoma.     

Complex mammary carcinoma with metastases to lymph nodes,subcutaneous tissue,and multiple joints in a dog

An 8‐year‐old, intact female, mixed‐breed dog presented to the Oklahoma State University Boren Veterinary Medical Teaching Hospital for evaluation of progressive lameness and joint effusion of multiple joints. Physical examination revealed joint effusion of the elbow, hock, and stifle joints bilaterally, enlarged left axillary and right popliteal lymph nodes, a subcutaneous mass over the left elbow, and a subcutaneous mass involving the left second and third mammary glands. Cytologic examination of the mammary mass, enlarged lymph nodes, and joint fluid from most affected joints revealed a monomorphic population of loosely cohesive neoplastic epithelial cells. The patient was humanely euthanized, and subsequent necropsy with histopathologic examination revealed a complex mammary carcinoma with metastases to enlarged lymph nodes, subcutaneous tissue over the left elbow, and the synovium of multiple joints. Immunohistochemical stains were performed and showed diffusely positive pan cytokeratin, CK8/18, and CK19 staining in the neoplastic luminal epithelial cells of the mammary carcinoma, synovium, and lymph nodes, and showed diffusely positive vimentin staining of the myoepithelial cells. Myoepithelial calponin positivity was diffuse in the mammary mass and lymph nodes but minimal in the synovium. Only the mammary mass showed p63 positivity. Metastatic mammary neoplasia is relatively common in dogs; however, metastasis to the synovium has only been reported once previously in the literature. This is the first case utilizing immunohistochemistry for confirmation and characterization of metastases.     

COMPARISON OF SONOGRAPHIC FEATURES OF BENIGN AND NEOPLASTIC DEEP LYMPH NODES IN DOGS

The differentiation of benign vs. neoplastic lymph nodes impacts patient management. Specific sonographic features are typically considered when assessing lymph nodes in dogs. However, the usefulness of these criteria in distinguishing benign vs. malignant lymph nodes remains largely unknown, especially for deep lymph nodes. Our aim was to compare sonographic features in benign and neoplastic deep lymph nodes with the hope of identifying predictive criteria. Thirty‐one deep lymph nodes (16 mesenteric, 10 medial iliac, three hepatic, one sternal, and one cranial mediastinal) in 31 dogs were examined prospectively with B‐mode and Color flow Doppler. Lymph nodes were aspirated using ultrasound‐guidance and final diagnosis were established based on cytologic and/or histopathologic interpretation. Prevalence of each sonographic feature and combinations of two features was calculated for each group and compared using a χ²‐test or Student's t‐test for unequal variances. Ten lymph nodes were benign (hyperplastic and/or inflammatory) and 21 were neoplastic. All were hypoechoic, except for one neoplastic lymph node. Maximal short‐axis diameter (P=0.0006) and long‐axis diameter (P=0.01), and SA/LA ratio (P=0.008) were increased significantly for neoplastic (2.8, 5.5 cm, and 0.50, respectively) vs. benign (1.2, 3.8 cm, and 0.34, respectively) lymph nodes. The prevalence of other features was similar between groups. Doppler evaluation was possible in 77% of lymph nodes, but there was no significant difference between groups. When any two ultrasound features were combined, the only difference between benign and neoplastic lymph nodes was for the combination of contour regularity and appearance of the perinodal fat (P=0.03).     

Multicentric mast cell tumors in a horse

Abstract: A 6‐year‐old female Rocky Mountain horse was presented for evaluation of draining tracts and distal limb subcutaneous edema on the left front and left hind limbs that had been present for 2 weeks. Direct smears of fluid collected by fine‐needle aspiration of subcutaneous fluid from both limbs were highly cellular with a predominance of eosinophils accompanied by numerous, moderately atypical, variably granulated mast cells. The cytologic diagnosis was mast cell tumor (MCT) with prominent eosinophilic infiltration with a differential diagnosis of eosinophilic granuloma. Histologic evaluation of surgical biopsies of lesions from both limbs was performed on sections stained with H&E, toluidine blue, and Luna stains. The histologic diagnosis was MCT, and staining with toluidine blue and Luna stains confirmed the presence of mast cells and eosinophils, respectively. In addition, the mast cells strongly expressed CD117. This is the first reported case of cutaneous mast cell neoplasia in a horse in which primary presenting complaints were draining tracts and distal limb subcutaneous edema involving multiple limbs. This case illustrates the utility of staining for CD117 expression in combination with traditional stains, such as toluidine blue and Luna, in differentiating MCTs from other eosinophilic lesions in horses.     

Pilot study utilizing Fluorine‐18 fluorodeoxyglucose‐positron emission tomography/computed tomography for glycolytic phenotyping of canine mast cell tumors

The goal of this prospective pilot study was to use naturally occurring canine mast cell tumors of various grades and stages as a model for attempting to determine how glucose uptake and markers of biologic behavior are correlated. It was hypothesized that enhanced glucose uptake, as measured by 2‐[fluorine‐18]fluoro‐d ‐glucose‐positron emission tomography/computed tomography (F18 FDG PET‐CT), would correlate with histologic grade. Dogs were recruited for this study from a population referred for treatment of cytologically or histologically confirmed mast cell tumors. Patients were staged utilizing standard of care methods (abdominal ultrasound and three view thoracic radiographs), followed by a whole body F18 FDG PET‐CT. Results of the F18 FDG PET‐CT were analyzed for possible metastasis and standard uptake value maximum (SUV_max) of identified lesions. Incisional or excisional biopsies of the accessible mast cell tumors were obtained and histology performed. Results were then analyzed to look for a possible correlation between the grade of mast cell tumors and SUV_max. A total of nine animals were included in the sample. Findings indicated that there was a correlation between grade of mast cell tumors and SUV_max as determined by F18 FDG PET‐CT (p‐value = 0.073, significance ≤ 0.1). Based on the limited power of this study, it is felt that further research to examine the relationship between glucose utilization and biologic aggressiveness in canine mast cell tumors is warranted. This study was unable to show that F18 FDG PET‐CT was a better staging tool than standard of care methods.     

CD34+, CD41+ acute megakaryoblastic leukemia in a dog

A clinically normal, 5-year-old intact female German Shepherd dog was presented to the local veterinarian to be spayed. Results of a preoperative CBC included mild nonregenerative anemia, severe thrombocytopenia, and 17% unclassified cells. On cytologic examination of aspirates from the dog's enlarged spleen and peripheral lymph nodes, a population of primitive round cells that occasionally resembled megakaryocytes was observed. A bone marrow aspirate specimen was markedly hypercellular with approximately 65% of marrow cells comprising a homogeneous population of immature hematopoietic cells similar to those found in the spleen, lymph nodes, and peripheral blood. Using immunocytochemical stains with canine-specific antibodies, all neoplastic cells strongly expressed cytoplasmic CD41 and 20-70% of the neoplastic cells expressed CD34 weakly to moderately. Rare (<0.5%) neoplastic cells weakly expressed vWF. The cells were negative for all other markers. Based on these results and the morphology of the neoplastic cells, a diagnosis of acute megakaryoblastic leukemia (AMegL) was made. In spite of treatment, results of a CBC performed 1 week later indicated progressive anemia and thrombocytopenia, and the dog was euthanized. To our knowledge, this report documents the first case of canine AMegL diagnosed with both anti-canine CD34 and CD41 antibodies.     

Disseminated mast cell tumor infiltrating the sphenoid bone and causing blindness in a dog

Mast cell tumors are found in most organs and tissues with variable biologic behavior in dogs. This case illustrates the clinical and magnetic resonance imaging (MRI) findings in a dog with disseminated mast cell tumor infiltrating the sphenoid bones. A 6‐year‐old male neutered Greyhound presented with a 3‐day history of acute onset of blindness. General physical examination was normal. Neurological examination revealed mildly disorientated mental status, absent menace response in both eyes, bilaterally decreased vestibulo–oculocephalic reflexes and absent direct and consensual pupillary light reflex in both eyes. An electroretinogram indicated normal retinal function in both eyes. A lesion involving the middle and rostral cranial fossa was suspected. Hematology and serum biochemistry were normal except decreased urea (1.2 mmol/L). MRI of the head revealed heterogeneous signal intensity of the sphenoid bones on T2‐weighted images and loss of their normal internal architecture. Cerebrospinal fluid analysis was normal. Abdominal ultrasound revealed hepatosplenomegaly and mesenteric lymphadenopathy. Fine needle aspirates were taken from the jejunal lymph nodes and the spleen. Results were consistent with disseminated mast cell tumor. The owner declined any treatment and the dog was euthanatized. Postmortem examination confirmed disseminated mast cell tumor affecting multiple organs, including the sphenoid bones. To our knowledge, this is the first case describing MRI features of disseminated mast cell tumor affecting the sphenoid bones and causing acute onset of blindness in a dog.     

Subcutaneous embryonal rhabdomyosarcoma in a dog: cytologic, immunocytochemical, histologic, and ultrastructural features

Abstract: A subcutaneous mass on the left antebrachium of an 11‐year‐old intact female English Pointer dog was evaluated presurgically by cytologic examination and immunocytochemical staining. The sample consisted of discrete, variably sized, markedly pleomorphic neoplastic cells that expressed vimentin with diffuse cytoplasmic staining, desmin with focal paranuclear staining, and myoglobin with diffuse cytoplasmic staining, consistent with a diagnosis of rhabdomyosarcoma. Lymphocytic and histiocytic markers were negative. Aspirates of the enlarged ipsilateral prescapular lymph node were positive for metastatic disease. Surgical excision of the tumor and lymph node were followed by histologic and electron microscopic examination. Histomorphologic appearance of neoplastic cells from the mass and the lymph node paralleled cytologic findings; the histologic diagnosis was round cell variant of embryonal rhabdomyosarcoma. By ultrastructural evaluation, cells contained numerous mitochondria and masses of cytoplasmic tangled myofilaments, features typical of rhabdomyoblasts. The dog received doxorubicin (30 mg/m²) every 3 weeks for 5 treatments. Local recurrence developed 6 months after resection but was not treated. Despite a guarded prognosis and untreated local recurrence, the dog was still alive 18 months after surgery. Cytologic evaluation and immunocytochemical staining were pivotal for the presurgical diagnosis of rhabdomyosarcoma.     

Pleural fluid from a dog with marked eosinophilia

A 12-year-old neutered male Shar-Pei was presented to the North Carolina State University Veterinary Teaching Hospital cardiology service with a 2-week history of coughing and a 2-day history of lethargy and anorexia. Pleural effusion and a mediastinal mass were detected with thoracic radiographs. Ten mL of fluid were removed via thoracocentesis, and cytologic examination of the fluid revealed marked eosinophilic inflammation and few atypical mast cells. Mast cell neoplasia was suspected. Aspirates of the mediastinal mass, abdominal lymph nodes, and bone marrow contained similar pleomorphic mast cells and increased numbers of eosinophils. The dog was diagnosed with systemic (visceral) mastocytosis, a rare form of neoplasia in dogs, and was euthanized. These tumors carry a poor to grave prognosis and the etiology is uncertain.     

Lymph node staging of oral and maxillofacial neoplasms in 31 dogs and cats

A retrospective study was performed to report the histologic examination results of regional lymph nodes of dogs and cats with oral or maxillofacial neoplasms. Twenty-eight dogs and 3 cats were evaluated. Histologic examination results of standard and serial tissue sectioning of regional lymph nodes were recorded. When available, other clinical parameters including mandibular lymph node palpation, thoracic radiographs, and pre- and postoperative fine needle aspiration of lymph nodes were compared with the histologic results. Squamous cell carcinoma, fibrosarcoma, and melanoma were the most common neoplasms diagnosed in dogs. Squamous cell carcinoma and fibrosarcoma were diagnosed in cats. Of the palpably enlarged mandibular lymph nodes, 17.0% had metastatic disease histologically. Radiographically evident thoracic metastatic disease was present in 7.4% of cases. Preoperative cytologic evaluation of the mandibular lymph node based on fine needle aspiration concurred with the histologic results in 90.5% of lymph nodes examined. Postoperative cytologic evaluation of fine needle aspirates of regional lymph nodes concurred with the histologic results in 80.6% of lymph nodes examined. Only 54.5% of cases with metastatic disease to regional lymph nodes had metastasis that included the mandibular lymph node. Serial lymph node sectioning provided additional information or metastasis detection. Cytologic evaluation of the mandibular lymph node correlates positively with histology, however results may fail to indicate the presence of regional metastasis. Assessment of all regional lymph nodes in dogs and cats with oral or maxillofacial neoplasms will detect more metastatic disease than assessing the mandibular lymph node only.     

Morphometrical approach for predicting regional lymph node micrometastatic load in canine mast cell tumours: preliminary results

Canine cutaneous mast cell tumours (MCTs) have a variable biologic behaviour, and accurate staging is necessary to dictate therapy and predict outcome. Regional lymph node (RLN) involvement is a relevant prognostic factor. While obvious lymph node (LN) metastases are relatively easy to be diagnosed, micrometastatic disease recognition is challenging. The main aim of the study was to evaluate the number of mast cells (MCs) in the LNs of clinically healthy dogs ( n = 4, group 1), dogs with inflammatory diseases ( n = 31, group 2) and dogs with cutaneous MCT ( n = 27, group 3), including animals with no RLN metastases (subgroup 3.1), those with occasional MCs in RLNs (3.2) and those with obvious RLN metastasis (3.3). MCs also were morphometrically evaluated for the following nuclear parameters: mean nuclear area (MNA), mean nuclear perimeter (MNP), largest to smallest diameter length (LS ratio), mean nuclear form factor and coefficient of variation of nuclear area. The average percentages of MCs were 0.0 and 0.01 in groups 1 and 2, respectively, and 0.07, 2.4 and 47.1 in subgroup 3.1, 3.2 and 3.3. MNA and MNP were significantly higher in subgroup 3.3 than in group 2 ( P < 0.05). MNA and MNP in subgroup 3.2 suggested the presence of neoplastic MCs; this prediction of micrometastatic load correlated with outcome. Analysis of preliminary results shows that nuclear morphometry is useful to detect micrometastatic disease in RLN of dogs bearing cutaneous MCTs.     

Metastatic pancreatic polypeptide‐secreting islet cell tumor in a dog

Abstract: A 14‐year‐old female spayed Golden Retriever was presented to the University of Florida's Veterinary Medical Center with history of lymphoplasmacytic gastroenteritis, intermittent vomiting, watery diarrhea, and weight loss for over a year. CBC, biochemical profile, and urinalysis were within reference intervals. Abdominal ultrasonographic examination revealed mesenteric and jejunal lymphadenopathy and hyperechoic hepatic nodules. Cytologic examination of the enlarged lymph nodes revealed loosely cohesive cells with moderate nuclear pleomorphism and rare punctate eosinophilic cytoplasmic granules. The cytologic interpretation was metastatic neuroendocrine neoplasia. On surgical exploration, a mass was detected in the right lobe of the pancreas. Histologic evaluation determined the mass to be an islet cell tumor. Approximately 98% of cells were positive by immunolabeling for pancreatic polypeptide (PP), and only rare cells were positive for insulin or somatostatin. All cells were negative for glucagon, gastrin, vasoactive intestinal polypeptide, protein gene product 9.5, synaptophysin, and chromogranins A and B. Pancreatic tumors that primarily produce PP are rare in dogs, and this is the first report of both the cytologic and histologic features of an islet cell tumor predominantly secreting PP. Clinical signs for these tumors are typically absent or nonspecific; signs may include watery diarrhea, as noted in this dog, although the diarrhea may have resulted from lymphoplasmacytic gastroenteritis. Additional case studies are needed to further characterize the cytomorphologic features and clinical presentation of PP‐secreting islet cell tumor, or polypeptidoma, in dogs.