Key Clinical Message:
A woman underdiagnosed as endometrial hyperplasia on a ThinPrep cytology
test was proved to be well-differentiated mesonephric adenocarcinoma by
subsequent pathology. The lesson was that cell block was necessary for
detecting ER, PR,Gata-3 and TTF-1.
As a rare tumor entity in female genital tract, mesonephric
adenocarcinoma (MA) develops from mesonephric remnants in the stroma
[1]. Only one article about cytological features of cervical MA is
available. The mild morphology in cytology is a pitfall and a challenge
[2]. In this report we demonstrate a well-differentiated case
underdiagnosed on a ThinPrep Cytology Test.
A 44-year-old woman, gravida 2, para 2, had symptom of irregular
red-brown vaginal bleeding for 9 months. Ultrasound showed a hyperechoic
mass in the anterior uterine wall measured approximately 49*32mm. The
ThinPrep cytology with Papanicolaou (Pap) stain demonstrated several
tubular glands composed of overlapping cells (Figure 1A). There were
individual atypical cells accompany with endocervical cells in a dirty
background (Figure 1B). Additionally, some clusters of atypical cells
with inconspicuous cytoplasm showed round-to-oval or slightly irregular
nuclei (Figure 1C). Intraglandular content was not found. Based on these
cytological features, we reported the case as atypical endometrial
cells.Endometrial hyperplasia was
considered [3].
Endometrial curettage was performed. Most of atypical cells with
small-to-medium nuclei were arranged with well-differentiated tubular
glands (Figure 2A). Some tubules contained eosinophilic luminal
secretions. The scant and clear cytoplasm was again seen. In some areas,
the stroma was hyaline degeneration. Immunohistochemical stains
established that the tumor cells were diffusely positive to Gata-3,
Pax-8 and vimentin (Figure 2B, C). There was focal positive of p16 and
CK7,but no expression of estrogen receptor, progesterone
receptor,androgen
receptor,α-inhibin, carcinoembryonic antigen(CEA), Calretinin, CD10,
P53 and thyroid transcription factor-1(TTF-1). Except that TTF-1 was
negative, these attributes were consistent with mesonephric-like
adenocarcinoma (ML-CA) [4]. Although the mass was located in uterine
body, it might have originated from cervical mesonephric remnants.
Because different origin suggested different biological features
[4], it was necessary to examine the whole sample of uterus
carefully.
The patient received total hysterectomy with bilateral adnexectomy
combined with pelvic cavity lymph node dissection. Macroscopically, the
grey-yellow mass with grey cut face measured 39*30*10mm and was located
in the uterine cavity and cervical canal (Figure 3A). Microscopically,
mesonephric
proliferation involved nearly the full circumference of the cervix
(Figure 3B). In the stoma, the hyperplastic mesonephric glands were
accompanied with atypical glands (Figure 3C). However, only neoplastic
glands extruded into uterine cavity. Additionally, tumor cells exhibited
higher density of nuclear chromatin, nucleo-cytoplasmic ratio and
ki-67
proliferative index (Figure 3D). Based on these features, it was
diagnosed as cervical MA.
Three architectures such as ductal, tubular and sheet-like variants have
been characterized in cytology of cervical MA [2]. Additionally,
papillary, glandular and tubulopapillary patterns have been reported in
cytology of ML-CA [5]. Cord-like, solid, spindled, hobnail,
glomeruloid, and retiform patterns have been described in histologic
findings [5-6]. In our case, a few tubules with “mild” appearance
and some indivivual atypical cells accompanied with some normal
endocervical cells confused pathologists. In some clusters, the cells
with irregular nuclear membranes were similar to atypical endometrial
cells. The patterns of endocervical adenocarcinoma such as bird
tail-like, strip of cells and rosette were not found [3]. Therefore,
although the histological features were definite, the cytology was
difficult to be diagnosed as carcinoma by morphology. Assuming no
ultrasound data indicated the mass, our cytological diagnosis would
delay surgical treatment. Perhaps the most important lesson to
be learned was that cell block should be made using the residual
material. The atypical cells with wild-type P53 expression would be
positive for Gata-3 but negative for ER and PR [7]. These
immunochemical features were helpful to exclude endometrial cells and
confirm mesonephric lesions.
Sometimes remnants of the mesonephric duct are noted in cytology
occasionally. These cuboidal cells with foamy vacuolated cytoplasm might
be suspected as atypical cells such as abnormal endometrial cells
[8]. However, eosinophilic material is present within the lumen in
most cases [8]. In usual cervical specimen, diffusely mesonephric
proliferation is not common. In our case, the florid hyperplastic
mesonephric glands in the paracervical soft tissue were accompanied by
neoplastic glands.The well differentiated neoplastic glands composed of
overlapping cells with tall columnar appearance also projected into
uterine cavity. The only immunohistochemical difference was the tumor
glands possessed higher ki-67 proliferative index [9].
Distinguish between cervical
mesonephric
carcinoma and mesonephric-like carcinoma from corpus is important
[10]. First, no mesonephric remnants have been observed in the
untrine body neoplasm, while they are concomitants of the neoplasm in
the cervical case. Some analyses suggest that uterine ML-ACs represent
an aggressive subtype of endometrial carcinomas [6, 11]. Second,
ML-ACs usually show TTF-1 positivity which is absent in benign
mesonephric remnants and malignant cervical mesonephric carcinoma
[10].
In conclusion, mesonephric carcinoma has its unique and mild cytological
characteristics which can be easily underdiagosed as atypical
endometrium cells; therefore, knowledge of its cytology is important in
order to eliminate it as a differential diagnose. Cell block with the
support of immunocytochemical staining is indispensable.