Cutaneous T cell lymphoma mimicking cutaneous histiocytosis: differentiation by flow cytometry

A two-year-old, neutered female cross-bred labrador had multiple cutaneous nodules, biopsies of which revealed pathological changes consistent with cutaneous histiocytosis. During a period of one month the dog developed multicentric lymphadenopathy, a retrobulbar mass and masses within the quadriceps and cervical muscles. Fine needle aspiration cytology of the cutaneous nodules and lymph nodes and histological examination of the cutaneous nodules and muscle masses suggested the presence of lymphoblastic lymphoma. A definitive diagnosis of CD8+ T cell lymphoma was achieved by immunophenotyping the tumour cells by flow cytometry.     

Unique cytologic and histologic features of a suspected cutaneous xanthoma in a dog

A 4‐year‐old spayed female American Staffordshire Terrier presented to the U‐Vet Animal Hospital, Werribee, Australia, with a cutaneous mass that had been slowly growing over 12 months. Cytologic evaluation showed cohesive to individualized, vacuolated spindled cells often arranged in a perivascular pattern. The mass was completely excised, and the histopathologic examination demonstrated sheets of vacuolated spindled to round cells expanding the full thickness of the dermis. The cells demonstrated both Iba1 and CD18 antibody binding, leading to an initial interpretation of histiocytic sarcoma. Given the discordance with the clinical presentation, further immunohistochemistry (IHC) was performed. The cells demonstrated strong CD204 antibody binding and did not bind E‐cadherin antibody, consistent with a dermal macrophage origin. Ki‐67 antibody binding was regionally variable from <5% to 25%, with more regions that had low Ki‐67 expression. A fasted serum biochemistry panel revealed hypertriglyceridemia and persistent hypercholesterolemia. Based on clinical, microscopic, biochemical, and IHC results, the final interpretation was an indolent dermal histiocytic proliferation of macrophage origin, with a preference for cutaneous xanthoma or reactive dermal fibrohistiocytoma.     

Progression of cutaneous plasmacytoma to plasma cell leukemia in a dog

A 5‐year‐old male neutered Bernese Mountain Dog was presented for cutaneous plasmacytoma, which was treated by surgical excision. Four months later, the dog developed multiple skin masses, hyphema, pericardial and mild bicavitary effusions, myocardial masses, and marked plasmacytosis in the peripheral blood. Circulating plasma cells expressed CD34 and MHC class II by flow cytometry. Immunocytochemistry demonstrated that these cells were strongly positive for multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM‐1) and weakly to moderately positive for Pax5. The dog was hypoglobulinemic but had a monoclonal IgA gammopathy detected by serum immunofixation electrophoresis. The PCR analysis of antigen receptor gene rearrangements (PARR) by fragment analysis using GeneScan methodology revealed that plasmacytoid cells in the original cutaneous plasmacytoma and peripheral blood had an identical immunoglobulin heavy chain gene (IgH) rearrangement, indicating that both populations were derived from the same neoplastic clone. Canine cutaneous plasmacytoma rarely progresses to a malignant form and plasma cell leukemia is rarely diagnosed in the dog. This report describes a case of cutaneous plasmacytoma progressing to plasma cell leukemia with a rapid and aggressive clinical course. This report also highlights the utility of flow cytometry, immunocytochemistry, immunofixation electrophoresis, and PARR by fragment analysis using GeneScan methodology in the diagnosis of this hematopoietic neoplasm.     

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.     

Nasal tumor with widespread cutaneous metastases in a Golden Retriever

An intact, 8-year-old, male Golden Retriever dog was presented for evaluation of a nasal mass and approximately 30 firm, raised, variably ulcerated dermal and subcutaneous masses. Histopathology of both nasal and multiple skin masses revealed multiple nonencapsulated, infiltrative masses comprising clusters, anastomosing trabeculae, and packets of neoplastic, round to ovoid, hyperchromatic cells with marked nuclear molding. Surrounding the neoplastic cells was a marked stromal response in which many of the spindle-shaped cells expressed muscle-specific actin and had ultrastructural features consistent with myofibroblasts. A literature search indicates that this is the first report in a peer-reviewed journal of cutaneous metastasis of a nasal neuroendocrine tumor in any domestic animal species.     

Visceral leishmaniasis with cardiac involvement in a dog: a case report

A dog presented with cutaneous nodules, enlarged lymph nodes and oedema in limbs, face and abdomen. The diagnosis of visceral leishmaniasis was established by identification of Leishmania amastigotes within macrophages from skin and popliteal lymph node biopsies. At necropsy, lesions were found in different organs, but it was particularly striking to observe large areas of pallor in the myocardium. Histological examination revealed an intense chronic inflammatory reaction in many organs, and numerous macrophages were found to contain amastigote forms of Leishmania. The inflammatory reaction was especially severe in the heart, where large areas of the myocardium appeared infiltrated with huge numbers of mononuclear immune cells, causing cardiac muscle atrophy and degeneration. Despite the severe inflammation, the number of parasitized macrophages was low in the myocardium, as revealed by immunohistochemical staining of Leishmania amastigotes. Because cardiac involvement is not usually described in this condition, this dog represents a very rare case of canine visceral leishmaniasis with affection of the myocardium.     

Cytologic appearance of a keloidal fibrosarcoma in a dog

A 5-year-old neutered male, mixed-breed dog was presented with a single 4-mm, nodular, firm, haired subcutaneous mass on the left flank that had been present for approximately 2 weeks. Cytologic preparations of the mass revealed many spindle cells, few mast cells, rare eosinophils, rare macrophages, abundant hyalinized collagen, and moderate numbers of erythrocytes. The spindle cells were oval to fusiform, with oval nuclei, finely stippled to lacy chromatin, 1-5 variably sized prominent nucleoli, and moderate to abundant cytoplasm with indistinct cell borders, wispy cytoplasmic extensions, and occasionally, fine magenta granulation. The cell population exhibited moderate anisocytosis, moderate anisokaryosis, and rare binucleation. The eosinophilic material occurred both in large angular aggregates with blunt ends and in amorphous aggregates with fine wispy projections. Histologic findings were consistent with a keloidal fibrosarcoma. To the authors' knowledge, this report is the first to describe the cytomorphologic characteristics of a keloidal fibrosarcoma in a dog.     

Cytologic diagnosis of generalized cutaneous sporotrichosis in a hunting hound

A 1-year-old male Foxhound/Walker Hound mix was presented to the small animal internal medicine service at Louisiana State University School of Veterinary Medicine with a 6-week history of progressive, multifocal, ulcerative and draining, well-circumscribed lesions in a generalized distribution. Prior to referral, a presumptive diagnosis was made of sterile pyogranulomatous disease; immunosuppressive therapy was instituted but resulted in clinical deterioration. At presentation, the dog had marked neutropenia (1100 neutrophils/microL), and a mild toxic left shift (400 bands/microL). Cytologic findings in the exudates from a draining skin lesion included high numbers of markedly degenerate neutrophils (about 95% of nucleated cells) as well as low numbers of macrophages, small mature lymphocytes, and eosinophils. Low numbers of intracellular (within neutrophils and macrophages) and extracellular, pleomorphic, cigar-to-ovoid shaped organisms ( approximately 3x9 microm) consistent with Sporothrix were observed. Histopathologic examination of a skin biopsy showed marked, chronic, active, ulcerative, pyogranulomatous dermatitis and panniculitis, with intralesional yeast consistent with Sporothrix sp. The etiologic agent was confirmed as Sporothrix schenckii by macerated tissue fungal culture. The patient was treated with itraconazole, enrofloxacin, and clindamycin, with clinical resolution occurring over a 3-month period. This case is a rare example of the cytologic diagnosis of Sporothrix schenckii in a canine patient. Diagnosis of canine sporotrichosis is often challenging and usually requires tissue culture, as infected dogs typically harbor very few organisms. The patient's prior immunosuppressive therapy likely contributed to higher numbers of organisms in exudates from the cutaneous lesions, facilitating cytologic diagnosis.     

Lymphangiosarcoma with bone formation of the auricle in a dog

A 12-year-old mixed-breed neutered female dog was referred with cutaneous tumors at the left auricle. Histologically, the cutaneous tumor located in the dermis comprised numerous clefts and cavernous channels lined by neoplastic endothelial cells with no erythrocytes. Bone tissue without direct contact with neoplastic cells was seen in the well-developed stromal connective tissue. The neoplastic endothelial cells exhibited mild to moderate atypia. Immunohistochemically, neoplastic cells were positive for vimentin and negative for cytokeratin and factor VIII-related antigen. Basement membrane around the neoplastic lumens was positive for laminin in a linear or granular pattern. Ultrastructural examination revealed discontinuous basement membrane beneath the tumor cells. Histopathological features of this case were consistent with lymphangiosarcoma, and stromal ossification was characteristic.     

A case of xanthoma in a Saanen goat

This report describes a case of a subcutaneous xanthoma of the sacral region in a 2-year-old female Saanen goat. The tan-coloured mass was 8.5 cm × 4.0 cm × 0.5 cm in size. Yellow-white areas were present across the cut surface. Histopathologically, the mass was composed of foamy macrophages, numerous giant cells, abundant lipid material and cholesterol clefts. The structure consisted of lobular areas surrounded by a stroma. Tissue sections were negative for bacteria, fungi and mycobacteria. Frozen tissue from the mass stained positively with Oil Red O, confirming lipid accumulation in both the extracellular spaces and the large foamy macrophages. Immunohistochemically, the mass was positive for vimentin, proliferating cell nuclear antigen and CD68, but negative for smooth muscle actin, glial fibrillary acidic protein and S100 protein antibodies. As the animal was presented dead, it was not possible to analyse blood lipid levels. To the authors' knowledge, this is the first report of a xanthoma in a goat.     

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.     

Multiple cutaneous ganglioneuromas in a dog

A 3-year-old male Labrador retriever dog was presented with multifocal small cutaneous nodules, distributed mainly over the thoracic wall, the flank and the scrotum. The dog was otherwise in good health and had no significant past medical history. Radio- and sonographic examination revealed no evidence of internal tumours, including endocrine tumours. Histological examination of two excised samples revealed round, non-ulcerated nodules in the superficial corium, characterized by two different neoplastic cell components and mild inflammation. The first tumour cell population showed histomorphological characteristics of mature ganglion cells; the second featured small, spindle-shaped tumour cells with scant cytoplasm. Both neoplastic cell components expressed vimentin, neurofilament protein, pan-neuronal neurofilament, amyloid-precursor protein and chromogranin A. In addition, the spindle-shaped tumour cells were positive for 2', 3'-cyclicnucleotide 3'-phosphodiesterase. The findings had many histological and immunohistochemical features in common with primary cutaneous ganglioneuromas in humans, enabling the canine tumours to be also classified as multiple cutaneous ganglioneuromas.     

Gastric mucinous adenocarcinoma with cutaneous metastases in a dog: diagnosis by fine-needle aspiration cytology

A 12-year-old, intact, male mixed-breed dog was presented with anorexia, vomiting and multiple cutaneous nodules on its neck, trunk and hindlimbs. Fine-needle aspiration cytology of the nodules was characterised by a pleomorphic population of cells arranged singly or in small cohesive clusters, embedded in an amorphous mucinous material stained positive by periodic acid-Schiff (PAS). Acinar structures were occasionally found. Cells appeared either small with scant basophilic cytoplasm or large with a histiocytic appearance. Large cells had cytoplasm filled with a PAS-positive granular material. A presumptive diagnosis of cutaneous metastases of a mucinous adenocarcinoma was made. A primary, gastric, signet-ring mucinous adenocarcinoma was confirmed at postmortem examination and by histopathology. To the authors' knowledge, this is the first report of a gastric mucinous adenocarcinoma with cutaneous disseminated metastases in a dog.     

Anaplastic atypical myeloma with extensive cutaneous involvement in a dog

A 7-year-old, male, mixed breed dog was referred to the Veterinary Teaching Hospital at Kitasato University because of anorexia, lameness and multiple cutaneous lesions. Observation of bone marrow plasmacytosis, osteolytic bone lesions, serum myeloma protein and cutaneous infiltration of myeloma cells led us to a diagnosis of multiple myeloma (MM) with cutaneous involvement. Polymerase chain reaction and sequence analysis for the rearranged genes of immunoglobulin and T-cell receptor demonstrated that the neoplastic cells found in skin lesions or bone marrow are of B-lymphocyte lineage and share a common original precursor cell. The dog was treated with UW-Madison protocol or melphalan/prednisone protocol and survived 175 days. This is rare case of anaplastic MM with cutaneous involvement in dog.     

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.     

Leishmania infantum and Neospora caninum simultaneous skin infection in a young dog in Italy.

Leishmania infantum, the agent of canine leishmaniasis in Mediterranean countries, and Neospora caninum, a recently recognized protozoal pathogen in dogs, were diagnosed in a 9-month-old Argentine Dogo dog. Both skin lesions and neurological signs were present. Histopathology of cutaneous lesions revealed a suppurative, diffuse dermatitis with numerous intracellular protozoa. Serology was positive for both L. infantum (1:640) and N. caninum (1:800). Double-label immunohistochemical staining of skin samples with hyperimmune serum from L. infantum-infected dogs was positive for protozoa within macrophages, while the polyclonal antibody specific for N. caninum showed positive reactions for protozoa in endothelial cells and fibroblasts. Transmission electron microscopy (TEM) confirmed the infection with both protozoa. This is, to the authors' knowledge, the first case of simultaneous infection with L. infantum and N. caninum in a dog. It is possible that the immunosuppressive effects of Leishmania infection or long-term steroid therapy may have been a contributing factor to the development of N. caninum in this dog.     

What is your diagnosis? Hemorrhagic effusion in a dog

Abstract: A 2‐year‐old spayed female, German Shepherd dog was presented to the University of Illinois Veterinary Teaching Hospital with a history of intermittent lethargy. On physical examination, lung sounds were increased. The dog had a mild fever (103.7°F) and mild tachycardia (120 bpm). Thoracic ultrasound revealed a sternal mass and pericardial effusion, both of which were aspirated. On cytologic examination, the pericardial fluid contained a large amount of blood and was interpreted as a hemorrhagic effusion. Nucleated cells consisted mainly of macrophages containing phagocytized RBCs and hemosiderin and many clusters of reactive mesothelial cells. The majority of mesothelial cells contained variable amounts of rod‐shaped brown pigment granules that were suspected to be iron. The granules were positive for Prussian blue and carbol–fuschin, indicative of iron potentially mixed with lipofuscin. The granules stained negatively with Melan A, rhodamine, Hall's, and periodic acid‐Schiff. The iron within the mesothelial cells was likely secondary to hemorrhage, based on the erythrophagia and accumulation of hemosiderin in macrophages. Iron deposition and phagocytic activity in mesothelial cells has been reported previously in humans and rats, but not in dogs.     

Waldenström's macroglobulinemia in a dog with a bleeding diathesis

Abstract: An 11‐year‐old female spayed Whippet dog was referred to the Veterinary Hospital of the National Veterinary School of Lyon with a 3‐month history of chronic bleeding, cutaneous masses suggestive of hematomas, and hemorrhagic diarrhea. Laboratory abnormalities included leukopenia with neutropenia and lymphopenia, rouleaux formation, marked hyperproteinemia with hyperglobulinemia and normoalbuminemia, hypercalcemia, markedly increased serum urea concentration, mildly increased creatinine concentration, and proteinuria. Hemostatic screening tests showed marked prolongation of thrombin time, increased concentrations of fibrin(ogen) degradation products and D‐dimers, and slightly prolonged activated partial thromboplastin time. Serum and urine protein electrophoresis revealed a monoclonal peak identified as IgM by immunoelectrophoresis and an M‐spike, respectively. Cytologic evaluation of bone marrow revealed a hypocellular sample with lymphoplasmacytic cells comprising approximately 50% of all nucleated cells. These findings were consistent with a diagnosis of Waldenström's macroglobulinemia with secondary bleeding diathesis. Treatment with prednisone and chlorambucil was initiated, and the dog had a good response.     

Interdigital involvement in a case of primary cutaneous canine histoplasmosis in Japan

A 5-year-old male Siberian husky bred outdoor in Tokyo had a swollen paw with interdigital granulomatous lesions in the left hindlimb. The dog had no apparent pulmonary or gastrointestinal involvement. Histopathological analysis of the skin lesions demonstrated yeast-like organisms predominantly within macrophages. Sequence analysis of fungal ribosome RNA gene isolated from a paraffin sample revealed a 100% homology with the teleomorph of Histoplasma capsulatum. The present case may support the concept of primary cutaneous canine histoplasmosis as an endemic phenotype recognized in Japan.