JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2026 P-N04

HISTOPATHOLOGIC DESCRIPTION:

Nasal cavity: Arising from the respiratory epithelium and infiltrating the underlying lamina propria and submucosa is an unencapsulated, poorly circumscribed, moderately cellular, multi-lobulated neoplasm forming papillary projections supported by a fine fibrovascular stalk or 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 basal nucleus with coarsely stippled chromatin, and one variably distinct nucleolus. Anisocytosis and anisokaryosis are mild and the mitotic rate is 2 per 2.37mm². Neoplastic cells occasionally pile up to 5 layers thick and there is rare scattered single cell necrosis. Occasionally, neoplastic lumina contain 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 moderate aggregates of lymphocytes and plasma cells with fewer macrophages, neutrophils, and eosinophils. Multifocally neoplastic tubules are ectatic up to 1.5 mm (cysts). Remaining respiratory epithelium is attenuated, 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).

GENERAL DISCUSSION:

• Viral respiratory tract disease of sheep and goats; worldwide distribution (except Australia, New Zealand) with variable prevalence; clinical disease only in adults; multiple animals may be affected over long periods of time
  • Beta-retrovirus
  • ENTV-1 (Enzootic nasal tumor virus-1): Sheep
    • Lambs as young as 6m of age reported to be affected
  • ENTV-2: Goats
• Ethmoid turbinate tumor ; originates from the surface epithelium and glands of the ethmoidal conchae
• Tumor is invasive but does not metastasize; fills most of caudal nasal cavity prior to developing clinical signs; term adenocarcinoma reserved when there is demonstrable bone invasion
• ENTV-1 and -2 are genetically closely related to Jaagsiekte sheep retrovirus (JSRV), the causative agent of ovine pulmonary adenocarcinoma (OPA, P-V16)
  • Jaagsiekte sheep retrovirus (JSRV, P-V16) has been associated with sheep nasal adenocarcinoma; indistinguishable from ENTV-1-induced adenocarcinoma

PATHOGENESIS:

• Infectious: Caused by ENTV-1 and -2; neoplasms are experimentally induced in naive sheep and goats by transmission of nasal fluids from clinically affected animals; retrovirus-like particles have been demonstrated in neoplastic cells by electron microscopy in both sheep and goats
  • Incubation periods in natural disease thought to be 1-3 year; transmission is direct contact with nasal secretions
• Viral envelope glycoprotein is thought to be responsible for tumor development (in mice); detectable in neoplastic epithelial cells but not adjacent normal tissue
• Viral genes: gag, pol, env

TYPICAL CLINICAL FINDINGS:

• Insidious, progressive clinical symptoms including uni or bilateral serous to mucopurulent nasal discharge, inspiratory dyspnea, open mouth breathing, flared nostrils, respiratory stertor, and sneezing
• Nasal deformity and weight loss; tumor may protrude from the nostrils
• Facial deformities, exophthalmos, and lacrimation secondary to space occupying lesions
• Subclinical infection is common; most experimentally infected animals do not develop tumors

TYPICAL GROSS FINDINGS:

• Unilateral or bilateral masses in the nasal cavities originating from ethmoid turbinates, with compression of the surrounding structures
• Appear white, multinodular, firm to soft, covered by mucus
• Can extend into pharynx, sinuses, and/or infiltrate through the cribriform plate

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• 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 non-ciliated epithelial cells form orderly acinar, tubular, or papillary arrangements on a scant fibrovascular stroma; neoplastic cells have basal round nuclei and variable mitotic rates
• Occasionally have abundant mucus production, and rarely squamous metaplasia
• Lymphocytic infiltrate within and adjacent of neoplasm
• May be accompanied with nasal inflammatory polyps and glandular hyperplasia

ULTRASTRUCTURAL FINDINGS:

• Retrovirus
  • Intracytoplasmic, intranuclear, 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
• Electron microscopy
• PCR - important to distinguish between viruses, since ENTV-1 and JSRV can produce identical lesions
• ELISA- for identifying infected animals in a flock

DIFFERENTIAL DIAGNOSIS:

• Sporadic (nonviral) nasal tumor (IHC, PCR, EM to differentiate)
• Jaagsiekte sheep retrovirus (JSRV, P-V16) (PCR to differentiate)
• Fungal granulomas
• Nasal polyp: Fibrous/myxomatous core covered by hyperplastic epithelium with inflammatory cell infiltrate

COMPARATIVE PATHOLOGY:

• In general, nasal tumors are rare in domestic animals except in sheep and goats.
• Goats: Retrovirus-associated nasal carcinoma also seen in goats (ENTV-2)
• Bighorn sheep:
  • Paranasal sinus tumors of unknown causative agent, similar to enzootic nasal tumor of sheep:
    • Seromucinous nasal discharge, soft to cystic mass in the sinus cavity that can extend into underlying bone, frontal or palatine sinus, or nasal turbinates
    • While some masses are classified as adenocarcinomas, a more robust neoplastic mesenchymal component differentiates this from enzootic nasal adenocarcinoma in domestic sheep
    • Bone production prominent in some cases
    • Acini and cystic structures may contain PAS positive mucin
• Nasal tumors in other species:
  • Enzootic nasal adenocarcinomas have been identified in horses and pigs, especially in farms where endemic nasal tumors of ruminants occur; clear viral etiology not established
  • NHPS: Nasal adenocarcinoma, nasal adenoma, and olfactory neuroepithelioma reported in macaques
  • Canids
    • Main site is nasal passages > sinuses for dogs; nasal tumors are usually large and invasive at diagnosis
      • Occurs in medium to large breed dogs: Collies, Airedale terrier, basset hound and German shorthair pointer
      • Other DDX include olfactory neuroblastoma.
    • Mexican gray wolves predisposed to developing nasal adenocarcinomas that are sinonasal, squamous cell carcinomas
    • Nasal adenosquamous carcinoma reported in a red fox
  • Cats
    • Lymphoma is the common primary nasal tumor; diffuse large B cell immunoblastic type.
    • Main site is tip of the nose and nasal passages; tumors are large and invasive at diagnosis
  • Horses
    • Main site maxillary sinus > nasal passage
    • Ethmoidal hematomas may resemble nasal tumors
    • Other DDX includes squamous cell carcinoma
  • Laboratory animals’ nasal tumors reported secondary to exposure of high concentration of formaldehyde fumes
• Beta retrovirus
  • Mouse mammary tumor virus
  • Mason-Pfizer monkey virus (monkey mammary tumor)
  • Jaagsieke sheep retrovirus
  • Virions have been reported in mammary tumors of monkeys, baboons, cats, dogs, lemmings, and rats; causal role remains elusive

REFERENCES:

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