994601

brief-report2021
VDIXXX10.1177/1040638721994601Ocular teratoid medulloepithelioma in a macawLeal de Araújo et al.

Brief Report

Journal of Veterinary Diagnostic Investigation

Ocular teratoid medulloepithelioma 2021, Vol. 33(3) 600­–604

© 2021 The Author(s)
Article reuse guidelines:
in a northern red-shouldered macaw: sagepub.com/journals-permissions
DOI: 10.1177/1040638721994601
https://doi.org/10.1177/1040638721994601
jvdi.sagepub.com
case report and literature review

Jeann Leal de Araújo,1 Alice C. A. M. Arruda, Nayadjala T. A. Santos,

Glenison F. Dias, Thiago F. L. Nery, Fabio Del Piero, Richard Ploeg,
Brian F. Porter, Ingeborg M. Langohr

Abstract. A 4-mo-old northern red-shouldered macaw (Diopsittaca nobilis) was admitted to the veterinary hospital of
the Arruda Câmara Zoo, in the State of Paraiba, Brazil, for investigation of an orbital mass. Given rapid progression and
lack of response to treatment, the bird was euthanized, and an autopsy was performed. Histologically, the mass consisted of
a retrobulbar invasive tumor characterized by tubular and rosette-like structures, with interspersed heteroplastic tissues, such
as aggregates of neuroglial cells and islands of hyaline cartilage. The tumor was immunopositive for pancytokeratin, GFAP,
NSE, and S100. These findings were compatible with an ocular teratoid medulloepithelioma, a neoplasm best described in
humans but also reported rarely in young cockatiels and African Grey parrots.

Key words: Diopsittaca nobilis; eye; ocular tumors; psittacine birds; retrobulbar teratoid medulloepithelioma; wildlife.

Ocular lesions are commonly documented in birds but
reports of primary ocular neoplasms are scarce. Reported
tumors include undifferentiated carcinomas, melanocytic
tumors, intraocular osteosarcomas, multicystic adenomas,
pigmented iridociliary adenomas, ganglioneuromas, and
teratoid medulloepitheliomas.23
Medulloepitheliomas are embryonal tumors that can
affect the central nervous system (CNS), the neuroepithelial
structures of the eye, and the optic nerve. In humans, they
are rare congenital tumors that usually affect children.16
Medulloepitheliomas are also rare in domestic animals and
are most frequently reported in horses.2,3,7,17,28,29 These neo-
plasms have also been described in several other species,
including llamas, a cat, dogs, and a goldfish.10,12,14,15 Ocular
forms are uncommon in birds, and all reports of medulloepi-
thelioma in avian patients are from psittacine birds, specifi-
cally cockatiels and African Grey parrots.4,23,25
Here we describe the gross, microscopic, and immunohis-
tochemical features of an ocular teratoid medulloepithelioma
in a northern red-shouldered macaw (Diopsittaca nobilis).
In addition, we reviewed the literature relevant to this neo-
plasm.
A 4-mo-old northern red-shouldered macaw was kept at
the João Pessoa Zoo in northeastern Brazil. Zookeepers
noted that the bird had a slight swelling of the periocular
region and redness of the conjunctiva of the left eye. The bird
was hospitalized and treated with tobramycin and ketoprofen
eye drops, but the swelling rapidly progressed, accompanied
by mucohemorrhagic discharge. By day 7, a large mass
covered by intact skin protruded from the orbit, with perfora-
tion of the cornea (Fig. 1). Abscess, fungal granuloma, and
neoplasia with consequent exophthalmia were considered
possible differentials. Given the ongoing enlargement of
the mass, the macaw was euthanized after 15 d of hospital-
ization. The mass was collected, immersed in 10% neutral-
buffered formalin, and sent to the Federal University of
Paraiba. Unfortunately, the carcass was not sent for autopsy.
The sample sent for examination consisted of a 5-cm
diameter, firm, gray mass that obliterated the orbit, causing
marked compression of the globe. The cut surface was brown,
interspersed throughout with scattered areas of black discol-
oration. Three representative sections of formalin-fixed tissue
Department of Veterinary Sciences, Federal University of Paraíba,
Areia, Paraiba, Brazil (Leal de Araújo, Arruda, Santos); School of
Veterinary Medicine, Faculdade Nova Esperança–FAMENE, João
Pessoa, Paraiba, Brazil (Dias); Division of Veterinary Medicine, Parque
Zoobotânico Arruda Câmara, João Pessoa, Paraiba, Brazil (Nery);
Department of Pathobiological Sciences, School of Veterinary Medicine,
Louisiana State University, Baton Rouge, LA (Del Piero, Langohr);
Anatomic Pathology, Faculty of Veterinary and Agricultural Sciences,
University of Melbourne, Werribee, Victoria, Australia (Ploeg);
Department of Veterinary Pathobiology, College of Veterinary Medicine
and Biomedical Sciences, Texas A&M University, College Station,
TX (Porter).
1
Corresponding author: Jeann Leal de Araújo, Department of
Veterinary Sciences, Federal University of Paraíba (UFPB), Areia, Paraiba
58397-000, Brazil. lealjeann@gmail.com
 Ocular teratoid medulloepithelioma in a macaw
Figure 1.  Ocular medulloepithelioma in a young northern red-
shouldered macaw. A large mass covered by intact skin protrudes
from the orbit. The cornea is dark red and roughened. Day 15 of
observation.
were processed routinely for histology and stained with
hematoxylin and eosin and alcian blue stains.
Histologically, most of the tissue consisted of a non-
encapsulated, infiltrative neoplasm composed of small
tubules and cords of epithelial cells within a small amount
of fibrovascular stroma (Fig. 2). In some areas, the neo-
plasm consisted of single-to-multiple layers of cuboidal-to-
columnar cells arranged in tubules and occasional rosettes,
which were consistent with both Flexner–Wintersteiner
rosettes (Fig. 3) and Homer Wright rosettes (Fig. 4). Neo-
plastic cells had indistinct cell borders, a small-to-moderate
amount of eosinophilic cytoplasm, and ovoid hypochro-
matic nuclei with 1 or 2 distinct nucleoli. Anisokaryosis
was mild-to-moderate, and mitoses were relatively frequent
(15 in an area of 2.37 mm2). Multifocally, neoplastic cells
had brightly eosinophilic cytoplasm with occasional accu-
mulations of extracellular brightly eosinophilic material
interpreted as keratin (squamous differentiation). Some
areas of the neoplasm were more variably cellular and less
differentiated, composed of small spindle-shaped cells with
a minimal-to-small amount of cytoplasm, and cells with
round nuclei, conspicuous nucleoli, and scant cytoplasm.
These were interpreted as areas of neuroglial differentia-
tion. Rare islands of hyaline cartilage were interspersed
among groups of neoplastic cells (Fig. 2). The neoplasm
had large foci of necrosis. The globe was collapsed, and the
uveal tract was the only recognizable intraocular structure.
The cornea was perforated and replaced by a thick layer of
601
degenerate heterophils and extravasated erythrocytes with
embedded foreign material and abundant bacterial colo-
nies. The globe was encircled by abundant fibrous connec-
tive tissue, which was variably expanded by hemorrhage
and a heterophilic infiltrate. Cystic areas scattered through-
out the tumor were filled with alcian blue–positive, amor-
phous, basophilic material.
Immunohistochemistry was performed for further charac-
terization of the neoplasm. The antibodies used were glial
fibrillary acidic protein (GFAP; Z0334, 1:500; Dako), S100
protein (Z0311, 1:4,000; Dako), neuron-specific enolase
(NSE; M0873, 1:150; Dako), and pancytokeratin AE1-AE3
(M3515,1:40; Dako). Tissues from a blue-and-gold macaw
(Ara ararauna) were used as a control. The cells in the areas
of neuroglial differentiation were strongly immunoreactive
for GFAP, the cells forming some of the multilayered tubules
and solid nests had positive immunolabeling for S100 and
cytokeratin, and virtually all cells expressed NSE (Figs.
5–7). Based on these findings, the diagnosis was malignant
teratoid medulloepithelioma.
The classification of human embryonal tumors of the
CNS has undergone substantial modification over the past
decade, especially with the release of the most recent 2016
WHO classification.19 The term primitive neuroectodermal
tumor (PNET), which used to encompass the medulloepi-
theliomas, was removed from the diagnostic lexicon.
Embryonal tumors that display amplification of the C19MC
region on chromosome 19 (19q13.42), including embryonal
tumor with abundant neuropil and true rosettes (ETANTR),
ependymoblastomas (EBL), and some medulloepitheliomas
are now under the umbrella term embryonal tumor with
multi­layered rosettes (ETMR), C19MC-altered.19 Tumors
with histologic characteristics of medulloepithelioma that do
not display C19MC expression should continue to be called
medulloepithelioma.19,27 This new classification is restricted
to humans and is not currently applicable to animals.
Embryonal tumors of the CNS are rare in animals and are
reported most commonly in dogs.9 There are only a few
reports of these tumors in birds, including a cerebral neuro-
blastoma in a budgerigar (Melopsittacus undulatus),5 a cere­
bellar medulloblastoma in an umbrella cockatoo (syn. white
cockatoo; Cacatua alba),6 and a poorly differentiated embry-
onal tumor in the brain of a domestic goose (Anser anser).20
Intraocular medulloepitheliomas are congenital tumors
that originate from primitive neuroectodermal cells and
therefore have the same cellular origin as CNS medulloepi-
theliomas; however, in humans, the intraocular tumors usu-
ally have a better prognosis than their cerebral counterparts.4,27
The vast majority of intraocular medulloepitheliomas origi-
nate from the nonpigmented epithelium of the ciliary body
and are named ciliary body medulloepitheliomas (previ-
ously known as diktyomas given their net-like histologic
features).27 Less frequently, intraocular medulloepithelio-
mas originate from the primitive medullary epithelium of
the iris, retina, and optic nerve.13 Most (75–80%) intraocular
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Leal de Araújo et al.

Figures 2–7.  Histologic and immunohistochemical features of an ocular teratoid medulloepithelioma in a young macaw. Figure 2.
The neoplasm is composed of single and multilayered tubules (green asterisks) and some dispersed islands of hyaline cartilage (yellow
asterisk). Foci of neuroglial differentiation (inset) were scattered throughout the tumor. H&E. Figure 3. A rosette composed of columnar
cells and a distinct lumen (Flexner–Wintersteiner rosette) with a background of poorly differentiated spindle-shaped cells. H&E. Figure 4.
A more primitive single cell–layered rosette with an indistinct lumen (Homer Wright rosette). H&E. Figures 5–7. Immunohistochemical
staining of the teratoid medulloepithelioma, hematoxylin counterstain. Figure 5. The cells in the neuroglial component of the neoplasm are
immunoreactive for glial fibrillary acidic protein (GFAP). Figure 6. Neoplastic cells are immunoreactive for neuron-specific enolase (NSE).
Figure 7. The epithelium of the tubular formations has strong immunoreactivity for S100.
 Ocular teratoid medulloepithelioma in a macaw
medulloepitheliomas occur in children, and they are the
second most common primary intraocular tumor of children
after retinoblastoma.27 Although they are congenital neo-
plasms, their clinical manifestation may be delayed for
years.27
In humans, the tumors are typically cystic and range in
color from white to gray to yellow.25 Associated clinical
signs may include glaucoma, cataract formation, poor vision,
blindness, leukocoria, exophthalmos, proptosis, buphthal-
mos, and iritis.27 Intraocular medulloepitheliomas are unilat-
eral in most cases and, given their slow growth, may not
become noticeable until they protrude into the anterior cham-
ber or invade surrounding structures.27 These tumors are usu-
ally only locally aggressive, and enucleation can be curative;
however, when the diagnosis is delayed, the tumor can spread
through adjacent structures, including the optic nerve, conse-
quently gaining access to the brain.11
On the other hand, in veterinary medicine, the most com-
monly associated clinical signs include buphthalmia,4,14,26
exophthalmia,2,25glaucoma,1,21 anterior uveitis and corneal
edema,10 and leukocoria.4 Medulloepitheliomas usually
manifest at a young age in animals, and a history of trauma
is commonly reported.4,15,25 As seen in our case, once the first
clinical signs are noted, the disease progresses rapidly.4,29
The buphthalmia and the mucohemorrhagic discharge seen
in our case have also been described in cockatiels with
medulloepithelioma.4
Histologically, medulloepitheliomas are characterized by
thick multilayered tubular structures with distinct lumens
resembling primitive medullary epithelium.27 They can also
have rosettes known as Flexner–Wintersteiner rosettes (cell
layers with apical tight junctions and distinct lumens) and
Homer–Wright rosettes (more primitive and less distinct
structures that lack tight junctions and have indistinct
lumens), but neither type of rosette is specific for medullo-
epithelioma. Medulloepitheliomas are classified as teratoid
or non-teratoid based on the presence or absence of hetero-
plastic tissues, such as striated muscle, neural tissue, and
hyaline cartilage.27 Indicators of malignancy include an
invasive growth pattern, high mitotic count, and cellular
pleomorphism.16
The neoplasm in our case had several of the classic histo-
logic features of teratoid medulloepithelioma, including
simple and complex rosettes, hyaline cartilage, and neural
differentiation. The tubular and rosette-like structures
are consistent with the histologic features of intraocular
medulloepithelioma observed previously in cockatiels.4,25
The most common heteroplastic tissue in teratoid medullo-
epithelioma is hyaline cartilage, which has been described
previously in teratoid medulloepitheliomas of a cockatiel,4
dogs,15 a llama,10 horses,17 and children.27 The mitotic count
observed in our case was similar to that in previous reports
of malignant medulloepitheliomas, which report 0–30 mito-
ses in an area of 2.37 mm2 (0–3 mitoses per 400× field).4,10,15
603
Unfortunately, the carcass of the bird was not submitted
for autopsy, so the occurrence of metastasis could not be
assessed.
Medulloepitheliomas are possibly the most primitive
tumor of the neuroepithelium, and the great variability of
immunolabeling patterns probably reflects the diversity of
differentiation of the neoplastic cells.4 The positive immuno-
labeling for GFAP (Fig. 5) and NSE (Fig. 6) in our case was
consistent with that seen in medulloepitheliomas in an Afri-
can grey parrot,23 cockatiels,4 llama,26 horses,17 and humans.11
In contrast, GFAP was negative in another llama,10 and both
GFAP and NSE were negative in a dog.1 In our case, some
neoplastic cells were also positive for S100 (Fig. 7), similar
to reports in llamas10,26 and humans.16 Unlike the reports
of medulloepitheliomas affecting llamas,10,26 horses,17 and
dogs,1 tissues were variably positive for pancytokeratin
immunolabeling in our case, similar to reports in some
human studies of patchy areas of positive immunolabeling.16
There are no reports of pancytokeratin immunohistochemis-
try in other cases of medulloepithelioma in birds,4,23,25 to our
knowledge.
Teratoid medulloepitheliomas should be differentiated
from teratomas. Both can have heteroplastic tissues; how-
ever, teratomas usually exhibit differentiation from all 3
germ layers (endoderm, mesoderm, and ectoderm), produc-
ing a wide variety of tissue components, whereas teratoid
medulloepitheliomas have a predominance of neuroepithe-
lial differentiation with a few interspersed heteroplastic
foci.30 Most medulloepitheliomas are classified as malignant,
but teratomas in birds are usually benign.22 Most avian tera-
tomas are gonadal or intracelomic tumors,8 although there
are a few reports of ocular teratomas in a kestrel,18 a heron,24
and a turkey.22
In most available reports of medulloepitheliomas in psit-
tacine patients, the birds were 11 mo to 3 y old.4,25 In one
report describing the occurrence of this tumor in an African
grey parrot, the age of the bird was unknown.23 The occur-
rence of this tumor in a 4-mo-old red-shouldered macaw
reinforces the importance of including this tumor as a dif-
ferential diagnosis for a unilateral ocular mass in a young
psittacine bird.
Acknowledgments
We thank the Histology Laboratory of the Louisiana Animal
Disease Diagnostic Laboratory for the immunohistochemistry.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, author-
ship, and/or publication of this article.
604
Leal de Araújo et al.
ORCID iDs
Jeann Leal de Araújo https://orcid.org/0000-0001-8688-9864
Brian F. Porter https://orcid.org/0000-0003-4258-3219
Ingeborg M. Langohr https://orcid.org/0000-0001-7366-4391
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