Symptomatic granular cell tumor involving the pituitary gland in a dog: a case report and review of the literature

A granular cell tumor involving the pituitary gland, optic chiasm and ventral pyriform lobes was discovered in a 12-year-old Labrador Retriever. Clinical signs included acute blindness, seizures, ataxia, weakness, and behavioral changes. The diagnosis was established by histopathologic and ultrastructural examination of neoplastic tissues collected at necropsy. Granular cell tumors involving the central nervous system are well documented in humans but rarely have been described in dogs. The location of the neoplasm and the clinical symptoms seen in this dog closely parallel those of a rare syndrome in humans commonly described as symptomatic parasellar or pituitary granular cell tumors. The cell of origin for these tumors is still highly debated, and attempts to characterize human granular cell tumors through immunohistochemistry have produced conflicting results. An immunohistochemical profile of this neoplasm revealed focal positive staining for vimentin with a lack of staining for neuron-specific enolase, glial fibrillary acidic protein, S-100, and synaptophysin. All neoplastic cells were strongly positive with the periodic acid-Schiff reaction.     

Canine mesenchymal hamartoma of the eyelid

Objective Characterization of a benign disease syndrome involving the eyelids of dogs, describing the signalment, clinical appearance, anatomic location, and pathologic features. Animal studied The records and submitted tissue of 10 dogs with mesenchymal hamartomatous lesions of the periocular connective tissues were retrieved from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database. Procedure The submitted tissue in each case was stained with hematoxilyn & eosin and Masson’s Trichrome stain and examined histopathologically. Clinical information was collected from the submission requests. The clinical history, treatment, and follow‐up are described in more detail for one of the 10 dogs. Results Seven different breeds, including four Golden Retrievers, were represented. The ages of affected dogs ranged from 6 to 11 years. Eight of 10 lesions were located at the temporal canthus, ranging in diameter from 0.6 to 3 cm. Clinically, the masses were subcutaneous, firm, lobular soft‐tissue growths, which were in some cases adherent to the underlying orbital rim, and in others, freely palpable between the skin and conjunctiva of the eyelid. Histologically, all had distinct margins but were not encapsulated and contained normal appearing collagen‐rich connective tissue with some adipose tissue. Five also contained fully differentiated skeletal muscle tissue arranged in poorly formed aggregates or as individual muscle fibers. Conclusion Mesenchymal hamartoma of the eyelid has not been previously described. The mass has a predisposition to occur at the temporal canthus and should be included in the list of differential diagnoses of benign eyelid masses in dogs.     

Standard and modified glabellar flap for medial canthus reconstruction following mass removal in three dogs and two cats

Purpose

To describe the surgical technique and clinical outcomes of the glabellar flap and its modification for the reconstruction of the medial canthus following resection of tumors in three dogs and two cats.

Methods

Three dogs (7-, 7-, and 12.5-year-old mixed breeds) and two cats (10- and 14-year-old Domestic shorthair) presented with a 7–13 mm tumor affecting the eyelid and/or conjunctiva in the medial canthal region. Following en bloc mass excision, an inverted V-shaped skin incision was made in the glabellar region (i.e., the area between the eyebrows in humans). The apex of the inverted V-shaped flap was rotated in three cases, whereas a horizontal sliding movement was performed in the other two cases to better cover the surgical wound. The surgical flap was then trimmed to fit the surgical wound and sutured in place in two layers (subcutaneous and cutaneous).

Results

Tumors were diagnosed as mast cell tumors (n = 3), amelanotic conjunctival melanoma (n = 1), and apocrine ductal adenoma (n = 1). No recurrence was noted in a follow-up time of 146 ± 84 days. Satisfactory cosmetic outcome with normal eyelids closure was achieved in all cases. Mild trichiasis was present in all patients and mild epiphora was noted in 2/5 patients, but there were no associated clinical signs such as discomfort or keratitis.

Conclusions

The glabellar flap was easy to perform and provided a good outcome in terms of cosmetic, eyelid function, and corneal health. Postoperative complications from trichiasis appear to be minimized by the presence of the third eyelid in this region.     

Granular cell lesions in the distal female reproductive tract of aged Sprague-Dawley rats

During the review of a rat carcinogenicity study, a spectrum of granular cell lesions was recognized in the distal female reproductive tract. To verify the diagnoses, cell populations of nine granular cell alterations of the cervix or vagina were characterized immunohistochemically and four were evaluated ultrastructurally. Immunoreactivity was demonstrated in 8/9 cases with S100 protein, 6/9 cases with neuron-specific enolase, and 7/9 cases with Leu-7. Granular cells were negative for smooth muscle-specific actin and calretinin. The immunohistochemical profile of these lesions was similar to that previously reported in other species, including humans. Ultrastructurally, as expected many lysosomal bodies were present in the cytoplasm of granular cells in all specimens evaluated. Based on the detailed evaluation of a series of lesions, we adopted the following diagnostic criteria and nomenclature for the granular cell changes of the female reproductive tract of rats. Granular cell aggregates were non-space-occupying lesions composed of clusters of typical granular cells. Benign granular cell tumors were space occupying lesions that typically contained prominent interstitial collagen and were either discrete masses or were difficult to discern from the surrounding tissues. Some benign tumors also contained foci of spindle cells with decreased granularity. Malignant tumors exhibited pleomorphism and an increased nucleus: cytoplasm ratio morphologically but had the same biologic behavior as the benign tumors. We applied these diagnostic criteria during the review of controls from 9 carcinogenicity studies. Up to 23% of control females in those carcinogenicity studies had granular cell lesions that could be classified into one of the three categories. Granular cell lesions appear to be common in the cervix/vagina of the Sprague-Dawley rat, and tumors may develop from granular cell aggregates.     

Feline conjunctival melanoma: histopathological characteristics and clinical outcomes

Purpose  We report on the histopathology and clinical features of 21 cases of feline conjunctival melanoma.
Methods  A total of 18 cases are from the COPLOW collection and three cases from Antech Diagnostics. We tabulated the location of the tumor, pigmentation, cell shape, mitotic index and presence of multinucleated tumor cells. Surveys were sent to referring ophthalmologists to obtain further information about each case.
Results  The mean age of the cats was 12.4 years. A total of 11 cases were neutered males, six spayed females, and one each of intact female and male. Thirteen of the 21 cases were located on the bulbar conjunctiva, three on third eyelid only, three on palpebral conjunctiva. Sixteen tumors were pigmented while five were amelanotic. Seventeen of the cases consisted of round cell only while four cases were mixed populations of round and spindle cell. Fourteen of the cases contained multinucleated cells. The mitotic index ranged from 0 to 45 mitotic figures/10 HPF. Of the 13 cases with adequate follow-up information, four showed local recurrence while three reported metastasis. Eight cats had died at the time of the survey. Survival time post-diagnosis ranged from 0.5 to 36 months. Two cases had metastasized to the submandibular lymph nodes and in a third case, an abdominal mass was detected.
Conclusions  Feline conjunctival melanoma is most frequently found on the bulbar conjunctiva, are mostly round cells and suggest that conjunctival melanoma in cats has a poorer long term prognosis than the same neoplasm in dogs.     

Cytology of canine malignant histiocytosis

Cytologic features of bone marrow, tissue, and abdominal fluid in seven cases of malignant histiocytosis in dogs are described, and histopathology, hematology, and serum biochemistry of the cases are reviewed. Diagnosis of malignant histiocytosis was confirmed by tissue morphology and immunohistochemistry; neoplastic cells in all cases had positive immunoreactivity to lysozyme. This stain can be used to definitively establish the diagnosis of malignant histiocytosis on cytology specimens as well as tissue sections. Cytologic findings included numerous pleomorphic, large, discrete mononuclear cells with abundant, lightly basophilic, vacuolated, granular cytoplasm. Nuclei were round to oval to reniform with marked anisocytosis and anisokaryosis; nucleoli were prominent. Mitotic figures, often bizarre, were occasionally seen. Multinucleated giant cells and phagocytosis of erythrocytes and leukocytes were prominent features in cytologic preparations in four cases. Four dogs were anemic, five dogs were thrombocytopenic, and three dogs were hypercalcemic. Breeds affected included Doberman Pinscher (1), Golden Retriever (2), Flat Coated Retriever (3), and mixed-breed dog (1).     

Macromorphometric study on ciliary body location in canine eyes

This macroscopic study firstly examined the precise locational information of the canine ciliary body, i.e., the ciliary crown and the ciliary ring in the beagle. The safe and effective transscleral laser photocoagulation technique requires the accurate location of the ciliary body. In both sides of the eyeball in 10 beagle dogs, the width of the ciliary ring and the distance from the limbus to the ciliary ring were measured with calipers using a stereomicroscope at the 8 points. The widest portion of ciliary body was found at the dorsal to ventro-temporal area of the lateral canthus (lateral portion of the eyelid; ear side). In contrast, the narrowest portion was seen at the ventro-nasal to nasal area of the medial canthus (medial portion of the eyelid; nasal quadrants). Use of transscleral photocoagulation at the present narrowest area of ciliary body may carry a high risk of destruction of the optic portion of retina.     

Small intestine large granular lymphoma in a horse

A 12-year-old Appaloosa gelding was referred to the Texas Veterinary Medical Center with a history of chronic diarrhea and weight loss. At necropsy, numerous oval, craterlike ulcers were observed throughout the small intestine. Histologically, these lesions were composed of a neoplastic proliferation of round cells with intracytoplasmic phosphotungstic acid-hematoxylin-positive granules. The tumor cells stained positively for the CD3 antigen and negatively for a B-cell marker. A diagnosis of large granular lymphoma was based on the morphologic and immunohistochemical characteristics of the neoplasm. The postmortem presentation of this case depicted unusual multifocal, ulcerative lymphomatous lesions throughout the small intestine without involvement of the regional lymph nodes. The histologic and ultrastructural morphology of the neoplastic lymphocytes was similar to that in previously reported cases of abdominal equine large granular lymphomas, but in this case the neoplasm was restricted to the small intestine.     

Co-existing squamous cell carcinoma and hemangioma on the ocular surface of a cat

A 14-year-old spayed female domestic short-haired cat was presented for evaluation of a mass in the right eye. Ophthalmic examination revealed a blind right eye and presence of two distinct masses: a pink and a red-to-brown mass, the latter occupying most of the cornea and part of the conjunctiva. Exenteration was performed under general anesthesia, and the ocular tissues were processed routinely for histopathology. Upon microscopic examination, a malignant epithelial neoplasm and a benign vascular neoplasm were present in the cornea. The conjunctiva and the third eyelid were also affected. Upon immunohistochemistry, the epithelial tumor was positive for cytokeratin and negative for vimentin and the endothelial tumor was negative for cytokeratin and positive for vimentin. A diagnosis of squamous cell carcinoma (SCC) and hemangioma was made. The SCC was affecting the cornea, bulbar conjunctiva (lateral and inferior) and the base of the third eyelid, whereas the hemangioma was affecting the cornea and medial limbus. To the authors' knowledge, this is the first report of concomitant SCC and hemangioma affecting the ocular surface in a cat.     

Cytologic appearance of hibernoma in two dogs

Hibernomas are rare benign tumors of brown fat (adipose tissue) that have been reported in several different species. The cytologic characterization of these tumors has not been described in dogs. In this case report, we describe two dogs with hibernomas, focusing on the cytologic appearance of these unique neoplasms. Both cytologic specimens were highly cellular and predominated by vacuolated neoplastic cells with no evidence of concurrent inflammation. The cells contained a moderate to large number of variably sized cytoplasmic vacuoles, with occasional, irregularly shaped pink granular material. Most cells contained a single nucleus; however, cells displayed moderate anisokaryosis. A biopsy with histologic examination was performed in both cases, confirming the cytologic suspicion of hibernoma. Immunohistochemistry revealed that both tumors were positive for UCP1 and vimentin, and negative for cytokeratin. Hibernoma is an important differential diagnosis in dogs with conjunctival and periocular swellings that exfoliate numerous, mildly atypical, vacuolated cells.     

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.     

Canine lobular orbital adenoma: a report of 15 cases with distinctive features

Objective To describe a unique orbital neoplasm in dogs, of lacrimal or salivary gland origin. Animals studied Fifteen dogs with lesions consistent with a diagnosis of lobular adenomas involving the orbit were identified from the Comparative Ophthalmic Pathology Laboratory of Wisconsin from 1994 to 2001. Results The neoplasm occurred in nine females and six males. Affected dogs ranged in age from 7 to 17 years (mean = 9.7 years). Follow‐up information was available for 13 of the 15 cases. The clinical presentation included swollen/hyperemic eyelids (4/15), third eyelid protrusion (3/15), conjunctival mass (6/15), exophthalmos (4/15), resistance to retropulsion (2/15), or strabismus (1/15). In 13 cases the masses were composed of nodular, friable tissue and they were solid in two cases. Histologically, the tissue was found in encapsulated lobules resembling well differentiated lacrimal or salivary glands but completely lacking ducts. Granular PAS‐positive material was found within the cytoplasm. There was recurrence in 10 of the 13 cases available for follow‐up. Of those cases in which enucleation or exenteration was performed (3/15), there was recurrence of disease in one case. In three cases the dogs were euthanized before recurrence at 3 months, 5 months and 3 years post surgery. None of the deaths was related to the tumor. Conclusion In the 15 cases reviewed, lobular adenomas of the orbit presented clinically and histologically as a benign neoplasm of lacrimal or salivary gland origin. Recurrence was likely unless the mass was completely excised, at times requiring orbital exenteration.     

Nature and cause of bilateral ocular dermoids in Hereford cattle

Nature and cause of bilateral ocular dermoids were investigated by field studies, pedigree analysis, clinical examination, light microscopy, scanning electron microscopy, and transmission electron microscopy. It was determined that ocular dermoids in Hereford cattle are a genetically transmitted defect; characteristics of autosomal recessive and polygenic inheritance were observed. Calves typically were affected bilaterally with multiple, connected ocular growths that clinically, histologically, and ultrastructurally mimicked normal haired skin. Sites most commonly involved included ventro-lateral limbus, third eyelid, medial canthus, eyelid and conjunctiva. Centro-corneal and anterior segmental dermoids also were observed.     

Follicular stem cell carcinoma: histologic,immunohistochemical, ultrastructural,and clinical characterization in 30 dogs

Diagnostic records of 30 primary and one metastatic follicular stem cell carcinomas in 30 dogs were reviewed. Neoplastic cells had a clear cytoplasm and formed lobules and nests surrounded by a basement membrane. Trichoepitheliomatous and apocrine differentiations were noted in 22 of 30 (73%) and 21 of 30 (70%) primary tumors, respectively. Glycogen was present in 20 of 20 (100%) tumors tested, suggesting tricholemmal differentiation. Antibodies against AE1/AE3 cytokeratin, vimentin, and melanA/MART1 stained 29 of 30 (97%), 29 of 30 (97%), and 12 of 27 (44%) primary tumors, respectively. Small amounts of melanin were identified in 14 primary tumors, either on the hematoxylin and eosin-stained section (n = 6), or on the Fontana-stained section (n = 8 of 14). Ultrastructural features of neoplastic cells included cell junction complexes, swollen mitochondria, neuroendocrine-like granules, and intracytoplasmic non-membrane-bound accumulation of proteinaceous material. Features of this neoplasm are consistent with a follicular stem cell origin. Follow-up information was available for eight dogs. Metastases developed in the draining lymph node at the time of excision of the primary tumor (n = 1) or subsequently (n = 3).     

Occurrence and expression of p53 suppressor gene and c‐Myc oncogene in dog eyelid tumors

Purpose To detect the occurrence and expression of the suppressor gene p53 and of the oncogene c‐Myc in eyelid tumors of dogs using the PCR, RT‐PCR, PCR‐ELISA and RT‐PCR‐ELISA techniques. These genes have not been described in dog eyelid tumors before. Methods Nine samples of eyelid or third eyelid epithelial tumors were obtained from the archives of the Department of Veterinary Pathology. Tumor diagnosis was confirmed by evaluation of hematoxylin‐eosin stained sections, and immunohistochemistry for cytokeratin AE1/AE3 and vimentin V9. A canine mammary tumor was used for positive control. Agarose gel electrophoresis, PCR‐ELISA and RT‐PCR‐ELISA were used to detect p53 and c‐Myc genes. Results The occurrence of p53 was detected in most of the eyelid tumors and third eyelid tumors studied (88.8%, n = 8) and was expressed in 75% of the positive samples, as indicated by ELISA. The c‐Myc gene was found in 77.7% (n = 7) of the samples and was expressed in eight samples. Conclusions Eyelid and third eyelid tumors of dogs express both the p53 and the c‐Myc genes as shown by PCR and RT‐PCR. However, PCR ELISA and RT‐PCR ELISA were more efficient in assessing occurrence and expression of these genes because they identified amplified products that were not detected by agarose gel electrophoresis.     

Paratracheal cervical mass in a dog

A 14-year-old female Welsh Terrier was presented for evaluation of multiple skin masses. Two of them were diagnosed as a follicular (epidermal) cyst and a sebaceous epithelioma by cytology and histopathology. The third mass was located in the subcutis adjacent to the cervical trachea. Clinical findings, thoracic radiography, and laboratory results were otherwise unremarkable. Cytologically, the cervical mass was characterized by the presence of round to polygonal cells with distinct cell borders, mild to moderate anisocytosis, round to oval eccentric nuclei with prominent nucleoli, and a variable amount of finely granular, eosinophilic cytoplasm. Differential diagnoses included endocrine/neuroendocrine tumors such as thyroid adenocarcinoma, medullary thyroid carcinoma, carotid body chemodectoma, and parathyroid carcinoma. The mass was removed surgically and submitted for histopathologic and immunohistochemical examination. Histologically, the mass was composed of rows and nests of densely packed cells separated by thin fibrovascular stroma. Neoplastic cells had moderate to large amounts of pale eosinophilic dusty or finely vacuolated cytoplasm and round to oval nuclei with finely dispersed chromatin and 1 or 2 small nucleoli. On immunohistochemistry, neoplastic cells were positive for chromogranin A, calcitonin, and neuron-specific enolase, and were negative for cytokeratin and thyroglobulin. The final diagnosis was medullary thyroid carcinoma, an uncommon endocrine tumor of dogs that has cytologic and histopathologic features similar to other endocrine and neuroendocrine tumors. Immunohistochemistry or immunocytochemistry should be performed to differentiate medullary thyroid carcinoma from other endocrine/neuroendocrine tumors of dogs.     

Mast cell tumour in the third eyelid of a mare

A 4‐year‐old Missouri Fox Trotter mare was referred to the Veterinary Teaching Hospital, Koret School of Veterinary Medicine with a reddish mass protruding from the third eyelid and adjacent palpebral conjunctiva of the left eye. On ophthalmic examination, the mare showed mild blepharospasm, mild mucopurulent discharge and mild corneal oedema in the left eye. Menace response, pupillary light reflexes and intraocular examination were normal. A rounded, fleshy red ulcerated mass, approximately 3 cm in diameter, expanded the edge of the outer surface of the medial third eyelid and conjunctiva of the ventromedial palpebral region. Physical examination was otherwise unremarkable. Based on history and clinical findings, surgical removal was elected. The tumour was excised and the conjunctiva in the area of tumour treated with cryotherapy. Histological evaluation revealed a mast cell tumour on the third eyelid. Nine months follow‐up revealed no recurrence.