Sheep Pulmonary Adenomatosis

Antigenicity

• The virus cannot be grown in culture, although it can be seen by EM on tumor cells of infected sheep

Pathogenesis

• Causes a proliferation of alveolar lining cells, producing massive amounts of fluid
• Proliferative foci project into alveoli and bronchi and from slow-growing tumors
• Death occurs between 3-4 years of age

Clinical signs:

• Low exercise tolerance
• Gradual weight loss
• Dyspnoea
• Coughing
• Nasal fluid discharges during wheelbarrow test
• Secondary bacterial infection by Pasteurella hemolytica often precipitates death
• PM reveals fawn-gray tumor (for more see here)

Epidemiology

• Found in 25% of pneumonia cases in Scotland
• Absent in USA, common in UK

Diagnosis

• Electron microscopy on lung biopsy

Control

• Cull clinically affected animals

• Also called pulmonary carcinomatosis
• Infectious bronchiolar-alveolar carcinoma caused by a retrovirus
• Commonest under intensive management systems which favour aerosol transmission and close contact of disease
• Behaves like chronic pneumonia
• Takes months to years to express itself clinically as coughing and exercise intolerance
• Gross pathology:
  • Heavy lungs which fail to collapse
  • The lesions progress from small firm grey/white nodular lesions to extensive confluent areas with replacement by neoplastic tissue
  • Cut surface oozes fluid
  • There is often coexistent infection present
  • Occasional metastases to bronchial and mediastinal lymph nodes can occur
• Histopathology:
  • Widespread proliferation of alveolar (Type 2) and terminal bronchiolar epithelium, lining the alveoli and lower airways
  • Multiple neoplastic foci of cuboidal/columnar cells forming papillary projections into the lumen
  • Metastases of the same in the bronchial and mediastinal lymph nodes
• There is no serological test, and diagnosis depends upon raising the animal by the hind limbs whereupon a clear fluid issues from the nose = "Wheelbarrow test"

More information

Overview

Etiology: Type B/D Retrovirus (also known as the jaagziekte retrovirus‑‑JSRV)

Condition: Pulmonary carcinomatosis.

Synonyms: Jaagsiekte, sheep pulmonary adenomatosis, ovine pulmonary carcinoma.

General

• Pulmonary carcinomatosis (OPC) is an infectious form of bronchioalveolar tumor with behavior of a low-grade carcinoma.
• Associated with (and strong evidence that is caused by) a type B/D retrovirus of family Retroviridae (single-stranded RNA).
• Occurs in Africa, Europe and the Americas.
• Susceptibility among breeds varies; Merino sheep are highly susceptible.
• The condition is considered to be a transmissible neoplasm with uncommon metastasis to regional lymph nodes and rare metastasis to other sites. Most growth is by local expansion and infiltration.
• The disease spreads via aerosol transmission and is less common in areas where the sheep are dispersed.

Pathogenesis

• The retrovirus associated with OPC is generally referred to as the jaagsiekte retrovirus (JSRV). This virus is morphologically distinct from all known retroviruses but has yet to be cultured.
• The target cells are type II alveolar epithelial cells and, less frequently, nonciliated bronchiolar epithelium.
• The virus-transformed epithelial cells proliferate, filling alveoli, spilling into adjacent airways and compressing and invading pulmonary parenchyma.
• The exact mechanism of carcinogenesis is unknown.
• Naturally occurring ovine pulmonary carcinomatosis has a long incubation period (months to up to 2 years), but experimentally, the time course of the disease can be reduced to a few weeks by inoculating lung tumor or lung fluid from affected sheep into neonatal lambs.

Clinical Signs

• Coughing
• Exercise intolerance (thus the Afrikaan name jaagsiekte, “driving sickness”).
• Crackles and wheezes.
• Abundant watery exudate which is discharged from the nose, especially when the head is lowered. The discharge is an important diagnostic clinical feature.
• Dyspnea.

Findings

Gross Findings

• Lung parenchymal masses ranging from 1 – 20 mm dia. gray-blue-white nodules (early) to large gray nodular and confluent masses (later). The larger masses often have fibrotic centers.
• The lungs are enlarged, heavy, and fail to collapse.
• Coexisting bronchopneumonia, verminous pneumonia, chronic progressive pneumonia, or combinations of the three.
• Right ventricular hypertrophy and dilation.
• Deaths result from heart failure, hypoxia or secondary bacterial pneumonias.

Laser Disc: 2395; 2396; 11702; 15547.

Microscopic Findings

• Multiple proliferative foci of cuboidal or columnar cells which line alveoli and form papillary projections into their lumina (i.e., adenomatous hyperplasia, adenomas and adenocarcinomas).
• In larger masses the pattern is obscured and fibroplasia often occurs in more disorganized and degenerative areas.
• Early or uncomplicated lesions may have little to no accumulation of inflammatory cells; however, there are usually low to moderate aggregations of alveolar macrophages in alveolar lumina.

Ultrastructure

Some cells have cytoplasmic lamellar bodies characteristic of alveolar type II epithelial cells; others have secretory granules and glycogen compatable with secretory bronchiolar epithelial (Clara) cell origin.

Differential Diagnosis

1. Chronic progressive pneumonia (maedi - lentivirus) --lymphofollicular interstitial pneumonia (with little to no significant alveolar epithelial hyperplasia).
2. Remember, bacterial bronchopneumonias and verminous pneumonias may be present in addition to OPC.

Comparative Pathology

• Human bronchio‑alveolar carcinoma shares many histologic and behavioral characteristics with OPC.
• Type D retroviruses have been implicated in caprine and ovine nasal adenocarcinomas.

References

1. Hecht SJ, Sharp JM, and Demartini JC: Retroviral Aetiopathogenesis of Ovine Pulmonary Carcinoma: A Critical Appraisal. Br Vet J (1996) 152:395-406. 2. Dungworth DL: The Respiratory System, In:Pathology of Domestic Animals, 4th edition, ed. Jubb KVF, Kennedy PC, and Palmer N, pp.690-2, Academic Press, San Diego, CA, 1993. 3. Fenner FJ, Gibbs EPJ, Murphy FA, Rott R, Studdert MJ, and White DO: Retroviridae, In: Veterinary Virology, 2nd edition, pp. 578-9, Academic Press, Inc., San Diego CA, 1993. 4. Kimberling CV: Diseases of Adult Sheep, In: Jensen and Swift’s Diseases of Sheep, 3rd edition, pp. 270-3, 1988.

Written and revised by GD Young, 1988; BH Williams, 1991; WD Fall, 1994; TO Johnson, 1999.