Tumors of the Genital Systems

16
Tumors of the Genital Systems


Dalen W. Agnew1 and N. James MacLachlan2


1Michigan State University, USA,


2University of California, Davis, USA,


INTRODUCTION AND EMBRYOLOGY


An understanding of the embryology of the reproductive tract is relevant to classification of the various tumors that occur therein. The determination of genetic sex is fixed at the time of fertilization. The genetic sex is then imposed on the undifferentiated gonad. While the mechanism by which this occurs is not entirely clear, the Y chromosome clearly is male‐determining in all eutherian mammals, and a DNA‐binding protein encoded by the Y chromosome (testis‐determining factor) exerts a major (but not necessarily exclusive) influence in conversion of the undifferentiated gonad to a testis. Ovarian differentiation occurs in the absence of a Y chromosome and at a later gestational age than testicular differentiation.1 All other differences between the sexes are secondary effects due to hormones or factors produced by the gonads. To a considerable extent the determination of a sex is, therefore, equivalent to testis determination, although much remains to be determined regarding the mechanisms and regulation of gonadal differentiation.2–4


The urogenital system arises from mesoderm. Primordial germ cells originate in the fetal yolk sac and migrate into the gonadal ridge. The gonads then form within the gonadal ridge. The nongonadal portion of the genital tract of both sexes derives from either the mesonephric (Wolffian) or paramesonephric (Mullerian) ducts, and the bipotential sinusal and external genital primordia. The paramesonephric ducts arise as invaginations of the coelomic epithelium adjacent to the urogenital ridge, whereas the mesonephric ducts arise from the mesonephros. Female differentiation occurs in the absence of male gonadal hormones, which are secreted by the fetal testicle; thus, in the male fetus, Sertoli cells in the fetal testicle secrete anti‐Mullerian hormone that brings about Mullerian duct regression, and interstitial (Leydig) cells secrete testosterone, which prevents mesonephric duct regression and so induces development of the male tubular tract. Dihydrotestosterone induces development of the male external genitalia. Female differentiation and atrophy of the mesonephric duct system occurs in the absence of these male gonadal hormones.2–4


Interest has grown over the last 10 years or more on the effects of dietary and environmental toxins on reproductive development and the development of tumors in the reproductive tract. Certainly, the role of dichlorodiphenyltrichloroethane (DDT) in the mid‐twentieth century and growing importance of other hormonally active compounds in the environment, such as bisphenol A and phthalates, should not be underestimated and further research may perhaps better define the significance of these agents in various reproductive diseases.5


Classification of tumors in this chapter is a modification of systems used in the World Health Organization (WHO) fascicle,6 as well as extensive reviews by McEntee, Foster and Ladds, and Schlafer and Miller.7–9


References



  1. 1. Sizonenko, P.C. (1993) Human sexual differentiation. In Reproductive Health, Vol. 2 (eds. A. Campana, J.J. Dreifuss, et al.). Ares Serono Symposia Publications, Rome.
  2. 2. Greenfield, A. and Koopman, P. (1996) SRY and mammalian sex determination. Curr Top Dev Biol 34:1–23.
  3. 3. Fritsch, M.K. (2007) Reproductive systems. In Potter’s Pathology of the Fetus, Infant and Child, Vol. 2 (ed. E. Gilbert‐Barness). Mosby Elsevier, Philadelphia, PA, pp. 1375–1452.
  4. 4. McClelland, K., Bowles, J., et al. (2012) Male sex determination: insights into molecular mechanisms. Asian J Androl 14:164–171.
  5. 5. Borchers, A., Teuber, S.S., et al. (2010) Food safety. Clin Rev Allergy Immunol 39:95–141.
  6. 6. Kennedy, P.C., Cullen, J.M., et al. (1998) World Health Organization. Histological Classification of Tumors of the Genital System of Domestic Animals. Armed Forces Institute of Pathology, Washington, D.C.
  7. 7. Schlafer, D. H. and Miller, R.B. (2007) Female genital system. In Pathology of the Domestic Animals, 5th edn., Vol. 3 (ed. G. Maxie). Elsevier Saunders, Philadelphia, PA, pp. 429–564.
  8. 8. McEntee, K. (1990) Reproductive Pathology of Domestic Animals. Academic Press, San Diego,CA.
  9. 9. Foster, R.A. and Ladds, P.W. (2007) Male genital system. In Pathology of the Domestic Animals, 5th edn., (ed. G. Maxie). Elsevier Saunders, Philadelphia, PA.

TUMORS OF THE OVARY


Introduction


Current classification of tumors of the gonads in domestic animals is primarily based upon the histological appearance of the tumor, specifically upon the similarity of the appearance of the neoplastic cells to cellular constituents of the normal gonad.1–4 Classification also is based on the purported embryological derivation of the predominant cellular constituent of each tumor; thus, tumors of the ovary (Box 16.1) are considered to arise from three broad embryological origins: (1) the epithelium of the ovary, which includes the lining (surface) epithelium of modified mesothelium, the rete ovarii, and in the bitch and some other species, the subsurface epithelial structures (SES); (2) the germ cells; and (3) the ovarian stroma including the sex cords (sex cord stromal or gonadostromal elements), which together contribute the endocrine apparatus of the ovary. There are also a group of rare tumors that are not readily classified on this basis. Furthermore, primary ovarian tumors must be distinguished from tumors that are metastatic to the ovary.


Germ cells (ova) that migrate from the fetal yolk sac into the gonadal ridge become surrounded by cords of cells termed the sex cords, which are precursors of the follicular granulosa in the developing ovary.5,6 Thus the association of germ cells and sex cords during development leads to the formation of primary follicles. The precise origin of the sex cords is conjectural, and it is unresolved if they are derived from the rete ovarii, primitive gonadal mesenchyme, or the mesothelial lining of the developing gonad.7–9 All of these structures ultimately are derived early in development from nephrogenic tissue, and it may be that the precise origin of the somatic elements of the ovary is species dependent.7 Sex cord stromal elements of the differentiated ovary include the theca and granulosa cells, as well as their luteinized derivatives. Subsurface epithelial structures (SES), also referred to as egg cords or tubules, or as cortical cords or tubules were first reported in the fetal and newborn dog, but have since been identified in several carnivore families, as well as in some species of primates and rodents. Their significance is unclear, but they may be involved in early oogenesis.10 Regardless, no differences have been described in their histologic or immunohistochemical (IHC) properties with those of the surface lining epithelium.11,12


The granulosa cell cords are another characteristic feature of the canine ovary, though they are not epithelial (see Figure 16.1A). They consist of elongate, spindle‐shaped cells arranged in tubules. Granulosa cell cords are most numerous near the corticomedullary junction, and enlarged, hyperplastic cords frequently are present adjacent to the medullary blood vessels of the ovary of older bitches.2,13

Micrograph of epithelial tumor of the ovary displaying granulosa cell cords pointed by arrows located between two follicles in the corticomedullary junction.
Micrograph of epithelial tumor of the ovary displaying normal subsurface epithelial structures in a bitch.
Micrograph of epithelial tumor of the ovary displaying cysts of SES.
Micrograph of epithelial tumor of ovary displaying cytokeratin IHC labeling of SES cysts denoting strong positive labeling of cells lining large cysts and smaller structures, with normal SES (near the surface).
Micrograph of epithelial tumor of the ovary displaying cystadenoma of the SES.
Micrograph of cystic rete ovarii displaying scant remnant of germinal structures.
Magnified micrograph of epithelial tumor of the ovary displaying some flattened epithelial cells retaining cilia, characteristic of the rete and not of SES.
Photo of epithelial tumors of the ovary displaying proliferative cauliflower-like growths that project from the surface of the ovary to involve adjacent structures.
Photo of epithelial tumors of the ovary that exfoliate and disseminate through the peritoneal cavity as carcinomatosis and produce ascites.
Micrograph of ovarian adenocarcinoma consisting of arboriform papillae that project into the lumen of cystic cavities and subclassified as papillary (papillary carcinoma).
Magnified micrograph of the papillary carcinoma demonstrating epithelial cells lining arboriform trabeculae.
Micrograph of adenocarcinoma in ovary characterized as cystic (cystadenocarcinoma).

Figure 16.1 Epithelial tumors of the ovary. (A) Granulosa cell cords (arrowheads) located between two follicles in the corticomedullary junction. Ovary, dog. (B–E) Subsurface epithelial structures (SES), ovary, dog. (B) Normal SES in a bitch. (C) Cysts of the SES are rarely more than 5 mm in diameter, and can be difficult to distinguish from cystic epithelial neoplasms. Cysts tend to be multiple, bilateral, and lined by a single layer of epithelium, whereas tumors can be single or multiple, uni‐ or bilateral, and may have a complex arboriform pattern. (D) Cytokeratin IHC labeling of SES cysts demonstrates strong positive labeling of cells lining the large cysts and smaller structures, including normal SES (near the surface). (E) Cystadenoma of the SES. (F,G) Rete, ovary, guinea pig. (F) Cystic rete ovarii. Note the scant remnant of germinal structures at the lower right margin. Tumors and cysts of the rete ovarii may be distinguished from those that arise from the surface epithelium or SES only on the basis of their location in the medulla of the ovary, as their histological appearances are similar. IHC for S100 or PLAP may be helpful. If present, cilia suggest derivation from the rete. (G) Higher magnification of previous image shows some flattened epithelial cells retaining cilia, characteristic of the rete and not of SES. (H–L) Adenocarcinoma, ovary, dog. (H) Adenocarcinomas can be either uni‐ or bilateral, and characteristically appear as cystic, multinodular enlargements. They are typically composed of multiple cysts interspersed between solid regions. Carcinomas also may appear as proliferative cauliflower‐like growths that project from the surface of the ovary to involve adjacent structures. (I) Carcinomas may exfoliate and disseminate through the peritoneal cavity as carcinomatosis and produce ascites. Once implantations have occurred throughout the abdomen, identification of the origin requires careful examination of both ovaries. (J) Ovarian adenocarcinoma. These usually consist of arboriform papillae that project into the lumen of cystic cavities. This example may be further subclassified as papillary (papillary carcinoma). (K) Higher magnification of the papillary carcinoma shown in (J), demonstrating epithelial cells lining arboriform trabeculae. (L) This adenocarcinoma would be further characterized as cystic (cystadenocarcinoma), though both forms may exist in the same tumor.


Epithelial tumors


Tumors that arise from the ovarian epithelium occur in all domestic species.14–21 Most epithelial tumors of the ovary arise from the surface epithelium and, in the bitch, the SES (both are modified mesothelium), but they can arise less frequently in the hilus of the ovary from the rete ovarii. Epithelial tumors of the ovary are common only in the bitch, presumably because tumors of the SES are most common and these are unique to the canine among the domestic species.13


The rete ovarii includes intra‐ and extra‐ovarian portions. Cysts of the rete ovarii are relatively common in both the bitch and queen, and adenomatous hyperplasia of the ciliated lining epithelium sometimes accompanies cystic dilatation of the structure. The rete ovarii enlarges with age, and distinction between adenomatous hyperplasia and rete adenoma is arbitrary, with larger lesions being considered adenomas.2


In the bitch, the SES are very prominent at certain stages of development in the fetal ovary and again increase in prominence and number with advancing age. Hyperplasia and cystic dilatation of the SES occur commonly in geriatric bitches, often with papillary infolding of the lining epithelium. Cystic dilation can become very extensive, such that the entire cortex of the affected ovary is involved. Cysts arising from the SES are rarely more than 5 mm in diameter, but these cysts can be difficult to distinguish from cystic epithelial neoplasms. Cysts tend to be multiple, bilateral, and lined by a single layer of epithelium, whereas tumors can be single or multiple, uni‐ or bilateral, and may have a complex arboriform pattern that is not consistent with SES cysts.2,13,22


The surface lining epithelium of the canine ovary also normally changes with age, progressing from simple cuboidal to pseudostratified columnar.


Sites and gross morphology


Epithelial tumors of the ovary can be either uni‐ or bilateral, and characteristically appear as cystic, multinodular enlargements. The cut surface typically has multiple cysts that contain thin yellow to brown fluid, interspersed between solid regions. Carcinomas also may appear as proliferative cauliflower‐like growths that project from the surface of the ovary to involve adjacent structures (Figure 16.1H). They may also exfoliate and disseminate through the peritoneal cavity as carcinomatosis and produce ascites (Figure 16.1I). Small tumors may be localized to their site of origin; specifically, those that arise from the surface epithelium or the SES initially are confined to the cortex of the ovary, whereas those that arise from the rete ovarii are initially confined to the medulla adjacent to the hilus of the ovary.


Primary epithelial tumors of the ovary must be distinguished from those that arise in the oviduct and endometrium that involve the ovary secondarily, which can be difficult if based solely on histological criteria.23 If an epithelial tumor is present in the ovary and one is also present in the oviduct or uterus, then size of the largest tumor is the likely the site of origin; furthermore it is rare for an ovarian tumor to metastasize to the uterus or oviduct. The distinction between these tumors is important as ovarian carcinomas tend to be more malignant and aggressive; however, this impression requires epidemiologic confirmation.


Histological features


Both adenomas and carcinomas of the ovary usually consist of arboriform papillae that project into the lumen of cystic cavities (Figure 16.1J). They sometimes are further subclassified as papillary (papillary adenoma or carcinoma; Figure 16.1 ,K) or cystic (cystadenoma or cystadenocarcinoma; Figure 16.1L), but in animals generally without further classification into the serous (low and high grade), endometrioid, clear cell, and mucinous types that are prognostically important in women.23 The papillae that characterize these tumors consist of connective tissue stalks that are lined by single or multiple layers of cuboidal or columnar epithelial cells that may or may not be ciliated. The wall of each cyst usually is lined by single or multiple layers of epithelium, and the lumen of the cyst may contain proteinaceous material. Anaplastic carcinomas that lack the characteristic arboriform pattern occur occasionally and consist of broad, disorganized sheets of neoplastic cells.


In the absence of metastasis or obvious vascular invasion, malignant tumors (ovarian carcinomas) are identified as such on the basis of their larger size, the presence of foci of necrosis and hemorrhage, cellular atypia and a tendency for the neoplastic cells to pile up on one another, mitotic count, and in particular, stromal invasion. The cyst wall, the connective tissue papillae, or the stroma of the ovary may be invaded and these invasions are features of malignancy. Extension of the tumor into adjacent structures, such as the ovarian bursa or peritoneum, is unequivocal evidence of malignancy.


Epithelial tumors of the canine ovary usually arise from the SES (Figure 16.1B–D).13 The incidence of hyperplasia of the SES also increases with age; thus neoplasia and hyperplasia of the SES can occur together and may be difficult to differentiate. Whereas the SES do not normally extend into the ovary beyond the level of the primary follicles, tumors of the SES can invade and efface the gonad or protrude from its surface. Adenomas of the SES (SES adenoma; Figure 16.1E) may be distinguished from hyperplasia because of the focal nature of the former as compared to the multicentric distribution of SES hyperplasia, although the two conditions may coexist in the ovaries of older bitches. Similarly, distinction of age‐related hyperplasia of the rete ovarii from adenoma of this structure is difficult, and it usually is based arbitrarily on the size of the lesion (though a specific size cut‐off has not been determined). Tumors of the rete ovarii may be distinguished from those that arise from the surface epithelium or SES only on the basis of their location in the medulla of the ovary, as their histological appearances are similar, though IHC may also be helpful (Figure 16.1F). If present, cilia suggest derivation from the rete (Figure 16.1G).


Immunohistochemistry


IHC staining is used increasingly to characterize ovarian tumors of animals but it often does not unambiguously identify potential cells of origin, nor does it distinguish hyperplasia from neoplasia.24,25 Hyperplastic and neoplastic proliferations of the ovarian epithelium, including the SES, usually stain strongly for cytokeratins (Figure 16.1B); however, they also may stain positively for vimentin, which is a reflection of the mesothelial derivation of the ovarian surface (lining) epithelium. Placental alkaline phosphatase (PLAP) has been used to distinguish surface epithelial cysts and tumors and SES from other epithelial tumors cysts and tumors and SES from other epithelial tumors, including cysts of the rete ovarii.12 IHC for S100 has also distinguished rete cysts (positive) from cysts of the surface epithelium.12 The neoplastic cells in sex cord stromal tumors (see below) also characteristically stain positively for vimentin, and are variably positive for cytokeratin, requiring evaluation for other markers. For example, the neoplastic cells in equine benign granulosa cell tumors (sex cord stromal tumors), strongly express vimentin but in contrast to epithelial neoplasms of the ovary, the tumor cells also express inhibin‐α as well as glutathione S‐transferase α, and c‐erbB‐2 oncogene.26 Inhibin‐α is useful to distinguish sex cord stromal tumors from ovarian epithelial neoplasms in bitches and mares, although it is important to assess multiple areas of the neoplasm as labeling may vary regionally.21,27,28


Recent studies indicate that canine ovarian epithelial tumors express the IHC marker HBME‐1 (Hector Battifora mesothelial epitope), whereas sex cord stromal tumors do not.29 Although there has been a substantial effort to associate estrogen and progesterone receptor expression with malignancy in numerous animal reproductive cancers, to date there has been no link equivalent to that documented in women.


Biological behavior


Adenomas and carcinomas of the ovary cause enlargement of the affected gonad that may cause the animal discomfort. Metastasis of carcinomas frequently occurs transcoelomically after rupture of cysts within the neoplasm or invasion of the tumor through the capsule of the ovary, leading to implantation of the neoplasm within the abdominal cavity (carcinomatosis; Figure 16.1I) and often subsequent ascites and abdominal distention from lymphatic blockage. Metastasis also can occur after lymphatic or venous invasion. Although data are lacking on the frequency of metastasis of any of the epithelial tumors to regional lymph nodes, lungs, and other organs, it has been reported in most domestic species, though the site of origin has not been clearly identified.


Sex cord stromal tumors


These are tumors that are derived from, or that histologically resemble, the normal cellular constituents of the endocrine apparatus of the ovary. Specifically, sex cord stromal tumors are considered to arise from the theca, follicular granulosa, or their luteinized derivatives. The precise embryological origins of these structures are not certain and might be species specific.6,7 The granulosa cell cords are another characteristic feature of the canine ovary. They consist of elongate, spindle‐shaped cells arranged in tubules. Granulosa cell cords are most numerous near the corticomedullary junction, and enlarged, hyperplastic cords frequently are present adjacent to the medullary blood vessels of the ovary of older bitches.2,13


Included in this group of tumors are neoplasms with a diverse array of histological appearances that have been given an equally diverse, and confusing, array of names, including granulosa cell tumor, granulosa‐theca cell tumor, luteoma, thecoma, Sertoli cell tumor of the ovary, Leydig cell tumors, androblastoma, arrhenoblastoma, interstitial gland tumor, and lipid cell tumor of the ovary. The term sex cord stromal (gonadostromal) is preferred as it reflects the uncertainty of the embryological and histogenetic origin of cells in these tumors, which may include gonadal stroma, follicles, sex cords, interstitial glands of the ovary, and undifferentiated rest cells. In many of these tumors there is coexistence of multiple cell types in the same tumor.30,31


Tumors derived from sex cord stromal tissues of the ovary share the potential to be hormonally active and to secrete steroid hormones.17,18,20,26,32–37 They are the principal, but not exclusive, source of hormonally functional ovarian tumors (Figure 16.2). Ovarian sex cord stromal tumors are capable of producing a diverse mixture of female and male sex hormones as, in the normal ovary for example, progesterone is converted in the theca interna to androgen by cytochrome P45017α, and in turn, androgens are converted to estrogen by P450 aromatase in the follicular granulosa in a process termed aromatization.38

Line graphs of days vs. estradiol (filled circle) (left) and testosterone (open circle) (right) profiles in a mare with an ovarian tumor before and after surgery.

Figure 16.2 Testosterone (open circle) and estradiol‐17‐beta (filled circle) profiles in a mare with an ovarian tumor before and after surgery (Day 0). The mare exhibited male‐like behavior and no cyclical ovarian activity before surgery.


(Source: Stabenfeldt, G.H., Hughes, J.P., et al. (1979) Clinical findings, pathological changes, and endocrinological secretory patterns in mares with ovarian tumors. J Reprod Fert Suppl 27:277–285. Reproduced with permission of Society for Reproduction and Fertility.)


Sex cord stromal tumors can produce varying amounts of progesterone, estrogen, testosterone, and inhibin (made up of two forms, A and B, distinguished by the α and β subunits),39 and these hormones can profoundly influence the reproductive behavior of the affected animal and induce changes in extra‐ovarian tissues. Animals with hormonally productive sex cord stromal tumors often exhibit abnormal reproductive behavior that may manifest as persistent anestrus, intermittent or continuous estrus, or masculinization. Bitches with sex cord stromal tumors also may manifest signs of hyperestrinism, including endocrine alopecia, bone marrow suppression with consequent nonregenerative anemia, leukopenia following an initial period of leukocytosis, thrombocytopenia and hemorrhagic diathesis, and cystic endometrial hyperplasia.1,2,15,19,20,40 These changes are reversible by removal of the tumor. Hyperadrenocorticism also has been described in a bitch with an ovarian sex cord stromal tumor.41


Tumors of the endocrine‐producing tissue of the ovary are not readily classified on the basis of their endocrine products, as the types and amounts of the different hormones secreted by individual tumors vary considerably within a tumor or within the day if measured. The products of ovarian tumors other than steroid hormones also can influence reproductive behavior. For instance, mares with granulosa‐theca cell tumors exhibit abnormal reproductive activity and atrophy of the contralateral gonad. It appears that inhibin, rather than elevated levels of plasma testosterone, is responsible for some of these effects. Inhibin is a normal glycoprotein secretory product of granulosa cells that decreases pituitary secretion of follicle‐stimulating hormone (FSH), and the high levels of inhibin in mares with granulosa cell tumors likely prevent normal FSH‐mediated stimulation of the unaffected ovary.37 Rarely, however, mares with granulosa‐theca cell tumors continue to cycle, and folliculogenesis occurs in the unaffected, contralateral ovary.42 Serum profiles of anti‐Mullerian hormone also may provide a useful biomarker for detection of sex cord stromal tumors in cattle and mares.43,44


Sites and gross morphology


With the possible exceptions of the sow and bitch, sex cord stromal tumors are the most common ovarian neoplasms in domestic species. They clearly are the most common ovarian tumors in the cow and mare. Sex cord stromal tumors are more common in older animals but occur in animals of all ages and even the very young. These frequently are large tumors that are either multinodular or symmetrical, uni‐ or bilateral, and they include both solid and cystic areas, with or without scattered areas of hemorrhagic necrosis. The cysts frequently contain yellow to red thin fluid. Some tumors contain a single large central cystic cavity. Analysis of the cyst fluid cytologically or hormonally has been used in human medicine, but no published studies have been performed in animals and there is no evidence that it might help establish a diagnosis or prognosis.


Histological types


Classification of sex cord stromal tumors is based on the appearance of the predominant cell population and its resemblance to the normal constituents of the ovarian endocrine apparatus. It must be stressed, however, that more than one cell type often is present in a single neoplasm and that the histological appearance of an individual tumor may vary markedly in different areas. Inhibin‐α can be especially effective as an IHC marker of these tumors.26,29 Antibodies against Melan‐A, commonly used to identify melanomas, also shows inconsistent labeling of granulosa cell tumors, but not germ cell or epithelial neoplasms.45 An immunodiagnostic cocktail containing antibodies against Melan‐A, PNL2, TRP‐1, and TRP‐2, used for melanoma diagnostics, has also been used to label granulosa cell tumors.46 The specific epitope with which these antibodies react has not been demonstrated, and this may be an entirely spurious (but useful) cross‐reaction. In human studies, mRNA for Melan‐A has not been identified in steroid‐producing tissue, though the A103 anti‐Melan‐A antibody is strongly immunoreactive.47


Granulosa cell tumor

Granulosa cell tumor is the most common sex cord stromal tumor. It consists of irregular accumulations of granulosa cells separated by a supporting stroma of spindle cells, imparting a distinct resemblance to disorganized attempts at follicle formation. In some, the stroma resembles thecal tissue, giving rise to the designation granulosa‐theca cell tumor. Within the follicular structures are multiple layers of cells that resemble granulosa cells, with palisading at the periphery (Figure 16.3A). The follicular pattern may be less prominent in some tumors, with the neoplastic granulosa cells being arranged in solid sheets, cords, trabeculae, or nests (Figure 16.3B,C). A variety of patterns may occur in different areas within the same tumor. The appearance of some granulosa cell tumors, particulary in the bitch but also in the mare, closely resembles that of testicular Sertoli cell tumors, thus the designation of Sertoli cell tumor of the ovary for tumors with this appearance (Figure 16.3D,E). Tumor cells in this variant are spindle shaped and are arranged in tubules that frequently are separated by a fibrous stroma. Variably sized areas of apparent luteinization may occur in some granulosa‐theca cell tumors, especially in the mare; these areas are characterized by accumulations of polyhedral cells, with abundant vacuolated eosinophilic cytoplasm, that usually are prominent adjacent to the margins of follicular structures.

Photo of the granulosa cell tumor in horse’s ovary featuring large cavernous cysts.
Photo of the granulosa cell tumor in dog’s ovary, displaying areas of hemorrhage or necrosis.
Image described by caption.
Micrograph of granulosa cell tumor in dog’s ovary with cords embedded in dense fibrous stroma, producing Sertoli cell tumor-like pattern.
Magnified micrograph of granulosa cell tumor in dog’s ovary, displaying Sertoli-like cells stretching across a tubular structure.
Micrograph of luteoma in cat’s ovary, displaying multiple nodules which are well vascularized and composed of polygonal neoplastic cells with abundant granular cytoplasm and lipid vacuoles.
Magnified micrograph of luteoma in cat’s ovary.
Micrograph of thecoma in horse’s ovary, featuring spindle-shaped cells which are arranged in streams and bundles.
Micrograph of thecoma in dog’s ovary, featuring spindle-shaped and vacuolated cells which are often embedded in dense stroma.

Figure 16.3 Sex cord stromal tumors. (A) Granulosa cell tumor, ovary, horse. Note the large cavernous cysts, characteristic of this tumor in horses. (B) Granulosa cell tumor, ovary, dog. In dogs, granulosa cell tumors are more often solid, though there may also be large areas of hemorrhage or necrosis. (C) Photomicrograph of a benign, well‐differentiated, granulose cell tumor with multiple Call–Exner bodies. Ovary, dog. (D) Granulosa cell tumor, ovary, dog. Cords of poorly differentiated tumor cells are embedded in a dense fibrous stroma, creating the Sertoli cell tumor‐like pattern. (E) Granulosa cell tumor, ovary, dog. Higher magnification of previous image showing Sertoli‐like cells stretching across a tubular structure. (F) Luteoma, ovary, cat. Multiple nodules are well vascularized and composed of polygonal neoplastic cells with abundant granular cytoplasm and lipid vacuoles. (G) Luteoma, ovary, cat. Higher magnification of previous photomicrograph. (H) Thecoma, ovary, horse. Tumor cells are arranged in streams and bundles, and are spindle shaped with vacuolated cytoplasm that may contain lipid. (I) Thecoma, ovary, dog. Tumor cells in the dog are similarly spindle shaped and vacuolated, often embedded in a dense stroma.


Call–Exner bodies are present in some granulosa cell tumors and, when present, are a useful diagnostic feature (Figure 16.3C). Call–Exner bodies consist of a radial aggregate of tumor cells about a central deposit of eosinophilic proteinaceous material.


Luteoma, Leydig cell tumor of the ovary, and lipid cell tumor

Luteoma, Leydig cell tumor of the ovary, and lipid cell tumors are composed of cells that resemble those of the corpus luteum in all species, and those of the interstitial glands of the normal feline ovary.2 These tumors consist of multiple lobules of neoplastic cells separated by a well‐vascularized connective tissue stroma. The neoplastic cells are polygonal with abundant granular eosinophilic cytoplasm that contains lipid vacuoles (Figure 16.3F,G).


Thecoma

Thecoma consists of irregular, loosely arranged unencapsulated aggregates of spindle‐shaped cells (Figure 16.3H,I). Individual cells have elongated nuclei, and the cytoplasm may contain lipid vacuoles, which are indicative of steroid hormone production. The distinction between a thecoma and mesenchymal tumors such as leiomyoma and fibroma can be difficult. However, a thecoma has the capacity to produce steroid hormones, elevated levels of which often can be detected in blood. Cytoplasmic lipid vacuoles in the cells of thecoma can be stained with fat stains such as Sudan black. If necessary, histochemical or IHC staining can be used to identify muscle or collagen in order to distinguish thecoma from mesenchymal tumors, as can staining to detect the presence or absence of reproductive hormones and other markers common to sex cord stromal tumors (e.g., antibodies to inhibin or anti‐Mullerian hormone).


Miscellaneous

Other types of sex cord stromal tumors have been described, usually based on comparison of their histological appearance to that of ovarian tumors that have been described in women. These include androblastoma (Sertoli–Leydig cell tumor or arrhenoblastoma) in the cow, mare, ewe, and queen.2,48,49 These are tumors that include elements that resemble both granulosa cell tumor and luteoma; however, foci of apparent luteinization within granulosa‐theca cell tumors can produce this same appearance.


Granulosa or granulosa‐theca cell tumors are especially common in the mare and cow, although thecomas and luteomas also have been described in the latter.50 Granulosa cell tumors in cattle frequently have a solid pattern, whereas the thecal component and follicular pattern usually are more prominent in similar tumors in mares, hence the usual designation of granulosa‐theca cell tumor in the latter species. Some sex cord stromal tumors of the ovary of both the cow and the mare resemble Sertoli cell tumors. A variety of patterns of sex cord stromal tumors have been described in the bitch, including granulosa cell tumors, Sertoli cell tumors of the ovary, luteomas, and nonspecific stromal tumors.


The histological appearance of granulosa cell tumors of the bitch is variable, ranging from follicular to solid. Sex cord stromal tumors with the Sertoli cell pattern are proposed to have a better prognosis than those with the typical granulosa cell pattern. In the queen, granulosa cell tumors, luteomas (including lipid cell tumor), and androblastomas have been described. Luteomas or lipid cell tumors of the queen are composed of cells that closely resemble those found in the so‐called interstitial glands that are a feature of the normal feline ovary.


Biological behavior


All sex cord stromal tumors share the propensity to be hormonally active, producing signs of hyperestrinism, masculinization, or persistent anestrus. The metastatic behavior of the various sex cord stromal tumors also differs among the species. Granulosa cell tumors in mares almost invariably are benign, whereas metastasis is anecdotally relatively common in the queen and, less so, the bitch. Reported malignancy of bovine sex cord stromal tumors has varied considerably among studies, but metastasis, if it occurs, is late. Metastasis can occur to the regional lymph nodes, via the blood to a variety of organs or, rarely, by implantation into the peritoneal cavity. Malignant sex cord stromal tumors are disorganized as compared to their benign counterparts, and may exhibit cellular anaplasia, with numerous mitotic figures, foci of necrosis and/or hemorrhage, and vascular invasion by the tumor cells.


Germ cell tumors


Germ cells initially are found in the yolk sac and, early in differentiation, migrate to the gonadal ridge. In the developing ovary, association of germ cells and sex cords precedes formation of primary follicles. Dysgerminomas and teratomas are tumors of domestic animals derived from germ cells. Other ovarian germ cell tumors that occur in women and laboratory animals, such as embryonal carcinoma, choriocarcinoma, and endodermal sinus tumor, have yet to be adequately described in domestic animals.


Dysgerminoma


Dysgerminoma is the female equivalent of testicular seminoma (Figure 16.4A,B). This is an uncommon ovarian tumor in domestic animals, but it has been described in most species and appears to be most common in the bitch and queen.1,2,15–19,30,35,51–53 Aged animals typically are affected and occasionally may manifest signs of hyperestrinism. Mares with disseminated germ cell tumors also may manifest hypertrophic osteopathy (Figure 16.4C).54

Micrograph of dysgerminoma in dog’s ovary with sheets of tumor cells compressing adjacent ovarian tissue.
Micrograph of dysgerminoma in dog’s ovary, with cells featuring large pleomorphic nuclei, prominent nucleoli, scant cytoplasm, and numerous often abnormal mitotic figures.
Photo of horse’s limbs affected with hypertrophic osteopathy.
Micrograph of teratoma in dog’s ovary consisting of various mature but disorganized tissues.
Micrograph of cysts in dog’s ovary containing keratin shards lined by stratified squamous epithelium, plates of hyaline cartilage (depicted by asterisk), and nerve fibers (pointed by arrow).

Figure 16.4 Germ cell tumors. (A) Dysgerminoma, ovary, dog. Sheets of tumor cells compress adjacent ovarian tissue. (B) Dysgerminoma, ovary, dog. Tumor cells have large pleomorphic nuclei, prominent nucleoli, scant cytoplasm, and numerous often abnormal mitotic figures. (C) Hypertrophic osteopathy has been reported in several horses with dysgerminomas. Limbs, horse. (D) Teratoma, ovary, dog. The tumor consists of a variety of mature, but disorganized, tissues. (E) Note cysts containing keratin shards lined by stratified squamous epithelium, plates of hyaline cartilage (asterisk) and nerve fibers (arrow). Ovary, dog.


Dysgerminomas can be large tumors that produce spherical or ovoid enlargement of the affected ovary. On cut surface the tumor characteristically is white or gray, firm, and homogeneous, although hemorrhage and/or necrosis can produce areas of discoloration and cysts of variable size. Dysgerminomas are highly cellular tumors, consisting of broad sheets, cords, and nests of cells separated by occasional thin connective tissue septa (Figure 16.4A). Individual tumor cells resemble primitive germ cells; they are large and polyhedral, uniformly similar, with vesicular nuclei, prominent nucleoli, and scant amphophilic or basophilic cytoplasm that imparts a “blastic” appearance. Mitotic figures, which often are abnormal, may be very numerous (several per HPF) (Figure 16.4B). Multinucleate tumor cells and focal aggregations of lymphocytes are regularly present. Metastasis occurs frequently, either to regional lymph nodes and adjacent organs or transcoelomically, likely due at least in part, to the occult nature of these neoplasms.


Teratoma


Teratoma is composed of abnormal tissue derived from at least two, and often all three, germinal layers. They presumably arise from pluripotential germ cells that have undergone differentiation.55 Ovarian teratomas are uncommon in domestic animals, but they have been described and are most common in the bitch.1,2,16,19,20,30,35,52,53,56 They cause spherical or ovoid enlargement of the affected ovary, with solid and cystic areas on cut surface. The latter may contain sebaceous material and hair. A variety of other tissues may be present, including bone, cartilage, and teeth (Figure 16.4D,E). Teratomas of the bovine ovary frequently are dermoid cysts, especially in zebu cattle.2 Most teratomas are benign and are composed of well‐differentiated mature tissues, but any of the tissues that make up a teratoma may be malignant. Malignant teratomas of the ovary are unusual but are well described in the bitch and mare.2,20,53,57,58


Other tumors


Mixed tumors


Ovarian tumors that include elements of more than one of the three traditional lineages occur, but these must be distinguished from the presence of two different tumors in the same ovary or histological variation within a single tumor. Mixed tumors include both epithelial and sex cord stromal elements or both germ cells and sex cord stromal cells, although definitive descriptions currently are limited.59 Gonadoblastoma is a specific mixed tumor of human ovary or testicle that includes germ cells and sex cord stromal derivatives. It occurs in humans with abnormal sexual development and dysgenic gonads. Ovarian gonadoblastoma has yet to be adequately described in animals. Mixed epithelial–stromal tumors such as adenosarcoma (carcinosarcoma, sarcomatoid carcinoma) and malignant mixed Mullerian tumor are rare but well recognized in women.60 Both of these tumors include carcinomatous and sarcomatous portions. Bilateral ovarian mixed malignant Mullerian tumor has been described in a bitch.61


Mesenchymal tumors


These are tumors derived from the mesenchymal elements of the ovary. They include fibromas, hemangiomas, leiomyomas, or their malignant counterparts. Hemangioma is the most common ovarian neoplasm of the sow, although it still is rare and usually occurs only in older animals.18,62 These tumors consist of numerous endothelium‐lined channels filled with blood that manifest grossly as discrete, rubbery, red‐brown nodules within the affected ovary. Morphologically similar lesions have been described in the ovary of older cows, mares, and beagle bitches.2,13 Ovarian fibroma and leiomyoma have the same appearance as tumors of these cell types in other tissues, as do their malignant counterparts.1,2,19,30,35,63 They can be difficult to distinguish from thecomas. The presence of lipid droplets in the cytoplasm of tumor cells is consistent with thecoma, and IHC labeling for inhibin‐α may also be helpful.


Metastatic non‐ovarian cancer


Secondary tumors of the ovary do occur in domestic animals, but their frequency is uncertain because detailed examinations are rarely made. Lymphomas can occur at this site, especially in the bitch, sow, queen, cow, and mare, but will also be present in lymphoid tissues.2,63,64 Other tumors are less common, but carcinomas and sarcomas of other sites clearly do metastasize to the ovary and, because of its rich vasculature, the corpus luteum may be especially prone.2,19,35


Cysts


Ovarian cysts


A wide variety of cysts occur in and around the ovary.1,13,22,30 Some may interfere with normal reproductive cyclicity, but most are innocuous. Cysts that occur within the ovarian parenchyma include cysts derived from anovulatory Graafian follicles (luteal and follicular cysts), cystic corpora lutea, cystic rete ovarii, inclusion cysts derived from the ovarian surface epithelium, and cysts of the SES. Parovarian cysts are common in the bitch and mare but as the name implies they are adjacent to and not within the ovarian parenchyma and are described in the next section.


Luteal and follicular cysts both are derived from anovulatory Graafian follicles and differ only in the degree of luteinization of the cyst wall. Cysts derived from anovulatory Graafian follicles are most common in the cow and sow, but also occur sporadically in the bitch and queen. They often cause altered reproductive activity through secretion of steroid hormones. Affected animals, especially bitches, may show marked manifestations of hyperestrinism, such as altered reproductive behavior, anemia, and hemorrhagic diathesis. In the cow and sow they may be associated with anestrus, persistent estrus, or nymphomania. These signs can mimic those in animals with hormonally productive sex cord stromal tumors. Anovulatory cysts persist longer than the normal mature follicle, and they frequently are larger than normal follicles. These cysts are lined by multiple layers of granulosa cells (follicular cyst) or with luteal cells that result from luteinization of the theca (luteal cyst, or sometimes called a luteinized follicular cyst). The two types of cyst can coexist in the same ovary.


In contrast, cystic corpora lutea are otherwise apparently normal corpora lutea with a central cavity, but because they are derived from postovulatory follicles, they typically have a discrete ovulation papilla. Cystic corpora lutea are essentially a variation of a normal luteal structure and the animal may be pregnant. The cells lining ovarian cysts of follicular origin are typically stained immunohistochemically for both vimentin and inhibin‐α.


Cysts of the surface epithelium are most common in the mare and the bitch (Figure 16.1B–D). SES cysts of the bitch may be lined by an attenuated epithelium and are distinguished from atretic follicles and follicular cysts by the lack of theca interna and follicular granulosa.13 Epithelial cysts of the mare’s ovary are clustered adjacent to the ovulation fossa, hence the name fossa cyst. Fossa cysts are variably sized but can become large (several centimeters in diameter).2 They are lined by cuboidal epithelium. Unlike SES cysts in the bitch, fossa cyts may obstruct the ovulation fossa resulting in a loss of fertility. Cystic rete ovarii is most common in the bitch and queen, though the best examples can be reliably seen in aged guinea pigs (Figure 16.1F). Rete cysts appear as dilated epithelium‐lined tubules that may become so large as to compress the cortex of the affected ovary.22,65


The epithelium lining cysts of both the SES and rete ovarii is immunoreactive for desmin and cytokeratins, but negative for inhibin‐α.12 The lining epithelium of some SES cysts may also contain PLAP.


Parovarian cysts


Cysts that occur adjacent to the ovary can derive from a variety of structures, including the mesonephric duct and tubule, paramesonephric duct, uterine tube, and mesosalpinx.1,2,30 Cysts derived from the Mullerian duct remnants are sometimes termed hydatids of Morgagni. These are fluid‐filled cysts that are located adjacent to the ovary or uterine tube. They can become quite large, especially in the mare (up to 7 cm). Cysts derived from the paramesonephric duct (cystic epoophoron) usually are lined by a single layer of cuboidal epithelium that includes both ciliated and nonciliated secretory cells, and a thin layer of smooth muscle surrounds the cyst. Parovarian cysts are most common in the mare and bitch.


Vascular hamartoma


Vascular hamartoma of the ovary has been described in cattle, swine, and horses.66,67 These manifest as cystic, blood‐filled spaces in the affected ovary and can be difficult to distinguish from vascular neoplasms, especially hemangioma and ovarian hematoma. Both hemangioma and vascular hamartoma include proliferations of vessels with prominent endothelial lining, thus differentiation is very difficult. The difference is that vascular hamartoma is a congenital lesion, whereas hemangioma is acquired though this is rarely clear to the clinician or the pathologist. Thrombosis can occur in the tortuous vessels within vascular hamartomas. Endothelial IHC markers (factor VIII or CD31) may be helpful if the vascular nature of the lesion is unclear.


Ovarian hematoma


Ovarian hematoma is common in mares and is thought to arise from excessive hemorrhage into the follicular cavity following ovulation.68,69 They can become large (up to 10 cm) but generally resolve spontaneously, though death can occur due to rupture and exsanguinations.70


Ovarian choristoma


Choristoma is normal tissue in an ectopic location. Ectopic adrenal gland may occur within the ovary, particularly in the mare. 71,72


References



  1. 1. Schlafer, D. H. and Miller, R.B. (2007) Female genital system. In Pathology of the Domestic Animals, 5th edn., Vol. 3 (ed. G. Maxie). Elsevier Saunders, Philadelphia, PA, pp. 429–564.
  2. 2. McEntee, K. (1990) Ovarian neoplasms., Reproductive Pathology of Domestic Animals. Academic Press, San Diego, CA, pp. 69–93.
  3. 3. Kennedy, P.C., Cullen, J.M., et al. (1998) Histologic Classification of Tumors of the Genital System of Domestic Animals, Vol. IV. Armed Forces Institute of Pathology, Washington, D.C., p. 79.
  4. 4. Scully, R. E., Young, R. H., et al. (1991) Tumors of the Ovary, Maldeveloped Gonads, Fallopian Tube, and Broad Ligament: Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Bethesda, MD, p. 527.
  5. 5. McEntee, K. (1990) Embryology of the reproductive organs. In Reproductive Pathology of Domestic Animals. Academic Press, San Diego, CA, pp. 1–7.
  6. 6. Byskov, A.G. (1986) Differentiation of the mammalian embryonic gonad. Physiol Rev 66:71–117.
  7. 7. Ullman, S.L. (1996) Development of the ovary in the brushtail possum Trichosurus vulpecula (Marsupiala). J Anat 189:651–665.
  8. 8. Byskov, A.G., Skakkebaek, N.E., et al. (1977) Influence of the ovarian surface epithelium and rete ovarii on follicle formation. J Anat 123:77–86.
  9. 9. Fritsch, M.K. (2007) Reproductive systems. In Potter’s Pathology of the Fetus, Infant and Child, Vol. 2 (ed. E. Gilbert‐Barness). Mosby Elsevier, Philadelphia, PA, pp. 1375–1452.
  10. 10. Mossman, H.W. and Duke, K.L. (1973) Comparative Morphology of the Mammalian Ovary. The University of Wisconsin Press, Madison, WI, p. 461.
  11. 11. Akihara, Y., Shimoyama, Y., et al. (2007) Histological and immunohistochemical evaluation of canine ovary. Reprod Domest Anim 42:495–501.
  12. 12. Akihara, Y., Shimoyama, Y., et al. (2007) Immunohistochemical evaluation of canine ovarian cysts. J Vet Med Sci 69:1033–1037.
  13. 13. Andersen, A.C. and Simpson, M.E. (1973) The Ovary and Reproductive Cycle of the Dog (Beagle). Geron‐X, Los Altos, CA.
  14. 14. Anderson, L.J. and Sandison, A.T. (1969) Tumors of the female genitalia in cattle, sheep, and pigs found in a British abbatoir survey. J Comp Pathol 79:53–63.
  15. 15. Cotchin, E. (1961) Canine ovarian neoplasms. Res Vet Sci 2.
  16. 16. Gelberg, H.B. and McEntee, K. (1985) Feline ovarian neoplasms. Vet Pathol 22:572–576.
  17. 17. Jergens, A.E. and Shaw, D.P. (1987) Tumors of the canine ovary. Compendium of Continuing Education for the Practicing Veterinarian 9:489–495.
  18. 18. Nelson, L.W., Todd, G.C., et al. (1967) Ovarian neoplasms in swine. J Am Vet Med Assoc 151:1331–1333.
  19. 19. Norris, H.J., Garner, F.M., et al. (1970) Comparative pathology of ovarian neoplasms. IV. Gonadal stromal tumors of canine species. J Comp Pathol 80:399–405.
  20. 20. Patnaik, A. K. and Greenlee, P.G. (1987) Canine ovarian neoplasms: A clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors. Vet Pathol 24:509–514.
  21. 21. Pauwels, F.E., Wigley, S.J., et al. (2012) Bilateral ovarian adenocarcinoma in a mare causing haemoperitoneum and colic. N Z Vet J 60:198–202.
  22. 22. McEntee, K. (1990) Cysts in and around the ovary. In Reproductive Pathology of Domestic Animals. Academic Press, San Diego, CA, pp. 52–68.
  23. 23. Prat, J. (2012) Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch Pathol Anat Physiol Klin Med 460:237–249.
  24. 24. Akihara, Y., Shimoyama, Y., et al. (2007) Immunohistochemical evaluation of canine ovarian tumors. J Vet Med Sci 69:703–708.
  25. 25. Park, J.K., Goo, M.J., et al. (2009) Immunohistochemistry diagnosis of an ovarian dysgerminoma in one bitch. Reprod Domest Anim 44:855–858.
  26. 26. Ellenberger, C., Bartmann, C.P., et al. (2007) Histomorphological and immunohistochemical characterization of equine granulosa cell tumours. J Comp Pathol 136:167–176.
  27. 27. Marino, G., Nicotina, P.A., et al. (2003) Alpha‐inhibin expression in canine ovarian neoplasms: preliminary results. Vet Res Commun 27:237–240.
  28. 28. Riccardi, E., Grieco, V., et al. (2007) Immunohistochemical diagnosis of canine ovarian epithelial and granulosa cell tumors. J Vet Diagn Invest 19:431–435.
  29. 29. Banco, B., Antuofermo, E., et al. (2011) Canine ovarian tumors: an immunohistochemical study with HBME‐1 antibody. J Vet Diagn Invest 27:977–981.
  30. 30. MacLachlan, N.J. (1987) Ovarian disorders in domestic animals. Environ Health Perspect 73:27–33.
  31. 31. Scully, R.E. (1977) Ovarian tumors: A review. Am J Pathol 87:686–720.
  32. 32. Arthur, G.H. (1972) Granulosa cell tumor of the bovine ovary. Vet Rec 91:78.
  33. 33. Farin, P.W. and Estill, C.T. (1993) Infertility due to abnormalities of the ovaries in cattle. Vet Clin North Am Food Anim Pract 9:291–308.
  34. 34. Meinecke, B. and Gips, H. (1987) Steroid hormone secretory patterns in mares with granulosa cell tumors. J Vet Med A: Physiol Pathol Clin Med 34:545–560.
  35. 35. Norris, H.J., Garner, F.M., et al. (1969) Pathology of feline ovarian neoplasms. J Pathol Bacteriol 97:138–143.
  36. 36. Gee, E.K., Dicken, M., et al. (2012) Granulosa theca cell tumour in a pregnant mare: concentrations of inhibin and testosterone in serum before and after surgery. N Z Vet J 60:160–163.
  37. 37. McCue, P.M., Roser, J.F., et al. (2006) Granulosa cell tumors of the equine ovary. Vet Clin North Am Equine Pract 22:799–817.
  38. 38. Sasano, H. (1994) Functional pathology of human ovarian steroidogenesis: Normal cycling ovary and steroid producing neoplasms. Endocrinol Pathol 5:81–94.
  39. 39. Drummond, A.E., Findlay, J.K., et al. (2004) Animal models of inhibin action. Sem Reprod Med 22:243–252.
  40. 40. McCandlish, I.A., Munro, C.D., et al. (1979) Hormone producing ovarian tumors in the dog. Vet Rec 105:9–11.
  41. 41. Yamini, B., VanDenBrink, P.L., et al. (1997) Ovarian steroid cell tumor resembling luteoma associated with hyperadrenocorticism (Cushing’s Disease) in a dog. Vet Pathol 34:57–60.
  42. 42. Hinrichs, K., Watson, E.D., et al. (1990) Granulosa cell tumor in a mare with a functional contralateral ovary. J Am Vet Med Assoc 197:1037–1038.
  43. 43. Almeida, J., Ball, B.A., et al. (2011) Biological and clinical significance of anti‐Müllerian hormone determination in blood serum of the mare. Theriogenology 76:1393–1403.
  44. 44. Kitahara, G., Nambo, Y., et al. (2012) Anti‐Müllerian hormone profiles as a novel biomarker to diagnose granulosa‐theca cell tumors in cattle. J Reprod Dev 58:98–104.
  45. 45. Ramos‐Vara, J.A., Beissenherz, M.E., et al. (2001) Immunoreactivity of A103, An antibody to Melan A, in canine steroid‐producing tissues and their tumors. J Vet Diagn Invest 13:328–332.
  46. 46. Smedley, R.C., Lamoureux, J., et al. (2011) Immunohistochemical diagnosis of canine oral amelanotic melanocytic neoplasms. Vet Pathol 48:32–40.
  47. 47. Bursam, K.J., Iversen, K., et al. (1998) Immunoreactivity for A103, an antibody to Melan A (Mart‐1), in adrenocortical and other steroid tumors. Am J Surg Pathol 22:57–63.
  48. 48. Hofmann, W., Arbiter, D., et al. (1980) Sex cord stromal tumor of the cat: So‐called androblastoma with Sertoli‐Leydig cell pattern. Vet Pathol 17:508–513.
  49. 49. Mills, J.H.L., Fretz, P.B., et al. (1977) Arrhenoblastoma in a mare. J Am Vet Med Assoc 171:754–757.
  50. 50. Perez‐Martinez, C., Duran‐Navarrete, A.J., et al. (2004) Biological characterization of ovarian granulosa cell tumours of slaughtered cattle: Assessment of cell proliferation and oestrogen receptors. J Comp Pathol 130:117–123.
  51. 51. Andrews, E.J., Stookey, J.L., et al. (1974) A histopathological study of canine and feline ovarian dysgerminomas. Can J Comp Med Vet Sci 38:85–89.
  52. 52. Dehner, L.P., Norris, H.J., et al. (1970) Comparative pathology of ovarian neoplasms. III. Germ cell tumors of canine, bovine, feline, rodent, and human species. J Comp Pathol 80:299–306.
  53. 53. Greenlee, P.G. and Patnaik, A.K. (1985) Canine ovarian tumors of germ cell origin. Vet Pathol 22:117–122.
  54. 54. Meuten, D.J. and Rendano, V. (1978) Hypertrophic osteopathy in a mare with dysgerminoma. J Equine Med Surg 2:445–450.
  55. 55. Linder, D., McCaw, B.K., et al. (1989) Parthenogenic origin of benign ovarian teratomas. N Engl J Med 292:790–793.
  56. 56. Basaraba, R.J., Kraft, S.L., et al. (1998) An ovarian teratoma in a cat. Vet Pathol 35:141–144.
  57. 57. Frazer, G.S., Robertson, J.T., et al. (1988) Teratocarcinoma of the ovary in a mare. J Am Vet Med Assoc 193:953–955.
  58. 58. Van Camp, S.D., Mahler, J., et al. (1989) Primary ovarian adenocarcinoma associated with teratomatous elements in a mare. J Am Vet Med Assoc 194:1728–1730.
  59. 59. Patnaik, A.K. and Mostofi, F.K. (1993) A clinicopathologic, histologic, and immunohistochemical study of mixed germ cell‐stromal tumors of the testis in 16 dogs. Vet Pathol 30:287–295.
  60. 60. Scully, R.E., Young, R.H., et al. (1999) Tumors of the Ovary, Maldeveloped Gonads, Fallopian Tube, and Broad Ligament: Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Bethesda, MD, p. 527.
  61. 61. Antuofermo, E., Cocco, R., et al. (2009) Bilateral ovarian malignant mixed Mullerian tumor in a dog. Vet Pathol 46:453–456.
  62. 62. Hsu, F. (1983) Ovarian hemangioma in swine. Vet Pathol 20:401–409.
  63. 63. Norris, H.J., Garner, F.M., et al. (1969) Comparative pathology of ovarian tumors II. Gondal stromal tumors of bovine species. Vet Pathol 6:45–58.
  64. 64. Neufeld, J.L. (1973) Lymphosarcoma in the horse: A review. Can Vet J 14:129–135.
  65. 65. Gelberg, H.B., McEntee, K., et al. (1984) Feline cystic rete ovarii. Vet Pathol 21:304–307.
  66. 66. Lee, C.G. and Ladds, P.W. (1976) Vascular hamartoma in the ovary of a cow. Aust Vet J 52:236.
  67. 67. Rhyan, J.C., D’Andrea, G.H., et al. (1981) Congenital ovarian vascular hamartoma in a horse. Vet Pathol 18:131.
  68. 68. Bosu, W.T. K., Van Camp, S.C., et al. (1982) Ovarian disorders: Clinical and morphological observations in 30 mares. Can Vet J 23:6–14.
  69. 69. Hughes, J.P., Stabenfeldt, G.H., et al. (1972) Estrous cycle and ovulation in the mare. J Am Vet Med Assoc 161:1367–1374.
  70. 70. Pusterla, N., Fecteau, M.E., et al. (2005) Acute hemoperitoneum in horses: a review of 19 cases (1992–2003). J Vet Intern Med 19:344–347.
  71. 71. McEntee, K. (1990) The ovary. In Reproductive Pathology of Domestic Animals. Academic Press, San Diego, CA, pp. 31–51.
  72. 72. Long, S.E., Thomas, I., et al. (2000) Ectopic adrenal tissue in the cow. Vet Rec 147:303–304.

TUMORS OF THE UTERINE TUBE (OVIDUCT) AND UTERUS


Epithelial tumors


Tumors of the uterine epithelium


Epithelial tumors of both the uterus and oviduct are rare in domestic animals. Adenoma of the uterus is very rare. It consists of a proliferative mass of glandular elements, and must be distinguished from uterine carcinoma, uterine stromal polyp, and focal areas of adenomyosis, although distinction often is very difficult. Carcinoma of the uterus also is rare in domestic animals, in marked contrast to the prevalence of this tumor in women. Among the domestic species, it is most often reported in the cow, and it is fairly common in older cows at slaughter (Figure 16.5A,B). There are a number of reports of similar tumors in the mare, ewe, bitch, potbellied pig, and queen.1–7 There is some controversy as to the validity of some published descriptions of canine uterine carcinomas because hyperplastic lesions of the canine endometrium and carcinomas metastatic to the uterus can be confused with primary endometrial carcinomas.

Photo of the endometrial carcinoma in cow’s uterus.
Micrograph featuring carcinomatosis of an endometrial carcinoma in cow’s peritoneal cavity and forestomachs.
Micrograph of tumors of the uterus and vagina illustrating leiomyoma of the uterus of a cat, with a well-differentiated leiomyoma that compresses the adjacent endometrium.
Magnified micrograph of leiomyoma in dog’s uterus.
Photo of tumors of the uterus and vagina illustrating cystic endometrial hyperplasia of the uterus a dog, with diffuse proliferation of endometrial glands and stroma, associated with pyometra.
Micrograph of tumors of the uterus and vagina illustrating cystic endometrial hyperplasia of the uterus of a cat, with marked variation and disorientation of glands
Micrograph of tumors of the uterus and vagina illustrating cystic endometrial hyperplasia of the uterus of a cat, with progestational epithelium lining the cysts, superficial epithelium, and glands.
Photo of a cat's uterus with stromal polyps associated with endometrial hyperplasia.
Micrograph of tumors of the uterus and vagina illustrating stromal polyps of the uterus of a cat with dilated endometrial glands within a proliferative stroma.
Micrograph of tumors of the uterus and vagina illustrating remnants of mesonephric (Wolffian) duct becoming cystic with the serosal surface grossly (asterisk) and cystic endometrial hyperplasia (arrow).

Figure 16.5 Tumors of the uterus and vagina. (A) Endometrial carcinoma, uterus, cow. Although rare, this is most often seen in cows at slaughter. Transmural invasion with desmoplasia is typical in these cases. (B) Carcinomatosis of an endometrial carcinoma is a frequent sequel of these tumors in cattle. Peritoneal cavity and forestomachs, cow. (C) Leiomyoma of the uterus, uterus, cat. A well‐differentiated leiomyoma that compresses the adjacent endometrium. (D) A higher magnification of leiomyoma, uterus, dog. (E) Cystic endometrial hyperplasia, uterus, dog. This diffuse proliferation of endometrial glands and stroma is very common in dogs and cats, frequently associated with pyometra. It is linked to prolonged exposures to progesterone or estrogen. (F) Cystic endometrial hyperplasia, uterus, cat. Photomicrograph shows marked variation and disorientation of glands. (G) Cystic endometrial hyperplasia, uterus, cat. Higher magnification shows progestational epithelium lining the cysts, superficial epithelium, and glands which is characteristic of this lesion. (H) Stromal polyps, uterus, cat. These are often associated with endometrial hyperplasia, and can obstruct the lumen. (I) Stromal polyps are composed of dilated endometrial glands within a proliferative stroma. The attenuated lining and lumen is along the longer right aspect in the image. Uterus, cat. (J) Remnants of mesonephric (Wolffian) duct can become cystic and are commonly seen along the serosal surface grossly (asterisk). Histologically, they are lined by epithelium and have a muscular wall. Cystic endometrial hyperplasia is often also present, as in this case (arrow). Uterus, dog.


Uterine carcinomas in cattle manifest as discrete, firm enlargements of the uterus that are composed of very firm, dense, white to yellow tissue. Widespread metastasis also can occur (Figure 16.5B). These tumors tend to be solitary and develop in the uterine horn. The histological appearance of these tumors is characterized by nests and cords of anaplastic epithelium in a dense and abundant fibrous connective tissue stroma. The tumor develops deep in the endometrium and often extends into the myometrium early in the disease. Invasion of the tumor into veins and/or lymphatics frequently is present, and lymphatic spread initially is via the internal iliac and sublumbar nodes. Metastasis to other parenchymal organs such as lungs and liver also can occur, and the neoplasm can implant in the abdomen.


Tumors of the chorionic epithelium


Choriocarcinoma and hydatiform mole are gestational trophoblastic tumors of women that arise from the placental chorionic epithelium. Initial descriptions of similar tumors in animals have not been substantiated; thus, it is not clear whether placental tumors occur in domestic animals, though there has been a recent report of gastric choriocarcinoma in a dog and other reports of choriocarcinomas in primates and rabbits.8 Tumors of placental origin must be distinguished from non‐neoplastic infiltration of placental trophoblastic cells, as occurs in subinvolution of placental sites in the bitch.9


Mesenchymal tumors


A variety of mesenchymal tumors occur in the uterus of domestic animals, including leiomyoma, fibroma, fibroleiomyoma and, far less commonly, their malignant counterparts. Unquestionably, different titles have been applied to similar tumors, and the specific designation frequently reflects the bias of individual pathologists. Leiomyomas of the myometrium are most common, especially in the bitch, queen, potbellied pig, and cow.5,10 The development appears to be associated with increasing age, and likely, nulliparity. Those in the bitch typically are accompanied by similar, concurrent tumors in the vagina. Leiomyosarcomas appear much less frequently, but have been reported in most domestic species, particularly in goats of the Saanen breed.11,12


Gross morphology


Mesenchymal tumors manifest as a firm, nodular proliferation within the myometrium that may project into the uterine lumen or from the serosa. Mesenchymal tumors of the tubular tract tend to be multiple.


Histological types


Leiomyoma of the myometrium has the expected appearance of a tumor of smooth muscle with interlacing bundles of muscle fibers mixed with variable amounts of collagenous stroma, hence the designation fibroleiomyoma that is preferred by some pathologists (Figure 16.5C,D). Fibroma, on the other hand, is exclusively composed of fibrous connective tissue and is devoid of smooth muscle. Malignant mesenchymal tumors, especially leiomyosarcomas, also can occur. These usually are larger than their benign counterparts, and cells within the tumor exhibit cellular atypia and a relatively high mitotic count. IHC staining for the presence of vimentin and desmin can be used to distinguish tumors derived from smooth muscle and fibrous tissue.


A variety of other mesenchymal tumors can occur in the tubular tract, including lipoma within the broad ligament and ovarian bursa in the bitch and lymphosarcoma. Lymphosarcoma frequently involves the uterus of adult cattle with the disseminated form of enzootic leukosis, and it is the most common neoplasm of the uterus in cows.13 Lymphosarcomas involving the uterine wall can be very extensive; they have the homogeneous gray/yellow appearance that is characteristic of these tumors. The histological appearance is similar to those in other locations of the tumor, with frequent accumulation of neoplastic B lymphocytes within the endometrium and effacement of normal tissue architecture. Invariably the tumor is in the other characteristic locations in the cow and is not just in the uterus. Disseminated lymphosarcoma also may involve the uterus in the mare. Post‐inflammatory sarcoma has been reported in the uterus of a cat with longstanding pyometra.14


Hyperplastic and tumor‐like lesions of the uterus


Adenomyosis


Adenomyosis is a non‐neoplastic proliferation of uterine glands characterized by multicentric infiltration of these glands into the myometrium. It is most often seen in the dog, associated with cystic endometrial hyperplasia, but has also been reported in the cat, potbellied pig, cow, and other species.10


Cystic endometrial hyperplasia


Cystic endometrial hyperplasia (CEH) is a diffuse proliferation of the endometrial glands and stroma (Figure 16.5E,F). In ruminants it is induced by excessive estrogenic stimulation of the endometrium from either exogenous sources such as estrogenic plants (such as specific varieties of clover) or from endogenous production of estrogens by sex cord stromal tumors of the ovary or anovulatory cystic follicles.15 Iatrogenic administration of exogenous estrogen also can induce CEH in the bitch; however, spontaneous CEH in the bitch and queen most often is the result of a heightened sensitivity of the endometrium to stimulation by endogenous progesterone.15,16 Both the bitch and the queen normally retain their corpora lutea for extended periods after ovulation, regardless of whether or not they are pregnant. Irritation of the endometrium under the influence of progesterone leads to CEH; if the irritation is due to bacterial infection, it also can result in pyometra. The histological appearance of CEH induced by estrogen and progesterone is quite different. The epithelium of the endometrium is cuboidal to low columnar under estrogenic stimulation and tall columnar with extensively vacuolated cytoplasm under progestational influence (Figure 16.5G).15


Uterine stromal polyp


Endometrial stromal polyp of the bitch and queen consists of a focal proliferation of both glandular and stromal elements of the endometrium, and may be single or multiple (Figure 16.5H,I). These polyps usually project into the lumen of the affected uterus as sessile or pedunculated masses emanating from the endometrium. They can become large and may readily be confused with tumors of the uterus. Polyps consist of dilated uterine glands within a proliferative endometrial stroma.17 Idiopathic nodular endometrial hyperplasia occurs sporadically in mares, and focal regions of apparent endometrial hyperplasia may develop at sites of adventitial placentation in ruminants.18


Subinvolution of placental sites


Subinvolution of placental sites occurs in young bitches. Failure of the endometrial sites of placental implantation to regress following whelping leads to a persistent discharge from the vulva. A vaginal discharge is expected for up to two weeks post whelping but when the discharge continues beyond this period subinvolution of placental sites should be considered. The histological appearance of these sites of placentation is characterized by inflammation with persistence of placental trophoblast cells within the endometrium.9


Miscellaneous uterine cysts


A variety of cysts that occur in the uterine wall have been described in domestic animals. Lymphatic cysts, which may be transmural, are most commonly adjacent to the uterine bifurcation of multiparous mares. Remnants of the ducts and embryonic structures associated with sexual development also can give rise to cysts in all species, and remnants of the mesonephric duct are especially commonly affected. Mesonephric duct cysts are epithelium lined and have a muscular wall (Figure 16.5J). Serosal inclusion cysts may be single or multiple, thin‐walled cysts on the serosal surface of the uterus. Endometrial cysts derived from very dilated uterine glands occur in the endometrium of old bitches.


References



  1. 1. Chaffin, M.K., Fuentealba, I.C., et al. (1990) Endometrial carcinoma in a mare. Cornell Vet 80:65–73.
  2. 2. Cotchin, E. (1964) Spontaneous uterine cancer in animals. Br J Cancer 18:209–227.
  3. 3. Migaki, G., Carey, A.M., et al. (1970) Pathology of bovine uterine adenocarcinoma. J Am Vet Med Assoc 157:1577–1584.
  4. 4. Preiser, H. (1964) Endometrial adenocarcinoma in a cat. Vet Pathol 1:485–490.
  5. 5. Stein, B.S. (1981) Tumors of the feline genital tract. J Am Anim Hosp Assoc 17:1022–1025.
  6. 6. Augustijn, M., Kuller, W., et al. (2010) Neoplasms of the genital tract in a Vietnamese potbellied pig. Tijdschr Diergeneeskd 135:4–7.
  7. 7. Pires, M.A., Seixas, F., et al. (2010) Histopathologic and immunohistochemical exam in one case of canine endometrial adenocarcinoma. Reprod Domest Anim 45:545–549.
  8. 8. Poutahidis, T., Doulberis, M., et al. (2008) Primary gastric choriocarcinoma in a dog. J Comp Pathol 139:146–150.
  9. 9. Dickie, M.B. and Arbeiter, K. (1993) Diagnosis and therapy of the subinvolution of placental sites in the bitch. J Reprod Fertil 47:S471–475.
  10. 10. Ilha, M.R.S., Newman, S.J., et al. (2010) Uterine lesions in 32 female miniature pet pigs. Vet Pathol 47:1071–1075.
  11. 11. Cooper, T.K., Ronnett, B.M., et al. (2006) Uterine myxoid leiomyosarcoma with widespread metastases in a cat. Vet Pathol 43:552–556.
  12. 12. Whitney, K.M., Valentine, B.A., et al. (2000) Caprine genital leiomyosarcoma. Vet Pathol 37:89–94.
  13. 13. Burton, A.J., Nydam, D.V., et al. (2010) Signalment and clinical complaints initiating hospital admission, methods of diagnosis, and pathological findings associated with bovine lymphosarcoma (112 cases). J Vet Intern Med 24:960–964.
  14. 14. Jelínek, F. (2003) Postinflammatory sarcoma in cats. Exp Toxicol Pathol 55:167–172.
  15. 15. Schlafer, D.H. and Gifford, A.T. (2008) Cystic endometrial hyperplasia, pseudoplacentational endometrial hyperplasia, and other cystic conditions of the canine and feline uterus. Theriogenology 70:349–358.
  16. 16. Nomura, K., Kawasoe, K., et al. (1990) Histologic observations of canine cystic endometrial hyperplasia induced by uterine scratching. Jap J Vet Sci 52:237–240.
  17. 17. Gelberg, H. and McEntee, K. (1984) Hyperplastic endometrial polyps in the dog and cat. Vet Pathol 21:570–573.
  18. 18. Hamir, A.H., Hunt, P.R., et al. (1989) Hyperplastic endometrial polyp in a two‐year‐old filly. Vet Pathol 26:185–187.

TUMORS OF THE CERVIX, VAGINA, AND VULVA


Epithelial tumors


Primary epithelial tumors of the cervix are extremely uncommon in domestic animals, in contrast to the frequency of these tumors in women. Carcinomas of the vagina and vulva, on the other hand, are relatively common, particularly squamous cell carcinomas (SCC) in ruminants and carcinomas of urinary epithelial (urothelial) origin in the vestibule of the bitch. As in women, papillomaviruses are associated with the development of neoplasms of the genital epithelium in horses.1,2


Papilloma


Papilloma is a virus‐induced epithelial proliferation that may affect the skin over any part of the body, including the external genitalia.3,4 The appearance is that of a typical “wart” with papillary projections of epithelium with a scant fibrovascular stroma. The lesions usually undergo spontaneous regression. Transmissible genital papilloma is a specific, virus‐induced papilloma in swine that manifests as a raised epithelial proliferation that emanates from the vaginal mucosa of the sow and the prepuce in the boar, but has been rarely reported.5 Virus‐induced fibropapilloma is a similar tumor that occurs in cattle and will be described elsewhere in this chapter. Similarly, a distinct papillomavirus (equine papillomavirus‐2) has recently been incriminated as the cause of both benign and malignant epithelial proliferations of the external genitalia in mares.2


Squamous cell carcinoma


SCC of the vulva is well recognized in sheep, goats, and cattle, particularly those in areas where they are exposed to high levels of solar irradiation.4,6,7 Unpigmented regions of the body that are not protected by wool or hair are most commonly affected by SCC.8 These lesions in the vulva may be either ulcerative or proliferative or both, and histologically are typical SCCs. They are occasionally invasive but rarely metastatic. Progression from focal epidermal hyperplasia and dysplasia to squamous papilloma and eventually SCC can occur with time and actinic exposure, thus precancerous lesions of solar keratosis are often present in cattle with SCC of the vulva.7


Carcinoma of the vestibule


Carcinoma of the vestibule is a distinct entity in the bitch, with the majority likely being of urothelial origin rather than the vaginal mucosa.9–11 The distal two‐thirds of the bitch’s urethra is lined with stratified squamous, rather than transitional, epithelium. The majority of urethral carcinomas in the bitch arise in the distal urethra, and thus the vagina and vestibule adjacent to the urethral papillae typically are affected secondarily. The histological appearance is that of a carcinoma with islands and nests of anaplastic epithelial cells within a fibrous stroma, lacking any of the features of TCC or SCC. Metastasis to regional lymph nodes is common. Adenocarcinoma of the vestibular gland (Bartholin’s gland) is an extremely rare tumor of the vestibule that has been described in a cow.12 Adenocarcinoma of the clitoris with accompanying hypercalcemia of malignancy has been described in a bitch.13


Mesenchymal tumors


Mesenchymal tumors of the lower genital tract are relatively common, producing firm nodules within the wall of the tract, which may encroach on the lumen. The canine transmissible venereal tumor will be described elsewhere in this chapter.


Leiomyoma is a common tumor of the vagina of the bitch and, less commonly, other species, and resembles the same tumor in the uterus.4,9,14 Leiomyomas may be solitary or multiple, extraluminal or intraluminal, and they can become large (up to 12 cm in diameter in the bitch). These tumors are benign and are hormonally dependent as they often regress after ovariectomy and do not occur in neutered bitches. Fibroma of the vagina is less common than leiomyoma, with which it may be confused. Lipoma sporadically may occur in the wall of the canine vagina, as does rhabdomyosarcoma.15


Miscellaneous tumors that may involve the vulva and vagina include melanomas, particularly in gray mares, lymphosarcoma, plasmacytoma, hemangioma, transmissible venereal tumor in the bitch, embryonal sarcoma of the porcine vagina, and metastatic tumors such as mammary carcinoma.


Tumor‐like lesions of the vagina and vulva


Cysts of mesonephric duct remnants are most common in cattle and dogs. These are fluid‐filled structures on the serosal surface of the tubular genitalia.9,16


References



  1. 1. Scase, T., Brandt, S., et al. (2010) Equus caballus papillomavirus‐2 (EcPV‐2): An infectious cause for equine genital cancer? Equine Vet J 42:738–745.
  2. 2. Bogaert, L., Willemsen, A., et al. (2012) EcPV2 DNA in equine genital squamous cell carcinomas and normal genital mucosa. Vet Microbiol 158:33–41.
  3. 3. Borzacchiello, G. and Roperto, F. (2008) Bovine papillomaviruses, papillomas, and cancer in cattle. Vet Res 39:45–64.
  4. 4. Schlafer, D.H. and Miller, R.B. (2007) Female genital system. In Pathology of the Domestic Animals, 5th edn., Vol. 3 (ed. G. Maxie). Elsevier Saunders, Philadelphia, PA, pp. 429–564.
  5. 5. Parish, W.E. (1962) An immunological study of the transmissible genital papilloma of the pig. J Pathol Bacteriol 83:429–442.
  6. 6. McEntee, K. (1990) The uterus: atrophic, metaplastic, and proliferative lesions. In Reproductive Pathology of Domestic Animals. Academic Press, San Diego, CA, pp. 167–190.
  7. 7. Yeruham, I., Perl, S., et al. (1999) Tumours of the vulva and vagina in cattle – a 10‐year survey. Vet J 158:237–239.
  8. 8. Mendez, A., Perez, J., et al. (1997) Clinicopathological study of an outbreak of squamous cell carcinoma in sheep. Vet Rec 141:597–600.
  9. 9. McEntee, K. (1990) Cervix, vagina, and vulva. In Reproductive Pathology of Domestic Animals. Academic Press, San Diego, CA.
  10. 10. Magne, M.L., Hoopes, P.J., et al. (1985) Urinary tract carcinomas involving the canine vagina and vestibule. J Am Anim Hosp Assoc 21:767–772.
  11. 11. Tarvin, G., Patnaik, A., et al. (1978) Primary urethral tumors in dogs. J Am Vet Med Assoc 172:931–933.
  12. 12. Tanimoto, T., Fukunaga, K., et al. (1994) Adenocarcinoma of the major vestibular gland in a cow. Vet Pathol 31:246–247.
  13. 13. Neihaus, S.A., Winter, J.E., et al. (2010) Primary clitoral adenocarcinoma with secondary hypercalcemia of malignancy in a dog. J Am Anim Hosp Assoc 46:193–196.
  14. 14. Manothaiudom, K. and Johnson, S.D. (1991) Clinical approaches to vaginal/vestibular masses in the bitch. Vet Clin North Am Small Anim Pract 21:509–521.
  15. 15. Suzuki, K., Nakatani, K., et al. (2006) Vaginal rhabdomyosarcoma in a dog. Vet Pathol 43:186–188.
  16. 16. Bartel, C., Berghold, P., et al. (2011) Ectopic endometrial tissue in mesonephric duct remnants in bitches. Reprod Domest Anim 46:950–956.

TUMORS OF THE TESTICLE


Introduction


The histogenesis of tumors of the testicle is similar to that of the ovary; however, only two of the three potential embryological derivations are significant; specifically, testicular tumors of domestic animals generally arise from either the sex cord stromal elements of the gonad or from germ cells (Box 16.2). Seminoma is the testicular homolog of ovarian dysgerminoma, with both being derived from germ cells. Teratomas also are derived from germ cells. Sex cord stromal tumors of the testicle include Leydig (interstitial) and Sertoli (sustentacular) cell tumors, which closely resemble some forms of ovarian granulosa cell tumors and luteomas (and related lipid cell tumors and ovarian Leydig cell tumor). The Sertoli cell tumor, like many sex cord stromal tumors of the ovary, frequently is hormonally productive. Leydig cell tumors are much more rarely hormonally active.1

Tags:
Mar 30, 2020 | Posted by in INTERNAL MEDICINE | Comments Off on Tumors of the Genital Systems

Full access? Get Clinical Tree
Get Clinical Tree app for offline access