N. Yoshimura et al. / Modern Chemotherapy 2 (2013) 66-68 67
biopsy of these skin lesions was performed, and it re-
vealed HER2 overexpression on the tumorcellular mem-
brane. The patient was therefore administrated an
anti-HER2 drug, trastuzumab (4 kg/kg), followed by a 2
mg/kg maintenance dose at weekly intervals in combina-
tion with Taxanes (Docetaxel and Paclitaxel) according
to a protocol for HER2-positive metastatic breast cancer
beginning 14 months prior to his death. The metastatic
skin lesion rapidly decreased in size. However, multiple
small spots were found in his brain by MRI 10 months
before his death, which were diagnosed as brain metas-
tases. The regimen was then shifted to low dose 5-FU
(1000 mg/m2) and Cisplatin (15 mg/m2). Radiotherapy
for the brain was performed. The skin recurrence rapidly
spread over his body, and he suffered from gradual de-
bilitation, pneumonia, a urinary tract in fection, and ev en-
tually died.
We performed an autopsy on the patient. For the skin
lesion, HER2-positive skin recurrence was observed ex-
tending to the vulva, bilateral thighs and the lower ab-
domen (Figure 1). These exacerbated after discontinua-
tion of trastuzumab, and transudate was observed due to
the extensive necrosis and erosion. For brain metastases,
some small lesions were detected in the basal ganglion,
hippocampus, cerebellum, and pons. Some of them ex-
hibited vacuolar degeneration, indicating the effect of
whole brain radiotherapy (Figure 2). In the lungs, acute
bronchopneumonia and acute diffuse alveolar damage
with pleural effusion were detected. In the kidneys, acute
pyelonephritis and mild acute tubular necrosis were ob-
served. Other metastases were found in bilateral lungs,
the pancreas, and lymph nodes.
3. DISCUSSION
Our patient died 28 months after the diagnosis of
AEMPD. To the best of our knowledge, there are no re-
ports about autopsy case of AEMPD treated with anti-
HER2 therapy. Generally, most AEMPD cases are diffi-
cult to treat even with multimodality therapy. The mor-
tality rate associated with progressive EMPD is 13% -
(a) (b)
Figure 1. Histopathologic findings: (a) H.E stain ×40, (b) Im-
munohistochemical stain of skin lesion revealed HER2 were
positive.
(a) (b)
(c) (d)
Figure 2. Macroscopic findings: (a) Cerebrum; (b) Cerebellum.
small, multipulmetastatic nodules were found. Histopathologi-
cal findings; (c) Basal ganglion (H.E stain ×40); (d) hippocam-
pus (H.E stain ×100). The vacuolar degenerations were found
in some metastasis.
18% [5,6], and the 5-year survival rate of AEMPD is
reported to be 72% [7]. The general pattern of metastasis
in EMPD is lymphogenous, and less often, hematoge-
nous spread. Brain metastasis is relatively uncommon.
Furthermore, the detection of brain metastasis during the
course of disease is unlikely. There is no established che-
motherapy regimen for AEMPD and various regimens
have been administered, such as topical 5-Fluorouracil,
Mitomycin C, Cisplatin, Docetacel, etc. As noted previ-
ously, 20% - 60% of EMPD show HER2 expression,
which is approximately the same or higher percentage
than primary breast cancers. The combination of con ven-
tional chemotherapy regimens with anti-HER2 drugs is
therefore expected to improve the overall survival for
AEMPD patients. Previous reports show favorable local
control, but further investigations, such as those evaluat-
ing the response rate or survival, are difficult due to the
relative rarity of the condition. In our patient, the use of
trastuzumab plus taxanes showed a dramatic effect on the
skin metastasis, but brain metastases developed. Is this
situation coincidental? Trastuzumab does not cross the
blood-brain barrier and it has been reported that patients
with HER2-positive breast cancer have a significantly
higher incidence of brain metastasis after treatment with
trastuzumab [8]. Nevertheless, it has been suggested that
the metastasis of EMPD to the brain is rare. However,
since each metastasis was small and did not lead to neu-
rological symptoms, we may not have had to discontinue
administering trastuzumab. It might have been the tran-
sudate from the skin metastasis that caused low nutrient
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