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Canine neoplasia
Carol Naranjo, LV, DACVP, DECVP, PhD
IDEXX Laboratories
IRIDOCILIARY EPITHELIAL TUMORS
Iridociliary epithelial tumors – dogs
• 2nd most common primary intraocular neoplasm
• Middle-aged dogs
• Retrievers
• Origin:
– Pigmented or non-pigmented CB epithelium
– Posterior iris epithelium (pigmented)
Iridociliary epithelial neoplasia
• Adenoma
– Non uveo-invasive
– Uveo-invasive
• Adenocarcinoma (scleral invasion)
• Pleomorphic adenocarcinoma
Iridociliary adenoma/carcinoma – Gross
• Well-delineated
• PC >>> AC
• Cradling lens
• 90% non-pigmented (light tan – pink)
– Pigmented (DDX. melanocytic neoplasia)
Iridociliary epithelial neoplasms – Micro
• Ribbons, trabeculae, cords, papillae, acini
• Asteroid hyalosis
• 60% thick PAS-positive membranes
• 50% hyaluronic acid (Alcian blue +ive)
– DDx w/ metastastic neoplasia
Iridociliary epithelial neoplasms – IHC
• Vimentin, NSE +ive
• S100 variable
• Cytokeratin:
– Benign tumors –ive
– Increasing staining w/ invasiveness
Iridociliary epithelial neoplasms – IHC
Vimentin
Cytokeratin
Courtesy R. Dubielzig (COPLOW)
Iridociliary epithelial neoplasms –
Prognosis
• Benign despite variable invasiveness
• Secondary glaucoma
– Directly
– PIFM
• No metastatic dz
Pleomorphic adenocarcinoma
• Infrequent
• History of chronic ocular dz / trauma: 44%
– Trauma/uveitis
– Glaucoma
• Intraocular gentamicin injection: 25%
Zarfoss et al., 2007; Bell and Dubielzig, 2009 (ACVP abstract)
Pleomorphic adenocarcinoma
• Gross:
– Poorly defined mass  diffuse
– Filling the globe
• Histo: irregular cords, nests, anaplastic cells
• Poor prognosis (local recurrence, mets)
Pleomorphic adenocarcinoma – Gross
Pleomorphic
adenocarcinoma – Histo
Pleomorphic adenocarcinoma – IHC
Vimentin
100% positive (n =
Pancytokeratin
16)
75% positive (n = 16)
Bell & Dubielzig, ACVP abstracts, 2009
PNET
Neoplasia w/ neural differentiation
• PNET:
– Primitive neuroectodermal tumors
• Neuroblastoma, ependimoblastoma, retinoblastomas,
medulloepithelioma
• Eye:
– PNET: peripheral retina / CB
– Medulloepiteliomas: CB (dog) or ON (horse) >>> retina
Medulloepithelioma
• PNET
• Shared features with iridociliary tumors
• Rare in dogs, horses >>> others
• Not always young dogs
Medulloepithelioma – Gross
• CB: filling PC
• Can infiltrate retina
• Light tan
• Solid or papillary
Dubielzig et al., Veterinary Ocular
Pathology; A Comparative Review, 2010.
Medulloepithelioma – Micro
• Necrosis w/ survival around blood vessels
• Rosettes
• Teratoid: muscle, bone, cartilage, neuropil
• IHC:
– TERT +ive
– Vimentin and cytokeratin: limited +ivity
Dubielzig et al., Veterinary Ocular Pathology; A Comparative Review, 2010.
Medulloepithelioma – Prognosis
• Locally invasive
– Enucleation
• Mets very infrequent
¿Retinoblastoma?
• Sparse reports, some arguable
• Tumors with neural differentiation (PNET) but
do not meet all the criteria
Flexner-Wintersteiner rosettes
Fleurettes
Homer-Wright rosettes
Yanoff and Sassani’s Ocular Pathology, 2015
Courtesy of Dr. Dubielzig, COPLOW
Retinoblastoma in dogs?
• Retinoblastoma-like:
– Fleurettes / rosettes (1 layer)
• Medulloepithelioma
– Pseudorosettes
Retinoblastoma – like
IHC IRBP
Medulloepithelioma
Regan et al., 2013
UVEAL SCHWANNOMA OF BLUE EYED DOGS
Uveal schwannoma of blue-eyed dogs
• SCTBED
• Blue-eyed / partially blue-eyed
• Siberian huskies, Border Collies, Catahoula hound
Uveal schwannoma BED – Gross
• Anterior uvea (iris > CB) >>>> choroid
• Thickening of iris >> mass
– Confused with uveitis
– Only 50% neopl suspected
Courtesy of Dr. Dubielzig (COPLOW)
Case material from COPLOW
Uveal schwannoma BED – Histo
• Poorly demarcated
• Slender to plump spindle cells
• Bland to markedly atypical cells
• Loose fascicles to tight bundles and whorls
• May invade sclera
Uveal schwannoma BED – IHC
• Vimentin +
• S100 +
• GFAP +
Courtesy of Dr. Dubielzig (COPLOW)
– Schwann cells of nonmyelinated nerves of iris stroma
Uveal schwannoma BED – EM
• Long interdigitating cytoplasmic processes
• Intermittent basal laminae at plasma mb
• Peripheral nerve sheath origin
Zarfoss et al., 2007
Uveal schwannoma BED – Prognosis
• Invasive: recurrence w/in orbit / scleral shell
• Mets rarely reported:
– Lungs, liver, mesenteric LN
– Path features linked to malignancy? (scleral invasion?)
METASTATIC TUMORS Metastatic tumors to the globe (uvea)
• Dogs
– Lymphoma > histiocytic sarcoma
– Carcinoma, melanoma, hemangiosarcoma, OSA,…
– Carcinoma: mammary
– Extraskeletal OSA or chondrosarcoma
• Search for primary tumor!
Uveal lymphoma
• Most common metastatic neoplasm
• 37% dogs w/ lymphoma have uveal involvement
– Preceding systemic signs, presenting complaint
• 2nd clinical sign (after lymphadenopathy)
• Bilat (not always)
Uveal lymphoma – Gross
• Anterior > posterior uvea
• Mass-like lesion or diffuse (DDx. uveitis)
• Light tan
• Hematological abnormalities (hemorrhage)
Uveal lymphoma – Micro
• Monomorphic round cells
– Iris, CB > retina, choroid, limbus, ON, peripheral n.
• DDx. melanoma / histiocytic sarcoma
Uveal lymphoma – IHC
• B cell: CD20, CD79a, PAX5
• T cell: CD3
• Both described in the eye
Uveal lymphoma – Prognosis
• Guarded
• Systemic: stage V if associated w/ hemorrhage
• ¿Primary? (Wiggans et al., 2014)
– Neurologic signs indep of ON involvement
– ¿Staging?
Histiocytic sarcoma
• Metastatic
• Not infreq presented for ocular dz first
• Rottweiler > Retrievers > BMD
• Adult to senile
• Unilat (typically)
Histiocytic sarcoma – Gross
• Light tan
• Anterior uvea
Histiocytic sarcoma – Micro
• Round cells w/ abundant cytoplasm
– DDx. amelanotic melanoma
• Multinucleation, karyomegaly
Histiocytic sarcoma – IHC
• Vimentin +
• CD18 +
• Melan A –
• CD3/CD20 –
Histiocytic sarcoma – Prognosis
• Grave, survival 0-6 mo post-enucleation
Metastatic tumors to the globe
• Unilat  bilat
• Anterior > posterior uvea
• Neoplastic cells w/in blood vessels
• 2 patterns:
– Discrete mass
– Diffuse infiltrates lining the inner aspect of uvea
Primary vs. metastatic carcinomas
Primary
benign
Primary
malignant
Metastatic
Cytokeratin
-
+/-
+
Vimentin
+
+
-
Metastatic malignant melanoma
Thanks!
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