Leiomyoadenomatoid tumor of uterus: two case reports with literature review

Adenomatoid tumors (AT) are benign neoplasms of mesothelial origin that occur more frequently in the genital tracts. In uterus, AT are usually located in the subserosa of the cornual myometrium. Microscopically, it is characterized by interanastomosing pseudoglands or pseudovascular spaces and striking smooth-muscle hypertrophy is often present. In some cases, the prominence of smooth muscle component simulates a leiomyoma and the lesion is denoted as a leiomyoadenomatoid tumor. The microscopic appearance of the adenomatoid component (AC) may mimic a malignant tumor due to irregular pseudoinfiltration with tubular formations. Just 16 cases with this morphological presentation were found in the literature review. The first case, a 38-year-old female, showed lower abdominal pain, menorrhagia, postcoital bleeding and previous history of uterin leiomyoma. The second case, a 26-year-old female, had clinical complaint of metrorrhagia and received diagnostic hypothesis of leiomyoma after ultrasound image. Both underwent myomectomy. Microscopically, the uterine masses showed intersecting smooth muscle bundles and gland like areas lined by cuboidal epithelioid cells that stained positive for WT1, D2–40 and calretinin in immunohistochemical analysis. The cases were diagnosed as leiomyoadenomatoid tumor of the uterus. This is a benign and rare entity that may mimic malignant tumors due to the pseudo infiltrative appereance of the adenomatoid component, possibly leading to misdiagnosis.


Background
Adenomatoid tumors (AT) are benign neoplasms of mesothelial origin that occur more frequently in the genital tracts of both men and women. In uterus, AT are usually located in the subserosa of the cornual myometrium. Lesions are typically solitary, but multicentric cases have been reported (Amre et al. 2005;Mathew and Goel 2010;Kurman et al. 2014). Microscopically, AT show interanastomosing pseudoglands or pseudovascular spaces, and a smooth-muscle component is often present (Kurman et al. 2014).
In some cases, the prominence of smooth muscle component simulates a leiomyoma and the lesion is denoted as a "leiomyoadenomatoid tumor". In this morphological pattern, the microscopic appearance of the adenomatoid component (AC) may mimic a malignant tumor due to irregular pseudoinfiltration with tubular formations (Amre et al. 2005;Bedir et al. 2014;Kurman et al. 2014). There were found only 16 cases of this morphological presentation in our literature review.
In this paper we report two cases of leiomyoadenomatoid tumors of the uterus with emphasis on the morphologic and immunohistochemical findings, besides discussing the diagnostic difficulties along with a brief review of the literature.

Case presentation
The first case, a 38-year-old female attended the gynecology clinic with lower abdominal pain, menorrhagia, postcoital bleeding and ultrasound images of the uterus suggestive of leiomyoma. There was no abnormality in cervical cytology and no improvement of postcoital bleeding after cervical cauterization. The patient underwent a myomectomy. The other case was a 26year-old female with metrorrhagia. The patient received the diagnostic hypothesis of leiomyoma retrieved from ultrasound image and was also subjected to myomectomy.
A 3.8 × 2.9 × 2.5 cm mass was obtained from the first case. In the second, the mass measured 3.3 × 3.1 × 2.9 cm. Gross examination of the masses revealed a nodular aspect and ragged surface. The cut surface revealed a whorled appearance.
Microscopically, the uterine mass showed intersected hypertrophic smooth-muscle bundles. Organized multifocal pseudovascular and pseudoglandular areas arranged in cystic and tubular spaces were seen. These spaces were lined by cuboidal epithelioid cells with scanty, pale, and eosinophilic vacuolated cytoplasm with occasional signet ring-like cells. No abnormal mitotic activity or cytological atypia were seen.
Immunohistochemical investigations were performed in both cases. The first case stained positive for cytokeratin 7 (CK7) in AC and negative for CK20. CDX-2, PAX8 and vascular markers CD31, CD34 and ERG were negative. The second case presented positivity for cytokeratins EA1-AE3 and low proliferative Ki-67 index.
Both tumors showed expression of WT-1, D2-40 and calretinin, supporting the hypothesis of mesothelial nature of the lining epithelial cells in AC. The SMA expression was confirmed in smooth muscle component in both cases. Therefore, the cases were diagnosed as AT of the uterus with a prominent muscular component - leiomyoadenomatoid tumors -based on the histopathological and immunohistochemical findings ( Figs. 1 and 2).

Discussion and conclusion
The term leiomyoadenomatoid tumor was first used by Epstein in 1992 as a morphological variant of AT with a prominent smooth muscle component (Epstein 1992). According to the World Health Organization (2014), AT of the uterus affect patients in a wide age range (45 years, in average). Most of the tumors are incidental findings and are located in the outer myometrium. They usually present as a solitary, small (< 4 cm) and solid tumor, but sometimes can be diffuse, multifocal, large (> 10 cm), or predominantly cystic (Kurman et al. 2014).
Microscopically, AT are characterized by interanastomosing pseudovascular and pseudoglandular spaces, lined by flat or cuboidal cells, some with a signet ringlike appearance. A smooth-muscle hypertrophy component is often present. A lymphoid infiltrate can usually be seen (Kurman et al. 2014). The majority of AT are readily diagnosed based on location and typical microscopic features. However, sometimes can be challenging, especially when facing cases of leiomyoadenomatoid tumor (Erra et al. 2009;Amérigo et al. 2010;Prangsgaard et al. 2013;Kopuz et al. 2015;Junainah et al. 2017). The microscopic appearance of this morphological variant may mimic a malignant tumor due to irregular pseudoinfiltration, with tubular formations that suggest presence of an infiltrating carcinoma or a malignant mesothelial neoplasm into a leiomyoma or into the myometrium (Epstein 1992;Bedir et al. 2014).