Immunohistochemical study of autophagy associated molecules and cell adhesion molecules in canine intracranial granular cell tumors.

Granular cell tumors (GCTs) are characterized by abundant eosinophilic cytoplasmic granules. Based on the hypothesis that canine intracranial GCT is a subtype of meningioma and its cytoplasmic granules are formed through autophagy processes, histopathological and immunohistochemical examination were performed on biopsy samples from 7 cases of canine intracranial GCTs and 15 cases of conventional meningiomas. Histopathologically, 7/7 cases of GCTs involved the meninges; foci of meningothelial-like cells were observed in 3/7 cases; brain invasion was observed in 2/7 cases. Immunohistochemically, neoplastic cells of GCTs were positive for E-cadherin and negative for S100, cytokeratin, CD204, and ß-catenin in 7/7 cases. Neoplastic cells of 15/15 cases of meningiomas were positive for E-cadherin, and negative for S100 and CD204. Immunoreactivity of meningiomas for cytokeratin and ß-catenin was observed in 6/15 cases and 8/15 cases, respectively. Cytoplasmic granules of GCTs were positive for ubiquitin (5/7), p62 (5/7), and LC3 (7/7). Compared to GCTs, the ratios of ubiquitin (6/15) and p62 (3/15) positive cases were lower in meningiomas, and 15/15 cases were negative for LC3. These findings indicate that the biological natures of GCTs including anatomical location, histopathological features and immunoreactivity for E-cadherin are almost in conformity with those of meningiomas. The immunoreactivity for autophagy associated molecules may suggest the possible involvement of autophagy in cytoplasmic granule formation of canine intracranial GCTs.

Diagnostic imaging and pathological findings of an abdominal mesenteric granular cell tumour in a dog.

A 12-year-old mixed-breed dog was presented for a follow-up examination after ablation of an auricular mast cell tumour. An abdominal ultrasound and computed tomography were performed and an irregular, ill-defined and partially mineralised lesion was observed around the caudal duodenal flexure without evidence of metastasis. The cytologic examination was highly suggestive of a granular cell tumour. Partial surgical ablation with histological and immunohistochemical examination of the lesion confirmed the diagnosis. According to our review of the literature, this is the first report documenting an abdominal granular cell tumour in a dog.

Granular Cell Tumour in a California Kingsnake (Lampropeltis californiae).

A 21-year-old female California kingsnake (Lampropeltis californiae) was presented to the University of Veterinary Medicine, Vienna, Austria, with a space-occupying mass in the caudal abdomen. Following clinical, radiological and sonographical evaluation the mass was removed surgically. Histopathology and transmission electron microscopy confirmed the diagnosis of a granular cell tumour, but immunohistochemical labelling for a range of markers was negative. This lesion is rare in mammals and birds, but has not been reported previously in a reptile.

Meningeal Granular Cell Tumour in a Green Tree Python (Morelia viridis).

Granular cell tumours (GCTs) are uncommon neoplasms mostly reported in man, dogs and horses. The origin of GCT is thought to be Schwann cells, with the associated characteristics of neural crest morphology. Neoplastic cells often demonstrate positive immunoreactivity for S100, LC3, vimentin and p62. They are also periodic acid-Schiff (PAS) positive and diastase resistant. A female green tree python (Morelia viridis) was presented for severe constipation and hyporexia of 4 month's duration and, despite treatment, died the next day. A 4.8 × 3.4 mm intracalvarial GCT was identified, compressing the overlying cerebrum without invasion. Neoplastic cells were immunoreactive to S100 and had brightly eosinophilic cytoplasmic granules that were PAS positive and diastase resistant. Electron microscopy revealed numerous cytoplasmic lysosomes in neoplastic cells. GCTs are reported rarely in non-mammalian species with three reports in birds. This represents the first report of a GCT in a reptile.

Intradural extramedullary granular cell tumour in a cat.

A 7-year-old domestic shorthair cat was evaluated for progressive paraparesis, inability to jump, a paralysed tail and inability to void the bladder. Neurologic examination was consistent with a L4-S3 localisation. Survey radiographs of the lumbar vertebral column revealed L4-L7 vertebral body remodelling. A pre-contrast T1-weighted hyperintense, diffusely enhancing intradural lesion extending from L4 to S1 vertebral bodies was detected by MRI. Large, mesenchymal, round-to-polygonal cells arranged in nests or sheets were found on histologic examination at post mortem. These cells were characterised by abundant intracytoplasmic PAS-positive, diastase-resistant granules and positive immunoexpression of vimentin, S-100, neuron-specific enolase and desmin. This is the first report of a spinal granular cell tumour in a cat.

Predominance of Granular Cell Tumours among Testicular Tumours of Rabbits (Oryctolagus cuniculi f. dom.).

Testicular neoplasms are reported rarely in pet and laboratory rabbits (Oryctolagus cuniculi f. dom.), with interstitial cell tumours being the most commonly described testicular neoplasm. In this retrospective study, paraffin wax-embedded testicles with neoplastic changes from 52 rabbits were investigated. Five out of 52 animals exhibited more than one tumour type, resulting in a total of 57 tumours. Granular cell tumours were the most prevalent neoplasm with 36 examples (63%) out of the 57 testicular tumours. Interstitial cell tumours, Sertoli cell tumours and seminomas occurred less frequently. Granular cell tumours of the testis are rare in rabbits. Histological similarities between granular cell and interstitial cell (Leydig cell) tumours in haematoxylin and eosin-stained tissue sections may lead to misdiagnoses. The periodic acid-Schiff reaction or immunohistochemistry for periaxin and S100 protein, as well as ultrastructural analysis, are useful methods to confirm the diagnosis.

Granular Cell Tumor in a Horse: Multifocal Pulmonary Distribution and Evidence of Autophagy in Tumorigenesis.

Granular cell tumor (GCT) is a soft tissue neoplasm characterized by abundant intracellular eosinophilic granules. The majority of GCTs are benign, although some display malignant behavior. Furthermore, GCTs may mimic other neoplasms. The clinical course and biology of GCTs are poorly understood. Regarding the histogenesis of GCT, a Schwann cell origin is currently favored in light of immunohistochemical and ultrastructural analyses. However, based on literature data, some of the primitive GCTs show non-neural origin; therefore, the histogenesis of this tumor has remained enigmatic. Granular cell tumors can arise in almost any location of the body and typically present as solitary lesions. This study illustrates equine primary GCT with multifocal pulmonary distribution. The presence of GCT in the respiratory tract becomes a diagnostic challenge on initial presentation. The morphologic details of this case are presented. Immunohistochemical evaluation confirmed the neuronal origin of equine GCT and the relation of intracytoplasmic granules formation to an autophagy phenomenon. Most of the discussion is related to GCT nature to help characterize molecular aspects associated with the biological behavior of this tumor and its heterogeneity.

The utility of intraoperative impression smear cytology of intracranial granular cell tumors: Three cases.

Two adult male dogs (a 7-year-old shorthaired Chihuahua and 14-year-old Shih Tzu) and one adult female dog (a 9-year-old Maltese) presented for evaluation of new-onset seizure activity. Magnetic resonance imaging of the brain demonstrated a large, poorly marginated T2-weighted hyperintense, and strong contrast enhancing extra-axial mass in each case. A surgical biopsy for histopathologic evaluation was elected in all cases, and intraoperative impression smears were successfully obtained. Intraoperative cytology identified a homogenous population of round to polygonal cells with central to eccentric nuclei, coarse chromatin, and variably amphophilic to eosinophilic granular cytoplasm. Cytologic findings led to a suspected diagnosis of granular cell tumor (GCT) in all cases. Histopathologic review identified a densely cellular, unencapsulated neoplastic mass comprised of sheets of large round to polygonal cells with abundant eosinophilic cytoplasm containing numerous eosinophilic intracytoplasmic granules, confirming the diagnosis of GCT in all cases. The cases reported here are unique in that they reveal an accurate intraoperative cytologic diagnosis of a rare canine central nervous system neoplasm. Intraoperative cytology of the intracranial masses could provide clinicians with important and quick diagnostic and prognostic information; therefore, expediting decisions made intraoperatively. Further research is warranted to determine the diagnostic accuracy of intraoperative cytology for neoplasia in veterinary patients.

Magnetic resonance imaging features of intracranial granular cell tumors in six dogs.

Magnetic resonance (MR) imaging characteristics of intracranial granular cell tumors (GCTs) have been previously reported in three dogs. The goal of this retrospective study was to examine a larger number of dogs and determine whether distinctive MR characteristics of intracranial GCTs could be identified. Six dogs with histologically confirmed intracranial GCTs and MR imaging were included. Tumor location, size, mass effect, T1- and T2-weighted signal intensity, and peritumoral edema MR characteristics were recorded. In all dogs, GCTs appeared as well-defined, extra-axial masses with a plaque-form, sessile distribution involving the meninges. All tumors were located along the convexity of the cerebrum, the falx cerebri, or the ventral floor of the cranial vault. All tumors were mildly hyperintense on T1-weighted images, and iso- to hyperintense on T2-weighted images. A moderate-to-severe degree of peritumoral edema and mass effect were evident in all dogs. Findings indicated that, while several MR imaging characteristics were consistently identified in canine cerebral GCTs, none of these characteristics were unique or distinctive for this tumor type alone.

Laryngeal rhabdomyoma in a dog.

A 3-year-old, female spayed Australian Shepherd dog was presented to Veterinary Healthcare Associates in Winter Haven, FL with a history of respiratory stridor, difficulty swallowing, and a change in bark for approximately 3 months. Radiographs revealed a soft tissue mass caudal to the epiglottis. Oral and computerized tomographic (CT) examinations were performed under general anesthesia and revealed a small firm mass in the caudal larynx on the right side. Cytologic evaluation of a fine-needle aspirate of the mass revealed cells consistent with a rhabdomyoma, oncocytoma, or granular cell tumor. Histopathologic interpretation was rhabdomyoma or oncocytoma. Histochemical staining with periodic acid-Schiff was mostly negative with a low number of weakly positive cells and with phosphotungstic acid-hematoxylin was strongly positive with visible cross striations. Tumor cells did not express pancytokeratin AE1/AE3, were strongly immunoreactive for myoglobin and muscle-specific actin, and did not express vimentin except for a low number of weakly immunoreactive cells. These findings confirmed a diagnosis of rhabdomyoma. Primary neoplasia of the larynx is rare, and widely varying types of neoplasms have been documented in this location. Due to the cytologic and histologic similarities between rhabdomyoma, oncocytoma, and granular cell tumor, these neoplasms should be differentiated using histochemical staining and immunohistochemical analysis.

Histopathologic, immunohistochemical and ultrastructural features of a granular cell tumour in an Australian parakeet (Melopsittacus undulatus).

An adult male Australian parakeet (Melopsittacus undulatus) presented a firm nodular lesion in the lateral metacarpal region of the right wing. Microscopically, there were neoplastic cells, round and polyhedral in shape, with abundant, slightly eosinophilic granular cytoplasm; they were strongly periodic-acid Schiff-positive and resistant to diastase digestion. Some groups of neoplastic cells were immunopositive for smooth muscle actin and desmin. There was no immunopositivity for S-100 protein, CD68 and cytokeratin. Ultrastructurally, the neoplastic cells were round and polygonal in shape, and they were characterized by abundant cytoplasm with numerous homogeneous osmophilic bodies covered by an electron-dense membrane (lysosomes). The histopathologic, immunohistochemical and ultrastructural features of the neoplastic tissue are consistent with a granular cell tumour, which has been described in different animal species and anatomic locations; however, this seems to be an infrequent neoplasm in Australian parakeets. The immunopositivity of the neoplastic cells for smooth muscle actin and desmin, as well as slight positivity for muscle with Masson's trichrome, suggest that this is a tumour of myogenic origin.

Atypical meningeal granular cell tumor in a dog.

A 10-year-old, female spayed Chihuahua dog was presented to the Veterinary Teaching Hospital at the University of Georgia for evaluation of seizures, abnormal mentation, and cervical pain of 2 months duration. On magnetic resonance imaging, there was generalized thickening of the meninges overlying the left cerebral hemisphere and along the falx cerebri. Despite symptomatic treatment, the dog remained neurologically affected. Consequently, the owners elected euthanasia. On gross examination, the meninges covering the left cerebral hemisphere were severely thickened and firmly adhered to the calvaria. On transverse section, the white matter of the left cerebral hemisphere was swollen, enlarged, and extended across the midline with resultant compression of the right cerebral hemisphere. Cytologic evaluation of an impression smear of the thickened meninges showed numerous large, spindloid to polygonal cells with abundant, amphophilic, vacuolated cytoplasm, present either in clusters or in individual cells. Histopathologic evaluation of the meninges revealed a poorly circumscribed and infiltrative, moderately cellular neoplasm, composed of vacuolated, spindloid to polygonal cells with marked anisocytosis and anisokaryosis, arranged in sheets, and occasionally separated by thick bands of connective tissue. Immunohistochemistry for vimentin revealed diffuse cytoplasmic staining of the neoplastic cells. Although the periodic acid-Schiff reaction was negative, ultrastructural findings showed numerous vesicles that were empty or that contained membranous or electron-dense material. Based on gross, microscopic, immunohistochemical, and ultrastructural changes, the meningeal neoplasm was diagnosed as an atypical granular cell tumor.

Canine eyelid granular cell tumor: a report of eight cases.

To describe a previously unreported neoplasm of the medial canthus and eyelid in dogs. Clinical and pathologic features of granular cell tumors in the dog were reviewed. Granular cell tumors, arising from the medial canthal eyelid of eight dogs, were identified from the archives of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). The affected dogs ranged in age from 5 to 12 years (mean of 9.25 years). Follow-up information was available for seven of the eight cases. The clinical presentation included swollen hyperemic lids (4/8), ulcerated skin overlying the mass (2/8), and red conjunctiva (7/8). All eight of the cases had firm masses extending from the palpebral conjunctiva to the eyelid margin at the medial canthus. Histologically, the tissue was composed of a highly collagenous neoplastic growth. The neoplastic cells were oval to strap-like cells with an oval bland appearing nucleus and abundant amounts of granular cytoplasm with very distinct cell boundaries. These granular cells were embedded in a dense collagen matrix. A PAS stain faintly highlighted the granular appearance of the neoplastic cells, which is a defining characteristic of this tumor. There was no recurrence in the seven cases available for follow-up. Canine granular cell tumors of the medial canthus present clinically and histologically as a benign neoplasm. Granular cell tumors have a characteristic histological appearance. Granular cell tumors should be on the differential list for nodules of the medial canthus in dogs.

Cytologic, histologic, and immunohistochemical features of lingual liposarcoma in a dog.

A 9-year-old female spayed mixed-breed dog was presented to the referring veterinarian with a history of decreased appetite and difficulty with prehension and swallowing because of a firm oval mass in the tongue. On cytologic evaluation of a fine-needle aspirate of the mass there were numerous round to polygonal cells organized individually or in loose clusters with rare branching capillaries. The cells had eosinophilic granular cytoplasm, round to oval nuclei, and occasionally indistinct borders. The cytologic diagnosis was granular cell tumor (GCT) of the tongue. Impression smears of a biopsy sample of the lingual mass contained similar eosinophilic granular cells with variable numbers of clear vacuoles in the background, numerous perivascular arrangements, and occasional lipoblasts, suggestive of liposarcoma. On histologic examination the tumor was composed of numerous lipocytes with rare foci of round eosinophilic granular cells without evidence of vacuolation; occasionally, atypical mitotic figures were seen. Immunohistochemically, the cells were uniformly negative for periodic acid-Schiff and did not express smooth muscle actin, desmin, or cytokeratin but were immunoreactive for vimentin and S100. A diagnosis of well-differentiated liposarcoma was made on the basis of morphologic and immunohistochemical results. Eosinophilic granular cells may be a component of well-differentiated liposarcoma and are not limited to GCT. Liposarcoma should be considered in the differential diagnoses of lingual tumors in the dog when cytological evaluation reveals eosinophilic granular cells consistent with GCT.

Granular cell tumor in a lumbar spinal nerve of a dog.

A 2-year-old Great Dane dog with a 2.5-week history of progressive paraparesis was presented to the Veterinary Medical Teaching Hospital at the University of Wisconsin-Madison. Neurologic examination revealed nonambulatory paraparesis with reduced to absent withdrawal hind-limb reflexes and lumbar pain. Magnetic resonance imaging and gross pathology confirmed a larger regional lumbar mass and a second smaller extradural mass within the spinal canal. The left lumbar mass was associated with extensive hemorrhage; dissection showed a dark-red, soft, well-circumscribed mass measuring 2 cm x 1.5 cm x 0.5 cm within the left fourth lumbar spinal nerve. Histopathological evaluation with immunohistochemistry revealed sheets of round to polygonal cells with diffuse granular cytoplasm demonstrating diastase-resistant periodic acid-Schiff reactivity and positive immunoexpression of S100 and neuron-specific enolase. The smaller extradural mass within the spinal canal exhibited similar morphology. Based on gross, histological, and immunohistochemical evidence, the masses were diagnosed as granular cell tumor.

Characterization of uterine granular cell tumors in B6C3F1 mice: a histomorphologic, immunohistochemical, and ultrastructural study.

The granular cell tumor is most often a benign neoplasm of uncertain origin. Four uterine granular cell tumors in control and treated female B6C3F1 mice were identified in chronic studies at the National Toxicology Program. Two tumors occurred in untreated control animals and 2 in treated animals receiving different compounds. Tissue sections were evaluated histologically and stained with hematoxylin and eosin, periodic acid-Schiff with diastase resistance, Masson's trichrome, toluidine blue, phosphotungstic acid-hematoxylin, and stained immunohistochemically with a panel of antibodies to muscle (desmin, alpha smooth muscle actin), neural (S-100, neuron specific enolase), epithelial (wide-spectrum cytokeratin), and macrophage (F4/80) markers. The main histomorphologic feature of tumor cells was the presence of abundant cytoplasmic eosinophilic granules that stained positive for periodic acid-Schiff with diastase resistance. Tumors varied in appearance and were comprised of sheets and nests of round to polygonal cells with distinct borders. Nuclei were hyperchromatic, pleomorphic, and centrally to eccentrically located and often contained single nucleoli. Occasional multinucleated giant cells were observed. Tumors were pale pink and homogeneous with trichrome stain and negative with toluidine blue. Three tumors had positive to weakly positive immunoreactivity for desmin, and 1 was positive for alpha smooth muscle actin. Expression of S-100, wide-spectrum cytokeratin, and neuron-specific enolase was negative for all tumors. Ultrastructurally, prominent electron-dense cytoplasmic granules were abundant and contained secondary lysosomes with heterogeneous lysosomal contents. The characteristics of these uterine granular cell tumors were suggestive of a myogenic origin.

Granular cell tumor in the testis of a rabbit: cytologic, histologic, immunohistochemical, and electron microscopic characterization.

An adult pet rabbit (Oryctolagus cuniculus) presented with a progressively enlarging left testicle. Because neoplasia was suspected, the testicle was removed. Pathologic evaluation (exfoliative cytology, histopathology, immunohistochemistry, electron microscopy) indicated that the tumor was an intratesticular granular cell tumor. Granular cell tumor has not been described in rabbits before and has not been described in the testes of animals or postnatal humans. Granular cell tumor should be included as a differential diagnosis of testicular tumors, particularly Leydig cell tumor, because of potential histologic similarities.