Rodger C. Haggitt Slide Seminar: Lesions of Esophagus, Stomach, and Duodenum
Moderators: Dr. Cecilia Fenoglio-Preiser and Dr. Wendy Frankel
Case 4 -
Radiation And Chemotherapy-Associated Gastric Ulcers Vs Gastric Carcinoma/Dysplasia
Robert E. Petras, M.D., FASCP, FACG
Associate Professor of Pathology
Northeastern Ohio Universities, College of Medicine
National Director for Gastrointestinal Pathology Services, AmeriPath, Inc.
The patient, a 46 year old man, presents with marked epigastric pain. Upper endoscopy reveals a very
large gastric ulcer involving most of the anterior wall of the body and antrum of the stomach. The ulcer
is described as clean-based with smooth edges.
Description of Slide and Discussion
The biopsy specimen from this case demonstrates epithelial atypia mimicking dysplasia/adenocarcinoma
but shows many of the features described with HAIC-associated atypia. These findings prompted a phone
call to the referring gastroenterologist for a more detailed clinical history. Twenty days prior to his
presentation with severe epigastric pain, the patient had received selective internal radiation therapy
(SIRT) for metastatic colonic adenocarcinoma involving the liver. His hepatic artery had been injected
with an infusion of 35 micron, radioactive yttrium-90 microspheres made of biocompatible resin
(SIR-Spheres, SIRTeX Medical Inc., Lake Forest , IL ). This history helps explain not only the
epithelial atypia but the presence of the small black microspheres within the mucosal capillaries.
Case 4 - Slide 1
SIRT can be a useful palliative measure for metastatic carcinoma in liver
selective hepatic arterial infusion, forty times the radiation dose can be delivered to the tumor (vs.
conventional radiation techniques) while minimizing side effects. SIR-Spheres employ yttrium-90 which
emits beta irradiation with a half-time of 64 hours. Reported side effects of this therapy include
lethargy, anorexia, nausea, fever, pancreatitis and right upper quadrant pain. Gastrointestinal
hemorrhage has been reported in less than 2% of patients
Rare examples of gastric
and duodenal ulcer, cholecystitis and interstitial pneumanitis have been reported, some in association
with embolization and migration of the radioactive microspheres into extrahepatic organs
Based on our experience with two patients with gastric ulcer caused by SIRT, the gastric lesion
appears self limiting. With a relatively short half-time, the radiation dose to the tissues becomes
negligible in 2-3 weeks. Proton pump inhibitors may be effective as an aid in healing. Our patient was
treated with esomeprazole (40 mg bid) with relief of the epigastric pain in one week. Follow-up
endoscopy done 6 weeks later revealed near complete healing of the ulcer.
The atypia seen in gastric brushings and biopsy specimens from patients treated with hepatic arterial
infusion chemotherapy/radiation therapy may be prominent and alarming. Care must be taken to avoid
misinterpretation of the findings as adenocarcinoma/dysplasia. Documentation of a clinical history of
prior treatment with hepatic arterial infusion chemotherapy/radiation therapy should alert the
pathologist to this potential pitfall in interpretation .
Gastric epithelial atypia associated with hepatic arterial infusion of SIR-Spheres mimicking gastric
Regional forms of chemotherapy and radiation therapy are used clinically with increasing frequency.
Many employ hepatic arterial infusion and are used to treat primary and metastatic carcinoma involving
the liver. A number of complications can occur with these forms of therapy
These ulcer can closely mimic primary gastric carcinoma clinically, endoscopically, and
sometimes in biopsy and gastric brush cytology specimens
Similar atypia has been seen in small
intestinal epithelium in patients receiving this form of regional chemotherapy
In order to identify features useful in distinguishing hepatic arterial infusion chemotherapy
(HAIC)-associated atypia from gastric carcinoma, we reviewed gastric ulcers associated with HAIC. For
comparison we used a control group of 20 patients with early gastric carcinoma of intestinal type, the
lesion most likely to be confused with chemotherapy-associated ulcer. The chemotherapy-associated lesion
showed a marked resemblance to irradiation effect. The Table lists those features that were most helpful
in distinguishing chemotherapeutic effect (and radiation effect) from carcinoma/dysplasia in histologic
Table 1: Differential Features Between HAIC-associated Atypia and Early Gastric Adenocarcinoma
| ||HAIC ATYPIA ||GASTRIC CARCINOMA/DYSPLASIA|
|Mucosal architecture ||Preserved ||Distorted|
|Location of atypia ||Glands ||Foveolar|
|Cellular features ||Bizarre|
|N/C ratio ||Low ||High|
|Cytoplasmic eosinophilia ||Present ||Absent|
|Cytoplasmic vacuolization ||Present ||Absent|
|Mitotic figures ||Few or none ||Numerous|
|Atypia in granulation tissue ||Present ||Absent|
|Intestinal metaplasia ||Usually absent ||Present|
Similar bizarre cytologic atypia may be seen in gastric brushing specimens in patients receiving HAIC
The atypical features of the epithelial cells resemble pronounced radiation effect. Atypical
cells in gastric brushings can exist singly or in small clusters or flat sheets. Papillary formations or
three-dimensional cellular aggregates were not observed in the specimens we studied. The most consistent
feature of HAIC atypia was marked enlargement of the cytoplasm and nucleus. In spite of large size, the
nuclear-cytoplasmic size ratio remained relatively low. The cytoplasm of the atypical cells was often
foamy or vacuolated. The enlarged nuclei were vesicular, round to oval, and often eccentrically placed
in the cytoplasm. Nuclear contours were smooth. Massive round or angulated nucleoli, either single or
multiple, were characteristic. Binucleation and multinucleation were common.
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