JPC SYSTEMIC PATHOLOGY

REPRODUCTIVE SYSTEM

January 2025

R-N13

 

SLIDE A: Signalment: (JPC #2040147): 2 year old female sex-link chicken

 

HISTORY: This chicken died after a two day history of listlessness. She had a history of laying rubbery eggs with tissue/blood.

 

HISTOPATHOLOGIC DESCRIPTION: Ovary: There is moderate autolysis obscuring some cellular details. Effacing 80% of the ovary and compressing adjacent remaining ovarian stroma and follicles is an unencapsulated, well demarcated, moderately cellular, infiltrative neoplasm composed of polygonal cells forming islands, irregular tubules and acini on a moderate fibrovascular stroma. Neoplastic cells have indistinct cell borders and a moderate amount of eosinophilic cytoplasm that often contains multiple, 2-5µm, round, eosinophilic, cytoplasmic granules. Nuclei are irregularly round with finely stippled chromatin and indistinct nucleoli. Anisocytosis and anisokaryosis are mild and mitoses average less than 1 per 2.37mm² (10 40x HPF). Islands of neoplastic cells are often surrounded by fibroblasts and abundant, variably mature fibrous connective tissue (desmoplasia). Multifocally within the neoplasm are large areas of amorphous, eosinophilic material (secretory product). Within the neoplasm, there is multifocal scattered karyorrhectic (necrotic) debris. Multifocally adhered to the surface of the ovary and within the ovarian stroma are globules of bright eosinophilic yolk material; also adhered to the surface of the ovary, associated with the yolk material, are colonies of 1-2µm cocci admixed with fibrin and debris. Within the ovarian stroma there are moderate numbers of inflammatory cells including granulocytes, macrophages, and lymphocytes; macrophages often contain phagocytosed eosinophilic yolk material. 

 

MORPHOLOGIC DIAGNOSIS:

1. Ovary: Adenocarcinoma.

2. Ovary: Oophoritis, granulocytic and histiocytic, chronic, multifocal, moderate, with free yolk material, yolk peritonitis and bacterial colonies. 

 

SLIDE B: Signalment: (JPC #2040148): Chicken.

 

HISTORY: None available.

 

HISTOPATHOLOGIC DESCRIPTION (JPC #2040148): Mesentery with small intestine: There is moderate autolysis obscuring some cellular details. Multifocally infiltrating and replacing the serosal surfaces of the mesentery is an unencapsulated, infiltrative, poorly demarcated, moderately cellular neoplasm composed of polygonal cells forming islands, irregular tubules and acini on a moderate fibrovascular stroma. Neoplastic cells have indistinct cell borders, a moderate amount of eosinophilic cytoplasm that often contains multiple, 2-5µm, round, eosinophilic cytoplasmic granules, and irregularly round nuclei with finely stippled chromatin and indistinct nucleoli. Islands of neoplastic cells are often surrounded by fibroblasts and abundant variably mature fibrous connective tissue (desmoplasia). Anisocytosis and anisokaryosis are moderate and mitosis average less than 1 per 2.37mm² (10 40x HPF). Scattered throughout the neoplasm are moderate numbers of macrophages, lymphocytes, and plasma cells which are also multifocally adhered to the surface of the neoplasm and mesentery in aggregates. 

 

MORPHOLOGIC DIAGNOSIS: Mesentery: Metastatic adenocarcinoma.

 

GENERAL DISCUSSION: 

• 50-60% of hens have adenocarcinomas in both ovary and oviduct simultaneously, versus approximately 20-25% of animals with only one of the organs affected
  • Primary site cannot be determined if both organs are affected; the term “Reproductive (tract) adenocarcinoma” is used in this case
  • Oviductal adenocarcinomas are diagnosed more frequently than ovarian adenocarcinoma when only one organ is affected

Ovarian adenocarcinoma

• Most common ovarian neoplasm of the chicken
• Only affects the left ovary, (left is functional; right is vestigial)

Oviduct adenocarcinoma

• Oviduct contains five regions: Infundibulum (fertilization); magnum (deposition of albumen); isthmus (deposition of membranes); uterus (shell); and vagina (transport to the cloaca)
• Incidence of adenocarcinoma is most common in upper magnum, less commonly in infundibulum or shell gland
• Common metastasis to mesentery and serosal surface of abdominal organs (pancreas, duodenum, less so to other organs); metastasis occurs both by implantation of tumor cells from primary neoplasm and through vascular spread
• Incidence increases with age and is 45% in aged commercial laying hens and up to 80% by 2 years of age in some breeds
• Incidence higher in breeds with high body weight and egg weight
• In turkeys, long photoperiods stimulate tumor growth and short photoperiods cause regression, leading to remission; melatonin attenuates tumor growth, making this a good model for human spontaneous adenocarcinoma

 

PATHOGENESIS: 

• Cell of origin for ovarian adenocarcinoma thought to be overlying mesothelial covering of ovary (germinal epithelium), thecal cells, interstitial cells, mesonephros, or sex cord remnants
• These tumors are estrogen responsive

 

TYPICAL CLINICAL FINDINGS:

• Abdominal distension (ascites)
• Weight loss
• Dyspnea, depression

 

TYPICAL GROSS FINDINGS: 

Ovarian adenocarcinoma

• Small, firm nodules on the surface of the ovary that later coalesce to form light tan or gray-white; may be solid or pedunculated and have cauliflower-like appearance
• Adenocarcinoma often has characteristic transcoelomic metastatic nodules on the surfaces of abdominal organs 

Oviduct adenocarcinoma

• Neoplasms most often arise in the upper magnum; tend to be highly invasive
• May appear as thickened, firm area of oviduct wall, with bulging into body cavity or oviductal lumen; obstruction of the oviduct is possible with large neoplasms
• Widespread peritoneal implantation (similar to ovarian adenocarcinoma)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

Ovarian adenocarcinoma

• Acinar structures centered on intense PAS-positive material
• Less commonly solid or papillary structures
• Variable mitotic figures, often infrequent
• Intracytoplasmic intensely eosinophilic, homogeneous material (PAS-positive and mucicarmine-negative; mucicarmine – very specific for epithelial mucins, including adenocarcinomas)
• Foci of necrosis and hemorrhage

Oviduct adenocarcinoma

• Pattern and cell morphology vary
• Most often acinar and tubular patterns
• Neoplastic cells may penetrate through the wall of the oviduct and spread through the abdominal cavity; the muscularis mucosa under these implants becomes hyperplastic
• Similar intracytoplasmic intensely eosinophilic, homogeneous material 

 

ADDITIONAL DIAGNOSTIC TESTS: 

• Immunohistochemistry: Cytokeratin AE1/AE3 (pancytokeratin), EGFR, Lewis Y, CEA, Tag 72, and erbB-2 are all reportedly immunoreactive 
• Adenocarcinomas of oviduct origin are immunoreactive for ovalbumin, progesterone, and estrogen receptors

 

DIFFERENTIAL DIAGNOSIS:

• Oviductal adenoma (does not occur in ovary)
  • Soft, sessile or pedunculated, polypoid masses up to 1 cm in size 
  • Expansile, and glands may be somewhat irregular in orientation, but not invasive 

 Gross differentials for ovarian neoplasms in birds:

• Adenocarcinoma of unknown origin
• Lymphoma
• Granulosa cell tumor: Can be very large; generally attached to the ovary by a thin stalk, yellow, lobulated, round, and encapsulated by a smooth, glistening membrane, friable; often with hemorrhage and necrosis; Call-Exner bodies may be present
• Arrhenoblastoma: Seminiferous tubules proliferating within ovarian stroma; associated with sex reversal in hens; variable degrees of spermatogenesis
• Leiomyoma of the mesosalpinx: Ovarian, oviduct and uterine tumors; grow on the peritoneal surface of the oviduct or in the mesentery; single, firm, encapsulated, round masses; occur in flocks on 17 beta-estradiol
• Mesotheliomas: Lack glandular structures
• Myelocytomatosis (myeloid leukosis): Associated with avian leukosis

 

COMPARATIVE PATHOLOGY: 

• Humans: Chickens serve as a model of spontaneous ovarian adenocarcinoma
• Turkeys: Occasionally diagnosed with ovarian and oviduct adenocarcinomas
• Canine: Ovarian adenoma/adenocarcinoma is rare
  • Tumor of the surface celomic epithelium
  • Only occur in the bitch as papillary cystadenoma and cystadenocarcinoma
  • Cauliflower like appearance
  • Low cuboidal to columnar epithelium with stratification and low mitotic rate
• Snakes: Reproductive tumors more common in females than males
  • Ovarian carcinoma and oviductal adenocarcinoma 
    • Oviductal adenocarcinoma: Exophytic and papillary neoplasm composed of cords and acini; hemorrhage, necrosis, and inflammation may be present; biologic behavior is variable
• Alpaca: Oviductal adenoma carcinoma with carcinomatosis reported in an adult alpaca (Womble, J Comp Pathol 2021)

 

REFERENCES: 

1. Barnes HJ, Fletcher OJ, Abdul-Aziz T. Chapter 13: Reproductive System. In: Abdul-Aziz T, Fletcher OJ, Barns HJ, eds. Avian Histopathology. 4th ed. Madison, WI: Omnipress; 2016: 592, 610-612.
2. Hafner S, Reece RJ, Williams SM. Other Tumors. In: Swayne DE, ed. Diseases of Poultry. 13th ed., Ames, IA: Iowa State University Press; 2013: 605, 609-610.
3. Kennedy PC, Cullen JM, Edwards JF, Goldschmidt MH, Larsen S, Munson L, Nielsen S. Histological classification of the tumors of the genital system of domestic animals. In: Schulman FY, ed. World Health Organization, Histological Classification of Tumors of Domestic Animals. Vol 4. 2nd ed. Washington, DC: The Armed Forces Institute of Pathology, 1998: 24-28.
4. Ossiboff RJ. Serpentes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:906-907. 
5. Schlafer DH, Foster RA. Female Genital System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 3. 6th ed. St Louis, MO: Elsevier; 2016: 377.
6. Schmidt RE, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd Ed., Ames, IA: Wiley-Blackwell, 2015: 152, 155-156.
7. Shivaprasad HL. Miscellaneous Diseases. In: Boulianne M, ed. Avian Disease Manual. 8th ed., Jacksonville, FL; AAAP Inc.;2019:174. 
8. Womble M, Schreeg ME, Hoch A, et al. Concurrent Clostridial Enteritis and Oviductal Adenocarcinoma with Carcinomatosis in an Adult Alpaca (Vicugna pacos). J Comp Pathol. 2021;189:52-58.

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