Morphologic characteristics of a transplantable tumor derived from a spontaneous malignant fibrous histiocytoma in the rat

Malignant fibrous histiocytoma (MFH) developed spontaneously in subcutaneous tissue of the head of a 15-month-old male Fischer 344 rat. The tumor was serially transplanted into syngeneic rats up to the 45th generation and was designated MFH-MT. Light and electron microscopic examinations revealed that the original and serially transplanted tumors were composed of an admixture of fibroblast-like and histiocyte-like cells arranged in a storiform pattern. Neoplastic cells gave positive reactions for acid phosphatase, alkaline phosphatase, nonspecific esterase, alpha-1 antitrypsin and lysozyme. The tumors transplanted into the lungs and cutaneous tissue of the tail had a mixed histologic appearance of storiform, pleomorphic, myxoid and giant cell types. Moreover sclerosing hemangioma-like and osteosarcoma-like structures were also found. MFH-MT grew well in athymic nude mice showing neoplastic proliferation of pleomorphic cells strongly positive for alpha-1 antitrypsin. Development of MFH-MT was significantly retarded by the two antitumor drugs tested. The retarded tumors consisted predominantly of fibroblast-like cells and abundant collagenic fibers, whereas histiocytic cells decreased in number.     

Amelanotic melanocytic tumors of the pinna in six F344 rats.

Spontaneous amelanotic melanocytic tumors of the pinna were found in six females of 960 male and 960 female albino (F344/DuCrj) rats which had been used in three different 24-month chronic toxicity studies. The age when the pinnal tumors were detected ranged from 37 to 59 weeks. The tumors were located unilaterally in the pinna and observed as subcutaneous spherical to irregular, solid white masses measuring 7 to 25 mm in diameter. The pinnal tumors were histologically classified into spindle cell and pleomorphic cell types. The spindle cell type was observed in four rats and composed of fusiform cells arranged in interlacing bundles. The pleomorphic cell type was observed in the remaining two rats and composed of pleomorphic large cells arranged in sheets. One tumor of the latter type metastasized to the submaxillary lymph node and lung. Melanin pigments were not demonstrated in any of the tumors. In immunohistochemistry, nuclei and cytoplasm of tumor cells in all the tumors were slightly positive for S-100 protein. Ultrastructurally, tumor cells contained a considerable number of premelanosomes in the cytoplasm. Desmosomes were occasionally observed between the cell membranes of the adjacent tumor cells. No distinct basal lamina was seen around tumor cells.     

Giant cell osteosarcoma in the calvarium of a cat

Feline primary osteosarcomas involving the skull are extremely rare. When they occur, orbit, mandible, and maxilla are the most common sites. Microscopically, scattered multinucleated giant cells (MGCs) are not an uncommon occurrence in osteosarcoma (OSC), but they are generally in low number. Only in a rare variant, the giant cell-rich OSC, are MGCs the prevalent cell type. Although osteoclast and osteoblast origin have been postulated in human and veterinary literature, the origin of MGCs in osteosarcomas is poorly understood. This report describes a giant cell-rich OSC in the calvarium of a 13-year-old spayed female shorthair cat. The animal exhibited a range of neurologic signs, including left circling, compulsive gait, lack of proprioception, and bilateral absence of menace reaction, with indication of left forebrain involvement. Gross lesions were characterized by a multilobate, spherical mass located in the left calvarium, compressing the left forebrain. Histologically, the tumor was characterized by scattered nests of MGCs separated by small bundles of pleomorphic, fusate to polygonal cells. Between spindle cells, osteoid was very sparse and arranged in thin strands. Immunohistochemical stains for vimentin were positive, with no detectable cellular staining for cytokeratin, S-100 protein, or Class II major histocompatibility complex. Ultrastructurally, MGCs contained profiles of rough endoplasmic reticulum; no lysosomes were observed. The origin of MGCs in osteosarcoma remains obscure, and our results confirm their ambiguous identity.     

Anaplastic and aggressive subcutaneous sarcoma in a seven-month-old dog

A seven-month-old female, Italian hound which was presented with anorexia, dyspnoea and weight loss showed two subcutaneous masses at physical examination. Radiographs showed multiple opacities in the lungs, thorax, liver and spleen, and cytology showed discrete pleomorphic cells, with variable nuclear : cytoplasmic ratio, foamy cytoplasm and round to oval nuclei. Incisional biopsy histology showed the infiltrative proliferation of highly pleomorphic spindle to roundish large cells, discrete or arranged in a storiform pattern, with scattered multinucleated giant cells. Immunohistochemistry exhibited strong positivity for vimentin and mild labelling for alpha-smooth muscle actin and lysozyme; other mesenchymal or histiocytic lineage markers stained negatively. Because of the poor prognosis, the owner elected euthanasia. Post-mortem examination confirmed massive metastatic spread. Cytology, histology and immunohistochemistry suggested the diagnosis of anaplastic sarcoma with giant cells, although disseminated histiocytic sarcoma was a reliable differential diagnosis. The authors underline the difficulties in definitively categorising poorly differentiated sarcomas, even if a large panel of markers is applied.     

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.     

Cytologically atypical anal sac adenocarcinoma in a dog

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

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.     

Three cases of canine gastrointestinal stromal tumors with multiple differentiations and c-kit-expression

Three canine gastrointestinal stromal tumors (GISTs) were examined. Histopathologically, the tumor mass in the jejunum (Case 1) consisted of the proliferation of epithelioid cells with abundant eosinophilic or vacuolated cytoplasm. Gangliocyte-like or multinucleated giant cells were scattered. The tumor cells exhibited neural natures mimicking human gastrointestinal autonomic nerve tumors, which were immunopositive for several neuronal markers. Another jejunal mass (Case 2) was composed by a solid proliferation of spindle-shaped cells, arranging in interlacing fascicles and occasional storiform pattern. The tumor seemed to be classified undifferentiated GISTs, that showed no apparent neural or muscular features by ultrastructural and immunohistochemical examinations. In the pyloric mass (Case 3), the spindle cells having eosinophilic processes and elongated nuclei were arranged in sheets. Immunohistochemically, the tumor cells showed muscular natures as regards alpha smooth muscle actin and desmin expression.     

Giant cell tumour of bone in a cat with extraskeletal metastases: pathological and immunohistochemical study

A case of giant cell tumour of bone (GCTb) in the lung and in a subcutaneous mass located in the right flank, with a probable primary origin in the mid-diaphysis of the right tibia, was described in a 8-year-old female cat. Numerous multinucleated giant cells were homogeneously distributed among a population of ovoid or spindle-shaped mononuclear cells. All of them were positive for vimentin suggesting a mesenchymal origin. Spindle-shaped tumour cells resemble fibroblastic cells, showing collagen fibres in their vicinity. Ovoid mononuclear cells are similar to macrophages, with a cytoplasm rich in electron-dense lysosomes. Multinucleated giant cells appear morphologically similar to osteoclasts. These findings are supported for the positive reaction to tartrate-resistant acid phosphatase (TRAP) and lysozyme, encountered only in ovoid and multinucleated giant cells. No immunoreactivity against human oestrogen receptors was observed in the nuclei of any neoplastic cells.     

Malignant fibrous histiocytoma (giant cell type) associated with a malignant mixed tumor in the salivary gland of a dog

A 12-year-old male Boxer dog presented with a 5 x 5 x 7-cm partially encapsulated mass in the right mandibular salivary gland. Histologically, the mass was composed of neoplastic epithelial and mesenchymal cells. The mesenchymal component consisted of two cell populations arranged in different patterns: coalescing nodules of neoplastic mononuclear cells with rare osteoid and numerous osteoclastlike giant cells; and sheets of neoplastic spindle cells intermingled with neoplastic epithelial cells and containing osteoid and well-formed bone trabeculae lined by osteoblasts and few osteoclastlike giant cells. On the basis of these histological features, two malignant salivary tumors were diagnosed: a malignant fibrous histiocytoma (giant cell type) and a malignant mixed tumor. Immunohistochemical studies demonstrated keratin 5 and 8 expression by the neoplastic epithelial cells, indicating a probable salivary ductal origin, and vimentin expression by all mesenchymal elements, suggesting a fibroblastic line of differentiation.     

Appearance of multinucleated giant cells in association with an adenovirus infection in two guinea pigs

In two guinea pigs (five years old, neutered male, and two and a half months old male, respectively) suffering from interstitial pneumonia, multinucleated giant cells were observed histologically in lungs, spleen and liver. The giant cells showed intranuclear, pale basophilic inclusions. Adenovirus could be demonstrated by electron microscopy.The multinucleated cells are supposed to be of histiocytic origin, since they contained variable amounts of haemosiderin in their cytoplasm. Formation of histiocyte-derived syncytia as a result of virus-induced cell fusion is discussed.     

Gastrointestinal stromal tumors of the equine cecum

Ten cecal tumors were identified during the postmortem examination of seven horse carcasses at slaughter (one horse had three tumors). The multinodular and hemorrhagic tumors ranged from 1 to 10 cm in diameter and consisted of spindle cells arranged in thin, interconnected trabeculae that were often separated by sinuses filled with mucinous fluid, erythrocytes, and siderophages. Spindle cells of all tumors were immunopositive for vimentin, neuron-specific enolase, and c-kit protein but lacked reactivity with antibodies to glial fibrillary acidic protein, S100 protein, and desmin. In one tumor, spindle cells diffusely bound antibodies to synaptophysin. Most tumors contained focal reactivity to smooth muscle actin antibodies; one tumor reacted diffusely. Ultrastructurally, tumor cells were connected by desmosome-like structures and exhibited extended cell processes; some contained dense core neurosecretory granules. These equine stromal tumors appeared to share some characteristics with human gastrointestinal stromal tumors.     

Clinical,histopathological, and immunohistochemical studies of histiocytic sarcoma in four-toed hedgehogs (Atelerix albiventris): A retrospective study

Histiocytic sarcoma was investigated histopathologically and immunohistochemically in 17 four-toed hedgehogs (Atelerix albiventris), along with a review of their clinical data. Cases were histopathologically classified into two types: round-polygonal cell type (6 cases) and spindle cell type (11 cases). Round-polygonal cell type was found in visceral organs such as the spleen, lymph nodes, and more, and most cases of this type were consistent with disseminated histiocytic sarcoma. On the other hand, spindle cell type occurred mainly in skin, and almost all cases were consistent with localized histiocytic sarcoma. The prognosis of patients with round-polygonal cell type appeared worse than that of spindle cell type. Immunohistochemically, neoplastic cells of spindle cell type showed stronger reactivity against human leukocyte antigen-DR than round-polygonal cell type. Neoplastic cells of all cases showed strong reactivity against ionized calcium-binding adapter molecule-1 (Iba-1) and various reactivities against cluster of differentiation (CD) 204. Regardless of morphological classification, most tumor cells were negative for CD163, suggesting that this marker is less effective for the diagnosis of histiocytic sarcoma. The results of this study suggest that Iba-1 is the most effective marker for histiocytic sarcoma.     

Morphologic and immunohistochemical features of two spontaneous peripheral nerve tumors in Wistar rats

Morphologic features and S-100 protein immunoreactivity of a benign and malignant peripheral nerve sheath tumor were studied in two Wistar rats. Neoplasms that developed in untreated control rats from tumor bioassays were S-100 protein positive and had similar histopathologic features. Each peripheral nerve sheath tumor was encapsulated and composed of spindle cells arranged around small thin-walled blood vessels. Palisaded tumor cells were in the benign peripheral nerve sheath tumor while cells of the malignant peripheral nerve sheath tumor had cellular atypia and moderate numbers of mitoses. Ultrastructural examination of the malignant peripheral nerve sheath tumor revealed cells with external lamina and interdigitation of cytoplasmic processes. Intracytoplasmic concentric lamellae were seen; they were regularly spaced with a periodicity of about 15 nm. Such structures, indistinguishable from myelin sheaths, have not been commonly associated with peripheral nerve sheath tumors in man. Electron microscopy and immunohistochemistry were useful in the diagnosis of these tumors as Schwannomas and in differentiation from other spindle cell tumors.     

Malignant giant cell tumor of soft parts in a mare

Two subcutaneous masses were removed from the elbow of a mare. Histologically they were composed of islands of polygonal to plump spindlelioid cells with large nuclei, coarsely stippled chromatin, and eosinophilic cytoplasm. Findings were diagnostic for a malignant giant cell tumor of soft parts, a rare tumor with a fair prognosis.     

Epididymal interstitial (Leydig) cell tumors in B6C3F1 mice

Six primary interstitial cell tumors of the epididymis were identified from 46,752 male B6C3F1 mice used in chronic toxicity and carcinogenicity studies. Five of the tumors occurred at the end of 2-year studies; none were attributed to treatment. None of the mice with epididymal tumors had a primary testicular tumor. Histologically, tumors were characterized by a nodular or diffuse proliferation of tumor cells in the epididymal interstitium. Most cells were polygonal with highly vacuolated cytoplasm (vacuolated cells) or eosinophilic cytoplasm (eosinophilic cells). Smaller hyperchromatic cells with scant basophilic cytoplasm (basophilic cells) and cells with yellow-brown pigment characteristic of lipofuscin (pigmented cells) were less common. In each tumor two or more cell types were present. Extension of these tumors through the capsule, invasion of the testis, or metastasis did not occur. By electron microscopy both eosinophilic and vacuolated cell types had a large round or oval nucleus with sparse heterochromatin, abundant mitochondria with tubulovesicular cristae, and frequent desmosome structures between cell membranes. Vacuolated cells contained numerous lipid droplets. Morphological features of the epididymal tumors are similar to those of the testicular interstitial (Leydig) cell tumor in mice and rats.     

Malignant fibrous histiocytoma of the deep peri-articular tissue of the stifle in a dog

A Belgian shepherd dog aged 4 years and 9 months was presented with acute onset of non-weight bearing lameness and stifle effusion of the left hind limb, caused by the deep form of a malignant fibrous histiocytoma originating in the deep musculature and fascia surrounding the stifle joint. The tumour progressed rapidly in the tissues along the femoral diaphysis with marked periosteal new bone formation. Cytology of a stifle joint aspirate revealed numerous large polygonal neoplastic cells with considerable anisocytosis and anisokaryosis. These cells were present in clusters, with cytoplasmic projections between the cells, but occasionally also occurred singly. Several cells contained multiple cytoplasmic vacuoles and occasional giant cells were also encountered. Adequate tumour-free margins were not possible with radical limb amputation and the dog was euthanased. Macroscopically the tumour appeared as an extensive pale tan, firm mass with scattered small haemorrhages and foci of yellow discolouration. Histologically the tumour consisted of dense neoplastic expanses or multiple nodules, composed of spindle-shaped fibroblastic cells, polygonal histiocytic cells or cell clusters and scattered giant cells with 2-3 nuclei. The polygonal neoplastic cells were frequently present around and invading lymphatics and blood vessels, causing neoplastic emboli. This is the 1st report of the clinical behaviour, radiography and cytology of the deep form of malignant fibrous histiocytoma in the dog.     

Retrospective study of 338 canine oral melanomas with clinical, histologic, and immunohistochemical review of 129 cases

Diagnostic records from 338 canine oral melanomas in 338 dogs received at the Veterinary Medical Diagnostic Laboratory (1992-1999) were reviewed. Of these tumors, 122 plus an additional 7 metastatic melanomas of unknown origin were selected for clinical follow-up, histologic review, and immunohistochemistry. Chow Chow, Golden Retriever, and Pekingese/Poodle mix breeds were overrepresented, whereas Boxer and German Shepherd breeds were underrepresented. There was no gender predisposition and the average age at presentation was 11.4 years. Forty-nine dogs were euthanized due to recurrence or metastasis. The average postsurgical survival time was 173 days. The gingiva and the labial mucosa were the most common sites. Most tumors were composed of either polygonal cells (27 cases, 20.9%), spindle cells (44 cases, 34.1%), or a mixture of the two (polygonal and spindle) (54 cases, 41.9%). Clear cell (3 cases, 2.3%) and adenoid/papillary (1 case, 0.8%) patterns were uncommon. The metastases of 6/6 oral melanomas had morphologic and immunohistochemical features similar to those of the primary tumors. Immunohistochemically, Melan A was detected in 113/122 oral (92.6%) and 5/7 (71.9%) metastatic melanomas. Only 4/163 nonmelanocytic tumors were focally and weakly positive for Melan A. Antibodies against vimentin, S100 protein, and neuron-specific enolase stained 129 (100%), 98 (76%), and 115 (89.1%) of 129 melanomas, respectively. Antibodies against other melanocytic-associated antigens (tyrosinase, glycoprotein 100) did not yield adequate staining. We conclude that Melan A is a specific and sensitive marker for canine melanomas.     

Dermal melanoma with schwannoma-like differentiation in a brown bullhead catfish (Ictalurus nebulosus).

A dermal melanoma with histologic similarities to mammalian melanocytic schwannomas was diagnosed in a wild-caught brown bullhead catfish (Ictalurus nebulosus). The diagnosis was based on cytologic, histopathologic, immunohistochemical, and ultrastructural findings. The neoplasm protruded from the cutaneous surface of the dorsal midline immediately caudal to the dorsal fin, was diffusely black and focally ulcerated, and was attached to the underlying skin by a broad-based stalk. Cytologically, the tumor was composed of a monomorphic population of melanophores, the melanin-producing and storing cells within the dermis and epidermis of fish that are partially responsible for rapid color changes. Histopathologic examination of the neoplasm revealed an unencapsulated, well-circumscribed, moderately cellular neoplasm composed of 2 distinct cell populations: spindle cells arranged in a "herringbone" pattern and numerous melanophores. The spindle cells had scant bipolar eosinophilic cytoplasm, with small centrally located vesicular nuclei; nucleoli were not seen. The histologic appearance was similar to that described for mammalian melanocytic schwannomas. Immunohistochemically, the spindle cells exhibited positive cytoplasmic staining for S-100 protein but were negative for vimentin, neurofilament protein, and glial fibrillary acidic protein. Ultrastructurally, the tumor consisted of neoplastic spindle cells with rudimentary cell junctions, actin bundles, and few melanosomes and melanophores with abundant intracytoplasmic melanosomes.