Case 1 -
Metastatic Malignant Melanoma to the Breast
Melinda F. Lerwill, Mass General Hospital, Boston, MA
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83-year-old woman with a 4.5 x 3 cm hard, palpable mass in the upper outer quadrant of the right breast.
Case 1 - Slide 1
An 83-year-old woman was referred to our institution with a
diagnosis of locally advanced breast cancer. The patient had
self-palpated a right breast mass in the upper outer
quadrant. Mammogram confirmed the presence of a large mass,
and she underwent a core biopsy of the lesion at an outside
institution. The pathological findings were interpreted as
infiltrating ductal carcinoma, grade 3 of 3. The tumor was
negative for ER, PR, and Her-2/neu. She was referred to our
multidisciplinary breast clinic for consideration of
The outside pathology slides were forwarded to our
department for routine review. The requisition form gave the
clinical history as "breast cancer." It was not until the
case was reviewed at the multidisciplinary clinic that the
pathologist became aware that the patient had a history of a
malignant melanoma of the right shoulder that was excised 2
years earlier. This revelation prompted further work-up of
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
The core biopsy demonstrates a diffuse proliferation of
pleomorphic epithelioid tumor cells with broad areas of
necrosis. For the most part, the growth is patternless,
although focal vague nesting is observed. In areas, there is
a suggestion of mild spindle-shaped elongation of the tumor
cells. The large, round to oval nuclei have vesicular
chromatin and prominent red macronucleoli. Occasional
binucleate cells and rare intranuclear pseudoinclusions are
seen. The tumor cells contain abundant eosinophilic
cytoplasm. Only minimal pigment is present and is easily
The tumor cells are negative for ER, PR, and Her-2/neu.
After learning of the history of melanoma, additional
immunohistochemical studies were performed. These show that
the tumor cells are diffusely positive for S-100, HMB-45,
and MART-1, and focally positive for cytokeratin.
High-grade invasive ductal carcinoma
Metastatic malignant melanoma.
Metastatic malignant melanoma to the breast
Certainly, common things being common, a
poorly-differentiated breast carcinoma is a leading
consideration in this case. The diffuse growth
of high-grade epithelioid tumor cells with necrosis is
compatible with a breast carcinoma, particularly one with
triple-negative receptor status. Only subtle findings on the
H&E suggest that the diagnosis might be otherwise: loose
cellular cohesion, mild spindling of some tumor cells,
binucleate cells, pseudoinclusions, and focal pigment. These
findings, coupled with the belatedly obtained history of
melanoma, swing the diagnostic pendulum towards metastatic
melanoma. In the absence of such history, a low threshold
for further diagnostic testing when even subtly unusual
histologic features are present is important.
In this case, subsequent immunohistochemical studies
demonstrated diffuse positivity for S-100, HMB-45, and
MART-1, confirming a diagnosis of metastatic malignant
melanoma. It should be noted that S-100 is also positive in
nearly 50% of breast carcinomas,  and therefore this
marker is not reliable for distinguishing melanoma from
breast carcinoma. HMB-45 and MART-1 are more specific
markers for this purpose. Focal cytokeratin positivity was
also present in this case, a recognized phenomenon in
occasional melanomas, but which may be misleading if
evaluated in the absence of accompanying melanoma markers. 
Although the presence of melanin pigment strongly suggests a
diagnosis of melanoma, occasional breast carcinomas that
breach the skin may contain melanin pigment or even
melanocytes.  Additionally, rare variants of metaplastic
carcinoma of the breast can demonstrate melanocytic
differentiation. Although regions of these tumors
histologically, immunohistochemically, and ultrastructurally
resemble melanoma, other areas clearly represent carcinoma. 
Review of the Literature/Treatment Options
The breast is a remarkably uncommon site of secondary tumor
involvement.  Metastases to the breast can easily be
misdiagnosed as primary breast carcinomas due to histologic
patterns that mimic breast carcinoma and to a lack of
suspicion on the part of the pathologist and clinician. When
spread from contralateral breast cancers, hematologic
malignancies, and solid tumors are all considered, secondary
tumors of the breast account for 1.3% to 3% of breast
malignancies.  The most common source of metastatic
disease is actually the contralateral breast. When tumors of
mammary origin are excluded, metastatic solid tumors account
for 0.2% to 1.1% of all breast malignancies. The most common
solid non-mammary malignancy to spread to the breast is
melanoma, followed by pulmonary and gynecological
carcinomas. Secondary breast involvement occurs most often
in the setting of disseminated metastatic disease and is
accordingly associated with a poor prognosis.
Metastatic melanoma to the breast is reported over a wide
age range, from 13 to 84 years, with a median of 48 years.
The median time interval from the diagnosis of melanoma to
the development of breast metastases is 36 to 52 months,
although late recurrences up to 23 years later have been
reported. Approximately 30% of cases represent metastases
from melanomas arising on the trunk or abdomen, 25% from the
lower extremities, 24% from the upper extremities, and the
remainder from miscellaneous or unknown primary locations.
The most common presentation for metastatic melanoma, like
that for metastases to the breast in general, is that of a
solitary discrete mass in the upper outer quadrant. 23% of
patients have multiple nodules. Most patients have
disseminated disease by the time breast metastases are
identified, and median survival is only 9 months to 1
Metastases to the breast are rare but represent an important
diagnostic pitfall. Malignant melanoma is the most common
solid, non-mammary tumor to secondarily involve the breast.
It can be mistaken for poorly-differentiated breast
carcinoma based on histology alone. Clinical history is
critical but may be unavailable or unknown. Attention to
unusual histologic findings, even if focal, can help prevent
misdiagnosis as a primary breast carcinoma and save the
patient from unnecessary or inappropriate therapies.
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