Emily Brinker Auburn University Ejb0036@auburn.edu Signalment and short history: 2-month-old, female-intact Domestic Shorthair cat A 1-month-old, female, intact, domestic shorthair cat housed in the Scott-Ritchey Research Center at Auburn University developed nasal discharge, dyspnea, anorexia, weight loss, and both resting and intention tremors. The patient was treated symptomatically with systemic and topical antibiotics and anti-inflammatory therapies; however clinical signs continued despite intervention. Eyes, brain and liver were collected at necropsy. Diagnosis: GM2 gangliosidosis variant 0 (Sandhoff-like disease). Discussion:

A diagnosis of GM2 gangliosidosis – more specifically, Sandhoff-like disease - was reached based on clinical signs, histological findings and PCR amplification of the known HEXB genetic defect within the colony. This mutation is a 25-base-pair inversion at the 3’ end of the HEXB gene, leading to an 8-amino-acid premature truncation of the protein8.

GM2 gangliosidoses are a group of genetic defects that result in a functional deficiency of a hydrolytic enzyme, β-N-acetylhexosaminidase (Hex), which is comprised of 2 subunits (α and β). Hexosaminidase has three isozymes: HexA (αβ), HexB (ββ), and Hex S (αα). In humans, genetic mutations resulting in the loss of function of the α subunit and the β subunit correspond to Tay-Sachs disease and Sandhoff disease, respectively. In Tay-Sachs disease, a mutation in the HEXA gene encoding the α subunit leads to defective Hex A and Hex S activity. Similarly, in Sandhoff disease, a mutation in the HEXB gene encoding the β subunits leads to defective Hex A and Hex B activity6.

In cats, there are no described cases of Tay-Sachs-like disease, but there are many described variants of Sandhoff-like disease resulting from variable mutations in the HEXB gene6. Cats affected with Sandhoff-like disease typically develop progressive neurological symptoms around 6 – 8 weeks of age. Specific findings include intention tremors, ataxia, hypermetria, falling, dysphagia, and seizures2,4. Clinical signs eventually become so severe that humane euthanasia is often elected around 4 – 10 months of age2,10,11. In cats with Sandhoff-like disease, ocular manifestations are reported in later stages and include bilateral miosis, slowed pupillary light reflexes, weak menace response, lateral strabismus, horizontal nystagmus, and eventual blindness10,11.

Histopathological findings in Sandhoff-like disease include intracytoplasmic vacuoles within swollen neurons in the brain and spinal cord and an increase in Iba1-immunoreactive microglial cells (microgliosis)2,6,10,11. In frozen sections, Periodic acid-Schiff (PAS) highlights the intracytoplasmic material; however, in many cases, this feature is lost with formalin fixation5. Ultrastructurally, numerous laminated membranous bodies are evident in the cytoplasm, without nuclear abnormalities5,10. Despite cats being typically small in stature, the gross postmortem evaluation is typically otherwise unremarkable. A report in a Korat cat describes hepatomegaly that grossly

resembled hepatic lipidosis. This report describes single, large cytoplasmic vacuoles in hepatocytes and Kupffer cells that are PAS-positive on frozen sections and contain laminated membranous bodies on ultrastructure9.

Cats have been used as an animal model of Sandhoff disease in the pursuit of finding a cure for this disease in children. One promising experimental therapy being developed with cats uses an intracranially delivered, adeno-associated viral vector-mediated gene delivery to express hexosaminidase1.Treated cats lived 4.5 times as long as their untreated counterparts and had a delayed decrease in quality of life7. Histologically, treated cats have an attenuation in microglial expansion and activation3.

References: 1. Bradbury AM, Cochran JN, McCurdy VJ, et al. Therapeutic Response in Feline Sandhoff Disease

Despite Immunity to Intracranial Gene Therapy. Mol Ther. 2013 Jul;21:1306–1315. 2. Bradbury AM, Morrison NE, Hwang M, Cox NR, Baker HJ, Martin DR. Neurodegenerative

lysosomal storage disease in European Burmese cats with hexosaminidase β-subunit deficiency. Mol Genet Metab. 2009 May;97:53–59.

3. Bradbury AM, Peterson TA, Gross AL, et al. AAV-mediated gene delivery attenuates neuroinflammation in feline Sandhoff disease. Neuroscience. 2017 Jan;340:117–125.

4. Cork LC, Munnell JF, Lorenz MD. The pathology of feline GM2 gangliosidosis. Am J Pathol. 1978;90:723–734.

5. Garner A. Ocular pathology of GM2 gangliosidosis--Type 2 (Sandhoff’s disease). Br J Ophthalmol. 1973 Jul 1;57:514–520.

6. Lawson C, Martin D. Animal models of GM2 gangliosidosis: utility and limitations. Appl Clin Genet. 2016 Jul;Volume 9:111–120.

7. Martin DR. Personal Communication. 8. Martin DR, Krum BK, Varadarajan GS, Hathcock TL, Smith BF, Baker HJ. An inversion of 25 base

pairs causes feline G M2 gangliosidosis variant 0. Exp Neurol. 2004 May;187:30–37. 9. Neuwelt EA, Johnson WG, Blank NK, et al. Characterization of a new model of GM2-gangliosidosis

(Sandhoff’s disease) in Korat cats. J Clin Invest. 1985 Aug 1;76:482–490. 10. Yamato O, Matsunaga S, Takata K, et al. GM2-gangliosidosis variant 0 (Sandhoff-like disease) in a

family of Japanese domestic cats. Vet Rec. 2004;155:739–744. 11. Yamato O, Hayashi D, Satoh H, et al. Retrospective Diagnosis of Feline GM2 Gangliosidosis

Variant 0 (Sandhoff-Like Disease) in Japan: Possible Spread of the Mutant Allele in the Japanese Domestic Cat Population. J Vet Med Sci. 2008;70:813–818.

Submitters: Dr Deborah Chong

● Acknowledgements: Dr Terence William O’Neill, Dr Julia Burco, Ms Katrina Voll

Institution: Oregon State University

Contact information: deborah.chong@oregonstate.edu

Signalment: 14kg, male, black-tailed deer (Odocoileus hemionus columbianus) fawn

History:

The fawn was found circling in a member of the public’s yard. It was darted, euthanized with

intravenous EUTHASOL ®, and submitted for necropsy at the Oregon Veterinary Diagnostic Laboratory

(OVDL) later that same day.

Diagnosis:

Left eye: Persistent hyperplastic primary vitreous with secondary retinal detachment, dysplasia

and ganglion layer atrophy, anterior synechiae formation and aphakia

Right eye: Anterior staphyloma with chronic marked endophthalmitis, secondary retinal

detachment, dysplasia and ganglion layer atrophy, hyphema, hemopthalmos and lens rupture

Discussion

We suspect a significant degree of the changes in the right eye to be secondary to previous penetrating

trauma or keratoconjunctivitis, while the changes in the left eye to due to congenital/developmental

abnormalities. Due to the degree of damage in the right eye and the chronic nature of the inflammation,

it is unclear if there were similar congenital/developmental abnormalities. The presence of the

persistent hyperplastic primary vitreous in the left eye suggest that a lens was present in utero and its

absence may have been due to in utero degeneration and resorption. This may not be the case for the

left eye as we suspect the free floating, curled, thicker, eosinophilic membrane is the lens capsule, and

some of the proteinaceous material in the chambers is lens protein, some of which is mineralized. The

congenital abnormalities noted in this case have been reported in wild cervids, most commonly in white-

tailed deer fawns. Overall these are still rare occurrences in wild population and an exact etiology

remain unknown.

Megan Climans University of Wisconsin Madison; Comparative Ocular Pathology Laboratory climans@wisc.edu Signalment: 16-year-old neutered male domestic shorthaired cat History: Chronic keratitis progressed to corneal perforation, eventually leading to enucleation, approximately 1 week prior to submission of the globe. Diagnoses: 1. Post-traumatic B cell lymphoma (AKA Post-traumatic sarcoma – round cell variant) 2. Axial corneal perforation with moderate neutrophilic keratitis with epithelial

hyperplasia and keratinization and stromal vascularization 3. Multifocal breaks in Descemet's membrane 4. Hypermature cataract 5. Moderate, chronic intraocular hemorrhage 6. Retinal hypertensive vasculopathy Discussion: Immunohistochemistry revealed that many of the infiltrating cells were faintly positive for CD79a and only rarely positive for CD20. The number of CD3 positive cells are interpreted as infiltrating inflammatory T lymphocytes in this case. Lymphocytes of various lineages can cause intraocular lymphoma in cats. The neoplastic cells of post-traumatic lymphoma most reliably stain with CD79a, a B lymphocyte marker, and may stain negatively for CD20, a B lymphocyte marker with a known narrower range of detection/expression. The round cell variant of feline post-traumatic sarcoma, aka feline post-traumatic lymphoma, is thought to represent neoplastic transformation of lymphocytes following a protracted history of chronic inflammation, which can be years in length. This may occur secondary to chronic uveitis frequently accompanied by cataract (confirmed histologically in this case) and/or a historic traumatic event. As trauma is not always confirmed historically or with corroborating histologic lesions, the name can be mis-leading. Feline post-traumatic sarcoma is an entity encompassing several histologic variants of typically malignant, locally invasive sarcomas. Spindle cell, osteochondrosarcoma, and round cell variants can occur with the spindle cell variant being the most common. The spindle cell variant arises from lens epithelium.(3) Risk factors for development of post-traumatic sarcoma include historic trauma, chronic uveitis, chronic history of phthisis bulbi, history of previous intraocular surgery typically involving the lens, and gentamicin injection/chemical ciliary body ablation procedures.(2) While metastases are reportedly rare, invasion and destruction of local tissues is common, including extension of

neoplasia to the brain along the optic nerve. Extension of neoplastic cells beyond the sclera or into the optic nerve are poor prognostic indicators.(2) In a recent study of feline primary ocular lymphoma with no evidence of systemic involvement (presumed solitary ocular lymphoma – PSOL), 75% of 172 cases of intraocular lymphoma had concurrent uveitis, and 64% of 99 cases were distinguished as PSOL based on follow-up data that excluded systemic involvement. Median survival time was significantly higher for cases of PSOL than cases with systemic involvement.(1) Considering post-traumatic lymphomas are thought to originate in the eye, systemic involvement is not expected; however, this hypothesis has not been evaluated thoroughly. In this case, keratitis with subsequent perforation may have been caused by lagophthalmos following distortion of the globe by neoplasia, as an extension of inflammation from inside the eye, via direct invasion and tissue destruction into the posterior cornea by the neoplasm, secondary to an initial unreported trauma, or due to a separate etiology, and then likely progressed to perforation as a secondary lesion. It is not uncommon for cases of intraocular neoplasia to present initially with the more noticeable clinical complaints, for example buphthalmia due to glaucoma, eye color change, or keratitis, prior to implication of the neoplasm in the pathologic process during surgery and/or by histology. The vascular changes noted within the retina are interpreted as being associated with the patient’s reported systemic hypertension, which may explain some of the intraocular hemorrhage. Other possible causes of intraocular hemorrhage in this case include necrotic uvea and/or neoplasm or detached retina. 1. Musciano, AR, Lanza, MR, Dubielzig, RR, Teixeira, LBC, Durham, AC. Clinical and histopathological classification of feline intraocular lymphoma. Vet Ophthalmol. 2020; 23: 77– 89. 2. Wood C, Scott EM. Feline ocular post-traumatic sarcomas: Current understanding, treatment and monitoring. Journal of Feline Medicine and Surgery. 2019;21(9):835-842. 3. Zeiss CJ, Johnson EM, Dubielzig RR. Feline intraocular tumors may arise from transformation of lens epithelium. Vet Pathol. 2003 Jul;40(4):355-62. doi: 10.1354/vp.40-4-355.

College of Veterinary Medicine

Department of Pathology

College of Veterinary Medicine | vet.uga.edu

501 D. W. Brooks Drive | Athens, GA 30602 | Telephone 706-542-5837 | Fax 706-542-5828

Education, Research and Medicine

Case #: B17-00608

Presenter: Chloe Chan Goodwin

1 DVM, ChloeCGoodwin@uga.edu

Contributors: Carmen Jerry, DVM, PhD, DACVP2, Sarah Schmidt, DVM, DACVP

3, K. Paige Carmichael, DVM, PhD,

DACVP1

1University of Georgia, College of Veterinary Medicine, 501 D. W. Brooks Drive, Athens, GA 30602

2California Animal Health and Food Safety Lab, 1550 N Soderquist Rd, Turlock, CA 95380

3IDEXX Laboratories, One IDEXX Drive, Westbrook, Maine 04092

Signalment: 11-year-old, female spayed, Tibetan Terrier dog History: The patient was examined by the ophthalmology service for right-sided exophthalmos and phthisis bulbi due to a right retrobulbar mass. A right upper conjunctival mass was removed six years previously and had not recurred. The dog was medically managed for bilateral glaucoma for the past three years. Diagnosis: Right eye: 1) Retrobulbar hibernoma 2) Phthisis bulbi with anterior and posterior synechiae, lens rupture, subcapsular fibrosis, and retinal degeneration Discussion: Hibernomas are rare, benign neoplasms derived from brown fat that have been reported in dogs, cats, rodents (Sprague-Dawley rats in particular), and humans. Brown fat is normally found in neonates, rodents, hibernating animals, and small mammals adapted to cold environments, and is important for utilizing intracellular triglycerides to generate heat through nonshivering thermogenesis. In domestic animals, hibernomas have been documented in the omentum of a dog, body wall of a cat, and various parts of the orbit in dogs, including the conjunctiva and retrobulbar space. Patients are often mature adults, coinciding with human cases. Neoplastic cells display strong cytoplasmic and nuclear immunoreactivity against uncoupling protein 1, a mitochondrial protein responsible for thermogenic respiration. Ultrastructurally, there are abundant mitochondria and lipid-like droplets within the cytoplasm. Surgical resection is curative, with rare incidences of recurrence. The conjunctival mass removed six years prior to presentation at the University of Georgia was diagnosed as a hibernoma, suggesting the retrobulbar mass arose from the remaining neoplastic cells. References: Bruner, Richard H., et al. "Spontaneous hibernomas in Sprague-Dawley rats." Toxicologic pathology 37.4 (2009): 547-552. Ozturk-Gurgen, Hazal, et al. "Abdominal Wall Hibernoma in a Cat: A Case Report." Kafkas Üniversitesi Veteriner Fakültesi Dergisi 26.3 (2020).

Piccione, Julie, and Sharon M. Dial. "Cytologic appearance of hibernoma in two dogs." Veterinary Clinical Pathology 49.1 (2020): 125-129. Ravi, M., et al. "Clinical, morphologic, and immunohistochemical features of canine orbital hibernomas." Veterinary pathology 51.3 (2014): 563-568. Stuckey, Jane A., et al. "Subconjunctival hibernoma in a dog." Veterinary Ophthalmology 18.1 (2015): 78-82.

Department of Pathobiology

3900 Delancey St

Philadelphia, PA 19104

(215) 898-8857

Authors: Alexandra Harvey, DVM (harva@upenn.edu); Charles-Antoine Assenmacher, DVM,

MSc, Dipl. ACVP; Amy Durham, MS, VMD, Dipl. ACVP

History and Signalment: A 13-year-old, intact female, husky mixed breed canine presented

with a two-week history of a bulging left eye. Ophthalmologic examination revealed mild

buphthalmos, moderate hyperemia, diffuse corneal edema, and dense neovascularization with a

central ulcer. The intraocular pressure was 32 mm HG and there was no menace, consensual

PLR, or dazzle. During routine enucleation, the ophthalmologist noted a dorsonasal scleral bulge.

Diagnosis: Undifferentiated sarcoma (primary or metastatic) or a pleomorphic iridociliary

adenocarcinoma

Discussion:

The exact diagnosis in this case remains a mystery. Within three months of enucleation

the patient died at home and a postmortem examination was not performed. Given the spindle

cell morphology and patient signalment, differentials for this neoplasm included a uveal

schwannoma of blue-eyed dogs, amelanotic malignant melanoma, pleomorphic iridociliary

adenocarcinoma, or metastatic sarcoma.

Canine uveal schwannomas of blue-eyed dogs typically occur as pleomorphic spindle cell

neoplasms in the anterior uvea.1 Purebred or mixed Siberian huskies are overrepresented.1 The

neoplastic cells frequently exhibit nuclear palisading and stain positively for vimentin, S100,

glial fibrillary acidic protein (GFAP), and protein gene product 9.5 (PGP 9.5).1 Given the

negative S100 and GFAP immunohistochemical labeling, a uveal schwannoma is considered less

likely.

Canine ocular melanocytic neoplasms are classified as melanocytomas or malignant

melanomas based upon a mitotic count; malignant melanomas have greater than four mitoses

in10 high-power fields.2 Malignant melanomas are typically comprised of sheets of

predominantly spindle cells within the anterior uvea with variable pigmentation, and amelanotic

melanomas have been reported.2 Oral amelanotic melanocytic neoplasms label positively with

PNL2, Melan-A, tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2), and S100.3 Considering

ocular amelanotic melanocytic neoplasms are presumed to exhibit similar immunohistochemical

staining patterns, the negative PNL2 and S100 of this neoplasm make an amelanotic malignant

melanoma less likely.

Canine iridociliary epithelial tumors are composed of pleomorphic cells arising from the

pigmented or non-pigment epithelium of the anterior uvea with a solid or papillary arrangement.4

Oftentimes, neoplastic cells are lined by smooth, thick, PAS-positive basement membranes.4

These neoplasms are classified as adenomas or adenocarcinomas based upon invasion into the

sclera, as seen in adenocarcinomas.4 A subset of adenocarcinomas with marked cellular anaplasia

are designated pleomorphic adenocarcinomas.5 Immunohistochemically, iridociliary epithelial

tumors label positively with vimentin and neuron-specific enolase (NSE), and variably with

S100.4 Adenocarcinomas also frequently label positively with pancytokeratin and have increased

telomerase reverse transcriptase (TERT) labeling relative to benign iridociliary epithelial

tumors.4,6-7 Iridociliary epithelial tumors are typically benign, however, confirmed or suspected

Department of Pathobiology

3900 Delancey St

Philadelphia, PA 19104

(215) 898-8857

metastasis has been reported, predominantly in association with pleomorphic adenocarcinomas.4-

6 A possible correlation between ciliary body ablation by intravitreal gentamicin injection and

intraocular neoplasia has been described, including iridociliary epithelial tumors with an

increased proportion of pleomorphic iridociliary adenocarcinomas.5 Given the marked cellular

anaplasia and weak positive NSE labeling of the neoplasm, a pleomorphic iridociliary

adenocarcinoma is considered a likely differential diagnosis in this patient.

A metastatic sarcoma is also a consideration in this patient. Lymphoma and histiocytic

sarcoma are the most common metastatic intraocular neoplasms in dogs.8 The cellular

morphology is not consistent with an anaplastic lymphoma. Intraocular histiocytic sarcoma

typically occurs in the anterior uvea and is composed of pleomorphic round to polygonal cells

with frequent karyomegaly and multinucleation.9 Neoplastic cells label positively with

panhistiocytic markers, such as CD18.9 Given the cellular pleomorphism of the neoplasm in this

patient, immunohistochemical staining with the panhistiocytic marker ionized calcium-binding

adapter molecule 1 (Iba1) was performed. The neoplasm was negative, and thus histiocytic

sarcoma is unlikely. A metastatic undifferentiated sarcoma cannot be ruled out as postmortem

examination was not performed in this patient.

Ultimately, given the cellular morphology and the gamut of immunohistochemical stains

performed in this case, the top two differential diagnoses are a metastatic undifferentiated

sarcoma or a pleomorphism iridociliary adenocarcinoma. This case demonstrates the importance

of keeping a broad differential list when approaching pleomorphic intraocular neoplasms and

provides an opportunity to discuss the immunohistochemical labelling of common intraocular

neoplasms.

References:

1. Zarfoss MK, Klauss G, Newkirk K, et al. Uveal spindle cell tumor of blue-eyed dogs: an

immunohistochemical study. Vet Pathol. 2007;44:276-284.

2. Wilcock BP, Peiffer RL. Morphology and behavior of primary ocular melanomas in 91 dogs.

Vet Pathol. 1986;23:418-424.

3. Smedley RC, Lamoureaux J, Sledge DG, et al. Immunohistochemical diagnosis of canine oral

amelanotc melanocytic neoplasms. Vet Pathol. 2011;48(1):32-40.

4. Dubielzig RR, Steinberg H, Garvin H, et al. Iridociliary epithelial tumors in 100 dogs and 17

cats: a morphological study. Vet Ophthalmol. 1998;1:223-231.

5. Duke FD, Strong TD, Bentley E. et al. Canine ocular tumors following ciliary body ablation

with intravitreal genatmicin. Vet Ophthalmol. 2012;16(2):159-162.

6. Zarfoss MK, Dubielzig RR. Metastatic iridociliary adenocarcinoma in a Labrador retriever.

Vet Pathol. 2007;44(5):672-676.

7. Klosterman E, Colitz CMH, Chandler HL, et al. Immunohistochemica properties of ocular

adenomas, adenocarcinomas and medulloepitheliomas. Vet Ophthalmol. 2006;9(6):387-394.

8. Labelle AL, Labelle P. Canine ocular neoplasia: a review. Vet Ophthalmol. 2013;16:3-14.

9. Naranjo C, Dubielzig RR, Friedrichs KR. Canine ocular histiocytic sarcoma. Vet Ophthalmol.

2007;10(3):179-185.

Kaylin McNulty, DVM, Mississippi State University, kaylin.mcnulty@msstate.edu

Diagnosis interpreted by The University of Wisconsin Madison COPLOW

History: Hunny Pot is a 3 day old calf that was donated to Mississippi State University for

teaching purposes. After physical exam, euthanasia was elected due to a large cleft palate defect

that was determined to be inoperable.

Signalment: 3-day old female mixed breed beef calf

Diagnosis:

1. Synophthalmos

2. Exposure keratopathy with focally extensive full-thickness corneal necrosis

3. Neutrophilic endophthalmitis, mild (hypopyon)

4. Cortical cataract

Discussion:

Synophthalmia is a form of cyclopia where portions of two distinct globes are fused together

within a single bony orbit, usually located in the center of the forehead. This calf is not a cyclops

as it has two normal eyes in addition to the fused central eye. Therefore, an interesting question

to consider is whether this is a single malformed calf or conjoined identical twin calves that

failed to undergo separation.

We suspect that this calf exhibits diprosopus, a congenital defect known as craniofacial

duplication. Diprosopus is a rare form of symmetric conjoined twins characterized by a single

neck and body with various forms of duplication of craniofacial structures. The etiology of this

rare malformation is unknown.

There are two reports of calves exhibiting diprosopia in the literature. Witt reported on a calf

with two normal lateral eyes and a median blind eye. Dozsa reported on a purebred Hereford calf

that had two muzzles, two sets of rudimentary teeth and lower lips, four cerebral hemispheres,

two eyes on the lateral aspects of the face with degenerate lenses, and a median fused orbit

containing one eye. This report termed the eye anomaly “triophthalmos”. These reports differ

from our case in that the central orbit was fused containing a single globe rather than a single

orbit containing two fused globes.

In cows, various degrees of cyclopia occur in Guernsey and Jersey fetuses that undergo

prolonged gestation. Experimentally, pregnant cattle fed Veratrum californicum at approximately

14-day gestation birthed cyclopic calves. Other sporadic reports of cyclopia are reported in a

Brown Swiss cross calf, Friesian calf, German Fleckviech calf, Hariana calf, and Holstein calf

with no definitive etiology. In this case, there was no history of prolonged gestation or Veratrum

californicum ingestion by the dam. This calf only had facial malformations, and the facial

malformations were only present above the mandible. The congenital defects include a fused

globe within a single bony orbit (synophthalmia), hydrocephalus, porencephaly, multiple open

fontanels, cleft palate, and maxillary duplication.

The cause of the congenital defects in this calf are undetermined, and there is room for debate for

whether this was one or two separate embryos. Additional chromosome testing to evaluate this

question is being pursued.

References:

Jubb, K. V., Kennedy, P. C., & Palmer, N. (2007). Pathology of Domestic Animals (Vol. 1). San

Diego, Calif.: Academic Press.

Dozsa, L. (1966). A Case of Rare Monstrosity in a Calf. Path. Vet. 3: 226-233.

Witt, M. Doppelgesicht (Diprosopus) beim Kalb. Dtsch. tierarztl. Wschr. 70: 327 (1963).

Nourani, H., Karimi, I., & Rajabi Vardanjani, H. (2014). Synophthalmia in a Holstein Cross

Calf. Retrieved September 10, 2020, from

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300002/.

Roberts, S. J. (2004). Veterinary Obstetrics and Genital Diseases (2nd ed.). Delhi: J.S. Offset

Printers.

Zaitoun A. A. M., Chang J., and Booker, M. (1998). Diprosopus (Partially Duplicated Head)

Associated with Anencephaly: A Case Report. Pathology Research and Practice. Urban &

Fischer Verlag.