Article

Mucinous Cystadenocarcinoma of the Breast with Estrogen Receptor Expression: A Case Report and Review of the Literature

Department of Radiation Oncology, Atatürk University Faculty of Medicine, Erzurum, Turkey.
Case Reports in Oncology 11/2009; 2(3):210-216. DOI: 10.1159/000253866
Source: PubMed

ABSTRACT

Primary mucinous cystadenocarcinoma (MCA) of the breast was first described by Koenig and Tavassoli in 1998. To our knowledge, only 9 cases of MCA of the breast have been reported. The optimal treatment of MCA could not be defined yet. This article aims to increase the knowledge about this rare variant of breast cancer and to review the literature.

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Case Rep Oncol 2009;2:210–216
DOI: 10.1159/000253866
Published online: November 14, 2009
© 2009 S. Karger AG, Basel
ISSN 1662–6575
www.karger.com/cro
Dr. Sema Rakıcı
Department of Radiation Oncology, Atatürk University Faculty of Medicine
TR–25240 Erzurum (Turkey)
Tel. +90 50 5402 8302, Fax +90 44 2236 0988, E-Mail sema.neslihan@gmail.com
210
Mucinous Cystadenocarcinoma
of the Breast with Estrogen
Receptor Expression:
A Case Report and Review of the
Literature
Sema Rakıcı
a
Güzin Gönüllü
b
Ş. Bilge Gürsel
c
Levent Yıldız
d
İ. Koray Bayrak
e
İdris Yücel
b
a
Department of Radiation Oncology, Atatürk University Faculty of Medicine,
Erzurum, Departments of
b
Medical Oncology,
c
Radiation Oncology,
d
Pathology,
and
e
Radiology, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey
Key Words
Mucinous cystadenocarcinoma · Breast · Estrogen receptor · Treatment
Abstract
Primary mucinous cystadenocarcinoma (MCA) of the breast was first described by Koenig
and Tavassoli in 1998. To our knowledge, only 9 cases of MCA of the breast have been
reported. The optimal treatment of MCA could not be defined yet. This article aims to
increase the knowledge about this rare variant of breast cancer and to review the
literature.
Introduction
Mucinous cystadenocarcinoma (MCA) is a very rare tumor of the breast. In the
literature, only a handful of cases have been reported [1]. These tumors are a rare,
clinicopathologically distinct type of primary breast carcinoma that should be
distinguished from typical mucinous (colloid) carcinomas of the breast and, more
importantly, metastases from other sites such as the pancreas and ovaries [2–4].
Case Report
A 52-year-old premenopausal woman presented with a mass in her left breast. There were neither
nipple discharge nor skin retraction. She has no children and no history of hormonal treatment or
tumor history in the family. Physical examination revealed a big firm tumor of 5 × 10 cm in size in the
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Case Rep Oncol 2009;2:210–216
DOI: 10.1159/000253866
Published online: November 14, 2009
© 2009 S. Karger AG, Basel
ISSN 1662–6575
www.karger.com/cro
211
breast. No axillary lymph node involvement was noticed. Mammography showed a well-defined
multilobular mass in the left breast involving nearly the whole breast. The tumor was well-defined and
had neither spiculated margins nor intralesional microcalcification (fig. 1
).
Fine-needle aspiration biopsy revealed a benign mass that had suspicious malignant findings.
Therefore, an excisional biopsy was performed. Gross inspection revealed a grey, gelatinous,
multilocular cystic tumor containing mucinous material with some necrosis. Microscopically, variably
sized cystic spaces were observed. The tumor was confined with atypical cells containing
intracytoplasmic mucin (fig. 2
). Also extracellular mucin was present in the tumor (fig. 3).
The tumor was diagnosed as mucinous cystadenocarcinoma (MCA). After this diagnosis, an
abdominopelvic ultrasonography was performed and proved to be normal. There was no pathology in
the ovaries and pancreas. Modified radical mastectomy was performed. There was residual tumor in the
specimen and tumor in the nipple, but no skin infiltration. The specimen had atypical ductal
hyperplasia. In the axillary dissection material, there were 10 reactive lymph nodes.
Immunohistochemically, the tumor cells were positive for estrogen receptor (ER; 95%) (fig. 4
), and
completely negative for progesterone receptor (PR) and C-erb-B2 receptor. Also cytokeratin 7 (CK7), 20
(CK20), and chromogranin immunoreactivities were negative.
According to the American Joint Committee on Cancer Staging System [6], the tumor was staged as
Stage IIA (T3N0M0). Because of ER positivity, tamoxifen was given. The patient has been followed for
24 months without chemotherapy (CT) and radiotherapy (RT) and has no metastasis or recurrence.
Discussion
Mucin-producing breast carcinomas have been broadly categorized into mucinous
carcinoma, in which malignant cells are suspended in extracellular mucin, and signet ring
cell carcinoma, in which the mucin is predominantly intracellular. Primary MCA of the
breast, however, demonstrates both intracellular and extracellular mucin and is
histologically similar to primary MCA of the pancreas and ovary [7]. It may be
misinterpreted as a benign lesion because the small biopsy specimens may only consist of
tumor cells with bland nuclei [8]. This case is the 10th case of breast MCA. In the
literature, all the known MCA cases showed loss of ER and PR expression, but this case
shows that MCA can also be ER-positive. According to the literature, the prognosis seems
good even in tumors with a size of 10 cm [8].
Ovary and pancreas mucinous adenocarcinoma are usually CK7+/CK20+, while MCA
of the breast is usually CK7+ and CK20–. The antibody panel including CK7 and CK20
may be useful to make a differential diagnosis between primary and metastatic mucinous
tumors, but detailed clinical evaluation is necessary [8]. Neuroendocrine differentiation
with expression of chromogranin is frequently demonstrated in mucinous carcinoma, but
not in all MCAs nor in our case [8].
The MCAs of the breast in the literature, including the present case, are presented in
table 1
. Notably, in the 9th case reported in the literature, too, both ER and PR in the
primary MCA of the breast were negative, whereas ER and PR in the MCA were often
expressed [10]. Since the MCAs were ER- and PR-negative, the hypothesis can be made
that these tumors have been developed free from estrogen stimulation [5]. Therefore, no
patients received hormonotherapy. The fact that our case was stained highly ER-positive
led to the idea that these tumors are also estrogen-sensitive, as the other primary breast
tumors. Therefore, when determining the treatment of patients presenting with this kind
of tumor, hormonotherapy should also be considered as an option. This inhibits both
translocation and nuclear binding of tamoxifen receptor, thereby preventing estrogen
responsive genes from transcriptional activation. Tamoxifen induces apoptosis and
prevents tumor growth, protein inhibits kinases and provides the regulation of tumor
growth factors [11, 12]. Moreover, insulin growth factor affects regulatory cytokines such
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Case Rep Oncol 2009;2:210–216
DOI: 10.1159/000253866
Published online: November 14, 2009
© 2009 S. Karger AG, Basel
ISSN 1662–6575
www.karger.com/cro
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as TGFβ, and basic fibroblast growth factor inhibits angiogenesis [13]. In in vivo studies,
it was determined that the level of VEGF that has an impact on angiogenesis was also
decreased [13–15]. We hoped that tamoxifen would be effective in our patient
considering all the mechanisms mentioned above. ER, PR and c-erb-B2 is stained
negative in MCA [5, 8]. Our case was stained ER-positive and PR- and c-erb-B2-negative.
As it is known, ER, PR and c-erb-B2 triple negative breast tumors are associated with
poor prognosis [16]. Indeed, it could be expected that the receptors of these tumors,
which are nonmetastatic, without local recurrence and with good prognosis, would be
positive.
Patients were between 47 and 96 years old and older patients were likely to develop
MCA [5, 8]. Patients were often postmenopausal and the age of average incidence was 68
[8]. Our patient was also postmenopausal.
MCA was noted to originate from the main ductus close to the papilla [5, 8]. Papilla
involvement in the mammographic images and histopathological investigation in our case
also supported this hypothesis.
Out of 10 patients, 2 developed lymph node metastasis, which is considered to be
associated with the long history of the primary tumor [2, 5]. Our patient had a short
history and presented with no axillary lymph node metastasis. Honma et al. [5] treated a
patient presenting with a 6-cm conglomerate of axillary metastatic lymph nodes with
mastectomy (M) and lymph node dissection (LND), and after 46 months of follow-up
without adjuvant therapy, the patient died from a disease other than MCA. These facts
lead to the assumption that axillary lymph node metastasis is not associated with poor
prognosis.
The general treatments were M and LND; however, 3 patients underwent lumpectomy.
With respect to postoperative adjuvant therapy, 1 patient [2] received RT, while 2 patients
[2, 8] received CT. In the study of Koenig and Tavassoli [2], a third case presenting with a
8.5-cm diameter sarcomatous component was exposed to adjuvant CT and RT after M
and LND. The CT given to this patient was a combination including antracyclin, which
seems logical as it included a sarcomatous component. This patient presented with no
disease during an 11-month follow-up. The second patient [8] receiving CT in the
literature was the one presenting with a 3-cm diameter tumor but no nodal metastasis,
and undergoing M and LND. RT indication was not suggested when the patient was
assessed for RT to the chest wall.
In the literature, a patient presenting with a 19-cm tumor and lymph node metastasis
was treated with M and LND, but did not receive CT and RT [2]. If the case had been
assessed classically, as the other invasive breast cancer types, this patient would have been
delivered RT and CT. However, during a 24-month follow-up, no disease was observed in
the patient. The other patient presenting with lymph node metastasis [5] and with a 2-cm
diameter tumor was treated with lumpectomy and LND, but did not receive RT and CT,
and the patient died from a disease other than MCA at the end of a 46-month follow-up.
This contributes to the hypothesis that surgery is indeed sufficient for the treatment of
this disease. In the study of Rosen et al. [3], the patient presenting with a 6-cm diameter
tumor and undergoing mastectomy and LND, but not receiving adjuvant therapy, did not
experience any symptoms related to this disease in a 9-year follow-up.
As indicated in table 1, for the 4th, 6th and 9th patients undergoing breast-conserving
surgery, for the first patient presenting with a 19-cm diameter tumor, and for the patients
presenting with metastatic axillary lymph nodes [3, 8] RT was not suggested. None of
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Case Rep Oncol 2009;2:210–216
DOI: 10.1159/000253866
Published online: November 14, 2009
© 2009 S. Karger AG, Basel
ISSN 1662–6575
www.karger.com/cro
213
these patients developed locoregional recurrence, and therefore, we should pay attention
when suggesting RT for these patients. Compatible with this, in the light of current
literature we did not suggest CT and RT for our patients. Because ER was highly positive
in our patient and because we found invasive atypical epithelial hyperplasia, tamoxifen
was started.
Although it is not sufficient to discuss only a few patients with good prognosis of these
rare breast tumors, it can be seen that the patients were not affected by CT and RT. No
recurrence or death related to disease occurred in any of the patients [8]. The follow-up
period reported was 9 years at the most and 8 months at least. Although the nature of
breast MCAs is invasive, these carcinomas are associated with a good prognosis [7].
However, it is necessary to differentiate primary MCA of the breast from other benign
lesions of the breast releasing the typical mucin and mucinous carcinoma [5, 7, 8]. More
importantly, it is necessary to conduct detailed clinical and histopathological
investigations in order to differentiate the organs in the abdomen and pelvis from MCA
metastases in the pancreas and ovaries [2, 5, 8].
In conclusion, we need to observe a certain disease progression and therefore more
cases to answer the question whether only surgery or, as in other invasive breast tumors, a
combination of surgery, CT and RT is to be used for the treatment of this rare breast
cancer with good prognosis.
Table 1
. Summary of clinicopathologic features
Case
No.
R Age Tumor
size, cm
LNM Treatment Follow-up ER PR CK7 CK20
1 2 54 19.0 + M, LND 24 months
a
+
2 2 67 02.3 M, LND 22 months
a
+
3 2 49 08.5 M, LND, CT, RT 11 months
a
+
4 2 61 00.8 Lumpectomy, LND
b
+
5 4 74 10 M, LND 02 years
a
+
6 5 96 02.0 + Lumpectomy, LND 46 months
*
+
7 3 79 06.0 M, LND 09 years
*
+
8 8 65 03.0 M, LND, CT 08 months
a
+ rare
9 7 51 04.0 Lumpectomy
b
+
Present case 52 10.0 M, LND, TMX 24 months
a
+
LNM = Lymph node metastasis; M = mastectomy; LND = lymph node dissection; CT = chemotherapy;
RT = radiation therapy; TMX = tamoxifen.
a
Alive with no evidence of disease;
b
unknown.
*
Died of
disease other than MCA.
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Case Rep Oncol 2009;2:210–216
DOI: 10.1159/000253866
Published online: November 14, 2009
© 2009 S. Karger AG, Basel
ISSN 1662–6575
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Fig. 1
. Mediolateral oblique mammographic graphs of the left breast: a well defined multilobular mass
involving the whole breast which has neither spiculated margins nor intralesional microcalcification.
Fig. 2
. The extracellular free mucin in the tumor. ×100. HE.
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DOI: 10.1159/000253866
Published online: November 14, 2009
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ISSN 1662–6575
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Fig. 3
. The intracytoplasmic mucin in the tumor.
Fig. 4
. Tumor of cells positive for estrogen receptor. ×400.
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Case Rep Oncol 2009;2:210–216
DOI: 10.1159/000253866
Published online: November 14, 2009
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ISSN 1662–6575
www.karger.com/cro
216
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