Mesonephric Adenocarcinoma of the Uterine Cervix Associated with Florid Mesonephric Hyperplasia: A Case Report

Abstract

Hyperplasia and neoplasia of mesonephric remnants in the uterine cervix are uncommon conditions that are often mis-diagnosed as usual forms of cervical adenocarcinoma. Here, we report a case of mesonephric adenocarcinoma with florid mesonephric hyperplasia of the uterine cervix in a 48-year-old female patient. The cervix was slightly enlarged eccentrically, without a definite mass-like lesion. Microscopically, the tumor cells infiltrated the cervical stroma with focal myometrial extension and were composed of predominantly round to polygonal cells arranged in ductal, tubular, or cystic structures. The remaining stroma revealed diffuse and florid mesonephric hyperplasia intertwined with tumor cells. Immunohistochemically, the tumor cells were positive for pancytokeratin, epithelial membrane antigen, and CD10. The Ki-67 proliferation index was slightly increased. The patient received routine adjuvant treatment and was alive and clinically free of disease at two-year follow-up.

INTRODUCTION

Malignant mesonephric adenocarcinoma arising from the mesonephric remnants in the uterine cervix are the rarest tumors in the female genital tract and are often mis-diagnosed as common forms of cervical adenocarcinoma. In women, small mesonephric remnants may persist in the broad ligaments or the lateral walls of the uterine cervix or vagina, where they may give rise to cysts and, rarely, to neoplasm [1]. To our knowledge, there have been only 30 cases of hyperplasia and neoplasia of mesonephric remnants in the uterine cervix reported in the English literature. Many cases previously designated as cervical mesonephric adenocarcinomas have been later reinterpreted as clear cell carcinomas of Mullerian origin [1]. Here, we report the first case of mesonephric adenocarcinoma in Korea along with a review of the literature.

CASE REPORT

A 48-year-old, gravid 4, para 2 woman was admitted to our hospital due to change in size of a known uterine mass. The result of a cervical Papanicolau smear examination was normal. Physical examination revealed a slightly enlarged uterus with multiple masses and normal vagina and uterine cervix. On the routine laboratory check up, the serum levels of carcinoembryonic antigen (CEA) and CA19-9 were within the normal ranges, and there was a mild increase in CA125 level (44.6 U/ml). Vaginal hysterectomy was performed for an initial diagnosis of uterine adenomyosis. Grossly, the entire cervix was eccentrically slightly enlarged, 3.5 × 2.5 × 2.5 cm in size without a definite mass-like lesion. The myometrium had a diffuse nodular appearance with multiple scattered bloody punctuations. Microscopically, the tumor cells infiltrated the entire cervical stroma with focal myometrial extension (Fig. 1A). The tumor was predominantly composed of round to polygonal cells arranged in ductal, tubular, or cystic structures and had round to oval hyper-chromatic large nuclei, small nucleoli, and small amounts of cytoplasm (Fig. 1B). The remaining cervical stroma revealed diffuse and florid mesonephric hyperplasia intermingled with tumor cells. The myometrium showed focal extension of tumor with diffuse adenomyosis. The immunohistochemical findings showed positive reactions in the tumor cells for pancytokeratin (CK), epithelial membrane antigen (EMA), and CD10 and negative reactions for CEA, inhibin, estrogen receptor (ER), and progesterone receptor (PR). The Ki-67 proliferation index was slightly increased (Fig. 2). A summary of the present case with regard to immunohistochemical studies as compared with previous reported cases in the literature is given in Table 1. The patient received six cycles of adjuvant chemotherapy and radiotherapy. There was no evidence of lymph node involvement, metastatic disease, or recurrence during a two-year follow-up period.

Fig. 1.

(A) The stroma shows diffuse florid mesonephric hyperplasia admixed with tumor cells that infiltrated the entire cervical stroma. (B) The tumor is predominantly composed of round to polygonal cells arranged in a ductal, tubular, or cystic pattern.

Fig. 2.

Immunohistochemical findings show positive reaction in the tumor cells for (A) epithelial membrane antigen (EMA) and (B) CD10 and negative reaction for (C) CEA. (D) The Ki-67 proliferation index was slightly increased.

Table 1.

Comparative immunohistochemical results of mesonephric adenocarcinoma between the literature and the present case

Antibodies	Literature [1,5–8]	Present case
Pancytokeratin	(+)	(+)
EMA	(+)	(+)
CD10	(+) & (−)	(+)
CEA	(−)	(−)
Inhibin	(−) & focal (+)	(−)
ER	(−)	(−)
PR	(−)	(−)

DISCUSSION

Vestigial remnants of the mesonephric ducts are identified in up to 22% of adult female cervices [2]. They are not uncommonly encountered deep in the lateral walls of the cervix, where they give rise to hyperplasia and, rarely, malignant mesonephric tumors [3]. Five categories of mesonephric cervical lesions have been described: mesonephric remnants, lobular mesonephric hyperplasia, diffuse mesonephric hyperplasia, mesonephric ductal hyperplasia, and mesonephric carcinoma [4].

Malignant mesonephric tumors have been described in the uterine corpus and cervix, broad ligament, urinary bladder, urethra, and urethral diverticulum [5]. The differential diagnosis of mesonephric adenocarcinoma includes clear cell carcinoma, serous carcinoma, malignant Mullerian mixed tumors (MMMT), mesonephric hyperplasia, and endometrioid adenocarcinoma [6]. The greatest diagnostic dilemma presented in the literature is differentiating between malignant mesonephric adenocarcinoma and clear cell carcinoma [4]. However, clear cell carcinoma usually shows varying degrees of cystic, papillary, or solid patterns, and two cell types may be found: clear cells with abundant clear cytoplasm around a central nuclei and hobnail cells with a lesser amount of opaque granular cytoplasm and eccentric nuclei [6]. Therefore, we were able to rule out clear cell carcinoma due to the absence of clear or hobnail cells. Benign mesonephric hyperplasia was excluded due to the diffuse infiltrative growth pattern of the tumor cells, focal invasion of the myometrium, and the cytologic atypia of tumor cells in this case. The ductal pattern of mesonephric adenocarcinoma may be similar to endometrioid adenocarcinoma, which is composed of glandular or villoglandular structures lined by cytologically malignant stratified columnar epithelial cells. Endometrioid adenocarcinoma is usually positive for ER and PR immunohistochemical stains. In this case, we excluded this diagnosis based on microscopic morphology and immunohistochemical studies. Biphasic mesonephric adenocarcinomas with a sarcomatoid component have been reported [6] and can be confused with MMMT. However, in the present case, the stroma was benign without a sarcomatoid component, and we were able to rule out the possibility of MMMT.

The typical findings of mesonephric adenocarcinoma are the presence of florid mesonephric remnants and hyperplasia [7]. However, in the absence of associated mesonephric duct remnants, the neoplasm’s immunohistochemical profiles may be useful in establishing a diagnosis. Recently, immunohistochemical studies have been characterized with regard to mesonephric adenocarcinoma of the uterine cervix; stains for epithelial markers, including pancytokeratin, CK7, CAM5.2, and EMA, were consistently positive in the tumor cells [3,7]. It has been reported that vimentin was positive in 70% of 11 cases of cervical mesonephric adenocarcinoma, calretinin in 88%, and androgen receptor in 33%. Monoclonal CK20, CEA, ER, and PR were negative. However, all authors accept the fact that the immunophenotypes of paramesonephric (Mullerian) and mesonephric (Wolffian) structures and their tumors are not substantially different, and that there is no specific marker for mesonephric structures [8]. CD10 expression in mesonephric adenocarcinoma may be an exception to this idea and may be a good marker of mesonephric remnants and neoplasms in the female genital tract. All but two of the previously reported cases (22 of 24) of mesonephric remnants and tumors, as well as our case, were positive for CD10, whereas normal glandular epithelia of the female genital tract and their tumors were almost invariably negative. The Ki-67 proliferation index in this case was similar to the cases reported by Silver et al. [7], where the Ki-67 labeling index did not exceed 2% in the hyperplastic area and was increased in the area of the adenocarcinoma. Except for a few higher stage tumors that follow an aggressive course [7], these tumors were associated with good prognoses and long survival. A total abdominal hysterectomy with salpingo-oophorectomy is the treatment of choice for these tumors.

In conclusion, mesonephric adenocarcinoma is characterized by morphologic diversity and an unusual appearance and is almost always associated with mesonephric hyperplasia. A panel of immunohistochemical stains may be useful in the differential diagnosis of this neoplasm. Specifically, CD10 has recently been shown to be a useful marker for this lesion [7]. Although this type of tumor is rare, it should be considered in the differential diagnosis of cervical lesions encountered in clinical practice.