Case 12 -

Gastric Hyperplastic Polyp with Malignant Transformation Gregory Y. Lauwers, M.D. Director, Gastrointestinal Pathology Service Massachusetts General Hospital Harvard Medical School

Clinical history: 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 Click to view with ImageScope Click to view with a Web-Based Viewer 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. [1, 2, 3] Various 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), [4, 5] autoimmune gastritis (51.3%) with or without pernicious anemia, adjacent to ulcers and erosions, [5, 6] 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 metaplasia. [7] 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 only 10%. Microscopic Appearance 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. [8] 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; [9] this can cause major diagnostic problems, since true carcinoma [3] 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. [10, 11] 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%). [10] 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. [7] 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%), [12, 13, 14] and dysplasia has been reported in 1.8% to 16.4% of hyperplastic polyps. [3, 13, 14, 15] In one 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. [16] 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. [17] Also, given the frequent surrounding background of intestinal metaplasia and dysplasia, an association with a synchronous carcinoma elsewhere in the stomach is recognized, [1, 2, 3] and therefore, careful endoscopic assessment of the surrounding mucosa is important. References Laxen F, Sipponen P, Ihamaki T, Hakkiluoto A, Dortscheva Z. Gastric polyps: their morphological and endoscopical characteristics and relation to gastric carcinoma. Acta Pathol Microbiol Immunol Scand [A]1982;90:221-228. Nakamura T, Nakano G. Histopathological classification and malignant change in gastric polyps. J Clin Pathol1985;38:754-764. Hattori T. Morphological range of hyperplastic polyps and carcinomas arising in hyperplastic polyps of the stomach. J Clin Pathol1985;38:622-630. Veereman Wauters G, Ferrell L, Ostroff JW, Heyman MB. Hyperplastic gastric polyps associated with persistent Helicobacter pylori infection and active gastritis. Am J Gastroenterol 1990;85:1395-1397. Dirschmid K, Platz-Baudin C, Stolte M. Why is the hyperplastic polyp a marker for the precancerous condition of the gastric mucosa? Virchows Arch2006;448:80-84. Mori K, Shinya H, Wolff WI. Polypoid reparative mucosal proliferation at the site of a healed gastric ulcer: sequential gastroscopic, radiologic and histologic observations. Gastroenterology1971;61:523–529. Ohkusa T, Takashimizu I, Fujiki K, et al. Disappearance of hyperplastic polyps in the stomach after eradication of Helicobacter pylori. A randomized, clinical trial. Ann Intern Med 1998;129:712-715. Muller-Lissner SA, Wiebecke B. Investigations on hyperplasiogenous gastric polyps by partial reconstruction. Pathol Res Pract, 1982:368–378. Dirschmid K, Walser J, Hügel H. Pseudomalignant erosion in hyperplastic gastric polyps. Cancer1984;54:2290–2293. Abraham SC, Singh VK, Yardley JH, Wu TT. Hyperplastic polyps of the esophagus and esophagogastric junction: histologic and clinicopathologic findings. Am J Surg Pathol 2001;25:1180-1187. Voutilainen M, Juhola M, Farkkila M, Sipponen P. Foveolar hyperplasia at the gastric cardia: prevalence and associations. J Clin Pathol2002;55:352-354. Orlowska J, Jarosz D, Pachlewski J, Butruk E. Malignant transformation of benign epithelial gastric polyps. Am J Gastroenterol1995;90:2152-2159. Hizawa K, Fuchigami T, Iida M, et al. Possible neoplastic transformation within gastric hyperplastic polyp. Application of endoscopic polypectomy. Surg Endosc 1995;9:714-718. Kamiya T, Morishita T, Asakura H, Munakata Y, Miura S, Tsuchiya M. Histoclinical long-standing follow-up study of hyperplastic polyps of the stomach. Am J Gastroenterol 1981;75:275-281. Zea-Iriarte WL, Sekine I, Itsuno M, et al. Carcinoma in gastric hyperplastic polyps. A phenotypic study. Dig Dis Sci1996;41:377-386. Ginsberg GG, Al-Kawas FH, Fleischer DE, Reilly HF, Benjamin SB. Gastric polyps: relationship of size and histology to cancer risk. Am J Gastroenterol 1996;91:714-717. Lauwers GY, Wahl SJ, Melamed J, Rojas-Corona RR. p53 expression in precancerous gastric lesions: an immunohistochemical study of PAb 1801 monoclonal antibody on adenomatous and hyperplastic gastric polyps. Am J Gastroenterol1993;88:1916-1919.