Conference 15 - 2014 Case: 03 20150121

Signalment:

22-month-old female Syrian hamster, Mesocricetus auratusControl hamster from an experimental study

Gross Description:

No significant gross lesions were seen.

Histopathologic Description:

Ovary: The normal ovarian architecture is effaced and compressed by an encapsulated and well differentiated neoplasm. The neoplasm is composed of polygonal neoplastic cells arranged in nests, sheets, and cords supported by moderate fibrovascular stroma. Neoplastic cells have variably distinct cell borders and moderate amounts of foamy to fibrillar eosinophilic cytoplasm. Nuclei are round to oval with finely stippled chromatin and 2-3 distinct nucleoli. Mitotic figures average 1-2 per HPF and neoplastic cells often undergoes individual cell necrosis. Cellular pleomorphism is characterized by mild anisokaryosis. The adjacent stroma, bursa, and adipose tissue are infiltrated by low to moderate numbers of neutrophils, macrophages, lymphocytes and low numbers of mast cells. The lumen of the oviduct and uterus have moderate numbers of neutrophils admixed with epithelial cells, cellular debris and amphophilic fibrillar material.

Morphologic Diagnosis:

Ovary: Granulosa cell tumor

Condition:

Granulosa cell tumor

Contributor Comment:

Granulosa cell tumors are the most common sex-cord stromal tumors reported in domestic animals and have been reported in horses, cows, and dogs, and laboratory animals such as non-human primates, mice, and rats.(15,10,6) They are usually unilateral and benign in mares.(14) Malignant granulosa cell tumors have been reported in cows, dogs, cats, and laboratory mice.(2,5,12,18) Clinical signs associated with granulosa cell tumor in mares include anestrus, stallion-like behavior, and nymphomania. In mares, neoplastic granulosa cells produce inhibin a peptide hormone that may cause atrophy of the contralateral ovary.(15) Granulosa cell tumors are the most common ovarian tumors of Syrian hamsters.(8,13) Occurrence of both benign and malignant granulosa cell tumors in Syrian hamsters have been reported.(11)

In humans, granulosa cell tumors represent 2-5% of all ovarian tumors and usually have clinical features of hyperestrogenism.(16) Mutations in transcription factor FOXL2 is pathognomonic for adult-type granulosa cell tumors in humans.(17) Further, 17β-estradiol, inhibin, and mullerian inhibiting substance are considered to be reliable diagnostic and prognostic markers in humans.(8) While inhibin-α is a reliable marker in canine granulosa cell tumors(14) calretinin, GATA-4, and neuron-specific enolase are consistently expressed in non-human primate granulosa cell tumors.(3) No such markers have been reported in Syrian hamsters.

JPC Diagnosis:

1. Ovary: Granulosa cell tumor.
2. Oviduct: Salpingitis, suppurative, diffuse, moderate, with ductular ectasia.

Conference Comment:

The common occurrence of granulosa cell tumors in hamsters and its histologic difference from those which occur in domestic animals makes this a noteworthy case. The common histologic patterns are follicular (microfollicular and macrofollicular), insular, trabecular, and diffuse. The distinctive microcavities containing eosinophilic material lined by a rosette arrangement of granulosa cells are known as Call-Exner bodies and occur most commonly in the microfollicular pattern.(7) This type of arrangement is observed in early stages of bovine neoplasms, but less common in other species.(15) These tumors have a very characteristic gross presentation, especially in the mare, composed of numerous cysts with areas of solid white or yellow content. The cystic cavities are often observed histologically lined by granulosa cells and surrounded by a variable population of thecal cells, and often identified as granulosa-theca cell tumors.(15) In our sections, the neoplasm is a densely cellular population of granulosa cells in nests and packets, with each outlined by a fine fibrous stroma. No cystic cavities or Call-Exner bodies are present in this particular case, which may be indicative of its species-specific differences.

The interesting aspect of sex cord-stromal tumors is their ability to produce a variety of hormones and induce corresponding clinical signs. The contributor mentioned those exhibited by mares, and recent publications have demonstrated increased levels of testosterone and inhibin can be useful in obtaining a presumptive diagnosis.(4) Additionally, anti-M+â-+llerian hormone concentrations are elevated in mares and cows with these neoplasms.(1,4) Estrogen and progesterone may also be secreted, as cystic endometrial hyperplasia and pyometra are common in bitches with sex cord-stromal tumors.(15) In this case, we believe the oviduct and uterus are moderately distended, and there is suppurative inflammation in some sections within the oviduct. The relationship of these inflammatory changes with the ovarian neoplasm is unclear.

References:

1. Ball BA, Almeida J, Conley AJ. Determination of serum anti-Mullerian hormone concentrations for the diagnosis of granulose-cell tumours in mares. Equine Vet J. 2013;45(2):199-203.

2. Beamer WG, Hoppe PC, Whitten WK: Spontaneous Malignant Granulosa Cell Tumors in Ovaries of Young SWR Mice. Cancer Res. 1985:45(11 Part 2):5575-5581.

3. Durkes A, Garner M, Juan-Sall+â-¬s C, Ramos-Vara J: Immunohistochemical Characterization of Nonhuman Primate Ovarian Sex CordStromal Tumors. Vet Pathol. 2012:49(5):834-838.

4. Gee EK, Dicken M, Archer RM, Herdan CL, Pauwels FE, Drayton BM. Granulosa theca cell tumour in a pregnant mare: concentrations of inhibin and testosterone before and after surgery. N Z Vet J. 2012;60(2):160-163.

5. Gelberg HB, McEntee K: Feline Ovarian Neoplasms. Vet Pathol. 1985:22(6):572-576.

6. Gregson RL, Lewis DJ, Abbott DP: Spontaneous ovarian neoplasms of the laboratory rat. Vet Pathol. 1984:21(3):292-299.

7. Kennedy PC, Cullen JM, Edwards JF, et. al. Histological Classification of Tumors of the Genital System of Domestic Animals. 2nd series, Vol. 4. Washington, D.C.: Armed Forces Institute of Pathology; 1998:24-25.

8. Kondo H, Onuma M, Shibuya H, Sato T: Spontaneous tumors in domestic hamsters. Vet Pathol. 2008:45(5):674-680.

9. Kottarathil VD, Antony MA, Nair IR, Pavithran K: Recent advances in granulosa cell tumor ovary: a review. Indian J Surg Oncol. 2013:4(1):37-47.

10. Maclachlan NJ, Kennedy PC: Tumors of the Genital Systems, Sex-cord stromal tumors. In: Meuten DJ, ed. Tumors in Domestic Animals. 4 ed. Ames, IA: Iowa State Press; 2002: 550-551.

11. McInnes EF, Ernst H, Germann P-G: Spontaneous Neoplastic Lesions in Control Syrian Hamsters in 6-, 12-, and 24-Month Short-Term and Carcinogenicity Studies. Toxicol Pathol. 2012.

12. Patnaik AK, Greenlee PG: Canine Ovarian Neoplasms: A Clinicopathologic Study of 71 Cases, Including Histology of 12 Granulosa Cell Tumors. Vet Pathol.1987:24(6):509-514.

13. Pour P, Mohr U, Althoff J, Cardesa A, Kmoch N: Spontaneous tumors and common diseases in two colonies of Syrian hamsters. III. Urogenital system and endocrine glands. J Natl Cancer Inst. 1976:56(5):949-961.

14. Riccardi E, Greco V, Verganti S, Finazzi M: Immunohistochemical Diagnosis of Canine Ovarian Epithelial and Granulosa Cell Tumors. J Vet Diagn Invest. 2007:19(4):431-435.

15. Schlafer DH, Miller RB: Female genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. St. Louis, MO: Saunders Elsevier; 2007: 450-451.

16. Schumer ST, Cannistra SA: Granulosa Cell Tumor of the Ovary. J Clin Oncol. 2003:21(6):1180-1189.

17. Shah SP, K+â-¦bel M, Senz J, Morin RD, Clarke BA, Wiegand KC, et al.: Mutation of FOXL2 in Granulosa-Cell Tumors of the Ovary. N Engl J Med. 2009:360(26):2719-2729.

18. Zachary JF, Haliburton JC: Malignant Granulosa Cell Tumor in an Angus Cow. Vet. Pathol.1983:20(4):506-509.