JPC SYSTEMIC PATHOLOGY
MUSCULOSKELETAL SYSTEM
April 2022
M-V03 (NP)

Signalment (JPC #1692713):  Chicken   

 

HISTORY:  This chicken had enlarged long bones of the wings and legs.

 

HISTOPATHOLOGIC DESCRIPTION:  Long bone, diaphysis, cross section:  Diffusely and circumferentially, the cortex is markedly thickened and the medullary cavity markedly reduced by an increase in both subperiosteal and endosteal woven bone (hyperostosis) that surrounds and separates a variably distinct layer of preexisting cortex composed of mature lamellar bone.  Hyperostotic areas are composed of irregular, often basophilic, variably thick, irregularly interlacing trabeculae of immature woven bone containing numerous closely arranged, disorganized lacunae containing osteocytes.  There are few osteoclasts within Howship’s lacunae.  These trabeculae of new woven bone predominantly lack normal bone marrow elements and are separated by loose fibromyxomatous connective tissue; however, there are large, irregular spaces within the outer third of the hyperostotic bone that contain moderate amounts of hematopoietic marrow elements admixed with few loosely arranged spindle cells.  Multifocally the periosteum is moderately thickened by disorganized spindle cells that extend into and occasional are surrounded by underlying bone (fibrosis).

 

MORPHOLOGIC DIAGNOSIS:  Long bone, diaphysis:  Hyperostosis, subperiosteal and endosteal, diffuse, circumferential, severe (osteopetrosis), with multifocal periosteal thickening, chicken, avian.

 

ETIOLOGIC DIAGNOSIS:  Avian alpharetroviral osteopetrosis

 

CAUSE:  Avian leukosis virus (alpharetrovirus)

 

SYNONYMS:  Thick leg disease, marble bone disease

 

GENERAL DISCUSSION:

• Osteopetrosis: Avian osteopetrosis is induced by avian leukosis virus (ALV) and causes uniform or irregular diaphyseal or metaphyseal thickening, usually in the long bones of the leg
• Avian Leukosis Virus: The avian leukosis/sarcoma viruses are strains of a single-stranded, RNA, oncogenic alpharetrovirus; strains are classified by lesions they cause, with 10 subgroups A – J
  • The most common lesion is lymphoid leukosis (gradual onset in a flock, persistent low mortality predominantly in older chickens 16+ weeks old, bursal neoplasia with metastasis to other organs); in the United States, subgroup A viruses are the most common and most frequently associated with lymphoid leukosis
  • A relatively new strain, ALV-J, is the second most common strain in the United States, and primarily causes myeloid lesions like myelocytomatosis but may cause other tumors such as hemangiomas and a recent report of pleomorphic malignant mesothelioma with myelocytoma in a broiler-breeder (Murakami, J Comp Pathol. 2018); meat-type chickens appear more susceptible than layers to this strain
  • Subgroup B is occasionally identified
  • Subgroups C and D are rare
  • Subgroup E is considered endogenous because it is integrated into the host DNA
  • Subgroups F-I primarily cause leukosis in non-chicken species

 

PATHOGENESIS:

• Avian Leukosis Virus:
  • Egg transmission (vertical) of virus is an important mechanism of spread of avian leukosis virus, and infected chicks are immune tolerant and persistently infected, with increased risk of death from lymphoid leukosis and prolific viral shedding
  • Horizontal transmission also occurs, especially with ALV-J
  • Provirus integrates into the host DNA close to the c-myc gene; activation of this oncogene is considered the primary event in starting the neoplastic process
  • Mutations in p53 may play a role in tumorigenesis of myelocytomas
• Osteopetrosis: Avian leukosis virus alters the growth and differentiation of osteoblasts (rather than a defect in osteoclastic function, as in mammalian osteopetrosis [M-M02])

 

TYPICAL CLINICAL FINDINGS:

• Avian leukosis virus: Commonly nonspecific or no clinical signs, poor thrift, pallor, emaciation, decreased egg production, anemia, neoplasia in chickens 16+ weeks old
• Osteopetrosis: Limping, elevated alkaline phosphatase

 

TYPICAL GROSS FINDINGS:

• Avian leukosis virus, variable presentations:
  • Lymphoma may cause abdominal enlargement due to massive hepatomegaly, and commonly also affects kidney, ovary, and bursa of Fabricious; lesions can be diffuse or focal
    • The bursa is nearly always involved, but may not be detected without incision and examination of the epithelial surface
  • Myelocytomatosis causes multiple masses on the shanks, head, and thorax
  • Osteopetrosis: affects the long bones resulting in “boot” shanks appearance, due to thickening of the diaphysis and metaphysis of long bones

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Lymphoid leukosis: Lymphomatous cells are lymphoblastic and originate from the bursa (B-lymphocytes with surface IgM expression)
• Osteopetrosis: Initially, focal hypertrophy and hyperplasia of periosteum with increased numbers of large, basophilic osteoblasts; spongy bone converges centripetally towards center of the shaft; large, irregular Haversian canals; an increase in number and size of lacunae with numerous large eosinophilic osteocytes; increased basophilic and fibrous new bone

 

ADDITIONAL DIAGNOSTICS:

• PCR, IHC
• All avian leukosis viruses produce a group-specific antigen that can be detected in egg albumen and body tissues and fluids
• Transmission electron microscopy: 85-105nm diameter icosahedral virions with central cores

 

DIFFERENTIAL DIAGNOSIS:

Other osteopathies in birds:

• Rickets: Abnormal endochondral ossification characterized by failure of cartilage and osteoid matrix mineralization in young animals (see M-M08)
• Osteoporosis: Reduction in bone mass with increased porosity (see M-M16)
• Tibial dyschondroplasia: Defect in endochondral ossification due to inability of chondrocytes to hypertrophy,  with retention of nonvascularized, unmineralized cartilage in the proximal metaphysis of the tibiotarsus and tarsometatarsus of rapidly growing birds (see M-T06)

 

COMPARATIVE PATHOLOGY:

Osteopetrosis in other species:

• Virus-associated hyperostosis (osteopetrosis-like lesions):
  • Bovine viral diarrhea virus can induce multifocal retention of primary spongiosa à osteopetrosis-like lesions
  • Feline leukemia virus is associated with medullary osteosclerosis
• Mammalian osteopetrosis (see M-M02): defect in osteoclastic bone resorption à accumulation of primary spongiosa; described in the ox, sheep, deer, rat, rabbit, mouse, dog, cat, pig, and horse; probably autosomal recessive condition
• Congenital cortical hyperostosis in pigs (see M-M05): Excessive periosteal new bone formation on long bones (radius and ulna most severely affected), extensive edema, muscle atrophy of affected limb; presumed autosomal recessive

 

Other Alpharetroviruses:

• Rous sarcoma virus

 

REFERENCES:

1. Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2016:50-52, 91-94.
2. Murakami T, Sassa Y. Pleomorphic malignant mesothelioma in a broiler breeder infection with avian leucosis virus subgroup J.  J Comp Pathol.  2018;160:50-55.
3. Ojkic D, Sellers H, et al. Viral diseases.  In: Boulianne M., ed. Avian Disease Manual. 8^th Jacksonville, FL: American Association of Avian Pathologists; 2019: 37-39.
4. Olson EJ, Carlson CS. Bones, joints, tendons, and ligaments. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 1057-1059.
5. Yue Q, Yulong G, Liting Q, et al. Mutations in and expression of the tumor suppressor gene p53 in egg-type chickens infected with subgroup J avian leukosis virus. Vet Pathol. 2015;52(6):1052-1056.

Click the slide to view.

---