ORIGINAL ARTICLE
Gastrointestinal Tract Vasculopathy
Clinicopathology and Description of a Possible “New Entity”
With Protean Features
Christine Y. Louie, MD,* Michael A. DiMaio, MD,* Gregory W. Charville, MD, PhD,†
Gerald J. Berry, MD,† and Teri A. Longacre, MD†
Abstract: Noninfectious gastrointestinal (GI) vasculopathic
disorders are rare and are often overlooked in histopathologic
examination or when forming differential diagnoses due to
their rarity. However, involvement of the GI tract may lead to
serious complications, including ischemia and perforation. Since
awareness of the types of vasculopathy that may involve the GI
tract is central to arriving at a correct diagnosis, we reviewed our
institutional experience with GI tract vasculopathy in order to
enhance diagnostic accuracy of these rare lesions. We report the
clinical and histologic features of 16 cases (excluding 16 cases of
immunoglobulin A vasculitis) diagnosed over a 20-year period.
Of the 16 patients, 14 presented with symptoms related to the GI
vasculopathy (including 2 presenting with a mass on endoscopic
examination). The remaining 2 patients presented with in-
carcerated hernia and invasive adenocarcinoma. The vasculop-
athy was not associated with systemic disease and appeared
limited to the GI tract in 8 patients. Eight had associated sys-
temic disease, but only 6 had a prior diagnosis. The underlying
diagnoses in these 6 patients included systemic lupus erythema-
tosus (1), dermatomyositis (2), rheumatoid arthritis (1), eosino-
philic granulomatosis with polyangiitis (1), and Crohn disease
(1). One patient with granulomatous polyangiitis and 1 patient
with systemic lupus erythematosus initially presented with GI
symptoms. The 8 cases of isolated GI tract vasculopathy con-
sisted of enterocolic lymphocytic phlebitis (4), idiopathic my-
ointimal hyperplasia of the sigmoid colon (1), idiopathic
myointimal hyperplasia of the ileum (1), granulomatous vascu-
litis (1), and polyarteritis nodosa-like arteritis (1). Isolated GI
tract vasculopathy is rare, but appears to be almost as common
as that associated with systemic disease. The chief primary vas-
culopathies are enterocolic lymphocytic colitis and idiopathic
myointimal hyperplasia. Although the latter occurs predom-
inantly in the left colon, rare examples occur in the small bowel
and likely represent a complex, more protean disorder.
From the *Department of Pathology, Veterans Affairs Palo Alto Health
Care System, Palo Alto; and †Department of Pathology, Stanford
University School of Medicine, Stanford, CA.
Conflicts of Interest and Funding Statements: The authors have disclosed
that they have no significant relationships with or financial interest in
any commercial companies pertaining to this study.
Correspondence: Teri A. Longacre, MD, Department of Pathology,
Stanford Medicine, Stanford, CA 94305 (e-mail: longacre@stanford.
edu).
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Key Words: gastrointestinal tract, vasculopathy, vasculitis, GI
biopsy, phlebitis, autoimmune disease
(Am J Surg Pathol 2018;42:866–876)
N oninfectious vasculitis is defined as inflammation of
blood vessel walls that may affect vessels of all sizes,
with classification based on several features including size
or type of affected vessel, cellular inflammatory compo-
nents, typical organ distribution, etiology, pathogenesis,
and clinical or laboratory parameters.1 Involvement of the
gastrointestinal (GI) tract by vasculitis is rare; however,
recognition of GI tract vasculopathy is crucial as prompt
management is frequently necessary to avoid irreversible
end-organ damage. Complications including ischemia and
perforation of visceral organs may occur, which may be
fatal in the setting of a delayed diagnosis. As such,
knowledge of the spectrum of vasculopathies that may
affect the GI tract is critical for timely diagnosis. This
report includes 16 cases of GI tract vasculopathy (ex-
cluding immunoglobulin A [IgA] vasculitis) collected at a
single institution over a 20-year period, and reviews the
pertinent clinical and histopathologic aspects of each case.
MATERIALS AND METHODS
The archival pathology files at our institution
(Stanford Department of Pathology) were searched for
cases of GI biopsies and/or resections showing involve-
ment by vasculitis or vasculopathy. Search terms included
“vasculitis,” “vasculopathy,” “capillaritis,” “arteritis,”
and “phlebitis.” Thirty-two cases of GI tract vasculitis or
vasculopathy were identified over a 20-year period. Six-
teen of these were IgA vasculitis (Henoch-Schönlein pur-
pura), reported elsewhere.2 Clinical information, including
signs and symptoms at presentation, evidence of systemic
involvement outside of the GI tract, and endoscopic im-
pressions was collected for the remaining 16 cases. Rele-
vant laboratory findings, including serology, were also
noted. The slides for each case were reviewed and perti-
nent histologic features were confirmed for each case.
RESULTS
Sixteen cases of vasculitis or vasculopathy involving
the luminal GI tract were identified; these included 8 cases
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Am J Surg Pathol  Volume 42, Number 7, July 2018 GI Tract Vasculopathy and Vasculitis

TABLE 1. Clinical and Pathologic Features of Systemic GI Tract Vasculopathy

Age (y) Sex Vasculitis Type Classification Involved Site(s) Clinical Presentation Systemic Disease
13 F Small vessel Leukocytoclastic vasculitis Small bowel Bloody diarrhea SLE
36 F Small vessel Leukocytoclastic vasculitis Small bowel Abdominal pain SLE
47 F Small vessel Leukocytoclastic vasculitis Descending colon Abdominal pain, Dermatomyositis
anemia
51 F Small and medium Dermatomyositis-associated Small bowel Abdominal pain Dermatomyositis
vessel vasculopathy
77 F Small and medium Necrotizing granulomatous vasculitis Cecum, stomach Abdominal pain, GPA
vessel anemia
56 M Small and medium Eosinophilic vasculitis Small bowel, Abdominal pain EGPA
vessel appendix
74 F Small and medium Necrotizing vasculitis Descending colon Abdominal pain Rheumatoid
vessel arthritis
15 M Predominantly veins Venulitis with thrombosis Jejunum Abdominal pain Crohn disease
EGPA indicates eosinophilic granulomatosis with polyangiitis; F, female; GPA, granulomatosis with polyangiitis; M, male; SLE, systemic lupus erythematosus.

of vasculitis with associated underlying systemic disease
(Table 1) and 8 cases that appeared to be isolated to the GI
tract (Table 2). The 8 cases with accompanying systemic
disease included 2 cases of systemic lupus erythematosus
(SLE), 2 cases of dermatomyositis, 1 case of rheumatoid
arthritis, 1 case of granulomatosis with polyangiitis (GPA)
(formerly Wegener granulomatosis), 1 case of eosinophilic
granulomatosis with polyangiitis (EGPA) (formerly Churg-
Strauss syndrome), and 1 case of Crohn disease. Five of
these patients had a prior diagnosis of systemic vasculitis,
while 3 patients (eosinophilic granulomatosis with
polyangitis, SLE, Crohn) did not have a prior diagnosis.
In 2 of these patients, their GI manifestations were the
initial presentation of disease. The clinical and histologic
features of the isolated GI tract vasculitis or vasculopathy
varied, but in all cases resections were curative and the
disease was self-limited and appeared to be confined to the
GI tract on follow-up.
Systemic Lupus Erythematosus
Two of the patients had vasculitis associated with
SLE. One of these patients, a 13-year-old female, presented
to the hospital with anemia, 20-pound weight loss, and
intermittent bloody diarrhea. Biopsies were obtained by
the gastroenterology service due to concern for possible
inflammatory bowel disease, given the intermittent bloody
diarrhea. Biopsies of the sigmoid colon showed leukocyto-
clastic vasculitis, while the remaining biopsies of the esoph-
agus, stomach, duodenum, terminal ileum, ascending
colon, transverse colon, and rectum appeared unremarkable
(Fig. 1). The possibility of a vasculitis-associated SLE was
suspected based on laboratory findings obtained several days
before the GI biopsies were taken. These findings included:
positive antinuclear antibody (ANA), positive double-
stranded DNA antibody, positive Smith antibody, low
complement, Coombs positive anemia, and lymphopenia.
A concurrent renal biopsy demonstrated class IV nephritis.
Additional evaluation revealed pericardial and pleural
effusions, along with photosensitivity. The patient was
subsequently treated with Cytoxan, solumedrol, and
prednisone with improvement of symptoms.
The second patient, a 36-year-old female with a
history of SLE, presented with severe abdominal pain and
hematemesis. Abdominal computed tomography (CT)

TABLE 2. Clinical and Pathologic Features of Isolated GI Tract Vasculopathy

Age (y) Sex Vasculitis Type Classification Involved Site(s) Clinical Presentation Other History
47 M Small and Granulomatous Small bowel Hernia Alcoholic cirrhosis
medium vessel vasculitis
45 M Veins Idiopathic myointimal Rectosigmoid GI bleeding
hyperplasia
55 F Veins Enterocolic lymphocytic Left colon Acute abdominal pain Prior right colectomy
phlebitis
57 M Small and Isolated PAN-like Cecum, left colon Crohn disease vs.
medium vessel vasculitis ulcerative colitis
56 F Veins Enterocolic lymphocytic Right, transverse, and Acute abdominal pain
phlebitis proximal left colon
81 M Veins Enterocolic lymphocytic Transverse colon Incidental finding Chronic renal failure, gout,
phlebitis hypertension
57 F Veins Idiopathic myointimal Jejunum Chronic abdominal pain ITP
hyperplasia
17 M Veins Enterocolic lymphocytic Cecum, terminal ileum Acute abdominal pain Heterozygous Factor V
phlebitis Leiden
F indicates female; ITP, immune thrombocytopenic purpura; M, male; PAN, polyarteritis nodosa.

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Louie et al
FIGURE 1. Sigmoid colon biopsy in a 13-year-old girl with
abdominal pain. Scanning magnification shows preservation of
mucosal glands with cellular infiltrates in and around intra-
mucosal vessels (hematoxylin and eosin). Inset: Leukocyto-
clastic vasculitis of intramucosal vessel characterized by
neutrophilic vasculitis with karyorrhectic debris (hematoxylin
and eosin).
imaging showed duodenal wall thickening. An esoph-
agogastroduodenoscopy was performed, which showed
dusky-appearing mucosa in the duodenum with overlying
exudate. Duodenal biopsies showed a necrotizing vasculitis
within submucosal vessels, characterized by a neutrophilic
and lymphocytic inflammatory infiltrate involving vessel
walls, with associated fibrinoid necrosis. Intravascular
fibrin thrombi were also noted.
Dermatomyositis
Two patients with a history of dermatomyositis de-
veloped a vasculitic disorder. One patient presented with
persistent anemia and was found to have a single 1-cm ulcer
within the descending colon. Biopsies were submitted with a
request to rule out colitis and Behçet disease. Histologic
examination revealed leukocytoclastic vasculitis within the
superficial submucosa. Colonic biopsies 3 months later
demonstrated mucosal ischemic changes, but no apparent
vasculitis; however, when the patient developed abdominal
pain 2 years later, biopsies of ulcers from the hepatic flexure
and splenic flexure again demonstrated a leukocytoclastic
vasculitis. A second patient presented with small bowel
perforation, requiring 3 resections. The diagnosis of a vas-
culitic disorder was not established until the third resection,
where the small bowel exhibited a vasculopathy involving
medium caliber veins and arteries with various degrees of
occlusion. The arteries showed intimal hyperplasia with
scattered foamy macrophages, some of which demonstrated
concentric medial hypertrophy (Fig. 2). There was venous
occlusion with recanalization, in addition to 1 artery that
exhibited adventitial neoangiogenesis, which underlined
the chronicity of the process. The prior resections were
reviewed, which, in retrospect, demonstrated similar vessel
changes. No active vasculitis was seen. No fungal
organisms were identified. Overall, the histologic findings
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Am J Surg Pathol  Volume 42, Number 7, July 2018
were interpreted as dermatomyositis-associated GI
vasculopathy.
GPA (Wegener Granulomatosis)
A single case of GPA (Wegener granulomatosis) was
identified. The patient was a 77-year-old woman who pre-
sented with abdominal pain, anemia, and weight loss.
Panendoscopy revealed a gastric ulcer, in addition to a large
cecal mass concerning for malignancy. Biopsies of both the
gastric ulcer and cecal mass revealed necrotizing arteritis
(Fig. 3). Further workup revealed a large left lower lobe
mass, suspicious for metastasis; however, a CT-guided
needle biopsy of the pulmonary mass showed necrotizing
granulomatous inflammation with parenchymal necrosis,
consistent with a diagnosis of GPA. Additional history from
the patient disclosed bilateral otitis media and additional
laboratory studies demonstrated positive c-antineutrophil
cytoplasmic antibodies (c-ANCAs).
EGPA (Churg-Strauss Syndrome)
One patient with a known diagnosis of EGPA (Churg-
Strauss syndrome) presented with increasing abdominal
pain and distension, with imaging revealing peritoneal free
air, suspicious for perforation. A small intestinal resection
was performed and intraoperatively, a jejunal perforation
was noted. Histologic sections showed patchy necrotizing
arteritis of submucosal vessels. The vessel walls were in-
filtrated predominantly by histiocytes and giant cells, with
focal vague granuloma formation. Numerous eosinophils
were noted surrounding the affected vessels with only few
eosinophils identified within the vessel wall itself. Scattered
lymphocytes were also present. Fibrinoid necrosis and
associated vascular occlusion were prominent (Fig. 4).
Crohn Disease
One patient with a recent diagnosis of Crohn disease
presented with abdominal pain and shock following a flu-like
illness. Resection of the jejunum showed intramural, mes-
enteric, and nodal thrombosis with organization associated
with full thickness gangrenous necrosis. Minimal venulitis
was present. A complete infectious and thrombotic workup
was negative. No viral inclusions were identified. The patient
was placed on anticoagulant therapy and there were no re-
ported recurrent thrombotic episodes on follow-up.
Isolated GI Tract Vasculitis
Eight patients had GI resections showing vasculitis or
vasculopathy without associated systemic disease (Table 2).
Specific histologic findings included granulomatous venulitis
(1), necrotizing arteritis and venulitis (1), enterocolic
lymphocytic phlebitis (4), idiopathic myointimal hyperplasia
of the rectosigmoid (1), and idiopathic myointimal
hyperplasia of the jejunum (1). Five of the cases involved
colectomy specimens, and 2 of the cases involved small
intestinal resections. The patient with granulomatous
vasculitis had a reported prior diagnosis of rheumatoid
arthritis, but concurrent serologic studies were negative. As
such, the vasculitis was interpreted as likely unrelated.
Enterocolic lymphocytic phlebitis was identified in 4
patients. One patient had a history of hypertension, gout, and
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Am J Surg Pathol  Volume 42, Number 7, July 2018 GI Tract Vasculopathy and Vasculitis

FIGURE 2. Small bowel resection in a 51-year-old woman with dermatomyositis-associated vasculopathy. A, Low-power magni-
fication showing narrowing of submucosal arteries (hematoxylin and eosin). B, Noninflammatory luminal occlusion of small artery
by a cellular myointimal proliferation (hematoxylin and eosin). C, Corresponding elastin stain showing intact internal elastic
membrane. The adjacent vein shows minimal intimal thickening (EVG).

chronic renal disease. Diagnosis of the phlebitis was made on
a resection specimen for carcinoma (Fig. 5). Another patient
had a prior history of right colectomy for “colitis” and
presented with chronic constipation. The third patient
presented with an acute abdomen while on vacation;
studies suggested colitis with intussusception; however, no
intussusception was identified on intraoperative examination.
The fourth patient, a 17-year-old male, presented with acute
abdomen with hematochezia. An exploratory laparotomy
was performed for a cecal mass. Several days later he
developed abdominal distension. The histology from both
procedures was that of a lymphocytic phlebitis. Shortly after
discharge, he developed iliac vein thrombosis with an
apparent pulmonary embolus. Thorough workup for
possible clotting disorder and/or blood dyscrasia was
negative. Follow-up endoscopic biopsies were normal and
there were no recurrent clinical manifestations.
Idiopathic myointimal hyperplasia was identified in the
sigmoid colon of a 45-year-old male who presented with
lower GI bleeding (Fig. 6). Ulcerative colitis was suspected.
A second patient initially presented 26 years prior with lower
extremity bruising and heavy menstrual cycles. Laboratory
studies at that time showed thrombocytopenia. At initial
presentation, she reported no alopecia, photosensitivity, or
arthralgias, and ANA testing for lupus was negative. She
was treated with corticosteroids for 6 months with
normalization of her platelet count. Three years later,
bruising recurred, and she was treated with corticosteroids
again and underwent splenectomy. She was asymptomatic
for another 17 years until she presented with abdominal pain
which was related to food intake. CT scan showed
thrombosis of the renal vein, inferior vena cava, and
superior mesenteric vein. She was treated with warfarin
which was discontinued after 6 months. Thereafter, she was
asymptomatic for another 5 years when she developed
nausea and abdominal pain, which occurred within 30 to
60 minutes of eating. Laboratory testing revealed a normal
complete blood count, erythrocyte sedimentation rate, C
reactive protein, and creatinine. Repeat CT scan showed
progressive thickening of the bowel wall and was concerning
for bowel ischemia. She underwent exploratory laparotomy
with resection of a 24-cm segment of ileum. The histologic
sections demonstrated myointimal hyperplasia involving
small and medium caliber veins, but no vasculitis (Fig. 7).

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Louie et al Am J Surg Pathol  Volume 42, Number 7, July 2018

FIGURE 5. Isolated vasculopathy in an 81-year-old man with

adenocarcinoma in the transverse colon. High-power magni-
fication from colonic resection showing occlusive narrowing
with pinpoint lumen by inflammatory and spindle cells. This
vasculopathy was an incidental finding in the resection speci-
men and the only vasculopathy in this series that appeared to
be entirely asymptomatic (hematoxylin and eosin).

were normal. In addition, screening for paroxysmal noctur-

FIGURE 3. Cecal biopsy from a 77-year-old woman with ab-
dominal pain and an ulcerated mass showing a necrotizing
granulomatous arteritis (hematoxylin and eosin). The lung
needle biopsy showed similar changes and c-ANCA serologies
were positive.
Laboratory testing for ANA, complement, rheumatoid
factor, anti–double-stranded DNA antibodies, lupus anti-
coagulant, anticardiolipin. Beta-2 glycoprotein and ANCA
nal hemoglobinuria, JAK2 V617F mutation, and Factor V
Leiden was negative. The patient was treated with anti-
coagulant therapy and was without symptoms at 24-month
follow-up.
DISCUSSION
The current classification of noninfectious vasculitic
disorders is based primarily on size or type of the affected
vessel (Table 3).1 Further classification is determined by
the constituent cellular inflammatory components, typical
organ distribution, etiology, pathogenesis, and clinical or

FIGURE 4. Small bowel resection from a 56-year-old man with known EGPA presenting with multifocal ischemia and perforation.
A, Low-power magnification showing sloughed mucosa. Submucosal vessels exhibit transmural infiltrates (hematoxylin and eosin).
B, High-power magnification showing necrotizing arteritis with numerous eosinophils (hematoxylin and eosin).

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Am J Surg Pathol  Volume 42, Number 7, July 2018 GI Tract Vasculopathy and Vasculitis

FIGURE 6. Rectosigmoid colonic resection in a 45-year-old man presenting with bleeding. A, Low power showing transmural
necrosis and loss of glandular crypts (hematoxylin and eosin). B, High-power magnification from mucosa adjacent to muscularis
mucosa showing arterialization of capillaries and fibrinoid alterations (hematoxylin and eosin). C, Submucosal veins and artery
showing concentric venous thickening by myointimal cells and luminal narrowing (hematoxylin and eosin). D, Elastin stain
highlighting myointimal narrowing of the vein. The adjacent artery is normal (EVG).

laboratory parameters.1 Involvement of the GI tract is
uncommon, but the ability of the pathologist to recognize
a GI tract vasculitis may prove critical to avoid irreversible
end-organ damage. The most common vasculitic disorders
to involve the GI tract are immune complex mediated
(systemic lupus, IgA vasculitis [Henoch-Schönlein purpura],
mixed connective tissue disease, and rheumatoid arthritis,
among others) (Table 4) and drug-induced vasculitis, but, as
demonstrated in this series, solitary organ vasculitis with no
evidence of systemic vasculitis may be almost as common.8,9
In our series, SLE was the most common systemic
disorder associated with GI vasculitis, followed by
dermatomyositis. SLE is a disorder that may show a
multisystemic pattern of involvement, with a diagnosis
requiring at least 4 of 11 criteria, including laboratory
findings and signs and symptoms from various organ
systems.10 GI symptoms have been reported in up to 50%
of cases, with symptoms including nausea, vomiting, and
abdominal pain. GI vasculitis has been reported to affect
35% of SLE patients presenting with acute abdomen, with
a higher incidence of vasculitis (53%) in patients with
active SLE.11 However, in a cohort of 540 SLE patients,
only a single patient was found to have vasculitis involving
the GI tract.12 Biopsies of GI sites involved by SLE may
show variable histologic findings, affecting small to me-
dium caliber arteries and/or veins with inflammation
comprised of neutrophils, lymphocytes, plasma cells, and/
or histiocytes.13–15 Fibrinoid necrosis and thrombosis may
also be seen, with accompanying ischemic changes of the
associated mucosa. Fibrinogen deposition within vessel
walls has also been reported, in addition to deposition of
IgG, IgA, and IgM within the surface epithelial basement
membrane of adjacent mucosa.16
Dermatomyositis is a subset of the idiopathic in-
flammatory myopathies, diagnosis of which requires a
combination of signs and symptoms related to muscle
weakness, other clinical manifestations including skin and
esophageal findings, laboratory parameters, and histologic
features of muscle biopsy.17 Microscopic characteristics of
GI involvement in dermatomyositis have been reported

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Louie et al Am J Surg Pathol  Volume 42, Number 7, July 2018

FIGURE 7. Small bowel resection from a 57-year-old woman with recurrent abdominal pain. A, Small bowel segment with
mucosal sloughing (hematoxylin and eosin). B, Submucosal vein showing occlusive myointimal thickening without mural
inflammation (hematoxylin and eosin). C, Elastin stain highlighting the minimal changes and absence of active vasculitic
changes (EVG).

to range from nonspecific acute colitis with vascular

TABLE 3. Classification of Vasculitic Disorders
ectasia,18 to vasculitis or vasculopathic changes with as-
Large Medium Variable sociated ulceration19 and, in severe cases, perforation.20–22
Vessel Vessel Small Vessel Vessel In cases where the initial presentation of GI involvement is
Vasculitis Vasculitis Vasculitis Vasculitis
intestinal perforation, the disease course is often fatal.
Giant cell Polyarteritis ANCA-associated vasculitis: Behçet Vasculitis has been reported more frequently in juvenile
arteritis nodosa EGPA (Churg-Strauss) disease* dermatomyositis.23
GPA (Wegener)
Microscopic polyangiitis GPA (Wegener granulomatosis) is a subtype of
Takayasu Kawasaki Immune complex Cogan ANCA-associated vasculitis. The American College of
arteritis disease IgA vasculitis syndrome Rheumatology classification criteria for GPA include na-
(Henoch-Schönlein) sal or oral inflammation, abnormal chest radiograph,
Cryoglobulinemic vasculitis microscopic hematuria, and granulomatous inflammation
Antiglomerular basement
membrane disease on biopsy.24 If 2 or more of these criteria are present, the
Hypocomplementemic sensitivity and specificity for the diagnosis of GPA is 88%
urticarial vasculitis and 92%, respectively. Although GPA rarely shows GI
(anti-C1q vasculitis) involvement, as seen in this series, GI symptoms may
The more common diseases to affect the GI tract are bolded. dominate the presenting disease. Granulomatous vasculi-
*Although IgA vasculitis and Beçhet disease appear to be frequently tis is characteristic (but may not always be seen in the GI
associated with GI manifestations, an actual vasculitis or vasculopathy is rarely
detected. biopsies), sometimes with associated necrosis, usually
involving small and medium caliber vessels.25,26 In rare

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Am J Surg Pathol  Volume 42, Number 7, July 2018
TABLE 4. Clinical and Pathologic Features of Myointimal Hyperplasia of Small Bowel Mesenteric Veins
Age (y) Sex Presentation Pathology*
57 F Acute onset nausea and Mucosal ischemia and
abdominal pain after eating ulceration
36 M Acute onset abdominal pain Mucosal ischemia and
ulceration
42 F Sudden death, likely incidental No abnormality
62 M Acute onset abdominal pain, Deep ulcer
diarrhea, small bowel
perforation
59 F Abdominal pain, diarrhea, Ileal stenosis with mucosal Concurrent small bowel NETs
cramping (6 mo) ischemia and ulceration
81 M Weight loss, abdominal Ileal stenosis; appendiceal Sigmoid diverticulitis;
distension and crampy mucinous lesion; ascites
abdominal pain
(6 mo)
*In addition to venous myointimal hyperplasia.
†Ingestion of cashew nuts, chili peppers and food possibly contaminated by mycobacterial toxins.
F indicates female; HTN, hypertension; ITP, immune thrombocytopenic purpura; M, male; NETs, neuroendocrine tumors; PBC, primary biliary cirrhosis.
cases, active colitis mimicking inflammatory bowel disease
may be noted.27 Severe cases may result in mucosal ul-
ceration secondary to ischemic changes with subsequent
perforation and risk of mortality. Endoscopic findings
may be nonspecific and mild; as such, the clinical picture
may mimic inflammatory bowel disease.28 If appropriate
laboratory studies are not performed (specifically, serol-
ogy for ANCA), the diagnosis may be missed. GPA may
also respond to steroids, which can further confound the
diagnosis.
EGPA (Churg-Strauss syndrome) is a vasculitis of
small and medium caliber vessels, characterized by
marked eosinophilia and the presence of asthma. The
American College of Rheumatology criteria for the diag-
nosis of EGPA, in a patient with documented vasculitis,
include 4 of 6 of the following: asthma, > 10% eosinophils
on white blood cell differential count of peripheral blood,
mononeuropathy or polyneuropathy, transient pulmonary
opacities on radiograph, paranasal sinus abnormality, and
an eosinophil-rich infiltrate surrounding blood vessels on
biopsy.29 GI involvement has been noted in multiple case
reports, with a majority of the reports also describing ul-
ceration and subsequent perforation of the small intestine
secondary to vasculitis.30–35 Histologic examination of
resection specimens typically reveals a necrotizing vascu-
litis with histiocytes and occasional giant cells within the
vessel walls, accompanied by an eosinophilic infiltrate
surrounding the vessels.9 Given the frequent reports of
perforation secondary to vasculitis in the setting of EGPA,
this diagnosis should be considered in a patient presenting
with perforation, ischemia, or multiple small intestinal
ulcers; the diagnosis is facilitated by the identification of a
granulomatous vasculitis with associated eosinophilic in-
filtrates.
One patient with recent diagnosis of Crohn disease
on therapy presented with acute abdomen secondary to
extensive thrombosis of small and medium caliber veins
throughout the jejunal mesentery and bowel wall. In-
flammatory bowel disease is associated with a 2-fold to
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GI Tract Vasculopathy and Vasculitis
Other Medical History Medications Reference
ITP None This series
None None† 3
HTN Propranolol 4
Renal transplant, PBC Tacrolimus, 5
mycophenolate
mofetil, prednisone
None 6
None 7
normocytic anemia;
hypoalbuminemia
3-fold increased risk of venous thromboembolism.36,37
The risk appears to be higher during active disease36,38 and
hospitalization,38,39 as well as in younger patients.37,40
Cerebral vessels are most frequently affected, followed by
limb, abdominal vessels, retina, and lungs.40 Thrombotic
complications appear to respond to anticoagulant therapy,
but may recur.
A variety of other systemic disorders, such as mixed
connective tissue disorder, polyarteritis nodosa, and
microscopic polyangiitis, may be associated with GI
vasculitis.9 Rarely, rheumatoid vasculitis, a necrotizing
vasculitis involving small to medium caliber vessels, may
develop in the GI tract. Affected patients typically have
long-standing, seropositive, severe and uncontrolled
disease.41 Despite the strong association of Behçets’ dis-
ease with GI manifestations,42 we did not encounter any
bona fide cases of Behçet vasculitis in our retrospective
review. Instead, endoscopic biopsies from patients sus-
pected to harbor a systemic vasculitis, such as Behçet,
demonstrated either no abnormality or less commonly,
nonspecific chronic inflammation or other mucosal fea-
tures that could be compatible with underlying ischemia or
ulceration secondary to a variety of disorders.43
In this series, isolated GI tract vasculitis or vascul-
opathy was as common as vasculitis associated with sys-
temic disease. Under the 2012 Chapel Hill consensus
nomenclature, isolated GI tract vasculitis is classified as
“single organ vasculitis,” which is defined as vasculitis of
arteries or veins restricted to a single organ without evi-
dence of an accompanying systemic vasculitis.1 Several
studies have addressed the incidence of localized vasculitis
of the GI tract, but, as some patients were subsequently
found to have systemic disease, the true incidence of
“single organ vasculitis” is uncertain.44,45 In our series, the
most common form of isolated vasculitis in the GI tract
was enterocolic lymphocytic phlebitis followed by idio-
pathic myointimal hyperplasia. Since both processes are
restricted to veins, some authors have considered these
entities as a single disease that also encompasses cases
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Louie et al
previously described as mesenteric veno-occlusive disease.8
However, in our opinion, the constellation of clinical and
pathologic features of these 2 diseases differ significantly.
Enterocolic lymphocytic phlebitis is characterized by a
lymphocytic phlebitis that involves small and medium
caliber veins.46–48 Fresh or organizing venous thrombi
may also be seen. Most cases occur in older adults (median
age, 63 y), often with underlying disease (cardiovascular
disease, hypertension, renal failure, malignancy, etc.), and
the right colon and/or small intestine is typically
affected.46–48 Patients typically present with signs of an
acute abdomen (i.e., acute abdominal pain, nausea,
vomiting, diarrhea, and rectal bleeding). Surgical resection
is diagnostic and curative, although rare patients have
required additional surgical resections. The resected bowel
often shows ischemic changes which range from mucosal
ischemia to hemorrhagic transmural infarction; strictures
may be present.46–48 Although various degrees of myointimal
hyperplasia may also be seen in enterocolic lymphocytic
phlebitis, there is almost always some degree of lymphocytic
venulitis, which may be necrotizing or granulomatous.
In contrast, idiopathic myointimal hyperplasia occurs
predominantly in middle-aged, previously healthy men and
affects the left colon and rectum.49–51 Rare examples of
more extensive colonic involvement have been reported.
Patients present with complaints of several months (mean,
5.3 mo) of abdominal pain and bloody diarrhea. Up to 70%
of patients may be misdiagnosed with inflammatory bowel
disease before surgical intervention.49–51 There is no venous
inflammation; rather, there is a striking narrowing of the
lumens of medium and large caliber intramural and mes-
enteric veins by profound myointimal hyperplasia. The
presence of arteriolized capillaries, subendothelial fibrin
deposits, and perivascular hyalinization may suggest the
diagnosis in biopsy specimens.52 Although the latter disease
is considered “idiopathic,” chronic mechanical stress on
mesenteric veins due to hypermobility of the rectosigmoid
colon has been proposed as a possible cause.52 As with
enterocolic lymphocytic phlebitis, surgical resection is
curative. Neither of these disease processes respond to
medical therapy and the use of steroids may predispose to
perforation.
One of the patients in our series who presented with
acute small bowel ischemia had mesenteric and mural
myointimal hyperplasia with luminal occlusion of small
and medium caliber veins in the small intestine. There was
no associated inflammation. At least 5 additional cases of
myointimal hyperplasia involving the small bowel have
been reported (Table 4).3–7 Although the histologic
features in each of these cases are identical to that seen
in typical idiopathic myointimal hyperplasia of the lower
GI tract, we believe this likely represents a separate entity.
The presenting symptoms are more variable and in no
case, has the clinical impression been that of suspected
inflammatory bowel disease. Two of the reported patients
presented with acute symptoms while 1 presented with
sudden death (Table 4). The latter patient had a history of
hypertension treated with propranolol and the degree of
venous changes was mild to moderate and likely an
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Am J Surg Pathol  Volume 42, Number 7, July 2018
incidental finding.4 Two other patients presented with a
more prolonged clinical course marked by intermittent
abdominal pain.6,7 In each case, surgical resection resulted
in complete resolution of symptoms. In 1 patient, who was
otherwise healthy, the vasculopathy was ascribed to
consumption of chili peppers and nuts or to food
contaminated by mycobacterial toxins.3 No history of
unusual food consumption was reported in any of the
other cases. However, the clinical presentation, variation
in onset of symptoms and more frequent association with
underlying medical disease suggests that myointimal
hyperplasia involving the tributaries of the superior
mesenteric vein may reflect a more complex, protean
disorder than that typically involving those of the inferior
mesenteric vein. The relationship, if any, to immune
thrombocytopenic purpura and prior thrombosis in our
patient is unclear. Thrombotic episodes have been reported
to occur in the setting of immune thrombocytopenic
purpura,53 but there was no evidence of thrombosis in the
resected small bowel. Although mechanical factors may
present a unifying underlying cause of idiopathic myointimal
hyperplasia in the large bowel, the pathogenesis of this
disorder in the small bowel is less clear, and it is possible that
a variety of factors may contribute, including immune
dysfunction, drugs, and toxins, among others. Until more
cases of small bowel myointimal hyperplasia are studied, we
think they should be distinguished from idiopathic
myointimal hyperplasia of the left colon, due to their
apparent more varied clinical presentation and possible
association with other underlying medical diseases.
Although a variety of systemic vasculitic disorders
are associated with GI manifestations, bona fide GI tract
vasculitis is rare. Patients present with varied symptoms,
and workup for inflammatory bowel disease or malig-
nancy is often initiated. In our series, mass lesions were
present in 2 patients and another 2 were undergoing
evaluation for possible ulcerative colitis or Crohn disease.
Endoscopic biopsies have a low sensitivity to diagnose GI
vasculitis, even though the presence of ulcerative or is-
chemic changes may be suggestive. Colon biopsies may
contribute to establishing a specific diagnosis of vascul-
opathy, especially in the setting of left colic idiopathic
myointimal hyperplasia. Clinical history, including con-
current disease, renal function, skin rash, lung symptoms,
serum Ig profile, tissue immune complex status (if known),
and medication history is required. However, even with a
compelling history of possible vasculitic disorder, estab-
lishing the diagnosis may be difficult. Underscoring this
challenge, in our series, 1 patient with dermatomyositis
underwent 3 resections before the vasculitis could be
identified. Ultimately, classification is based on the type
and caliber of vessel involved. Extensive sampling of the
resection specimen including areas of viable bowel and/or
mesentery should be obtained to ensure that there is un-
equivocal vasculitis present. Vascular damage with
thrombi may be seen in association with bowel infarction
and should not be interpreted as vasculitis. A Verhoef-Van
Gieson (EVG) elastic stain is recommended to identify
vessel type and confirm vessel damage. Isolated GI tract
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Am J Surg Pathol  Volume 42, Number 7, July 2018
vasculitis or vasculopathy is rare but appears to be as
common as that associated with systemic disease. The
chief primary vasculopathies are enterocolic lymphocytic
colitis and idiopathic myointimal hyperplasia. Although
the latter occurs predominantly in the left colon, rare ex-
amples occur in the small bowel and likely represent a
more complex, protean disorder.
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