A Case of Mediastinal Lymph Node Carcinoma of Unknown
Primary Site Treated with Docetaxel and Cisplatin with
Concurrent Thoracic Radiation Therapy
Yutaro Shiotaa＊, Shigeo Imaib, Naomi Sasakic, Koo Taharad,
Bunjiro Nomaa, Naokatsu Horitaa, Akihiko Taniguchie, and Tetsuya Onoa
Departments of aInternal Medicine, bThoracic Surgery, cPathology, and dSurgery, Kure Kyosai Hospital,
Kure, Hiroshima 737-8505, Japan, eDepartment of Hematology, Oncology, and Respiratory Medicine,
Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama 700-8558, Japan
Mediastinal lymph node carcinoma of unknown primary site is rare and may have a better prognosis
if extensive treatment is performed. Case, A 69-year-old-male presented with a persistent cough. Chest
computed tomography (CT) demonstrated a large tumor 9.5×8.2cm, in the mediastinum, compressing
the right main bronchus, the right pulmonary artery, and the superior vena cava. Because fiberoptic
bronchoscopy was insufficient for diagnosis, mediastinoscopic tumor biopsy under general anesthesia
was undertaken. Histological examination revealed adenocarcinoma. Extensive examinations revealed
no other neoplastic lesion except in the mediastinum. Mediastinal lymph node carcinoma of unknown
primary site was diagnosed. The patient was treated with docetaxel and cisplatin with concurrent
thoracic radiation therapy. A month after the start of chemoradiotherapy, the mediastinal tumor
regressed markedly. The patient remained free of symptoms without regrowth of the primary site.
Exploration of the body showed no further abnormalities 20 months after disease onset.
Key words: mediastinal lymph node, unknown primary site, chemoradiation
ediastinal lymph node carcinoma of unknown
primary site is a rare disorder. There are
several case reports describing patients treated by
surgical resection, but cases treated by chemoradio-
therapy have seldom been reported. Therefore, the
usefulness of chemoradiotherapy in this disease
remains to be determined. We report here a patient
with mediastinal lymph node carcinoma of unknown
primary site successfully treated by chemoradiother-
apy. The purpose of this report is to draw attention
to the potential usefulness of chemoradiotherapy for
A 69-year-old Japanese man was referred to our
hospital on March 14th 2008 because of an abnormal
mass in the right pulmonary hilum. The patient
described a persistent cough of 1 month duration and
a chest pain of a week. He had a 94 pack-year smoking
history. He had a 20-year history of hypertension,
hemorrhoids at the age of 64, and disc herniation at
Physical examination at his first visit showed no
abnormalities in the chest and abdomen. The chest
roentgenogram at his first visit showed a right hilar
Acta Med. Okayama, 2011
Vol. 65, No. 6, pp. 407ﾝ411
CopyrightⒸ 2011 by Okayama University Medical School.
http :/ /escholarship.lib.okayama-u.ac.jp/amo/
Received February 21, 2011 ; accepted July 22, 2011.
＊Corresponding author. Phone : ＋81ﾝ823ﾝ22ﾝ2111; Fax : ＋81ﾝ823ﾝ21ﾝ1597
E-mail : email@example.com (Y. Shiota)
mass 9.2×2.5cm. Computed tomography (CT) of the
chest revealed a mediastinal tumor mass measuring
9.5×8.2cm compressing the trachea, the right main
bronchus, the pulmonary artery, and the superior
vena cava (Fig. 1). Computed tomography-supported
positron emission tomography showed increased fluo-
rodeoxyglucose retention in the mediastinum (maxi-
mum standard uptake values (SUV max 13.8) and a
right supraclavicular lymph node (SUV max 4.5) (Fig.
2). The serum examination showed an elevated level
of carcinoembryonic antigen, 7.8ng/ml.
Fiberoptic bronchoscopy showed extrinsic com-
pression and deformity of the trachea and the right
main bronchus. The bronchial mucosa was intact. No
endoluminal mass was present. Transbronchial needle
aspiration of the subcarina node was insufficient for
diagnosis. The patient underwent mediastinoscopic
examination, and a tumor biopsy was performed.
Microscopically, the tumor cells replaced most of the
lymph node, showing a solid growth pattern and occa-
sionally formed palisading arrangements. The tumor
cells have a slightly eosinophilic cytoplasm and eccen-
tric round pleomorphic nuclei and small nucleoli.
There was anisonucleosis (Fig. 3). No mucinous cells
were detected by PAS or Alucian blue staining. In the
immunohistochemical study, tumor cells stained posi-
tive for cytokeratin and AE1/AE3 and negative for
chromogranin A or synaptophysin. A small number of
cells were positive for CEA. Pathological diagnosis
was adenocarcinoma of the thoracic lymph node.
The mediastinal mass had a clear margin separated
from the lung parenchyma, and there was no sign of
pleural effusion; it therefore seemed unlikely that lung
cancer had invaded the adjacent mediastinum (T4N3M0).
Acta Med. Okayama Vol. 65, No. 6
Shiota et al.
Fig. 1 Chest CT showing the mediastinal mass compressing
superior vena cava, trachea, and main bronchi. Scale divisions
represent 1cm each.
Fig. 2 An image of whole-body fluorodeoxyglucose-positron
emission tomography demonstrating high uptake in the mediastinal
region and a right supraclavicular lymph node.
Fig. 3 Microscopic findings of resected mediastinal lymph node
showing a solid growth pattern of tumor cells replacing the lymph
node without recognizable gland formation. Adenocarcionoma was
diagnosed. (hematoxylin-eosin; scale bar indicates 50µm)
Despite the extensive diagnostic work-up, including
gastroscopic and colonoscopic examinations, enhanced
CT of the body, and PET/CT, no primary cancer site
was detected. Mediastinal lymph node carcinoma of
unknown primary site was diagnosed.
The patient had been treated with a protocol for
lung cancer with external beam radiation to the thorax
and chemotherapy with cisplatin and docetaxel .
Both docetaxel 40mg/m2 and cisplatin 40mg/m2 were
given on days 1, 8, 29, and 36. Beginning on day 1
of chemotherapy, thoracic radiation therapy was given
at a total dose of 61.4 Gy over 6 weeks. A month
after the start of chemoradiotherapy, the mediastinal
tumor regressed markedly (Fig. 4). Grade 3 granulo-
cytopenia was observed on day 12, and recombinant
human granulocyte colony stimulating factor was
administered. Reticular shadow, compatible with
radiation pneumonitis, was observed in the right
upper lung field on chest CT 86 days after the start of
chemoradiation therapy. Because the patient noted a
high fever with elevated serum CRP levels, methyl-
prednisolone, 500mg/day, was administered for 3
days for the treatment of radiation pneumonitis and
was tapered gradually.
The patient remained free of symptoms without
regrowth of the primary site 22 months after disease
onset, and exploration of the body with enhanced CT
or PET showed no further abnormalities.
It has been reported that metastatic cancers of
unknown primary tumor comprise 0.6-6.7ｵ of all
Greager et al. studied 286 cases of primary
unknown cancer and reported that the major sites of
metastasis are lymph nodes . However, metastatic
cancer in the thoracic lymph nodes from unknown
primary site is a rare disorder  and has seldom
been reported in English [7-11].
Several hypotheses regarding the development of
primary unknown cancer are possible. One possibility
is that the primary site of the cancer is the lymph
node. It is a well-known fact that benign epithelial
inclusions exist in cervical [12, 13], pelvic and peri-
toneal [14, 15], and axillary lymph nodes [16-18].
Neoplastic cells in lymph nodes may have resulted
from the transformation of ectopic epithelial inclu-
sions. In fact, there has been a report describing a
carcinoma that originated from benign epithelial inclu-
sion in an axillary lymph node . The second
hypothesis is that the primary is too small to be
detected by our means of the clinical investigation.
Recent advances in diagnostic techniques such as high-
resolution CT or PET/CT enable us to detect very
small cancer lesions, making the possibility of an
occult primary site very low. However, the possibility
of an occult primary site could not be denied even after
an extensive radiological or endoscopical workup. The
third hypothesis is that the spontaneous regression of
primary cancer lesion occurred, while the metastatic
lesion remained intact. The host immunologic mecha-
nism might destroy a small primary tumor but fail to
destroy an established metastatic tumor. It has been
reported that spontaneous regression occurs no more
than once in 60,000-100,000 cancer cases . The
incidence of spontaneous regression is extremely low
compared to that of cancer of unknown primary site,
0.6-6.7ｵ of all cancers, as described previously, and
we could not explain the pathogenesis of cancer of
unknown primary based on this hypothesis alone.
Although it is not widely accepted, the most prob-
able hypothesis seems to be that neoplastic cells arise
from endogenous epithelium in the lymph node.
The term T0N2M0 lung cancer has been used as a
synonym of mediastinal lymph node carcinoma of
unknown primary site. However, the possibility of the
Primary Unknown Cancer in Mediastinum December 2011
Fig. 4 Chest CT, a month after the start of chemotherapy,
showing a markedly regressed mediastinal tumor. Scale divisions
represent 1cm each.
endogenous cancer origin in the mediastinal node has
not been ruled out, as described previously, and the
most widely accepted term currently in use, and that
we adopt here, is ʻMediastinal lymph node carcinoma
of unknown primary site. ʼ
Miyoshi has reported 70 cases of mediastinal lymph
node carcinoma of an unknown primary site in Japan
. In the study group, a male predominance was
seen. The age ranged from 5 to 85 years with a
median age of 57.7 years. The most frequent histology
type was adenocarcinoma in 41ｵ of patients, followed
by small cell carcinoma in 19ｵ, large cell carcinoma
in 17ｵ, and squamous cell carcinoma in 16ｵ.
In general, it appears that patients with cancer of
an unknown primary site have a limited life expectancy
with a median survival of 6-9 months . However,
when limiting such cases to mediastinal lymph node
carcinoma, the survival period is far longer . It
is suggested that surgical resection of the mediastinal
lymph node should be the first treatment of choice
because the best survival benefit is obtained by com-
plete dissection of the tumor [6, 11]. There are some
papers suggesting that radical resection of mediastinal
lymph node carcinoma either combined with chemo-
therapy or radiation therapy may offer a chance of
cure and may increase long-term survival [6, 11, 21,
23, 24]. In our patient, complete excision of the
mediastinal tumor was difficult, and supraclavicular
involvement was prominent.
There have been only a few reports showing the
effectiveness of chemoradiotherapy in the treatment of
mediastinal lymph node carcinoma from an unknown
origin. It has been reported that patients with medi-
astinal lymph node carcinoma from unknown origin do
poorly when treated only medically . On the other
hand, Miwa et al. have reported two cases of medi-
astinal lymph node carcinoma treated by chemoradio-
therapy. Both cases were alive 33 and 24 months,
respectively . Watanabe et al. also reported a
case of carcinoma of unknown primary site with
involvement of the mediastinal lymph node that was
successfully treated by chemotherapy with carboplatin
and paclitaxel followed by sequential radiation ther-
apy . This protocol is designed for nonsmall cell
lung cancer. These reports suggest the potential
usefulness of chemoradiation therapy for mediastinal
lymph node carcinoma of unknown primary site. Kiura
et al. have reported promising treatment results of
docetaxel and cisplatin with radiation therapy for
nonsmall cell lung cancer . In the study, the over-
all response rate was 79ｵ and the survival rate was
54ｵ at 2 years. We have therefore chosen to treat
the patient with this protocol, and he is still alive 22
months after the diagnosis.
In conclusion, it is suggested that appropriate
chemoradiotherapy for mediastinal lymph node carci-
noma of an unknown primary site may offer a chance
of long-term survival in patients who are not eligible
for radical exsection.
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