Incidental finding of uterine adenomyosis in a bitch with reproductive disorders: a case report

Uterine adenomyosis, a disease not widely addressed in dogs, is characterised by the progressive penetration of endometrial glands and stroma into the myometrium, together with smooth-muscle hyperplasia. This report describes a case of adenomyosis in an 8-year-old German Shepherd bitch with mammary tumours, concomitant with cystic ovarian disease and endometrial cystic hyperplasia. Clinical signs included presence of small nodules and enlargement of mammary glands, and bloody uterine discharge. Ultrasonography confirmed the uterine and ovarian abnormalities, while the diagnosis was later confirmed by histopathological examination. The findings are discussed as possibly related to the reproductive disorders observed, and a hypothetical participation of hormonal factors, as has been described in woman, is suggested. However, further studies must be realized.

adenomyosis; ovarian cysts; mammary tumour; infertility Uterine adenomyosis is a non-neoplastic lesion resulting from the abnormal down-growth of the endometrial glands and endometrial stroma into the myometrium (Kennedy et al., 1998). Although it is a rare, sporadic disorder in dogs (Tamada et al., 2005), it is much more common in women. Uterine adenomyosis results in no symptoms during much of its development, and is usually diagnosed in adult dogs. Since it is generally found as an incidental lesion in pathological changes of the uterus – includ- ing endometritis, pyometra and glandular-cystic hy- perplasia – it tends to be investigated as a histological finding rather than a clinical disorder. Adenomyosis has recently been associated with infertility in hu - mans (Barrier et al., 2004; Matalliotakis et al., 2005), although little is known of the precise mechanisms involved. Possible causes of adenomyosis in women include defects in the formation of the myometrium (Parrott et al., 2001), an abnormal immune response in the endometrium (Ota et al., 1998), surgery and hormone manipulation (Mori and Nagasawa, 1989, Baskin et al., 2002), and age (Barrier et al., 2004). Diagnosis of adenomyosis in animals is always post-surgical, since the diagnostic techniques used in humans, such as the measurement of se - rum cancer antigen 125 (CA 125) levels (Halila et al., 1987), hysterosalpingography (Marshak and Eliasoph, 1955) and magnetic resonance imaging (Bazot et al., 2001) are not used in canine veteri - nary practice. This paper reports a case of adenomyosis diag - nosed from a tissue specimen taken from a bitch with cystic endometrial hyperplasia, ovarian cysts and ovarian papillary cystadenoma, together with a previously-diagnosed mammary carcinosarcoma. Case history An 8-year-old nulliparous German Shepherd bitch was admitted to the University of Cordoba, Veterinary Clinic after the owner noticed a number of mammary nodules. Vital signs were normal except for a mild increase in temperature (39.2°C). Blood biochemistry and metabolic tests were normal, with the exception of mild leukocytosis (Table 1). Physical examination revealed bilateral mammary tumours, involving the caudal abdominal (enlarged) and inguinal mammary Supported by the Consejeria de Innovacion, Ciencia y Empresa, Junta de Andalucia, Spain (Research Group Project BIO287). Veterinarni Medicina, 53, 2008 (11): 636–640 Case Report 637 glands of the right chain, and the abdominal and inguinal mammary glands of the left chain (smaller tumour masses). Laterolateral thoracic radiographs revealed no pulmonary metastases and surgical re - section of both mammary chains was decided upon as the course of action. Histological examination of the right mammary chain, the first to be removed, confirmed malignant disease; one tumour was diag - nosed as a carcinosarcoma (Figure 1 and 2). Bloody vulvar discharge – which the owner as - sociated with the heat period – was observed one month later, one day prior to the second operation (resection of the left mammary chain). The vaginal smear comprised mainly intermediate and superfi - cial cells showing signs of keratinization with oc - casional endometrial cells. Vaginal disorders were not considered during the clinical exploration. Subsequent abdominal ultrasonography showed Table 1. Biochemical and haematological parameters Parameter Values Reference values WBC 13.8 × 10–3 μl 6–12 × 10 –3 μl RBC 7.53 × 10–6 μl 5.0–8.0 × 10 –6 μl HGB 18 g/dl 11–17 g/dl HCT 49% 37–50% MCV 69.2 fl 60–77 fl MCH 23.9 pg 20–25 pg MCHC 34.5 g/dl 32–36 g/dl PLT 167 × 10–3 μl 200–400 × 10 –3 μl Urea 32 mg/dl 20–40 mg/dl Creatinin 1.2 mg/dl 0.5–1.3 mg/dl Total proteins 7.6 g/dl 6.0–7.5 g/dl Fibrinogen 200 mg/dl 100–400 mg/dl Glucose 91 mg/dl 60–115 mg/dl WBC = white blood cells; RBC = red blood cells; HGB = hemoglobin; HCT = hematocrit; MCV, mean corpuscular volume; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; PLT = platelets Figure 1. Mammary carcinosarcoma (hematox - ylin-eosin, 40×) showing rounded neoplastic epithelial cells with rounded-to-ovoid, vesicu - lar nuclei, marked nucleoli and high-grade atypia. Myoepithelial cells with high-grade atypia Case Report Veterinarni Medicina, 53, 2008 (11): 636–640 638 that both ovaries were abnormal in size, with large anechoic structures; ovarian cystic disease was diagnosed (Figure 3). Uterine ultrasonography findings were consistent with endometrial cystic hyperplasia (Figure 4). In the light of these findings, ovariohysterectomy was performed in addition to the programmed mastectomy. At gross examina - tion, numerous cysts were visible on the ovaries. One ovary displayed a brownish-black, morula- like multilobar lesion, measuring 3.5 × 2.5 × 2 cm and containing solid, chocolate-coloured mate - rial (Figure 5). A bleeding cyst was also observed, comprising several thin-walled cavities containing a translucent fluid. A large, thin-walled, multilobar cyst containing amber-coloured material was ob - served. The cervix was slightly enlarged (approx. 50 mm). Microscopic examination disclosed a highly-edema- tous endometrial mucosa, which hindered interpreta- tion of possible hyperplasia; endometrial cysts with fluid retention were also observed. The cervical mucosa lamina propria displayed chronic inflammatory infil- trate and cystic glandular dilation; evidence of fibrosis among muscle-fiber bundles suggested a possible cause of enlargement. Glandular structures surrounded by endometrial stroma were visible in the cornual and cervical myometrium (Figure 6). This finding enabled diagnosis of adenomyosis.

In the present case, uterine adenomyosis was an in- cidental finding in a bitch with mammary tumours and Figure 2. Resected mammary chain Figure. 4. Echoic uterus containing anechoic cysts, indicative of endometrial cystic hyperplasia Figure 3. Left: ultrasonograph of cystic ovary (anechoic); right: kidney for purposes of comparison Figure 5. Ovary showing brownish-black multilobar lesion containing solid, chocolate-coloured material, with a thin- walled, bleeding cyst containing translucent fluid Veterinarni Medicina, 53, 2008 (11): 636–640 Case Report 639 ovarian cystic disease. In studies with mice, Nagasawa et al. (1987) and Nagasawa and Kusakawa (2001) sug- gested a possible link between mammary tumours and uterine adenomyosis: the two disorders develop simultaneously pointing to a powerful genetic, as well as environmental, influence. The joint presence of the two disorders here indicates that the clinical signs as a whole may have a hormonal aetiology. The literature contains three reports of canine ad- enomyosis, in which clinical signs were only apparent at an advanced stage (Stocklin-Gautschi et al., 2001; Tamada et al., 2005) (Table 2). Although adenomyosis is certainly found in numerous cases of uterine pa - thology, the present case study suggests a link among adenomyosis, mammary tumour and ovarian cystic disease, perhaps mediated by the influence of oestro- gen hormone associated with polycystic ovaries. Although the mechanism responsible for uterine adenomyosis is not known, research in women has suggested a link between changes in the endometri - um and in ovarian hormones, and increased lo - cal production of oestrogen (Leyendecker, 2006). Oestrogen-related hyperperistalsis together with a progesterone-induced increase in intrauterine pressure might result in myometrial dehiscencies that are infiltrated by basal endometrium with the secondary development of peristromal muscular tissue. This would lead to diffuse or focal adenomy - osis of varying extent, and local aromatase produc - tion would contribute to the proliferation of lesions through local oestrogen synthesis (Ferenczy, 1998; Leyendecker, 2006). This is why adenomyosis may constitute a progressive disease. With regard to the impact of adenomyosis on fertility, the most likely explanation is the impairment of uterine mecha - nisms of rapid and sustained sperm transport as a consequence of the destruction of normal uterine architecture (Leyendecker, 2006). Figure 6. Cervix. Mild chronic inflamma - tory infiltrate in mucosal lamina propria; cystic glandular dilation; fibrosis among smooth-muscle-fiber bundles (hematoxy - lin-eosin, 4×) Table 2. Findings in the present case study, compared with reports of canine uterine adenomyosis in the litera - ture

Age Breed Weight Litters Hormone treatment Cervix involve - ment Other pathologies Vaginal discharge Tamada et al., 2005 13 Shiba-inu 5.9 1 no yes OCD CEH purulent Stocklin-Gautschi et al., 2001 10 Crossbred 41 no no yes OCD cervical enlargment * bloody, milky, mucosa Stocklin-Gautschi et al., 2001 12 Toy Poodle 4.5 no no yes no uterine torsion no, tense abdomen *the remainder of the uterus was normal Case Report Veterinarni Medicina, 53, 2008 (11): 636–640 640 Corresponding Author: Carlos C. Perez Marin, University of Cordoba, Veterinary Faculty, Department of Animal Medicine and Surgery, 140-14 Cordoba, Spain Tel. +34 957 218 716, fax +34 957 211 093, e-mail: [email protected] Here, the joint presentation of endometrial hyper- plasia with cysts suggested that adenomyosis may perhaps be due to an endocrine impairment. Ovarian hormones are known to favour the development of mammary tumours; thus, early ovariectomy has been found to limit tumour development (Schneider et al., 1969). However, the aetiology of uterine adenomyosis remains unclear, and the disorder is rarely addressed in the literature. Reported symptoms vary widely, which is suggestive of a multifactorial aetiology.

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