Presumptive increase in protein‐bound serum calcium in a dog with multiple myeloma

Abstract: An 11‐year‐old male castrated Australian Shepherd was presented with a history of lethargy, panting, and weight loss for 1 month. Physical examination revealed a moderately enlarged spleen. Laboratory abnormalities included thrombocytopenia and marked hypercalcemia, with hyperglobulinemia, hypoalbuminemia, and a monoclonal spike in the β‐globulin region on serum protein electrophoresis. Serum total calcium concentration was markedly increased (16.5 mg/dL, reference interval 8.9–11.4 mg/dL) but ionized calcium concentration (1.39 mmol/L) was within the reference interval (1.25–1.45 mmol/L). Isosthenuria was noted, but the dog was not polyuric or polydipsic. Serum parathyroid hormone concentration was within reference limits and parathyroid hormone‐related peptide concentration was 0 pmol/L. Radiographic findings were largely unremarkable. Results of cytologic evaluation of a fine‐needle aspirate specimen from the spleen indicated plasma cell neoplasia. Based on the results of the electrophoresis, splenic aspirates, radiographs, and hypercalcemia, a diagnosis of splenic multiple myeloma was made. The marked hypercalcemia, normal ionized calcium and parathyroid hormone concentrations, and lack of osteolytic lesions indicated a presumptive increase in protein‐bound serum calcium, likely due to binding to molecules of the paraprotein (M protein). Protein binding of calcium in dogs with multiple myeloma should be considered as a potential mechanism of elevated total serum calcium concentration.     

IgA multiple myeloma in a dog

Multiple myeloma was diagnosed in a 10-year-old female Labrador which showed signs of weight loss, lethargy and skeletal pain. Radiography revealed well circumscribed osteolytic lesions in vertebrae, sternebrae, and the left humerus and radius along with generalised osteoporosis. The number of plasma cells in the bone marrow was increased and the serum gamma globulin concentration was elevated. Treatment with cyclophosphamide, mephalan and prednisone successfully controlled the malignancy but also resulted in suppression of the bone marrow. There was a remission time of 21.5 months.     

IgA multiple myeloma in a dog

Multiple myeloma was diagnosed in a lo-year-old female Labrador which showed signs of weight loss, lethargy and skeletal pain. Radiography revealed well circumscribed osteolytic lesions in vertebrae, sternebrae, and the left humerus and radius along with generalised osteoporosis. The number of plasma cells in the bone marrow was increased and the serum gamma globulin concentration was elevated. Treatment with cyclophosphamide, mephalan and prednisone successfully controlled the malignancy but also resulted in suppression of the bone marrow. There was a remission time of 21.5 months.     

Expression of tissue factor in canine mammary tumours and correlation with grade,stage and markers of haemostasis and inflammation

Tissue factor (TF) expression in human cancers has been associated with a procoagulant state and facilitation of metastasis. This study was conducted in order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial mammary tumours from 28 dogs were included. TF expression of the tumours was evaluated by immunohistochemistry using a polyclonal antibody against recombinant canine TF. In addition, thromboelastography, haemostatic and inflammatory parameters were evaluated in the patients. TF was recognized in 44% of benign and 58% of malignant tumours. TF localized to the cytoplasmic membrane of neoplastic luminal epithelial cells and/or diffusely in the cytoplasm. No association was found between TF expression and stage or grade of disease. A significant association between TF expression and antithrombin and plasminogen was found, and extensive TF expression was seen in a lymph node metastasis classified as anaplastic mammary carcinoma from a dog with concomitant disseminated intravascular coagulation (DIC).     

Biclonal gammopathy associated with immunoglobulin A in a dog with multiple myeloma

A 10-year-old neutered male Airedale Terrier was evaluated for inappetance, weight loss, and lameness. Multiple myeloma was diagnosed based on bone marrow plasmacytosis, multiple lytic bone lesions, and hyperglobulinemia with a clonal gammopathy on serum protein electrophoresis. Splenic plasmacytosis, and retinal lesions consistent with hyperviscosity syndrome also were found. Temporary responses to 2 different chemotherapy protocols (melphalan and prednisone, and cyclophosphamide and prednisone) were seen, with remission of clinical signs and a decrease in the biclonal gammopathy but no resolution of the splenic mass. Eventual return of clinical signs led to euthanasia at 175 days postdiagnosis. Necropsy examination confirmed multiple myeloma involving bone marrow and spleen, and glomerulonephritis. An immunoglobulin-A (IgA) gammopathy was demonstrated by immunoelectrophoresis; biclonality was ascertained by immunofixation electrophoresis. The clonal components consisted of intact Ig with a heavy chain of the a class and a light chain of undetermined class. To our knowledge, this is the first report of undimerized biclonal gammopathy in a dog caused by a single heavy chain class involving IgA.     

Neurologic complications of IgA multiple myeloma associated with cryoglobulinemia in a dog

A diagnosis of vertebral multiple myeloma, based on radiographic evidence of osteolytic lesions and the finding of monoclonal paraprotein and large numbers of plasma cells in bone marrow biopsies, was made in a mature Doberman Pinscher. The abnormal serum paraprotein was a cryoglobulin of the immunoglobulin A class. Neurologic signs associated with the tumor included pain, progressive pelvic limb paresis, and paraplegia that developed during a 6-week period.     

"Flaming" plasma cells in a dog with IgA multiple myeloma

Multiple Myeloma with "flaming" plasma cell infiltration of the bone marrow was found in an 8-year-old Shetland sheepdog. Immuno-electrophoresis results indicated that the myeloma protein was IgA. Flaming plasma cells frequently have been associated with human IgA myeloma.     

Severe hydrocephalus in a raccoon dog (Nyctereutes procyonoides)

Hydrocephalus is one of the most common central nervous system malformations in domestic dogs, yet they are poorly documented and studied in wild carnivoran mammals. A pup of raccoon dog (Nyctereutes procyonoides) was rescued and brought to Wildlife Center. The pup showed generalized ataxia, a domed skull, and an open bregmatic fontanelle. Ultrasound and MRI showed severe enlargement of the lateral ventricle with the loss of septum pellucidum resulting in a single large ventricle and cervical syringohydromyelia. Although treatment was attempted, the animal was euthanized due to poor prognosis. At necropsy, macroscopic findings were identical to the diagnostic imaging, where marked enlargement of the calvarium, and attenuated gyri and sulci were observed. Finally, hydrocephalus was confirmed. Here, we describe a case of hydrocephalus in a raccoon dog (Nyctereutes procyonoides).     

Mitotane (o, DDD) resistance in a dog with pituitary-dependent hyperadrenocorticism and phaeochromocytoma

A dog was presented with a 2 year history of polyuria and polydipsia due to pituitary-dependent hyperadrenocorticism. A low-dose dexamethasone suppression test and measurement of plasma ACTH concentration confirmed the diagnosis. Treatment was instituted with mitotane at 44 mg/kg/day and then 88 mg/kg/d without complete resolution of signs. The dog collapsed with signs consistent with liver disease and was euthanased. Necropsy revealed a phaeochromocytoma of the left adrenal medulla with extensive metastases to the liver. A chromophobe adenoma of the pars intermedia of the pituitary was found.     

Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a dog

A seven-year-old castrated male Yorkshire terrier dog was presented for a recurrent skin disease. Erythematous skin during the first visit progressed from multiple plaques to patch lesions and exudative erosion in the oral mucosa membrane. Biopsy samples were taken from erythematous skin and were diagnosed with epitheliotropic T cell cutaneous lymphoma by histopathology and immunochemical stain. In serum chemistry, the dog had a hypercalcemia (15.7 mg/dl) and mild increased alkaline phosphatase (417 U/l). Immunohistochemistry was performed to detect parathyroid hormone-related peptide (PTH-rP) in epitheliotropic cutaneous lymphoma tissues but the neoplastic cells were not labeled with anti-PTH-rP antibodies. The patient was treated with prednisolone and isotretinoin. However, the dog died unexpectedly.     

Intracranial extension of retrobulbar blastomycosis (Blastomyces dermatitidis) in a dog

Blastomycosis (Blastomyces dermatitidis) is a fungal disease that is endemic in the southern United States. This case report illustrates the clinical, MRI and histopathologic findings in a dog with invasion of a retrobulbar blastomycotic lesion into the calvarium. A 5‐year‐old intact female Weimaraner was referred for a 2‐month history of change in behavior and recent onset of visual deficits. Magnetic resonance imaging (MRI) examination revealed a large (5.8 × 2.0 × 2.5 cm) mass extending from the left orbit through a circular defect in the left cranioventral aspect of the calvarium caudally to the level of the pituitary fossa and interthalamic adhesion. The mass was heterogeneously iso‐ to hypointense on T2‐W images, slightly hypointense on T1‐W images, did not attenuate on fluid attenuated inversion recovery (FLAIR) images, and did not show evidence of susceptibility artifact on T2*‐W gradient recalled echo (GRE) images. Vasogenic edema and associated mass effect were noted. The mass showed strong homogeneous contrast enhancement with well‐defined margins and had thickening of the adjacent meninges (dural tail sign). Based on MRI findings a malignant neoplastic process was considered most likely and the patient was placed on oral prednisone to decrease peri‐tumoral inflammation. The dog initially improved but was euthanized 3 weeks later for worsening clinical signs. Histopathologic assessment of the mass revealed marked pyogranulomatous optic neuritis with intralesional fungal yeasts consistent with blastomycosis (Blastomyces dermatitidis). To our knowledge this is the first report of invasion of a retrobulbar blastomycotic lesion into the calvarium in a dog.     

Blindness in a dog with IgA-forming myeloma

A 9-year-old dog with a 2-month history of weight loss and a 1-week history of blindness had an IgA-forming myeloma. Seemingly, the blindness was a result of bilaterally detached retinas. The dog also had leukopenia, anemia, hypoalbuminemia, hyperglobulinemia, and proteinuria as well as lytic lesions in the cervical portion of the spine and high IgA concentrations in serum and urine. Evaluation of aspirates from the subretinal spaces revealed lymphocytes in a proteinaceous fluid. Histologically, retinal lesions consisted of vascular endothelial cell damage and intraretinal cysts and hemorrhages.     

Malignant transformation of a giant congenital pigmented nevus (hamartoma) in a dog

A male Golden Retriever was born with a large area of abnormal skin and hair on the distal pelvic limb. A tumour arose from the proximal margin of this area at 5 years of age. Histopathological examination of the abnormal area of skin revealed an area in which follicles were surrounded by nodular accumulations of densely packed round to spindle-shaped cells with fine granular intracytoplasmic melanin. Similar cells were present within the subcutaneous fat, and clusters of densely pigmented melanocytes were scattered within the basal epidermis, follicular epithelium, and dermis. A diagnosis of giant congenital pigmented nevus (hamartoma) was made. The tumour from the proximal end of this area was composed of densely packed, moderately pleomorphic, poorly differentiated and pigmented, spindle-shaped to epithelioid melanocytes, and was diagnosed as malignant melanoma. Metastasis of the malignant melanoma to the stifle and inguinal regions occurred within 6 months. To date, the authors are unaware of prior reports of a canine giant congenital pigmented nevus (hamartoma) with transformation to a malignant melanoma.     

Malignant ocular melanoma in a dog

A mongrel male dog of three years old was referred to the Seoul National University Veterinary Teaching Hospital following a one month history of glaucoma. On ophthalmic examination, hyphema, glaucoma, uveitis, iridal mass, and loss of vision were noted in the right eye. Ultrasonography and computed tomography revealed a mass with involvement of the entire uvea. Radiographic evaluation did not reveal any evidence of distant metastasis. The right eye was surgically removed because of the high likelihood of neoplasia. A histologic diagnosis of malignant uveal melanoma was made.     

Hyperalbuminemia associated with hepatocellular carcinoma in a dog

Abstract: A 12‐year‐old, neutered male, mixed‐breed dog was presented to The Ohio State University Veterinary Teaching Hospital with a history of weight loss and weakness. Laboratory abnormalities reported by the referring veterinarian during the past year included increased alkaline phosphatase (ALP) activity, hyperalbuminemia, and nonregenerative anemia. On referral, the dog appeared hydrated and had moderate muscle wasting and hepatomegaly. A large lobular hepatic mass was observed ultrasonographically. Laboratory results included mild to moderate nonregenerative anemia, urine‐specific gravity of 1.035, 3+ proteinuria, increased serum activities of alanine aminotransferase (229 U/L, reference interval 10–55 U/L), ALP (813 U/L, reference interval 15–120 U/L), and the steroid‐induced isoform of ALP (676 U/L, reference interval 0–6 U/L), marked hyperalbuminemia (5.3 g/dL, reference interval 2.9–4.2 g/dL), and an increased A/G ratio (1.7). Hyperalbuminemia was confirmed by reanalysis on 2 different analyzers and by agarose gel electrophoresis, and colloid osmotic pressure (COP) was markedly increased (42.5 mmHg, reference interval 20–25 mmHg). Cytologic examination of a fine‐needle aspirate of the hepatic mass indicated hepatocellular proliferation; histologic examination of an excisional biopsy confirmed hepatocellular carcinoma. Three weeks after surgery, the albumin concentration, A/G ratio, COP, and ALT activity had normalized, but ALP activities remained high. We hypothesized that hyperalbuminemia developed secondary to hepatocellular carcinoma due to increased synthesis of albumin by malignant hepatocytes or due to decreased negative feedback from impaired hepatocellular osmoreceptivity. Hepatocellular carcinoma has been associated with paraneoplastic secretion of other proteins, but hyperalbuminemia has been reported only once in a human patient and has not previously in dogs.     

Extensive cutaneous metastases in a dog with duodenal adenocarcinoma

Abstract: A 6-year-old Rottweiler was presented to the North Carolina State University College of Veterinary Medicine for evaluation of multiple cutaneous nodules. The dog had a history of anorexia, vomiting, and hind-limb paraplegia. Results of cytologic examination of the cutaneous nodules were consistent with a round cell tumor. At necropsy, primary tumors were found coalescing in the duodenum and the pancreas and extending into the associated mesentery. Numerous masses also were found throughout the skin, abdominal and thoracic viscera, and lumbar spinal cord. Histologically, the duodenal tumor had variable morphology, with some areas resembling adenocarcinoma and others resembling anaplastic round cell neoplasia; the skin and other metastatic lesions resembled round cell neoplasia. Immunohistochemistry of the cutaneous, duodenal, and pancreatic masses showed the neoplastic cells were positive for pancytokeratin, supporting an epithelial origin. In addition, low numbers of neoplastic cells were positive for periodic acid-Schiff and Alcian blue, consistent with acid mucin production by duodenal epithelium. These findings confirmed that the cutaneous nodules were metastatic lesions originating from the duodenal adenocarcinoma. Cutaneous metastasis of intestinal carcinoma is rare in domestic animals. This case demonstrates the potential difficulty in diagnosing metastatic lesions based on cytologic and histologic morphology alone, because the cutaneous metastases may not resemble the primary neoplasm morphologically.     

Cutaneous lymphoma in a juvenile dog

Abstract: An 18-month-old male Doberman Pinscher was referred to the Veterinary Medical Teaching Hospital of the College of Veterinary Medicine for an erythemic nodular mass on the right forelimb. The mass was diagnosed as cutaneous lymphoma, based on cytologic examination of a mass aspirate and histopathology. Using immunohistochemistry the neoplastic cells were positive for CD3 but negative for CD79a, E-cadherin, and pancytokeratin, confirming their origin as T lymphocytes. No tumor recurrence was noted 18 months after surgery. To our knowledge, this is the first report of a solitary nodular form of cutaneous lymphoma in a young dog.     

Keratoconjunctivitis associated with Toxoplasma gondii in a dog

A 12-year-old Pug presented with a 3-mm corneal mass OD. The dog was currently being treated for keratoconjunctivitis sicca (KCS) and pigmentary keratitis OU. A superficial keratectomy followed by cryotherapy was performed OD. A histopathologic diagnosis of epithelial dysplasia and suppurative keratitis was made and the lesion resolved. Two months later, a yellow/tan conjunctival mass, diffuse chemosis and conjunctival thickening was discovered OD. Necrotizing conjunctivitis with protozoal parasites was diagnosed with histopathology. Complete blood count and a serum biochemistry panel were normal. Neospora caninum and Toxoplasma gondii titers were negative. The conjunctivitis resolved after a 6-week course of oral clindamycin. Two months later, the patient presented with a similar conjunctival mass OS. Toxoplasma gondii was confirmed as the etiologic agent with immunohistochemical staining. Repeat T. gondii titers were negative. Oral clindamycin was re-instituted. The corneal biopsy was re-reviewed and protozoal organisms were discovered. Three months later, a recurrence was suspected and oral ponazuril was initiated for 28 days. There has been no evidence of recurrence since this treatment. Ocular toxoplasmosis is rare in the dog but reports have included episcleritis, scleritis, retinitis, anterior uveitis, ciliary epithelium hyperplasia, optic neuritis and polymyositis. To our knowledge, this is the first confirmed report of toxoplasmosis causing only corneal and conjunctival disease in the dog. We hypothesize that these localized lesions may be associated with topical immunomodulating therapy for KCS. Toxoplasmosis should be considered as a differential for canine conjunctivitis and corneal disease and has the potential to manifest in one or both eyes.