Here, we present a case that highlights the crucial pitfalls related to the presence of morular metaplasia (MM) in endometrioid carcinoma, which are insufficiently recognized in the routine pathology practice. A 45-year-old woman underwent hysterectomy with rectosigmoidectomy due to a 11-cm mass involving uterus, right ovary, and rectosigmoid colon. Histologically, the lesion appeared as a predominantly solid carcinoma with a minor glandular component. Results of the first immunohistochemical analysis suggested a colorectal origin (PAX8-, CK7-, WT1-, hormone receptors-, and CDX2+ in the absence of mucinous features). Subsequent immunohistochemistry (nuclear β-catenin+, CD10+, and low ki67 in the solid areas) supported a diagnosis of endometrioid carcinoma with diffuse MM. This case remarks that morphological and immunohistochemical features of MM may conceal the glandular architecture and the typical immunophenotype of endometrioid carcinomas. Acknowledging the diagnostic issues related to MM appears crucial to avoid misdiagnosis and inappropriate patient management.

1.
Nicolae
A
,
Preda
O
,
Nogales
FF
.
Endometrial metaplasias and reactive changes: a spectrum of altered differentiation
.
J Clin Pathol
.
2011
;
64
(
2
):
97
106
. .
2.
McCluggage
WG
,
Van de Vijver
K
.
SATB2 is consistently expressed in squamous morules associated with endometrioid proliferative lesions and in the stroma of atypical polypoid adenomyoma
.
Int J Gynecol Pathol
.
2019 Sep
;
38
(
5
):
397
403
. .
3.
Blanco
LZ
 Jr
,
Heagley
DE
,
Lee
JC
,
Gown
AM
,
Gattuso
P
,
Rotmensch
J
, et al
Immunohistochemical characterization of squamous differentiation and morular metaplasia in uterine endometrioid adenocarcinoma
.
Int J Gynecol Pathol
.
2013 May
;
32
(
3
):
283
92
. .
4.
Houghton
O
,
Connolly
LE
,
McCluggage
WG
.
Morules in endometrioid proliferations of the uterus and ovary consistently express the intestinal transcription factor CDX2
.
Histopathology
.
2008 Aug
;
53
(
2
):
156
65
. .
5.
Wani
Y
,
Notohara
K
,
Saegusa
M
,
Tsukayama
C
.
Aberrant Cdx2 expression in endometrial lesions with squamous differentiation: important role of Cdx2 in squamous morula formation
.
Hum Pathol
.
2008
;
39
(
7
):
1072
9
. .
6.
Chiarelli
S
,
Buriticá
C
,
Litta
P
,
Ciani
S
,
Guarch
R
,
Nogales
FF
.
An immunohistochemical study of morules in endometrioid lesions of the female genital tract: CD10 is a characteristic marker of morular metaplasia
.
Clin Cancer Res
.
2006
;
12
(
14 Pt 1
):
4251
6
. .
7.
Chinen
K
,
Kamiyama
K
,
Kinjo
T
,
Arasaki
A
,
Ihama
Y
,
Hamada
T
, et al
Morules in endometrial carcinoma and benign endometrial lesions differ from squamous differentiation tissue and are not infected with human papillomavirus
.
J Clin Pathol
.
2004
;
57
(
9
):
918
26
. .
8.
Travaglino
A
,
Raffone
A
,
Saccone
G
,
Fuggi
M
,
Placido
GD
,
Mascolo
M
, et al
Immunophenotype of atypical polypoid adenomyoma of the uterus: diagnostic value and insight on pathogenesis
.
Appl Immunohistochem Mol Morphol
.
2019 Jun 6
;
28
:
646
53
.
9.
Lin
MC
,
Lomo
L
,
Baak
JP
,
Eng
C
,
Ince
TA
,
Crum
CP
, et al
Squamous morules are functionally inert elements of premalignant endometrial neoplasia
.
Mod Pathol
.
2009 Feb
;
22
(
2
):
167
74
. .
10.
Travaglino
A
,
Raffone
A
,
Gencarelli
A
,
Raimondo
D
,
Moretta
P
,
Pignatiello
S
, et al
Relationship between morular metaplasia and squamous differentiation in endometrial carcinoma
.
Pathol Res Pract
.
2020 Nov 30
.
11.
Brachtel
EF
,
Sánchez-Estevez
C
,
Moreno-Bueno
G
,
Prat
J
,
Palacios
J
,
Oliva
E
.
Distinct molecular alterations in complex endometrial hyperplasia (CEH) with and without immature squamous metaplasia (squamous morules)
.
Am J Surg Pathol
.
2005
;
29
(
10
):
1322
9
. .
12.
Saegusa
M
,
Hashimura
M
,
Kuwata
T
,
Hamano
M
,
Okayasu
I
.
Upregulation of TCF4 expression as a transcriptional target of beta-catenin/p300 complexes during trans-differentiation of endometrial carcinoma cells
.
Lab Invest
.
2005
;
85
(
6
):
768
79
. .
13.
Travaglino
A
,
Raffone
A
,
Gencarelli
A
,
Zullo
F
,
Di Spiezio Sardo
A
,
Insabato
L
.
Significance of stromal markers in atypical polypoid adenomyoma
.
Pathol Res Pract
.
2020 Aug 1
;
216
(
11
):
153133
. .
14.
Kurman
R
,
Carcangiu
M
,
Herrington
C
,
Young
R
.
World health organisation classification of tumors of female reproductive organs
. 4th ed.
Lyon France
:
International Agency for Research on Cancer (IARC) Press
,
2014
.
15.
Colombo
N
,
Creutzberg
C
,
Amant
F
,
Bosse
T
,
González-Martín
A
,
Ledermann
J
, et al
ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up
.
Ann Oncol
.
2016 Jan
;
27
(
1
):
16
41
.
16.
Santoro
A
,
Piermattei
A
,
Inzani
F
,
Angelico
G
,
Valente
M
,
Arciuolo
D
, et al
Frozen section accurately allows pathological characterization of endometrial cancer in patients with a preoperative ambiguous or inconclusive diagnoses: our experience
.
BMC Cancer
.
2019 Nov 12
;
19
(
1
):
1096
. .
17.
Travaglino
A
,
Raffone
A
,
Saccone
G
,
Mascolo
M
,
D’Alessandro
P
,
Arduino
B
, et al
Nuclear expression of β-catenin in endometrial hyperplasia as marker of premalignancy
.
APMIS
.
2019 Nov
;
127
(
11
):
699
709
. .
18.
Saegusa
M
,
Okayasu
I
.
Frequent nuclear beta-catenin accumulation and associated mutations in endometrioid-type endometrial and ovarian carcinomas with squamous differentiation
.
J Pathol
.
2001
;
194
(
1
):
59
67
. .
19.
Takahashi
H
,
Yoshida
T
,
Matsumoto
T
,
Kameda
Y
,
Takano
Y
,
Tazo
Y
, et al
Frequent β-catenin gene mutations in atypical polypoid adenomyoma of the uterus
.
Hum Pathol
.
2014 Jan
;
45
(
1
):
33
40
. .
20.
Travaglino
A
,
Raffone
A
,
Saccone
G
,
De Luca
C
,
Mollo
A
,
Mascolo
M
, et al
Immunohistochemical nuclear expression of β-catenin as a surrogate of CTNNB1 exon 3 mutation in endometrial cancer
.
Am J Clin Pathol
.
2019
;
151
(
5
):
529
38
. .
21.
Zannoni
GF
,
Angelico
G
,
Santoro
A
.
Aberrant non-canonical WNT pathway as key-driver of high-grade serous ovarian cancer development
.
Virchows Arch
.
2020 Aug
;
477
(
2
):
321
2
. .
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.