Journal of
Case Report
Vol. 3, No. 2, 117-120
Lifestyle Medicine
Mesonephric Adenocarcinoma of the Uterine Cervix Associated with Florid Mesonephric Hyperplasia: A Case Report Jamshid Abdul-Ghafar1, Yosep Chong1, Hyuck Dong Han2, Dong Soo Cha2, Minseob Eom1,* Departments of 1Pathology and 2Obsterics and Gynecology, Yonsei University Wonju College of Medicine, Wonju, Korea
Hyperplasia and neoplasia of mesonephric remnants in the uterine cervix are uncommon conditions that are often misdiagnosed 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. Key Words: Adenocarcinoma, Cervix uteri, Hyperplasia, Immunohistochemistry, Mesonephric duct
INTRODUCTION
Many cases previously designated as cervical mesonephric adenocarcinomas have been later reinterpreted as clear cell
Malignant mesonephric adenocarcinoma arising from the
carcinomas of Mullerian origin [1]. Here, we report the first
mesonephric remnants in the uterine cervix are the rarest
case of mesonephric adenocarcinoma in Korea along with
tumors in the female genital tract and are often mis-
a review of the literature.
diagnosed as common forms of cervical adenocarcinoma. In women, small mesonephric remnants may persist in the
CASE REPORT
broad ligaments or the lateral walls of the uterine cervix or vagina, where they may give rise to cysts and, rarely,
A 48-year-old, gravid 4, para 2 woman was admitted to
to neoplasm [1]. To our knowledge, there have been only
our hospital due to change in size of a known uterine mass.
30 cases of hyperplasia and neoplasia of mesonephric rem-
The result of a cervical Papanicolau smear examination was
nants in the uterine cervix reported in the English literature.
normal. Physical examination revealed a slightly enlarged uterus with multiple masses and normal vagina and uterine
Received: April 18, 2013, Accepted: June 20, 2013
cervix. On the routine laboratory check up, the serum levels
*Corresponding author: Minseob Eom
of carcinoembryonic antigen (CEA) and CA19-9 were with-
Department of Pathology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju 220-701, Republic of Korea Tel: 82-33-741-1554, Fax: 82-33-731-6590 E-mail: [email protected]
in the normal ranges, and there was a mild increase in CA125 level (44.6 U/ml). Vaginal hysterectomy was performed for
Journal of Lifestyle Medicine Vol. 3, No. 2, September 2013
an initial diagnosis of uterine adenomyosis. Grossly, the en-
with tumor cells. The myometrium showed focal extension
tire cervix was eccentrically slightly enlarged, 3.5 × 2.5 ×
of tumor with diffuse adenomyosis. The immunohistochemical
2.5 cm in size without a definite mass-like lesion. The my-
findings showed positive reactions in the tumor cells for pan-
ometrium had a diffuse nodular appearance with multiple
cytokeratin (CK), epithelial membrane antigen (EMA), and
scattered bloody punctuations. Microscopically, the tumor
CD10 and negative reactions for CEA, inhibin, estrogen re-
cells infiltrated the entire cervical stroma with focal my-
ceptor (ER), and progesterone receptor (PR). The Ki-67 pro-
ometrial extension (Fig. 1A). The tumor was predominantly
liferation index was slightly increased (Fig. 2). A summary
composed of round to polygonal cells arranged in ductal, tub-
of the present case with regard to immunohistochemical stud-
ular, or cystic structures and had round to oval hyper-
ies as compared with previous reported cases in the literature
chromatic large nuclei, small nucleoli, and small amounts of
is given in Table 1. The patient received six cycles of adjuvant
cytoplasm (Fig. 1B). The remaining cervical stroma revealed
chemotherapy and radiotherapy. There was no evidence of
diffuse and florid mesonephric hyperplasia intermingled
lymph node involvement, metastatic disease, or recurrence
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 find-
ings 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.
118
Jamshid Abdul-Ghafar, et al : Cervical Mesonephric Adenocarcinoma
Table 1. Comparative immunohistochemical results of mesonephric
may be similar to endometrioid adenocarcinoma, which is
adenocarcinoma between the literature and the present case
composed of glandular or villoglandular structures lined by
Antibodies
Literature [1,5-8]
Present case
cytologically malignant stratified columnar epithelial cells.
Pancytokeratin EMA CD10 CEA Inhibin ER PR
(+) (+) (+) & () () () & focal (+) () ()
(+) (+) (+) () () () ()
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 sarcoma-
during a two-year follow-up period.
toid component, and we were able to rule out the possibility of MMMT.
DISCUSSION
The typical findings of mesonephric adenocarcinoma are the presence of florid mesonephric remnants and hyperplasia
Vestigial remnants of the mesonephric ducts are identi-
[7]. However, in the absence of associated mesonephric duct
fied in up to 22% of adult female cervices [2]. They are
remnants, the neoplasm’s immunohistochemical profiles may
not uncommonly encountered deep in the lateral walls of
be useful in establishing a diagnosis. Recently, immunohisto-
the cervix, where they give rise to hyperplasia and, rarely,
chemical studies have been characterized with regard to mes-
malignant mesonephric tumors [3]. Five categories of meso-
onephric adenocarcinoma of the uterine cervix; stains for
nephric cervical lesions have been described: mesonephric
epithelial markers, including pancytokeratin, CK7, CAM5.2,
remnants, lobular mesonephric hyperplasia, diffuse meso-
and EMA, were consistently positive in the tumor cells [3,7].
nephric hyperplasia, mesonephric ductal hyperplasia, and
It has been reported that vimentin was positive in 70% of
mesonephric carcinoma [4].
11 cases of cervical mesonephric adenocarcinoma, calretinin
Malignant mesonephric tumors have been described in the
in 88%, and androgen receptor in 33%. Monoclonal CK20,
uterine corpus and cervix, broad ligament, urinary bladder,
CEA, ER, and PR were negative. However, all authors accept
urethra, and urethral diverticulum [5]. The differential diag-
the fact that the immunophenotypes of paramesonephric
nosis of mesonephric adenocarcinoma includes clear cell car-
(Mullerian) and mesonephric (Wolffian) structures and their
cinoma, serous carcinoma, malignant Mullerian mixed tu-
tumors are not substantially different, and that there is no
mors (MMMT), mesonephric hyperplasia, and endometrioid
specific marker for mesonephric structures [8]. CD10 ex-
adenocarcinoma [6]. The greatest diagnostic dilemma pre-
pression in mesonephric adenocarcinoma may be an ex-
sented in the literature is differentiating between malignant
ception to this idea and may be a good marker of meso-
mesonephric adenocarcinoma and clear cell carcinoma [4].
nephric remnants and neoplasms in the female genital tract.
However, clear cell carcinoma usually shows varying degrees
All but two of the previously reported cases (22 of 24) of
of cystic, papillary, or solid patterns, and two cell types may
mesonephric remnants and tumors, as well as our case, were
be found: clear cells with abundant clear cytoplasm around
positive for CD10, whereas normal glandular epithelia of the
a central nuclei and hobnail cells with a lesser amount of
female genital tract and their tumors were almost invariably
opaque granular cytoplasm and eccentric nuclei [6].
negative. The Ki-67 proliferation index in this case was sim-
Therefore, we were able to rule out clear cell carcinoma due
ilar to the cases reported by Silver et al. [7], where the Ki-67
to the absence of clear or hobnail cells. Benign mesonephric
labeling index did not exceed 2% in the hyperplastic area
hyperplasia was excluded due to the diffuse infiltrative
and was increased in the area of the adenocarcinoma. Except
growth pattern of the tumor cells, focal invasion of the my-
for a few higher stage tumors that follow an aggressive
ometrium, and the cytologic atypia of tumor cells in this
course [7], these tumors were associated with good prognoses
case. The ductal pattern of mesonephric adenocarcinoma
and long survival. A total abdominal hysterectomy with sal-
119
Journal of Lifestyle Medicine Vol. 3, No. 2, September 2013
pingo-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.
REFERENCES 1. Bague S, Rodriguez IM, Prat J. Malignant mesonephric tumors of the female genital tract: a clinicopathologic study of 9 cases. Am J Surg Pathol 2004;28:601-7. 2. Yap OW, Hendrickson MR, Teng NN, Kapp DS. Mesonephric adenocarcinoma of the cervix: a case report and review of the literature. Gynecol Oncol 2006;103: 1155-8.
120
3. Fukunaga M, Takahashi H, Yasuda M. Mesonephric adenocarcinoma of the uterine cervix: a case report with immunohistochemical and ultrastructural studies. Pathol Res Pract 2008;204:671-6. 4. Bifulco G, Mandato VD, Mignogna C, Giampaolino P, Di Spiezio Sardo A, De Cecio R, De Rosa G, Piccoli R, Radice L, Nappi C. A case of mesonephric adenocarcinoma of the vagina with a 1-year follow-up. Int J Gynecol Cancer 2008;18:1127-31. 5. Wani Y, Notohara K, Tsukayama C. Mesonephric adenocarcinoma of the uterine corpus: a case report and review of the literature. Int J Gynecol Pathol 2008;27: 346-52. 6. Ersahin C, Huang M, Potkul RK, Hammadeh R, Salhadar A. Mesonephric adenocarcinoma of the vagina with a 3-year follow-up. Gynecol Oncol 2005;99:757-60. 7. Silver SA, Devouassoux-Shisheboran M, Mezzetti TP, Tavassoli FA. Mesonephric adenocarcinomas of the uterine cervix: a study of 11 cases with immunohistochemical findings. Am J Surg Pathol 2001;25:379-87. 8. Ordi J, Nogales FF, Palacin A, Marquez M, Pahisa J, Vanrell JA, Cardesa A. Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation. Am J Surg Pathol 2001;25: 1540-5.
Case Report
Vol. 3, No. 2, 117-120
Lifestyle Medicine
Mesonephric Adenocarcinoma of the Uterine Cervix Associated with Florid Mesonephric Hyperplasia: A Case Report Jamshid Abdul-Ghafar1, Yosep Chong1, Hyuck Dong Han2, Dong Soo Cha2, Minseob Eom1,* Departments of 1Pathology and 2Obsterics and Gynecology, Yonsei University Wonju College of Medicine, Wonju, Korea
Hyperplasia and neoplasia of mesonephric remnants in the uterine cervix are uncommon conditions that are often misdiagnosed 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. Key Words: Adenocarcinoma, Cervix uteri, Hyperplasia, Immunohistochemistry, Mesonephric duct
INTRODUCTION
Many cases previously designated as cervical mesonephric adenocarcinomas have been later reinterpreted as clear cell
Malignant mesonephric adenocarcinoma arising from the
carcinomas of Mullerian origin [1]. Here, we report the first
mesonephric remnants in the uterine cervix are the rarest
case of mesonephric adenocarcinoma in Korea along with
tumors in the female genital tract and are often mis-
a review of the literature.
diagnosed as common forms of cervical adenocarcinoma. In women, small mesonephric remnants may persist in the
CASE REPORT
broad ligaments or the lateral walls of the uterine cervix or vagina, where they may give rise to cysts and, rarely,
A 48-year-old, gravid 4, para 2 woman was admitted to
to neoplasm [1]. To our knowledge, there have been only
our hospital due to change in size of a known uterine mass.
30 cases of hyperplasia and neoplasia of mesonephric rem-
The result of a cervical Papanicolau smear examination was
nants in the uterine cervix reported in the English literature.
normal. Physical examination revealed a slightly enlarged uterus with multiple masses and normal vagina and uterine
Received: April 18, 2013, Accepted: June 20, 2013
cervix. On the routine laboratory check up, the serum levels
*Corresponding author: Minseob Eom
of carcinoembryonic antigen (CEA) and CA19-9 were with-
Department of Pathology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju 220-701, Republic of Korea Tel: 82-33-741-1554, Fax: 82-33-731-6590 E-mail: [email protected]
in the normal ranges, and there was a mild increase in CA125 level (44.6 U/ml). Vaginal hysterectomy was performed for
Journal of Lifestyle Medicine Vol. 3, No. 2, September 2013
an initial diagnosis of uterine adenomyosis. Grossly, the en-
with tumor cells. The myometrium showed focal extension
tire cervix was eccentrically slightly enlarged, 3.5 × 2.5 ×
of tumor with diffuse adenomyosis. The immunohistochemical
2.5 cm in size without a definite mass-like lesion. The my-
findings showed positive reactions in the tumor cells for pan-
ometrium had a diffuse nodular appearance with multiple
cytokeratin (CK), epithelial membrane antigen (EMA), and
scattered bloody punctuations. Microscopically, the tumor
CD10 and negative reactions for CEA, inhibin, estrogen re-
cells infiltrated the entire cervical stroma with focal my-
ceptor (ER), and progesterone receptor (PR). The Ki-67 pro-
ometrial extension (Fig. 1A). The tumor was predominantly
liferation index was slightly increased (Fig. 2). A summary
composed of round to polygonal cells arranged in ductal, tub-
of the present case with regard to immunohistochemical stud-
ular, or cystic structures and had round to oval hyper-
ies as compared with previous reported cases in the literature
chromatic large nuclei, small nucleoli, and small amounts of
is given in Table 1. The patient received six cycles of adjuvant
cytoplasm (Fig. 1B). The remaining cervical stroma revealed
chemotherapy and radiotherapy. There was no evidence of
diffuse and florid mesonephric hyperplasia intermingled
lymph node involvement, metastatic disease, or recurrence
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 find-
ings 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.
118
Jamshid Abdul-Ghafar, et al : Cervical Mesonephric Adenocarcinoma
Table 1. Comparative immunohistochemical results of mesonephric
may be similar to endometrioid adenocarcinoma, which is
adenocarcinoma between the literature and the present case
composed of glandular or villoglandular structures lined by
Antibodies
Literature [1,5-8]
Present case
cytologically malignant stratified columnar epithelial cells.
Pancytokeratin EMA CD10 CEA Inhibin ER PR
(+) (+) (+) & () () () & focal (+) () ()
(+) (+) (+) () () () ()
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 sarcoma-
during a two-year follow-up period.
toid component, and we were able to rule out the possibility of MMMT.
DISCUSSION
The typical findings of mesonephric adenocarcinoma are the presence of florid mesonephric remnants and hyperplasia
Vestigial remnants of the mesonephric ducts are identi-
[7]. However, in the absence of associated mesonephric duct
fied in up to 22% of adult female cervices [2]. They are
remnants, the neoplasm’s immunohistochemical profiles may
not uncommonly encountered deep in the lateral walls of
be useful in establishing a diagnosis. Recently, immunohisto-
the cervix, where they give rise to hyperplasia and, rarely,
chemical studies have been characterized with regard to mes-
malignant mesonephric tumors [3]. Five categories of meso-
onephric adenocarcinoma of the uterine cervix; stains for
nephric cervical lesions have been described: mesonephric
epithelial markers, including pancytokeratin, CK7, CAM5.2,
remnants, lobular mesonephric hyperplasia, diffuse meso-
and EMA, were consistently positive in the tumor cells [3,7].
nephric hyperplasia, mesonephric ductal hyperplasia, and
It has been reported that vimentin was positive in 70% of
mesonephric carcinoma [4].
11 cases of cervical mesonephric adenocarcinoma, calretinin
Malignant mesonephric tumors have been described in the
in 88%, and androgen receptor in 33%. Monoclonal CK20,
uterine corpus and cervix, broad ligament, urinary bladder,
CEA, ER, and PR were negative. However, all authors accept
urethra, and urethral diverticulum [5]. The differential diag-
the fact that the immunophenotypes of paramesonephric
nosis of mesonephric adenocarcinoma includes clear cell car-
(Mullerian) and mesonephric (Wolffian) structures and their
cinoma, serous carcinoma, malignant Mullerian mixed tu-
tumors are not substantially different, and that there is no
mors (MMMT), mesonephric hyperplasia, and endometrioid
specific marker for mesonephric structures [8]. CD10 ex-
adenocarcinoma [6]. The greatest diagnostic dilemma pre-
pression in mesonephric adenocarcinoma may be an ex-
sented in the literature is differentiating between malignant
ception to this idea and may be a good marker of meso-
mesonephric adenocarcinoma and clear cell carcinoma [4].
nephric remnants and neoplasms in the female genital tract.
However, clear cell carcinoma usually shows varying degrees
All but two of the previously reported cases (22 of 24) of
of cystic, papillary, or solid patterns, and two cell types may
mesonephric remnants and tumors, as well as our case, were
be found: clear cells with abundant clear cytoplasm around
positive for CD10, whereas normal glandular epithelia of the
a central nuclei and hobnail cells with a lesser amount of
female genital tract and their tumors were almost invariably
opaque granular cytoplasm and eccentric nuclei [6].
negative. The Ki-67 proliferation index in this case was sim-
Therefore, we were able to rule out clear cell carcinoma due
ilar to the cases reported by Silver et al. [7], where the Ki-67
to the absence of clear or hobnail cells. Benign mesonephric
labeling index did not exceed 2% in the hyperplastic area
hyperplasia was excluded due to the diffuse infiltrative
and was increased in the area of the adenocarcinoma. Except
growth pattern of the tumor cells, focal invasion of the my-
for a few higher stage tumors that follow an aggressive
ometrium, and the cytologic atypia of tumor cells in this
course [7], these tumors were associated with good prognoses
case. The ductal pattern of mesonephric adenocarcinoma
and long survival. A total abdominal hysterectomy with sal-
119
Journal of Lifestyle Medicine Vol. 3, No. 2, September 2013
pingo-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.
REFERENCES 1. Bague S, Rodriguez IM, Prat J. Malignant mesonephric tumors of the female genital tract: a clinicopathologic study of 9 cases. Am J Surg Pathol 2004;28:601-7. 2. Yap OW, Hendrickson MR, Teng NN, Kapp DS. Mesonephric adenocarcinoma of the cervix: a case report and review of the literature. Gynecol Oncol 2006;103: 1155-8.
120
3. Fukunaga M, Takahashi H, Yasuda M. Mesonephric adenocarcinoma of the uterine cervix: a case report with immunohistochemical and ultrastructural studies. Pathol Res Pract 2008;204:671-6. 4. Bifulco G, Mandato VD, Mignogna C, Giampaolino P, Di Spiezio Sardo A, De Cecio R, De Rosa G, Piccoli R, Radice L, Nappi C. A case of mesonephric adenocarcinoma of the vagina with a 1-year follow-up. Int J Gynecol Cancer 2008;18:1127-31. 5. Wani Y, Notohara K, Tsukayama C. Mesonephric adenocarcinoma of the uterine corpus: a case report and review of the literature. Int J Gynecol Pathol 2008;27: 346-52. 6. Ersahin C, Huang M, Potkul RK, Hammadeh R, Salhadar A. Mesonephric adenocarcinoma of the vagina with a 3-year follow-up. Gynecol Oncol 2005;99:757-60. 7. Silver SA, Devouassoux-Shisheboran M, Mezzetti TP, Tavassoli FA. Mesonephric adenocarcinomas of the uterine cervix: a study of 11 cases with immunohistochemical findings. Am J Surg Pathol 2001;25:379-87. 8. Ordi J, Nogales FF, Palacin A, Marquez M, Pahisa J, Vanrell JA, Cardesa A. Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation. Am J Surg Pathol 2001;25: 1540-5.
