{"paper_id":"27dd5a5a-a0d5-4ccb-97fd-a3d37e93d2c2","body_text":"Case Report Veterinarni Medicina, 53, 2008 (11): 636–640\n636\nIncidental finding of uterine adenomyosis in a bitch \nwith reproductive disorders: a case report\nC.C. Perez-Marin, L. Molina, J.M. Dominguez, Y. Millan,  \nJ. Martin de las Mulas\nVeterinary Faculty, University of Cordoba, Spain\nABSTRACT : Uterine adenomyosis, a disease not widely addressed in dogs, is characterised by the progressive \npenetration of endometrial glands and stroma into the myometrium, together with smooth-muscle hyperplasia. \nThis report describes a case of adenomyosis in an 8-year-old German Shepherd bitch with mammary tumours, \nconcomitant with cystic ovarian disease and endometrial cystic hyperplasia. Clinical signs included presence of \nsmall nodules and enlargement of mammary glands, and bloody uterine discharge. Ultrasonography confirmed the \nuterine and ovarian abnormalities, while the diagnosis was later confirmed by histopathological examination. The \nfindings are discussed as possibly related to the reproductive disorders observed, and a hypothetical participation \nof hormonal factors, as has been described in woman, is suggested. However, further studies must be realized. \nKeywords : adenomyosis; ovarian cysts; mammary tumour; infertility\nUterine adenomyosis is a non-neoplastic lesion \nresulting from the abnormal down-growth of the \nendometrial glands and endometrial stroma into \nthe myometrium (Kennedy et al., 1998). Although \nit is a rare, sporadic disorder in dogs (Tamada et al., \n2005), it is much more common in women.\nUterine adenomyosis results in no symptoms during \nmuch of its development, and is usually diagnosed in \nadult dogs. Since it is generally found as an incidental \nlesion in pathological changes of the uterus – includ-\ning endometritis, pyometra and glandular-cystic hy-\nperplasia – it tends to be investigated as a histological \nfinding rather than a clinical disorder. Adenomyosis \nhas recently been associated with infertility in hu -\nmans (Barrier et al., 2004; Matalliotakis et al., 2005), \nalthough little is known of the precise mechanisms \ninvolved. Possible causes of adenomyosis in women \ninclude defects in the formation of the myometrium \n(Parrott et al., 2001), an abnormal immune response \nin the endometrium (Ota et al., 1998), surgery and \nhormone manipulation (Mori and Nagasawa, 1989, \nBaskin et al., 2002), and age (Barrier et al., 2004).\nDiagnosis of adenomyosis in animals is always \npost-surgical, since the diagnostic techniques \nused in humans, such as the measurement of se -\nrum cancer antigen 125 (CA 125) levels (Halila et \nal., 1987), hysterosalpingography (Marshak and \nEliasoph, 1955) and magnetic resonance imaging \n(Bazot et al., 2001) are not used in canine veteri -\nnary practice.\nThis paper reports a case of adenomyosis diag -\nnosed from a tissue specimen taken from a bitch \nwith cystic endometrial hyperplasia, ovarian cysts \nand ovarian papillary cystadenoma, together with a \npreviously-diagnosed mammary carcinosarcoma.\nCase history\nAn 8-year-old nulliparous German Shepherd bitch \nwas admitted to the University of Cordoba, Veterinary \nClinic after the owner noticed a number of mammary \nnodules. Vital signs were normal except for a mild \nincrease in temperature (39.2°C). Blood biochemistry \nand metabolic tests were normal, with the exception \nof mild leukocytosis (Table 1). Physical examination \nrevealed bilateral mammary tumours, involving the \ncaudal abdominal (enlarged) and inguinal mammary \nSupported by the Consejeria de Innovacion, Ciencia y Empresa, Junta de Andalucia, Spain (Research Group Project \nBIO287).\n\nVeterinarni Medicina, 53, 2008 (11): 636–640 Case Report\n637\nglands of the right chain, and the abdominal and \ninguinal mammary glands of the left chain (smaller \ntumour masses). Laterolateral thoracic radiographs \nrevealed no pulmonary metastases and surgical re -\nsection of both mammary chains was decided upon \nas the course of action. Histological examination of \nthe right mammary chain, the first to be removed, \nconfirmed malignant disease; one tumour was diag -\nnosed as a carcinosarcoma (Figure  1 and 2). \nBloody vulvar discharge – which the owner as -\nsociated with the heat period – was observed one \nmonth later, one day prior to the second operation \n(resection of the left mammary chain). The vaginal \nsmear comprised mainly intermediate and superfi -\ncial cells showing signs of keratinization with oc -\ncasional endometrial cells. Vaginal disorders were \nnot considered during the clinical exploration. \nSubsequent abdominal ultrasonography showed \nTable 1. Biochemical and haematological parameters\nParameter Values Reference values\nWBC 13.8 × 10–3  μl 6–12 × 10 –3  μl\nRBC 7.53 × 10–6  μl 5.0–8.0 × 10 –6  μl\nHGB 18 g/dl 11–17 g/dl\nHCT 49% 37–50%\nMCV 69.2 fl 60–77 fl\nMCH 23.9 pg 20–25 pg\nMCHC 34.5 g/dl 32–36 g/dl\nPLT 167 × 10–3  μl 200–400 × 10 –3  μl\nUrea 32 mg/dl 20–40 mg/dl\nCreatinin 1.2 mg/dl 0.5–1.3 mg/dl\nTotal proteins 7.6 g/dl 6.0–7.5 g/dl\nFibrinogen 200 mg/dl 100–400 mg/dl\nGlucose 91 mg/dl 60–115 mg/dl\nWBC = white blood cells; RBC = red blood cells; HGB = hemoglobin; HCT = hematocrit; MCV, mean corpuscular volume; \nMCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; PLT = platelets\nFigure 1. Mammary carcinosarcoma (hematox -\nylin-eosin, 40×) showing rounded neoplastic \nepithelial cells with rounded-to-ovoid, vesicu -\nlar nuclei, marked nucleoli and high-grade \natypia. Myoepithelial cells with high-grade \natypia\n\nCase Report Veterinarni Medicina, 53, 2008 (11): 636–640\n638\nthat both ovaries were abnormal in size, with \nlarge anechoic structures; ovarian cystic disease \nwas diagnosed (Figure 3). Uterine ultrasonography \nfindings were consistent with endometrial cystic \nhyperplasia (Figure 4). In the light of these findings, \novariohysterectomy was performed in addition to \nthe programmed mastectomy. At gross examina -\ntion, numerous cysts were visible on the ovaries. \nOne ovary displayed a brownish-black, morula-\nlike multilobar lesion, measuring 3.5 × 2.5 × 2  cm \nand containing solid, chocolate-coloured mate -\nrial (Figure 5). A bleeding cyst was also observed, \ncomprising several thin-walled cavities containing \na translucent fluid. A large, thin-walled, multilobar \ncyst containing amber-coloured material was ob -\nserved. The cervix was slightly enlarged (approx. \n50 mm).\nMicroscopic examination disclosed a highly-edema-\ntous endometrial mucosa, which hindered interpreta-\ntion of possible hyperplasia; endometrial cysts with \nfluid retention were also observed. The cervical mucosa \nlamina propria displayed chronic inflammatory infil-\ntrate and cystic glandular dilation; evidence of fibrosis \namong muscle-fiber bundles suggested a possible cause \nof enlargement. Glandular structures surrounded by \nendometrial stroma were visible in the cornual and \ncervical myometrium (Figure 6). This finding enabled \ndiagnosis of adenomyosis.\nDISCUSSION\nIn the present case, uterine adenomyosis was an in-\ncidental finding in a bitch with mammary tumours and \nFigure 2. Resected mammary chain\nFigure. 4. Echoic uterus containing anechoic cysts, \nindicative of endometrial cystic hyperplasia\nFigure 3. Left: ultrasonograph of cystic ovary (anechoic); \nright: kidney for purposes of comparison\nFigure 5. Ovary showing brownish-black multilobar lesion \ncontaining solid, chocolate-coloured material, with a thin-\nwalled, bleeding cyst containing translucent fluid\n\nVeterinarni Medicina, 53, 2008 (11): 636–640 Case Report\n639\novarian cystic disease. In studies with mice, Nagasawa \net al. (1987) and Nagasawa and Kusakawa (2001) sug-\ngested a possible link between mammary tumours \nand uterine adenomyosis: the two disorders develop \nsimultaneously pointing to a powerful genetic, as well \nas environmental, influence. The joint presence of the \ntwo disorders here indicates that the clinical signs as \na whole may have a hormonal aetiology.\nThe literature contains three reports of canine ad-\nenomyosis, in which clinical signs were only apparent \nat an advanced stage (Stocklin-Gautschi et al., 2001; \nTamada et al., 2005) (Table 2). Although adenomyosis \nis certainly found in numerous cases of uterine pa -\nthology, the present case study suggests a link among \nadenomyosis, mammary tumour and ovarian cystic \ndisease, perhaps mediated by the influence of oestro-\ngen hormone associated with polycystic ovaries.\nAlthough the mechanism responsible for uterine \nadenomyosis is not known, research in women has \nsuggested a link between changes in the endometri -\num and in ovarian hormones, and increased lo -\ncal production of oestrogen (Leyendecker, 2006). \nOestrogen-related hyperperistalsis together with \na progesterone-induced increase in intrauterine \npressure might result in myometrial dehiscencies \nthat are infiltrated by basal endometrium with the \nsecondary development of peristromal muscular \ntissue. This would lead to diffuse or focal adenomy -\nosis of varying extent, and local aromatase produc -\ntion would contribute to the proliferation of lesions \nthrough local oestrogen synthesis (Ferenczy, 1998; \nLeyendecker, 2006). This is why adenomyosis may \nconstitute a progressive disease. With regard to the \nimpact of adenomyosis on fertility, the most likely \nexplanation is the impairment of uterine mecha -\nnisms of rapid and sustained sperm transport as a \nconsequence of the destruction of normal uterine \narchitecture (Leyendecker, 2006).\nFigure 6. Cervix. Mild chronic inflamma -\ntory infiltrate in mucosal lamina propria; \ncystic glandular dilation; fibrosis among \nsmooth-muscle-fiber bundles (hematoxy -\nlin-eosin, 4×)\nTable 2. Findings in the present case study, compared with reports of canine uterine adenomyosis in the litera -\nture\nReference Age Breed Weight Litters Hormone \ntreatment\nCervix involve -\nment \nOther  \npathologies\nVaginal  \ndischarge\nTamada et al., 2005 13 Shiba-inu 5.9 1 no yes OCD \nCEH purulent\nStocklin-Gautschi et \nal., 2001 10 Crossbred 41 no no yes\nOCD \ncervical  \nenlargment *\nbloody,  \nmilky,  \nmucosa\nStocklin-Gautschi et \nal., 2001 12 Toy Poodle 4.5 no no yes no \nuterine torsion\nno, tense \nabdomen\n*the remainder of the uterus was normal\n\nCase Report Veterinarni Medicina, 53, 2008 (11): 636–640\n640\nCorresponding Author: \nCarlos C. Perez Marin, University of Cordoba, Veterinary Faculty, Department of Animal Medicine and Surgery, \n140-14 Cordoba, Spain\nTel. +34 957 218 716, fax +34 957 211 093, e-mail: pv2pemac@uco.es\nHere, the joint presentation of endometrial hyper-\nplasia with cysts suggested that adenomyosis may \nperhaps be due to an endocrine impairment. Ovarian \nhormones are known to favour the development of \nmammary tumours; thus, early ovariectomy has been \nfound to limit tumour development (Schneider et al., \n1969). However, the aetiology of uterine adenomyosis \nremains unclear, and the disorder is rarely addressed \nin the literature. Reported symptoms vary widely, \nwhich is suggestive of a multifactorial aetiology.\nREFERENCES\nBarrier B.F., Malinowski M.J., Dick E.J., Hubbard G.B., \nBates W.B. (2004): Adenomyosis in the baboon is as -\nsociated with primary infertility. Fertility and Sterility, \n82, 1091–1094.\nBaskin G.B., Smith S.M., Marx P.A. (2002): Endometrial \nhyperplasia, polyps, and adenomyosis associated with \nunopposed estrogen in rhesus monkeys ( Macaca mu -\nlatta ). Veterinary Pathology, 39, 572–575.\nBazot M., Cortez A., Darai E., Rouger J., Chopier J., An -\ntoine J.M., Uzan S. (2001): Ultrasonography compared \nwith magnetic resonance imaging for the diagnosis of \nadenomyosis: correlation with histopathology. Human \nReproduction, 16, 2427–2433.\nFerenczy A. (1998): Pathophysiology of adenomyosis. \nHuman Reproduction, Update 4, 312–322.\nHalila H., Suikkari A.M., Seppala M. (1987): The effects \nof hysterectomy on serum CA-125 levels in patients \nwith adenomyosis and uterine fibroids. Human Re -\nproduction, 2, 265–266.\nKennedy P .C., Cullen J.M., Edwards J.F., Goldschmidt \nM.H., Larsen S., Munson L., Nielson S. (1998): Histo-\nlogical Classification of Tumors of the Genital System \nof Domestic Animals . Armed Forces Institute of Pa -\nthology, Washington, DC.\nLeyendecker G. (2006): Adenomyosis and reproduction. \nBest Practice & Research. Clinical Obstetrics & Gy -\nnaecology, 201, 1–24.\nMarshak R.H., Eliasoph J. (1955): The roentgen findings \nin adenomyosis. Radiology, 64, 846–851.\nMatalliotakis I.M., Katsikis A.K., Panidis D.K. (2005): \nAdenomyosis: what is the impact on fertility? Current \nOpinion in Obstetrics & Gynecology, 17, 261–264.\nMori T., Nagasawa H. (1989): Multiple endocrine syn -\ndrome in SHN mice: mammary tumors and uterine \nadenomyosis. In: Kaiser H.E. (ed.): Comparative As -\npects of Tumor Development. Kluwer, Dordrecht. \n121–130.\nNagasawa H., Kusakawa S. (2001): Relationship between \nincidence and onset age of mammary tumours and \nuterine adenomyosis in four strains of mice: compar -\nison with the findings of 40 generations previously. In \nVivo, 15, 345–349.\nNagasawa H., Ishida M., Mori T. (1987): Effects of treat -\nment with prolactin or progesterone on the coinci -\ndence of mammary tumors and uterine adenomyosis \nin young SHN mice. Laboratory Animal Science, 37, \n200–202.\nOta H., Igarashi S., Hatazawa J., Tanaka T. (1998): Is \nadenomyosis an immune disease? Human Reproduc -\ntion, Update 4, 360–367.\nParrott E., Butterworth M., Green A., White N.H., \nGreaves P . (2001): Adenomyosis – A result of disor -\ndered stromal differentation. The American Journal \nof Pathology, 159, 623–630.\nSchneider R., Dorn C.R., Taylor D.O. (1969): Factors \ninfluencing canine mammary cancer development and \npost surgical survival. Journal of the National Cancer \nInstitute, 43, 1249–1261.\nStocklin-Gautschi N.M., Guscetti F., Reichler I.M., Geiss-\nbuhler U., Braun S.A., Arnold S. (2001): Identification \nof focal adenomyosis as a uterine lesion in two dogs. \nThe Journal of Small Animal Practice, 42, 413–416.\nTamada H., Kawate N., Inaba T., Kuwamura M., Maeda \nM., Kajikawa T., Sawada T. (2005): Adenomyosis with \nsever inflammation in the uterine cervix in a dog. The \nCanadian Veterinary Journal, 46, 333–334.\nReceived: 2008–08–13\nAccepted: 2008–11–23","source_license":"CC0","license_restricted":false}