Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 131e134

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Taiwanese Journal of Obstetrics & Gynecology

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Research Letter

Synchronous endometrial and gastric metastases of invasive lobular

breast carcinomas
Mei-Ju Lai a, Chien-Liang Lai b, I-Hsuan Huang c, Jyh-Cherng Yu d, Herng-Sheng Lee a, e,
Ming-Shen Dai f, *
a
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
b
Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
c
Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
d
Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
e
Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
f
Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

a r t i c l e i n f o

Article history: cytological examinations showed reactive change and periodical

Accepted 2 October 2014
Dear Editor,
Breast cancer is a major health problem worldwide. The lung,
bone, liver, and brain are the common metastatic sites of breast
cancer. Metastatic diseases to the gynecological tract or to the
gastrointestinal (GI) tract are both considered rare in clinical
practice [1,2]. Synchronous gastric and uterine metastasis in pure
signet-ring cell feature has never been previously reported. Herein
we described a breast cancer patient who was found to have rare
synchronous gastric and uterine metastasis without evident
radiographic recurrence.
A 54-year-old postmenopausal woman was previously diag-
nosed with left-side invasive lobular breast carcinoma and under-
went modied radical mastectomy 7 years ago. Pathological
examination of tumor showed invasive lobular carcinoma with
lymphovascular space invasion, Stage IIIc (T3N3M0 and G2;
Figures 1A, 1D, 1G, and 1J). Immunohistochemical staining revealed
strongly positive for estrogen receptors (90%), progesterone re-
ceptors (80%), and negative for Her-2/neu by uorescence in situ
hybridization. She received postoperative sequential adjuvant
chemotherapy, followed by radiotherapy and hormone therapy.
Gynecologic follow-up was arranged due to endocrine therapy
with Tamoxifen. Slight endometrial thickening without any path-
ologic change was noted during the patient's annual gynecological
ultrasound follow-up 3 years after mastectomy. Annual cervical
* Corresponding author. Division of Hematology and Oncology, Department of
Internal Medicine, Tri-Service General Hospital, National Defense Medical Center,
Number 325, Chenggong Road, Section 2, Neihu 114, Taipei, Taiwan.
E-mail address: dms1201@gmail.com (M.-S. Dai).
endometrial samplings revealed simple hyperplasia without nu-
clear atypia histopathologically.
She was found to have rising serum levels of CEA and the CA153
4 years after initial surgery despite the switch to anastrozole or
exemestane as endocrine therapy (Figure 2A). Serial positron-
emission tomography/computed tomography, chest radiography,
or abdominal ultrasonography presented no evidence of recurrent
cancer during follow-up.
Subsequent endometrial sampling 6 years after mastectomy
revealed signet-ring cell carcinoma of the endometrium inciden-
tally (Figure 1B). An immunohistochemical stain of the endome-
trial tumor cells showed positive for GCDFP-15 and mammaglobin
(cocktail antibodies; Figure 1E) indicating breast origin. The cells
were also positive for estrogen receptors (intensity 2, 40%)
and progesterone receptors (intensity 3, 70%) and negative
for Her-2/neu (DAKO score 1). The staining also revealed posi-
tivity for CK7, CEA (Figure 1H), and CA153 (Figure 1K), and
negative staining for the CK20, E-cadherin, PAX8, and Hep Par 1,
consistent with the diagnosis of the metastatic invasive lobular
carcinoma.
In addition, esophagogastroduodenoscopy found multiple
diffuse nodular lesions with surface ulceration over the body of the
stomach (Figure 2D). Biopsies were performed and showed signet
ring cell carcinoma with positive for CK, CK7, GCDFP-15 and
mammaglobin, CEA, and CA153 (Figures 1F, 1I, and 1L), and nega-
tive for Her-2/neu, CK20, PAX8, and Hep Par 1. Synchronous gastric
and uterine metastatic invasive lobular carcinoma with the histo-
logical feature of signet-ring cells was diagnosed instead of primary
gastric or endometrial cancer (Figures 2B and 2C). She was treated
with palliative chemotherapy for the metastatic breast cancer and
achieved stable disease in subsequent follow-ups.
Metastatic breast cancer occurs via lymphatic involvement,
hematogeneous dissemination, or contiguous spread. Pulmonary,
hepatic, brain, and skeleton are the common sites of dissemination

http://dx.doi.org/10.1016/j.tjog.2014.10.012
1028-4559/Copyright 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
132 M.-J. Lai et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 131e134

Figure 1. Histopathological staining (magnication 400, bar 50 mm) of the breast, endometrium, and stomach in order in each panel: (A,E,I) hematoxylin and eosin; (B,F,J)
GCDFP-15 and mammaglobin (GM); (C,G,K) CEA; and (D,H,L) CA153. Breast invasive lobular carcinoma in a single le (Indian-le) pattern and (A) target-like growth, and signet-
ring cell morphology in metastatic carcinomas in (B) endometrium and (C) stomach are recognized. (D,E,F) Cytoplasmatic positivity for GM supported the breast origin. (G,H,I) CEA
and (J,K,L) CA153 immunohistochemical staining shows positivity in the breast, endometrium, and stomach biopsy specimens. The intensity of the metastatic signet ring carcinomas
in the endometrium and stomach biopsy specimens are stronger than that in breast biopsy specimens.

[1]. Metastases to the female genital tract and to the GI tract are
rare. There are case reports on gynecologic tract or GI tract
metastases.
Signet-ring cell breast cancer, characterized by a particularly
high proportion of signet ring-shaped cells, accounts for approxi-
mately 1% of all breast cancer and considered to be a subtype of the
lobular carcinoma. Breast cancer with signet-ring cells is more
aggressive [3,4] and has a greater tendency to metastasize to the GI
and gynecological tract. However, signet-ring cells may present
only in metastases and absent in the primary tumor, causing
diagnostic uncertainties and challenges [3]. As in our case, there
was no typical signet-ring cell morphology with eccentric nucleus
and intracytoplasmic mucin noted in the primary lobular carci-
noma retrospectively. Histological examination of the metastatic
tumor supported the metastatic breast origin.
Uterine metastases usually originate from other genital sites,
most commonly from the ovaries, by secondary to local lymphatic
spread from the ovarian involvement and thus isolated uterine
metastases from the extragenital tumors are rare and probably
hematogenous. While metastases to the gynecological tract from
extragenital cancers remain as rare events, they are usually from
breast and the GI tract malignancies [1], and both cause diagnostic
challenges. In addition, hormone therapy is widely used as adju-
vant treatment of advanced, endocrine-responsive breast carci-
noma and responsible for endometrial abnormalities, such as
simple and complex hyperplasia, with and without nuclear atypia,
polyps, and carcinoma [5]. The relative risk of developing endo-
metrial cancer following Tamoxifen treatment is approximately
two to four times higher [6]. It is important to distinguish the
primary or metastatic endometrial tumors when a patient reveals
no systemic involvement.
GI-tract metastases from the breast usually present as linitis
plastica and may occur many years after the initial treatment. The
clinical presentation mimics a primary gastric tumor, as symptoms
can be nonspecic or asymptotic, making diagnosis of gastric me-
tastases more difcult. In clinical practice, the discovery of a gastric
tumor in a patient with a history of breast cancer needs further
investigation to differentiate metastatic breast cancer from primary
GI malignancy for the optimal treatment strategy. Reports on
this subject in the literature are rare and mostly limited to case
reports [2,7,8].
The immunohistochemical stains may aid in distinguishing the
primary origin of the tumor. There is signicant mammaglobin
expression in breast and gynecologic tissues; about 40% of endo-
metrial carcinomas show mammaglobin immunoreactivity and
absent expression of the mammaglobin in gastric carcinomas [9].
Besides, GCDFP-15 staining of the gastric and colonic signet ring
cell carcinoma is nonreactive. Hep Par 1 has also been identied
with strong expression in > 80% of gastric signet ring cell carci-
nomas [10]. PAX8 staining is positive in endometrial carcinoma.
Breast and gastrointestinal tumors are negative for PAX8 [11].
In our instance, strongly positive GCDFP-15 and mammaglobin
cocktail staining was seen in primary breast, gastric, and endo-
metrial tumor cells, with immunoreactivity in the normal endo-
metrial glands but negative in gastric glands. PAX8 showed positive
nuclear staining in the normal endometrial glands but was
nonreactive in tumor cells in the primary breast, endometrial, and
gastric specimens. Hep Par 1 was negative in the breast, gastric, and
 M.-J. Lai et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 131e134 133

Figure 2. (A) Schematic representation of the clinical events, cancer-related treatments, and the changes of the tumor markers. (B) Magnetic resonance dynamic imaging with T1WI
SGEFS oblique axial plane of the pelvis with gadolinium-administration shows one lobulated hypointense lesion (~2.0 cm, white arrow) in the endometrial mucosa with adjacent
junction zone disruption and myometrial invasion. (C) Contrast-enhanced computed tomography of the abdomen demonstrates the diffuse-thickening of the gastric wall (black
arrowheads). (D) Gastroscopy nds diffuse nodular lesions with surface ulceration.

endometrial tumor cells. Therefore, from the immunohistochem-
ical staining prole, it is conceivable that the endometrial and
gastric tumors were metastatic breast cancer.
The CEA and the CA153 antigens are not suitable for diagnosing
breast cancer at an early stage. However, they serve as sensitive
markers for the evaluation, treatment monitoring, and follow-up of
patients with breast cancer and have been considered a valuable
indicator of metastasis. The simultaneous determination of CEA
and CA153 can give a slight increase in sensitivity (5%). The
elevation of the marker levels for the CEA and the CA153 is known
to precede the clinicoradiologic demonstration of metastases [12].
Positron-emission tomography/computed tomography is a valu-
able tool for diagnosis, disease staging and restaging, as well as for
treatment monitoring in patients with various cancers. However, it
is limited in detecting some particular histological subtypes or
signet-ring cell carcinoma [13].
In conclusion, this is the rst instance of a patient incidentally
diagnosed with synchronous distinctive unusual metastases
involving the uterine endometrium and the stomach without other
visceral involvement. Both presented with pure signet-ring cell
features consistent with breast cancer histology. This synchronous
rare occurrence of breast cancer metastases illustrates the clinical
diagnostic challenges to differentiate from primary gastric or
endometrial cancer. It highlights that the clinicians need more
cautious surveillance of gynecologic and gastrointestinal tract in
patients who have had elevation of the tumor markers without
evidence of obvious radiographic recurrence. In addition, the
mechanisms of the different pattern of metastases seen in patients
with invasive lobular carcinoma deserve further investigation and
attention.
Conicts of interest
The authors have no conicts of interest relevant to this article.
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