• View in gallery

    Postmortem image of the head and neck of a 2-year-old 2.9-kg female, domestic backyard turkey (Meleagris gallopavo) with a history of weight loss and blindness of unknown duration. Multiple, raised, white-to-tan, firm cutaneous nodules ranging from 0.5 to 2.5 cm in diameter (arrows) are evident. The snood and nares are covered by a light-yellow, dry, crusty material.

  • View in gallery View in gallery

    Photomicrographs of sections of the neoplasm from the head of the turkey in Figure 1. A—The neoplasm is composed of sheets of round cells. H&E stain; bar = 100 µm. B—Neoplastic cells express cluster of differentiation 3 (CD3), a T-lymphocyte marker, and have dark brown nuclear and cytoplasmic staining. Immunohistochemical staining for CD3; bar = 20 µm.

  • 1.

    Allison AB, Keel M, Philips J, et al. Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen? Virology. 2014;450–451:212.

    • Search Google Scholar
    • Export Citation
  • 2.

    Crespo R, Woolcock PR, Fadly AM, Hall C, Shivaprasad HL. Characterization of T-cell lymphomas associated with an outbreak of reticuloendotheliosis in turkeys. Avian Pathol. 2002;31:355361.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Thomas JM, Allison AB, Holmes E, et al. Molecular surveillance for lymphoproliferative disease virus in wild turkeys (Meleagris gallopavo) from the eastern United States. PLoS One. 2015;10:e0122644.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Payne LN, Venugopal K. Neoplastic diseases: Marek’s disease, avian leukosis, and reticuloendotheliosis. Rev Sci Tech. 2000;19:544564.

  • 5.

    Biggs PM, McDougall JS, Frazier JA, Milne BS. Lymphoproliferative disease of turkeys 1: clinical aspects. Avian Pathol. 1978;7:131139.

  • 6.

    Elsmo EJ, Allison A, Brown J. A retrospective study of causes of skin lesions in wild turkeys (Meleagris gallopavo) in the eastern USA, 1975–2013. J Wildl Dis. 2016;52(3):582591.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Hydock K, Brown H, Nemeth N, et al. Evaluation of cytology for diagnosing avian pox in wild turkeys (Meleagris gallopavo). Avian Dis. 2018;62:4549.

  • 8.

    Hauck R, Mays J, Dunn JR, Shivaprasad HL. Two cases of Marek’s disease in backyard turkeys. Avian Dis. 2020;64:347351.

  • 9.

    Niedringhaus KD, Nemeth NM, Sellers HS, Brown JD, Fenton HMA. Multicentric round cell neoplasms and their viral associations in wild turkeys (Meleagris gallopavo) in the southeastern United States. Vet Pathol. 2019;56:915920.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Powell PC, Howes K, Lawn AM, et al. Marek’s disease in turkeys: the induction of lesions and the establishment of lymphoid cell lines. Avian Dis. 1983;13:201214.

    • Search Google Scholar
    • Export Citation
  • 11.

    Ahmed H, Mays J, Kiupel M, Dunn JR. Development of reliable techniques for the differential diagnosis of avian tumour viruses by immunohistochemistry and polymerase chain reaction from formalin-fixed paraffin-embedded tissue sections. Avian Pathol. 2018;47:364374.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Venugopal K, Howes K, Flannery DMJ, Payne LN. Subgroup J avian leukosis virus infection in turkeys: induction of rapid onset tumors by acutely transforming virus strain 966. Avian Pathol. 2000;29:319325.

    • Search Google Scholar
    • Export Citation
  • 13.

    Alger K, Bunting E, Schuler K, Jagne J, Whipps CM. Diagnosing lymphoproliferative disease virus in live wild turkeys (Meleagris gallopavo) using whole blood. J Zoo Wildl Med. 2015;46:806814.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Hafez HM. Serological investigation on reticuloendotheliosis in turkey flocks. J Vet Med B Infect Dis Vet Public Health. 2001;48:547550.

    • Search Google Scholar
    • Export Citation
  • 15.

    Davidson I, Braverman Y. Insect contribution to horizontal transmission of reticuloendotheliosis virus. J Med Entomol. 2005;42:128133.

  • 16.

    Bohls RL. Extensive investigation of reticuloendotheliosis virus in the endangered Attwater’s Prairie chicken. Doctoral dissertation. Texas A&M University; 2003.

  • 17.

    Motha MXJ, Egerton JR, Sweeny AW. Some evidence of mechanical transmission of reticuloendotheliosis virus by mosquitos. Avian Dis. 1984;28:858867.

  • 18.

    Gopal S, Manoharan P, Kathaperumal K, Chidambaram B, Divya KC. Differential detection of avian oncogenic viruses in poultry layer farms and turkeys by use of multiplex PCR. J Clin Microbiol. 2012;50:26682673.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Chapman HD. Coccidiosis in the turkey. Avian Pathol. 2008;37:205223.

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  • 1 Department of Pathobiological Sciences, Louisiana State University, School of Veterinary Medicine, Baton Rouge, LA
  • | 2 Louisiana Animal Disease Diagnostic Laboratory, Baton Rouge, LA
  • | 3 Southeastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, University of Georgia, Athens, GA
  • | 4 U.S. National Poultry Research Center, U.S. Department of Agriculture–Agricultural Research Service, Athens, GA
  • | 5 California Animal Health and Food Safety Laboratory System, University of California, Davis, Tulare Branch, Tulare, CA
  • | 6 Poultry Diagnostic and Research Center, University of Georgia, Athens, GA

Abstract

In collaboration with the American College of Veterinary Pathologists

Abstract

In collaboration with the American College of Veterinary Pathologists

History

A 2-year-old 2.9-kg female domestic turkey (Meleagris gallopavo) with a history of weight loss and blindness of unknown duration died and was then submitted for postmortem examination. Other birds from the same backyard flock were not reported to have been sick or to have had any abnormal clinical signs.

Clinical and Gross Findings

The turkey was in thin nutritional condition. A raised, immovable cutaneous nodule (2.5 X 2.0 X 2.0 cm) was present above the left orbit, with multiple smaller cutaneous nodules on the neck (Figure 1). On cut surface, the nodules were white to pale tan and contained soft, homogenous, material that dissected into the underlying subcutis, skeletal muscles, and orbital spaces. A raised, ulcerated mass was present on the third digit of the left limb at the base of the nail. The snood and neck were multifocally ulcerated and covered with a dark-red to yellow, dry crusted material that also covered both nares. Necropsy of the bird revealed a raised white nodule (1.5 X 1.5 X 0.5 cm) on the surface of the liver that extended into the parenchyma. A pale-tan nodule (0.5 X 1.0 X 1.5 cm) was present on the cranial pole of the right kidney. No other meaningful gross abnormalities were noted.

Figure 1
Figure 1

Postmortem image of the head and neck of a 2-year-old 2.9-kg female, domestic backyard turkey (Meleagris gallopavo) with a history of weight loss and blindness of unknown duration. Multiple, raised, white-to-tan, firm cutaneous nodules ranging from 0.5 to 2.5 cm in diameter (arrows) are evident. The snood and nares are covered by a light-yellow, dry, crusty material.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.20.12.0677

Formulate differential diagnoses, then continue reading.

Histopathologic and Laboratory Findings

Histologically, the nodules on the head and neck consisted of variably demarcated, expansile, and infiltrative, densely cellular dermal and epidermal neoplasms composed of round cells arranged in solid sheets and supported by fine fibrovascular stroma (Figure 2). The neoplastic cells had distinct cell borders with scant to moderate amounts of homogenous, lightly eosinophilic cytoplasm. The nuclei were round to oval and were located centrally to paracentrally with coarsely clumped to condensed chromatin and inconspicuous nucleoli. Anisokaryosis and anisocytosis were moderate, and mitotic figures were rare (0 or 1 mitotic figure/hpf [400X]). Neoplastic cells infiltrated skeletal muscle and vessel walls. There were multifocal areas of necrosis scattered throughout the masses. The epidermis overlying the masses was often ulcerated, and the exposed dermis was covered with a serocellular crust admixed with degenerate heterophils. Numerous short bacillary bacterial colonies and degenerate heterophils were embedded within the crust. The nasal passages, skull, and major structures of both eyes including the retina, ciliary body, choroid, sclera, conjunctiva, and periorbital connective tissue were also infiltrated by neoplastic cells. Similarly, the heart, great vessels, crop, cerebrum, lung, liver, kidney, right abdominal air sac, thyroid glands, thymus, pancreas, peripancreatic mesenteric adipose tissue, spleen, small intestine, and large intestine were variably infiltrated by neoplastic cells. Neoplastic cells revealed immunoreactivity for cluster of differentiation 3 (CD3), a T-cell marker (nuclear and cytoplasmic staining).

Figure 2
Figure 2
Figure 2

Photomicrographs of sections of the neoplasm from the head of the turkey in Figure 1. A—The neoplasm is composed of sheets of round cells. H&E stain; bar = 100 µm. B—Neoplastic cells express cluster of differentiation 3 (CD3), a T-lymphocyte marker, and have dark brown nuclear and cytoplasmic staining. Immunohistochemical staining for CD3; bar = 20 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.20.12.0677

Results were negative for PCR assays for lymphoproliferative disease virus (LPDV) and reticuloendotheliosis virus (REV) performed on thymus, spleen, heart, lung, and liver samples; and PCR assays for Marek disease virus (MDV) performed on liver and spleen samples. Escherichia coli and Pseudomonas aeruginosa were isolated from the air sacs, facial mass, and nose, and E coli was also isolated from the lung. The air sacs had histologic evidence of inflammation, and bilateral crusted material was grossly observed in both nares. There was no histologic evidence of inflammation of the nasal mucosa or the lungs, only the presence of lymphoid neoplastic cells. Coccidial organisms were not observed microscopically in the intestines, but were detected in the contents of the colon through fecal flotation.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis: multicentric T-cell lymphoma.

Case summary: spontaneous multicentric T-cell lymphoma in a domestic turkey.

Comments

Viral-induced neoplasms are not uncommon in domestic poultry, including turkeys.14 Clinical signs are nonspecific but can include anorexia and lethargy, as was observed in this case.1,4,5 Microscopically, neoplastic proliferation of lymphoid cells often disrupts and infiltrates the normal architecture in multiple organs. The neoplastic cells can also manifest as nodules that cover featherless skin or that are found within the upper respiratory and digestive tracts. Skin nodules caused by avian pox virus or LPDV are difficult to distinguish grossly, but avian pox can be differentiated histologically by the presence of epidermal hyperplasia, ballooning degeneration, and eosinophilic, intracytoplasmic inclusion bodies (Bollinger bodies).6,7

In turkeys, LPDV and REV are the most commonly reported oncogenic retroviruses associated with neoplasms, and MDV, which is the oncogenic herpesvirus (Gallid alphaherpesvirus 2) is less likely.4,8 The immunoreactivity to CD3 indicated T-cell lymphoma in this case. T-cell lymphomas have been reported in turkeys associated with oncogenic viruses including LPDV, REV, and MDV.2,810 In this case, a virus associated with neoplasia was not detected, but because false-negative results can occur with any PCR-based testing, viral involvement cannot be ruled out completely. However, the absence of detection of a virus in this case suggested that a spontaneous, noninfectious neoplastic process must be considered. Immunohistochemistry for virus antigens, such as Meq protein for Marek disease, would further strengthen the diagnosis.11 Avian leukosis virus is another oncogenic retrovirus that causes lymphoid, erythroid, or myeloid leukosis, alone or in combination, but was not considered in this case as lymphoma has not been reported in turkey populations and is associated with B-cell lymphomas rather than T-cell lymphomas.4,12 Turkey herpesvirus coinfection with LPDV was detected from a free-ranging turkey with multicentric neoplasia with morphology consistent with myeloid origin.9 Turkey herpesvirus was not tested for in this case; it is a nononcogenic virus and its use in vaccination is associated with reduced development of lymphoma in Marek disease in chickens. LPDV is an oncogenic C-type retrovirus that has been found in both wild and domestic turkeys.1,3 Historically a disease limited to Europe and Israel, LPDV was detected in United States’ wild turkey populations in 2009. Since that first report,1 LPDV has been isolated in wild turkeys throughout the United States, but clinical disease is thought to be uncommon. The method of transmission of retroviruses associated with neoplasia in wild turkeys is not known, but is suspected potentially to be vector borne. LPDV has been demonstrated to infect both turkeys and chickens experimentally, but natural LPDV infection has been reported only in turkeys. Histologically, lymphoproliferative disease is characterized by a pleomorphic infiltration of lymphocytes in different organs.1,6 The spleen, thymus, liver, and pancreas are affected most commonly, although other organ systems, including skin, can also be affected. Confirmation of LPDV infection can be determined through PCR assay, which is reported to have high specificity and sensitivity when performed on samples of either whole blood, buffy coat, or bone marrow.13

REV is another oncogenic C-type retrovirus that can cause acute reticular or chronic lymphoid neoplasia in a variety of avian species, including turkeys.2,14 Natural outbreaks are not common, economic losses are minimal, and disease is rarely reported in commercial flocks in the United States.2 Horizontal or vertical transmission can occur.2,14,15 Mosquitos from the genus Culex, insects from the genera Musca and Triatoma, and ticks from the genus Ornithodoros potentially play a role in spreading REV; however, further studies are needed to prove their role in transmission of the disease.1517 Chronic lymphoid neoplasms and acute reticulum cellular neoplasia are the major histopathologic findings.2 The ability to differentiate REV from other viral-induced neoplasia is difficult, which is why virus detection is the gold standard test.18 The virus can be detected through serology for antibodies, virus isolation, or PCR assay.14,15

The presence of systemic neoplasia in the turkey in this report likely caused immunosuppression, leading to secondary bacterial infections in a similar pathogenesis of Marek disease.4 Bacteria were isolated from the air sacs, lungs, and nasal passages, and an airsacculitis was confirmed histologically. Evidence of pneumonia or rhinitis was not observed microscopically. The presence of crusted material from the nares was suggestive of rhinitis, and histologic evidence of inflammation may have been masked by the marked presence of infiltrative neoplastic round cells. The lung parenchyma was less affected by the neoplastic round cells than the nasal passages, so the absence of histologic inflammation suggests the E coli isolated was a result of possible contamination during processing. In addition to cachexia from neoplasia and potential behavioral changes in accessing and eating food from the associated blindness and likely also olfactory changes, the bacterial infection likely played a role in the poor body condition in this case. The importance of coccidia identified on fecal flotation was unknown, as intestinal disease resulting from coccidiosis was not observed microscopically, but subclinical coccidial infection has been documented to affect weight gain negatively.19

Viral-induced neoplastic processes in poultry cause more economic losses than spontaneous, noninfectious causes, which is why identification of a viral agent is important in maintaining flock health in commercial operations. Spontaneous, systemic round cell tumors occur in older turkeys, but are not a common cause of death.3 If an operation reports an increased number of turkey deaths, further diagnostic procedures are warranted to rule out a viral agent. Cases of viral-induced neoplasia are rarely reported in backyard poultry, but they may be underdiagnosed because full workups, including retroviral testing, are not always pursued. Clinicians should be aware of viral-induced and spontaneous neoplasms as causes of nonspecific clinical signs and skin lesions in domestic backyard turkeys.

References

  • 1.

    Allison AB, Keel M, Philips J, et al. Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen? Virology. 2014;450–451:212.

    • Search Google Scholar
    • Export Citation
  • 2.

    Crespo R, Woolcock PR, Fadly AM, Hall C, Shivaprasad HL. Characterization of T-cell lymphomas associated with an outbreak of reticuloendotheliosis in turkeys. Avian Pathol. 2002;31:355361.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Thomas JM, Allison AB, Holmes E, et al. Molecular surveillance for lymphoproliferative disease virus in wild turkeys (Meleagris gallopavo) from the eastern United States. PLoS One. 2015;10:e0122644.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Payne LN, Venugopal K. Neoplastic diseases: Marek’s disease, avian leukosis, and reticuloendotheliosis. Rev Sci Tech. 2000;19:544564.

  • 5.

    Biggs PM, McDougall JS, Frazier JA, Milne BS. Lymphoproliferative disease of turkeys 1: clinical aspects. Avian Pathol. 1978;7:131139.

  • 6.

    Elsmo EJ, Allison A, Brown J. A retrospective study of causes of skin lesions in wild turkeys (Meleagris gallopavo) in the eastern USA, 1975–2013. J Wildl Dis. 2016;52(3):582591.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Hydock K, Brown H, Nemeth N, et al. Evaluation of cytology for diagnosing avian pox in wild turkeys (Meleagris gallopavo). Avian Dis. 2018;62:4549.

  • 8.

    Hauck R, Mays J, Dunn JR, Shivaprasad HL. Two cases of Marek’s disease in backyard turkeys. Avian Dis. 2020;64:347351.

  • 9.

    Niedringhaus KD, Nemeth NM, Sellers HS, Brown JD, Fenton HMA. Multicentric round cell neoplasms and their viral associations in wild turkeys (Meleagris gallopavo) in the southeastern United States. Vet Pathol. 2019;56:915920.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Powell PC, Howes K, Lawn AM, et al. Marek’s disease in turkeys: the induction of lesions and the establishment of lymphoid cell lines. Avian Dis. 1983;13:201214.

    • Search Google Scholar
    • Export Citation
  • 11.

    Ahmed H, Mays J, Kiupel M, Dunn JR. Development of reliable techniques for the differential diagnosis of avian tumour viruses by immunohistochemistry and polymerase chain reaction from formalin-fixed paraffin-embedded tissue sections. Avian Pathol. 2018;47:364374.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Venugopal K, Howes K, Flannery DMJ, Payne LN. Subgroup J avian leukosis virus infection in turkeys: induction of rapid onset tumors by acutely transforming virus strain 966. Avian Pathol. 2000;29:319325.

    • Search Google Scholar
    • Export Citation
  • 13.

    Alger K, Bunting E, Schuler K, Jagne J, Whipps CM. Diagnosing lymphoproliferative disease virus in live wild turkeys (Meleagris gallopavo) using whole blood. J Zoo Wildl Med. 2015;46:806814.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Hafez HM. Serological investigation on reticuloendotheliosis in turkey flocks. J Vet Med B Infect Dis Vet Public Health. 2001;48:547550.

    • Search Google Scholar
    • Export Citation
  • 15.

    Davidson I, Braverman Y. Insect contribution to horizontal transmission of reticuloendotheliosis virus. J Med Entomol. 2005;42:128133.

  • 16.

    Bohls RL. Extensive investigation of reticuloendotheliosis virus in the endangered Attwater’s Prairie chicken. Doctoral dissertation. Texas A&M University; 2003.

  • 17.

    Motha MXJ, Egerton JR, Sweeny AW. Some evidence of mechanical transmission of reticuloendotheliosis virus by mosquitos. Avian Dis. 1984;28:858867.

  • 18.

    Gopal S, Manoharan P, Kathaperumal K, Chidambaram B, Divya KC. Differential detection of avian oncogenic viruses in poultry layer farms and turkeys by use of multiplex PCR. J Clin Microbiol. 2012;50:26682673.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Chapman HD. Coccidiosis in the turkey. Avian Pathol. 2008;37:205223.

Contributor Notes

Corresponding author: Dr. Wakamatsu (nutsuki@purdue.edu)