JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V16

 

Signalment (JPC #2055944): Sheep, breed not specified

 

HISTORY: Exhibited respiratory distress.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Replacing 60% of normal pulmonary architecture and compressing adjacent alveoli (atelectasis) are multifocal to coalescing, variably-sized, up to 1 mm diameter, unencapsulated, expansile neoplastic foci composed of a single to multiple layers of cuboidal to columnar epithelial cells forming acinar or papillary projections into alveolar lumina, less often tracking along pre-existing alveolar septa (lepidic), supported on a fine fibrovascular stroma. Neoplastic cells have distinct cell borders, a moderate amount of finely granular to vacuolated amphophilic cytoplasm, round to oval nuclei with finely-stippled chromatin, and 1‑3 variably distinct nucleoli. Anisocytosis and anisokaryosis are mild, and there is 1 mitotic figure per 10 HPF (2.37mm²). Multifocally, alveolar and bronchiolar lumina contain an exudate composed of abundant viable and necrotic neutrophils, and/or foamy alveolar macrophages, fibrin, and edema. Bronchiolar epithelium is frequently hyperplastic, piling up to 6 layers thick, and multifocally contains moderate numbers of goblet cells (goblet cell hyperplasia). The pleura and interlobular septa are expanded up to 5 times normal by increased clear space and ectatic lymphatics (edema) and scattered previously-described inflammatory cells. Multifocally, there are increased numbers of bronchiole-associated lymphocytes which occasionally form germinal centers (BALT hyperplasia).

 

MORPHOLOGIC DIAGNOSIS: Lung: Pulmonary adenocarcinoma, breed unspecified, ovine.

 

ETIOLOGIC DIAGNOSIS: Retroviral pulmonary carcinomatosis 

 

CAUSE: Betaretrovirus (Jaagsiekte sheep retrovirus [JSRV])

 

CONDITION: Ovine pulmonary adenocarcinoma (OPA)

 

SYNONYMS: Jaagsiekte, ovine pulmonary carcinoma (OPC), ovine pulmonary adenomatosis

 

GENERAL DISCUSSION: 

• Contagious retroviral pulmonary carcinoma of sheep, and rarely goats, caused by jaagsiekte sheep retrovirus (JSRV), an enveloped single-stranded RNA betaretrovirus (Family Retroviridae); JSRV induces oncogenic transformation of alveolar and bronchiolar secretory epithelial cells
• Exists worldwide (except Australia and New Zealand); rare in North America; significant problem in Scotland, South Africa, and South America
• Long incubation period (typically 2 years); occurrence mostly seen in adult sheep (aged 2-4 years), but can occur at any age and in as little as 10 days post-exposure

 

PATHOGENESIS:

• JSRV is consistently present within neoplastic cells, but minimally in non-neoplastic epithelium or stroma; envelope glycoprotein induce oncogenic transformation (no oncogenes) of alveolar and bronchiolar secretory epithelial cells 
  • There is also one report of JSRV causing a nasal adenocarcinoma in a sheep (tumor cells were positive for JSRV and negative for ovine enzootic nasal tumor virus [ENTV-1, the usual cause]) (Jahns et al, JDVI 2020)
• Transmission via direct contact of young animals with infective nasal secretions or infected colostrum or milk (retrovirus found in milk macrophages (Borobia et al, JDVI 2022) 
• Often occurs as devastating epizootics with 5-80% mortality when first introduced into a flock, then gradually tapers off 

 

TYPICAL CLINICAL SIGNS: 

• Progressive dyspnea, tachypnea, exercise intolerance, nasal discharge, coughing, and weight loss +/- fever and anorexia with concurrent infection 

• Copious frothy fluid draining from nostrils when head lowered or hindlimbs elevated characteristic
• Dyspnea accentuated by exercise (Jaagsiekte = “driving sickness” in Afrikaans)

 

TYPICAL GROSS FINDINGS: 

• Classical OPA: Multifocal or locally extensive firm, expansile, gray nodules that exude fluid from cut section; lungs are heavy and airways filled with foam

• Metastasis to regional lymph nodes in 10% of cases; rarely other locations 
• +/- secondary bronchopneumonia, abscesses, and mediastinal adhesion 

• Atypical OPA (subclinical, non-progressive disease): Well demarcated, dry, more firm

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Adjacent alveoli: Compression (atelectasis), fibrosis, lymphohistiocytic alveolar infiltrate
• +/- Lymphocytic interstitial pneumonia (i.e. Maedi), peribronchiolar lymphoid or cranioventral suppurative bronchopneumonia when co-infection is present

 

ADDITIONAL DIAGNOSTIC TESTS:

• Retrovirus antigen (Jaagsiekte Sheep Retrovirus Capsid Protein, JSRV CA) demonstrated in the cytoplasm of neoplastic cells within the lung and lymph node (De Las Deras et al, Vet Pathol 2021)
• IHC: Cells are of type II pneumocyte or club cell origin 
• PCR
  • Blood samples: JSRV-infected cells (high false negatives)
  • Bronchoalveolar lavage samples: Most successful method

 

DIFFERENTIAL DIAGNOSIS:    

• Non-viral (spontantous) pulmonary carcinoma of sheep (P-N02): Rare; cannot be distinguished from JSRV associated pulmonary carcinoma without additional testing to exclude JSRV
• Maedi (P-V17, ovine progressive pneumonia; OPP): Small ruminant lentivirus, family Retroviridae; prominent peribronchiolar and perivascular lymphocytic inflammation and lacks papillary growths characteristic of OPA; dual infection with JSRV and small ruminant lentivirus is common
• Lungworms
• Bacterial bronchopneumonia (primary or secondary)
• Enzootic nasal tumor virus (ENTV-1)(P-N04):   Another betaretrovirus-induced respiratory tumor in sheep; causes tumors within the nasal cavity that originate from the ethmoid conchae

 

COMPARATIVE PATHOLOGY: 

 

REFERENCES:

1. Borobia M, De Las Heras M, Godino J, et al. Jaagsiekte sheep retrovirus found in milk macrophages but not in milk lymphocytes or mammary gland epithelia of naturally infected sheep. J Vet Diagn Invest. 2022;34(1):112-115. 
2. Caswell JL, Williams KJ. The respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. 6th ed. Vol 2. Philadelphia, PA: Elsevier Saunders; 2016:560-562.
3. De Las Heras M, Resendiz RA, Gonzalez-Sainz JA, et al. Exogenous small ruminant betaretrovirus envelope protein is detected in draining lymph nodes in contagious respiratory tumors of sheep and goats. Vet Pathol. 2021;58(2):361-368.
4. Jahns H, Cousens C. Nasal adenocarcinoma associated with jaggsiekte sheep retrovirus infection in a sheep. J Vet Diagn Invest. 2020; 32(1):152-155.
5. Lopez A, Martinson SA. The respiratory system, thoracic cavities, mediastinum, and pleurae. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:623-624.

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