Canine neoplasia

Carol Naranjo, LV, DACVP, DECVP, PhDIDEXX 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

Courtesy R. Dubielzig (COPLOW)

Vimentin Cytokeratin

Iridociliary epithelial neoplasms – IHC

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

Pleomorphicadenocarcinoma – Histo

Pleomorphic adenocarcinoma – IHCVimentin

100% positive (n = 16)

Pancytokeratin

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 Homer-Wright rosettes

Fleurettes Yanoff and Sassani’s Ocular Pathology, 2015

Courtesy of Dr. Dubielzig, COPLOW

Retinoblastoma in dogs?

• Retinoblastoma-like:– Fleurettes / rosettes (1 layer)

• Medulloepithelioma– Pseudorosettes

Regan et al., 2013IHC IRBP

Retinoblastoma – like Medulloepithelioma

UVEAL SCHWANNOMA OF BLUE EYED DOGS

Uveal schwannoma of blue-eyed dogs

• SCTBED

• Blue-eyed / partially blue-eyed

– Siberian huskies, Border Collies, Catahoula hound

• Recent report in a brown-eyed dog (Marlo et al., 2018)

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 +

– Schwann cells of nonmyelinated nerves of iris stroma

Courtesy of Dr. Dubielzig (COPLOW)

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

– Survival 60-70% of those w/o ocular involvement

• ¿Primary?

Primary uveal lymphoma?• Wiggans et al., 2014

– Neurologic signs indep of ON involvement

– ¿Staging?

• Lanza et al., 2017:

– 61% w/o systemic signs (@ Dx)

– No progression

– Median survival: 769 d vs 103 d

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

• Unilat bilat

• Anterior > posterior uvea

• Neoplastic cells w/in blood vessels

• 2 patterns:

– Discrete mass

– Diffuse infiltrates lining the inner aspect of uvea

Metastatic tumors to the globe

Primary vs. metastatic carcinomas

Primary

benign

Primary

malignant

Metastatic

Cytokeratin - +/- + Vimentin + + -

Metastatic malignant melanoma

Thanks!Carolina-Naranjo@idexx.com