Adenofibroma of the uterine tube in a pig

In general, adenofibromas are biphasic tumors composed of both epithelial and mesenchymal tissue components that resemble a fibroma. ⁷ In the case of the female reproductive tract, all layers of the wall are derived from paramesonephric duct, originating from mesoderm. ¹ Although rare occurrences of uterine tube adenofibroma have been reported in humans and a dog, we found no reported cases in pigs, searching PubMed, Google Scholar, and Elsevier databases using the search terms “adenofibroma”, “fibroadenoma”, “ovarian tumor”, “pig.’’^2,14 Tumors of the uterine tube are rare across all domestic species. ⁶

Despite their historical status as production or food animals, the number of pet pigs has steadily increased; the Vietnamese pot-bellied pig in particular has gained popularity since 1986, with ~35,000 pigs reported in the United States between 1991 and 1995. ¹² Given that most production pigs have short lives, information regarding reproductive neoplasia in swine is scant.^9,15 Pot-bellied pigs apparently have a higher prevalence of uterine leiomyomas compared to production pigs.^8,15 Reproductive pathology in pigs, particularly involving the uterus, is not well-documented. However, a 2010 publication reported paramesonephric duct cysts in 5 female miniature pet pigs. ¹⁰

A 10-y-old female Large Black pig was submitted for postmortem examination due to heart failure and abdominal swelling, which was unresponsive to furosemide. An 11-kg, 30-cm, pale-pink, firm, multinodular mass was found in the region of the right ovary (Fig. 1A); it was white on cross-section. The mass incorporated the ovary and uterine tube and was separate from the uterus.

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Figure 1.

Uterine tube adenofibroma in a pet Large Black domestic pig. A. The multilobulated, tan to red-brown paraovarian mass (left). Note the right periovarian area (chevron), right uterine horn (arrowhead), uterine body (star), and left uterine horn (arrow). B. Epithelial cells admixed with spindle cells in the tumor, arranged in streams and bundles. Note basophilic matrix in stroma. H&E. Inset: epithelial cells and blue (alcianophilic) mucin. Alcian blue–PAS. C. The abundant collagen fibers stained blue. Masson trichrome. D. A band of smooth muscles (red) and collagen fibers (blue). Masson trichrome. E. The epithelial component is positive for pancytokeratin; the spindle component is negative. Immunohistochemistry (IHC). F. Spindle cells are immunolabeled with smooth muscle actin; the epithelial component is negative. IHC.

Tissue samples were collected and fixed in 10% neutral-buffered formalin, processed routinely, and sections stained with H&E, Masson trichrome, and Alcian blue combined with periodic acid–Schiff (PAS) stain. ¹¹ Sections were placed on charged slides and immunolabeled with pancytokeratin (clone AE1/AE3; Bond-Max, Leica), smooth muscle actin (SMA; mouse monoclonal clone 1A4, 1:200; Autostainer Plus, Dako) and desmin (mouse monoclonal clone DE33, 1:200; Discovery Ultra, Ventana). Appropriate positive and negative controls were included.

The mass was expansile, unencapsulated, and well-demarcated. Although the right ovary was not found, one section included a single normal smooth muscle layer of the right uterine tube that appeared to be pushed aside by the mass. The neoplasm was made up of 2 neoplastic cell populations—mesenchymal and epithelial tissue (Fig. 1B). The mesenchymal tissue population was ~95% of the mass. The cells were spindle shaped, arranged in streams and bundles, and widely separated from each other. Individual neoplastic cells were thin and had indistinct cell borders and minimal eosinophilic homogeneous cytoplasm. Nuclei were vesicular, and most had pointed ends and indistinct nucleoli. Randomly distributed throughout the mesenchymal population was an epithelial population that was arranged in tubules and clusters. Individual neoplastic epithelial cells were cuboidal with well-defined cell borders, eosinophilic cytoplasm, and round, central-to-basal nuclei with distinct nucleoli. Anisocytosis and anisokaryosis were mild, and no mitotic figures were identified. With Alcian blue combined with the PAS stain, occasional blue intracytoplasmic staining was seen within epithelial cells (Fig. 1C). The intercellular matrix was abundant fine collagen that stained pink with Alcian blue stain (Fig. 1C) and blue with Masson trichrome stain (Fig. 1D). In the epithelial population, cytoplasmic immunolabeling was intense with pancytokeratin (Fig. 1E). The mesenchymal cells did not stain red with Masson trichrome stain; they had strong, diffuse cytoplasmic immunolabeling with SMA (Fig. 1F) and ~20% were desmin positive. The uterus had mild cystic endometrial hyperplasia.

Based on the location, the biphasic nature of the neoplasm, and the phenotype of the mesenchymal tissue with pointed vesicular nuclei, minimal cytoplasm, abundant collagen, and lack of cytoplasmic red staining with Masson trichrome, we diagnosed this mass as an adenofibroma of the uterine tube. ¹¹ Other tumors were considered, including endometrial stromal tumor, smooth muscle tumor (leiomyoma, leiomyosarcoma), adenofibroleiomyoma, and adenosarcoma. The biphasic appearance of well-differentiated fibrous and glandular components that lacked the criteria of malignancy, and histochemical staining, support a diagnosis of adenofibroma. Adenoleiomyoma, adenofibroleiomyoma, and leiomyoma were excluded because the spindle cells did not have the phenotypic appearance of smooth muscle but rather had the appearance of fibroblasts and fibrocytes embedded in abundant collagenous matrix. Additionally, the intercellular matrix stained blue with Masson trichrome stain, and the cytoplasm of the cells were not red, as expected for smooth muscle. ¹¹ The normal-appearing smooth muscle cells were SMA- and partially desmin-positive, interpreted as normal smooth muscle of the uterine tube. Cells that stain with SMA are generally considered to be smooth muscle cells. However, the cells of the ovarian capsule and cortical stroma, and uterine tube and endometrial lamina proprial (stromal) cells, are often SMA-positive. They are thought to be myofibroblasts. ¹¹ A tumor of ovarian origin was discounted because the inner wall of the uterine tube appeared to be the site of origin of the tumor. An adenofibroma with endometrial-type glandular epithelium and with surrounding myofibroblasts was considered the phenotype of this tumor.

In humans, uterine tube adenofibromas are exceedingly rare.^2,4,14 Five cases of adenofibroma and 20 cases of fimbrial serous adenofibroma have been reported.^2,4,14 Adenofibromas are distinguished from adenofibrosarcomas based on the absence of mitotic figures or cellular atypia in adenofibroma. ⁵ In human adenofibromas, the mitotic count is typically <4 whereas adenosarcomas have >4 mitoses per 2.37 mm². ⁵ Sarcomatous components usually invade surrounding tissue, and the mesenchymal elements have criteria of malignancy, including cellular atypia. ⁵ Although adenofibromas of the uterus are reported more frequently in humans than in animals, adeno(fibro)sarcoma is even more common. ¹⁶ Human adenofibromas can invade surrounding tissues, complicating differentiation from adenosarcoma, even when meeting histologic criteria. ⁵

In non-human primates, a biphasic fimbrial neoplasm consistent with fimbrial adenomyofibroma in a cynomolgus macaque (Macaca fascicularis) was reported. ¹³ Features differentiating the fimbrial adenomyofibroma from other neoplasms were based on mesenchyme, which additionally contained smooth muscle cells, collagen, and an epithelial component forming large, plump finger-like projections. The projections had an overlying normal ciliated simple columnar epithelium. ¹³

Understanding the full clinical significance of the tumor in our case is challenging. The clinical details of our case were minimal; ultrasound, hematology, and biochemistry testing were not performed. The reproductive history of the sow was not known. The mass was large (30 cm diameter, 11 kg) and contributed to abdominal enlargement. Lymphatic compression can lead to ascites and may have occurred in our case. ³ Adenofibroma should be included in the differential diagnosis for neoplasia of the reproductive tract of female pigs.