Case 4 -
Mesonephric Adenocarcinoma of the Uterine Cervix
Nilsa C. Ramirez
Ohio State University
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55-year-old woman presented with postmenopausal bleeding and a past history of an abnormal PAP smear.
Colposcopy followed by cervical conization revealed a neoplastic process involving the cervix.
Clinically she had disease consistent with stage IB1. She underwent radical hysterectomy with bilateral
salpingo-oophorectomy and pelvic lymphadenectomy.
Case 4 - Figure 1 - The neoplastic process diffusely infiltrates the myometrium of the lower uterine segment without a significant stromal reaction
Case 4 - Figure 2 - Glands with a tubular architecture arranged in a back to back pattern. Note the presence of intraluminal eosinophilic secretions.
Mesonephric adenocarcinoma of the uterine cervix
The uterine cervix was firm and barrel shaped. A healing ulcer was noted in the area where the prior
cone biopsy was removed. The adenocarcinoma was characterized by a proliferation of small glands with a
predominant tubular architecture that diffusely infiltrated the vaginal cuff, the cervix, and the lower
uterine segment. The neoplastic process involved the vaginal and parametrial surgical margins of
resection. There was a focal desmoplastic response. A single layer of columnar cells with low-grade
nuclei lined the majority of the glands; cellular stratification was focally noted. Many glands had
luminal eosinophilic secretions. Mitotic activity was identified in some areas. Perineural and neural
invasion was prominent. Benign appearing hyperplastic mesonephric duct remnants were noted in the
background. The immunohistochemical profile of the adenocarcinoma included diffuse positivity for
vimentin and EMA, focal positivity for CD10, and negative staining for estrogen receptors, progesterone
receptors, and monoclonal CEA.
Mesonephric adenocarcinoma (MA), a rare subtype of cervical carcinoma, arises from mesonephric
(Wolffian) duct remnants. These remnants can be identified mainly in the lateral walls of up to 22% of
uterine cervices . The clinical presentation of cervical MA is similar to other types of cervical
carcinoma, with the majority of patients initially complaining of vaginal bleeding
patients range from 34 to 72 years
. Although a grossly evident tumor is not uncommon, microscopic
lesions may be discovered as incidental findings in hysterectomy specimens, in cervical or endometrial
currettings, or in cervical biopsies obtained for the purpose of evaluating an abnormal Pap smear
These adenocarcinomas may involve the cervix in a circumferential fashion, be confined to the lateral or
posterolateral aspects of the cervix, or extend to the lower uterine segment
. The involvement of
the cervical wall is usually transmural and includes mucosal involvement
Several morphologic patterns can be identified, and even though one may be dominant, a combination of
patterns is frequently seen. In one study Clement et. al.  described five patterns: ductal, small
tubular, retiform, solid, and sex cord-like. The most frequently identified are ductal and tubular .
In the tubular pattern, numerous small neoplastic tubules are arranged in a back-to-back fashion, with
many containing intraluminal eosinophilic secretions similar to the secretions observed in mesonephric
duct remnants. The ductal pattern is characterized by larger glands resembling the glands of
endometrioid adenocarcinoma, and may also contain intraluminal eosinophilic secretions. These PAS +
intraluminal secretions are also weakly mucicarmine positive
. Luminal debris may occasionally be
seen in association with the neoplastic tubules . Clement et. al. described cervical MAs associated
with a malignant spindle cell (sarcomatoid) component resembling endometrial stromal sarcoma or a non
specific stromal sarcoma ("malignant mesonephric mixed tumors") which may rarely be associated with
heterologous differentiation . In spite of the infiltrative nature of mesonephric carcinomas, a
desmoplastic stromal response is absent in many cases . Lymphovascular space invasion and perineural
invasion have been described in association with these tumors
. The cytologic features of the
neoplastic cells vary from mild to severe, even within the same tumor
. Most tumors are
characterized by mild nuclear atypicality
. Mitotic activity is also variable. According to a
series of 11 cases published by Silver et. al. considerable variation in the mitotic index was identified
among tumors and within a given tumor . These authors noted the highest mitotic counts in tumor areas
with ductal and solid architectural patterns. In their series of 11 cases the maximal mitotic counts
ranged from 3 to 50 mitoses per 10 HPFs and the two tumors with the highest mitotic counts were
associated with metastatic spread .
The immunohistochemical profile of MAs is similar to that of mesonephric remnants
rete ovarii . In the series reported by Silver et. al.  all cases of mesonephric adenocarcinomas
were immunopositive for epithelial markers CK1, AE1/AE3, CK7, and EMA. Immunopositivity for the
following markers was noted in a percentage of cases: vimentin (70%), calretinin (88%), androgen (33%)
and inhibin (focal in 30%). Negative immunostaining was demonstrated with CK20, ER, PR, and mCEA. The
sarcomatoid component of the biphasic ("mixed") tumor studied in this particular series was diffusely
immunopositive for vimentin, and focally for pan-cytokeratin and CAM 5.2. Other studies have
demonstrated immunopositivity for CA125 and focally for CEA
. Recently, Ordi et. al. reported
immunopositivity for CD10 in mesonephric remnants of the uterine cervix, and in cervical mesonephric
adenocarcinomas . In one study HPV DNA was not identified in a case of mesonephric adenocarcinoma
tested as part of a larger series of cervical adenocarcinomas . Ki-67 proliferation index appears to
be higher in cases of mesonephric carcinoma than in hyperplastic processes
The differential diagnosis includes mesonephric hyperplasia
, and primary endocervical
carcinomas of mucinous, endometrioid, clear cell, and serous differentiation
. Also in the
differential diagnosis are malignant mixed mullerian tumors
, uterine tumors resembling sex cord
, and endometrial endometrioid adenocarcinomas  secondarily involving the cervix. It is
not uncommon to identify hyperplastic mesonephric duct remnants in the background of MAs
These benign proliferations may display a diffuse or a lobular pattern. Care should be taken not to
confuse this hyperplastic process with an invasive carcinoma, especially when dealing with the diffuse
pattern . The presence of architectural features associated with malignancy (solid patterns,
back-to-back glandular arrangement), significant cellular atypicality, mitotic activity, and a
desmoplastic response favor a malignant process. A grossly identifiable tumor is more commonly seen in
association with a malignant process, although cases of mesonephric hyperplasia associated with gross
cervical distortion (resembling a tumor) have been described . In cases in which the differential
diagnosis includes mucinous endocervical, endometrioid, clear cell or serous carcinoma
immunohistochemical stains may assist in the characterization of the process.
MA is usually confined to the cervix at the time of initial diagnosis
and late recurrences are
not uncommon . Some cases may be associated with an aggressive clinical course, resulting in
metastases and death
, but most have a prognosis that is better than cervical carcinomas of
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