MA is a rare malignancy of the female genital tract occurring mostly in the cervix [
11] and rarely in the vagina [
12]. Few cases of MA have been reported in the uterine corpus [
2‐
10]. A unique histologic pattern of uniform small tubules containing intraluminal hyaline material is reminiscent of mesonephric remnants [
13]. The remnants are sometimes found within the lateral wall of the cervix, mesoovaries, or broad ligaments. Although much more rare, the remnants can also be found in the lateral wall of the vagina or uterine corpus [
14]. MA of the cervix or vagina is believed to originate in the mesonephric remnants. However, the question about a real corpus MA has been raised by McFarland et al., who described corpus mesonephric-like adenocarcinomas that appeared to arise in the endometrium and infiltrate into the myometrium [
9]. These authors proposed that corpus MA originated from Müllerian tissue and obtained the morphological and immunohistochemical phenotype characteristic of mesonephric differentiation; this tumor is described as a ‘mesonephric-like adenocarcinoma’ rather than MA. In addition to that case, 10 additional cases of corpus MA, including the present tumor, have been reported [
2‐
8,
10]. While one case was believed to be derived from the endometrium, the epicenter of five tumors was in the myometrial layer [
5,
6,
8,
10], and three tumors were completely confined to the myometrial layer [
2,
3] (Table
2). It is reasonable to conclude that the tumors originated within the myometrial layer in the latter eight cases. Carcinomas rarely occur within the myometrial layer, with most originating from the ectopic endometrial tissue (adenomyosis). Since adenomyosis is common, it is not unusual to detect the lesion, even in cases of MA. In fact, the presence of adenomyosis was described in two cases, including the present case [
10]. In these cases, despite a thorough examination, ectopic endometrial tissue was not found in the tumor. Moreover, we did not observe a carcinoma with the morphologically conventional Müllerian phenotype. Therefore, evidence suggesting that these two tumors arose from ectopic endometrial tissue, even in the presence of adenomyosis, is not convincing. In addition, it is important to remember that most MAs that originated within the corpus myometrium were found in the lateral wall [
2,
5,
8,
10], where mesonephric remnants were often observed in the cervix and rarely in the vagina and corpus (Table
2). Since both tumors and mesonephric remnants show a predilection for the lateral wall, it is not unreasonable to believe they are related. Because of the lack of reliable evidence, some pathologists propose to call the tumor of the corpus a “mesonephric-like” adenocarcinoma. Nevertheless, we would like to consider that a “mesonephric-like” adenocarcinoma whose epicenter is in the myometrial layer could be diagnosed as MA if the existence of MA in the cervix is confirmed and the morphology is consistent with that of MA. The cases presented by McFarland et al. are of great interest [
9]. In their uterine cases, all the tumors predominantly involved the endometrium and appeared to arise there with subsequent invasion into the myometrium. Therefore, they suggested the intriguing possibility that MAs do not actually arise from mesonephric remnants, but could arise from Müllerian structures and differentiate along a mesonephric pathway. However, based on the morphological features and immunophenotype, they believe these tumors to represent MA. When taking into consideration the description by McFarland et al., it is reasonable to believe that MA can originate in the uterine corpus in two ways: 1) direct development from the mesonephric remnants of the corpus wall and 2) mesonephric differentiation of a Müllerian adenocarcinoma originating from the endometrium, as proposed by McFarland et al.
Table 2
Reported cases of mesonephric adenocarcinoma in the uterine corpus
1 | | 58 | 14 | Cervix | MYO (left lateral) | - | Normal | Normal |
2 | | 33 | 8 × 6 | - | MYO | - | 47 IU/mL | NA |
3 | | 37 | 3.5 | - | END | + | NA | NA |
4 | | 81 | 3.7 × 3.0 × 2.3 | NA | MYO (right lateral) | + | 55 kU/mL | NA |
5 | | 73 | 8 × 7 | - | MYO | + | Normal | Normal |
6 | | NA | NA | cervix | corpus | NA | NA | NA |
7 | | 55 | 3.5 × 2.5 × 2.0 | NA | MYO, endocervix, (lateral) | + | 163.8 U/mL | 193.6 U/mL |
8 | | 62 | 8 × 7 × 3 | NA | MYO | NA | Normal | Normal |
9–15 | | NA | NA | - | END, subsequent to MYO | + | NA | NA |
16 | | 66 | 2.5 × 2.0 | - | MYO (left anterolateral) | + | Normal | NA |
17 | Ando et al. (present case) | 61 | 8 × 6.5 | - | MYO (left posterolateral) | - | 389 U/mL | 785 U/mL |
MA typically exhibits a variety of architectural growth patterns, even within the same tumor [
13]. Although this admixture of growth patterns is a somewhat characteristic feature and can be useful for diagnosis, it may also result in diagnostic issues and mimicry of other neoplasms. The differential diagnosis of MA of the uterus includes endometrioid carcinoma, serous adenocarcinoma, and clear cell carcinoma. The distinction of MA from endometrioid carcinoma and serous adenocarcinoma may be straightforward when the characteristic feature of relatively uniform small tubules containing intraluminal hyaline material, as well as a variety of growth patterns, is found in the tumor. The absence of squamous metaplasia, nuclear stratification, and ER/PgR expression may exclude the diagnosis of endometrioid carcinoma [
6]. A similar appearance of uniform small tubules containing intraluminal eosinophilic material is sometimes observed in clear cell carcinoma. Clear cell carcinoma comprises higher-grade atypical tumor cells, even in the uniform small tubules, whereas MA comprises relatively bland-looking tumor cells. A Hobnail-like appearance of the tumor cells and hyalinization of the stroma can also aid in the differential diagnosis. Immunohistochemistry may also be helpful. CD10 and calretinin have been commonly used for supporting mesonephric differentiation, and recently GATA3 has been shown to be a useful marker for mesonephric lesions in the lower female genital tract [
15]. However, neither CD10 nor calretinin is highly sensitive or specific for mesonephric differentiation, and GATA3 staining has great variability in both intensity and extent. In addition, weak reactivity of GATA3 has been observed in 7% of endometrial carcinomas [
16]. Therefore, at this time, there are no antibodies that distinguish MA from Müllerian carcinomas.
Compared with previously reported cases, the present tumor showed two unique features. The first was its unique gross appearance. Most of the tumor component was present in the cyst within the myometrial layer. There have been only two cases, including ours, that have exhibited an intracystic growth pattern. Yamamoto et al. described a tumor with large cyst formation containing brownish fluids, as seen in the present case [
2]. This growth pattern has not been described in cervical MA. The other feature is the possible higher-grade transformation in the same tumor. The tumor is comprised of two different geographical and biological components: 1) the intracystic component composed of low-grade carcinoma with typical MA histology and 2) a higher-grade invasive component within the myometrial layer that merges with the intracystic component. The biological differences in the components correspond to differences in their cytological atypia and Ki67 labeling indices. It is possible that the tumor described in the present case arose as the former type of MA, obtained higher malignant potential, and transformed into adenocarcinoma, invading the myometrium.