JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1758838): 1‑year‑old Icelandic ewe
HISTORY: This ewe had dyspnea and mucopurulent nasal discharge of 4-5 months duration.
HISTOPATHOLOGIC DESCRIPTION: Nasal cavity: Arising from the respiratory epithelium and infiltrating the underlying lamina propria, submucosa and bone is an unencapsulated, poorly circumscribed, densely cellular, multilnodular neoplasm forming papillary projections supported by a fine fibrovascular stalk with tubules, and acini on fine fibrovascular stroma. Neoplastic cells are ciliated cuboidal to columnar epithelial cells with indistinct cell borders, a moderate amount of finely granular eosinophilic cytoplasm, a single round nucleus with moderately stippled chromatin, and one variably distinct nucleolus. Anisocytosis and anisokaryosis are mild and the mitotic rate is 1 per 10 HPF. Occasionally, neoplastic lumina contain a flocculent blue gray material (mucin) admixed with low numbers of neutrophils and necrotic cellular debris. Multifocally, separating neoplastic cells and expanding the adjacent submucosa there are ectatic lymphatics (edema), abundant mucin, and aggregates of lymphocytes and plasma cells, with fewer macrophages, and neutrophils. Remaining respiratory epithelium is attenuated, mildly eroded or occasionally hyperplastic. Neoplastic cells efface nasal turbinates and there is significant loss of pre-existing nasal bone with replacement by abundant fibrous connective tissue with reactive fibroblasts (fibrosis). Few remaining trabeculae of bone appear fragmented and lytic, or exhibit evidence of bony remodeling with irregular scalloped margins, resting and reversal lines, and new woven bone lined by osteoblasts.
MORPHOLOGIC DIAGNOSIS: Nasal cavity: Adenocarcinoma, Icelandic sheep, ovine.
CAUSE: Enzootic Nasal Tumor Virus (β-retrovirus – ENTV-1 in sheep; ENTV-2 in goats)
CONDITION: Endemic ethmoidal tumor; enzootic intranasal tumor; enzootic nasal adenocarcinoma; ethmoid tumor; infectious nasal adenopapilloma; ethmoid adenocarcinoma; tumor of the ethmoid olfactory mucosa; papillary adenoma of ethmoid origin
- Worldwide distribution (except Australia and New Zealand) infectious respiratory tract disease of sheep and goats
- ENTV-1: Sheep
- ENTV-2: Goats
- Ethmoturbinate tumor associated with a beta-retrovirus
- Originates from the surface epithelium and glands of the ethmoidal conchae
- Typically invasive but they do not metastasize
- Infectious: Neoplasms are experimentally induced in naive sheep and goats by transmission of nasal fluids from animals exhibiting clinical signs and lesions of the disease
- Retrovirus-like particles have been demonstrated in neoplastic cells by electron microscopy in both sheep and goats
- Genetically very closely related to Jaagsiekte sheep retrovirus (JSRV), the causative agent in sheep pulmonary adenomatosis
- Viral envelope glycoprotein is thought to be responsible for tumor development (in mice); detectable in neoplastic cells but not adjacent normal tissue
TYPICAL CLINICAL FINDINGS:
- Uni‑ or bilateral serous to mucopurulent nasal discharge, dyspnea, open mouth breathing, flared nostrils, respiratory stridor, and sneezing
- Facial deformities, exophthalmos, and lacrimation secondary to space occupying lesions
TYPICAL GROSS FINDINGS:
- Unilateral or bilateral masses in the ethmoid turbinates, with compression of the surrounding structures
- Appear white, grey, pink and/or dark red; soft, irregular, or friable with a granular surface covered by mucus
- Can extend into pharynx, sinuses and/or infiltrate through the cribiform plate
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Originate from olfactory mucosa of the turbinates in sheep and respiratory or olfactory mucosa in goats
- Morphologic features do not distinguish between viral and sporadic neoplasms
- Locally aggressive, destructive, and space-occupying
- Appearance is of an adenoma or low-grade adenocarcinoma
- Adenocarcinoma if there is invasion of bone
- Cuboidal or pseudostratified nonciliated epithelial cells form orderly acinar, tubular, or papillary arrangements
- Abundant mucus production and squamous metaplasia
- May be accompanied with nasal inflammatory polyps and glandular hyperplasia
- Metastasis to regional lymph nodes has been reported in cattle
- Intracytoplasmic or extracellular viral particles
- Viral particles are 90-135 nm in diameter with a core surrounded by an electron dense or translucent zone enveloped by a spiked unit membrane
- Viral particles occasionally bud from apical microvilli of neoplastic cells
- Neoplastic cells have characteristic proteinaceous-like secretory granules, rough endoplasmic reticulum, and many mitochondria
ADDITIONAL DIAGNOSTIC TESTS:
- IHC, PCR, electron microscopy to search for virus
- Sporadic (nonviral) nasal tumor
- Fungal granulomas
- Nasal polyp: Fibrous/myxomatous core covered by hyperplastic epithelium with inflammatory cell infiltrate
- Retro-viral associated nasal carcinoma also seen in goats (ENTV-2)
- Although not proven to be of viral origin bighorn sheep also acquire paranasal sinus masses and the similarities between these masses and enzootic nasal tumor of sheep include:
- Seromucinous nasal discharge
- Soft white mass in the sinus cavity
- Some masses are classified as adenocarcinomas
- Enzootic nasal adenocarcinomas have been identified in cattle, horses, and pigs, but a clear viral etiology has not been established
- In dogs nasal neoplasms occur in collies, Airedale terrier, basset hound and German shepherd
- Main site for nasal neoplasms are nasal passages for dogs, tip of nose and nasal passages for cats and maxillary sinus and nasal passages for horse
- Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016: 560.
- Constable PD, Hinchcliff KW, Done SH, Grünberg W. Veterinary Medicine. 11th ed. Louis, MO: Elsevier; 2017:875, 969-970.
- Cousens C, Minguijon E, Garcia M, et al. PCR-Based detection and partial characterization of a retrovirus associated with contagious intranasal tumors of sheep and goats. Journal of Virology. 1996;70(11):7580-7583.
- Cousens C, Minguijon E, Dalziel RG, et al. Complete sequence of enzootic nasal tumor virus, a retrovirus associated with transmissible intranasal tumors of sheep. Journal of Virology. 1999;73(5):3986-3993.
- De Las Heras, Garcia de Jalon JA, Sharp JM. Pathology of enzootic intranasal tumor in thirty-eight goats. Vet Pathol. 1991;28(6):474-481.
- Fox KA, Wootton SK, Quackenbush SL, et al. Paranasal sinus masses of Rocky mountain bighorn sheep. Vet Pathol. 2011:48(3)706-712.
- Lopez A. Martinson, SA. Respiratory system, mediastinum, and pleurae. In: Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:495-496.
- Scocco P, Mariotti F, Ceccarelli P, Fagioli O, Renzoni G, Vitellozzi G. Origin of enzootic intranasal tumor in the goat (Capra hircus): a glycohistochemical approach. Vet Pathol. 2001;38(1):98-104.