Signalment:  

Age unknown (adult) male silver carp (Hypophthalmichthys molitrix)Abnormal growth noted in both eyes over a period of several months; left eye enucleated 2 months prior to enucleation of the right eye.

Gross Description:  

A 1cm diameter homogenous, soft white-tan mass occupies the vitreous, posterior and part of the anterior chamber in both globes, obscuring the lenticular and iridial structures.

Histopathologic Description:

109.001998 Left eye: Six sections of the globe are examined (slides A-C.) There is a densely cellular, poorly circumscribed population of neoplastic cells filling the anterior and posterior chambers and vitreous. Neoplastic cells are dimorphic: the first population is spindloid with a small amount of fibrillar eosinophilic cytoplasm, a large oval nucleus with finely stippled chromatin and infrequent visible nucleoli. Mitotic figures average six per ten high power fields. The second neoplastic cell population is composed of well differentiated neurons, and this population is scattered throughout the fibroblastic neoplastic cell population. Neoplastic cells are arranged in thick interlacing fascicles and are infiltrated by a diffuse population of heterophils and macrophages. Neoplastic cells dissect through the stroma of the cornea and sclera.

109.006781 Right eye: One section of completely excised tissue is examined. The architecture of the iris, ciliary body and lens is diffusely effaced by a poorly circumscribed population of neoplastic cells that fills the vitreous body and protrudes into the anterior chamber. Neoplastic cells are dimorphic: the first population is spindloid with tapered cell borders, a moderate amount of fibrillar eosinophilic cytoplasm and a large elongate nucleus with stippled chromatin. These neoplastic cells are arranged in thick interlacing fascicles. Interspersed within this population of neoplastic spindle cells, there is a subpopulation of polyhedral to stellate neoplastic cells with abundant eosinophilic cytoplasm, a large eccentric nucleus with a fine chromatin pattern and prominent eosinophilic nucleolus. Mitotic figures average three per ten high power fields for all neoplastic cell types. Neoplastic cells invade the lens capsule and disrupt the lens, and there is moderate histiocytic and lymphoplasmacytic inflammation surrounding the lens fragments.

Morphologic Diagnosis:  

Left and right globes: Ganglioneuroma

Condition:  

Ganglioneuroma

Contributor Comment:  

A diagnosis of ganglioneuroma is made based on the presence of the well differentiated neuronal and spindle neoplastic cell populations within the mass. Reported tumors of nerve cell origin within the peripheral nervous system of fish are rare and include schwannomas, neurilemmomas, retinoblastomas and ganglioneuromas. Ganglioneuromas are associated with spinal ganglia in both marine and freshwater species, and are typically reported within body cavities(6) and in association with gill filaments and the root of the tail fin(1). These tumors are soft, pale and whitish and sometimes lobulated. The histologic features of this tumor include a classic single or grouped neoplastic ganglion cell with prominent vesicular chromatin and eosinophilic nucleoli, separated by interlacing fascicles of spindle neoplastic cells. Unlike retinoblastomas, ganglioneuromas do not exhibit rosette formation, and unlike schwannomas, they contain neuronally differentiated cells. Neoplasms of the retina in fish have been reported in association with exposure to methylazoxymethanol experimentally(2, 5). The species in which this tumor more frequently occurs include cats, pigs, cattle, dogs and horses, as well as reports of cockatiels and rats. The bilateral origin of the tumor in this case suggests an underlying genetic predisposition, which may be analogous to that of retinoblastomas.

Immunohistochemical staining with GFAP and vimentin was performed. Few foci of cellular processes within the spindloid cell population in the neoplasm were positive for GFAP, and there was positive internal control staining within the optic nerve. Vimentin staining, however, was negative for neuronal and spindle cells and there was no positive internal control staining within the optic nerve or elsewhere in the tissue.

JPC Diagnosis:  

Eye, globe: Ganglioneuroblastoma

Conference Comment:  

The differential diagnoses proposed by conference participants included neuroblastoma, ganglioneuroma, and ganglioneuroblastoma. Neuroblastomas are derived from neural crest cells, may metastasize, and common sites include the adrenal medulla and sympathetic ganglia. Ganglioneuromas may arise from primitive neuroepithelial cells which exhibit neuronal differentiation and usually exhibit a benign behavior. Common sites include the neuraxis, autonomic and cranial nerve ganglia, and adrenal medulla.

Conference participants felt that there were three distinct cell populations in this particular neoplasm, including the spindle cells, ganglion cells, and neuroblast cells with carrot-shaped nuclei that formed scattered rosettes. For this reason, we favor a diagnosis of ganglioneuroblastoma. Ganglioneuroblastomas exhibit histologic features of both well-differentiated neurons and neuroblastic cells(4). Conference participants also felt this neoplasm was malignant due to its locally invasive nature.

Additional differential diagnoses considered for this neoplasm include medulloepithelioma, melanoma, and retinoblastoma. Retinoblastomas present with numerous neuroblasts arranged in rosettes and can be easily confused with medulloepitheliomas in fish, except they are generally not as invasive and do not form heteroplastic elements such as undifferentiated mesenchymal cells, bone, or cartilage(7).

There was some variation among sections due to the submission of both eyes, and some conference participants had evidence of retinal detachment and atrophy, as well as a lenticular cataract with Morgagnian globules in the lens. There were also areas of woven bone surrounding some sections of the cornea, and conference participants hypothesized that this could represent osseous metaplasia from the neoplasm or from exposed lens fibers.

S-100, neurofilament protein (NFP), synaptophysin, chromagranin A, and glial fibrillary acidic protein (GFAP) immunohistochemical stains were performed on this case, but all were non-contributory, which is likely due to the fact that the immunohistochemical stains at the Joint Pathology Center laboratory are not optimized for piscine tissues.

References:

1 Gill BS. On the occurrence of ganglioneuroma and cysts of Henneguya ophiocephali Chakravarty 1938 in a fish. J of Wildlife Dis 11: 314-317, 1975.
2 Hawkins WE, Overstreet RM, Fournie JW, Walker WW. Development of aquarium fish models for environmental carcinogenesis: tumor induction in seven species. J Appl Toxicol. 5: 261-264, 1985.
3 Hawkins WE, Fournie JW, Overstreet RM, Walker WW. Intraocular neoplasms induced by methylazoxymethanol acetate in Japanses medaka (Oryzias latipes.) J Natnl Cancer Inst. 76: 453-65, 1986.
4 Maxie MG, Youssef S. Nervous system. In: Maxie, MG, ed. Jubb, Kennedy, and Palmers Pathology of Domestic Animals. 5th ed., Philadelphia, PA: Elsevier; 2007:372, 453-455.
5 Porter BF, Storts RW, Payne HR, Edwards JF. Colonic ganglioneuromatosis in a horse. Vet Pathol 44: 207-210, 2007.
6 Roberts RJ. In: Fish Pathology, 2nd ed., p 169. Bailliere Tindall, London, England, 1989.
7 Roberts RJ. Neoplasia of teleosts. In: Roberts RJ, ed. Fish Pathology. 3rd ed. Edinburgh, Scotland: Saunders; 2003:166-7.

Click the slide to view.

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1-1 Globe

1-2. Globe

1-3. Globe

1-4. Globe

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