Lung Cancer 84 (2014) 92–95

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Lung Cancer
journal homepage: www.elsevier.com/locate/lungcan

Case report

Adenocarcinoma arising in an extralobar sequestration: a case report

and review of the literature
Deborah Belchis d,∗ , Morgan Cowan a , Keith Mortman b , B. Rezvani c
a
Johns Hopkins University, Baltimore, United States
b
George Washington University, Hospital 900 23rd St, NW, Washington DC 20037, United States
c
Georgetown University School of Medicine, 110 Irving St, NW, Washington DC 20007, United States
d
Johns Hopkins University, Bayview Medical Center, 4940 Eastern Ave. , Baltimore, MD, United States

a r t i c l e i n f o a b s t r a c t

Article history: Extralobar sequestration is a type of bronchopulmonary foregut malformation defined as an isolated
Received 17 October 2013 portion of lung tissue with a systemic arterial supply, its own pleural investment, and no bronchial
Received in revised form communication. While it may be recognized in utero or in the neonatal period, depending on its location
17 December 2013
and associated anomalies, it can also go unrecognized until later in life when it may present as a mass. We
Accepted 27 January 2014
report the first case of adenocarcinoma arising in an extralobar sequestration. The patient was a 70-year
old man with a 55 pack year smoking history who presented with chest discomfort and was found to
Keywords:
have a 6.5 cm right lower lobe mass. Percutaneous biopsy of the mass was positive for adenocarcinoma. At
Extralobar sequestration
Intralobar sequestration
surgery, the mass was noted to have a separate arterial connection, no bronchial communication, and its
Adenocarcinoma own pleural investment, consistent with an extralobar sequestration. Malignancy arising in pulmonary
Bronchopulmonary foregut malformations sequestrations is rare and the few reported cases have been in intralobar types. Carcinoma arising in
this setting adds to the dilemma of whether or not these developmental anomalies should be excised or
followed. Our tumor, while small, did have vascular invasion.
© 2014 Elsevier Ireland Ltd. All rights reserved.

1. Introduction
Pulmonary sequestrations (PS) form a subset of bronchopul-
monary foregut malformations, defined as portions of lung tissue
lacking a bronchial connection and possessing their own systemic
arterial blood supply. They are further segregated into extralobar
(ELS) and intralobar (ILS) variants depending on whether or not
they are encased in their own visceral pleura or are enclosed within
the normal visceral pleura of the lung [1]. ELS’s are more likely
than ILS’s to be associated with other congenital anomalies such
as diaphragmatic hernia or congenital heart disease. While PS’s are
typically identified early in life, approximately 15% may go unrec-
ognized until adolescence or adulthood. At that time patients may
present with hemoptysis, mass effect and secondary symptoms, or
signs of infection [2]. We present the first case of malignancy arising
in an ELS.
2. Case report
The patient was a 70-year old man with a 55 pack year smok-
ing history who presented with chest discomfort on December
∗ Corresponding author. Tel.: +1 410 550 0671; fax: +1 410 550 0075.
E-mail addresses: dbelchi1@jhmi.edu (D. Belchis), mcowan6@jhmi.edu
(M. Cowan), kmortman@mfa.gwu.edu (K. Mortman).
2012. A chest x-ray was read as abnormal and subsequent chest
CT scan confirmed the presence of a 6.5 cm right lower lobe mass
(Fig. 1A) and subcarinal lymphadenopathy. The lesions were hyper-
metabolic with an SCV of 2.2. Percutaneous biopsy identified a
moderately differentiated adenocarcinoma. The patient was stage
IIA (T2BN0M0) by PET/CT and staging mediastinoscopy. Preoper-
ative pulmonary function testing was within normal limits and a
thoracoscopic right lower lobectomy was performed.
At surgery, isolated lung tissue with a separate pleural invest-
ment and an independent blood supply arising within fatty tissue
above the right hemi-diaphragm was identified (Fig. 1B). The fis-
sure between the pulmonary sequestration and the right lower
lobe was divided; no communication with the right lung was
appreciated—consistent with an extralobar sequestration.
The specimen consisted of a 108 g (post fixation)
8.5 × 6.0 × 4.0 cm segment of lung tissue. The entire specimen
was invested by pleura. An 8.0 cm white tan rubbery pleural
plaque was present. On sectioning, a firm lesion with an associated
4 mm calcified nodule was noted.
Pathologic examination revealed a 6 mm moderately differen-
tiated TTF-1 positive adenocarcinoma (Fig. 2A). The tumor could
be seen arising from a bronchiole (Fig. 2B.) A focus of large ves-
sel invasion was identified (Fig. 2C). Next generation sequencing
identified a BRAF-mutation. The background lung parenchyma is
distorted with diffuse interstitial fibrosis and pulmonary hyperten-
sive changes (Fig. 2D). An associated congenital pulmonary airway

0169-5002/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.lungcan.2014.01.025
 D. Belchis et al. / Lung Cancer 84 (2014) 92–95 93

Key: M, male; F, female; Y, yes; N, no;?, unknown; R, right lung; L, left lung; ILS, intralobar sequestration; ELS, extralobar sequestration; BPFM, communicating bronchopulmonary foregut malformation; Adeno, adenocarcinoma;
report
Refs.

This
[10]
[3]

[4]

[5]

[6]

[7]
[8]

[9]
pathologic findings

vascular changes,

vascular changes
Fibrosis, HTN

Fibrosis, HTN
metaplasia
Additional

squamous

AWNED 10 months

Widely metastatic

Squam, squamous cell carcinoma; LEL, lymphoepithelial lesion; EBV+, Ebstein-Barr Virus positive; AWNED, alive with no evidence of disease; DOD, dead of disease; HTN hypertensive.
AWNED, 5 years

AWNED, 4 years
Follow-up

None

None

None

DOD
Sleeve segment-ectomy

Pneumo-nectomy
Lobectomy

Lobectomy

Lobectomy

Lobectomy

Lobectomy
Treatment
Location of tumor

Proximal margin
L upper division

Fig. 1. (A) CT scan of mass (arrow), (B) intraoperative photograph illustrating the
vascular pedicle (arrowhead) and the pleural plaque (thick arrow).
Subpleural

Subpleural

Subpleural
bronchus
Medial

Hilus

malformation (CPAM) was absent. A pleural plaque was noted. A

?

small bronchus with associated cartilage was noted in one section,

Diagnosis

suggestive of bronchial atresia. Precursor mucinous cells were not

Squam

Squam

Squam

Squam
Adeno

Adeno

Adeno

Adeno

identified in the examined sections.

EBV+
LEL-

3. Discussion
BPFM
Type

?ELS

Malignancy is a rare complication of bronchopulmonary foregut

ELS
ILS

ILS

ILS

ILS

ILS

ILS

malformations. To our knowledge this is the first report of ade-

nocarcinoma arising in an extralobar sequestration. Our review
Location

of the literature revealed seven other cases of carcinoma arising

in a pulmonary sequestration and one arising in a sequestered
R

R
L

portion of lung tissue with an esophageal communication (com-

municating bronchopulmonary foregut malformation) (Table 1)
[3–10]. Six of these were ILS and in one case the type of seques-
Long standing dysphagia

tration was unclear. Including our case, the patients’ ages ranged
Non-productive cough,

Cough, digital clubbing

Hemoptysis, recurrent

from 31 to 70, and there were six men and three women. All of the
hemoptysis, fever

Chest discomfort

sequestrations were in the lower lobes except for case 3 where the
Fever, infection

exact location within the left lung was not described. Three of the
Presentation

pneumonia
Chest pain
Incidental

Incidental

patients smoked, three were non-smokers and in three the smok-

ing history was not indicated. Five of the tumors were squamous
cell carcinomas, three were adenocarcinoma, and one was an EBV
associated lymphoepithelioma–like carcinoma. The location of the
tumor within the malformation was variable and not mentioned in
Smoker

every case. The patients were treated by surgical resection and most
did well. One patient had widely metastatic disease and it remains
Patient characteristics.

N
Y

Y
?

uncertain if the tumor within the sequestration was a metastasis

or primary.
Sex

M
F

F
F

The exact pathway leading to the development of carcinoma in

the sequestrations is not known. One hypothesis is that seques-
Table 1

Age

trations are manifestations of an underlying cancer predisposition

50

69

59

65

36
31

67

40

70

syndrome like cystic pleuropulmonary blastoma, where there is

94 D. Belchis et al. / Lung Cancer 84 (2014) 92–95
Fig. 2. (A) Invasive adenocarcinoma, (B) partial replacement of bronchiolar structure by in situ carcinoma, (C) vascular invasive, and (D) background interstitial fibrosis and
vascular hypertensive changes (Hematoxylin and Eosin, 100x, 400x, 400x, 40x, A, B, C, D respectively).
progression from an indolent premalignant cystic lesion to an
aggressive sarcoma [11]. However, malignancy is rare in seques-
trations and there is no reason to suspect that sequestrations form
part of a cancer predisposition syndrome. A second hypothesis is
that sequestrations have an innate propensity to undergo malig-
nant degeneration as is believed to occur in the mucinous cells in
type 1 CPAMs. However, this hypothesis does not explain malig-
nancy in sequestrations, as similar precursor cells have not been
identified in sequestrations. Mutation analysis of non-mucinogenic
cells in sequestrations was negative for MUC5a and KRAS wild type
[12].Therefore, regarding the sequestration cases, the lack of muci-
nous cells, the absence of mucinous adenocarcinoma morphology,
and the relative frequency of squamous cell carcinoma suggest
a different pathway for the development of carcinoma than that
hypothesized for the mucinous adenocarcinomas arising in type 1
CPAMs. Additionally, all of the sequestration malignancies occur in
older patients (the youngest patient was 31 years of age), whereas
pleuropulmonary blastomas arise solely in children (median age
of 43 months) and CPAM-related mucinous adenocarcinomas are
usually identified in younger patients (median age of 20 years) [11].
A third possible pathway is that of chronic inflammation and irri-
tation. This is quite likely the pathogenesis for the EBV+ related LEL
case. In our case and case 2, there was extensive interstitial fibrosis
and hypertensive changes which have been described in sequestra-
tions and is most likely related to the aberrant arterial blood supply.
In case 2 areas of bronchiolar and squamous metaplasia were noted
raising the possibility that chronic hypoxic conditions play a role
in the pathogenesis.
Therefore, the etiology of the carcinomas in the sequestration
cases may be multifactorial and may include chronic inflammation
and irritation. The possibility that the developmental lesion is more
susceptible to these insults may be a factor although the lack of
young affected patients argues against this.
These cases present difficulty in management, since standard
diagnostic approaches may fail. As these lesions do not communi-
cate with the bronchial tree, sputum cytology and bronchoscopic
sampling are useless. Our patient underwent a percutaneous needle
biopsy to obtain a diagnosis.
The therapy for pulmonary sequestrations is controversial. If
asymptomatic, they are often left alone. For those patients with
recurrent infections or other symptoms, surgery or embolization or
both have been recommended [13]. Although the incidence of car-
cinoma is low, its existence has provided an argument for surgery
[14]. At the least, it seems these patients should have close clinical
follow up.
In summary, we present the first reported case of adenocarci-
noma arising in an extralobar sequestration.
Conflict of interest
None declared for all authors.
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