A 47-year-old woman was referred to our institution because of menometrorrhagia and pelvic pain of unknown duration. Her medical history was significant for endometriosis. Physical examination revealed a pelvic mass, and ultrasound examination showed a 6.0-cm right adnexal multiloculated cyst. A recent Papanicolaou test was reported as normal. Clinically, the differential diagnoses were endometrioma, functional cyst, and ovarian cystadenoma/carcinoma. Exploratory laparotomy and total abdominal hysterectomy were performed. A cervical mass was palpated during surgery, and vaginal cuff tissues were also resected.

The specimen consisted of a 150-g uterus with attached cervix, measuring 6.5 × 3.0 × 2.0 cm, and bilateral adnexa. The right ovary was cystic and contained a 3.0-cm endometrioma. The uterus was slightly nodular, the cervix was enlarged, and a 3.0-cm polypoid mass occupied more than half of the ectocervix (Figure 1). The surface was eroded and hemorrhagic. Low-power microscopy revealed an unremarkable squamous mucosa overlying a stroma distended by a diffusely infiltrating tumor that showed prominent tubule formation (Figure 2). Foci of cordlike infiltration of the stroma were present. The tubules were separated by an intervening stroma that showed minimal desmoplasia (Figures 2 and 3). High-power examination showed cells with a very high nuclear-cytoplasmic ratio and mild nuclear pleomorphism and atypia. The nuclear chromatin was coarsely granular with indistinct nucleoli (Figure 3). The lumina of the tubules contained dense, eosinophilic hyaline material that stained with periodic acid– Schiff and was digested by diastase. The tumor involved the entire cervix with varying depths of penetration. A portion of the vaginal cuff was invaded. The endocervical mucosa was unremarkable. Perineural invasion was seen. Immunohistochemistry revealed diffuse positivity for cytokeratins AE1/AE3, cytokeratin 7, cytokeratin 19, epithelial membrane antigen, CA 125, and estrogen and progesterone receptors; focal positivity was noted for CD10 (Figure 4). The tumor cells lacked immunoreactivity for cytokeratin 20, carcinoembryonic antigen, and inhibin.

What is your diagnosis?

These tumors are very rare and only a few dozen have been reported to date. Patients typically are in their 50s, but ages range from 32 to 72 years. Patients generally present with abnormal vaginal bleeding, and a visible cervical tumor is usually apparent on examination.1–3 These tumors arise from mesonephric remnants in the lateral wall of the cervix.

The embryo has 2 different genitourinary systems. The presence of testosterone and the mullerian-inhibiting factor inhibit the growth of mullerian structures in males. Their absence leads to the involution of wolffian structures in females. The remnants are divided in 2 parts. The upper part gives rise to the epoophoron, paroophoron, and the rete ovarii in the ovary, fallopian tubes, and uterus, respectively. The lower remnants give rise to the Gartner or wolffian duct in the cervix and vagina. These remnants may give rise to tumors. The upper remnants rarely develop into female adnexal tumors of wolffian origin and cyst of the rete ovarii. A single case of mesonephric carcinoma of the uterine corpus has been reported.4 The lower remnants generally give rise to hyperplasia. However, carcinomas rarely arise.

Mesonephric carcinomas show varying morphologies. The most common pattern, either alone or in combination with other patterns, is the ductal pattern that is composed of varying sizes lined by cuboidal to columnar epithelium showing moderate atypia. The small tubular pattern consists of back-to-back, small, round, uniform tubules containing dense, eosinophilic, hyaline secretions and lined by flattened to cuboidal cells. The retiform pattern consists of elongated, slitlike branching tubules containing intraluminal papillae lined by flattened to cuboidal cells. The solid pattern is devoid of lumina, while the biphasic pattern is accompanied by a malignant sarcomatoid component.1,2 These neoplasms are associated with a very subtle and minimal desmoplastic stromal reaction. This feature, along with the mild chronic inflammation surrounding mesonephric adenocarcinoma, markedly contrasts the prominent desmoplasia in the vicinity of endometrial and endocervical adenocarcinomas.3 

In the past, epithelial membrane antigen, calretinin, and vimentin were believed to be the only markers of mesonephric carcinoma. These antibodies were very nonspecific and are shared to some degree by tumors of mullerian origin. A study published in 2003 convincingly showed that CD10 was almost always expressed in mesonephric remnants and tumors, in sharp contrast to mullerian glandular epithelia of the female genital tract and their tumors.5 It is also noteworthy that normal wolffian derivatives in males are reactive for CD10. A study published in the same year showed that mesonephric adenocarcinomas may be positive for CD10, but the value is limited by the positivity of a third of cases of ordinary endocervical adenocarcinoma.6 Our case did stain for estrogen and progesterone receptors, which is an unusual feature; in a study in 2001, none of the cases of mesonephric adenocarcinoma stained for estrogen or progesterone receptors.3 The prognostic significance of such an occurrence is currently unknown.

The recognition of these tumors is important because of possible difficulty in differentiating mesonephric carcinomas from more common tumors of the cervix. Well-differentiated villoglandular adenocarcinoma of the cervix shows prominent papillary growth and some stratification of cells. Adenoma malignum consists of complex branching glands lined by cells with minimal cytologic atypia. Both of these tumors have cells with apical intracytoplasmic mucin. Endometrioid adenocarcinoma of the cervix usually demonstrates complex branching of glands lined by pseudostratified cells. Mesonephric carcinomas may also show pseudostratification. Features favoring an endometrioid adenocarcinoma of the cervix are involvement of the mucosa, higher nuclear grade, presence of adjacent adenocarcinoma in situ, and immunoreactivity for carcinoembryonic antigen. Clear cell carcinomas may exhibit prominent tubules filled with eosinophilic hyaline material. The points of differentiation are greater cytologic atypia and the presence of hobnailing. Perhaps the most difficult differential diagnosis is mesonephric hyperplasia. Features characteristic of hyperplasia are a lobulated architecture, lack of infiltrative margins, and absence of cytologic atypia.

Because of their rarity, the behavior of these tumors is uncertain. In a study of 4 patients published in 1990, 3 had local recurrence and 2 died of the disease, 3 and 9 years after diagnosis.2 In a study of 8 cases published in 1995, 3 tumors recurred: 1 patient died of disease 8.5 months after diagnosis, another was alive with disease after 13 years of follow-up, and the third was free of disease after 2 years of follow-up.1 In a study of 11 cases published in 2001, 4 patients had recurrences and 3 patients died of the disease, 0.8 to 6.2 years after the diagnosis.3 Radiation therapy was used to treat tumors, some of which recurred and some of which did not. In these studies, most recurrences were associated with stage IB disease at presentation. The limited cases to date show that long periods of survival could still be achieved with or without radiotherapy. Our patient received radiotherapy in the form of cesium implants, and she is currently without evidence of disease after 1 year of follow-up.

In summary, mesonephric carcinomas may assume a variety of morphologies; the most common is a ductal pattern. Recently, CD10 has been shown to be a useful marker for this lesion. These tumors are rare, but clinically should be considered in the differential diagnoses of cervical lesions. Clinically, they are characterized by local recurrences, but with long periods of survival.

The authors thank Michael R. Pins, MD, of Northwestern University's Feinberg School of Medicine, Chicago, Ill, for confirming our diagnosis.

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The authors have no relevant financial interest in the products or companies described in this article.

Reprints not available from the authors.

Author notes

Corresponding author: Elliot Weisenberg, MD, Advocate Illinois Masonic Medical Center, Department of Pathology, 836 W Wellington Ave, Chicago, IL 60657 ([email protected])