Rodger C. Haggitt Slide Seminar: Lesions of Esophagus, Stomach, and Duodenum
Moderators: Dr. Cecilia Fenoglio-Preiser and Dr. Wendy Frankel
Case 12 -
Gastric Hyperplastic Polyp with Malignant Transformation
Gregory Y. Lauwers, M.D.
Director, Gastrointestinal Pathology Service
Massachusetts General Hospital
Harvard Medical School
A 75-year-old woman, previously healthy, presented to her family doctor for general fatigue. Routine
tests demonstrated an iron deficiency anemia. A full colonoscopy had been performed in the recent past
and had demonstrated 2 hyperplastic polyps. She again was referred to a gastroenterologist, who this
time performed an upper endoscopy. The examination demonstrated an atrophic antral mucosa. In addition,
a large 2 cm polyp was identified. Of note, the polyp appeared friable when touched by the tip of the
endoscope, and bled easily. A polypectomy was attempted.
Case 12 - Slide 1
Diagnosis: Gastric Hyperplastic Polyp with Malignant Transformation.
Most gastric polyps are incidental findings found in about 2% of endoscopies performed for other
reasons. Occasionally, though, they may become inflamed and eroded, but subsequent bleeding is rarely
apparent. Rarely, a large polyp may lead to gastric obstruction.
Hyperplastic polyps are the most or second most common type of gastric polyp.
terminology have used to describe these polyps: "hyperplasiogenous" or "regenerative" polyps.
Clinical Features and Pathogenesis
Hyperplastic polyps are randomly distributed throughout the stomach. When distal, the larger polyps
also can manifest with gastric outlet obstruction, and there are rare reports of hyperplastic polyps
prolapsed into the duodenum, with obstruction of the ampulla of Vater and secondary pancreatitis.
The stimuli for the development of hyperplastic polyps are not known. They are thought to result
from excessive regeneration following mucosal damage and, as such, occur in chronic Helicobacter-associated gastritis (25% to 37% of the cases),
autoimmune gastritis (51.3%) with or without pernicious anemia, adjacent to ulcers and erosions,
or at gastroenterostomy sites.
They also occur in gastric remnants adjacent to gastro-jejunostomy stomas and in the gastric
cardia/GE junction of patients with chronic esophageal reflux.
The majority seat in gastric mucosa, showing some degree of chronic atrophic gastritis and intestinal
Hyperplastic polyps have a wide age range but are more common with increasing age (mean age: 57.3 to
66 years. Notably, all series report a peculiar predisposition in women that represents between 58 and
63.5% of patients. Depending on various series, 32 to 60% of hyperplastic polyps are located in the
antrum, 29 to 49% are in the body fundus, and only about 2.5% in the cardia.
Gross and endoscopic features
Hyperplastic polyps are single in about two thirds of cases. The small polyps are smooth-surfaced,
dome-shaped, sessile lesions, while the large ones are frequently lobulated and sometimes pedunculated.
Superficial erosion commonly occurs. Their size ranges from less than one centimeter up to an
exceptional 13 cm. However, most cases measure less than 1 cm, and polyps larger than 2 cm represent
Histologically, hyperplastic polyps are characterized by two features: a) Marked elongation of the
pits with branching, resulting in a corkscrew appearance or in cystic dilatation of foveolae lined by
tall mucin-secreting cells, and 2) excess of edematous lamina propria with inflammation characterized by
an infiltrate composed of plasma cells, lymphocytes, eosinophils, mast cells, macrophages, and variable
numbers of neutrophils. Interspersed wisps of smooth muscle fibers are quite commonly seen between the
gastric pits and arise from thickened split and fragmented muscularis mucosae. The gastric glands do not
normally participate in the formation of the polyps.  The glands are lined by a single layer
of hyperplastic foveolar-type epithelium, though pyloric-type glands, chief cells, parietal cells, and
foci of intestinal metaplasia may be found, especially in the deeper zones.
The surface of the polyp may be ulcerated and acutely inflamed, showing degenerative and regenerative
atypia in the epithelial and stromal cells within a prominent reparative granulation tissue with numerous
capillaries. There also may be invagination of the surface mucosa with budding, which may produce a
back-to-back appearance, as well as the appearance of pseudo-invasion;  this can cause major
diagnostic problems, since true carcinoma  may be found in hyperplastic polyps.
Polypoid hyperplasia or hyperplastic polyps of the cardia and gastro-esophageal junction, either of
foveolar type or mixed with squamous epithelium, can be observed. They are believed to represent a
regenerative response to surrounding mucosal injury, such as ulcers, erosive esophagitis, or "junctitis"
of the gastro-esophageal junction.
They have been observed variably in the setting of
gastroesophageal reflux disease. Histologically, they are mostly comprised of cardiac-type mucosa.
Admixed squamous mucosa also can be seen and, rarely, parietal cells. Intestinal metaplasia is variably
seen and dysplasia is rare (<3%). 
Differential Diagnosis of Hyperplastic Polyps
The differential diagnosis is that of Ménétrier's disease, Cronkhite-Canada syndrome, and juvenile
polyposis. Hyperplastic polyps are easily distinguished from Ménétrier's disease by their smaller size
and the presence of intervening normal mucosa (unless they are numerous). The distinction from juvenile
polyposis rests entirely on the clinical diagnosis and the demonstration of juvenile polyposis in the
large bowel. The differentiation from Cronkhite-Canada may be difficult, and unless diffuse, may depend
on the typical ectodermal features clinically.
Among the diagnostic challenges that may occur when evaluating hyperplastic polyps, distinguishing
between regenerative changes and dysplasia may be the most difficult. When attenuated epithelium is seen
actively growing over an ulcerated surface, then it reasonably can be presumed that the pits in the
immediate vicinity of the ulceration, as well as the attenuated epithelium, are all showing regenerative
changes. In some polyps, however, the typical appearance of dysplasia may be seen, and very rarely one
is surprised to find a focus of carcinoma.
Evolution/Prognosis of Hyperplastic Polyps
Over time, hyperplastic polyps can increase in number or regress, either spontaneously or following
Helicobacter eradication. 
Historically, they were believed to confer no risk of malignant transformation. However, malignant
transformation, although rare, is well-documented. Malignant degeneration has been reported to occur in
0.3% to 7.1% of hyperplastic polyps (average 2.1%),
and dysplasia has been reported in 1.8% to 16.4% of hyperplastic polyps.
study, dysplasia was identified in 19.4% of hyperplastic polyps, but this figure may be inflated, since
polyps smaller than 5 mm in diameter were excluded.  Polyp size greater than 2 cm is
associated with an increased risk of its harboring dysplastic or malignant foci. Thus, larger polyps
should be completely excised for histologic exclusion of neoplasia. The molecular genetics of carcinoma
arising in gastric hyperplastic polyps are likely to follow the classical gastric adenocarcinoma. An
immunohistochemical analysis showed that p53 reactivity was observed in the adenomatous foci of all
transformed polyps, while it was negative elsewhere. 
Also, given the frequent surrounding background of intestinal metaplasia and dysplasia, an
association with a synchronous carcinoma elsewhere in the stomach is recognized,
therefore, careful endoscopic assessment of the surrounding mucosa is important.
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