Case 10-2012 A 16-Year-Old Boy with Epigastric Pain and a Mediastinal

Mass
Cassandra M. Kelleher, M.D., David G. Forcione, M.D., Michael S. Gee, M.D., Ph.D., and Mari MinoKenudson, M.D.
N Engl J Med 2012; 366:1241-1249March 29, 2012
Article
References
Video

Upper Gastrointestinal Endoscopy and Endoscopic Ultrasonography.

Presentation of Case
Dr. Jennifer C. Hensley (Pediatrics): A 16-year-old boy was admitted to this hospital because of
abdominal pain and a mediastinal mass.
The patient had been well until 4 days before admission, when he began to feel vaguely ill. The
next day, nonbloody emesis occurred. Two days before admission, epigastric pain, nausea,
decreased appetite, and constipation developed. On the morning of admission, he took laxatives
and acetaminophen, without relief. He saw his pediatrician; a tentative diagnosis of pancreatitis
was made, and the patient was sent to the emergency department at an affiliated hospital. On
arrival, he rated the pain at 10 on a scale of 0 to 10 (with 10 indicating the most severe pain). He
had not had fever, additional episodes of vomiting, or diarrhea. On examination, the weight was
138.5 kg, the temperature 36.7C, the blood pressure 155/75 mm Hg, the pulse 88 beats per
minute, the respiratory rate 36 breaths per minute, and the oxygen saturation 100% while he was
breathing ambient air. The abdomen was soft, with moderate tenderness in the epigastrium and
right upper quadrant; the remainder of the examination was normal. Levels of platelets,
electrolytes, albumin, alkaline phosphatase, calcium, creatine kinase isoenzymes, and troponin I
were normal, as were tests of renal function; other test results are shown in Table 1Table 1

Blood and Fluid Analyses.. An electrocardiogram was normal. Computed

tomography (CT) of the abdomen after the administration of intravenous contrast material

revealed a cystic mass, 12.4 cm by 6.1 cm by 6.2 cm, in the posterior mediastinum above the
gastroesophageal junction, which displaced the inferior vena cava, the heart, and the distal
esophagus; hepatic steatosis and trace bilateral pleural effusions were also present. Morphine (5
mg) was administered intravenously with transient improvement (the patient rated the pain at 3
out of 10) within 4 minutes; ranitidine and normal saline were also given. The patient was
transferred to this hospital by ambulance for further evaluation; morphine (4 mg) was
administered for recurrent pain en route.
On arrival, the patient described the pain as sharp; radiating to his back; worsening with
movement, deep inspirations, and swallowing; and improving slightly with sitting upright. He
reported having the sensation of food sticking in his throat and having a mild cough and sore
throat for 2 to 3 days. Blood-pressure recordings and serum levels of glycated hemoglobin and
insulin had reportedly been elevated in the recent past. He had no known allergies. He lived with
his mother, a sibling, and two dogs, and he attended high school. His father had had type 2
diabetes and hypertension and died at 50 years of age after a stroke; his mother had had
gestational diabetes and cholestatic pancreatitis and had hypertension.
On examination, the patient was obese, alert, and in distress because of pain. The blood pressure
was 159/67 mm Hg, the pulse 95 beats per minute, and the respiratory rate 20 breaths per minute;
the temperature and oxygen saturation while he was breathing ambient air were normal.
Respirations appeared slightly labored from pain, without crackles, rhonchi, wheezing, or stridor.
Bowel sounds were normal; there was epigastric tenderness to palpation, with guarding; there
was no rebound, palpable mass, or ecchymoses. The spine was tender to palpation in the
midlumbar region, and there was hyperpigmentation of the axillae consistent with acanthosis
nigricans. The remainder of the examination was normal. A chest radiograph showed retrocardiac
opacity. CT of the chest confirmed the presence of a posterior mediastinal cystic mass. Within the
mass, there was a linear area of hyperdensity adjacent to the esophagus that was mobile on
images obtained with the patient in the prone position and was thought to represent either
calcifications within the mass or extraluminal extravasation of oral contrast material due to
communication between the esophagus and the mass. Bilateral pleural effusions were greater than
those in the study performed less than 24 hours earlier. Morphine was administered intravenously,
and oral intake was withheld.
During the first day, the temperature rose to 39.0C. Thoracentesis of the right pleural effusion
was performed (Table 1). The prothrombin time was 14.9 seconds (reference range, 10.8 to 13.4);
serum levels of electrolytes, human chorionic gonadotropin, and alpha-fetoprotein were normal,
as were the partial-thromboplastin time and tests of renal function; other laboratory-test results
are shown in Table 1. A barium-swallow examination revealed a smooth extrinsic impression of
the distal esophagus, without extraluminal leakage of contrast material. During the next 2 days,
the temperature rose to 39.6C. Culture of the blood was sterile. Magnetic resonance imaging
(MRI) of the chest was aborted because of the patient's discomfort; limited imaging was
performed.
On the third day, a diagnostic procedure was performed.
Differential Diagnosis
Dr. Cassandra M. Kelleher: May we review the imaging studies?

Dr. Michael S. Gee: A chest radiograph showed a mass in the retrocardiac space that is visible

through the heart on the frontal view (Figure 1AFigure 1

Imaging Studies.). A
CT scan of the chest showed a large cystic mass in the posterior mediastinum, abutting the
esophagus (Figure 1B). The attenuation values of the mass were 10 to 20 Hounsfield units,
densities consistent with fluid with some proteinaceous component. The mass contained an area
of high density along its posterior margin that was mobile on images obtained while the patient
was in the supine and prone positions. Because the patient had received oral contrast material for
the abdominal CT that was performed earlier, it was unclear whether the area of high density
represented internal calcifications within the mass or retained contrast material from the
esophagus. Bilateral pleural effusions were present at the lung bases and had increased in size
since the study performed 24 hours earlier (Figure 1C). This suggested that the cystic lesion either
had eroded into the pleural space or was causing irritation of the pleura from mass effect or
associated inflammation.
To evaluate for communication between the cystic mass and the esophagus, a barium-swallow
study was performed during the administration of oral contrast material. Narrowing of the distal
esophagus and the gastroesophageal junction by the mass was apparent, without evidence of
communication. In order to characterize the enlarging pleural fluid collections, ultrasound-guided
thoracentesis was performed. Clear, serous pleural fluid was aspirated, which was not bloody,
purulent, or chylous.
MRI was then attempted to better characterize the nature of the cystic mass seen on CT. The
examination was terminated early because of the patient's discomfort and respiratory distress.
Limited T2-weighted images through the mediastinum (Figure 1D) in the coronal plane showed
that the large mass was predominantly cystic, with T2-weighted hyperintense fluid. The mass had
considerable internal complexity, as indicated by multiple T2-weighted hypointense linear
septations coursing through the lesion that were not apparent on CT. Because we were unable to
administer intravenous contrast material, we could not assess whether the mass had any solid
enhancing components.
In summary, the imaging studies show a large cystic mass in the posterior mediastinum, with
internal complexity evidenced by septations and probable calcifications. The lesion was
associated with enlarging bilateral pleural effusions; however, there was no evidence of
communication between the mass and the esophagus or the pleural space.
Dr. Kelleher: I am aware of the diagnosis in this case. Because of the patient's presenting
symptom of severe pain and the presence of mobile, high-attenuation areas within the cystic
cavity on CT, we were initially concerned about an esophageal perforation. Esophagography
ruled out ongoing leakage from a perforation. Ultrasound-guided thoracentesis was performed
because of enlarging pleural effusions; examination of the fluid did not reveal evidence of
infection and showed that it was not chylous.
Posterior Mediastinal Cystic Masses in Children

Imaging studies in this patient revealed a posterior mediastinal cystic lesion. Anatomical division
of the mediastinum into its three compartments anterior, middle, and posterior or visceral
helps with the generation of the differential diagnosis, since mediastinal cysts are derived from
the anatomical structures that reside within the respective compartments; therefore, the types of

tumors and cysts vary among the compartments (Table 2Table 2

Mediastinal
Cystic Masses According to Mediastinal Compartment.). Of all mediastinal tumors in adults,
approximately 15% are cysts; in children, approximately 7.5% are cysts1 (Table 2). Although
delineation of the cyst in the posterior compartment narrowed the differential diagnosis, several
possible diagnoses with different treatment strategies remained in the differential diagnosis.
Myelomeningocele
Myelomeningocele or meningocele is a form of spina bifida, in which failure of the neural tube to
close during the first month of gestation results in herniation of meninges with or without neural
tissue; this usually involves the posterior lumbar spine and is typically diagnosed prenatally or in
the neonatal period. Paralysis and bladder and bowel incontinence can be severe consequences.2
Rare cases involving the anterior spine and presenting in the posterior mediastinum have been
reported.1-3 In this previously healthy teenager, myelomeningocele would be a very unlikely
diagnosis.
Lymphatic Malformations
Lymphatic malformations, formerly called cystic hygroma or lymphangioma, are thought to result
from the failure of lymphatic channels to connect to the efferent system during development. This
results in a collection of abnormal, dilated lymphatic channels or cysts. These commonly present
before the second year of life but have also been diagnosed in adolescents and adults.4,5 Patients
with lymphatic malformations can present with symptoms from compression of surrounding
structures that can include cough, dyspnea, stridor, dysphagia, superior vena cava syndrome, and
Horner's syndrome.6 Acute symptoms such as severe chest pain, shortness of breath, and fever
can result from hemorrhage into the lesion or infection.7,8 There are also reports of chylous
pericardial and pleural effusions developing in patients who have mediastinal lymphatic
malformations.9,10 CT and MRI reveal thin-walled, nonenhancing, multiloculated cystic
structures that may have fluidfluid levels indicating previous hemorrhage. Both the presenting
symptoms and imaging findings in this patient were consistent with a lymphatic malformation.
Foregut Duplications
Foregut duplications (e.g., bronchogenic cysts; esophageal, gastric, and duodenal duplications;
and neurenteric cysts) arise from aberrant budding of the trachea from the primitive foregut,
abnormal separation of the trachea and esophagus, or the persistent adherence of the endoderm to
the notochord early in development. The presence of gastric or pancreatic secretory mucosa
within the wall of these duplications can lead to ulceration, as well as bleeding, stricture
formation, or perforation, causing acute symptoms such as those seen in this patient.
Thoracic foregut duplications are reasonably common and include bronchogenic cysts,
esophageal duplications, and neurenteric cysts. Bronchogenic cysts are typically located in the
middle mediastinum, often in the hilum of the lung, and may have a connection to the airway.
Esophageal duplications are usually seen in close association with the distal esophagus, in the

posterior mediastinum. Neurenteric cysts are a rare form of duplication cyst that is connected to
the dura of the spinal canal; these are often seen in conjunction with vertebral anomalies.
Presenting symptoms in patients with foregut duplication cysts are similar to those seen in this
patient and include respiratory symptoms such as cough, hemoptysis, pneumonia, dyspnea and
asthma, and vomiting; a minority of patients are asymptomatic.11 Hemorrhage into the cyst,
infection, and perforation can lead to presentation with acute symptoms such as chest or
epigastric pain, dyspnea, and fever.12,13 Patients with neurenteric cysts can initially present with
neurologic symptoms associated with cord or nerve-root compression as well as with intralesional
hemorrhage or infection.11,14,15 In this patient, diagnostic imaging with the use of CT, contrast
esophagography, and MRI revealed a thin-walled cyst, extrinsic compression of the esophagus,
no evidence of perforation, and no relationship to the spinal cord all findings consistent with a
foregut duplication cyst.11,15 A neurenteric cyst was no longer considered a possibility, since no
connection to the spinal canal and no vertebral abnormalities were detected. Although the location
in the posterior mediastinum favored an esophageal duplication cyst, both a lymphatic
malformation and a bronchogenic cyst remained in the differential diagnosis.
The acute presentation in this previously well patient suggested that there was either infection or
hemorrhage into the cyst. We were particularly concerned that the lesion might be infected, since
the patient was febrile and had an elevated white-cell count. Distinguishing between infection and
hemorrhage was important in determining the treatment. Treatment of a lymphatic malformation
could include percutaneous sclerotherapy, resection, or both. If the lesion were infected, we
would initiate a course of antibiotics and perform an operation later, since there is increased risk
of complications when operating on infected lesions of these types.
The diagnostic test of choice was endoscopic ultrasonography.
Dr. David G. Forcione: Endoscopic ultrasonography is a technique in which a specially designed
endoscope (echoendoscope) that has both optical and ultrasound functionality is placed into the
gastrointestinal lumen to view mural and extramural structures. Through an accessory channel on
the echoendoscope, fine-needle aspiration of structures such as intraperitoneal, retroperitoneal,
and mediastinal lesions may be performed across the wall of the gastrointestinal tract.
Cystic lesions of the mediastinum such the one in this patient are uncommon, and endoscopic
ultrasonography has allowed the characterization of these lesions both morphologically and by
fine-needle aspiration. On ultrasonography, the lesions can be characterized as anechoic (i.e.,
completely lacking internal echogenicity and appearing black on the images) or hypoechoic (i.e.,
having more complex, heterogeneic internal echogenicity).16 In one study, lesions that were
anechoic were confirmed to be benign foregut duplication cysts in all the cases, whereas those
that were hypoechoic were a heterogeneous group of lesions, with 40% representing necrosis or
cystic change in a malignant tumor or granulomatous lymphadenitis.16
Endoscopic ultrasonography was performed with the patient under general anesthesia, with
antibiotic prophylaxis. A standard upper endoscopy was also performed initially, to evaluate the
mucosa and to assess for luminal stenosis. The upper endoscopy revealed two key findings: a
normal squamous esophageal lining and extrinsic compression of the distal third of the
esophageal lumen (see Video 1, available with the full text of this article at NEJM.org).
Endoscopic ultrasonography was performed with a linear array echoendoscope at 5 MHz (see
Video 2). A large, complex cystic lesion was readily identified in the mediastinum. The lesion

measured 70 mm by 40 mm in maximal cross-sectional diameter. Echogenic material in the cystic

space was worrisome for the possibility of either purulent material or blood. On the basis of the
morphologic features of the endoscopic ultrasound examination, the differential diagnosis
included lymphangioma and a foregut duplication cyst (an esophageal duplication cyst or a
bronchogenic cyst). Because of the heterogeneous echogenicity, there was concern about the
possibility of intralesional hemorrhage, infection, or both.
Fine-needle aspiration of the cystic lesion with the use of a Doppler-guided, transesophageal

approach with a 19-gauge needle was performed (Figure 2AFigure 2

Endoscopic
Ultrasonography and Intraoperative Image.). The aspiration yielded 75 ml of nonchylous,
serosanguinous fluid, which was submitted for analysis and culture (Table 1).16-19
Dr. Kelleher: The results of the fluid analysis (Table 1) showed no evidence of infection, no
elevation of lipid levels to indicate the presence of chyle, and a markedly elevated amylase level.
Cytologic examination revealed no malignant cells. Together with the imaging results, these tests
gave us the definitive diagnosis of a noninfected esophageal duplication cyst. Elevated amylase
levels have been documented in esophageal duplication cysts, and the excess amylase is thought
to be secreted by ectopic pancreatic mucosa. Enzyme production most likely led to intralesional
hemorrhage, causing the patient's acute symptoms.
Discussion of Management
Dr. Kelleher: Complications of foregut duplication cysts include infection, bleeding, and clinical
symptoms from compression of the surrounding structures. There are also reports of malignant
tumors arising from esophageal duplications and bronchogenic cysts.20,21 For these reasons,
complete surgical excision is the treatment of choice. Excising lesions that are infected increases
the risk of operative complications and incomplete resection because of the inflammation of
surrounding tissues.22,23 Most surgeons advocate aggressive treatment of acutely infected
lesions with interval resection after resolution of the inflammation. Incomplete resection is
avoided because of the risk of malignant degeneration and recurrence of the cyst.24
Esophageal duplications can be approached through an open thoracotomy or a thoracoscopic
approach. Retrospective reviews indicate that thoracoscopic resection is effective and safe.21
Available evidence suggests that the duration of chest-tube drainage and recovery time may be
minimized by thoracoscopic resection.13,25 This patient underwent an uncomplicated resection
by means of a left thoracotomy. The cystic mass was easily visualized in the posterior inferior
mediastinum underlying the visceral pleura. Inflammatory lymph nodes were tethering the mass
to the inferior pulmonary vein but were separated from the cyst without incident. The cyst was
enveloped within the muscular wall of the esophagus and shared a common mucosal wall (Figure
2B). Inflammation between the wall of the cyst and the mucosa of the esophagus led to
inadvertent entry into the cystic cavity. Brownish gelatinous material, consistent with old blood,
was evacuated. Cultures of this material were sterile. The cystic mass was removed entirely, and
the muscular layer of the esophageal wall was reapproximated.

Dr. Cassandra M. Kelleher's Diagnosis

Esophageal duplication cyst.
Pathological Discussion
Dr. Mari Mino-Kenudson: The resected specimen was a multiseptated saccular cyst, 7 cm in
greatest dimension, with web formation suggestive of long-standing inflammation (Figure

3AFigure 3
Resected Posterior Mediastinal Cyst.). The cyst had been opened
before it was received in the pathology department and was empty. On gross examination, the
cyst lining was smooth except for scattered tannish-white discolorations measuring up to 0.3 cm.
On microscopical examination, the cyst wall consisted of well-formed muscular layers (Figure
3B) and was lined by either ciliated, pseudostratified columnar (respiratory) epithelium (Figure
3C) or attenuated squamous epithelium (Figure 3D). Pancreatic tissue or gastric mucosa was not
identified in multiple sections that were examined. In some areas, surface erosion with underlying
inflammation and calcifications replaced the cyst lining (Figure 3E), corresponding to the
tannish-white discolorations seen on gross examination. There were several collections of cellular
debris and foamy histiocytes (Figure 3F) within the muscular layers, fea-tures suggestive of
recent hemorrhage or necrosis.
For the pathologist, differentiation of a bronchogenic cyst from an esophageal duplication cyst
can be challenging, since both respiratory and gastrointestinal mucosa may be present in both
types of cysts. The distinction relies on the proximity to the bronchial tree, the presence of
bronchial elements such as cartilage and seromucinous glands, and the presence of well-formed
respiratory epithelium, which are characteristics of bronchogenic cysts; and on the intramural
location, the established muscular layers, and heterogeneous cyst lining, which are features of
esophageal duplication cysts.26 Given the intramural location of the lesion, which was confirmed
at the time of surgery, the pathological findings are consistent with an esophageal duplication cyst
with secondary inflammatory changes.
Esophageal duplications account for 10 to 20% of all gastrointestinal duplications and involve 1
in 8000 persons.27 The three types of esophageal duplications are cysts, diverticula, and tubular
malformations. A cyst is a localized duplication embedded in the esophageal wall. It usually does
not communicate with the native esophageal lumen but may enlarge because of the accumulation
of secretions, inflammation, or hemorrhage, or a combination of these. A diverticulum is a
localized outpouching that contains all the layers of the esophageal wall and communicates with
the lumen. A tubular malformation is a linear segment of duplication that runs parallel to the
native esophageal wall and may communicate with the esophageal lumen at the proximal end, the
distal end, or both. Luminal contents may accumulate in the duplicated segment, resulting in
cystic dilatation, inflammation, or both.
Cystic duplications, which this patient has, account for 80% of esophageal duplications. The cyst
lining usually consists of respiratory epithelium or squamous epithelium or both, as in this
case but also may contain enteric epithelium, gastric mucosa, or pancreatic tissue. The

presence of gastric and pancreatic tissue is associated with hemorrhage caused by acid or enzyme
secretion.
Dr. Nancy Lee Harris (Pathology): Dr. Kelleher, would you tell us what happened with the
patient?
Dr. Kelleher: This patient did well after surgery. He was able to start drinking liquids on the first
postoperative day and quickly resumed a normal diet. His chest tube was removed on
postoperative day 5, and he went home on postoperative day 6. While in the hospital, he had
persistently elevated blood glucose levels and glycosuria; endocrinology consultants made a
diagnosis of type 2 diabetes mellitus and initiated treatment with insulin and metformin. The
patient saw a nutritionist and an endocrinologist in follow-up 3 days after discharge. I saw him in
the office approximately 3 weeks after surgery, and his incision had healed well. He had no
dysphagia, no dyspnea, and no chest pain. I requested that he follow up again in approximately 3
months, but his mother, who is a nurse, declined additional follow-up and said that she would call
us if there were any problems. Since then, the patient has been followed by the endocrinologists
for his diabetes. Almost 2 years after discharge, he has had no recurrence of symptoms related to
the esophageal duplication cyst or the surgery.
Dr. Harris: Are there any questions?
Dr. Lloyd Axelrod (Endocrinology): What was the basis for the striking elevation in the amylase
level in the cystic fluid?
Dr. Kelleher: Most likely, pancreatic mucosa in the wall of the cyst secreted amylase but was not
seen during the pathology review.
Dr. Mino-Kenudson: We submitted representative sections of this very large cyst, but we may
have missed the pancreatic tissue. Mucosal erosions with underlying inflammation and
calcifications indicated the presence of inflammation. The calcifications could have been
replacing pancreatic tissue that had been inflamed and necrotic.
Anatomical Diagnosis
Esophageal duplication cyst with chronic inflammation, necrosis, and calcification.
Presented at the MedicinePediatrics Conference.
Disclosure forms provided by the authors are available with the full text of this article at
NEJM.org.
No potential conflict of interest relevant to this article was reported.
We thank Dr. Ashley Lamb, MedicinePediatrics chief resident, for helping to organize the
conference, and Dr. Lynn M. Lugnbuhl, Pediatric Infectious Diseases, for helping with the
preparation of the case history.
Source Information

From the Departments of Pediatric Surgery (C.M.K.), Gastroenterology (D.G.F.), Radiology

(M.S.G.), and Pathology (M.M.-K.), Massachusetts General Hospital; and the Departments of
Surg