Large anaplastic spinal B‐cell lymphoma in a cat

Abstract: A 5‐year‐old female spayed domestic shorthair cat was presented for evaluation of tetraparesis. The neurologic lesion was localized to the cervical spinal segment (C1–C6). A left axillary mass was identified, and the results of fine needle aspiration cytology indicated malignant round cell neoplasia of possible histiocytic origin. The cells were large, had marked anisocytosis and anisokaryosis, occasional bi‐ and multinucleation, and cytoplasmic vacuolation. Euthanasia was performed due to the poor prognosis associated with severe, progressive neurologic signs and a malignant neoplasm. Postmortem examination revealed spinal cord compression and an extradural mass at the C1–C2 spinal segment, with neoplastic cells in the adjacent vertebral bodies, surrounding skeletal muscle, left axillary lymph node, and bone marrow from the right femur. The initial histologic diagnosis was anaplastic sarcoma, but immunohistochemical results indicated the cells were CD20+ and CD45R+ and CD3?, compatible with a diagnosis of B‐cell lymphoma. CD79a staining was nonspecific and uninterpretable. Weak to moderate CD18 positivity and E‐cadherin positivity were also observed. Clonality of the B‐cell population could not be demonstrated using PCR testing for antigen receptor gene rearrangement. To the authors' knowledge, this is the first reported case of a feline spinal anaplastic B‐cell lymphoma exhibiting bi‐ and multinucleated cells. The prognostic significance of this cell morphology and immunophenotype is unknown.     

Primary gastric histiocytic sarcoma in a dog--a case report

A 12-year-old intact female mixed breed dog was presented for chronic, intermittent vomiting and diarrhoea. On endoscopic examination a protruding mass arising from the mucosal surface of the pyloric region was detected. Cytological and histological examination revealed an accumulation of pleomorphic round/oval phagocytic cells suggesting histiocytic origin. This was confirmed by immunohistochemistry. No extra-gastric involvement was detected on clinical examination or at necropsy. This is the first report of primary gastric histiocytic sarcoma in a dog.     

Of all the nerve! A subcutaneous forelimb mass on a cat

A 16-year-old, male, neutered cat had a 2.5 X 1.5 cm mass on the medial aspect of the right carpus. Cytologic examination of a fine-needle aspirate of the mass indicated a markedly pleomorphic population of plasmacytoid to histiocytic-appearing cells. The cytologic diagnosis was malignant neoplasia of probable mesenchymal or round cell origin. The right forelimb was surgically removed and the scapular, axillary, and prescapular lymph nodes were excised. Malignant fibrous histiocytoma was tentatively diagnosed histologically; however, the tumor cells subsequently were found to be negative for histiocytic (MAC 387, antitrypsin), T-cell (CD3), and B-lymphocyte (immunoglobulin light chains, Ly 5/CD45R) markers, and positive for glial fibrillary acidic protein, vimentin, and S-100. Based on the immunohistochemical results, the diagnosis was modified to malignant peripheral nerve sheath tumor (PNST). Six months after surgery, the cat was reported to be well and had no evidence of metastasis. PNSTs are rare tumors in cats, and are considered as synonymous with schwannomas, neurofibrosarcomas, and hemangiopericytomas. In this cat, the plasmacytoid and pleomorphic appearance of the PNSTcells in cytologic and histologic specimens was unusual, and made it difficult to reach an accurate diagnosis without immunocytochemistry.     

Disseminated histiocytic sarcoma with peripheral blood involvement in a Bernese Mountain dog

Abstract: A 6‐year‐old Bernese Mountain dog was presented with a history of lethargy and weight loss of 2 weeks duration. On physical examination the dog had pale mucous membranes and tachypnea. Ultrasound examination revealed hepatomegaly, splenomegaly, and mesenteric lymphadenomegaly. Results of a CBC included marked normocytic normochromic nonregenerative anemia, marked thrombocytopenia, and moderate leukocytosis with mild neutrophilia and a large population of unclassified round cells (6.2 × 10³/μL). The unclassified cells occasionally were bi‐ or multinucleated and had variably abundant pale basophilic cytoplasm that contained multiple irregular clear vacuoles and occasionally erythrocytes. Fine needle aspirate specimens of the mesenteric lymph nodes and spleen were composed of a population of round pleomorphic cells with the same features as the circulating cells. On flow cytometric analysis of peripheral blood, the unclassified cells expressed CD18, CD45, CD11c, CD1c, and CD14; immunocytochemical analysis of blood smears also indicated the cells were positive for CD1c, CD1a, and CD11c. The dog died a few hours after referral. The histologic interpretation of samples collected from spleen, liver, and lymph nodes was malignant neoplasia of histiocytic origin. Immunohistochemical staining yielded negative results for CD11d, a marker of red‐pulp macrophages, ruling out hemophagocytic histiocytic sarcoma. Based on clinical and pathologic findings, the final diagnosis was disseminated histiocytic sarcoma (DHS) with peripheral blood involvement. To our knowledge, DHS in a dog with evidence and immunophenotyping of neoplastic cells in peripheral blood has been reported only rarely.     

A comparative pathological study on granulomatous meningoencephalomyelitis and central malignant histiocytosis in dogs

Histiocytic proliferative disorders in canine central nervous system (CNS) including granulomatous meningoencephalomyelitis (GME) and malignant histiocytosis were compared pathologically. Lesions of GME mainly existed in the white matter of the cerebrum, brainstem and cerebellum and consisted of characteristic perivascular cuffing, parenchymal granuloma and leptomeningeal infiltrates of mononuclear cells. In malignant histiocytosis, there were two histological patterns, diffuse proliferation of neoplastic histiocytes through the leptomeninges and neoplastic nodule formation in the parenchyma. Neoplastic histiocytes exhibited mild to severe cellular atypia and high ability of invasion into the brain parenchyma. Mitotic and phagocytic figures were also observed. Several histiocytic markers, including lysozyme, alpha1-antitrypsin and lectin RCA-1, revealed histiocytic origin of both inflammatory and neoplastic cells, however, those were not determinative for the discrimination between GME and malignant histiocytosis. CD3- and PCNA-positive cells existed in the lesions of both diseases. The number of CD3-positive cells in GME tended to be greater than in malignant histiocytosis, while the difference was not statistically significant.     

Morphologic, immunohistochemical, and molecular characterization of hepatosplenic T-cell lymphoma in a dog

A 13-year-old neutered male Jack Russell Terrier (Parson Russell Terrier) was presented to the Texas Veterinary Medical Center with a history of lethargy, depression, vomiting, and fever. The dog had mildly regenerative anemia, severe thrombocytopenia and low antithrombin activity. Marked splenomegaly was found on physical examination and imaging studies, and malignant round cell neoplasia and marked extramedullary hematopoiesis were diagnosed on aspirates of the spleen. The dog underwent exploratory laporatomy and splenectomy. Because of a rapid decline in clinical condition postsurgery, the dog was euthanized. Splenic and hepatic biopsies were submitted for histopathologic evaluation. A neoplastic population of round cells was found throughout the splenic parenchyma and within hepatic sinusoids. The neoplastic cells stained strongly positive for CD3 (T-cell marker) and were negative for CD79a (B-cell marker) and lysozyme (histiocytic marker). A diagnosis of T-cell lymphoma was confirmed by assessment of T-cell clonality using canine-specific polymerase chain reaction-based techniques. Although expression of the gammadelta T-cell receptor was not evaluated, this case shares many similarities with a rare syndrome in humans known as hepatosplenic gammadelta T-cell lymphoma.     

Extramedullary plasmacytoma in a horse with ptyalism and dysphagia.

A Clydesdale mare was examined for weight loss, inappetence, ptyalism, and dysphagia. The main abnormality revealed by serum biochemistry was a marked hyperglobulinemia, and protein electrophoresis revealed a monoclonal gammopathy in the gamma region. The urine was positive for Bence Jones proteins. These findings suggested a plasma cell tumor. The neoplasm could not be located with extensive antemortem examination. At postmortem, neoplastic cells morphologically compatible with plasma cells and positive for equine IgG with imunoperoxidase staining infiltrated the pericardium, mediastinal stromal tissues, adrenal glands, meninges, atrioventricular valves, aorta, abdominal and thoracic fat, and nerves, including the trigeminal nerve. The neoplastic cells invading the cranial nerves were responsible for many of the presenting signs.     

Multifocal cutaneous histiocytic sarcoma in a young dog and review of histiocytic cell immunophenotyping

A 9‐month‐old male Great Dane had progressive generalized nodular dermatopathy for several months. There were > 100 raised, alopecic, firm, painful nodules throughout the skin. Aspirates from several lesions yielded moderate numbers of irregularly round or polygonal to spindle‐shaped cells with mild to moderate anisocytosis and few inflammatory cells, and the cytologic interpretation was proliferation of mesenchymal or histiocytic cells. On histopathologic examination, nodules were composed of densely packed sheets of round to spindle‐shaped cells with mild anisokaryosis and low mitotic activity. Multifocal histiocytic sarcoma with a spindle‐cell pattern was diagnosed based on morphologic features and intense expression of CD18. Additional immunophenotypic analysis on frozen sections of tissue confirmed the diagnosis of histiocytic sarcoma; expression of CD18, CD45, CD1a, CD11b, and CD11c, limited expression of Thy‐1 (CD90) and CD80, and lack of expression of CD4, CD11d, and CD86 indicated that the cells were likely interstitial dendritic cells; a review of reactive and neoplastic dendritic cells is provided. Based on staging, internal organs were not affected. Sequential treatment with lomustine and doxorubicin failed to prevent progression of the cutaneous lesions, and the dog died 3 months after initial diagnosis. At necropsy, a focus of neoplastic cells was present in one lymph node, but except for skin other organs were not involved. The clinical presentation of histiocytic sarcoma may be unusual, and neoplastic cells may lack overt features of malignancy on cytologic and histopathologic examination. In some instances, immunophenotyping is required to differentiate histiocytic sarcoma from other histiocytic disorders.     

Chromatophoroma in a crevice kelpfish (Gibbonsia montereyensis)

A captive adult crevice kelpfish, Gibbonsia montereyensis, developed a cutaneous mass, approximately 9 × 7 mm on the right side of the head in an area of nonscaled skin. Following surgical debulking, examination of both impression smears and histologic sections of the tumor revealed a predominant population of round to spindloid to polygonal cells with a moderate amount of lightly basophilic cytoplasm. The cytoplasm was filled with round, variably-sized reddish-brown granules that often obscured the nucleus. Nuclei were round to ovoid with coarsely granular chromatin. There was minimal anisocytosis and anisokaryosis. The cytoplasmic granules in histologic sections were weakly positive by the Fontana-Masson method, and staining was eliminated with melanin bleach. Immunohistochemical staining was strongly positive with a murine monoclonal antibody for melan A. As the specificity of melan A for melanophores is not clearly defined in nonmammalian species, the tumor was examined by transmission electron microscopy. Melanophores were not detected. Instead, neoplastic cells were filled with numerous intracytoplasmic organelles with triple-limiting membranes composed of concentric lamellae; these structures were most compatible with pterinosomes, which are the pigment-containing organelles of cells called xanthophores and erythrophores. As both of these organelles are ultrastructurally indistinguishable and as kelpfish skin is known to contain both xanthophores and erythrophores, a diagnosis of a mixed pigment cell tumor or chromatophoroma was made. As the tumor was grossly reddish-brown, the possibility of a neoplastic population of only erythrophores could not be excluded. Pigment cell tumors, arising from cells of the embryonic neural crest, are common in reptiles and bony fish.     

Immunohistochemical expression of E-cadherin does not distinguish canine cutaneous histiocytoma from other canine round cell tumors

Immunohistochemistry for E-cadherin (ECAD) has been used to distinguish canine cutaneous histiocytoma from other leukocytic neoplasms ("round cell tumors"). To determine the specificity of this test, 5 types of canine cutaneous round cell tumors were evaluated for immunohistochemical expression of ECAD. Tumors of all 5 types had variable cytoplasmic, plasma membrane, and/or paranuclear ECAD expression: All 13 cutaneous histiocytomas were ECAD+; all but 1 of 14 mast cell tumors expressed ECAD; 10 of 12 epitheliotropic lymphomas reacted with E-cadherin antibody; of 72 plasmacytomas, 54 were ECAD+; and 5 of 5 histiocytic sarcomas were positive. Conclusions based on these results include the following: First, immunoreactivity for ECAD is not limited to leukocytes of cutaneous histiocytoma; second, antibody to ECAD also labels neoplastic cells in most mast cell tumors, plasmacytomas, cutaneous histiocytic sarcomas, and epitheliotropic lymphomas; third, although most histiocytomas have membranous ECAD expression, the immunoreactivity varies among round cell tumors and is frequently concurrent in different cellular compartments; fourth, the distinctively paranuclear ECAD expression pattern in epitheliotropic lymphomas might distinguish them from other round cell tumors; and, fifth, ECAD should be used with other markers (eg, MUM1 for plasmacytomas, KIT for mast cell tumors, CD3 and CD79a for lymphomas) to distinguish among canine round cell tumors.     

Malignant fibrous histiocytoma in a Djungarian hamster

A subcutaneous malignant fibrous histiocytoma (MFH) was observed in the region between the right posterior trunk and right hind limb of a 2-year-old male Djungarian hamster weighing 45 g. Histologically, the tumor consisted of bizarre multinucleated giant cells, histiocytic cells, and fibroblastic cells with a storiform pattern, and was considered to be of the storiform-pleomorphic type of MFH. Severe nuclear atypia with prominent nucleoli and many mitotic figures was also observed. Electron microscopy demonstrated fibroblastic cells and histiocytic cells. The fibroblastic cells were spindle-shaped, and sometimes had an invaginated nucleus. The histiocytic cells were polygonal with an oval or kidney-shaped nucleus. The cytoplasm of both cells contained numerous free ribosomes, small amounts of rough endoplasmic reticulum, and round mitochondria. Tumor cells were immunohistochemically positive for vimentin, and were thought to be of undifferentiated mesenchymal cell origin. This is the first report of spontaneous MFH in a hamster.     

Anaplastic gangliocytoma with eosinophilic cytoplasmic granules in a cow.

In a 3-year-old Holstein cow, a tumor mass replaced the left olfactory bulb. The tumor was highly or moderately cellular, and consisted of tumor cells showing pleomorphism and anaplasia, sometimes with intracytoplasmic granules. The tumor showed weak reactivity for neurofilaments (NF) in most cells with distinct staining in a minority, and it was extremely rare to see neoplastic cells with positivity for glial fibrillary acidic protein (GFAP). The neoplastic cells displayed some ultrastructural features reminiscent of ganglionic cells, and the cytoplasmic granularity was due to the presence of numerous lysosomes. This tumor expressing both NF and GFAP may be histogenetically related to brain tumors of pluripotential cell origin in calves.     

Ultrastructure and lectin histochemistry of equine cutaneous histiolymphocytic lymphosarcomas

Tissues from subcutaneous lymphosarcomas and regional lymph nodes were examined by light and electron microscopy and by lectin histochemistry. Tumors were composed of two major cell types: small lymphocytes with few organelles and pleomorphic histiocytic cells with undulant surfaces, large numbers of cytoplasmic vacuoles, and many mitochondria with large crystalline inclusions. A large gram-positive coryneform bacterium was isolated from tumor nodules but was not identified morphologically in tumor tissues. Evaluation of sections of tumors with lectins as histochemical probes revealed three staining patterns: 1) lectin labeling histiocytic cells only (wheat germ, succinylated-wheat germ, Phaseolus vulgaris and soybean agglutinins); 2) lectins labeling histiocytic, interstitial and some lymphoid cells (concanavalin A, and Pisum sativum, Lens culinaris, and Ricinus communis I agglutinins); and 3) lectins failing to label any cell (peanut, Sophora japonica, and Ulex europaeus I agglutinins). In the lymph node, macrophages were labeled by lectins of groups 1 and 2; interdigitating reticular cells were labeled by group 2 lectins. Lectin staining of histiocytic cells in tumor tissues suggested that these were reactive cells and that lymphoid cells were the primary neoplastic component.     

Cutaneous plasmacytomas with amyloid in six dogs.

Cutaneous plasmacytomas associated with local deposition of amyloid were diagnosed by light microscopy in a series of six older dogs (mean age 10.7 years) consisting of two Cocker Spaniels, a Poodle, a Weimeraner, and two mixed-breed dogs. The neoplasms occurred on the digits (2 dogs), forelimb (2 dogs), lip (1 dog), and ear (1 dog). In most cases, groups of neoplastic plasma cells were widely separated by large homogeneous islands of amyloid. The neoplastic cells had characteristic plasmacytoid features, but the degree of pleomorphism varied greatly between different neoplasms. In four of the six tumors, the diagnosis of plasmacytoma was confirmed by the demonstration of a monoclonal plasma cell population using immunofluorescent staining for anti-canine immunoglobulins. In these tumors, the neoplastic cells reacted with only one class of immunoglobulins (IgG). The amyloid did not react with any of the reagents used. The suspicion that the amyloid was of immunoglobulin origin (primary amyloid) was supported by its retention of birefringence under polarized light after treatment with potassium permanganate and staining with Congo red.     

Multinodular Malignant Cutaneous Mast Cell Tumor in a Horse With Generalized Pruritus and Reactive Fibrosis: A Case Report

Mast cell tumor (MCT) has long been considered as an uncommon neoplasm in horses. Cytological and behavioral evidence of its malignancy is usually lacking, and only a few reports have described MCT displaying malignant behavior. An 18-year-old Friesian stallion presented with a one-year history of intermittent and progressive skin lesions on the left forelimb associated with intense, generalized pruritus and apathy temporarily responsive to glucocorticoids and antibiotics. The horse was alert and responsive with poor body condition and marked generalized pruritus. The left forelimb was markedly enlarged and surrounded by numerous firm 2- to 20-cm masses that were ulcerated and focally necrotic. A 7-cm round firm mass was observed on the left dorsal neck. Dermatological examination revealed generalized moth-eaten alopecia and scaling with erosions and ulcers secondary to pruritus. A direct skin smear from the affected leg showed severe eosinophilic inflammation and neutrophilic inflammation with pleomorphic bacteria. Histopathology of the skin and biopsies of the underlying tissues revealed an abundant population of atypical mast cells consistent with a malignant MCT. The horse was euthanized and necropsy revealed a marked fibrous reaction on longitudinal sections of the affected limb, and the tumor could be detected on only a few histological slides. Diagnosis of equine MCT can be challenging because of the massive accompanying fibrous reaction. Mast cell tumor should be suspected in the presence of eosinophilic infiltration of the affected tissue and in cases of generalized pruritus not attributable to other causes.     

Systemic AL amyloidosis associated with multiple myeloma in a horse

AL amyloidosis is the most common type of systemic amyloidosis in humans, and it is frequently associated with multiple myeloma. But, AL amyloidosis is very rare in domestic animals. A 16-year-old Quarter horse gelding was diagnosed with systemic AL amyloidosis associated with multiple myeloma. Clinical problems were rapid weight loss, muscle atrophy, soft unformed stool, and ventral edema. Grossly, diffuse gastrointestinal hemorrhage, markedly thickened jejunal mucosa, and splenomegaly were present. Microscopically, diffuse severe amyloid deposits were present in the lamina propria of glandular stomach, duodenum, and jejunum. Much of the spleen and sternal bone marrow was replaced by neoplastic round cells, and multiple foci of amyloid were also present in the spleen and bone marrow. Electron microscopy revealed the neoplastic round cells to be of plasma cell origin, and the amyloid showed a strongly positive immunoreactivity with polyclonal anti-human immunoglobin lambda light-chain antisera. To our knowledge, this is the second report describing systemic AL amyloidosis in domestic animals-associated plasma cell neoplasia and the first associated with multiple myeloma, as is common in humans.     

Multiple intestinal lymphomatous polyposis in a Jindo dog

A male, 5-year-old Jindo dog underwent enterectomy and enteroanastomosis due to ileus of the intestine at a local veterinary hospital. Grossly, the excised intestine showed markedly thickened multinodular masses in the serosal layer of the upper part, and soft-to-firm, cream-colored neoplastic masses that displayed extensive nodular mucosal protuberances into the lumen. The neoplastic masses were filled with large round cells that were ovoid in shape and they had pale and/or hyperchromatic nuclei. The neoplastic cells had mainly infiltrated into the mucosal and submucosal layers, and they had diffusely invaded the muscular and serosal layers. Therefore, the diagnosis of canine multiple intestinal malignant lymphomatous polyposis was made based on the gross and histopathological findings. The origin of these tumor cells was determined to be B-cells since they were positive for anti-CD20.     

Detection of squamous cell carcinoma of presumed pancreatic origin and its metastasis in a spotted seal (Phoca largha) using ultrasonography and computed tomography

A 21-year-old female spotted seal (Phoca largha), with a swollen abdomen, had a five-month history of anorexia and vomiting. Ultrasonography revealed an extended mass with central necrotic foci in the right cranial abdomen. Computed tomography revealed an abdominal mass with a low-density central lumen and a pulmonary nodular lesion. Cytology of an abdominal specimen collected through fine-needle aspiration indicated a malignant tumor with round, atypical cells with large nuclei. Three days after diagnosis, necropsy revealed a 10-cm large, solid, whitish mass in the pancreatic parenchyma and multiple small nodules in the liver, spleen, mesentery, lungs, and mediastinal lymph nodes. Histopathological analysis showed prolific neoplastic cells with marked atypia and occasional keratinization. Immunohistochemistry revealed that the neoplastic cells were positive for cytokeratin AE1/AE3 antibody. Thus, the seal was diagnosed with squamous cell carcinoma, of presumed pancreatic origin, which had metastasized to multiple organs.