CASE REPORT
Well differentiated fetal adenocarcinoma of the lungin a 38-year-old woman: dynamic computedtomography findings
Takana Yamakawa • Atsushi Nambu • Satoshi Kato •
Masashi Kawamoto • Shozo Fujino • Masato Watanabe •
Masao Tago
Received: 14 August 2012 / Accepted: 11 October 2012 / Published online: 31 October 2012
� Japan Radiological Society 2012
Abstract We report a case of well-differentiated fetal
adenocarcinoma (WDFA) of the lung, with emphasis on
dynamic CT (computed tomography) findings. The patient
was a 38-year-old woman who was found to have a mass in
the left upper lung field in chest radiograph screening. Chest
radiograph showed a 5.5 cm well-defined mass in the left
upper lung field. CT revealed a well-circumscribed mass
measuring 5.5 9 5.5 9 5.0 cm with a lobulated margin in
the left upper lobe. Intratumoral enhancing vasculature was
noted in the early phase of dynamic CT. In the delayed phase,
persistent and plateau enhancement was seen. The tumor
also had consistently unenhanced areas, suggesting the
presence of necrosis. Left upper lobectomy with mediastinal
lymph node dissection was performed. The pathology
specimen contained tubular glands consisting of non-ciliated
columnar cells with areas of solid nests of epithelial cells
with weakly eosinophilic cytoplasm (morule) mimicking
fetal lung tissue. The tumor was moderately vascularized
with areas of comedo necrosis; the stroma was relatively
scanty. Final pathological diagnosis was WDFA with left
hilar lymph node metastasis (stage T2bN1M0). This is the
first report of dynamic CT findings of WDFA, a rare lung
tumor. Although these findings are non-specific, they well
reflected the pathological characteristics of this tumor.
Keywords Well-differentiated fetal adenocarcinoma �Lung carcinoma � Dynamic CT � Pulmonary blastoma
Introduction
Well differentiated fetal adenocarcinoma (WDFA) is a rare
malignant pulmonary tumor. It is pathologically charac-
terized by immature epithelium that morphologically
mimics that of fetal lung without the sarcomatous
component [1–3]. WDFA was originally included in the
category pulmonary blastoma. However WDFA was
reclassified as a variant of adenocarcinoma by the WHO
classification in 1999 [4]; since 2011, in the newest inter-
national multidisciplinary classification of lung adenocar-
cinoma, it has been included in a category which includes
variants of invasive adenocarcinoma [5].
WDFA usually appears as an expansive solitary mass on
chest radiograph and CT. These findings are non-specific, and,
therefore, pre-operative diagnosis is regarded as difficult.
This report describes the imaging findings of a case of
WDFA, especially those of dynamic CT, with a literature
review.
Case report
A 38-year-old Japanese woman without clinical symptoms
visited our hospital for work-up of an abnormality found on
T. Yamakawa (&) � A. Nambu � S. Kato � M. Tago
Department of Radiology, Teikyo University School
of Medicine University Hospital, Mizonokuchi,
3-8-3 Mizonokuchi, Takatsu-ku, Kawasaki,
Kanagawa 213-8507, Japan
e-mail: [email protected]
M. Kawamoto
Department of Clinical Pathology, Teikyo University School
of Medicine University Hospital, Mizonokuchi,
3-8-3 Mizonokuchi, Takatsu-ku, Kawasaki,
Kanagawa 213-8507, Japan
S. Fujino � M. Watanabe
Department of Surgery, Teikyo University School
of Medicine University Hospital, Mizonokuchi,
3-8-3 Mizonokuchi, Takatsu-ku, Kawasaki,
Kanagawa 213-8507, Japan
123
Jpn J Radiol (2013) 31:143–147
DOI 10.1007/s11604-012-0154-8
chest radiograph screening performed at another hospital.
Although a 1 cm nodule had been noted in the left lung
field 9 years previously, she had not sought medical
attention since then. She had no other remarkable past
medical history. Physical examination, respiratory func-
tion, and blood examinations were normal. She had a his-
tory of smoking 10 cigarettes per a day for 15 years.
The chest radiograph showed a mass with a maximum
diameter in 55 mm in the left upper lung field (Fig. 1).
Subsequent computed tomography (CT) revealed a well-
circumscribed mass with a lobulated border measuring
55 9 55 9 50 mm in the left upper lobe (Fig. 2a). This
mass contained areas of air density; it could not be deter-
mined whether these corresponded to air bronchograms or
frank cavities. No intratumoral fat or calcification was
identified. The tumor was generally hypoattenuating with a
mean CT value of 29 HU (Hounsfield Unit) on unenhanced
CT. Dynamic contrast enhanced CT was performed with an
injection of 100 ml Iohexol 350 (Omnipaque; Daiichi-
Sankyo, Tokyo, Japan) at a injection rate of 3.2 ml/s.
Postcontrast CT was scanned 30, 110, and 240 s after the
beginning of injection of the contrast media (Fig. 2b), and
the mean attenuations of the tumor were calculated to be
50, 59, and 61 HU, respectively. Moderate and inhomo-
geneous enhancement with enhancing blood vessels pene-
trating the tumor was observed in early phase scan after
30 s; the subsequent scans after 110 and 240 s revealed
persistent and plateau enhancement, as shown by the CT
value measurements (Fig. 2c, d). A left upper lobe lymph
node was mildly prominent with a short-axis diameter of
8 mm. There was no other abnormal finding in images of
chest or abdomen. Although the imaging and clinical
findings were non-specific, a relatively slow growing
tumor, for example leiomyoma or giant hamartoma was
considered most likely preoperatively, given the history
that the tumor had already existed 9 years previously.
However, intraoperative frozen section diagnosis yielded a
suspicion of malignancy, and therefore, left upper lobec-
tomy with lymph node dissection was performed.
Gross pathological examination of the specimen
revealed a single, white, well defined, and elastic hard mass
measuring 5.5 9 5.5 9 5.0 cm with areas of necrosis and
hemorrhage (Fig. 3).
Microscopically, it contained abundant glands com-
posed of nonciliated cells, single to a few layers, with
prominent clear cytoplasm resembling the tubular epithe-
lium of fetal lung with a relatively scanty stroma (Fig. 4a).
In some areas, the cells merged to form very small rosette-
like glands, and focal areas of comedo necrosis and
hemorrhage were identified. No penetrating bronchi were
identified. Therefore, the air densities seen on CT were
regarded as corresponding to cavities. Also, there
were morules consisting of solid nests of epithelial cells
with weakly eosinophilic cytoplasm (Fig. 4b). These
epithelial cells were immunohistochemically positive for
synaptophysin, a neuroendocrine cell marker (Fig. 4c).
The histological pattern and immunohistochemical
profile were consistent with well differentiated fetal ade-
nocarcinoma (WDFA). The left upper lobe lymph node
was found to be metastatic. The final pathological stage
was T2bN1M0 by UICC-7.
The patient was treated with 4 cycles of postoperative
chemotherapy that included carboplatin and pemetrexed.
She followed an uneventful posttreatment course and has
been doing well without evidence of recurrence so far.
Discussion
WDFA is a very rare malignant lung tumor, constituting
0.1 % of all lung tumors. It is pathologically characterized
by immature epithelium that morphologically mimics that
of fetal lung at 10–15 weeks of gestation without sar-
comatous component [1–3]. This tumor was first reported
by Kradin et al. [6] as a subtype of pulmonary blastoma.
According to the third series of the American Forces
Institute of Pathology (AFIP) atlas of tumor pathology, the
category pulmonary blastoma also included biphasic pul-
monary blastoma (BPB) and cystic and pleuropulmonary
blastoma of childhood [3]. However WDFA lacks p53
genetic mutation, unlike BPB, and has a better prognosis
than BPB [1, 4, 7]. Therefore, WDFA was reclassified as a
variant of adenocarcinoma by the WHO classification in
1999 [4]; it has, since 2011, in the newest international
multidisciplinary classification of lung adenocarcinoma
[5], been included in a category which includes variants of
invasive adenocarcinoma. Currently, the term ‘‘pulmonary
blastoma’’ is reserved for tumors with a biphasic appear-
ance, i.e. consisting of both carcinomatous and sarcoma-
tous components, whereas WDFA is regarded as a purely
epithelial malignancy (i.e. carcinoma).
WDFA has a unimodal age peak during the third decade
with no sex predominance [1, 8]. Tobacco smoking is
believed to be a risk factor. Many cases of WDFA areFig. 1 Posteroanterior and lateral chest radiograph shows a mass
with a maximum diameter of 55 mm in the left upper lung field
144 Jpn J Radiol (2013) 31:143–147
123
Fig. 2 a Unenhanced CT shows a well-circumscribed mass with a
lobulated border measuring 55 9 55 9 50 mm in the left upper lobe.
This mass contained areas of air density. No intratumoral fat or
calcification was identified. b Images in the early phase (30 s after the
beginning of injection of the contrast media) of dynamic CT.
Moderate and inhomogeneous enhancement is apparent with
enhancing blood vessels penetrating the tumor. c Images from
3 phase dynamic CT. The images were scanned 30, 110, and 240 s
after the beginning of the injection of contrast media. d The time
intensity curve of the tumor’s mean attenuations. The delayed phase
scan revealed persistent and plateau enhancement of the contrast
material
Jpn J Radiol (2013) 31:143–147 145
123
asymptomatic with the number of cases incidentally found
on medical check-up radiographs accounting for 57–76 %
[1, 8]. In symptomatic cases, cough, dyspnea, and chest
pain are the common symptoms [1]. The prognosis is better
than that of pleuropulmonary blastoma. Koss et al. [1]
reported 5-year survival of 80 % for WDFA. Although the
standard treatment for WDFA is surgery, use of chemo-
therapy (usually platinum-based) has been reported [2, 10].
Radiologically, WDFA usually appears as an expansive
mass with or without cavity [1, 8]. Pleural effusion or
lymph node metastasis is rare [1, 8]. The CT findings of our
case are similar to those of previous reports except for the
presence of a prominent left hilar lymph node. However,
detailed contrast-enhanced CT findings of WDFA have not
yet been reported. To the best of our knowledge, this is the
first report of dynamic CT findings of WDFA. The tumor
was moderately vascularized, as evidenced by intratumoral
enhancing vasculature in the early phase. In the delayed
phase, persistent plateau enhancement was observed. Pro-
gressive enhancement was not seen, probably because of
Fig. 4 a The low-power microscopic view of the tumor shows the
fused glandular structure. The high-power view shows glands
composed of single or two layers of non-ciliated cells with prominent
clear cytoplasm resembling the tubular epithelium of fetal lung.
b High-power view showing morules consisting of solid nests of
epithelial cells with weakly eosinophilic cytoplasm (thin arrows).
c Immunohistochemistry for synaptophysin, a neuroendcrine cell
marker, shows positivity for the tumor cells
Fig. 3 Gross pathological examination of the specimen revealed a single, white, well defined, and elastic hard mass measuring
5.5 9 5.5 9 5.0 cm with areas of necrosis and hemorrhage
146 Jpn J Radiol (2013) 31:143–147
123
scanty extracellular spaces. Consistently inhomogeneous
enhancement of the tumor was also observed, probably
because of diffusely scattered comedo necrosis. There were
air densities that corresponded to frank cavities. A case of
WDFA with air bronchograms has also been reported; this
had a multicentric form with areas of ground-glass opacity
[9]. We believe this reported case is an unusual WDFA,
and air bronchogram is less likely to occur in WDFA
because it usually assumes expansive growth.
WDFA is regarded as a less aggressive tumor than other
lung carcinomas or pulmonary blastoma [1]. Our case had a
history of a nodule already present at the corresponding site
9 years previously, which might suggest slow growth of
WDFA. In addition, despite an expansive mass of sub-
stantial size, massive necrosis was absent and the sur-
rounding lung parenchyma was clear without evidence of
compression or secondary changes related to the tumor, for
example hemorrhage or inflammation. These findings may
also be suggestive of a relatively indolent course of WDFA.
In summary, the WDFA in our case had an expansive
mass with moderate vascularity and cavities on dynamic
CT. Although these imaging findings are non-specific,
WDFA should always be included in differential diagnosis
of an expansive mass lesion in young to middle-aged
patients with a history of smoking, especially when slow
growth of the tumor is clinically evident.
Acknowledgments We thank Dr. Yukio Nakatani, Professor of the
Department of Diagnostic Pathology, Chiba University Graduate
School of Medicine, for reconfirming the pathological diagnosis and
for giving us valuable comments on this unique lung tumor.
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