Keywords
Breast - extramammary - mammography - metastases - ultrasound
Introduction
Metastases to the breast from extra-mammary malignancies are extremely uncommon, with
a prevalence ranging from 1.7% to 6.6%.[1] The most common sources of metastases to the breast are lymphomas/leukemias and
melanomas. Rare primary tumors to metastasize to the breast include carcinomas of
the lung, ovary, and stomach, and even more uncommonly carcinoid tumors, hypernephromas,
carcinomas of the liver, tonsil, pleura, pancreas, cervix, endometrium, and bladder.
The dissemination occurs via both hematogenous and lymphatic routes.[1],[2]
The discovery of a breast mass in a patient with a known primary tumor elsewhere or
with a previous history of cancer at another site poses a diagnostic challenge to
the clinician. An awareness of the various malignancies that can metastasize to the
breast and accurate diagnosis of the same is essential in order to avoid an unnecessary
mastectomy and to guide further therapy.
In this article, we present six cases of metastases to the breast, in patients with
a primary extramammary malignancy. Metastases in these primary tumors are exceedingly
rare, and hence, this case series would serve as a valuable addition to the existing
literature. In addition, we present a review on the subject with an emphasis on imaging
findings.
Case 1
A 40-year-old lady presented with menorrhagia for about 8 months. She underwent a
contrast-enhanced CT scan of the abdomen and pelvis, which revealed a heterogeneously
enhancing myometrial mass, with atypical imaging features [Figure 1]A. There was no evidence of distant metastases on cross-sectional imaging. The patient
underwent a total hysterectomy with a bilateral salpingo-oophorectomy. Histopathological
evaluation of the myometrial mass revealed an intermediate grade leiomyosarcoma (Immunohistochemistry
IHC – Mib labeling index of 50%). Thereafter, she presented with a lump in the right
breast, progressively increasing in size over a period of 6 months.
Figure 1 (A-D): (A) Coronal sections of contrast-enhanced CT pelvis images showing a heterogeneously
enhancing mass involving the myometrium of the uterine fundus (red arrows). (C and
D) Right mammogram (extended CC view (C) and MLO view (D)) showing a well-circumscribed
isodense mass in the upper outer quadrant of the right breast (red asterisk). (B)
Ultrasonography image showing a well-defined, round hypoechoic mass at the 10 o’clock
position in the right breast
Mammography revealed the presence of a well-circumscribed isodense mass in the upper
outer quadrant of the right breast [Figure 1]C and [Figure 1]D. Breast ultrasonography demonstrated a well-defined solid, hypoechoic mass with
mild posterior acoustic enhancement, at the site of palpable abnormality [Figure 1]B. A core biopsy of the lesion revealed a spindle cell tumor exhibiting focally moderate
to marked nuclear atypia. On IHC, tumor cells were positive for smooth muscle actin,
desmin, H-caldesmon and showed a high Mib-1 count. The histopathology report was conclusive
for leiomyosarcoma in the clinical context. A contrast-enhanced CT abdomen scan was
subsequently done which revealed a metastatic lesion in the liver and a retroperitoneal
metastatic nodal mass. Thereafter, the patient received palliative chemotherapy for
2 years but did not survive.
Case 2
A 31-year-old lady, with poorly differentiated adenocarcinoma of the stomach (stage
T3N2M0), underwent a radical gastrectomy. She was receiving adjuvant chemo-radiotherapy
(CT-RT) during which she developed abdominal distention, along with diffuse pain in
the left breast with redness of the overlying skin over a period of 1 month. A contrast-enhanced
CT scan of the thorax and abdomen with a mammogram was performed. Contrast-enhanced
CT of the thorax and abdomen revealed ill-defined enhancement in the left breast [Figure 2]A.
Mammography revealed a diffuse increase in density involving the left breast, with
thickening of the overlying skin and the nipple–areola complex [Figure 2]B. Breast ultrasonography demonstrated an ill-defined hypoechoic lesion replacing
the fibro-glandular parenchyma [Figure 2]C. A left breast core biopsy revealed poorly differentiated carcinoma with signet
ring cell morphology. Immunohistochemistry revealed positivity for CK 7, ER, CDX2,
CK 20, and GCDFP, which was consistent with metastasis from carcinoma stomach. Contrast-enhanced
CT abdomen revealed ascites with peritoneal metastases. The patient is being treated
with palliative chemotherapy since then, with stable disease.
Figure 2 (A-C): (A) Axial sections of contrast-enhanced CT thorax images showing diffuse ill-defined
enhancement in the left breast (red arrows). (B) Bilateral mammograms (CC view) showing
a diffuse increase in density in the left breast (red arrows), with thickening of
the overlying skin and the nipple-areola complex (red asterisks). (C) Ultrasonography
image showing an ill-defined hypoechoic lesion replacing the fibro-glandular parenchyma
of the left breast (red asterisk)
Case 3
A 37-year-old lady, with carcinoma cervix (stage IIIa) receiving concomitant chemoradiation
and brachytherapy for the same, developed a lump in the left breast, gradually increasing
over a period of 3 months. A mammogram and a screening ultrasonography of the abdomen
were performed.
Mammography revealed a well-circumscribed, isodense mass in the upper central region
of the left breast [Figure 3]A and [Figure 3]B. A breast ultrasound revealed a predominantly hypoechoic lesion in the upper central
region showing mild internal vascularity [Figure 3]C. Fine-needle aspiration of the lesion revealed clusters of squamous epithelial
cells, consistent with metastasis from cervical carcinoma. An ultrasound of the abdomen
revealed evidence of liver metastases. The patient was put on palliative chemotherapy,
is now being followed up annually.
Figure 3 (A-C): (A and B) Bilateral mammograms (MLO view (A) and CC view (B)) showing a well-circumscribed,
isodense mass in the upper central region of the left breast (red arrows). (C) Ultrasonography
image showing a well-defined hypoechoic lesion at the 12 o’clock position in the left
breast (red asterisk)
Case 4
A 16-year-old girl, with Ewing’s sarcoma of the left ninth rib being treated with
chemotherapy, presented with a slow growing lump in the left breast. About 3 months
after commencement of therapy, a contrast-enhanced CT of the thorax was performed
for monitoring disease response. The CT revealed a heterogeneously enhancing mass
involving the left ninth rib causing bony destruction with intrathoracic extension.
In addition, an irregular heterogeneously enhancing mass with central necrosis was
also seen incidentally in the left breast. Bilateral pleural effusion was seen [Figure 4]A,[Figure 4]B,[Figure 4]C. A breast ultrasound revealed a predominantly hypoechoic mass with irregular margins
in the upper central region [Figure 4]D. A fine-needle aspiration cytology study of the left breast mass revealed cytologic
features of PNET (Primitive neuro-ectodermal tumor)/Ewing’s sarcoma with positivity
for CD99, consistent with metastases from the primary. The patient was treated with
systemic chemotherapy and received radiotherapy to the breast. This regimen yielded
a good response to therapy with a decrease in disease burden.
Figure 4 (A-D): (A) Axial contrast-enhanced CT image of the thorax showing a heterogeneously enhancing
mass with irregular margins in the left breast (yellow arrow). Incidentally seen is
bilateral pleural effusion. (B) Sagittal contrast-enhanced CT image of the thorax
showing a heterogeneously enhancing soft tissue with erosion of the left ninth rib
(red arrow). A heterogeneously enhancing mass with irregular margins is seen in the
left breast (yellow arrow). (C) Coronal bone window sections of the thorax showing
permeative destruction of the left ninth rib (red arrow). (D) Ultrasonography image
showing a heterogeneous mass with irregular margins in the left breast
Case 5
A 28-year-old girl, operated for mucinous adenocarcinoma of the rectum, presented
with recurrence at the anastomotic site, a year after the surgery. She also presented
with a lump in the left breast, increasing in size over a period of 4 months. Mammography
revealed high-density masses with partially obscured margins containing coarse calcifications
in the upper outer quadrant of the left breast [Figure 5]A, [Figure 5]B. A targeted ultrasound revealed hypoechoic masses with irregular margins and calcifications
within, showing posterior acoustic shadowing [Figure 5]C and [Figure 5]D. A core biopsy with IHC revealed features of metastases from mucinous adenocarcinoma,
positive for CK20 and negative for CK7. The patient was then treated with palliative
chemotherapy but was lost to follow-up.
Figure 5 (A-D): (A and B) Left mammogram ((A) CC view and (B) MLO view) showing high-density masses
(red arrows) with partially obscured margins containing coarse calcifications (yellow
arrows and yellow asterisk) in the upper outer quadrant of the left breast. (C and
D) Ultrasound images showing hypoechoic masses with irregular margins and coarse calcifications
within, showing posterior acoustic shadowing (red arrow) at the 2 o’clock position
in the left breast
Case 6
A 47-year-old lady presented with a history of nasal obstruction, worsening over a
period of 6 months associated with mild proptosis of the right eye. A contrast-enhanced
CT of the paranasal sinuses revealed an enhancing soft tissue in the right maxillary
sinus and nasal cavity causing bony erosion with orbital extension [Figure 6]A. Histopathologic examination of the tissue revealed Non-Hodgkin’s lymphoma (NHL)
of the diffuse large B-cell type. She received six cycles of chemotherapy for the
same. During the course of treatment, she developed painless lumps in bilateral breasts.
Mammography revealed multiple well-circumscribed high-density masses involving all
quadrants of bilateral breasts [Figure 6]B and [Figure 6]C. Ultrasonography revealed multiple hypoechoic masses with irregular margins showing
posterior acoustic shadowing [Figure 6]D. A core biopsy with IHC revealed B-cell type of NHL, positive for CD20, consistent
with metastases. The chemotherapy regimen was modified. However, the patient died
of fungal pneumonia after 6 months.
Figure 6 (A-D): (A) Contrast-enhanced coronal CT image of the paranasal sinuses showing an enhancing
soft tissue (red asterisk) in the right maxillary sinus extending to the ethmoidal
sinuses and nasal cavity causing bony erosion with orbital extension. (B and C) Bilateral
mammograms ((B) MLO view and (C) CC view) showing multiple well-circumscribed high-density
masses involving all quadrants of bilateral breasts (red asterisks). (D) Ultrasonography
images showing darkly hypoechoic masses with indistinct margins (yellow asterisks)
Discussion
The presence of a breast lesion in any patient with a known primary tumor elsewhere
poses a diagnostic challenge to the clinician. The diagnostic approach first involves
the differentiation of benign and malignant lesions, and if malignant, it is essential
to know whether the lesion is primary or secondary since the treatment and prognosis
differ greatly according to the nature of the lesion. Because of the rarity and unusual
clinico-pathologic characteristics of breast metastases, it can be difficult to make
an adequate diagnosis clinically and histologically.[1] This is particularly true if the breast abnormality is the first presentation of
unknown extramammary primary cancers metastatic to the breast.[1],[2]
Metastases to the breast may occur years after the diagnosis of a primary cancer.[2] Clinical differentiation from a primary carcinoma is challenging as majority of
metastases present as rapidly growing, painless, palpable, firm breast masses.[2] Radiology may play a critical role in aiding the diagnosis of metastatic breast
disease. On mammography, metastases generally present as one or more well-circumscribed
masses,[3] commonly located in the upper outer quadrants without spiculations, calcifications,
and features of desmoplastic reaction that characterizes majority of primary carcinomas.[3],[4] Exceptions do occur, such as cases of mucinous adenocarcinomas of the rectum, as
described in this article or metastatic ovarian carcinomas, in which metastatic lesions
to the breast may reveal calcifications.[5] Diffuseparenchymal involvement mimicking inflammatory carcinoma can be seen rarely,
which was seen in the case of metastatic stomach cancer that we encountered. A similar
pattern has been described in a previously described case series, in which metastatic
stomach cancer presented with diffuse parenchymal infiltration instead of a discrete
mass.[3]
Ultrasonographic appearance of metastases may reveal solitary or multiple lesions,
predominantly round or oval, with hypoechoic and solid echo patterns, with usually
well-defined posterior margins. Multiple lesions are known to present with similar
imaging findings.[3],[4] On ultrasound, hematogenous metastases tend to have circumscribed margins without
spiculations, calcifications, architectural distortion, or posterior acoustic shadowing.[6] Lymphangitic metastases however manifest as diffuse skin and trabecular thickening
because of obstruction of draining lymphatics.[6] On ultrasonography, metastases to the breast are usually seen in the subcutaneous
tissue, as noted in most of our cases or immediately adjacent to the parenchyma.
The primary sources of breast metastases in our case series were leiomyosarcoma, gastric
carcinoma, Ewing’s sarcoma, cervical carcinoma, colorectal carcinoma, and NHL.
The mammographic features of metastatic leiomyosarcoma to the breast, in our case,
were similar to the one reported by Vizcaino et al.[7] Both cases presented as discrete, well-circumscribed masses, though our patient
had a single deposit and Vizcaino et al. reported multiple deposits.[7] Two other cases of metastases from a primary leiomyosarcoma have been reported in
literature;[8],[9] however, the uterine origin of these deposits has not been documented.
Metastatic gastric adenocarcinoma to the breast has been reported to have variable
imaging features. The case reported by Qureshi et al. did not present with suspicious imaging features and was diagnosed purely on histopathology.[10] In the case reported by Cavazzini et al., the clinical features were similar to the ones reported by us; however, the imaging
features differed. They reported an irregular poorly defined mass without calcifications,
whereas our patient presented with a diffuse increase in parenchymal density with
thickening of the nipple–areola complex.[11] Kwak et al. reported two cases of metastatic signet ring cell carcinoma with increased parenchymal
density on mammography mimicking inflammatory breast carcinoma, similar to our case;
however, the organ of origin was not confirmed.[12]
Vergier et al. reported a case of metastasis to the breast in a patient of epidermoid cervical
carcinoma; however, the metastatic deposit in their case was found to have spiculated
margins.[13] Rarely, metastasis from cervical carcinoma may mimic an inflammatory breast cancer
as reported by Ward et al.[14] The imaging features in our case differed from both of these as the deposit in our
case was a discrete, well-circumscribed mass.
Mihai et al. reported a case of breast metastasis suspected to be from a primary rectal carcinoma
with imaging features not characteristic for malignancy, appearing as a well-defined
mass on mammography; however, the organ of origin could not be confirmed.[15] Li et al. and Zhang et al. reported cases of poorly differentiated adenocarcinoma of the rectum with metastasis
to the breast presenting as an indistinctly marginated mass.[16],[17] Ahmad et al. reported metastases to the breast from well-differentiated colo-rectal adenocarcinoma
presenting as a partially well-defined nodule with intermediate type of microcalcifications
on mammography, which suggested suspicious morphology favoring primary breast carcinoma;
however, it later turned out to be metastatic deposit from a colo-rectal primary.[18] Our case differed from the above cases as we encountered an extremely rare form
of metastasis presenting with coarse calcifications, which differed from all of these.
Very few cases of metastases to the breast from Ewing’ sarcoma have been documented.
Örgüç et al. have reported a case of breast metastasis from Ewing’s sarcoma of the right iliac
bone in a 12-year-old girl, with imaging features similar to ours.[19]
NHL of the breast is an extremely rare occurrence, accounting for about 0.5% of all
breast malignancies and 1% of NHL,[20],[21] and usually manifests as a secondary disease (i.e., in association with extramammary
NHL).[21] Surov et al. studied the imaging features of breast lymphoma in 36 patients. The most common
mammographic finding in their study was multiple intramammary masses with circumscribed
or microlobulated margins, similar to our case.[21] The ultrasound features were also identical to ours, with most lesions appearing
as hypoechoic, oval, or round masses with circumscribed margins. In the study by Yang
et al., most cases of breast lymphoma however presented with a solitary breast mass with
indistinct or irregular margins on mammography and ultrasound, which differed from
the findings in our study.[22]
In conclusion, our case series provides an overview of unusual cases of metastases
to the breast from various extramammary malignancies. The occurrence of a breast mass
in a patient with a known primary must be approached with caution, and the possibility
of metastasis must be excluded, as the disease prognosis and course of management
can be ascertained only after this distinction is made.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
