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Case Records of the Massachusetts General Hospital

Founded by RichardC. Cabot
EricS. Rosenberg, M.D., Editor
JoAnneO. Shepard, M.D., Associate Editor
SallyH. Ebeling, Assistant Editor

NancyLee Harris, M.D., Editor

AliceM. Cort, M.D., Associate Editor
EmilyK. McDonald, Assistant Editor

Case 7-2016: An 80-Year-Old Man

with Weight Loss, Abdominal Pain,
Diarrhea, and an Ileocecal Mass
Vijay Yajnik, M.D., Ph.D., Shaunagh McDermott, M.D.,
Hamed Khalili, M.D., M.P.H., and JamieM. Everett, M.D.

Pr e sen tat ion of C a se

From the Departments of Medicine (V.Y.,
H.K.), Radiology (S.M.), and Pathology
(J.M.E.), Massachusetts General Hospi
tal, and the Departments of Medicine
(V.Y., H.K.), Radiology (S.M.), and Pathol
ogy (J.M.E.), Harvard Medical School
both in Boston.
N Engl J Med 2016;374:970-9.
DOI: 10.1056/NEJMcpc1509455
Copyright 2016 Massachusetts Medical Society.

970

Dr. Amulya Nagarur (Medicine): An 80-year-old man with end-stage renal disease,
type 2 diabetes mellitus, peripheral arterial disease, hypertension, coronary arteriosclerosis, congestive heart failure, abdominal aortic aneurysm, hyperlipidemia, and
gout was admitted to this hospital because of anorexia, weight loss, abdominal
pain, diarrhea, and an ileocecal mass.
Three years before this admission, the patient had been seen in the emergency
department of this hospital because of neck pain. Computed tomography (CT) of
the neck revealed evidence of degenerative disk disease of the cervical spine and a
pulmonary nodule (8 mm in diameter) in the left upper lobe.
Dr. Shaunagh McDermott: Three months after that initial visit, follow-up CT of the
chest was performed, and the nodule in the left upper lobe had not changed in
size. Five months after the initial visit, combined 18F-fluorodeoxyglucosepositronemission tomography and CT (FDG-PETCT) revealed that the pulmonary nodule
had increased in size to 1 cm in diameter, was tethered to the overlying pleura in
the left upper lobe, and had increased FDG uptake; a contiguous nodule (7 mm in
diameter) with increased FDG uptake and new nodules in the right middle lobe
were also present. In addition, there was intense diffuse FDG uptake in the stomach, as well as wall thickening of the most distal aspect of the terminal ileum and
the cecum in the region of the ileocecal valve, with adjacent inflammatory fat
stranding (Fig.1).
Dr. Nagarur: Lung biopsy, upper endoscopy, and colonoscopy were recommended,
but the patient declined to undergo these procedures. Approximately 9 months after
the initial visit, induration (8 mm in diameter) developed at the site of a tuberculin
skin test that had been performed during a hemodialysis appointment at an outpatient care unit. Chest radiography was performed; pulmonary lesions were not noted.
Eleven months after the initial visit (25 months before this admission), severe
abdominal pain in the right lower quadrant and pain in the right flank developed
acutely, and the patient presented to the emergency department at this hospital.
Imaging studies were obtained.
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Case Records of the Massachuset ts Gener al Hospital

Figure 1. Positron-Emission Tomographic and CT Scans.

An 18Ffluorodeoxyglucosepositronemission tomo
graphic (FDGPET) scan (Panel A) shows increased
FDG uptake in a nodule in the left upper lobe (arrow
head) and in the region of the ileocecal valve (arrow).
A corresponding axial CT scan (Panel B) shows a 1cm
nodule in the left upper lobe (arrowhead). A correspond
ing coronal CT scan (Panel C) shows wall thickening
of the terminal ileum and ileocecal valve (arrow) and
adjacent fat stranding, as well as an infrarenal aortic
aneurysm (asterisk).

Dr. McDermott: CT of the abdomen and pelvis,

performed after the intravenous administration
of contrast material (Fig. 2A), revealed a hematoma in the right anterior pararenal space that
arose from a subcapsular hematoma in the right
kidney, with extravasation of blood into the retroperitoneal space. In addition, the soft-tissue
mass at the ileocecal junction had increased in
size.
Dr. Nagarur: The patient was admitted to the
hospital, and coil embolization of the right renal
artery was performed. On the fourth hospital
day, a colonoscopy was performed, and a nonobstructive fungating mass (4 cm by 2 cm) was
visualized at the ileocecal valve (Fig. 3). Examination of a biopsy specimen of the mass showed
severely active chronic colitis with fibrinopurulent exudate. On the 11th hospital day, colonoscopy was repeated and upper endoscopy was
performed. In addition to the ileocecal mass,
there were a few small inflammatory nodules
with a patchy distribution in the lower two
thirds of the esophagus, an oozing cratered ulcer in the gastric body with a visible vessel that
was clipped, a few nonbleeding superficial ulcers in the gastric antrum, and diffuse, moderately erythematous mucosa in the duodenal
bulb. Histopathological examination of biopsy
specimens revealed erosive gastritis with reactive
foveolar hyperplasia and markedly active chronic
ileitis and ileocolitis with ulceration and nonnecrotizing granulomas; no fungal forms or acid-fast bacilli were seen. The patient was discharged home while taking omeprazole.
Eight weeks after that discharge (approximately 23 months before this admission), the
patient was seen in the gastroenterology clinic at
this hospital. He reported having two or three
bowel movements each day, with formed stools
and without blood or pain during defecation. He

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Figure 2. Serial CT Scans Obtained over a 30-Month Period.

Coronal CT scans that were obtained over a 30month period (Panels A through E) show persistent thickening of
the terminal ileum and ileocecal valve (arrows in all panels) and adjacent fat stranding. There is highattenuation
fluid in the retroperitoneum (Panel A, asterisk), a finding consistent with hemorrhage due to a right renal subcapsu
lar hematoma (not shown). There is also an infrarenal aortic aneurysm (Panel B, asterisk), which shows endovascu
lar repair on followup images (Panels C and D).

had a reduced appetite but no abdominal pain.

The weight was 65.3 kg (decreased from 78.0 kg
3 years earlier), and the abdominal examination
was normal. The erythrocyte sedimentation rate
was 67 mm per hour (reference range, 0 to 13),
and the C-reactive protein level was 55.5 mg per
liter (reference value, <8.0). The dose of omeprazole was increased.
Approximately 19 months before this admission, 2 weeks after the patient was discharged
from a hospital stay for pacemaker placement,
he was seen in the primary care clinic with a
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5-day history of diarrhea, lower abdominal pain,

and tenderness. The weight was 59.3 kg. A stool
culture was negative for enteric pathogens, and
a test for Clostridium difficile was positive. A 10-day
course of oral metronidazole was prescribed; the
frequency of diarrhea initially decreased but returned to three or four times a day after the
medication was stopped. A 14-day course of oral
vancomycin was prescribed, and the symptoms
abated.
Sixteen months before this admission, severe
abdominal pain in the right lower quadrant de-

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Case Records of the Massachuset ts Gener al Hospital

veloped acutely, and the patient presented to the

emergency department at this hospital. He reported feeling weak; the right lower quadrant
was tender on palpation. Laboratory test results
are shown in Table 1. Additional imaging studies were obtained.
Dr. McDermott: CT of the abdomen and pelvis,
performed after the intravenous administration
of contrast material, revealed persistent irregular
wall thickening of the terminal ileum, with mild
adjacent inflammatory fat stranding (Fig. 2B).
Dr. Nagarur: Hemodialysis was performed, and
the patient was admitted to the hospital. Ciprofloxacin and metronidazole were administered,
and the abdominal pain improved during the
next 3 days. A stool culture and examinations
for ova and parasites were negative, and a test
for C. difficile was positive; ciprofloxacin was discontinued, and the patient was discharged with
a prescription for a 14-day course of oral metronidazole.
Thirteen months before this admission, the
patient returned to the gastroenterology clinic.
He reported that he had had three or four loose,
nonbloody bowel movements each day for several
weeks, with associated generalized abdominal
pain. His appetite continued to be reduced, and
he felt weak and fatigued. The weight was 55.8
kg, and the abdominal examination was normal.
Laboratory test results are shown in Table 1.
Dr. McDermott: CT angiography of the abdomen and pelvis had been performed 2 days before this visit to the gastroenterology clinic,
during routine follow-up after a recent endovascular procedure for the repair of an abdominal
aortic aneurysm. The imaging studies revealed
an increase in the circumferential wall thickening of the terminal ileum and cecum (Fig. 2C).
Dr. Nagarur: A diagnosis of Crohns disease
was considered. Treatment with prednisone and
methotrexate was recommended, but the patient
declined the treatment. Eleven weeks before this
admission, generalized weakness, diffuse abdominal discomfort and tenderness, and hypotension developed during an outpatient hemodialysis session. The patient was admitted to the
hospital, and fever (to a temperature of 38.4C)
developed. Cefepime and vancomycin were administered intravenously. Laboratory test results
are shown in Table 1.
Dr. McDermott: CT of the abdomen and pelvis
revealed increased diffuse wall thickening of
the terminal ileum and cecum, with persistent
n engl j med 374;10

mesenteric fat stranding and lymphadenopathy

(Fig. 2D).
Dr. Nagarur: By the third hospital day, the fever
had resolved and the abdominal pain had improved but diarrhea had developed; a test for
C. difficile was again positive. Cefepime and vancomycin were discontinued. The patient was discharged home with prescriptions for budesonide,
a 4-week course of ciprofloxacin and metronidazole, and a 6-week tapering course of oral vancomycin.
Three and a half weeks before this admission,
the patient underwent endarterectomies of the
right common femoral artery and the right superficial femoral artery at this hospital. Diarrhea and
tenderness of the right lower quadrant developed
postoperatively. The patient was uncertain whether he had been taking the budesonide and oral
vancomycin that had been prescribed during his
most recent hospitalization. Urinalysis revealed
cloudy urine with 3+ leukocyte esterase, 3+ occult
blood, 2+ albumin, and negative nitrites by dipstick, as well as more than 100 white cells and
20 to 50 red cells per high-power field. Other
laboratory test results are shown in Table 1.
Dr. McDermott: CT of the abdomen revealed
persistent circumferential wall thickening of the
terminal ileum and cecum and extensive adjacent
fat stranding that had increased slightly since
previous imaging studies had been obtained
(Fig. 2E).
Dr. Nagarur: On the sixth hospital day, a bowel
movement contained blood; a test for C. difficile

Figure 3. Colonoscopic Image.

An initial colonoscopy was performed approximately
25 months before the current admission. A nonobstruc
tive fungating mass (4 cm by 2 cm) was visualized at
the ileocecal valve. (Photograph courtesy of Drs. Ruma
Rajbhandari and Braden Kuo.)

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Table 1. Laboratory Data.*

16 Mo
Reference
before This
Range, Adults Admission

Variable

13 Mo
before This
Admission

11 Wk
before This
Admission

3.5 Wk
before This
Admission

2.5 Wk
before This
Admission

On
Admission

Hemoglobin (g/dl)

13.517.5

12.9

9.7

10.9

9.9

8.9

8.8

Hematocrit (%)

41.053.0

40.4

32.5

36.8

32.9

28.5

27.9

450013,000

10.9

9.6

14.40

8.11

11.44

11.46

Neutrophils

4062

58.7

74.6

71.8

Lymphocytes

2740

20.7

10.8

11.5

6.5

Monocytes

411

10.3

11.2

13.2

10.0

White-cell count (per mm3)

Differential count (%)

82.7

Eosinophils

08

9.2

2.5

2.3

Basophils

03

0.5

0.3

0.5

150,000
400,000

208

263

226

332

0.52.5

0.6

013

67

11.014.0

12.6

14.1

12.8

Prothrombin-time international normal

ized ratio

0.91.1

1.0

1.1

1.0

Platelet count (per mm3)

Reticulocytes (%)
Erythrocyte sedimentation rate (mm/hr)
Prothrombin time (sec)

158

0.2
211

1.0
90

96

65

Sodium (mmol/liter)

135145

140

137

143

138

139

Potassium (mmol/liter)

3.45.0

5.3

5.5

4.6

4.1

5.3

Chloride (mmol/liter)

100108

95

96

95

99

89

Carbon dioxide (mmol/liter)

2332

26.1

27

29

28

26

Anion gap (mmol/liter)

315

19

14

19

11

24

Calcium (mg/dl)

8.510.5

10.1

9.6

9.6

9.2

10.5

Phosphorus (mg/dl)

2.64.5

6.5

3.9

4.0

2.1

5.6

Magnesium (mg/dl)

1.72.4

2.2

2.0

2.3

1.9

2.4

Lactic acid (mmol/liter)

0.52.2

1.4

Urea nitrogen (mg/dl)

825

94

33

32

41

80

0.601.50

8.09

4.61

4.13

4.24

7.08

70110

123

110

99

120

130

Creatinine (mg/dl)
Glucose (mg/dl)

4.4

Protein (g/dl)
Total

6.08.3

7.9

7.2

5.4

Albumin

3.35.0

3.9

3.3

2.6

Globulin

2.34.1

4.0

3.9

2.8

Direct bilirubin (mg/dl)

00.4

0.1

0.1

Total bilirubin (mg/dl)

0.01.0

0.2

0.3

Alkaline phosphatase (U/liter)

45115

125

107

Alanine aminotransferase (U/liter)

1055

13

13

Aspartate aminotransferase (U/liter)

1040

21

Creatine kinase isoenzymes (ng/ml)

0.06.9

Troponin T (ng/ml)

26
2.6

<0.03

0.23

N-terminal proB-type natriuretic pep

tide (pg/ml)

01800

13,922

Lipase (U/liter)

1360

C-reactive protein (mg/liter)

57

<8.0

0.62

0.33

0.95

24,264

79,140

73.6

119.2

41
52.5

220.6

Iron (g/dl)

45160

70

25

24

Iron-binding capacity (g/dl)

230404

156

165

151

974

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Case Records of the Massachuset ts Gener al Hospital

Table 1. (Continued.)
16 Mo
Reference
before This
Range, Adults Admission

Variable

13 Mo
before This
Admission

11 Wk
before This
Admission

3.5 Wk
before This
Admission

Ferritin (ng/ml)

30300

1446

1743

1521

25-Hydroxyvitamin D (ng/ml)

33100

35

23

38

1060

295

207

228

Parathyroid hormone (pg/ml)

Enzyme-linked immunospot test for cellmediated immune response to
Mycobacterium tuberculosis
(interferon- release assay)

Negative

Positive

Red-cell thiopurine methyltransferase

activity (U/ml)

15.0

13.0

HIV-1 and HIV-2 antibodies and HIV-1

p24 antigen

Nonreactive

2.5 Wk
before This
Admission

On
Admission

Nonreactive

* HIV denotes human immunodeficiency virus. To convert the values for calcium to millimoles per liter, multiply by 0.250. To convert the
values for phosphorus to millimoles per liter, multiply by 0.3229. To convert the values for magnesium to millimoles per liter, multiply by
0.4114. To convert the values for lactic acid to milligrams per deciliter, divide by 0.1110. To convert the values for urea nitrogen to milli
moles 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 bilirubin to micromoles per liter, multiply by 17.1. To convert
the values for iron and iron-binding capacity to micromoles per liter, multiply by 0.1791. To convert the values for 25-hydroxyvitamin D to
nanomoles per liter, multiply by 2.496.
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.

was negative. The patient was discharged home

on the seventh hospital day with prescriptions
for budesonide, a 7-day course of ciprofloxacin,
and a tapering course of oral vancomycin.
During the 24 hours after discharge, the patient had four episodes of diarrhea containing
bright red blood and returned to the emergency
department of this hospital. He reported abdominal pain in the right lower quadrant and
fatigue. The temperature was 38.3C, and the
abdomen was tender in the right lower quadrant.
While the patient was in the emergency department, he had two bowel movements that were
loose and melanotic. A stool culture, an assay
for Shiga toxin, and examinations for ova and
parasites were negative. Other laboratory test
results are shown in Table1.
The patient was admitted to the hospital.
Pantoprazole was administered, and a series of
hematocrit measurements showed minimal
change. By the fourth hospital day, the melena
had resolved and the abdominal pain had lessened, although diarrhea persisted. The patient
was discharged home on the sixth hospital day.
On the day of this admission, the patient was
brought to the emergency department of this
hospital by ambulance because of shortness of
breath. He reported progressive fatigue and

weakness that had persisted since the most recent hospitalization; on the day of this admission, he had been unable to get out of bed.
Medications included aspirin, metoprolol, atorva
statin, cilostazol, budesonide, omeprazole, allopurinol, sevelamer carbonate, several vitamins,
darbepoetin alfa, tramadol, acetaminophen, and
vancomycin. Adverse drug reactions included
cough with lisinopril, edema with nifedipine,
confusion with morphine and oxycodone, and
rash with hydrochlorothiazide, felodipine, and
clonidine. The patient had emigrated from Southeast Asia 22 years earlier and now lived in an
urban area of New England with his wife and
daughter. His family history was negative for
gastrointestinal, renal, and immunodeficiency
diseases. He drank alcohol rarely and did not
smoke cigarettes or use illicit drugs.
On examination, the patient appeared thin
and chronically ill. The temperature was 36.7C,
the pulse 104 beats per minute, the blood pressure 114/65 mm Hg, the respiratory rate 16
breaths per minute, and the oxygen saturation
97% while he was breathing ambient air. Crackles were heard in the posterior lower lung fields
on auscultation. The abdomen was mildly tender,
and the legs were edematous. Laboratory test
results are shown in Table1. Chest radiography

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revealed changes consistent with mild interstitial pulmonary edema, with small bilateral pleural effusions and a confluent opacity in the left
lower lobe. Hemodialysis was performed. The
shortness of breath resolved, but weakness and
fatigue persisted. The patient was admitted to
the hospital. A diagnosis was made.

Differ en t i a l Di agnosis
Dr. Vijay Yajnik: This 80-year-old man with a complex medical history presented with a severalyear history of intermittent abdominal pain, diarrhea, gastrointestinal bleeding, anorexia, and
weight loss. Despite an extensive workup and
multiple hospital admissions, a unifying diagnosis remained unknown. I will focus my differential diagnosis on several features of this case,
including the findings on FDG-PETCT (i.e., FDG
uptake in several lung nodules, the stomach, and
the ileocecal region), the identification of an ileocecal mass, an 8-mm induration at the site of a
tuberculin skin test, and a positive interferon-
release assay for Mycobacterium tuberculosis. Given
this patients age and the constellation of findings, we need to consider processes that are
likely to cause disease in the ileocecal region of
the bowel, including cancer, Crohns disease,
and infection.

of

m e dic i n e

if the disease metastasizes to the liver. The endoscopic appearance of a carcinoid tumor can be
either a submucosal prominence or an ulcerative
lesion. On rare occasions, this tumor may cause
a fungating mass lesion. Midgut carcinoid tumors
are desmoplastic and, as a result, cause inflammation that leads to fibrosis and kinking of the
mesentery. However, carcinoid tumors are easy
to diagnose on histologic examination, and granulomas are not a typical pathological finding.
Primary Gastrointestinal Lymphoma

Primary gastrointestinal lymphoma may also occur in the region of the ileocecal valve and the
appendix. Lymphomas are low-grade lesions with
FDG uptake that can be stable for months; these
features are consistent with those seen in this
patient. On endoscopy, the lesions can be ulcerative in the upper tract and polypoid in the small
bowel and colon and may even appear to be
fungating. This patient had both an ulcerative lesion on upper endoscopy and a fungating lesion
on colonoscopy. However, I suspect that the gastric ulcer was a result of chronic illness and that
this process was distinct from the ileocecal mass.
Although primary gastrointestinal lymphoma is
a consideration in this patient, granulomas are
typically seen in patients with Hodgkins disease
and not in those with primary gastrointestinal
lymphoma; therefore, this diagnosis is unlikely.

Cancer

Colon or Small-Bowel Cancer

Crohns Disease

Cancers of the colon and small bowel are relatively common in elderly patients and appear as
a positive finding on PET. On endoscopy, the
lesion often appears to be fungating. However,
with an adequate biopsy specimen, such tumors
are easy to diagnose on histologic examination.
The tumors progress to invade local structures
and then metastasize to the liver. Granulomas,
which were described in this patients initial
pathology report, are not typically seen. Furthermore, this patients lesion remained relatively
stable on multiple imaging studies that were
obtained over time, and there was no evidence
of metastatic spread to the liver. For all these
reasons, the diagnosis of colon or small-bowel
cancer is unlikely in this case.

Throughout the case presentation, the diagnosis

of inflammatory bowel disease was considered
and the patient was offered therapy for Crohns
disease on several occasions. Although Crohns
disease can occur anywhere throughout the gastrointestinal tract, it commonly affects the ileocecal valve and terminal ileum. Crohns disease
can be manifested at any age, including in an
80-year-old patient. However, stomach lesions
are rare in elderly patients with Crohns disease,
but focally enhancing gastritis is described in
young patients with Crohns disease. Also, Crohns
disease is associated with FDG uptake. On endoscopy, the lesion is predominantly ulcerative, but
polypoid lesions are seen with expansion of
lamina propria and lymphoid structures; a mass
that appears to be fungating is rare. On histoCarcinoid Tumor
logic examination, granulomas are seen in 20 to
Could this patient have a carcinoid tumor? This 25% of cases and the disease can be stable for
type of tumor can involve the ileocecal valve and months; these features are consistent with the
appendix and may cause the carcinoid syndrome features of this patients presentation.
976

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Case Records of the Massachuset ts Gener al Hospital

Infection

Bacterial, fungal, and mycobacterial infection can

occur at the ileocecal valve, cecum, and terminal
ileum. Bacterial and fungal infections are typically acute and cause progressive disease. However, similar to Crohns disease, intestinal tuberculosis can be indolent and cause chronic disease
that remains stable for months; these features
are consistent with those seen in this patient.
Intestinal tuberculosis can be manifested at any
age and is associated with FDG uptake; the endoscopic appearance is relatively indistinguishable from that of Crohns disease. Ulcerative,
polypoid, and fungating lesions can be present.
Granulomas are seen in 20 to 25% of cases. The
mycobacterial load is low, so staining for acidfast bacilli is often negative.
I suspect that a clue in this case was the
positive interferon- release assay for M. tuberculosis that had been reported 11 months before
this admission. On presentation, the patient had
progressive anemia and leukocytosis. Both the
erythrocyte sedimentation rate and the C-reactive protein level were high, and an abdominal
CT scan that had been obtained 11 weeks before
admission showed progression of inflammatory
changes in the ileocecal area, with circumferential wall thickening and mesenteric fat stranding. Taken together, these findings are inconsistent with the diagnosis of primary epithelial,
stromal, or neuroendocrine cancer or lymphoma.
Other possible causes, such as gastrointestinal
amyloid, Whipples disease, occlusive and nonocclusive mesenteric ischemia, and stromal tumors, typically are not associated with an inflammatory mass. The mesenteric fat stranding is
suggestive of inflammation, and Crohns disease
and intestinal tuberculosis are the most likely
possibilities.
Crohns Disease versus Intestinal
Tuberculosis

Does this patient have Crohns disease or intestinal tuberculosis? Distinguishing between these
two entities is a challenge because there is
marked overlap in the clinical presentation and
the radiographic, laboratory, and endoscopic
findings, as well as in the presence of granulomas on histologic examination.1-3 Misdiagnosis
of Crohns disease in a patient with intestinal
tuberculosis would result in treatment with glucocorticoids and biologic agents, which then has
the potential to cause disease progression that

leads to increased morbidity and mortality. Misdiagnosis of intestinal tuberculosis in a patient

with Crohns disease would lead to prolonged
antitubercular therapy and delay the necessary
immunosuppression required to induce disease
remission.4
Both diseases have an insidious onset. Diarrhea, hematochezia, and extraintestinal manifestations are more common in patients with Crohns
disease. Intestinal tuberculosis can target extrapulmonary sites in a manner that resembles the
classic extraintestinal manifestations of Crohns
disease, such as reactive arthritis, erythema nodosum, and uveitis.5 Ascites and fever are more
commonly seen in patients with intestinal tuberculosis. Both diseases involve the ileum and colonic segments of the bowel. Isolated involvement of the terminal ileum is commonly seen in
patients with Crohns disease, whereas involvement of the ileocecal area and a patulous ileocecal valve is seen in patients with intestinal tuberculosis. In patients with Crohns disease, mucosal
injury has a cobblestone appearance with aphthous and longitudinal rake ulcers, whereas in
patients with intestinal tuberculosis, the ulcers
are transverse in orientation.6-8 Furthermore, the
granulomas associated with intestinal tuberculosis are more frequent and confluent and larger
than those associated with Crohns disease. Tissue
samples are positive for acid-fast bacilli in only 25
to 30% of cases of intestinal tuberculosis.7 The
use of molecular techniques, such as polymerasechain-reaction (PCR) assays of fresh biopsy specimens, can improve the diagnostic yield.
On admission, this patient was ill but did not
have diarrhea, hematochezia, extraintestinal
manifestations, or a fistula, features that are
commonly seen in patients with Crohns disease.
An inflammatory mass was present on endoscopy, and examination of the biopsy specimen
revealed granulomas without visible acid-fast
bacilli. However, these findings do not rule out
the diagnosis of intestinal tuberculosis, because
detection of acid-fast bacilli has poor sensitivity,
presumably due to low organism load. The patient is originally from Southeast Asia, where
tuberculosis is endemic, and an interferon- release assay for M. tuberculosis was positive, thus
indicating previous exposure. Tuberculosis can
be dormant in patients for several decades, and
reactivation can occur in patients with immunocompromise, long-term use of glucocorticoids,
diabetes, renal failure, and cancer. This patient

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977

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n e w e ng l a n d j o u r na l

m e dic i n e

had several of these risk factors, including glucocorticoid use, renal failure, and diabetes.
Taken together, these findings favor a diagnosis
of intestinal tuberculosis. Given the high likelihood for tuberculosis, I would perform a repeat
colonoscopy with a biopsy and send the tissue
for histologic examination, culture, and PCR assay for tuberculosis.
Dr. Virginia Pierce (Pathology): Dr. Khalili, what
was your impression when you initially evaluated
this patient?
Dr. Hamed Khalili: We met this patient on the
second hospital day to help with management of
his bloody diarrhea and abdominal pain. He had
previously received a diagnosis of Crohns ileocolonic disease; however, a number of atypical
features including his age, country of origin,
and previous endoscopic findings were not
entirely consistent with Crohns disease. Nevertheless, noncaseating granulomas that had been
noted in previous biopsy specimens were strongly suggestive of Crohns disease. Since he was an
elderly man originally from Southeast Asia and
had a previously positive interferon- release assay for M. tuberculosis, we considered the diagnosis of intestinal tuberculosis. Because of the
similarities in clinical and endoscopic findings
between intestinal tuberculosis and Crohns disease, it was particularly important to evaluate
the patient more extensively for intestinal tuberculosis. Given his coexisting conditions, we also
considered the possibility of ischemic colitis.
However, we thought that diagnosis was unlikely because of the location of involvement in
the bowel. We decided to reexamine his previous
biopsy specimens with a specific focus on the
possibility of intestinal tuberculosis and considered performing another colonoscopy to obtain
a fresh specimen specifically for M. tuberculosis
studies.

Cl inic a l Di agnosis

Figure 4. Biopsy Specimens Obtained during Colonoscopy.

Reexamination of biopsy specimens obtained on the
initial colonoscopy showed chronic active ileitis consist
ing of expansion of the lamina propria, intraepithelial
neutrophilic infiltrate, and architectural distortion
(Panel A). Reexamination of specimens obtained on
the second colonoscopy showed chronic active ileitis
with nonnecrotizing granuloma (Panel B, arrow). Ex
amination of a biopsy specimen obtained during this
hospital admission showed multiple acidfast bacilli in
the necrotizing component of the specimen (Panel C).

978

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n engl j med 374;10

Intestinal tuberculosis.

Dr . V ija y Y ajnik s Di agnosis

Intestinal tuberculosis.

Pathol o gic a l Discussion

Dr. Jamie M. Everett: Reexamination of the biopsy
specimens that had been obtained from the cenejm.org

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Case Records of the Massachuset ts Gener al Hospital

cal mass during the initial colonoscopy showed

multiple pieces of colonic mucosa with severely
active chronic colitis with foci of cryptitis and
fibrinopurulent exudate (Fig.4A). Reexamination
of the biopsy specimens of the terminal ileum
and ileocecal valve that had been obtained during the second colonoscopy showed active
chronic ileocolitis with ulceration and predominantly nonnecrotizing granuloma formation
(Fig.4B). On reexamination of the stain for acidfast bacilli, very few candidate organisms were
identified, which indicated the need to obtain an
additional tissue sample.
The diagnostic procedure was a third colonoscopy, and examination of the ileal-biopsy
specimens revealed ulcerated mucosa with granulation tissue and necrosis with vaguely palisading histiocytes. The corresponding stain for acidfast bacilli revealed numerous organisms that
were present in the highest concentrations in the
granulation tissue and necrotic areas (Fig.4C).
These findings were consistent with the diagnosis of mycobacterial ileitis. A smear for acid-fast
bacilli, a culture, and a PCR assay were also
positive, and M. tuberculosis was identified as the
causative organism, thus confirming the diagnosis of tuberculous enteritis.
Dr. Pierce: Dr. Chu, would you tell us what happened with this patient?
Dr. Jacqueline Chu (Infectious Diseases): A fourReferences
1. Tandon HD, Prakash A. Pathology of
intestinal tuberculosis and its distinction
from Crohns disease. Gut 1972;13:2609.
2. Almadi MA, Ghosh S, Aljebreen AM.
Differentiating intestinal tuberculosis from
Crohns disease: a diagnostic challenge.
Am J Gastroenterol 2009;104:1003-12.
3. Huang X, Liao WD, Yu C, et al. Differences in clinical features of Crohns disease and intestinal tuberculosis. World J
Gastroenterol 2015;21:3650-6.
4. Tandon R, Ahuja V. Differentiating

drug antituberculosis regimen (consisting of

isoniazid with vitamin B6, rifampin, ethambutol,
and pyrazinamide) was initiated while the patient awaited the results of susceptibility testing.
Within several days, he had clinically significant
improvement in his loose bowel movements, and
we planned for therapy with the conventional
four-drug regimen for 2 months followed by
therapy with a two-drug regimen (most likely
consisting of rifampin and isoniazid) for 4 to
7months, pending clinical improvement.
Unfortunately, the patient continued to have
fatigue and nausea and stayed briefly in a rehabilitation facility. While he was in the rehabilitation facility, chest pain developed and he had
cardiac arrest with pulseless electrical activity.
After resuscitation, the patient was transferred to
the cardiac care unit of this hospital; his family
opted for comfort measures only, and he died.

Fina l Di agnosis
Tuberculous enteritis.
This case was presented at the medical case conference.
Dr. Khalili reports receiving consulting fees from AbbVie. No
other potential conflict of interest relevant to this article was
reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
We thank Dr. Kathleen Corey for assistance with selection of
this case and review of a previous version of the manuscript.

intestinal tuberculosis from Crohns disease. In:Jewell DP, ed. Inflammatory

bowel disease. Tokyo:Macmillan Medical
Communications, 2014:41-60.
5. Singh B, Kedia S, Konijeti G, et al. Extraintestinal manifestations of inflammatory bowel disease and intestinal tuberculosis: frequency and relation with
disease phenotype. Indian J Gastroenterol
2015;34:43-50.
6. Lee YJ, Yang SK, Byeon JS, et al. Analysis of colonoscopic findings in the differential diagnosis between intestinal tuber-

culosis and Crohns disease. Endoscopy

2006;38:592-7.
7. Makharia GK, Srivastava S, Das P, et
al. Clinical, endoscopic, and histological
differentiations between Crohns disease
and intestinal tuberculosis. Am J Gastroenterol 2010;105:642-51.
8. Zhao XS, Wang ZT, Wu ZY, et al. Differentiation of Crohns disease from intestinal tuberculosis by clinical and CT
enterographic models. Inflamm Bowel
Dis 2014;20:916-25.
Copyright 2016 Massachusetts Medical Society.

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979