Granular variant of a histiocytic tumor on the toe of a cat: Case report and literature review

A 16-year-old female spayed domestic shorthaired cat was examined for lameness and a mass on the fourth digit of the right hindlimb. Cytologic examination of an aspirate of the mass revealed large discrete cells admixed with low numbers of well-granulated mast cells. The discrete cells contained single to many variably sized light pink to purple granules in their cytoplasm and had pleomorphic nuclei, with intranuclear cytoplasmic inclusions. Karyomegalic, binucleated and multinucleated cells were seen. Histologic examination of formalin-fixed sections of the excised mass showed a mildly infiltrative, unencapsulated, multinodular dermal mass that extended into the subcutis and consisted of similar discrete cells. On immunohistochemical staining, the tumor cells expressed ionized calcium-binding adapter molecule 1 (Iba1) and CD18. The tumor cells did not express CD3, CD20, CD117, pancytokeratin (AE1/AE3), melanoma antigen (Melan-A), multiple myeloma oncogene-1 (MUM1), melanoma-associated antigen (PNL-2), and S-100. Low numbers of tumor cells expressed CD204 and protein gene product 9.5 (PGP9.5). Granules were variably positive for Periodic-acid Schiff (PAS) and Alcian blue. On transmission electron microscopy, the cells contained filopodia, abundant endoplasmic reticulum, and moderate numbers of low-density membrane-bound granules. This case documents a previously undescribed granular variant of a histiocytic tumor in a cat.     

Comparison of tyrosinase-related protein-2, S-100, and Melan A immunoreactivity in canine amelanotic melanomas

Tyrosinase-related protein-2 (TRP-2) is a highly conserved melanogenic enzyme expressed in both pigmented and unpigmented melanomas of the mouse. To determine whether TRP-2 would be a good diagnostic marker for amelanotic melanomas of the dog, we performed immunohistochemistry for TRP-2, S-100, and Melan A on 21 canine tumors identified as amelanotic melanomas based on routine histopathologic examination. Thirteen of the tumors were TRP-2 positive, 10 were Melan A positive, and 19 were S-100 positive. TRP-2 was expressed in the cytoplasm of tumor cells in both primary and metastatic melanomas. S-100 staining was positive in all of three schwannomas and two of three gastrointestinal stromal tumors (one fibrosarcoma and one leiomyosarcoma) tested. Neither Melan A nor TRP-2 antibodies reacted with these tumors. Our findings indicate that staining for TRP-2 is a sensitive and specific method for confirming the diagnosis of amelanotic melanoma in dogs.     

Cerebral neuroblastoma and pituitary adenocarcinoma in two budgerigars (Melopsittacus undulatus)

Case 1: A tumor mass involving the rostral part of left cerebrum was found in a two-year-old female budgerigar (Melopsittacus undulatus) at necropsy. Histologically, the neoplastic cells were arranged in sheets or cords and occasionally showed nest growth patterns. These uniform tumor cells had a little cytoplasm and ovoid or round basophilic nuclei with clearly distinct cytoplasmic membranes. The tumor cells were strong diffusely immunostained with both neuron-specific enolase (NSE) and neurofilament protein and partially for synaptophysin. They lacked chromogranin A, glial fibrillary acidic protein (GFAP), vimentin, S-100, and cytokeratin antigen expression. Moreover, they had no reaction to antibodies against pituitary hormones, such as adrenocorticotrophic hormone (ACTH), growth hormone, and prolactin. The histological and immunohistochemical examination determined the tumor as neuroblastoma. Case 2: An extremely enlarged pituitary mass was found above the sella turcica of a male budgerigar. It was soft and well delineated from the adjacent structures. On histological examination, this tumor consisted of a sheet of large closely packed polyhedral cells that had scant to a large amount of pale to strongly eosinophilic cytoplasm. The pleomorphic nuclei were apparently variable in shape, from small round hyperchromatic to very large vesicular forms. The cell boundaries were not clearly distinct. The multifocal immunolabelling of neoplastic cells for NSE, synaptophysin, GFAP, and ACTH appeared, whereas a few cells reacted with vimentin and S-100 and stained negative for other markers, which were also utilized for case 1. Histological and immunohistochemical findings led to identification of corticotroph adenocarcinoma in the pituitary gland.     

Innervation of the circumvallate papilla of the cat tongue

Immunohistochemically, the distribution of S-100 protein and acetylated tubulin-positive nerve fibres was studied in the circumvallate papilla and its taste buds (TB) in the adult cat. The immunostaining for acetylated tubulin demonstrated an extensive innervation of the circumvallate papilla. Vegetative ganglionic cells were found in the central area of papilla, whereas fine nerve fibres were concentrated under epithelium. Individual positive axons were seen in relation to TB. Nerve fibres enter the TB and branch out among the supporting and sensory cells. Some nerve fibres reach the apical surface of the TB, including the taste pore. Nerve fibres positive for S-100 protein were observed as dense nerve plexus located in the core of the papilla. Satellite cells localized inside the papilla were seen to surround the ganglionic cells. Bands of fine nerve fibres were present under lining epithelium, mainly at the base of the TB. A weak reaction was displayed by taste bud cells and surrounding epithelial cells as well as by the epithelial cells of the papillary side of the moat. A dense network of the nerve fibres was present among the glandular acini and surrounding the ducts of the serous Ebner's glands.     

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.     

Nasal oncocytoma in a domestic shorthair cat

An oncocytoma was diagnosed in the nasal cavity of a 12-year-old Domestic Shorthair cat who presented with periocular swelling and sneezing. Histologic examination from biopsy material revealed monomorphic sheets, anastomosing cords, tubules, and acini composed of large polygonal to oval cells that contained abundant finely granular eosinophilic cytoplasm. No vascular or lymphatic invasions were noted. Histochemical stains revealed positive staining of tumor cells with periodic acid-Schiff (PAS) (before and after diastase digestion) and phosphotungstic acid-hematoxylin. Immunohistochemical evaluation of the tumor cells demonstrated positive staining for cytokeratin and negative staining for vimentin, desmin, S-100, glial fibrillar acidic protein, and neuronal specific enolase. Ultrastructurally, the tumor cells contained large numbers of mitochondria within their cytoplasm, which confirmed a diagnosis of oncocytoma.     

Cytologic and immunohistochemical characterization of a primitive neuroectodermal tumor in the brain of a dog

A 6-year-old intact female Pointer dog was presented for evaluation of acute onset of ataxia, circling, and head tilt. Neurologic assessment revealed overall decreased postural reaction, left-sided hemiparesis with incoordination, rigidity of fore- and hindlimbs, strabismus of the right eye, and bilateral horizontal nystagmus. Using magnetic resonance imaging, a mass lesion was identified in the cerebrum adjacent to the left side of the cerebellum compressing the brain stem ventrally. The mass was incompletely resected, and during surgery fine-needle aspiration and biopsy of the mass were performed. Cytologically, smears were highly cellular and contained predominantly small to medium-sized discrete round cells with high nuclear to cytoplasmic ratios and round nuclei with rare deep clefts or indentation, smooth chromatin, and indistinct nucleoli. Numerous cytoplasmic fragments were noted in the background. The primary diagnosis was lymphoma; other differential diagnoses included neuroendocrine tumor and poorly differentiated tumor of neural origin. The histologic diagnosis was lymphoma, and the lesion was presumed to be metastatic. On immunohistochemical analysis, the cells expressed neither CD3 nor CD79a. Re-examination of the histologic section revealed disorganized sheets of cells with multifocal palisading and perivascular arrangements of rosette-like structures. An expanded panel of antibodies to vimentin, cytokeratin, glial fibrillary acid protein (GFAP), neuron-specific enolase (NSE), synaptophysin (SYN), S-100, and CD45 was applied to histologic sections. Neoplastic cells were immunoreactive for vimentin, NSE, and S-100. Based on the histologic appearance and immunophenotype of the tumor, a diagnosis of primitive neuroectodermal tumor (PNET) was made. PNET, although rare in dogs, should be considered as a differential diagnosis for round cell tumors in the brain.     

Immunohistochemical evaluation of canine peripheral nerve sheath tumors and other soft tissue sarcomas

Seventeen cases of canine peripheral nerve sheath tumors (PNSTs), 11 malignant PNSTs (MPNSTs), and six benign PNSTs (BPNSTs) were examined. The prognosis in five of six dogs with BPNSTs was excellent, whereas all dogs with MPNSTs died within 2 years after the last surgical resection. One BPNST formed a recurrent mass with features of a MPNST. Histopathologically, the predominant tumor cell of MPNSTs was either spindle or round in shape with epithelioid characteristics. Other atypical cells had abundant granular cytoplasm or were multinucleated giant cells with periodic acid-Schiff-positive cytoplasmic globules. Furthermore, two MPNSTs contained cartilaginous and osseous metaplasia. On the contrary, most BPNSTs exhibited typical features of schwannoma or neurofibroma, whereas two BPNSTs had atypical morphology. One BPNST consisted of epithelioid cell proliferation with some tumor cells revealing nuclear atypia. Immunohistochemically, the expression of vimentin (100%), S-100 (73%), nerve growth factor receptor (NGFR, 64%), and myoglobin (64%) was commonly found in MPNSTs. The two BPNSTs with atypical histologic appearances were positive for vimentin, S-100, NGFR, and neuron-specific enolase, and one of these had moderate immunoreactivity for cytokeratin. Most BPNSTs were positive for glial fibrillary acidic protein, as well as S-100 and NGFR. Although most rhabdomyosarcomas (RMSs) and canine hemangiopericytomas (CHPs) also showed focal immunoreactivity for S-100, most RMSs were intensely positive for myoglobin and negative for NGFR. Most CHPs (80%) exhibited focal alpha-smooth muscle actin (alpha-SMA) expression, whereas all PNSTs were negative. These results indicate that immunohistochemistry for NGFR and alpha-SMA might be useful for differentiating canine PNSTs from RMSs or CHPs, respectively.     

Gastric stromal tumors in two rhesus macaques (Macaca mulatta)

Two female rhesus monkeys (Macaca mulatta, 10 and 24 years old) developed microcytic anemia and became terminally ill. At necropsy, large gastric masses were present, and, in one case, there were widespread abdominal metastases. Except for slightly atypical patterns, at the light microscopic level, the lesions resembled smooth muscle tumors. Ultrastructurally, however, cells in both tumors resembled primitive mesenchyme, while in one of the tumors, there were some characteristics of Schwann cells. No ultrastructural features of smooth muscle were present in either tumor. Vimentin and S-100 were detected immunohistochemically in both tumors. S-100 staining was more intense in the tumor with ultrastructural features of Schwann cells. Actin and desmin were not expressed in either gastric tumor, but diffusely stained a uterine tumor that was concomitantly present in one of the rhesus monkeys. The uterine tumor also exhibited typical ultrastructural features of smooth muscle. In the past, gastrointestinal stromal tumors in all species were thought to be of smooth muscle origin. Recently in human pathology, this conventional viewpoint has given way to the realization that there is a spectrum of neural crest and mesenchymal tumors. We report two gastric stromal tumors in two rhesus monkeys that histologically resembled smooth muscle tumors but were of neuroectodermal and primitive mesenchymal origin.     

Amyloid-producing odontogenic tumor and its immunohistochemical characterization in a Shih Tzu dog

A 10-year-old, male, Shih-Tzu dog presented with swelling of the right lower jaw caused by a mass arising from the right mandibular gingiva. Radiographic examination revealed bone lysis of the right wing of the mandible. Histopathologically, the growth was characterized by indistinctly lobulated nests, islands, and strands of proliferating odontogenic and squamous epithelial cells, intermingled in close association with large numbers of irregular extracellular deposits of amyloid and amorphous calcified substance. Immunohistochemically, both epithelial components stained strongly positive for cytokeratin (AE1/AE3); the squamous epithelial cells also reacted strongly with neuron-specific enolase (NSE) and S-100 protein, whereas the odontogenic epithelial cells displayed weak immunoreactivity to NSE and partial reactivity to S-100 protein. The amyloid deposits were AE1/AE3-negative. The growth was diagnosed as an amyloid-producing odontogenic tumor.     

Dermal malignant melanoma in a horse with multifocal pancytokeratin expression.

The current report describes a malignant melanoma in the dermis of a 13-year-old bay Thoroughbred mare. Microscopic examination revealed that tumor cells were arranged in cords and packets within an abundant collagenous stroma containing scattered myxomatous foci. Tumor cells stained positively for S-100, neuron-specific enolase, and vimentin and some contained melanin granules. Some clusters of tumor cells were also positive for pancytokeratin. Expression of epithelial cell markers has been described in small numbers of human melanomas but has not been reported previously in equine melanomas.     

Ganglioneuroma in the urinary bladder of a dog

An 11-year-old male Labrador retriever presented with chronic oliguria. Ultrasonography findings revealed a protruding mass at the neck of the urinary bladder. A cystotomy was performed, and the mass was removed by ligation with surgical sutures. Histopathological examination revealed conspicuous foci with a variable number of ganglion cells in the tumor and abundant interwoven bundles of schwannian cells with fine fibers. The ganglion cells were positive for neuron-specific enolase and neurofilament. The schwannian cells were positive for vimentin, S-100 protein, and glial fibrillary acidic protein. Thus, according to the classification of tumor with neuronal cell differentiation, the urinary tumor was diagnosed as a ganglioneuroma.     

Spontaneous extraskeletal osteosarcoma in the neck skeletal muscle of a Crlj:CD1 (ICR) mouse

Extraskeletal osteosarcoma is extremely rare in humans and animals, especially in rodents. This is the first case report on spontaneous extraskeletal osteosarcoma in the neck skeletal muscle of a Crlj:CD1 (ICR) mouse (36 weeks, dead). Necropsy revealed a solid white mass located in the neck skeletal muscle (scalenus muscle). Histological examination showed that the tumor consisted of atypical polygonal cells, a small osteoid clump, and bone tissue. Mitotic figures were observed. Serial sections showed that neoplastic cells lacked clear invasive proliferation to adjacent normal skeletal muscle and continuity with normal bone tissue. Immunohistochemical analysis showed that the neoplastic cells were positive for osteocalcin, osterix, vimentin, and S-100. Based on these results, the tumor was diagnosed as extraskeletal osteosarcoma in the neck skeletal muscle.     

Oral leiomyosarcoma in a woodchuck (Marmota monax)

We report the case of a 4-year-old female woodchuck (Marmota monax) which presented with a white, firm and discrete mass in the hard palate. The mass extended into the oral cavity but it was well separated from the surrounding tissues. Histology of the tumor showed a malignant mesenchymal tumor with pleomorphic spindle cells varying in degrees of differentiation and density. The neoplastic cells had moderate amounts of granular or fibrillar eosinophilic cytoplasm with indistinct cell margins. Nuclei were oval to elongated and frequently blunt-ended with vesicular chromatin. Immunohistochemical study showed that the neoplastic cells expressed vimentin and alpha-smooth muscle actin but did not express desmin, pan-cytokeratin, and S-100. Therefore, histology and immunohistochemistry revealed that the tumor was oral leiomyosarcoma. Oral cavity is an extremely rare site for leiomyosarcoma and the present case is the first report of spontaneous oral leiomyosarcoma in animals.     

Use of s-100 and chromogranin a antibodies as immunohistochemical markers on detection of malignancy in aortic body tumors in dog

To define the characteristics of malignancy we performed routine histology and an immunohistochemical study on seventeen aortic body tumors in dogs. We essayed tumors using a panel of immunohistochemical markers: neuron specific enolase (NSE), chromogranin A (CrA) and S-100. Among 17 cases, the neoplastic cells were positive for NSE (17 cases, 100%), S-100 (9 cases, 53%), and CrA (8 cases, 47%), respectively. The sustentacular cells density and chief cell staining intensity were both inversely related to tumor grade. The most relevant data was consistent with a negative staining of S-100 correlated with absence or decreased number of sustentacular cells in tumors grade III. This report indicates that the immunohistochemical panel has utility for the diagnosis of chemodectoma and the negative staining to CrA and S-100 markers in tumors grade III expresses an indication of malignant behaviour of the tumor.     

Naturally occurring multiple perineuriomas in a chicken (Gallus domesticus)

A 2-year-old, male Japanese native fowl (Gallus gallus domesticus) was presented with an inability to feed and torticollis. At a necropsy, there were cylindrical enlargements and yellow discoloration of multiple peripheral nerves, including nerves of the lumbosacral plexus, brachial plexus, and spinal ganglia. On histologic examination, these lesions consisted of diffuse proliferations of spindle cells with characteristic onion bulb-like structures around residual axons. The spindle cells were immunohistochemically positive for glucose transporter 1 (GLUT1) and negative for S-100 alpha/beta proteins. On the basis of microscopic, histologic, and immunohistochemical findings, the tumors were diagnosed as multiple perineuriomas.     

Benign peripheral nerve sheath tumor of the perianal region in a young pony.

A 20 x 10 cm, lobulated mass was present in the perianal region of a 4-year-old Dales pony. Histopathology revealed an unencapsulated, loose arrangement of sheets and whorls of narrow mesenchymal cells, situated in the deep dermis. Intervening areas had a myxomatous appearance. The whorls were often arranged around a central structure resembling an axon or a vascular structure. Immunohistochemistry revealed that the elongated mesenchymal cells and central axon-like structures expressed vimentin, S-100, and neuron-specific enolase, but not pancytokeratin, glial fibrillary acid protein, and the neurofilament markers, NR4 and 2F11. On the basis of the histopathology and immunohistochemistry, a diagnosis of benign peripheral nerve sheath tumor (schwannoma type) was made. This case was unusual in that the concentric laminations of Schwann cells were very loosely arranged, with an intervening myxomatous stroma (Antoni type B appearance) and despite its benign histological appearance, the mass extended deeply to the proximal sacral vertebrae. Its exact origin was unclear; it may have arisen from cutaneous nerves with deep extension or from neural structures in the sacral region. Due to the incomplete surgical removal, regrowth of the mass occurred.     

1例猫肾上腺皮质癌脾转移的病理及免疫组化分析

猫的肾上腺皮质癌转移至脾在兽医临床非常罕见。在本报告中,描述了1例10岁田园猫,其症状表现为腹部疼痛,频繁呕吐,消瘦,有慢性肾上腺功能损伤病史,影像学检查脾肿大。对患猫进行脾摘除手术,并对摘除的组织进行组织病理学检查和免疫组化分析。病理组织学结果显示,肿瘤细胞具有丰富的脂质样空泡,细胞体积大,有丝分裂象多见,且肿瘤细胞已发生血管侵袭,细胞核浓染;免疫组织化学结果显示,synaptophysin、S-100和GATA4阳性表达。根据病理组织学和免疫组织化学及病史和实验室检查,最后诊断为肾上腺皮质癌的脾转移。首次报道了猫肾上腺皮质癌脾转移临床病例及病理学诊断,对于临床相关疾病诊疗有一定的参考价值和借鉴意义。     

Intraocular peripheral nerve sheath tumor in a dog

A tumor within the right globe in a 9-year-old Shetland sheepdog was examined pathologically. The tumor was composed of spindle or oval cells arranged in interwoven bundles with intervening collagenous or mucinous matrices. Immunohistochemically, the tumor bound antibody directed to S-100 protein and vimentin, but not to desmin, actin smooth muscle, or neurofilament. Electron microscopy revealed that the tumor cells had poorly developed cytoplasmic processes, desmosomes between closely contiguous cells, and a discontinuous basement membrane-like material. Based on these findings, the tumor was diagnosed as a peripheral nerve sheath tumor (PNST) histologically. To the authors' knowledge, this is the first reported case of intraocular PNST in dogs.     

Spontaneous fibrosarcoma with pleomorphic appearance in an aged brown norway rat

An 18-month-old male Brown Norway (BN) rat showed a grayish-white subcutaneous mass in the right cheek. Histologically, the mass was composed of highly pleomorphic cells producing collagen. Immunohistochemical analysis showed that the tumor cells were strongly positive for vimentin and partially positive for Ki-67; however, they were negative for ED-1, ED-2, S-100, cytokeratin, desmin and myoglobin. Ultrastructurally, the cytoplasms of the tumor cells contained well-developed rough endoplasmic reticulum. Thus, the tumor had no characteristic feature other than collagen production and was diagnosed as a fibrosarcoma.