Case Report · Kasuistik
Breast Care 2009;4:192–194?
Published online: June 12, 2009
Dr. Francisco Santaolalla Montoya
E.N.T. Department, Basurto Hospital
School of Medicine, University of the Basque Country, UPV/EHU
Gurtubay, s/n. 48013 Bilbao, Spain
Tel. +34 94-4006080, Fax -6014545
© 2009 S. Karger GmbH, Freiburg
Accessible online at:
Fax +49 761 4 52 07 14
Mandibular Metastasis of a Signet Ring Cell Carcinoma
of the Breast in a Patient who Underwent
Bilateral Mastectomy more than 25 Years Earlier
Francisco Santaolallaa Cosme Ereñob Agustin Martíneza Ana Sánchez del Reya Aitor Zabalaa
a Department of Otolaryngology,
b Department of Pathology, Basurto Hospital, Bilbao, School of Medicine, University of the Basque Country, Spain
Unterkiefer · Metastasen · Brustkrebs · Siegelringzellen
Hintergrund: Weniger als 1% aller bösartigen Tumoren
der Mundhöhle sind metastatische Tumoren. Fallbericht:
Wir berichten über den Fall einer 94-jährigen Patientin
mit einem Unterkiefertumor. Mehr als 25 Jahre zuvor
war bei der Patientin eine bilaterale Mastektomie durch-
geführt worden. Die immunhistochemische Untersu-
chung ergab Hormonrezeptoren in Siegelringzellen, was
auf Brustkrebsmetastasen hindeutete. Schlussfolgerung:
Die immunhistochemische Diagnosestellung sowie eine
antineoplastische Hormontherapie bilden die Basis des
Fallmanagements bei dieser Patientin.
Mandible · Metastasis · Breast cancer · Signet ring cells
Background: Metastatic tumors account for less than 1%
of all malignant tumors occurring in the oral cavity. Case
Report: The clinical case of a 94-year-old patient with a
mandibular tumor is reported here. The patient had un-
dergone bilateral mastectomy more than 25 years before.
An immunohistochemical study found hormone recep-
tors in signet ring cells, suggesting a diagnosis of breast
cancer metastasis. Conclusion: Immunohistochemical
diagnosis and antineoplastic hormone therapy is the cor-
nerstone in the management of this clinical case.
Breast cancer is one of the most important tumors in the
Western world because it is among the most common and
causes both mortality and morbidity in affected women. In
the United States, this tumor ranks second in incidence after
lung cancer, and is the most fatal tumor in women, account-
ing for 15% of deaths from cancer . Signet ring cell breast
cancer was characterized in 1976 . This type of tumor
accounts for approximately 1% of all breast cancer . It
is characterized by a particularly high proportion of signet
ring-shaped cells and is considered as a subtype of lobular
carcinoma . The presence of signet ring cells is associated
with a more aggressive course and a greater trend to the de-
velopment of gastrointestinal and gynecological metastases.
Signet ring cells may occur in metastases only and not in
the primary tumor, which may cause diagnostic uncertainty
On the other hand, metastatic tumors in the oral cavity are
uncommon, accounting for approximately 1% of all malignant
tumors occurring in the oral cavity. Within the oral cavity,
metastatic tumors are most often located in jaw bones (85%).
The bone most commonly involved is the mandible (80–90%),
mainly at molar or retromolar sites . Seventy percent of
metastases in the oral cavity become evident after occurrence
of the primary tumor, while 30% represent the first sign of
extension of primary tumors of an unknown origin . In most
cases of metastases in the oral cavity, the primary tumor is
located below the collarbone, and tumors most commonly
metastasizing to the oral cavity are primary lung, breast, and
Breast Care 2009;4:192–194
Mandibular Metastasis in Breast Cancer 193
kidney tumors which account together for approximately 50%
of all oral metastases . Oral metastases occur at a mean age
of 50–60 years, but may appear at any age and with no sig-
nificant sex differences . As regards clinical signs and symp-
toms, oral metastases may be asymptomatic or may cause
tumors, pain, ulcers, paresthesia, bleeding, periodontitis, tris-
mus, or pathological fracture. Symptoms sometimes occur in
a short period of time. An X-ray study most commonly shows
a radiolucent osteolytic lesion with ill-defined margins. Os-
teoblastic images may be seen, and no evident radiographic
changes will be found in 5% of cases .
In this article, we report the clinical case of a patient with a
mandibular metastasis of a breast cancer she had experienced
more than 25 years before. The metastasis was diagnosed
based on the detection of hormone receptors using immuno-
A 94-year-old woman attended the office complaining of the presence
of a right mandibular tumor for the past 3 months. On palpation, a hard
non-tender submucosal tumor, adhered to the ramus of the mandible,
was felt. Oral cavity examination did not reveal the existence of any ulcer
or wound, and cervical examination to assess the status of lymph node
chains was normal.
The patient reported a history of hypertrophic cardiomyopathy, uri-
nary incontinence, and appendectomy, as well as surgery for anal fistula
and inguinal hernia. She also reported to have suffered from breast car-
cinoma that was treated by excision of the right and left breasts 34 and
26 years ago, respectively. The patient also said that she had received
postoperative supplemental treatment with radiotherapy, but because of
the time elapsed and the fact that she had been seen at another center in
another town, no more data could be obtained about these episodes.
A computed tomography (CT) scan with intravenous contrast from
the skull base to the neck revealed a soft tissue mass in the right side of
the neck that extended from the infratemporal fossa to the submaxillary
gland. This mass caused destruction of the bone walls of the right mandi-
ble and infiltrated muscles and adjacent fatty planes (fig. 1). A fine nee-
dle aspiration revealed the presence of an infiltrating epithelial neoplasm
that grew forming PAS- and alcian blue-positive cell cords and nests with
irregular, hyperchromatic, and eccentric nuclei (signet ring) (fig. 2). Pro-
liferating cells expressed strong and diffuse immunoreactivity to keratins
AE1-AE3 and GCDFP-15 (gross cystic disease fluid protein), with a rate
of estrogen and progesterone receptors >90%, consistent with a diagnosis
of metastasis from a signet ring cell carcinoma of a breast origin. HER2
status of the metastasis was measured by immunohistochemistry, and
the overexpression of the c-erB2 protein was scored as 3/3. The work-up
study adopted for the identification of an unknown primary tumor was
completed by performing thoracic and abdominal CT and positron emis-
sion tomography (PET) scans that were normal. Skeletal scintigraphy
showed increased uptake of the radiotracer in the mandible of the right
side suggesting metastatic bone involvement.
Based on the diagnosis of a mandibular metastasis of a breast carci-
noma and because of the age of the patient, antineoplastic hormone ther-
apy with letrozol 2.5 mg/day was prescribed. Fifteen months after starting
treatment, the patient has experienced a complete remission of the meta-
static mandibular tumor and remains under regular medical checks.
Patients with breast cancer remain exposed for many years
to the risk of dissemination of the disease because metasta-
ses may appear after very long disease-free intervals of up to
20 years during which the disease remains completely silent.
In this sense, guidelines for breast cancer follow-up and man-
agement have been recently updated .
Fig. 1. Facial computed tomography scan showing a tumor destroying
the bone walls of the right mandible.
Fig. 2. PAS and alcian blue stain; original magnification ×40. Alcian
blue-positive magenta bodies and signet ring eccentric nuclei are shown.
Breast Care 2009;4:192–194
In our case, the patient experienced a mandibular metas-
tasis 26 and 34 years after undergoing mastectomy. Thus,
in a patient diagnosed with a neoplastic disease, who has a
lesion in the oral cavity, the presence of a metastatic lesion
should be suspected. However, in 30% of the cases, oral
metastases are the first sign of a primary malignant tumor
of as yet unknown origin , and a high suspicion index
is therefore required to establish a diagnosis, particularly
in cases where metastases may have a similar histopatho-
logical appearance to other primary intraoral lesions, e.g.
an oral epidermoid carcinoma or a lung epidermoid carci-
noma . So, a metastatic dissemination of a breast cancer
also requires differential diagnosis with a second primary
tumor. The risk of confusion increases when diagnosis and
treatment are performed at different centers, as occurred
in our case, so that not all prior information may be avail-
able. It should also be noted that signet ring differentiation
may appear in metastases from a breast cancer regardless
of whether or not the primary breast tumor had signet ring
cells . However, tests for cytokeratins, CK-7 and CK-20,
and GCDFP-15, as well as hormone receptors, are proposed
for differential diagnosis of the breast origin of carcinomas
and their metastases . Thus, in the reported case prolifer-
ating cells showed immunoreactivity to keratins AE1-AE3
and GCDFP-15, with a >90% rate of estrogen and proges-
terone receptors. This is an odd phenomenon, because the
dedifferentiation involved in the presence of signet ring cells
in breast cancer metastases is not associated to a loss of ex-
pression of hormone receptors.
Occurrence of a metastatic lesion in the oral cavity is usual-
ly a poor prognostic sign indicating a disseminated neoplastic
disease and suggesting a fatal outcome, and less than 10% of
patients survive at 4 years of diagnosis . Surgery is usually
performed when the primary tumor is controlled and no ad-
ditional metastases are found. In cases where the oral metas-
tasis is the only one present, adequate surgical treatment may
slightly improve the prognosis. When soft tissue metastases
are very uncomfortable because of pain, bleeding, infection,
or interference with chewing, palliative excision of the lesion
should be performed. In our case report, the patient was treat-
ed with antineoplastic hormone therapy with letrozol, and she
is showing no symptoms 1 year later.
In summary, a rare case of breast cancer metastasis in the
oral cavity of a patient who was bilaterally mastectomized
25 years earlier is reported. Immunohistochemical diagnosis
and antineoplastic hormone therapy are the cornerstones in
the management of this clinical case.
Conflict of Interest
The authors have declared that no conflict of interest exists.
1 Greenlee R, Hill-Harmon M, Murray T, Thun M:
Cancer statistic 2001. CA Cancer J Clin 2001;51:15–
2 Steinbrecher JS, Silverberg SG: Signet-ring cell
carcinoma of the breast. The mucinous variant of
infiltrating lobular carcinoma? Cancer 1976;37:828–
3 Eltorky M, Hall JC, Osborne PT, el Zeky F: Sig-
net-ring cell variant of invasive lobular carcinoma
of the breast. A clinicopathologic study of 11 cases.
Arch Pathol Lab Med 1994;118:245–248.
4 Liu SM, Chen DR: Signet-ring cell carcinoma of
the breast. Pathol Int 2000;50:67–70.
5 Hirsberg A, Buchner A: Metastatic tumours to
the oral region. An overview. Eur J Cancer B Oral
6 Hirsberg A, Leibovich P, Buchner A: Metastatic
tumors to the jaws: analysis of 390 cases. J Oral
Pathol Med 1994;23:337–341.
7 Khatcheressian JL, Wolff AC, Smith TJ, Grunfeld
E, Muss HB, Vogel VG, Halberg F, Somerfield
MR, Davidson NE; American Society of Clinical
Oncology: American Society of Clinical Oncology
2006 update of the breast cancer follow-up and
management guidelines in the adjuvant setting. J
Clin Oncol 2006;24:5091–5097.
8 Raju U, Ma CK, Shaw A: Signet ring variant of
lobular carcinoma of the breast: a clinicopathologic
and immunohistochemical study. Mod Pathol 1993;
9 Tot T: The role of cytokeratins 20 and 7 and estro-
gen receptor analysis in separation of metastatic
lobular carcinoma of the breast and metastatic sig-
net ring cell carcinoma of the gastrointestinal tract.