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ISSN : 2508-755X(Print)
ISSN : 2288-0178(Online)
Journal of Embryo Transfer Vol.32 No.4 pp.325-329

Unusual Necrotizing Uterine Adenocarcinoma in a Dog

Tae-Jung Kim, Sung-Shik Shin, Sang-Ik Park†
College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea

* Tae-Jung Kim and Sung-Shik Shin contributed equally to this work.

Correspondence: Sang-Ik Park +82-62-530-2843, +82-62-530-0835,
20171115 20171201 20171215


A 2-year-old female Maltese dog was admitted with a history of pyometra and resulting peritonitis and septicemia. Uterine specimen sampled by ovariohysterectomy was processed routinely for histopathological observation. Grossly, the uterine mucosa was covered with necrotic debris and on the cut surface, lesion extended into the uterine wall. Microscopically, severe necrosis was observed throughout thickened mucosa, submucosa, and wall of uterus. Tumorous lesions composed of anaplastic cells with bizarre nuclei or tubular structures of cuboidal to short columnar cells were infrequently observed around the necrotic lesions and muscular layer far from necrotic areas. Immunohistochemically, central necrotic area with ambiguous cell and tissue structures, peri-necrotic tumor lesions, and muscular layer were strongly positive for cytokeratin. Since huge necrosis of adenocarcinoma lesions in this case made it difficult to diagnose, immunohistochemical results enable to diagnose as a severe necrotizing adenocarcinoma. Thus, histopathological and immunohistochemical findings in this case may serve as an important knowledge to diagnose uterine adenocarcinoma with huge necrosis in the veterinary field.



    Uterine tumors are known to rarely occur in dogs, ranging from 0.3 to 0.4 % of all canine tumors (Murphy et al., 1994; Cave et al.., 2002). They usually affect middle-aged to older female dogs that have not been spayed (Murphy et al., 1994; Cave et al.., 2002). These tumors arise from both uterine epithelial cells and mesenchymal cells. The classification of uterine tumors takes into consideration of the histological structure of uterus: epithelial tumors (adenoma and adenocarcinoma); mesenchymal tumors (fibroma; fibrosarcoma; leiomyoma; leiomyosarcoma; lipoma and lymphoma); unclassified tumors; and tumor-like lesions (adenomatosis, cystic endometrial h yperplasia; endometrial polyp; lymphangiectasia; mesonephric duct cysts; serous cysts; subinvolutioned placental sites and squamous metaplasia) (McEntee and Nelsen, 1976). Of these tumors reported, leiomyomas and leiomyosarcomas are most common. In contrast to human, the uterine adenocarcinoma is rare in most domestic animals except cattle and rabbits (Kennedy and Miller, 1993). The reports on canine uterine adenocarcinomas are occasional, and occur in young and geriatric bitch (Payne-Johnson et al., 1986; Baldwin et al., 1992; Murphy et al., 1994; Cave et al., 2002; Pires et al., 2010). The present study reports unusual necrotizing uterine adenocarcinoma which impeded the diagnosis of this case and requires additional diagnosis methods such as immunohistochemistry with tumor markers.


    A 2-year-old, female, Maltese dog was administrated to Chonnam National University Teaching Hospital with a history of severe depression, vomiting, purulent, and hemorrhagic vaginal discharge. Ultrasonography showed that two fistulas were found in the left uterine horn, followed by mesenteric swelling, multiple abdominal lymph node enlargements and hydroperitoneum. Consequently, peritonitis and septicemia, possibly resulting from uterine rupture, were suspected. Blood examination revealed severe anemia and pancytopenia. Animal was subjected to surgical removal of the uterus and both ovaries. Grossly, the uterine mucosa was covered with necrotic debris (Figure 1A). On the cut surface, this necrotic lesion extended deeper into the uterine wall (Figure 1B). The serosa also presented dark brown discolorations, which were possibly due to hemorrhage and/or necrosis (Figure 1B). For histopathological observation, tissue samples were fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Microscopically, severe necrosis was observed from the mucosal to the muscular layers (Figure 2A). Tubular structures were observed around the necrotic areas (Figure 2B). They were lined by simple cuboidal to short columnar cells, and were surrounded by spindle shaped cells (Figure 2C). Lymphoid cells infiltrated in the necrotic lesions (Figure 2B). In addition, anaplastic cells with bizarre nuclei were occasionally found (Figure 2D). To identify this necrotic lesions, immunohistochemical stains were performed with selected tissue sections using a Dako REAL™ EnVision™ Detection System (Dako, Santa Clara, CA, USA) according to manufacturer’s instructions. Tissue sections were incubated overnight in a moist chamber at 4°C with antibodies against cytokeratin AE1/3 (DakoCytomation, M3515), desmin (Novocastra, NCL-L-DESDERII), and vimentin (Dako, M0725). Out of these markers, only cytokeratin showed immunoreactivity with central necrotic areas showing ambiguous cell and tissue structures, peri-necrotic tumor lesions, and tumor cells in the muscular layer (Figure 3).

    Diagnosis of severe necrotizing adenocarcinoma of the uterus is difficult due to ambiguous cell and tissue structures. Moreover, it should be differentiated from tumor-like lesions such as adenomyosis, cystic endometrial hyperplasia, and uterine stromal polyps (Meuten, 2016). In this case, histopathological comparison of adenocarcinoma with other differential diagnoses was based on the presence of tubular structure made up of neoplastic epithelial cells and also the dispersed identification of anaplastic tumor cells throughout the lesion, which is not found in the above mentioned lesions. Immunohistochemistry with antibody specific for cytokeratin definitively enable the diagnosis of this case as a unusual necrotizing uterine adenocarcinoma since the tumor mass was strongly positive for cytokeratin but not to other markers used in this study.


    Uterine adenomas and carcinomas in domestic animals are very rare with only limited number of cases reported in veterinary literature (Baldwin et al., 1992; Cave et al., 2002). In dogs and cats, leiomyoma is the most common uterine tumor, which accounts for 85-90% of uterine tumors (O’Keefe, 1995). The factors that define causes of uterine adenomas and carcinomas in domestic animals are unknown, and were mostly compared with cases in women (Comparative Oncology). In women, prolonged estrogenecity with cystic endometrial hyperplasia are considered the predisposing factors that can lead to the development of these neoplasms (O’Keefe, 1995, Cave et al., 2002). However, the common form of endometrial hyperplasia in dogs is cystic hyperplasia which is usually mediated by high levels of progesterone (Baldwin et al., 1992). Thus, high levels of progesterone in dogs compared with the increase levels of estrogen in women might explain why there is a low frequency of cystic hyperplasia proceeding to a full blown adenoma/carcinoma in dogs (Baldwin et al., 1992).

    One notable feature of this case is the presence of huge necrosis of tumor lesion. However, only few reported cases discussed the occurrence of necrosis in association with malignant tumors in veterinary field. Necrosis was identified in cases of invasive adenocarcinoma in different organs in humans (Caruso et al., 2014). Tumor necrosis has been indicative of poor prognosis for different human neoplasm (Caruso et al., 2014). In this case, areas of necrosis were observed in the mucosa, submucosa, and muscular layers of the uterus. Considering area of necrosis, this occurrence might be caused by chronic ischemia due to the rapid and aggressive growth of the tumor, not by peritonitis or other bacterial infection. It is suggested that histological necrosis within tumors caused by ischemia is due to vascular collapse, high interstitial pressure and/or rapid tumor growth surpassing its blood supply (Caruso et al., 2014). Thus, this case provides important information which has high reproducibility among pathologists in the veterinary field.

    The primary treatment for uterine tumors in dogs is ovariohysterectomy and removal of any tumor that have metastasized to other parts of the body (Cave et al., 2002). The effectiveness of other treatment such as chemotherapy and/or radiotherapy in dogs is not well documented due to the low incidence of this tumor in this species (Baldwin et al., 1992; Cave et al., 2002). In this case, uterus was surgically removed and no tumor metastasis was observed via radiography. It will be interesting to know if treatments such as chemotherapy and radiotherapy will be effective in this kind of tumor, and will warrant further evaluation in the future.

    In conclusion, we described a case of unusual necrotizing uterine adenocarcinoma in a dog. Here, we provide additional information that immunohistochemistry with tumor markers may help characterizing and diagnosing necrotizing adenocarcinoma in the canine uterus. Additional studies are necessary to further aid in the understanding of this type of tumor in domestic animals.



    (A) Grossly, the uterine mucosa was covered with severe necrotic debris. (B and C) On the cut surface of figure A, necrotic (arrow), and tumorous lesions (asterisk) extended deeper into the uterine wall (arrow). Bar = 1 cm.


    (A) Mucosa and submucosa of the uterine showed severe diffuse necrosis in low magnification. (B) In medium magnification, severe diffuse necrosis was prominent in the mucosal and submucosa, hampering the recognition of cell and histological structures. Note the severe infiltration of lymphoid cells in the submucosa and muscular layer. (C) Tubular structures lined by simple cuboidal to short columnar cells with pleomorphic polyhedral to spindle cells containing ample eosinophilic cytoplasm were infrequently observed around the necrotic lesions or randomly in the muscular layer. (D) Some tumor cells were anaplastic and had bizarre nuclei (arrow). Hematoxylin and eosin stain. (A and B) Bar = 200 ㎛. (C and D) Bar = 50 ㎛.


    (A) Necrotic lesions observed from the mucosa to muscular layer were strongly positive for cytokeratin. (B) Tumor cells found in tubular structures (arrow) as well as non-tubular structures (double arrow) were positive for cytokeratin. Immunohistochemistry with antibody against cytokeratin. Counter straining with Mayer’s hematoxylin. (A) Bar = 200 ㎛. (B) Bar = 50 ㎛.



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