Background: Epithelioid Trophoblastic Tumor (ETT) and Placental Site Trophoblastic Tumor (PSTT) are two of the rarest GTNs that share certain features at diagnosis and management. Atypical Placental Site Nodule (APSN) is a relatively new entity considered as a premalignant lesion. Objectives and Methods: The aim of this review was to summarize the main characteristics of each of these entities, their diagnostic features, and their treatment’s standard of care including fertility-sparing treatments. Outcome: This study provides a thorough review of ETT, PSTT, and APSN. Conclusions: The reader will gain an insight view of these rare tumors arising from the intermediate trophoblast.

1.
Zhao
J
,
Lv
WG
,
Feng
FZ
,
Wan
XR
,
Liu
JH
,
Yi
XF
, et al
.
Placental site trophoblastic tumor: a review of 108 cases and their implications for prognosis and treatment
.
Gynecol Oncol
.
2016
;
142
(
1
):
102
8
. .
2.
Liu
W
,
Zhao
W
,
Huang
X
.
Outcomes and prognostic factors of placental-site trophoblastic tumor: a retrospective study of 58 cases
.
Arch Gynecol Obstet
.
2022
;
306
(
5
):
1633
41
. .
3.
Burkett
WC
,
Soper
JT
.
A review of current management of placental site trophoblastic tumor and epithelioid trophoblastic tumor
.
Obstet Gynecol Surv
.
2022
;
77
(
2
):
101
10
. .
4.
Kaur
B
.
Pathology of gestational trophoblastic disease (GTD)
.
Best Pract Res Clin Obstet Gynaecol
.
2021
;
74
:
3
28
. .
5.
Stichelbout
M
,
Devisme
L
,
Franquet-Ansart
H
,
Massardier
J
,
Vinatier
D
,
Renaud
F
, et al
.
SALL4 expression in gestational trophoblastic tumors: a useful tool to distinguish choriocarcinoma from placental site trophoblastic tumor and epithelioid trophoblastic tumor
.
Hum Pathol
.
2016
;
54
:
121
6
. .
6.
Hancock
BW
,
Tidy
J
.
Placental site trophoblastic tumour and epithelioid trophoblastic tumour
.
Best Pract Res Clin Obstet Gynaecol
.
2021
;
74
:
131
48
. .
7.
van der Lely
SJ
,
Boorsma
J
,
Hilhorst
M
,
Kers
J
,
Roelofs
J
,
Jakulj
L
, et al
.
“It’s not lupus.” A placental site trophoblastic tumor presenting as a lupus-like paraneoplastic syndrome. A grand round case
.
Lupus
.
2021
;
30
(
3
):
495
501
. .
8.
Brewer
CA
,
Adelson
MD
,
Elder
RC
.
Erythrocytosis associated with a placental-site trophoblastic tumor
.
Obstet Gynecol
.
1992
;
79
(
5(Pt 2)
:
846
9
.
9.
Nagamani
M
,
Kaspar
HG
,
Van Dinh
T
,
Hannigan
EV
,
Smith
E
.
Hyperthecosis of the ovaries in a woman with a placental site trophoblastic tumor
.
Obstet Gynecol
.
1990
;
76
(
5
):
931
5
. .
10.
Lan
C
,
Li
Y
,
He
J
,
Liu
J
.
Placental site trophoblastic tumor: lymphatic spread and possible target markers
.
Gynecol Oncol
.
2010
;
116
(
3
):
430
7
. .
11.
Baergen
RN
,
Rutgers
JL
,
Young
RH
,
Osann
K
,
Scully
RE
.
Placental site trophoblastic tumor: a study of 55 cases and review of the literature emphasizing factors of prognostic significance
.
Gynecol Oncol
.
2006
;
100
(
3
):
511
20
. .
12.
Hassadia
A
,
Gillespie
A
,
Tidy
J
,
Everard R G N
J
,
Wells
M
,
Coleman
R
, et al
.
Placental site trophoblastic tumour: clinical features and management
.
Gynecol Oncol
.
2005
;
99
(
3
):
603
7
. .
13.
Moutte
A
,
Doret
M
,
Hajri
T
,
Peyron
N
,
Chateau
F
,
Massardier
J
, et al
.
Placental site and epithelioid trophoblastic tumours: diagnostic pitfalls
.
Gynecol Oncol
.
2013
;
128
(
3
):
568
72
. .
14.
Gadducci
A
,
Carinelli
S
,
Guerrieri
ME
,
Aletti
GD
.
Placental site trophoblastic tumor and epithelioid trophoblastic tumor: clinical and pathological features, prognostic variables, and treatment strategy
.
Gynecol Oncol
.
2019
;
153
(
3
):
684
93
. .
15.
Schmid
P
,
Nagai
Y
,
Agarwal
R
,
Hancock
B
,
Savage
PM
,
Sebire
NJ
, et al
.
Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study
.
Lancet
.
2009
;
374
(
9683
):
48
55
. .
16.
Choi
MC
,
Jung
SG
,
Park
H
,
Joo
WD
,
Lee
C
,
Lee
JH
, et al
.
Placental site trophoblastic tumors: analysis of the clinicopathologic characteristics of 20 cases in Korea
.
Int J Gynecol Cancer
.
2016
;
26
(
8
):
1515
20
. .
17.
Papadopoulos
AJ
,
Foskett
M
,
Seckl
MJ
,
McNeish
I
,
Paradinas
FJ
,
Rees
H
, et al
.
Twenty-five years’ clinical experience with placental site trophoblastic tumors
.
J Reprod Med
.
2002
;
47
(
6
):
460
4
.
18.
Hyman
DM
,
Bakios
L
,
Gualtiere
G
,
Carr
C
,
Grisham
RN
,
Makker
V
, et al
.
Placental site trophoblastic tumor: analysis of presentation, treatment, and outcome
.
Gynecol Oncol
.
2013
;
129
(
1
):
58
62
. .
19.
Lee
HJ
,
Shin
W
,
Jang
YJ
,
Choi
CH
,
Lee
JW
,
Bae
DS
, et al
.
Clinical characteristics and outcomes of placental site trophoblastic tumor: experience of single institution in Korea
.
Obstet Gynecol Sci
.
2018
;
61
(
3
):
319
27
. .
20.
Chen
Y
,
Zhang
X
,
Xie
X
.
Clinical features of 17 cases of placental site trophoblastic tumor
.
Int J Gynaecol Obstet
.
2011
;
115
(
2
):
204
5
. .
21.
Ngan
HYS
,
Seckl
MJ
,
Berkowitz
RS
,
Xiang
Y
,
Golfier
F
,
Sekharan
PK
, et al
.
Diagnosis and management of gestational trophoblastic disease: 2021 update
.
Int J Gynaecol Obstet
.
2021
;
155
(
Suppl 1
):
86
93
. .
22.
Yordanov
A
,
Strateva
D
,
Kostov
S
,
Kornovski
Y
,
Slavchev
S
,
Ivanova
Y
, et al
.
Placental site trophoblastic tumour mimicking an intramural pregnancy: a case report and review of the literature
.
Prz Menopauzalny
.
2022
;
21
(
2
):
142
7
. .
23.
Khoiwal
K
,
Gill
P
,
Chawla
L
,
Agrawal
S
,
Chaturvedi
J
.
Placental site trophoblastic tumor masquerading as post-molar uterine arteriovenous malformation
.
J Turk Ger Gynecol Assoc
.
2022
.
24.
Zhao
CF
,
Du
ZQ
,
Li
N
,
Wang
Y
,
Zhao
SF
.
CARE-Placental site trophoblastic tumor presenting with thrombotic microangiopathy: a case report
.
Medicine
.
2018
;
97
(
43
):
e12698
. .
25.
Patacchiola
F
,
Di Stefano
L
,
Di Febbo
G
,
D’Alfonso
A
,
Di Fonso
A
,
Carta
G
.
Placental site trophoblastic tumor on endometrial polyp: a case report
.
Eur J Gynaecol Oncol
.
2014
;
35
(
1
):
87
90
.
26.
Gupta
N
,
Mittal
S
,
Misra
R
,
Vimala
N
,
Das
AK
.
Placental site trophoblastic tumor originating in a tubal ectopic pregnancy
.
Eur J Obstet Gynecol Reprod Biol
.
2006
;
129
(
1
):
92
4
. .
27.
Sakhel
K
,
Khalil
A
,
Kaspar
H
,
Azar
G
,
Mansour
A
,
Nassar
A
.
Placental site trophoblastic tumor in a patient with secondary infertility and radiological findings consistent with a leiomyoma: a case report
.
Int J Gynecol Cancer
.
2004
;
14
(
4
):
694
6
. .
28.
Ichikawa
Y
,
Nakauchi
T
,
Sato
T
,
Oki
A
,
Tsunoda
H
,
Yoshikawa
H
.
Ultrasound diagnosis of uterine arteriovenous fistula associated with placental site trophoblastic tumor
.
Ultrasound Obstet Gynecol
.
2003
;
21
(
6
):
606
8
. .
29.
Shaaban
AM
,
Rezvani
M
,
Haroun
RR
,
Kennedy
AM
,
Elsayes
KM
,
Olpin
JD
, et al
.
Gestational trophoblastic disease: clinical and imaging features
.
Radiographics
.
2017
;
37
(
2
):
681
700
. .
30.
Zhou
Y
,
Lu
H
,
Yu
C
,
Tian
Q
,
Lu
W
.
Sonographic characteristics of placental site trophoblastic tumor
.
Ultrasound Obstet Gynecol
.
2013
;
41
(
6
):
679
84
. .
31.
Brandt
KR
,
Coakley
KJ
.
MR appearance of placental site trophoblastic tumor: a report of three cases
.
AJR Am J Roentgenol
.
1998
;
170
(
2
):
485
7
. .
32.
Feltmate
CM
,
Genest
DR
,
Wise
L
,
Bernstein
MR
,
Goldstein
DP
,
Berkowitz
RS
.
Placental site trophoblastic tumor: a 17-year experience at the New England Trophoblastic Disease Center
.
Gynecol Oncol
.
2001
;
82
(
3
):
415
9
. .
33.
Froeling
FEM
,
Ramaswami
R
,
Papanastasopoulos
P
,
Kaur
B
,
Sebire
NJ
,
Short
D
, et al
.
Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours
.
Br J Cancer
.
2019
;
120
(
6
):
587
94
. .
34.
Ngu
SF
,
Ngan
HYS
.
Surgery including fertility-sparing treatment of GTD
.
Best Pract Res Clin Obstet Gynaecol
.
2021
;
74
:
97
108
. .
35.
Chiofalo
B
,
Palmara
V
,
Laganà
AS
,
Triolo
O
,
Vitale
SG
,
Conway
F
, et al
.
Fertility sparing strategies in patients affected by placental site trophoblastic tumor
.
Curr Treat Options Oncol
.
2017
;
18
(
10
):
58
. .
36.
Porter
A
,
Barcelon
JM
,
Budker
RL
,
Marsh
L
,
Moriarty
JM
,
Aguiar
X
, et al
.
Treatment of metastatic placental site trophoblastic tumor with surgery, chemotherapy, immunotherapy and coil embolization of multiple pulmonary arteriovenous fistulate
.
Gynecol Oncol Rep
.
2021
;
36
:
100782
. .
37.
Shih
IM
,
Ronnett
BM
,
Mazur
M
,
Kurman
.
Gestational Trophoblastic Tumors and related tumorlike lesions
. In:
Kurman
RJ
, editor.
Blaustein’s pathology of the female genital tract
.
New York
:
Springer
;
2002
. p.
1307
76
.
38.
Shih
IM
,
Kurman
RJ
.
Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma
.
Am J Surg Pathol
.
1998
;
22
(
11
):
1393
403
. .
39.
Oldt
RJ
3rd
,
Kurman
RJ
,
Shih
IM
.
Molecular genetic analysis of placental site trophoblastic tumors and epithelioid trophoblastic tumors confirms their trophoblastic origin
.
Am J Pathol
.
2002
;
161
(
3
):
1033
7
. .
40.
Shih
IM
.
Gestational trophoblastic neoplasia: pathogenesis and potential therapeutic targets
.
Lancet Oncol
.
2007
;
8
(
7
):
642
50
. .
41.
Horowitz
NS
,
Goldstein
DP
,
Berkowitz
RS
.
Placental site trophoblastic tumors and epithelioid trophoblastic tumors: biology, natural history, and treatment modalities
.
Gynecol Oncol
.
2017
;
144
(
1
):
208
14
. .
42.
Zhang
X
,
W
,
B
.
Epithelioid trophoblastic tumor: an outcome-based literature review of 78 reported cases
.
Int J Gynecol Cancer
.
2013
;
23
(
7
):
1334
8
. .
43.
Davis
MR
,
Howitt
BE
,
Quade
BJ
,
Crum
CP
,
Horowitz
NS
,
Goldstein
DP
, et al
.
Epithelioid trophoblastic tumor: a single institution case series at the New England Trophoblastic Disease Center
.
Gynecol Oncol
.
2015
;
137
(
3
):
456
61
. .
44.
Narita
F
,
Takeuchi
K
,
Hamana
S
,
Ohbayashi
C
,
Ayata
M
,
Maruo
T
.
Epithelioid trophoblastic tumor (ETT) initially interpreted as cervical cancer
.
Int J Gynecol Cancer
.
2003
;
13
(
4
):
551
4
. .
45.
Zhang
X
,
Shi
H
,
Chen
X
.
Epithelioid trophoblastic tumor after induced abortion with previous broad choriocarcinoma: a case report and review of literature
.
Int J Clin Exp Pathol
.
2014
;
7
(
11
):
8245
50
.
46.
Rodríguez-Trujillo
A
,
Martínez-Serrano
MJ
,
Saco
A
,
Torné
A
.
Two cases of epithelioid trophoblastic tumors in postmenopausal women
.
Menopause
.
2017
;
24
(
11
):
1304
8
. .
47.
Ohya
A
,
Higuchi
K
,
Shimojo
H
,
Fujinaga
Y
,
Kadoya
M
,
Shiohara
S
.
Epithelioid trophoblastic tumor of the uterus: a case report with radiologic-pathologic correlation
.
J Obstet Gynaecol Res
.
2017
;
43
(
8
):
1360
5
. .
48.
Tse
KY
,
Chiu
KWH
,
Chan
KKL
,
Chu
MMY
,
Ngu
SF
,
Cheung
ANY
, et al
.
A case series of five patients with pure or mixed gestational epithelioid trophoblastic tumors and a literature review on mixed tumors
.
Am J Clin Pathol
.
2018
;
150
(
4
):
318
32
. .
49.
Lei
W
,
Zhang
F
,
Zheng
C
,
Zhao
C
,
Tu
S
,
Bao
Y
.
Metastatic epithelioid trophoblastic tumor of the lung: a case report
.
Medicine
.
2018
;
97
(
16
):
e0306
. .
50.
Scott
EM
,
Smith
AL
,
Desouki
MM
,
Olawaiye
AB
.
Epithelioid trophoblastic tumor: a case report and review of the literature
.
Case Rep Obstet Gynecol
.
2012
;
2012
:
862472
. .
51.
Qin
J
,
Ying
W
,
Cheng
X
,
Wu
X
,
Lu
B
,
Liang
Y
, et al
.
A well-circumscribed border with peripheral Doppler signal in sonographic image distinguishes epithelioid trophoblastic tumor from other gestational trophoblastic neoplasms
.
PLoS One
.
2014
;
9
(
11
):
e112618
. .
52.
Palmer
JE
,
Macdonald
M
,
Wells
M
,
Hancock
BW
,
Tidy
JA
.
Epithelioid trophoblastic tumor: a review of the literature
.
J Reprod Med
.
2008
;
53
(
7
):
465
75
.
53.
Frijstein
MM
,
Lok
CAR
,
van Trommel
NE
,
Ten Kate-Booij
MJ
,
Massuger
LFAG
,
van Werkhoven
E
, et al
.
Management and prognostic factors of epithelioid trophoblastic tumors: results from the international society for the study of trophoblastic diseases database
.
Gynecol Oncol
.
2019
;
152
(
2
):
361
7
. .
54.
Shen
X
,
Xiang
Y
,
Guo
L
,
Ren
T
,
Feng
F
,
Wan
X
, et al
.
Analysis of clinicopathologic prognostic factors in 9 patients with epithelioid trophoblastic tumor
.
Int J Gynecol Cancer
.
2011
;
21
(
6
):
1124
30
. .
55.
Ghorani
E
,
Kaur
B
,
Fisher
RA
,
Short
D
,
Joneborg
U
,
Carlson
JW
, et al
.
Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia
.
Lancet
.
2017
;
390
(
10110
):
2343
5
. .
56.
Choi
MC
,
Oh
J
,
Lee
C
.
Effective anti-programmed cell death 1 treatment for chemoresistant gestational trophoblastic neoplasia
.
Eur J Cancer
.
2019
;
121
:
94
7
. .
57.
Pisani
D
,
Calleja-Agius
J
,
Di Fiore
R
,
O’Leary
JJ
,
Beirne
JP
,
O’Toole
SA
, et al
.
Epithelioid trophoblastic tumour: a case with genetic linkage to a child born over seventeen years prior, successfully treated with surgery and pembrolizumab
.
Curr Oncol
.
2021
;
28
(
6
):
5346
55
. .
58.
Bell
SG
,
Uppal
S
,
Sakala
MD
,
Sciallis
AP
,
Rolston
A
.
An extrauterine extensively metastatic epithelioid trophoblastic tumor responsive to pembrolizumab
.
Gynecol Oncol Rep
.
2021
;
37
:
100819
. .
59.
Mangili
G
,
Sabetta
G
,
Cioffi
R
,
Rabaiotti
E
,
Candotti
G
,
Pella
F
, et al
.
Current evidence on immunotherapy for gestational trophoblastic neoplasia (GTN)
.
Cancers
.
2022
;
14
(
11
):
2782
. .
60.
Kaur
B
,
Short
D
,
Fisher
RA
,
Savage
PM
,
Seckl
MJ
,
Sebire
NJ
.
Atypical placental site nodule (APSN) and association with malignant gestational trophoblastic disease; a clinicopathologic study of 21 cases
.
Int J Gynecol Pathol
.
2015
;
34
(
2
):
152
8
. .
61.
International Agency for Research on Cancer
.
WHO classification of female genital tumours
. 5th ed.
Iarc:France
:
WHO 2020
;
2020
; p.
309e22
.
62.
Shih
IM
,
Kurman
RJ
.
The pathology of intermediate trophoblastic tumors and tumor-like lesions
.
Int J Gynecol Pathol
.
2001
;
20
(
1
):
31
47
. .
63.
Dholakia
J
,
Chen
W
,
O’Malley
DM
,
Ronnett
BM
.
A rare case of atypical placental site nodule with an emerging intermediate trophoblastic tumor
.
Int J Gynecol Pathol
.
2020
;
39
(
3
):
238
46
. .
64.
Aiob
A
,
Cohen
HI
,
Naskovica
K
,
Tendler
R
,
Sharon
A
,
Bornstein
J
.
Coexisting epithelioid trophoblastic tumor and placental site trophoblastic tumor during asymptomatic relapse: a case report and literature review
.
Int J Gynecol Pathol
.
2022
;
41
(
4
):
423
30
. .
65.
Lok
C
,
van Trommel
N
,
Massuguer
L
,
Golfier
F
,
Seckl
M
, et al
.
Practical clinical guidelines of the EOTTD for the treatment and referral of gestational trophoblastic disease
.
European Journal of Cancer
.
2020
. https://pubmed.ncbi.nlm.nih.gov/32247260/.
In press
.
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