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Case Records of the Massachusetts General Hospital
From the Departments of Medicine
(D.E.D., D.M.D.), Radiology (M.P.M.),
Surgery (C.F.-C.), and Pathology ( J.H.C.),
Massachusetts General Hospital and
the Departments of Medicine (D.E.D.,
D.M.D.), Radiology (M.P.M.), Surgery
(C.F.-C.), and Pathology ( J.H.C.), Harvard
Medical School both in Boston.
N Engl J Med 2017;377:874-82.
DOI: 10.1056/NEJMcpc1706111
Copyright 2017 Massachusetts Medical Society.
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of m e dic i n e
Founded by Richard C. Cabot
Eric S. Rosenberg, M.D., Editor
Virginia M. Pierce, M.D., David M. Dudzinski, M.D., Meridale V. Baggett, M.D.,
Dennis C. Sgroi, M.D., Jo-Anne O. Shepard, M.D., Associate Editors
Allison R. Bond, M.D., Case Records Editorial Fellow
Emily K. McDonald, Sally H. Ebeling, Production Editors
Case 27-2017: A 32-Year-Old Man
with Acute Chest Pain
Douglas E. Drachman, M.D., David M. Dudzinski, M.D., J.D.,
Matthew P. Moy, M.D., Carlos Fernandez-del Castillo, M.D.,
and Jonathan H. Chen, M.D., Ph.D.
Pr e sen tat ion of C a se
Dr. David M. Dudzinski: A 32-year-old man was evaluated in the emergency depart-
ment of this hospital for the abrupt onset of postprandial chest pain.
Several hours before presentation, the patient had eaten pizza in his apartment.
Less than 1 hour later, while he was at rest and watching television, crushing
pain, diaphoresis, dyspnea, and nausea developed. He rated the pain at 7 on a scale
of 0 to 10 (with 10 indicating the most severe pain), and he noted that the pain
did not radiate or worsen with respiration. He attempted to induce vomiting and
took calcium carbonate tablets, but his condition did not improve. After 2 hours
of constant pain, he presented to the emergency department of this hospital.
The patient had no medical history and took no medications. His father had
had a myocardial infarction when he was 51 years of age. The patient was allergic
to penicillin (unknown reaction). He lived with his girlfriend, who had recently
had streptococcal pharyngitis. He had been under a great deal of stress because
of a new job as a sales manager, a move to a new apartment, and the recent death
of a family pet. He consumed a six-pack of beer daily. He had used cocaine (most
recently 3 months earlier) but did not report using other illicit substances.
On examination, the temperature was 36.3C, the heart rate 83 beats per min-
ute, the blood pressure 158/81 mm Hg, the respiratory rate 28 breaths per minute,
and the oxygen saturation 100% while the patient was breathing ambient air. The
body-mass index (the weight in kilograms divided by the square of the height in
meters) was 26.9. He appeared to be anxious and uncomfortable and had diapho-
resis. The jugular venous pressure was 6 cm of water with a normal waveform.
There was no evidence of a heart murmur or rub. When the patient was asked to
indicate the location of the pain, he pointed to the subxiphoid area; there was
some tenderness in that area on palpation. The stool was guaiac negative. The
remainder of the examination was normal.
Urinalysis revealed a specific gravity of greater than 1.040 and was otherwise
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 Case Records of the Massachuset ts Gener al Hospital

Table 1. Laboratory Data.*

Reference Range,
Variable Adults On Presentation 7 Hr after Presentation
Hemoglobin (g/dl) 13.517.5 14.6 12.1
Hematocrit (%) 41.553.0 40.6 34.1
White-cell count (per mm3) 450011,000 8000 10,700
Platelet count (per mm3) 150,000400,000 209,000 148,000
Neutrophils (%) 4070 49
Sodium (mmol/liter) 135145 141 139
Potassium (mmol/liter) 3.44.8 3.8 3.6
Chloride (mmol/liter) 100108 98 101
Carbon dioxide (mmol/liter) 2332 24.3 27.1
Urea nitrogen (mg/dl) 825 17 10
Creatinine (mg/dl) 0.601.50 1.21 1.08
Glucose (mg/dl) 70110 123
Calcium (mg/dl) 8.510.5 10.1 9.2
Albumin (g/dl) 3.35.0 4.9 4.3
Lipase (U/liter) 1360 47 39
Amylase (U/liter) 3100 25 38
Alanine aminotransferase (U/liter) 1055 51 284
Aspartate aminotransferase (U/liter) 1040 42 196
Alkaline phosphatase (U/liter) 45115 72 103
Total bilirubin (mg/dl) 01.0 0.8 5.0
Direct bilirubin (mg/dl) 00.4 0.2 2.6
Troponin I Negative Negative
Troponin T (ng/ml) <0.03 <0.01

* To convert the values for urea nitrogen to millimoles per liter, multiply by 0.357. To convert the values for creatinine to
micromoles per liter, multiply by 88.4. To convert the values for glucose to millimoles per liter, multiply by 0.05551. To
convert the values for calcium to millimoles per liter, multiply by 0.250. To convert the values for bilirubin to micromoles
per liter, multiply by 17.1.
Reference values are affected by many variables, including the patient population and the laboratory methods used. The
ranges used at Massachusetts General Hospital are for adults who are not pregnant and do not have medical conditions
that could affect the results. They may therefore not be appropriate for all patients.

normal. A urine toxicology screen revealed can-
nabinoids, and a blood toxicology screen was
negative; other laboratory test results are shown
in Table 1. An electrocardiogram showed con-
cave ST-segment elevations (1 to 2 mm) in the
inferior leads and V3 through V6 precordial leads,
along with a PR-segment elevation in lead aVR
and possible subtle PR-segment depressions
(Fig. 1). Imaging studies were obtained.
Dr. Matthew P. Moy: A chest radiograph was
normal. The lungs were clear, and there was
no evidence of pneumothorax, cardiomegaly, or
mediastinal widening.
Dr. Dudzinski: Aspirin, clopidogrel, intravenous
morphine sulfate, lorazepam, ranitidine, alu-
minum hydroxidediphenhydraminelidocaine
magnesium hydroxide, and intravenous infusions
of heparin and nitroglycerin were administered,
and emergency coronary angiography was ar-
ranged. A diagnosis was made.
Differ en t i a l Di agnosis
Dr. Douglas E. Drachman: This previously healthy
32-year-old man, who had a history of illicit-
drug use and a family history of premature heart

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 The n e w e ng l a n d j o u r na l
Figure 1. Electrocardiogram.
A 12-lead electrocardiogram shows probable sinus ar-
rhythmia, along with a subtle PR-segment elevation in
lead aVR and possible subtle PR-segment depressions,
as well as concave ST-segment elevations (1 to 2 mm)
in the inferior leads and V3 through V6 precordial leads.
disease, presented with acute chest pain. When
we evaluate a patient such as this one in real
time, we must consider a broad differential diag-
nosis, including cardiac, vascular, embolic, and
gastrointestinal causes of pain. After the patient
presented to the emergency department, the first
aim was to rule out myocardial infarction, and
he was treated with appropriate empirical ther-
apy; clinical concerns about an acute coronary
syndrome were probably raised in response to
the family history, history of cocaine use, and
abnormal findings on electrocardiography. Re-
viewing the patients history, the findings on
examination, and the results of additional stud-
ies and laboratory tests will help us to consider
most of the possibilities included in the differ-
ential diagnosis.
Pericardial Disease
In this patient, could the chest pain and abnor-
mal electrocardiographic findings be explained
by pericardial disease? The electrocardiogram
showed an elevated J point; the presence of con-
cave ST segments makes the pattern of early
repolarization a likely explanation, and this pat-
tern may be a normal variant, particularly in a
young man.1 In a patient with acute chest pain,
the presence of PR-segment depressions in some
leads (II, III, and aVF) and an elevated PR seg-
ment in lead aVR may be indicative of acute
pericarditis.2
Pericarditis may develop after exposure to
an infectious illness, and it is notable that this
patients girlfriend recently had streptococcal
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pharyngitis. Pericarditic chest pain may have an
abrupt onset.2 However, the pain is not typically
exacerbated by eating and is often positional in
nature, and these features are not consistent with
the pain that this patient described. In addition,
a pericardial friction rub was not identified on
examination, and the administration of aspirin
might have lessened the patients pain if it had
been pericardial in origin.
Acute Coronary Ischemia
The patient described chest pain, but he pointed
to the subxiphoid area and was found to have
tenderness in that area on palpation. Although
anatomical boundaries may be clear to clini-
cians, the distinction between chest pain and
abdominal pain may be blurred for many pa-
tients. Moreover, the symptoms associated with
myocardial infarction are highly variable, and
patients seldom report the classic characteristics
and location of disease. Pain that occurs in the
subxiphoid area may indeed be consistent with
coronary ischemia; in fact, it is well recognized
that patients with acute myocardial infarction
may present with toothache, jaw pain, and weak-
ness in the legs. The location of the pain in the
subxiphoid area may limit the overall differential
diagnosis for this patient but should not lead us to
rule out consideration of myocardial infarction.3
The presence of severe unremitting pain, which
is distinct from pain that waxes and wanes, is
worrisome and should be factored into our con-
sideration of coronary ischemia alongside other
vascular, pulmonary, and gastrointestinal causes.
I suspect it is because of concerns about coro-
nary ischemia that arrangements for cardiac
angiography were made shortly after the patient
presented to the emergency department.
Other features of this patients presentation
that indicate the possibility of myocardial in-
farction include the family history of coronary-
artery disease, the presence of hypertension (al-
though this finding could potentially be caused
by pain), and the history of cocaine use (which
may accelerate the development of atherosclero-
sis). Use of cocaine may precipitate acute myo-
cardial infarction, coronary atherosclerotic plaque
disruption, vasospasm, spontaneous coronary-
artery dissection, or coronary ischemia due to
occult coronary-artery disease in the context of
physiologic stress and high demand for myocar-
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 Case Records of the Massachuset ts Gener al Hospital
dial oxygen.4 Could this patient have used cocaine
recently? The urine and blood toxicology screens
were negative for the presence of cocaine, but in
some instances, a toxicology screen yields a nega-
tive result within a few days after cocaine use.
Factors that argue against a diagnosis of
acute myocardial infarction include the history
of pain after eating, the insidious onset and
abrupt worsening of symptoms, and the repro-
ducible pain on palpation.3 In addition, the mor-
phologic features of the ST segments on electro-
cardiography did not clearly indicate a current
of injury pattern, which is seen in acute myo-
cardial infarction, and a test for troponin I was
negative, although the proximity of testing to
the onset of symptoms may not have permitted
adequate time for the detection of myocardial
necrosis.
The patients recent episodes of emotional
stress may be implicated as a possible inciting
factor of a coronary ischemic event. In addition,
substantial acute emotional stress may provoke
the development of takotsubo (stress) cardiomy-
opathy, a syndrome that is classically character-
ized by severe left ventricular apical dysfunction,
which may mimic an acute myocardial infarc-
tion but occurs in the absence of epicardial
coronary disease.5 The syndrome is rare in young
men and commonly occurs immediately after
a profound, abrupt episode of stress. The ab-
sence of an elevated troponin I level also makes
takotsubo cardiomyopathy unlikely.
Aortic Dissection
On rare occasions, a young patient (in this pa-
tients age group) presents with suspected myo-
cardial infarction but has type A aortic dissection.
On examination, this patient had hypertension,
which could be a reflection of stress or clini-
cally significant pain but could also indicate
underlying vascular or aortic disease. In a young,
previously healthy man, however, the develop-
ment of aortic dissection is more commonly
preceded by a provocation, such as lifting of
heavy weights, followed by the abrupt onset of
severe (tearing) pain in the interscapular, chest,
or abdominal region.6,7 Although clinicians should
be aware of the possibility of aortic dissection, it
is unlikely that this patient has this diagnosis,
given the postprandial onset of symptoms and
the absence of characteristic findings (e.g.,
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asymmetric pulses, bruits, and diastolic murmur)
on clinical examination.6,7 In patients in this
patients age group, connective-tissue disorders
might confer a predisposition to aortic dissec-
tion, but in this case, there was no evidence in
the history or on physical examination to sup-
port the diagnosis of connective-tissue disease.
Acute Vascular Diseases
Is this patients presentation consistent with a
systemic or mesenteric acute vascular disease?
The postprandial onset of severe pain in the
subxiphoid area raises concerns about acute
mesenteric ischemia. Use of cocaine and mari-
juana may provoke an arteriopathy, which could
involve the mesenteric arteries. Acute mesenteric
ischemia, however, more commonly results from
a cardioembolic event, such as atrial fibrillation.
There were no findings on examination to sug-
gest peripheral embolization. Furthermore, the
blood amylase and lipase levels were not elevat-
ed, whereas elevated levels might be anticipated
in a patient with acute mesenteric ischemia.
Celiac-artery dissection is rare but can occur
in a young, otherwise healthy man. It often oc-
curs after an event, such as abdominal trauma,
sneezing or coughing, lifting of heavy objects, or
an abrupt increase in abdominal pressure asso-
ciated with swinging a golf club. The median
arcuate ligament syndrome could also be consid-
ered in this case.8 In this congenital syndrome,
the median arcuate ligament of the diaphragm
crosses over the celiac artery, and this results in
extrinsic compression of the vessel and associ-
ated mesenteric ischemia. Persons with this con-
dition may have insidiously progressive ab-
dominal and postprandial pain as the ligament
encroaches on the entire celiac artery. It would
be rare for a patient with the median arcuate
ligament syndrome to present with the abrupt
onset and severe pain seen in this patient. Neither
celiac-artery dissection nor the median arcuate
ligament syndrome would result in electrocar-
diographic changes, and therefore these entities
are not high in the differential diagnosis for this
patient.
Systemic vasculitis would confer a predisposi-
tion to early adverse cardiovascular events in this
patient and could have done so in his father.
Fibromuscular dysplasia in the renal arteries
could lead to hypertension in a young patient
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and could increase the risk of cardiovascular
disease. In a patient with systemic vasculitis,
findings on physical examination might include
joint laxity (which is associated with the Ehlers
Danlos syndrome), a bifid uvula and facies (which
are associated with the LoeysDietz syndrome),
and classic findings associated with Marfans
syndrome, but in this patient, neither the history
nor examination yielded additional evidence of
these disorders.
Venous thromboembolic disease also merits
consideration. Pulmonary embolism, which clas-
sically mimics myocardial infarction,9 is a consid-
eration in this patient who presented with dys-
pnea and mild tachypnea and diaphoresis. The
location of the pain in the subxiphoid area may
indicate that the pain was thoracic in origin, but
the pain was definitively not pleuritic in nature.
The absence of tachycardia and hypoxemia also
makes pulmonary embolism unlikely, although it
should be noted that the heart rate of 83 beats per
minute might be moderately elevated, given the
patients age and previous health status.
Noncardiovascular Causes of Chest Pain
Noncardiovascular causes of chest pain may
mimic cardiovascular disease. A gastric ulcer,
biliary colic, and a Schatzkis ring may each lead
to pain in the subxiphoid area that may occur
after eating. Some cases of musculoskeletal in-
jury and herpes zoster have resembled acute
myocardial infarction, but neither cause seems
likely in this case.
Additional Diagnostic Considerations
What types of cardiovascular testing might we
have considered if we had evaluated the patient
at the time of presentation? Transthoracic echo-
cardiography is a noninvasive study that could
help to identify focal left ventricular hypokine-
sis, which would indicate a territory of ischemia
associated with a coronary artery, stress cardio-
myopathy, or a pericardial abnormality or effu-
sion. Computed tomographic angiography could
help to identify aortic dissection, aortic aneu-
rysm, mesenteric-artery dissection, or embolus
to a visceral artery and could possibly help to
rule out pulmonary embolism. In this patient,
coronary angiography may have been performed,
since it is the standard study for the diagnosis
of coronary-artery stenosis. However, coronary
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ischemia is not my leading diagnosis in this case
because critical laboratory data were obtained
that will allow us to reframe the initial diagnos-
tic considerations.
In learning more about the evolution of this
patients hospital course, we have been provided
with additional laboratory data. Seven hours after
presentation, the alanine and aspartate amino-
transferase levels were four times as high as the
levels at presentation and the bilirubin level was
more than five times as high as the upper limit
of the normal range. The presence of such liver-
function abnormalities in a patient with no signs
of cardiogenic shock or congestive heart failure
points us away from a cardiac diagnosis. Does
the acute rise in aminotransferase levels signify
an embolus to the hepatic artery or a dissection
of the celiac artery? We do not know the patients
ethnic background or red-cell indexes (e.g., mean
corpuscular volume), but sickle cell disease can
result in arterial occlusion in the liver and as-
sociated abdominal pain. Could this patient have
the BuddChiari syndrome or a process that
leads to elevated pressures and congestion in the
hepatic veins? It is unlikely that the abrupt onset
of pain after eating, which was described by this
patient, would be consistent with a diagnosis of
the BuddChiari syndrome.
Acute cholecystitis is a diagnosis that war-
rants careful consideration. At the time of pre-
sentation, this patient had some features that
were typical for cholecystitis, including persis-
tent postprandial pain, increasing bilirubin and
aminotransferase levels, and mild leukocytosis.
Tenderness in the subxiphoid area could poten-
tially be consistent with acute cholecystitis, al-
though the patient did not describe pain in the
right upper quadrant. The change in the labora-
tory test results over time makes cholecystitis a
likely cause. Case reports have described patients
with subdiaphragmatic acute processes who have
ST-segment elevation on electrocardiography that
is due to diaphragmatic irritation.10,11 Canine
models of acute occlusion of the common bile
duct have revealed sluggish blood flow in the
coronary arteries, which is possibly due to
changes in coronary microvascular tone; such
changes could also explain the abnormal elec-
trocardiographic findings seen in this case.12
My recommendation for establishing the di-
agnosis would be to perform ultrasonography
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 Case Records of the Massachuset ts Gener al Hospital

of the right upper quadrant. While the results of A

the study are pending, general surgical consulta-
tion regarding further evaluation and treatment
could be provided.
Dr. Dudzinski: Because the patient had had on-
going pain, invasive coronary angiography had
been performed. It revealed normal epicardial
coronary arteries, mildly and diffusely sluggish
coronary-artery blood flow (Thrombolysis in Myo-
cardial Infarction [TIMI] flow grade, 2 out of 3),
normal left ventricular end-diastolic pressure, an
ejection fraction of 55 to 60%, and no left ven-
tricular wall-motion abnormalities (see Video 1, A video
available with the full text of this article at showing coronary
angiography is
NEJM.org).
available at
After angiography was performed, the patient NEJM.org
reported that the pain in the subxiphoid area B
had abated and that pain in the right upper
quadrant had developed. He then had focal ten-
derness in this area, and several hours later,
scleral icterus was noted. Dark urine was ob-
served, with +3 urobilinogen. The elevations in
aminotransferase and bilirubin levels prompted
the performance of abdominal ultrasonography
to rule out the diagnosis of acute cholecystitis or
choledocholithiasis.

Cl inic a l Di agnose s
Biliary pain due to cholecystitis or choledocholi-
thiasis.

Dr . D ougl a s E . Dr achm a ns Figure 2. Abdominal Imaging Studies.

Di agnosis
Acute cholecystitis.
Im aging S t udie s
Dr. Moy: On hospital day 2, abdominal ultraso-
nography revealed cholelithiasis (gallstones) and
mild distention of the gallbladder but no spe-
cific signs of acute cholecystitis (Fig. 2A). The
gallbladder wall measured 3 mm in thickness,
and Murphys sign was absent. There was no
dilatation of the bile ducts. The remainder of the
ultrasound examination was normal.
Given the evidence of cholestasis on labora-
tory testing and the strong clinical suspicion for
biliary disease, endoscopic retrograde cholangi-
opancreatography (ERCP) was performed on
An abdominal ultrasound image (Panel A) shows round,
echogenic structures with posterior acoustic shadowing
in the gallbladder, a finding consistent with cholelithia-
sis. The gallbladder is mildly distended, but there is no
gallbladder-wall thickening, pericholecystic fluid, or
Murphys sign. An endoscopic retrograde cholangio-
pancreatographic image (Panel B) shows no evidence
of dilatation of the bile ducts or choledocholithiasis.
There are filling defects in the gallbladder, which con-
firm the presence of gallstones (arrowheads).
hospital day 3. The caliber of the common bile
duct and intrahepatic bile ducts was normal. No
filling defects were seen in the ducts. There was
retrograde opacification of the cystic duct and
gallbladder, and the cholelithiasis was visible
(Fig. 2B). On endoscopic examination, the major
duodenal papilla had a normal appearance, with

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 The n e w e ng l a n d j o u r na l
no evidence of a mass or bleeding. Biliary sphinc-
terotomy was performed.
Although ultrasonography has high sensitivity
and specificity for the detection of acute chole-
cystitis, false negative examinations can occur.
The cause of acute calculous cholecystitis is
considered to be obstruction of the cystic duct,
and it is notable that the cystic duct was patent
on ERCP in this patient. It is possible that the
retrograde injection of contrast material under
pressure during ERCP could cause opacification
of the cystic duct. There were no findings on the
imaging studies to suggest biliary obstruction or
choledocholithiasis; however, if the patient had
spontaneously passed a stone, the results on
abdominal ultrasonography and ERCP may have
appeared to be normal.
Dr. Dudzinski: Dr. Fernandez-del Castillo,
what was your clinical impression and initial
treatment strategy when you evaluated this pa-
tient?
Surgic a l A sse ssmen t
a nd M a nagemen t
Dr. Carlos Fernandez-del Castillo: This patient present-
ed with nearly normal results on liver-function
tests, and within 1 day, his bilirubin level reached
5 mg per deciliter (85.5 mol per liter). Our ini-
tial differential diagnosis included acute chole-
cystitis and choledocholithiasis. Simultaneous
acute cholecystitis and choledocholithiasis would
be rare, because the cause of acute cholecystitis
is obstruction of the cystic duct whereas the cause
of choledocholithiasis is obstruction of the com-
mon bile duct. Patients with acute cholecystitis
may have jaundice and an elevated bilirubin level,
but the bilirubin level rarely rises above 4 mg per
deciliter (68.4 mol per liter). Features of this
patients presentation that argue against a diag-
nosis of acute cholecystitis include the absence
of fever, emesis, and any other gastrointestinal
symptoms. In addition, he did not have clinical-
ly significant leukocytosis or have gallbladder-
wall thickening or Murphys sign on ultrasonog-
raphy; these findings are all characteristic of
acute cholecystitis. However, the pain shifted
from the center of his abdomen to the right up-
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of m e dic i n e
per quadrant, and he had some tenderness in the
right upper quadrant on examination.
When we considered the possibility that this
patient had choledocholithiasis, we were dis-
suaded by the absence of dilatation of the com-
mon bile duct on ultrasonography and the ab-
sence of ductal filling defects on ERCP. However,
we thought that a gallstone could have caused the
underlying problem and then passed through the
common bile duct into the duodenum, which
would explain why there was no evidence of cho-
ledocholithiasis on ultrasonography and ERCP. In
light of this possibility, we elected to perform lapa-
roscopic removal of the gallbladder, not to treat the
acute condition but to prevent a future similar pre-
sentation with obstruction of the common bile duct.
We approached the operation with the inten-
tion of performing a semielective cholecystecto-
my. However, during the procedure, we found a
very distended gallbladder with a gangrenous
wall that had adhered to the omentum. On the
basis of the findings on ultrasonography, we
had not expected to find a thickened gallbladder
wall. The gallbladder was so distended and full
that we could not grasp it initially and had to
empty it before removal. The surgical dissection
was laborious and required placement of a surgi-
cal drain, which we normally would not do after
a laparoscopic cholecystectomy.
Pathol o gic a l Discussion
Dr. Jonathan H. Chen: The cholecystectomy speci-
men was tannish pink and had focal areas of
hyperemia and hemorrhage. The opened gall-
bladder had small amounts of greenish brown
bile and yellowish brown biliary sludge, along
with a large number of irregular, roughly spher-
ical yellow and yellowish green calculi, which
ranged from 2 to 15 mm in greatest dimension.
The gallbladder wall measured up to 4 mm in
thickness (normal thickness, <3 mm). Micro-
scopic examination revealed a lymphocytic and
neutrophilic infiltrate that extended transmu-
rally from the mucosa to the serosal and adven-
titial surfaces (Fig. 3). The gallbladder wall was
fibrotic and hemorrhagic and had surface necro-
sis. There was no evidence of cancer.
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The presence of cholelithiasis in itself is not A

diagnostic of acute cholecystitis. A high percent-
age of the general population has asymptomatic
stones.13,14 However, the wall edema, necrosis, and
degree of neutrophilic inflammation seen in this
patient support the diagnosis of acute cholecys-
titis. The mononuclear infiltrate and fibrosis are
sufficient to establish a diagnosis of chronic
cholecystitis. In addition, a RokitanskyAschoff
sinus (i.e., herniation of the mucosa through the
muscularis layer) is seen (Fig. 3A). Rokitansky
Aschoff sinuses are commonly associated with
chronic cholelithiasis and may result from in-
creased intraluminal pressure that is caused by B
obstruction of bile flow.
Some features of the patients presentation are
also suggestive of choledocholithiasis. The eleva-
tion in aminotransferase levels became marked
during the first hours after presentation and was
accompanied by elevation in bilirubin and alka-
line phosphatase levels, which is uncommon in
uncomplicated cholecystitis. These data suggest
that a gallstone might have entered and passed
through the cystic and common bile ducts and
temporarily impaired bile flow before ultimately
exiting into the duodenum. The gallbladder con-
tained many gallstones in a range of sizes. Unless C
it shattered en route, the stone that caused the
patients condition must have been large enough
to cause symptoms and obstruct bile flow yet
small enough to pass out of the gallbladder and
through the cystic and common bile ducts be-
fore the medical intervention was performed.
The gallbladder contained cholesterol stones
and not pigment stones. Therefore, causes of
cholelithiasis that are associated with pigment
stones, such as hemolytic disorders and alcohol-
ism, are unlikely to be factors in this case. That
said, the patient did not have the typical features
Figure 3. Resection Specimen of the Gallbladder
of a patient with cholesterol-stone formation; he (Hematoxylin and Eosin).
was a mildly overweight 32-year-old man and The mucosal surface of the gallbladder shows hernia-
not an obese woman in her forties. tion into the muscularis layer (Panel A, arrow). Inflam-
One factor that can contribute to cholesterol- mation extends from the mucosal surface down through
stone formation is helicobacter infection. In par- the adventitia (Panel B; arrow denotes the interface
ticular, Helicobacter pylori and H. hepaticus infections between the gallbladder and the liver). At high mag-
nification (Panel C), a neutrophilic infiltrate is visible
have each been associated with cholelithiasis.15 (arrows) and lymphocytes and plump, activated fibro-
Serologic testing for helicobacter might be use- blasts are present (arrowheads).
ful in determining whether the patient had a

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 Case Records of the Massachuset ts Gener al Hospital

past infection and in defining the cause of cho- A nat omic a l Di agnosis
lesterol-stone formation.
Dr. Dudzinski: The patient had an uneventful Acute and chronic cholecystitis and extensive
course after the cholecystectomy. The surgical cholelithiasis with transmural gallbladder in-
drain was removed before discharge, on post- flammation.
operative day 2. He completed a 10-day course This case was presented at the Medical Case Conference.
of ciprofloxacin and clindamycin. Three weeks Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
later, he presented for a postoperative follow-up We thank Dr. Gaurav A. Upadhyay for contributions to the
visit and was well. case history.

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