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Uveal spindle-cell tumor; dog No. 3. Antoni A behavior is shown. HE stain. Fig. 4. Uveal spindle-cell tumor; dog No. 1. Antoni B behavior is shown. HE stain. Fig. 5. Uveal spindle-cell tumor; dog No. 8. Intracytoplasmic immunopositivity is shown. S-100 immunohistochemistry. Fig. 6. Uveal spindle-cell tumor; dog No. 13. Intracytoplasmic immunopositivity is shown. Glial fibrillary acidic protein (GFAP) immunohistochemistry. Fig. 7. Uveal spindle-cell tumor; dog No. 7. Extracellular immunopositivity is shown. Laminin immunohistochemistry. Fig. 8. Uveal spindle-cell tumor; dog No. 11. Nuclear and cytoplasmic immunopositivity is shown. Growth arrest and DNA damage45 (Gadd45) immunohistochemistry. Fig. 9. Uveal spindle-cell tumor; dog No. 8. Nuclear immunopositivity is shown. UV single strand DNA (UVssDNA) immunohistochemistry. Fig. 10. Uveal spindle-cell tumor; dog No. 6. Nuclear and cytoplasmic immunopositivity is shown. Telomerase reverse transcriptase (TERT) immunohistochemistry.
Source publication
Immunohistochemical techniques were used to investigate the origin of a spindle cell tumor in the anterior uveal tract of dogs and the influence of ultraviolet radiation on the development of this tumor. Thirteen tumors were identified from the 4,007 canine ocular samples examined at the Comparative Ocular Pathology Laboratory of Wisconsin between...
Context in source publication
Context 1
... entirely of spindle-shaped mesenchymal cells (Figs. 1-4). Tumor cells formed solid sheets of interwoven bundles, streams or whorls, often with palisading nuclei. Tumor morphology, nuclear features, necrosis, and mitotic index were highly variable. Antoni A and/or Antoni B behavior were exhibited by all tumors, consistent with human schwannomas (Figs. 3, 4). 32 Tumors were graded as 1, 2, or 3 as previously described. 34 All cases exhibited some degree of lymphoplasmacytic uve- itis. Most cases (except for cases 2, 4, 11, and 13) exhibited either clinical or histopathologic evidence of glaucoma (historical ocular hypertension, loss of retinal ganglion cells, optic nerve cupping/gliosis). ...
Citations
... Table S1). 27,30,35 Immunohistochemical labeling for pan-cytokeratin was performed at the Penn Vet Diagnostic Laboratory and evaluated by a single pathologist (AD). IHC was performed on a Bond autostainer automated system (Leica Microsystems), using a biotin-free, polymeric alkaline phosphatase-linked antibody detection system with fast red chromogen and hematoxylin counterstain (Bond Polymer AP Red Detection Kit, Leica Microsystems) for melan-A, PNL-2, and CD34; and a biotin-free, polymeric horseradish peroxidase conjugated detection system with 3,3 0diaminobenzidine and hematoxylin counterstain (Bond Polymer HRP Detection System, Leica Microsystems) for S100 and laminin. ...
Oral malignant melanoma (OMM) is considered the third most common oral malignant neoplasm in cats, but its variable morphology and frequent lack of melanin pigment make it a diagnostic challenge. Twenty-two cases of cats with malignant oral neoplasms that were diagnosed as OMM or listed OMM as a suspected differential diagnosis on the biopsy report were examined using an immunohistochemistry (IHC) panel for S100, melan-A, PNL2, laminin, CD34, and pan-cytokeratin. Although OMM was suspected ( n = 14) or previously diagnosed ( n = 8), only 2 cases were immunohistochemically confirmed as OMM. Seven cases were classified as soft tissue sarcoma based on positive expression of CD34 or laminin, and one was classified as carcinoma based on positive expression of pan-cytokeratin. The majority of cases ( n = 12) were categorized as unclassified malignant neoplasms because they did not express melan-A, PNL2, laminin, CD34, or pan-cytokeratin; however, a proportion of these did express S100 ( n = 7). Long-term prognosis of all 22 cats was poor, with a median survival time of 87 days (range = 2–249 days). Cases with longer survival times (>100 days) were treated with surgery, radiation therapy, or a combination. For feline oral malignant neoplasms thought to be OMM, routine use of IHC is required for an accurate diagnosis.
... Bilateral corneal dystrophy was noted in 10% of the Husky dogs in this study population. Blue-eyed dogs such as the Siberian Husky can also develop low-grade spindle cell neoplasms of the iris, 26,27 though none were noted in this population studied. ...
Purpose
To compare cataract characteristics and complications related to cataracts and phacoemulsification in the Siberian Husky (Huskies) versus other canine breeds (non‐Huskies).
Animals
A total of 50 Huskies (92 eyes) and 96 non‐Huskies (182 eyes) were evaluated.
Methods
Medical records of Huskies (at four university veterinary hospitals, 2008–2018) and non‐Huskies (Colorado State University, 2017–2018) diagnosed with cataracts were reviewed. Age of dog, cataract stage at presentation, and pre‐ and post‐operative complications were recorded and analyzed.
Results
Mean (±standard deviation) age at presentation was significantly lower in Huskies (3.5 ± 3.3 years) compared to non‐Huskies (9.5 ± 2.9 years) (p < .0001). Huskies more commonly presented with hereditary cataracts than non‐Huskies (84% versus 52%) and a significantly higher percentage of non‐Huskies presented with diabetic cataracts than Huskies (48% versus 16%; p = .0001). Cataract stage at presentation did not differ between Huskies and non‐Huskies. Phacoemulsification was performed in 40% (20 out of 50 dogs, 39 out of 92 eyes) of Huskies and 42% (40 out of 96 dogs, 74 out of 182 eyes) of non‐Huskies. Pre‐operative and post‐operative retinal detachment were more common in Huskies than non‐Huskies (13% versus 2% and 10% versus 1%, respectively) but the difference was not significant. Other post‐operative complications occurred with similar frequency in both groups (p ≥ .17).
Conclusions
Huskies evaluated for cataracts were younger and less likely to present with diabetic cataracts than other canine breeds and, although not statistically significant, had a clinically important increased risk of retinal detachment pre‐ and post‐phacoemulsification.
... Spindle cell tumors, primitive neuroectodermal tumors, and medulloepithelioma have been described. [78][79][80][81][82] Intraocular spindle cell tumors of dogs are rare and include peripheral nerve sheath tumors and metastatic sarcoma with hemangiosarcoma, osteosarcoma, and anaplastic mesenchymal tumors. Schwannomas were characterized in a study of 13 blue-eyed dogs with uveal tumors and were histologically composed of spindle cells arranged in fascicles and whorls. ...
Cytologic evaluation of specimens collected from diseased canine eyes can be helpful in the diagnosis of ocular diseases. Cytologic analysis is a quick and simple method that can provide a diagnosis in inflammatory and neoplastic ocular disease. However, additional tests are often needed for a definitive diagnosis.
... 22, Incomplete surgical resection leads to recurrence and metastatic disease is rarely reported. 22,24,39,43,44,46,47,[49][50][51][52] Stereotactic radiation therapy for canine trigeminal and brachial plexus MPNSTs may prolong survival times when surgical resection is not possible. 28,53 Metronomic cyclophosphamide and piroxicam treatment delays recurrence in dogs with incompletely resected MPNST. ...
Case summary:
A 14-year-old male neutered domestic mediumhair cat presented with a 4 month history of inappetence and weight loss. Pertinent abnormalities on haematology and biochemistry included a mild microcytic regenerative anaemia (packed cell volume [PCV] 24% [reference interval (RI) 30-45%], mean cell volume 30.8 fl [RI 40-45 fl], absolute reticulocyte count 326.8 × 1012) and increased alkaline phosphatase activity (76 IU/l; RI <50 IU/l). Abdominal ultrasound and CT scan revealed masses in the transverse colon (2.0 cm × 1.2 cm) and right medial liver lobe (5.0 cm diameter). Thoracic radiographs were unremarkable. Right medial liver lobe resection and colectomy were performed. Immunohistochemistry was positive for S-100 protein, vimentin and glial fibrillary acidic protein, very weakly positive for c-kit and negative for muscle-specific actin and CD18, consistent with a colonic malignant peripheral nerve sheath tumour (MPNST) with a hepatic metastasis. Postoperative treatment with metronomic cyclophosphamide was well tolerated. Eighteen months postoperatively the cat re-presented after 3 days of progressive lethargy and inappetence. Haematology revealed a marked non- or pre-regenerative anaemia (PCV 10%). Coagulation times were prolonged (prothrombin time 39 s [RI 15-22 s] and activated partial thromboplastin time >300 s [RI 65-119 s]). Abdominal ultrasound identified multiple renal and hepatic nodules. Euthanasia was performed and post-mortem examination confirmed metastasis of the MPNST.
Relevance and novel information:
This report describes the treatment of a metastatic colonic peripheral nerve sheath tumour in a cat. Feline visceral MPNSTs are rare and little is known about prognosis or optimal treatment.
... Uveal schwannomas are comprised of two cell patterns: spindle cells with nuclei arranged in stacked alignments, or palisades (an Antoni-A pattern) and spindle cells arranged in interlacing bundles and sheets (an Antoni-B pattern) that are vimentin and S100 positive, indicating mesenchymal and neural crest origins. In addition, glial fibrillary acidic protein (GFAP) marker is commonly positive in these tumors, suggestive of central nervous system origin [1,3]. Biologic behavior of these tumors is unclear and although generally considered benign, malignancy is described in a Beagle [3], Labrador retriever [4], and a mixed breed dog [5]. ...
Key Clinical Message
A 4‐year‐old, female spayed Siberian husky with history of a uveal schwannoma presented for orbital swelling 9 months after enucleation. A second, malignant tumor developed in the same orbit. Therefore, uveal schwannomas may warrant early surgical intervention in the dog.
... Reported primary intraocular sarcomas in dogs include canine intraocular extraskeletal osteosarcoma, 24-26 schwannoma of blue-eyed dogs/peripheral nerve sheath tumors, [27][28][29] and astrocytomas (gliomas). [30][31][32] Intraocular histiocytic sarcoma has been reported in dogs with and without intraocular mass lesions, 33 although unlike our case, intraocular histiocytic sarcoma is presumed to represent metastatic disease. ...
This case report describes the clinical findings and ocular pathology in an adult Golden Retriever diagnosed with an intraocular sarcoma. Nineteen s prior to diagnosis with a lens capsule rupture and intraocular sarcoma, the dog was diagnosed with persistent hyperplastic primary vitreous and uveitis based on clinical signs and the ultrasonographic appearance of the eye. Two years after enucleation, there was no evidence of metastatic spread of the sarcoma. The immunohistochemical characteristics of the tumor as well as the limitations and supportive evidence used in attempting to identify the histogenesis of the tumor are outlined.
... Z0311, Dako) and anti-smooth muscle actin (catalog no. M0851, Dako) were used at 1:100 for 60 min at room temperature (41,42). Secondary antibodies (catalog nos. ...
Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations. We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors, with the most common toxicities being the expected symptoms associated with bacterial infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three complete and three partial responses. On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor within and surrounding the bone. Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted.
... Uveal schwannomas of blue-eyed dogs have been reported in adult canines and were first described in 2007 with the former name spindle cell tumor of blue-eyed dogs. 13 The present case is similar but has distinct characteristics that we believe distinguish the 2 entities. The first is the young age. ...
... Previous studies in goniodysgenic (nonneoplastic) canine eyes demonstrate a prominent difference between blue-and brown-eyed dogs, whereby blue-eyed dogs show a significant increase in linear iridal GFAP positivity consistent with nonmyelinated nerves. 13 This blue-eyed GFAP positivity is absent in the nonneoplastic iris tissue in our case, which resembles the GFAP-positive distribution in a brown-eyed dog (data not shown). We believe that the preponderance of GFAP-positive cells in the blue uvea predisposes those animals to schwannoma formation, and we believe that the animal in the present case does not share the predisposition, because it lacks this immunohistochemical feature. ...
The formalin-fixed, amber-colored right globe from a 12-week-old female silver Labrador Retriever dog was submitted to the Comparative Ocular Pathology Laboratory of Wisconsin for light microscopic evaluation. The clinical history described a collapsed anterior chamber and multifocal nodular lesions in the peripheral iris. Histologically, immunohistochemically, and ultrastructurally, the uveal mass was consistent with a malignant schwannoma; there was extension along peripheral nerves within the sclera. The signalment and behavior of the neoplasm distinguish it from the uveal schwannoma of blue-eyed dogs and bear some resemblance to the ocular lesions in human neurofibromatosis. The dilute color mutation may contribute to the cause. Six weeks later, the dog did not develop any additional masses.
... However, in a retrospective study of SCTBED (which are suggested to be from Schwann cells), only 2 of 9 cases expressed laminin immunoreactivity. 7 The immunonegativity to laminin may be due to multiple cellular origins, anaplasia, a poorly differentiated schwannoma or even the lack of laminin protein. ...
A female, eight-year-old, mixed-breed blue-eyed dog was presented for ophthalmic evaluation because its left eye had "changed color" one year previously. The before left eye was enucleated and submitted for evaluation. Histopathological analysis revealed an invasive neoplastic mass effacing most of the ventral aspect of the iris stroma. A diagnosis of an anterior uveal spindle cell tumor was made. Immunohistochemical results were strongly suggestive of a schwannoma, but some smooth muscle differentiation was also observed. Two and a half years after therapeutic enucleation there was no evidence of neoplasm recurrence or metastasis.
... Additionally, dogs with possible metastatic disease had no morphologic or immunohistochemical commonalities that might relate to prognosis. 1 Here, we describe a dog with a uveal schwannoma and subsequent metastasis 17 months later. The primary tumor had invaded the sclera. ...
... The eye was paraffin embedded, and 4 mm dorsoventral sections were stained with hematoxylin and eosin (HE) and labeled with immunohistochemical markers for GFAP, vimentin, and S100 as described previously. 1 Seventeen months later, the animal was euthanized, and a necropsy performed by the referring veterinarian. Abnormal tissues including lung, liver, and mesenteric lymph nodes were submitted to COPLOW for histopathologic evaluation. ...
... Furthermore, immunohistochemical studies of non-neoplastic globes with blue vs. brown uveas reveal a distinct distribution of GFAP positive cells in blue irides that are absent in the brown, suggesting the blue-eyed phenotype may be somehow predisposed schwannoma development. 1 A recent study of canine PNSTs, including schwannomas, provides an in-depth discussion of the morphologic and immunohistochemical differences between benign and malignant variants. The study shows that both benign and malignant PNSTs have variable morphologies, but variants of both present the combination of Antoni A and B that is classic for schwannomas. ...
A formalin-fixed left, blue eye, from a 9-year-old, spayed female beagle dog was submitted to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) for light microscopic evaluation. The history included glaucoma and an abnormal appearance for 6 months and then the development of a uveal mass. The histologic diagnosis was a spindle cell tumor of blue-eyed dogs (SCTBED). In June of 2012, the dog was euthanized due to ailing health, and there was radiographic and postmortem examination evidence of neoplastic metastasis. This is the first reported case of this primary ocular neoplasm metastasizing, and we propose to rename SCTBED as a uveal schwannoma of blue-eyed dogs.
