Case 5 -
Gastroduodenal Lymphocytic Phlebitis,
associated with Lymphocytic Gastritis and Gastric Antral Ulceration
Susan C. Abraham
Click on each slide thumbnail image for an enlarged view
A 68-year-old man was admitted to an outside hospital because
of epigastric pain, melena, and hematemesis that required multiple transfusions. His past medical
history was significant for cardiomyopathy that had required pacemaker insertion, and he was receiving
aspirin and Coumadin at the time of his gastrointestinal bleed. Upper endoscopic examination during that
admission revealed a large gastric ulcer located in the posterior aspect of the antrum. The patient was
told that he was negative for H. pylori (although it is not clear from the
medical record how that determination was made). He was started on Prevacid 30 mg b.i.d Because of
persistent mild epigastric pain as an outpatient, repeat upper endoscopy was performed 9 months later and
showed a persistent posterior antral ulcer that measured 5 cm. He eventually underwent hemigastrectomy
with vagotomy and a Billroth II gastroduodenal anastomosis. The slide shown includes both antral ulcer
and adjoining viable antral mucosa and wall. The duodenum (to be shown later) had similar findings but
Case 5 - Figure 1 - Active chronic ulcer site in the antrum shows luminal fibrinoinflammatory exudate and underlying granulation tissue.
Case 5 - Figure 2 - Obliterative phlebitis is present in a submucosal vein beneath non-ulcerated gastric mucosa. The adjacent artery is normal.
Case 5 - Figure 3 - Phlebitis also involves vessels of the muscularis propria and subserosa, seen here in the duodenal wall.
Case 5 - Figure 6 - Lymphocytic gastritis in the non-ulcerated gastric antral mucosa.
Case 5 - Figure 7 - Mild lymphocytosis is also present in the duodenal epithelium, and there is associated villous blunting.
The patient initially did well, but at 16 months after surgery
he began to complain of severe cramping epigastric pain, nausea, vomiting, intractable hiccupping, and
heartburn. He was hospitalized 8 times over the subsequent 7 months. An extensive clinical and
radiologic work-up included CT scans of the head, abdomen, and pelvis, and upper GI small bowel
follow-through, which were negative. Doppler ultrasound of the mesenteric arteries and celiac axis
showed patent vessels without significant stenoses. Upper endoscopy revealed diffuse bile reflux
gastritis, as well as grade 2-3 esophagitis and hiatal hernia, but there was no recurrence of the gastric
ulcer. A colonoscopy to the level of the terminal ileum showed no evidence for inflammatory bowel
disease. Gastric biopsies (taken 25 months after surgery) showed a pattern of reactive gastropathy
consistent with bile reflux in the setting of gastro-enteric anastomosis; lymphocytic gastritis was no
longer present and there was negligible chronic inflammation within the lamina propria. The remainder of
the biopsies from the duodenum, terminal ileum, and colon were normal.
The resection specimen included antrum,
antral-fundic transition zone, and proximal duodenum. At the time of gross examination, a 4 cm x 3 cm
red, hemorrhagic ulcer was noted in the distal antrum, whereas the remainder of the gastric mucosa was
reported to be normal, without focal lesions. The duodenum contained a 0.4 cm mucosal polyp within the
bulb (which proved to be heterotopic gastric fundic mucosa), but was otherwise grossly normal.
Histologic sections revealed a benign chronic
antral ulcer, with a granulation tissue base that extended into the submucosa. Lymphocytic and
granulomatous phlebitis involved veins in the submucosa and muscularis propria; there was limited
material for evaluation of the subserosal vessels, but one section containing subserosal adipose tissue
also demonstrated lymphocytic phlebitis of a small subserosal vein. The phlebitic lesions were present
in the veins deep to the antral ulcer as well as in the gastric and duodenal walls away from the ulcer
site. Adjacent arteries and nerves were completely spared and appeared histologically normal. In some
of the involved veins, vessel walls were infiltrated by small lymphocytes, which also formed cuffs in the
perivenular tissue. In other veins, the inflammatory infiltrate included a prominent component of
epithelioid histiocytes and rare multinucleated giant cells in addition to small lymphocytes; granulomas
outside of vein walls were completely absent. Smaller numbers of plasma cells and large activated
lymphocytes were also present. We saw no fibrinoid necrosis of the vein walls, and only a rare small
venous thrombus was identified. However, the lumens of involved veins were variably compromised,
including some veins with complete disruption of the wall and obliterative phlebitis.
The antral mucosa away from the ulcer site showed lymphocytic gastritis, with numerous small
intraepithelial T-cells within the surface epithelium and foveolar neck epithelium, and numerous plasma
cells within the superficial lamina propria. Both the resection specimen and a set of three previous
gastric biopsies were negative for H. pylori. The duodenal bulb contained
heterotopic gastric fundic mucosa as well as extensive gastric mucin cell metaplasia and near-complete
blunting of the duodenal villi. Both the metaplastic gastric-type epithelium and the non-metaplastic
intestinal epithelium also showed a lymphocytosis, which was much more prominent in the gastric-type
epithelium (>100 lymphocytes/100 epithelial cells) than in the intestinal epithelium (20-40
lymphocytes/100 epithelial cells).
phlebitis, associated with lymphocytic gastritis and gastric antral
Among the vasculitic diseases that have been described to
affect the gastrointestinal tract – e.g., polyarteritis nodosa, Churg-Strauss syndrome, Henoch-Schonlein
purpura, hemolytic-uremic syndrome, Wegener's granulomatosis, enterocolic lymphocytic phlebitis, Behcet's
disease, and collagen-vascular disease-associated vasculitis – only lymphocytic phlebitis exclusively
affects the mural and mesenteric venous system.
In 1976, Stevens first reported this distinctive form of vasculitis in a previously healthy
36-year-old woman who underwent a right hemicolectomy for sudden, severe abdominal pain and
diarrhea.  Histologically, there were numerous phlebitic lesions throughout the bowel wall,
ranging from fibrinoid necrosis of vein walls to a more chronic, granulomatous perivenular infiltrate
that resulted in partial to complete vein occlusions. Unexpectedly, the arteries and lymphatics were
completely spared from this inflammatory reaction, which the authors speculated might be the result of an
immunologic reaction to material absorbed from the bowel lumen.  Termed "necrotizing and giant
cell granulomatous phlebitis" by the authors, this unusual form of vasculitis was not described again in
the luminal GI tract for 13 years. In 1989, Saraga reported three patients who suffered from intestinal
ischemic necrosis associated with lymphocytic phlebitis and proposed the term "enterocolic lymphocytic
phlebitis."  It is this name (ELP) by which this distinctive type of primary gastrointestinal
vasculitis is now known, although various authors have referred to similar cases as "granulomatous giant
cell polyphlebitis,"  "mesenteric inflammatory veno-occlusive disease,"
intestinal lymphocytic microphlebitis,"  "isolated granulomatous phlebitis,"  and
"intramural mesenteric venulitis." 
ELP is rarely diagnosed, and although almost 40 patients have now been reported in the English
literature, most are in the form of case reports
or small case
The three largest series, by Burke,  Flaherty,  and
Saraga,  have respectively described 10, 7, and 6 patients with ELP. Several distinctive
clinicopathologic characteristics have emerged from these reports. Most patients with ELP present with
acute abdominal symptoms including severe abdominal pain, diarrhea, and/or
Patients with ELP have ranged from 27 – 78 years and there has been no
clear gender predilection.
Most cases of ELP have involved the colon (particularly the
but cases involving the ileum
small bowel and colon
have also been described; rarely, there is pancolonic
necrosis.  Characteristically, these patients recover quickly following resection of the
involved bowel, without intestinal or systemic recurrence of the vasculitis.
The patient presented here with lymphocytic phlebitis is unusual in two respects. First, his symptoms
followed a more chronic course than is typical, since his epigastric pain and gastric ulceration were
documented for a total of 9 months prior to surgical intervention. However, several patients with ELP
affecting the lower gastrointestinal tract have also been noted to have unusual, subacute, or chronic
presentations. In the series by Saraga, 4 of 6 patients suffered from prodromal abdominal pain, weight
loss, and/or rectal bleeding occurring from several weeks to months before the onset of acute abdominal
signs.  Two patients demonstrated histologic changes indicative of chronic ischemia in their
resection specimens. One of these patients in particular, a 70-year-old man, suffered from abdominal
pain for years and rectal bleeding for several months preceding surgery.  Furthermore, 4
patients in that series also complained of recurrent abdominal pain after surgery, although recurrent ELP
was histologically documented in only one of these cases, and no patient required
re-operation.  This suggests that ELP may not always be an acute illness, and may not always
fully resolve with surgical intervention. Although our patient did suffer from abdominal complaints
after his surgery, the fact that this occurred fully 16 months after an initially uneventful recovery, as
well as the fact that no recurrent gastric ulceration occurred, likely indicates that his complaints were
not the result of recurrent lymphocytic phlebitis.
Second, the lymphocytic phlebitis in our patient involved the stomach and duodenum, without evidence
for ileal or colonic ischemia. Involvement of the upper GI tract by lymphocytic phlebitis has not been
previously reported. However, lymphocytic/granulomatous phlebitis has been reported in other
extracolonic sites including the pulmonary veins,  liver,  skin (sometimes
affecting both the cutaneous and mesenteric veins),  gallbladder,  and
omentum.  Therefore, there is no theoretical reason why a similar process should not also
affect the gastric and/or duodenal venous system.
Aside from these differences in clinicopathologic presentation, the histologic findings in our patient
were otherwise typical for ELP. There was extensive phlebitis of the small and medium-sized submucosal,
mural, and perigastric veins, whereas the adjacent arteries were completely spared. The vein walls and
perivenular areas were infiltrated by cuffs of small, mature lymphoid cells which were admixed with
scattered plasma cells and eosinophils. Tuppy et al have previously shown
that the many of the perivenular T-cells are CD4-/CD8+/TIA-1+ cytotoxic T-cells,  and our
case confirmed this immunophenotypic profile. In some areas, there was also prominent granulomatous
perivenular inflammation. Giant cell phlebitis was reported in 30% of Burke's cases of ELP, 
as well as those reported by Stevens,  Flaherty,  Leu, 
Satge,  Martinet,  and Saraga.  Although some authors have described
thromboses and fibrinoid necrosis of the vein walls,
we found only rare small
thrombi and no fibrinoid necrosis. However, many of the vein lumens were markedly narrowed or
obliterated by the inflammatory reaction. Notably, the phlebitis in our patient was present not only in
association with the gastric antral ulceration but also within non-ischemic areas of the stomach and
duodenum – a phenomenon that has been well-described in some cases of ELP from the lower GI
The pathogenesis of lymphocytic phlebitis is unclear. In their initial report, Stevens proposed that
ELP might represent an immunologic reaction to material absorbed from the bowel,  and Saraga
likewise suggested a hypersensitivity-type reaction.  Many of the reported patients with ELP
were receiving one or multiple types of medications,
but this is not a universal
feature  and no one drug has emerged as a consistent etiologic agent. The fact that our
patient showed both lymphocytic gastritis and duodenitis which had completely resolved (without dietary
therapy and without other clinical evidence for celiac disease) 2 years after his surgical resection
would also suggest the possibility of a drug hypersensitivity reaction, since some cases of lymphocytic
colitis are drug-associated.
However, a detailed list of medications taken by the patient
at the time of his presentation and outside clinical workup was not available to us.
Why has lymphocytic phlebitis not been previously described to affect the upper gastrointestinal
tract? First, processes that result in classic histologic features of ischemia in the colon may not be
recognizable as such when they affect the stomach. For example, administration of Kayexalate in
hypertonic sorbitol, which causes acute ileal/colonic ischemic necrosis in a small subset of patients,
typically shows only nonspecific mucosal erosions or ulcerations when the upper gastrointestinal tract is
involved. Similarly, Burke et al described a non-healing gastric ulcer that
resulted from polyarteritis.  The diagnosis of lymphocytic phlebitis requires not only a
level of awareness on the part of the pathologist, but also requires deep submucosal or mural veins for
examination – material which is unlikely to be obtained except through surgical resection. As surgical
resection for benign gastric ulcers is not typical first-line therapy, we suggest that gastric
involvement by lymphocytic phlebitis may not be as rare as this single case would imply.
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