Case Report Invasive Mucinous Adenocarcinoma of the Lung ç— ä¾‹ ...

台 灣 癌 症 醫 誌 (J. Cancer Res. Pract.) 28(2),94-98, 2012
Case Report
journal homepage:www.cos.org.tw/web/index.asp
Invasive Mucinous Adenocarcinoma of the Lung
Han-Tsung Liu 1,2 , Shiou-Fu Lin 3 , Yuh-Ming Chen 4 *
1 Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
2 Division of Hematology and Oncology, Department of Internal Medicine, Taipei City Hospital Zhongxiao Branch,
Taipei, Taiwan
3 Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
4 Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Abstract.
Invasive mucinous adenocarcinoma of the lung is a rare disease with distinct pathological
features and uncommon biological manifestations. We report a 50 year-old woman who initially
presented with increasing shortness of breath and progressive facial swelling. She was diagnosed
with invasive mucinous adenocarcinoma of the lung with its immunohistochemistry revealed
as CK7 (+), CK20 (+), CDX2 (+), TTF-1 (-), CK5/6 (-), and P63 (-). We also describe
how the patient initially had a good response to chemotherapy with paclitaxel and cisplatin.
病 例 報 告
Keywords : invasive mucinous adenocarcinoma, diagnosis, treatment
侵 襲 性 黏 液 性 肺 腺 癌
劉 瀚 聰
1,2
林 脩 涪
3
陳 育 民
4 *
1
台 北 榮 民 總 醫 院 內 科 部 血 液 腫 瘤 科
2
台 北 市 立 聯 合 醫 院 忠 孝 院 區 血 液 腫 瘤 科
3
台 北 榮 民 總 醫 院 病 理 部
4
台 北 榮 民 總 醫 院 胸 腔 部
中 文 摘 要
侵 襲 性 黏 液 性 肺 腺 癌 是 一 種 罕 見 的 疾 病 , 它 的 病 理 特 徵 很 特 殊 , 而 且 生 物 表 現 也 不
同 於 一 般 的 肺 腺 癌 。 我 們 要 報 告 一 個 侵 襲 性 黏 液 性 肺 腺 癌 的 個 案 , 她 的 病 理 免 疫 細 胞 學
染 色 呈 現 CK7 (+)、CK20 (+)、CDX2 (+)、TTF-1 (-)、CK5/6 (-) 以 及 P63 (-)。 這 個 病 人 一
開 始 對 太 平 洋 紫 杉 醇 加 上 順 鉑 的 化 學 治 療 有 很 好 的 反 應 。
關 鍵 字 : 侵 襲 性 黏 液 性 肺 腺 癌 、 診 斷 、 治 療
INTRODUCTION
In 2011, the International Association for the
Study of Lung Cancer (IASLC), the American Thoracic
Society (ATS) and the European Respiratory Society
(ERS) developed a new classification of adenocarcinoma
of lung. In the new classification, use of the
term “bronchioloalveolar carcinoma” (BAC) describing
certain variants of lung cancer has been discon-

H. T. Liu et al./JCRP 28(2012) 94-98 95
tinued [1]. Unlike adenocarcinoma in situ (AIS) and
minimally invasive adenocarcinoma (MIA), which
both have nearly 100% 5-year survival rates, invasive
mucinous adenocarcinoma (formerly mucinous BAC)
has a comparatively poorer prognosis. Within the criteria
for the new staging system, there is no collected
survival data that has been fully presented for mucinous
adenocarcinoma of the lung. However, prior literature
shows that the disease has unusual clinical
presentation and distinct immunohistochemical features.
CASE REPORT
A 50-year-old woman was transferred to our hospital.
One month before admission, she had increasing
shortness of breath and progressive facial swelling.
She visited a local hospital for medical assistance,
where a subsequent chest X-ray showed massive right
pleural effusion and widening of the upper mediastinum.
Thoracentesis yielded bloody exudative effusion,
and a pig-tail tube was inserted for drainage. The
drainage volume was 400-500 ml per day. Subsequently,
the pig-tail tube was then replaced by a chest
tube due to blood clot occlusion. Cytological examination
indicated adenocarcinoma. The patient’s chest
CT scan depicted massive right pleural effusion, a
thrombus at the superior vena cava, and a 3 x 3 cm
mass at the anterior mediastinum. The thrombus was
thought to be tumor-related. CT-guided biopsy of the
anterior mediastinum mass revealed metastatic adenocarcinoma
with immunohistochemical stain as CK7
(-), TTF-1 (-), CK20 (+) and CDX2 (+), suggesting
metastatic adenocarcinoma of the lower gastrointestinal
tract. The patient underwent esophagogastroduo-
*Corresponding author: Yuh-Min Chen, M.D., Ph.D.
* 通 訊 作 者 : 陳 育 民 醫 師
Tel: +886-2-28757563
Fax: +886-2-28763466
E-mail: ymchen@vghtpe.gov.tw
Figure 1. Mucinous pools contain poorly differentiated
adenocarcinoma cells (200X)
denoscopy (EGD endoscopy) and colonoscopy, with
resulting negative findings. PET/CT scan revealed uptake
in the patient’s anterior mediastinum and the right
lower lung, and she was then treated as metastatic adenocarcinoma
of lower gastrointestinal origin. After this
diagnosis, the patient came to our hospital for a second
opinion, where additional diagnostic tests were performed.
Similar to her previous results, the patient’s
brain MRI and mammography were negative; gynecological
ultrasound exam revealed myomas only. We
repeated the chest CT scan and performed biopsy to the
pleural lesions. The pathology report showed metastatic
adenocarcinoma with immunohistochemistry noted as
CK7 (+), CK20 (+), CDX2 (+), TTF-1 (-), CK5/6 (-),
and P63 (-) (Figures 1, 2). EGFR sequencing reported
no mutation. Because of the discordance of immunochemistry
profiles between the pleural sample and the
anterior mediastinal tumor, we discussed this case in
our lung cancer multidisciplinary conference. The
members concluded that the tumor was compatible with
invasive mucinous adenocarcinoma of lung, and we
treated the patient with paclitaxel plus cisplatin. Three
days later, her pleural effusion markedly decreased, and
chest film indicated widening of the anterior mediastinum.
We maintained this regimen for 2 months, but
unfortunately her disease progressed (Figure 3).

96 H. T. Liu et al./JCRP 28(2012) 94-98
CK7(+)
CK20(+)
TTF‐1(‐)
CDX2(+)
Figure 2. The immunohistochemical stains show CK7 (+), CK20 (+), TTF-1 (-) and CDX2 (+) (400X)
Figure 3. The chest CT shows anterior mediastinal
tumor (black arrow) and pleural seeding
(white arrows)
DISCUSSION
The characteristics of invasive mucinous adenocarcinoma
were reported to be predominantly found in
female (58%), non-smoker (55%), positive CK7
(~88%), CK20 (~54%) and negative TTF-1 (~83%) in
immunohistostain. The genotypes of invasive mucinous
adenocarcinoma have frequent KRAS mutation
(~76%) and almost no EGFR mutation (~3%) [2]. The
radiographic appearance of these tumors are characterized
by majority consolidation, air bronchogram,
and frequent multifocal and multilobar presentation.
Mazziotta et al. also reported ten of 84 primary lung
carcinomas (12%) were immunoreactive for CDX2
expression (a gastrointestinal marker) [3]. They concluded
that primary lung adenocarcinoma can also

H. T. Liu et al./JCRP 28(2012) 94-98 97
A
B
Figure 4. (A) Series of chest films show initial response to a course of chemotherapy with paclitaxel
and cisplatin, and (B) progressive disease two months later
express CDX2, which was previously thought to be a
specific marker for tumors with intestinal differentiation.
Due to the introduction of the new classification
system and rare disease incidence rate, there were lim-

98 H. T. Liu et al./JCRP 28(2012) 94-98
ited studies that had mentioned the treatment of invasive
mucinous adenocarcinoma. According to WHO
2004 classification, research has shown that surgery
for resectable disease remains the mainstay treatment
of BAC [4]. However, for invasive mucinous adenocarcinoma,
there was no study which demonstrated an
optimum treatment response.
Some reports showed a good treatment response to
tyrosine kinase inhibitor (TKI) in MIA patients harboring
the EGFR mutation [5,6]. However, the EGFR
mutation represents a relatively low percentage of total
cases in comparison with other types of adenocarcinoma.
For this patient, comprehensive studies had been
done to exclude various metastatic origins. Ultimately,
she was diagnosed with stage IV primary lung cancer.
Because of the wild type EGFR sequencing, we chose
paclitaxel (175 mg/m 2 ) plus cisplatin (50 mg/m 2 ) (TC)
as first line chemotherapy. Although the patient’s initial
response to this course of treatment was good, her
disease progressed after three cycles of TC regimen
(Figure 4). The clinical course implied that the disease
had aggressive behavior, which often leads to a poor
prognosis as occurred in this case.
The valuable information we obtained from this
case was that invasive mucinous adenocarcinoma can
have unusual presentation and distinct pathological
features, highlighting the importance of multidisciplinary
cooperation for accurate diagnosis and treatment.
Although we have found no strong evidence of a particularly
efficacious, long-term treatment, we suggest
paclitaxel plus cisplatin as an option for the first line
chemotherapy.
REFERENCES
1. Travis WD, Brambilla E, Noguchi M, et al. International
association for the study of lung cancer/american
thoracic society/european respiratory
society international multidisciplinary classification
of lung adenocarcinoma. J Thorac Oncol
6: 244-285, 2011.
2. Morency E, Rodriguez Urrego PA, Szporn AH, et
al. The “drunken honeycomb” feature of pulmonary
mucinous adenocarcinoma: a diagnostic pitfall
of bronchial brushing cytology. Diagn Cytopathol:
n/a–n/a, 2011.
3. Mazziotta RM, Borczuk AC, Powell CA, et al.
CDX2 immunostaining as a gastrointestinal
marker: expression in lung carcinomas is a potential
pitfall. Appl Immunohistochem Mol Morphol
13: 55-60, 2005.
4. Whitson BA, Groth SS, Andrade RS, et al. Invasive
adenocarcinoma with bronchoalveolar features:
a population-based evaluation of the extent
of resection in bronchoalveolar cell carcinoma. J
Thorac Cardiovasc Surg 143(3):591-600,2012 .
5. Kitazaki T, Fukuda M, Kohno S, et al. Novel effects
of gefitinib on mucin production in bronchioloalvelar
carcinoma; two case reports. Lung
Cancer 49(1):125-8, 2005.
6. Popat N, Raghavan N, McIvor RA. Severe bronchorrhea
in a patient with bronchioloalveolar carcinoma.
CHEST 141(2): 513-514, 2012.