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

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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, *
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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 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-
Dear Editor, emission tomography/computed tomography, chest radiography,
or abdominal ultrasonography presented no evidence of recurrent
Breast cancer is a major health problem worldwide. The lung, cancer during follow-up.
bone, liver, and brain are the common metastatic sites of breast Subsequent endometrial sampling 6 years after mastectomy
cancer. Metastatic diseases to the gynecological tract or to the revealed signet-ring cell carcinoma of the endometrium inciden-
gastrointestinal (GI) tract are both considered rare in clinical tally (Figure 1B). An immunohistochemical stain of the endome-
practice [1,2]. Synchronous gastric and uterine metastasis in pure trial tumor cells showed positive for GCDFP-15 and mammaglobin
signet-ring cell feature has never been previously reported. Herein (cocktail antibodies; Figure 1E) indicating breast origin. The cells
we described a breast cancer patient who was found to have rare were also positive for estrogen receptors (intensity 2, 40%)
synchronous gastric and uterine metastasis without evident and progesterone receptors (intensity 3, 70%) and negative
radiographic recurrence. for Her-2/neu (DAKO score 1). The staining also revealed posi-
A 54-year-old postmenopausal woman was previously diag- tivity for CK7, CEA (Figure 1H), and CA153 (Figure 1K), and
nosed with left-side invasive lobular breast carcinoma and under- negative staining for the CK20, E-cadherin, PAX8, and Hep Par 1,
went modied radical mastectomy 7 years ago. Pathological consistent with the diagnosis of the metastatic invasive lobular
examination of tumor showed invasive lobular carcinoma with carcinoma.
lymphovascular space invasion, Stage IIIc (T3N3M0 and G2; In addition, esophagogastroduodenoscopy found multiple
Figures 1A, 1D, 1G, and 1J). Immunohistochemical staining revealed diffuse nodular lesions with surface ulceration over the body of the
strongly positive for estrogen receptors (90%), progesterone re- stomach (Figure 2D). Biopsies were performed and showed signet
ceptors (80%), and negative for Her-2/neu by uorescence in situ ring cell carcinoma with positive for CK, CK7, GCDFP-15 and
hybridization. She received postoperative sequential adjuvant mammaglobin, CEA, and CA153 (Figures 1F, 1I, and 1L), and nega-
chemotherapy, followed by radiotherapy and hormone therapy. tive for Her-2/neu, CK20, PAX8, and Hep Par 1. Synchronous gastric
Gynecologic follow-up was arranged due to endocrine therapy and uterine metastatic invasive lobular carcinoma with the histo-
with Tamoxifen. Slight endometrial thickening without any path- logical feature of signet-ring cells was diagnosed instead of primary
ologic change was noted during the patient's annual gynecological gastric or endometrial cancer (Figures 2B and 2C). She was treated
ultrasound follow-up 3 years after mastectomy. Annual cervical with palliative chemotherapy for the metastatic breast cancer and
achieved stable disease in subsequent follow-ups.
Metastatic breast cancer occurs via lymphatic involvement,
* Corresponding author. Division of Hematology and Oncology, Department of
Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, hematogeneous dissemination, or contiguous spread. Pulmonary,
Number 325, Chenggong Road, Section 2, Neihu 114, Taipei, Taiwan. hepatic, brain, and skeleton are the common sites of dissemination
E-mail address: (M.-S. Dai).
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
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 primary or metastatic endometrial tumors when a patient reveals
rare. There are case reports on gynecologic tract or GI tract no systemic involvement.
metastases. GI-tract metastases from the breast usually present as linitis
Signet-ring cell breast cancer, characterized by a particularly plastica and may occur many years after the initial treatment. The
high proportion of signet ring-shaped cells, accounts for approxi- clinical presentation mimics a primary gastric tumor, as symptoms
mately 1% of all breast cancer and considered to be a subtype of the can be nonspecic or asymptotic, making diagnosis of gastric me-
lobular carcinoma. Breast cancer with signet-ring cells is more tastases more difcult. In clinical practice, the discovery of a gastric
aggressive [3,4] and has a greater tendency to metastasize to the GI tumor in a patient with a history of breast cancer needs further
and gynecological tract. However, signet-ring cells may present investigation to differentiate metastatic breast cancer from primary
only in metastases and absent in the primary tumor, causing GI malignancy for the optimal treatment strategy. Reports on
diagnostic uncertainties and challenges [3]. As in our case, there this subject in the literature are rare and mostly limited to case
was no typical signet-ring cell morphology with eccentric nucleus reports [2,7,8].
and intracytoplasmic mucin noted in the primary lobular carci- The immunohistochemical stains may aid in distinguishing the
noma retrospectively. Histological examination of the metastatic primary origin of the tumor. There is signicant mammaglobin
tumor supported the metastatic breast origin. expression in breast and gynecologic tissues; about 40% of endo-
Uterine metastases usually originate from other genital sites, metrial carcinomas show mammaglobin immunoreactivity and
most commonly from the ovaries, by secondary to local lymphatic absent expression of the mammaglobin in gastric carcinomas [9].
spread from the ovarian involvement and thus isolated uterine Besides, GCDFP-15 staining of the gastric and colonic signet ring
metastases from the extragenital tumors are rare and probably cell carcinoma is nonreactive. Hep Par 1 has also been identied
hematogenous. While metastases to the gynecological tract from with strong expression in > 80% of gastric signet ring cell carci-
extragenital cancers remain as rare events, they are usually from nomas [10]. PAX8 staining is positive in endometrial carcinoma.
breast and the GI tract malignancies [1], and both cause diagnostic Breast and gastrointestinal tumors are negative for PAX8 [11].
challenges. In addition, hormone therapy is widely used as adju- In our instance, strongly positive GCDFP-15 and mammaglobin
vant treatment of advanced, endocrine-responsive breast carci- cocktail staining was seen in primary breast, gastric, and endo-
noma and responsible for endometrial abnormalities, such as metrial tumor cells, with immunoreactivity in the normal endo-
simple and complex hyperplasia, with and without nuclear atypia, metrial glands but negative in gastric glands. PAX8 showed positive
polyps, and carcinoma [5]. The relative risk of developing endo- nuclear staining in the normal endometrial glands but was
metrial cancer following Tamoxifen treatment is approximately nonreactive in tumor cells in the primary breast, endometrial, and
two to four times higher [6]. It is important to distinguish the 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- mechanisms of the different pattern of metastases seen in patients
ical staining prole, it is conceivable that the endometrial and with invasive lobular carcinoma deserve further investigation and
gastric tumors were metastatic breast cancer. attention.
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 Conicts of interest
patients with breast cancer and have been considered a valuable
indicator of metastasis. The simultaneous determination of CEA The authors have no conicts of interest relevant to this article.
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]. References
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