Primary transitional cell carcinoma of the endometrium: Exceptional presentation of a rare tumor

Abstract

Transitional cell carcinoma (TCC) is an extremely rare gynecologic tumor, particularly in the endometrium. All endometrial TCC cases reported so far in the literature were diagnosed at relatively advanced stages. In the present article, we report a pure primary endometrial TCC initially revealed by an abdominal mass and classified as an International Federation of Gynecology and Obstetrics stage IA. The patient was successfully treated with surgery and adjuvant radiotherapy. This case highlights the importance of early diagnosis of gynecologic malignancies, offering satisfactory outcomes even in the rarest types for which evidence-based recommendations are lacking.

Full text

Radiology Case Reports 18 (2023) 205–208
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/radcr
Case Report
Primary transitional cell carcinoma of the
endometrium: Exceptional presentation of a rare
tumor
✩
Souane Berhili, MD
a , b , 1 , ∗
, Karima Mouden, MD
c , 1
, Mohammed Moukhlissi, MD
a , b
,
Tijani El Harroudi, MD
a , d
, Loubna Mezouar, MD
a , b
a
Faculty of Medicine, Mohammed Premier University, Oujda, Morocco
b
Department of Radiotherapy, Hassan II Oncology Center, CHU Mohammed VI, PK8 Jerada Rd, 60000, Oujda,
Morocco
c
Department of Radiotherapy, Beni Mellal Oncology Center, Beni Mellal, Morocco
d
Department of Oncological Surgery, Hassan II Oncology Center, CHU Mohammed VI, Oujda, Morocco
          
Article history:
Received 30 September 2022
Revised 5 October 2022
Accepted 8 October 2022
Keywords:
Transitional cell carcinoma
Endometrial cancer
Early stage
Rare tumor
       
Transitional cell carcinoma (TCC) is an extremely rare gynecologic tumor, particularly in the
endometrium. All endometrial TCC cases reported so far in the literature were diagnosed
at relatively advanced stages. In the present article, we report a pure primary endometrial
TCC initially revealed by an abdominal mass and classied as an International Federation of
Gynecology and Obstetrics stage IA. The patient was successfully treated with surgery and
adjuvant radiotherapy. This case highlights the importance of early diagnosis of gynecologic
malignancies, offering satisfactory outcomes even in the rarest types for which evidence-
based recommendations are lacking.
© 2022 The Authors. Published by Elsevier Inc. on behalf of University of Washington.
This is an open access article under the CC BY-NC-ND license
( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
Introduction
Transitional cell carcinoma (TCC), also known as urothelial
carcinoma, is an exceptional histological type in gynecologic
oncology. The cases reported in the literature are most often
localized to the ovary, where they represent less than 2% of
ovarian cancers [ 1 ,2 ]. More importantly, endometrial TCC rep-
resents a diagnostic and therapeutic challenge for clinicians,
✩ Competing Interests: The authors declare that they have no conicts of interest related to this article.
∗Corresponding author.
E-mail address: berhili.souane@gmail.com (S. Berhili).
1 SB and KM contributed equally to this manuscript.
given the lack of specic recommendations for this tumor.
However, it is essential to perform an entire urinary tract ex-
ploration before making the diagnosis of primary endometrial
TCC to rule out a urologic origin of the tumor.
Only a few cases of endometrial TCCs have been re-
ported in the literature, almost all of which were diagnosed
at advanced stages with myometrial tumor invasion [ 2–16 ].
However, cases of invasive TCC discovered at an early stage
have never been published. We report below a case of pri-
https://doi.org/10.1016/j.radcr.2022.10.030
1930-0433/© 2022 The Authors. Published by Elsevier Inc. on behalf of University of Washington. This is an open access article under the
CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

206 Radiology Case Reports 18 (2023) 205–208
Fig. 1. –Pelvic axial-enhanced CT image showing a large
intrauterine uid collection (black continuous arrow)
thinning the uterine wall (white dotted arrow) upstream of
a 7 cm posterior isthmic tumor (black asterisk).
mary invasive TCC of the endometrium diagnosed at an early
stage.
Clinical presentation
A 58-year-old White-skinned female with no previous medi-
cal history presented with an abdominal mass associated with
whitish leukorrhea and intermittent vaginal bleeding lasting
for 2 months. Physical examination found a large, painless
subumbilical mobile mass of rm consistency. Gynecological
examination found endo-uterine bleeding without noting any
abnormality of the cervicovaginal tract. An abdominal-pelvic
computed tomography (CT) scan showed a dual-component
pelvic mass (cystic and eshy) at the expense of the uterine
body, measuring 12.96 ×15.55 cm. No deep adenomegaly was
detected, and the upper and lower urinary tract and digestive
structures were radiologically normal ( Fig. 1 ).
An endometrial biopsy brought poorly differentiated carci-
nomatous cells. Then the patient underwent a total hysterec-
tomy with bilateral adnexectomy, without lymph node dissec-
tion. Macroscopically, the uterus was enlarged, weighing 850
g, distended by endocavitary serous uid dilating the uterine
wall, which became thinned to less than 5 mm at the lateral
and fundal areas. This uid collection was accumulating up-
stream of a large friable isthmic tumor of 7 ×7 ×5 cm di-
ameters. A microscopic study found an inltrative malignant
epithelial proliferation, affecting only the endometrium at its
isthmic part, made of transitional-type cells of high-grade ma-
lignancy and assembled in inltrative sheets and papillary
structures resembling urinary tract TCC. Peri-tumoral vascu-
lar emboli were absent. The myometrium was tumor-free but
highly atrophic with only 5 mm thickness. No other associated
histological type was observed.
Immunohistochemical staining of the tumor cells found
positive labeling for anti-CK7, anti-CK20, and anti-P63 anti-
bodies and negative labeling for anti-P53, anti-WT1, and anti-
β-catenin antibodies ( Fig. 2 ).
Urinary panendoscopy performed postoperatively did not
detect any primary tumor of the urinary tract. We concluded
that the patient had a primary pure high-grade TCC of the en-
dometrium, without myometrial invasion and without vascu-
lar emboli, corresponding to the International Federation of
Gynecology and Obstetrics (FIGO) stage IA and to the European
Society of Medical Oncology high-intermediate risk category.
On the advice of the multidisciplinary team meeting, the
patient received adjuvant external radiotherapy to the pelvis
Fig. 2. – Microscopic examination (hematoxylin and eosin staining, magnication ×20 on the right and ×40 on the left) of
the tumor showing the malignant epithelial proliferation made of transitional cells arranged in papillary sheets, with
chorion invasion, resembling TCC of the urinary tract.

Radiology Case Reports 18 (2023) 205–208 207
Table 1. –Clinical and pathological features of previous reports of primary endometrial TCCs.
Author (year of publication) Patient age
(years)
Histological type Tu m o r size
(cm)
FIGO
stage
Follow-up
Chen et al. (1990) [3] 71 TCC
(95%) + endometrioid + mucinous
5.5 III A NED after 5 years
Spiegel et al. (1996) [4] 75 TCC (75%) + endometrioid 4 III A NED after 15 months
Lininger et al. (1997) [5] 53
a
TCC
(5%) + endometrioid + mucinous
3 I B NED after 4 months
83 TCC (50%) + squamous + spindle
cell sarcoma
3.2 I B NED after 8 years
64 TCC (70%) + endometrioid + sero-
papillary
7 I C NED after 35 months
76 TCC
(75%) + endometrioid + squamous
5 I C Tu m o r Relapse after 1
year
43 TCC
(80%) + endometrioid + squamous
2 I C Lost
60 TCC (95%) + squamous 1.5 I
b Lost
73 TCC (95%) + squamous 0.4 I
b Dead due to metastatic
colic cancer after 13
years
41
a
TCC
(40%) + endometrioid + papillary
0.8 III A Lost
Fukunaga et al. (1998) [6] 50 TCC (95%) + endometrioid 10 I B NED after 7 years
Labonté et al. (2001) [7] 46 TCC (90%) + endometrioid 8 IV A NED after 18 months
Lum et al. (2005) [11] 77 NR 8.6 IV A NED after 18 months
Ahluwalia et al. (2006) [12] 78 TCC (95%) + endometrioid 2 I B NED after 10 months
Giordano et al. (2007) [8] 61 TCC (100%) 1.5 I B NR
Ribeiro-Silva et al. (2007) [13] 84
a
TCC
(15%) + squamous + papillary
5 I B Dead after 1 year
Mariño-Enriquez et al. (2008)
[14]
55 TCC (100%) 4 I B NED after 6 months
76 TCC (80%) + endometrioid NR I B NED after 3 months
63 TCC (50%) + endometrioid 3.7 I B NED after 16 months
73
a
TCC (20%) + endometrioid 6.5 I B NED after 6 months
77 TCC (90%) + endometrioid 5.5 II B NED after 8 months
Tong et al. (2013) [15] 66 TCC (100%) 3.5 I B NR
Cuccia et al. (2018) [2] 65 TCC (100%) 2.2 I B Peritoneal relapse after
43 months
Cubo-Abert et al. (2018) [9] 40 TCC (100%) NR III C Stable residual disease
after 7 months
Azzakhmam et al. (2020) [16] 62
a
TCC (15%) + squamous papillary NR I B NR
Sahu et al. (2020) [17] 62 TCC (100%) NR I B NR
Amjad et al. (2022) [10] 58 TCC (100%) 0.1 II NED after 5 years
Present case 58 TCC (100%) 7 I A NED after 5 years
NED, no evidence of disease; NR, not reported.
a Not classied as endometrial TCC primaries as the TCC component represented less than 50% of the tumor
b Substages IA, IB, or IC not reported.
40 days after surgery using the 3D conformal technique. A to-
tal dose of 45 Gy in 1.8 Gy/fraction was delivered to the tumor
bed and pelvic lymphatic chains by 6 photon beams of 18 MV
energy in 25 fractions and 35 days. Five years after the end
of radiotherapy, the patient remained tumor-free, without any
side effects affecting her daily life.
Discussion
Because of its rarity, knowledge about primary endometrial
TCC has been exclusively limited to clinical case reports. To
date, only 27 cases have been published, almost all about tu-
mors discovered at relatively advanced stages ( Tabl e 1 ) [ 2–17 ].
Only one publication reported by Lininger et al. in 1997 did not
specify the presence or absence of myometrial involvement
for 2 FIGO stage I cases [5] . Thus, our observation is the rst in
the English literature to report a case of pure endometrial TCC,
specifying the absence of myometrial invasion (FIGO stage IA).
There are no specic features to recognize primary en-
dometrial TCC on imaging. However, we note the uncom-
mon presentation of our case where CT showed an enlarged
uterine cavity (15.5 cm) above the large isthmic tumor of
7 cm in size, which is among the largest sizes reported
so far.
TCC originating from the ovary or the urinary tract should
always be ruled out before making the diagnosis of primary
endometrial TCC. In addition to imaging, both immunohisto-
chemical study and urinary tract endoscopy are essential di-
agnostic tools to rule out other primaries and conrm the en-
dometrial origin of the tumor.

208 Radiology Case Reports 18 (2023) 205–208
Pathological examination is the cornerstone of diagnosis
process. Endometrial carcinoma is classied as primary TCC
when the transitional component represents more than 50%
of the tumor; otherwise, pathology response would be en-
dometrial carcinoma with transitional cell differentiation [10] .
Among the 27 published cases of endometrial TCC, 5 had less
than 50% of the TCC component, thus failing to comply with
the denition of primary endometrial TCC [ 5 ,13 ,14 ,16 ]. Only 7
cases were pure TCCs (TCC representing 100% of the tumor),
whereas the remaining 15 cases had a mixed histology where
TCC was associated with either endometrioid, mucinous, pap-
illary serous, squamous cell carcinoma, or spindle cell sar-
coma ( Tab le 1 ). Our case was a pure endometrial TCC, with
the particular presentation at an early FIGO stage IA despite
the large tumor size.
Based on the limited literature data, adding radiation ther-
apy after complete surgical removal is a reasonable adjuvant
option to maximize control of primary endometrial TCC. The
few published cases have also reported the use of adjuvant
radiotherapy, either external radiotherapy or brachytherapy
[ 2 –5 ,7 ]. In our case, the tumor was classied at the high-
intermediate risk category of the European Society of Medi-
cal Oncology, with propositions of adjuvant treatment rang-
ing between external-beam radiotherapy and local vaginal
brachytherapy. Given that the 7 cm tumor was entirely endo-
uterine without cervical involvement and that the vaginal
margins were negative, adjuvant external-beam radiotherapy
seemed more appropriate than vaginal brachytherapy, espe-
cially when considering the low probability of pelvic postradi-
ation toxicity (urinary and digestive) ensured by the conformal
technique at the dose of 45 Gy in 25 fractions.
Our patient remained in good tumor control after 5 years
of follow-up. Most published cases of primary endometrial
TCC had good control at the time of publication; only 2 cases
of relapse were noted during follow-up [ 2 ,5 ]. Nevertheless, it
should be noted that the majority of cases had less than 1
year of follow-up, and only 5 cases had prolonged follow-up
of 5 years or more.
Conclusion
The present case is the rst in the literature to report a pure
primary invasive endometrial TCC diagnosed at FIGO stage
IA, with excellent long-term oncological outcomes. It high-
lights the major role of early diagnosis in gynecologic malig-
nancies by facilitating patients’ access to early screening fa-
cilities. Early diagnosis increases the chances of therapeutic
success, even in rare tumors lacking evidence-based recom-
mendations.
Patient consent
Written consent was obtained from the patient for publication
of this article.
REFERENCES
[1] De Cecio R, Cantile M, Collina F, Marra L, Santonastaso C,
Scaffa C, et al. Borderline Brenner tumor of the ovary: a case
report with immunohistochemical and molecular study. J
Ovar Res 2014;7:101. doi: 10.1186/s13048- 014- 0101- 7 .
[2] Cuccia F, Mortellaro G, Spera A, Evangelista G, Lo Casto A,
Ferrera G. Transitional cell carcinoma of endometrium: a
case report of rare pure form. J Contemp Brachyther
2018;10(5):483–5. doi: 10.5114/jcb.2018.79411 .
[3] Chen KT . Extraovarian transitional cell carcinoma of female
genital tract. Am J Clin Pathol 1990;94(5):670–1 .
[4] Spiegel GW, Austin RM, Gelven PL. Transitional cell
carcinoma of the endometrium. Gynecol Oncol
1996;60(2):325–30. doi: 10.1006/gyno.1996.0047 .
[5] Lininger RA , Ashfaq R , Albores-Saavedra J , Tavassoli FA .
Transitional cell carcinoma of the endometrium and
endometrial carcinoma with transitional cell differentiation.
Cancer 1997;79(10):1933–43 .
[6] Fukunaga M, Ushigome S. Transitional cell carcinoma of the
endometrium. Histopathology 1998;32(3):284–6.
doi: 10.1046/j.1365-2559.1998.0372i.x .
[7] Labonté S, Têtu B, Boucher D, Larue H. Transitional cell
carcinoma of the endometrium associated with a benign
ovarian Brenner tumor: a case report. Hum Pathol
2001;32(2):230–2. doi: 10.1053/hupa.2001.20900 .
[8] Giordano G, D’Adda T, Gnetti L, Merisio C, Raboni S.
Transitional cell carcinoma of the endometrium associated
with benign ovarian Brenner tumor: a case report with
immunohistochemistry molecular analysis and a review of
the literature. Int J Gynecol Pathol 2007;26(3):298–304.
doi: 10.1097/01.pgp.0000236943.28969.b2 .
[9] Cubo-Abert M, Rodríguez-Mías NL, Capote S,
García-Jiménez A, Sánchez-Iglesias JL, De la Torre J, et al.
Advanced stage of primary transitional-cell carcinoma of the
endometrium: a case report and literature review. J Gynecol
Surg 2018;34(2):109–13. http://doi.org/10.1089/gyn.2017.0079 .
[10] Amjad R, Mogharbel H. Primary transitional cell carcinoma
of the endometrium: a case report and review of literature.
Cureus 2022;14(1):e21365. doi: 10.7759/cureus.21365 .
[11] Lum D. Primary transitional cell carcinoma of the
endometrium. Pathology 2005;37(6):554–7.
doi: 10.1080/00313020500368378 .
[12] Ahluwalia M, Light AM, Surampudi K, Finn CB. Transitional
cell carcinoma of the endometrium: a case report and review
of the literature. Int J Gynecol Pathol 2006;25(4):378–82.
doi: 10.1097/01.pgp.0000215296.53361.4b .
[13] Ribeiro-Silva A. Immunohistochemical features of a papillary
squamous cell carcinoma of the endometrium with
transitional cell differentiation. Diagn Pathol 2007;2:26.
doi: 10.1186/1746- 1596- 2- 26 .
[14] Mariño-Enríquez A, González-Rocha T, Burgos E, Stolnicu S,
Mendiola M, Nogales FF, et al. Transitional cell carcinoma of
the endometrium and endometrial carcinoma with
transitional cell differentiation: a clinicopathologic study of
5 cases and review of the literature. Hum Pathol
2008;39(11):1606–13. doi: 10.1016/j.humpath.2008.03.005 .
[15] Tong J, Kasznica J, Habib F. Transitional cell carcinoma of
endometrium arising in a polypoid adenomyoma in the
endometrial cavity. Am J Clin Pathol 2013;140(1):A188.
doi: 10.1093/ajcp/140.suppl1.188 .
[16] Azzakhmam M, Oukabli M. Squamous papillary carcinoma
with transitional differenciation of the endometrium: an
uncommon condition. Pan Afr Med J CM 2020;2:76.
doi: 10.11604/pamj-cm.2020.2.76.21869 .
[17] Sahu PR, Hiwale KM, Vag h a SJ. Transitional-cell carcinoma of
the endometrium: a rare case report. J Evol Med Dent Sci
2020;9(36):2666 + . doi: 10.14260/jemds/2020/579 .