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: yamakawa-cib@umin.ac.jp

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

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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

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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

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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.

References

1. Koss MN, Hochholzer L, O’Leary T. Pulmonary blastomas.

Cancer. 1991;67:2368–81.

2. Fujino S, Asada Y, Konishi T, Asakura S, Kato H, Mori A.

Well-differentiated fetal adenocarcinoma of lung. Lung cancer.

1995;13:311–6.

3. Colby TV, Koss MN, Travis WD. Pulmonary blastoma. In: Colby

TV, Koss MN, Travis WD, editors. Atlas of Tumor Pathology:

Tumor of the Lower Respiratory Tract. 3rd series. Washington,

DC: Armed Forces Institute of Pathology; 1995. pp 395–417.

4. Brambilla E, Travis WD, Colby TV, Corrinz B, Shimosato Y.

The new World Health Organization classification of lung

tumors. Eur Respir J. 2001;18:1059–68.

5. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger

KR, Yatabe Y, et al. International Association for the Study of

Lung Cancer/American Thoracic Society/European Respiratory

Society International Multidisciplinary Classification of Lung

Adenocarcinoma. J Thoric Oncol. 2011;6:244–85.

6. Kradin RL, Kirkham SE, Young EJ, Dickersin GR. Pulmonary

blastoma with argyrophil cells and lacking sarcomatous features

(pulmonary endodermal tumor resembling fetal lung). Am J Surg

Pathol. 1982;6:165–72.

7. Nakatani Y, Kitamura H, Inayama Y, Kamijo S, Nagashima Y,

Shimoyama K, et al. Pulmonary adenocarcinomas of the fetal

lung type. Am J Surg Pathol. 1998;22:399–411.

8. Sato S, Koike T, Yamato Y, Yoshiya K, Honma K, Tsukada H.

Resected well-differentiated fetal pulmonary adenocarcinoma

and summary of 25 cases reported in Japan. Jpn J Thorac

Cardiovasc Surg. 2006;54:539–42.

9. Furuya K, Yasumori K, Takeo S, Uesugi N, Otsu Y, Ichiki M,

et al. Well-Differentiated Fetal Adenocarcinoma of the Lung:

early-Phase Sequential High-Resolution Computed Tomographic

Findings. J Comput Assist Tomogr. 2008;32:806–9.

10. Esper A, Force S, Gal A, Wolfenden LL. A 36-year-old woman

with hemoptysis and a lung mass 3 months after delivery. Chest.

2006;130:1620–3.

Jpn J Radiol (2013) 31:143–147 147

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