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Joint Pathology CenterJoint Pathology Center Veterinary PathologyVeterinary Services Pathology Services WEDNESDAY SLIDE CONFERENCE 2020-2021 WEDNESDAY SLIDE CONFERENCE 2019-2020 Conference 16 C o n f e r e n c e 16 29 January 2020 27 January, 2021 Dr. Ingeborg Langohr, DVM, PhD, DACVP Professor Department of Pathobiological Sciences Louisiana State University School of Veterinary Medicine Joint Pathology Center Baton Rouge, LA Silver Spring, Maryland CASE I: CASE S1809996 1: MK1905835 (JPC 4135077 (4151722). -00) Microscopicsome Description: of the rosettes The interstitiumcontain PAS positive within thematerial. section Theis diffusely stromal cells infiltrated are elongated. by Stroma Signalment:Signalment: A 3-month -old, male, mixed- moderateis to composedlarge numbers of elongated of predominantly spindle cells and breed pig18 (Sus-year scrofa-old )female squirrel monkey, Saimirimononuclear numerous cells alongtubules. with Mitotic edema . Therefigures are not sciureus is abundantobserved type II. pneumocyte hyperplasia History: This pig had no previous signs of lining alveolar septae and many of the illness, andHistory: was found dead. Remaining ovary has hyperplasia of follicles the Euthanized for because of cardiac enlargementalveolar spacespredominance have central of areaswhich of lack ova and/or Gross Pathologyand symptoms: Approximately of heart failure. 70% of necrotic macrophagesprogression to admixed antral follicles. with other The periphery of the lungs, primarily in the cranial regions of mononuclearthe ovary cells hasand small fewer numbers neutrophils. of primary follicles. the lobes,Gross were Pathology:patchy dark red, and firm OccasionallyThe thereuterus is free has nuclear normal basophilic endometrium comparedThe to theheart more was severelynormal areasenlarged of lung.at 1.25% of body myometrium. weight and thoracic and peritoneal effusion was Laboratorypresent. results: The left Porcine ovary reproductivewas found to be enlarged and respiratorydue to syndrome7 mm diameter, (PRRS firm,) PCR tan wasnodule with an positive fromirregular splenic surface. tissue, The and cut PRRSsurface IHCwas solid. was strongly immunoreactive within the cytoplasmLaboratory of macrophages results: in the affected lung tissue.N/A Porcine influenza virus PCR, porcine circovirus – 2 IHC, and Microscopic description: Mycoplasma(Slides hyopneumoniae may have one IHCor two were sections all of ovary) negative. TheSmall tumor numbers is well of- demarcatedE. coli were and compresses isolated fromadjacent the cranioventralovary. It consists lung of with widely separated aerobic culture.follicle - like structures separated by bands of Lung, pig (HE, 6X). There is diffuse consolidation of stroma. Most of the follicles are oval but some arethe lung. At low magnification, airway are filled with irregular in shape. Some are cystic. Neoplasticexudate and the pleura and interlobular connective cells line up perpendicular to the stroma;tissue are mildly expanded. occasional rosettes are present. They are Ovary, squirrel monkey. The left ovary is enlarged with a composed of cuboidal cells with scant 7mm nodule. (Photo courtesy of: NIH, Division of Veterinary Medicine, Diagnostic and Research Services Branch, 28 eosinophilic cytoplasm. Nuclei are round to oval Library Drive, Bethesda, Maryland 20892) 1 with inconspicuous nucleoli. PAS stain reveals with abundant cytoplasm.3,4,7,12 The latter two tumors are benign. Also described in older squirrel monkeys is the proliferation of anovulatory follicle-like clusters of granulosa cells in the opposite ovary.3 An early paper describes granulosa cell aggregates in both ovaries; this may have been the hyperplastic lesions that we see in this case.14 A retrospective study of archived squirrel monkey ovaries found Ovary, squirrel monkey: Two sections of the affected ovary the granulosa cell proliferation was consistent and a section of fimbria are submitted for examination. (HE, feature starting at 8 years old. These occur prior 6X) to loss of reproductive ability and may be a Contributor’s morphologic diagnosis: feature of aging ovaries in this species. They are Ovary: Granulosa cell tumor. positive for anti-Müllerian hormone.16 Ovary: Granulosa cell hyperplasia, senescent change. In this case, the tumor is primarily solid with abundance of very cellular stroma suggests a Contributor’s comment: granulosa-theca tumor. The ovary of a different, Ovarian tumors can arise from the outer 17-year-old squirrel monkey has similar epithelium (papillary cystadenoma, proliferation of anovulatory follicles. cystadenocarcinoma), the interior sex cords and stroma, and germ cells (dysgerminoma and Contributing Institution: teratoma). “Sex cord” is a term that denotes the NIH, Division of Veterinary Medicine possible embryologic origin of cells in the Diagnostic and Research Services Branch mesonephros.14 SCSTs are the most commonly 28 Library Drive reported ovarian tumor in macaques.4 They have Bethesda, Maryland 20892 been reported in rhesus, stump-tailed and bonnet macaques, baboons, gibbons and JPC diagnosis: chimpanzees.3,12 Ovary: Sex cord stromal tumor (granulosa-theca cell tumor). Sex cord stromal tumors (SCST) are classified as either granulosa tumor (GCT), thecoma, or JPC comment: luteoma. GCT are often cystic and exude bloody Granulosa cell tumor (GCT) is most common in fluid on cut section. They can be hormonally the mare,7,15 but also occurs with some frequency active and cause either hyperestrogenism or in the cow,7,15 the queen,2 the gerbil,9 and masculine behavior. They can develop from nonhuman primates.5 Less frequently, GCT has ovarian remnants. The follicular structures that they form often have rosettes with eosinophilic material in the center, (Call-Exner bodies). They can be either benign or malignant. GCT are commonly reported in cows, mares and dogs.7,14 Inhibin produced by GCT which can cause atrophy of the opposite ovary.16 Other subtypes of SCST’s include thecomas, luteoma, and Brenner’s tumor (a type of epithelial Ovary, squirrel monkey. The neoplasm is composed of stromal tumor). Thecomas have spindle shaped granulosa cells in two distinct patterns – large follicles and cells that are often vacuolated due to lipid. They intervening nests and packets. (HE, 100X) tend to be solid. Luteomas have luteinized cells been reported in the rock hyrax,1 the Longjaw mudsucker fish (Gillichthys mirabilis),8 and some prosimians (Lesser bushbaby, Pygmy slow loris, Slender loris).11 In humans, GCT are classified into two groups. The first primarily affects post-menopausal women and has an association with a mutation in FOXL2, and the second is a juvenile type that primarily occurs in children and young adults and Ovary, squirrel monkey: Neoplastic cells between follicles is not associated with FOXL2 mutation. are arranged in nest and packets on a fine fibrovascular Immunohistochemical stains such as inhibin, stroma (HE, 380X) calretinin, steroid-factor-1 (SF-1), and FOXL2 MicroRNA 126 (miR-126) embeds in the are usually positive in sex cord-stromal tumors, genomic region of EGFL7, silencing expression while epithelial membrane antigen (EMA) is of this gene in pleural mesothelioma. Using usually negative. However, the availability of fluorescent in situ hybridization (FISH), it was validated products may limit their use in discovered that expression of miR-126 was veterinary cases.6 significantly lower in malignant and benign GCT tissues than non-neoplastic ovarian cyst tissue. A With a variety of hormone receptors on granulosa mouse model with overexpression of miR-126 cells, and the hormones produced by these cells, resulted in significantly smaller tumors than in hormone therapy has been explored as a control mice, suggesting the possibility of miR- treatment modality. Previous methods have 126 as a new biomarker for GCT. This also may 16 focused primarily on gonadotropin releasing represent a future therapeutic avenue to explore. hormone (GnRH) agonists/antagonists, estrogen antagonists, and synthetic progestins, but have Conference discussion included the paraovarian met with limited success. Androgen antagonism cyst in section, and its possible origins. Cysts has seen success in prostate, breast, and arising from the mesonephric tubules include endometrial carcinoma, but has efficacy in the cystic epoophoron, cyst rete ovarii, extraovarian treatment of GCT has not yet been explored. Also rete cyst, and cystic paroophoron. Mesonephric recently explored is immunotherapy targeting the duct cysts arise from peristent mesonephric ducts, programmed cell death 1/programmed cell death and fimbrial cysts and hydatid of Morgagni arise ligand 1 relationship, with one study from paramesonephric ducts. (NCT02923934) currently in Phase 2 trials.12 This case includes a prominent thecal component, Epidermal growth factor-like domain-containing which is consistent with many canine sex cord protein 7 (EGFL7) is a critical oncogene in the stromal tumors. While often called simple development of several cancers and its expression granulosa cell tumors, in order to more fully is a predictive biomarker for cervical cancer. capture the thecal component we prefer the diagnosis above. References: 1. Agnew D, Nofs S, Delaney MA, Rothenburger JL. Xenartha, Erinacoemorpha, Some Afrotheria, and Phloidota. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA:Elsevier. 2018:525. 2. Agnew DW, MacLachlan NJ. In: Tumors of Ovary, squirrel monkey: Follicles contain one or more
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