BACKGROUND: Fetal adenocarcinoma of the lung is a rare subtype of pulmonary adenocarcinoma with a relative estimated incidence of 0.5% or fewer of all lung cancers. Because of its extreme rarity, there have been no controlled clinical trials investigating treatment regimens for fetal adenocarcinoma and, as a result, there are no guidelines for management. CASE PRESENTATION: We report a case of a well-differentiated fetal adenocarcinoma, which is a variant of pulmonary blastoma, that is a low-grade malignancy and associated with a good prognosis. A 29-year-old Moroccan man presented with a well-differentiated fetal adenocarcinoma staged T3N0M0, who received 3 cycles of neoadjuvant chemotherapy followed by surgery, with no recurrence at 2 years follow-up. CONCLUSION: Fetal adenocarcinoma is a rare suptype of adenocarcinoma. Surgical resection is the treatment of choice for resectable disease. The role of chemotherapy in the neoadjuvant setting or adjuvant setting is not well defined

Abdellatif Benosman

Fahd Ouchen

Hassan Errihani

Meriem Aitelhaj

Nabil Ismaili

Saber Boutayeb

Sihame Lkhoyaali

BMC Research Notes

PubMed

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Lkhoyaali et al. BMC Research Notes 2014, 7:283
http://www.biomedcentral.com/1756-0500/7/283CASE REPORT Open AccessNeoadjuvant chemotherapy in well-differentiated
fetal adenocarcinoma: a case report
Sihame Lkhoyaali1*, Saber Boutayeb1, Nabil Ismaili2, Meriem Aitelhaj1, Fahd Ouchen3, Abdellatif Benosman3
and Hassan Errihani1Abstract
Background: Fetal adenocarcinoma of the lung is a rare subtype of pulmonary adenocarcinoma with a relative
estimated incidence of 0.5% or fewer of all lung cancers. Because of its extreme rarity, there have been no
controlled clinical trials investigating treatment regimens for fetal adenocarcinoma and, as a result, there are no
guidelines for management.
Case presentation: We report a case of a well-differentiated fetal adenocarcinoma, which is a variant of pulmonary
blastoma, that is a low-grade malignancy and associated with a good prognosis. A 29-year-old Moroccan man
presented with a well-differentiated fetal adenocarcinoma staged T3N0M0, who received 3 cycles of neoadjuvant
chemotherapy followed by surgery, with no recurrence at 2 years follow-up.
Conclusion: Fetal adenocarcinoma is a rare suptype of adenocarcinoma. Surgical resection is the treatment of
choice for resectable disease. The role of chemotherapy in the neoadjuvant setting or adjuvant setting is not
well defined.
Keywords: Well-differentiated fetal adenocarcinoma, Chemotherapy, PrognosisBackground
Fetal adenocarcinoma (FA) of the lung is a rare subtype
of pulmonary adenocarcinoma that exhibits the same
tissue architecture and cell characteristics to fetal lung
tissue in microscopic examination. It was considered as
a variant of blastoma but according to the latest World
Health Organization (WHO) classification (2004), it is
currently considered as a variant of solid adenocarcinoma
with mucin production [1].
FA is a rare tumor, with a relative estimated incidence
of 0.5% or fewer of all lung cancers [2-5]. Because of its
extreme rarity, there have been no controlled clinical trials
investigating treatment regimens for FA and, as a result,
there are no guidelines for management [5].
Complete surgical resection is the treatment of choice
of FA, similarly to all subtypes of non- small cell lung
cancer (NSCLC) [6]. Some case reports suggest that FA is
rarely sensitive to chemotherapy (CMT) or radiotherapy* Correspondence: s.lkhoyaali@gmail.com
1Department of Medical Oncology, National Institute of Oncology, Rabat,
Morocco
Full list of author information is available at the end of the article
© 2014 Lkhoyaali et al.; licensee BioMed Centr
Commons Attribution License (http://creativec
reproduction in any medium, provided the or
Dedication waiver (http://creativecommons.or
unless otherwise stated.[2]. An anecdotal case report shows that chemotherapy
with UFT® (tegafur uracil) may be useful in FA [7].
We report a case report of FA managed by neoadju-
vant CMT and surgery.
Case presentation
A 29-year-old Moroccan man without medical history,
had a five pack-years smoking history and stopped
smoking seven years ago. He presented with a four-
month history of chest pain and minimal hemoptysis.
The physical exam was normal. A chest X-ray (Figure 1)
showed a large left well- rounded pulmonary opacity.
A chest computed tomography (CT) scan showed a
tumoral lesion at the left upper lobe measuring 12.5 ×
8 cm. This process was well limited, heterogeneous con-
taining calcifications and areas of necrosis extended
into the chest wall without bone lysis or lymph nodes
(Figure 2A) staged T3N0.
Bone scintigraphy, cerebral and abdominal CT scan
showed no evidence of distant metastasis. Trans-thoracic
biopsy was performed, histopathological study of the
biopsy specimen showed a numerous glands showing an
endometrioid morphology, occasional squamoid morulesal Ltd. This is an Open Access article distributed under the terms of the Creative
ommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
iginal work is properly credited. The Creative Commons Public Domain
g/publicdomain/zero/1.0/) applies to the data made available in this article,
Figure 1 Chest X-ray showing a large left pulmonary opacity.
Lkhoyaali et al. BMC Research Notes 2014, 7:283 Page 2 of 4
http://www.biomedcentral.com/1756-0500/7/283and relatively clear cytoplasm, the Ki-67 was 1% (low pro-
liferation index) and based on these histopathological
findings, the diagnosis of fetal adenocarcinoma was con-
cluded (Figure 3), then the patient received neoadjuvant
CMT based on etoposide at dose of 120 mg/m2 day one
to three and cisplatin at 100 mg/m2 on day one every
three weeks. Evaluation after three cycles showed disease
stabilization according to Response Evaluation Criteria In
Solid Tumors (RECIST) (as immunohistochemistry was
unavailable).
Thirty days after the last cycle of CMT the patient
underwent a left upper lobectomy with lymphadenec-
tomy (Figure 4). The microscopic examination of the
specimen found a tumor characterized by two compo-
nent lesions, the first composed with well-differentiated
elements of glandular proliferation rarely isolated or
grouped in clusters (polyadenoid structures), which were
sometimes separated by undifferentiated beaches of
cells with blastomatous differentiation showing moderateFigure 2 Chest computed tomography scan. (A): lesional process of the
2 years.cytonuclear atypia and a high mitotic activity. The tumor
resection was complete with negative lymph node. The
postoperative course was without anomalies.
The patient underwent a chest CT scan assessment
every 3 months during the first year and then every
6 months during the second year. At 2 years of follow-up,
there is no evidence of disease recurrence (Figure 2B).
Discussion
In 1982, Kradin et al. described fetal adenocarcinoma
firstly as a very rare subtype of malignant lung cancer
[8]. In pulmonary blastoma, sex distribution was equal
and the peak incidence was (35-40 years) of age, 80% of
patients are smokers [4]. These are being commonly diag-
nosed at an early stage without involvement of lymph
node.
At the histological level, the element of WDFA charac-
teristically shows glandular elements with tubules com-
posed of glycogen-rich, non ciliated cells that resemble
fetal lung, tubuless and squamoid morules may be seen
with clear nuclei within lumens. The immature mes-
enchyme and epithelium mimic the embryonic lung
at 10-16 weeks gestation [9,10].
Surgical resection is the standard treatment for patients
with pulmonary blastoma [4,5], despite the fact that there
have been reports of limited success with adjuvant radio-
therapy and chemotherapy [5].
The prognosis of pulmonary blastomas is poor, although
prognosis of WDFA is better than biphasic [11], particu-
larly when resection is complete, with a mortality rate of
14% and 52% respectively [4].
Our understanding of fetal adenocarcinoma is derived
from case reports and small series. Koss et al. reported
28 cases of WDFA, with long follow up of 95 months,
and 5-year survival of 81%. Sato et al. reported 25 cases;
the vast majorities has small size and were N0 at 88% of
cases [11,12]. Van Loo et al. previously reported 9 cases
of WDFA there were beyond T3 stage and underwent
postoperative or radiation therapy however the benefit
of this treatment was unclear [13].left upper lobe before treatment. (B): No signs of recurrence after
Figure 3 Microscopic examination of trans-thoracic biopsy showing a numerous glands showing an endometrioid morphology,
occasional squamoid morules and relatively clear cytoplasm. (A): hematoxylin-eosin staining, original magnification ×10. (B): hematoxylin-eosin
staining, original magnification ×40.
Lkhoyaali et al. BMC Research Notes 2014, 7:283 Page 3 of 4
http://www.biomedcentral.com/1756-0500/7/283Our patient received 3 cycles of etoposide – cisplatin
protocol. We chose this protocol because of the sensibil-
ity of fetal tumors to the combination based on etoposid
and cisplatin-like nephroblastoma. Tumor response was
assessed by chest CT scan after 3 cycles of CMT, and we
showed 12% reduction of the tumor mass corresponding
to a stable disease according to RECIST Criteria, this is
due to a low proliferation of his tumor (index of prolifer-
ation, Ki-67 was 1%).
Thus the role of neoadjuvant CMT in WDFA remains
unknown, but we conclude that CMT is ineffectiveFigure 4 Macroscopic appearance of the tumor.probably because the tumor is not proliferative, however
it should be noted that Zaidi [14] has reported a case of
WDFA treated with neoadjuvant CMT with mitomycin,
ifosfamide and cisplatin for a WDFA staged T4N0M0 in a
woman of 27 years, which successfully downstaged the
tumor before surgical resection, with good control at
29 months. Also Chanhee et al. reported the first case of
locally advanced WDFA treated with concurrent chemora-
diation therapy with docetaxel with partial response [15].
But we have no idea of the proliferation index, and the
cornerstone of treatment is surgery as much as possible.
Lkhoyaali et al. BMC Research Notes 2014, 7:283 Page 4 of 4
http://www.biomedcentral.com/1756-0500/7/283Conclusion
Fetal adenocarcinoma is a rare suptype of adenocarcin-
oma with a better prognosis and is most commonly
diagnosed at early stage with no lymph node involvement.
Surgical resection is the treatment of choice for resectable
disease. The role of CMT in neoadjuvant setting or adju-
vant setting is not well defined.
Consent
Written informed consent was obtained from the patient
for publication of this Case report and any accompany-
ing images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
Abbreviations
FA: Fetal adenocarcinoma; WDFA: Well-differentiated fetal adenocarcinoma;
WHO: World health organization; NSCLC: Non small cell lung cancer;
RT: Radiotherapy; CMT: Chemotherapy; CT: Computed tomography;
RECIST: Response evaluation criteria in solid tumors.
Competing interests
The authors declare that they have no competing interests.
Authors’ contribution
SL was involved in the analysis of the data and the literature research, and
she also wrote the manuscript, SB and MA helped with the literature
research. NI helped with the patient management and revision of the
manuscript. FO and BA contributed to the surgical treatment, HE approved
the treatment and analyzed the literature data. All authors read and
approved the final manuscript.
Acknowledgments
We would like to thank F. Kettani of pathology center (nations unies) for its
cooperation and help in making the slides and the printing thereof.
Author details
1Department of Medical Oncology, National Institute of Oncology, Rabat,
Morocco. 2Department of Medical Oncolgy, Marrakech, Morocco.
3Department of thoracic surgery, Hospital Avicenne, Rabat, Morocco.
Received: 15 September 2013 Accepted: 28 April 2014
Published: 5 May 2014
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Neoadjuvant chemotherapy in well-differentiated fetal adenocarcinoma: a case report

http://dx.doi.org/10.1186/1756-0500-7-283

Neoadjuvant chemotherapy in well-differentiated fetal adenocarcinoma: a case report

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