Solitary Polypoid Hamartoma of the Oxyntic Mucosa of the Stomach

Path. Res. Pract. 182, 326-330 (1987)

Solitary Polypoid Hamartoma of the Oxyntic Mucosa of the Stomach G. Carfagna, F. P. Pilato and C. Bordi /stituto di Anatomia Patologica, Universita di Parma

P. Barsotti Dipartimento di Biopatologia Umana, Sezione di Patologia U/trastrutturale, Universita "La Sapienza ", Roma

C. Riva Centro di Diagnostica Istopatologica, Universita di Pavia

a Varese,

Italy

SUMMARY

A solitary pedunculated polyp of the oxyntic mucosa removed from a 66-year-old patient with atrophic gastritis and achlorhydria exhibited distinctive histological features consisting of submucosal, mostly oxyntic-type glands with a smooth muscular framework. Histochemical and immunohistochemical studies demonstrated that the glands were composed of well differentiated chief, parietal, and endocrine cells. Moreover, less frequent glands of the antro-pyloric type were also seen. The lesion was regarded as a previously unrecognized variety of gastric hamartoma.

Introduction The classic subdivision between hrJ'erplastic or regenerative and adenomatous polyps12, does notencompass the whole spectrum of varieties of gastric epithelial polyps, and additional types have been recognized (for review see4, 17). Moreover, the introduction of modern cytological techniques, though usually confined to the study of single cases, has sometimes revealed a heterogeneous, complex cytological composition of the polyps, indicating a different histogenetic and/or pathogenetic origin of these lesions and providing the basis for their classification3, 8, 21. This report describes a case of epithelial polyp of the fundic mucosa showing distinctive histological features. The polyp was interpreted as a hamartoma of the oxyntic mucosa and the different cell components were characterized by mean!lof histochemical and immunohistochemical techniques. 0344-0338/8710182-0326$3.5010

Report of a Case

A 66-year-old woman presented with symptoms of retching during defecation. She denied any familial or personal history of gastrointestinal polyps, neoplasia, or peptic ulcer. Upper gastrointestinal X-ray examination revealed a polyp of the fundus of the stomach. The polyp, which was removed endoscopically, was round with a smooth surface. It measured about 1.5 cm. in diameter and presented a short pedicle having a diameter of 0.5 cm. No additional polyps were detected in the gastric mucosa during endoscopic examination. Routine laboratory tests revealed moderate elevation of the fasting blood glucose level (157 mgldl). Analysis of the stools for occult blood yielded negative results. Gastric acid secretion was absent either in basal conditions or following pentagastrin stimulation (4 Jlg kg-I hr- I for 2 hr). Fasting gastrin level was 120 pglml which is slightly above the upper normal value in our laboratory (100 pglml). © 1987 by Gustav Fischer Verlag, Stuttgart

Solitary Gastric Hamartoma' 327

Methods Immediately after its recovery, the polyp was fixed in Bouin's fluid for 5 hours and embedded in paraffin. The sections were cut at 5 !-tm and stained with hematoxylin-eosin, Alcian blue-PAS for acid and neutral mucopolysaccharides, Grimelius 6 and SevierMunger14 silver methods for argyrophil endocrine cells. Immunocytochemical investigations were performed using the peroxidase-antiperoxidase (PAP) technique. The following antisera (all raised in rabbit) were used: 1) anti-lysozyme (Dakopatts, Copenhagen, Denmark) (working dilution: 11200); 2) anti-pepsinogen I (a gift of Sorin, Saluggia, Italy) (111000); 3) anti-pancreatic amilase (a gift of Dr. G. Chejfec, Chicago, USA) (11500). Sections of pancreatic acinar tissue were used as a control; 4) anti-gastrin (Miles Laboratories, Cavenago, Italy) (1/200); 5) anti-somatostatin (Dakopatts, Copenhagen, Denmark) (1/ 800); 6) anti-glucagon 05 Y (reacting with the N-terminal region of pancreatic glucagon in common with intestinal glicentin; a gift of Dr. R. H. Unger, Dallas, Texas, U.S.A.) (1/800). Controls for the specificity of reactions were done by incubating consecutive sections with non immune rabbit serum or with the antiserum adsorbed with an excess of the respective antigen as the primary step. Further characterization of glycoconjugates was assessed using horseradish peroxidase (HRP) labelled lectins for the detection of simple sugar residues 15 as previously detailed ll • The following lectins (all purchased from Sigma, St. Louis, USA) were used: 1) Arachis hypogaea (peanut agglutinin, PNA) (0.025 mg/ml) , with affinity for terminal ~"cD galactose residues and terminal dysaccharide ~-D-galactose (1-3 )-D-N-acetylgalactosamine; 2) Triticum vulgaris ,wheat germ agglutinin, WGA) (0.030 mg! ml), with affinity for ~-D-N-acetylglucosamine residues or olygomers; 3) Glycine max (soybean agglutinin, SBA) (0.050 mg/ml), with affinity for a- and ~-D-N-acetylgalactosamine residues. Controls were performed by adding an eccess of the appropriate inhibitory sugars (D-galactose, D-N-acetylglucosamine and D-N-acetylgalactosamine, respectively) to the staining solutions.

Results On conventional histological examination (Fig. 1 a-c), the polyp appeared to be manifested by a haphazard col-

a

Fig. 1. a) Histological survey of a sagittal section of the polyp including the short stalk (between curved arrows) with the diathermy mark (arrowheads). Note the micro cystic appearance of the polyp different from that of a well demarcated covering mucosa. b) The limit between the mucosa and the polyp is represented by a thick muscularis mucosae (*) occasionally discontinue~ by connecting glands. Atrophic gastritis with foci of intestinal metaplasia (arrowheads) is present only in the mucosa. c) Detail of the polyp showing oxyntic glands with cystic dilations of the lumen and some vacuolated cells. The stroma contains bundles of smooth muscle cells (haematoxylin and eosin, a: x 5.7; b: X 55; c: x 215).

328 . C. Bordi et al.

lection of glands with a framework of smooth muscle tissue and occasional, focal accumulations of mature lymphoid cells. Several glands, lined by a lowered, cuboidal epithelium, were dilated giving a cystic appearance to the lesion (Fig. 1 a). Other glands were composed of mucous cells resembling either those of the gastric surface epithelium or those of the pyloric glands. Moreover, numerous glands were composed of large, granular cells appearing either acidophilic or basophilic in their staining

properties and resembling parietal and chief cells of the oxyntic glands, respectively. The different types of glands tended to be segregated into discrete areas, the oxyntic type glands being largely predominant. In several areas all types of glandular cells presented single, empty vacuoles occupying most of the cell cytoplasm (Fig. 1 c). The polyp was covered with a thin oxyntic mucosa showing frequent foci of atrophic gastritis with pseudopyloric and intestinal metaplasia (Fig. 1 b). A thick mus-

Fig. 2. a) Immunostaining of pepsinogen I in the chief cells of the polyp with interspersed unreactive parietal cells (arrow) (PAP technique, X 210). b) Argyrophil endocrine cells of the polyp glands revealing a typical closed location at the base of the glandular epithelium (Sevier-Munger, X 260). c) HRP-PNA staining of oxyntic glands of the polyp for demonstration of parietal cells which present well delineated canaliculi (arrows). A PNA-positive mucous neck cell (arrowhead) is also evident (x 560). d) HRP-PNA staining shows PNA negative mucins (*) in foveolar-type epithelium and slightly PNA positive mucins in pylorictype glands of the polyp (**). Superficial mucous cells of the covering mucosa (arrows) present PNA-negative mucins with an intense staining of supranuclear cytoplasmic zones (no counterstaining) (x 46).

Solitary Gastric Hamartoma . 329

cularis mucosae separated the mucosa from the bulk of the polyp which was entirely in a submucosal location. Although the mucosal glands were occasionally in direct connection with those of the polyp (Fig. 1 b), the absence of cystic changes and the orderly arrangement of the glands in the mucosa coupled with the lack of gastritic changes (including fOel of intestinal metaplasia) in the polyp resulted in a sharp contrast of the respective histological appearance. By immunocytochemistry an intense reaction for pepsinogen I was seen in the chief cells of both the polyp (Fig. 2 a) and the covering mucosa. In contrast, immunostaining for lysozyme was seen only in metaplastic Paneth cells of the mucosa, while no reaction for pancreatic amylase was found. Several somatostatin cells and rare gastrin cells were seen in the polyp glands, the latter cells being confined to pyloric type glands. In contrast, cells immunoreactive for antiglucagon 05 Y antiserum were seen only in areas of intestinal metaplasia of the covering mucosa. Numerous, closed-type cells (i.e., unconnected with the gland lumen) showing an intense argyrophil reaction with either the Grimelius or the Sevier-Munger silver methods (Fig. 2 b) were seen within fundic type glands of the polyp. In consecutive sections these cells did not correspond to those containing gastrin, somatostatin or glucagon. These results were consistent with the argyrophil cells beinr enterochromaffin-like (EeL) cells of the oxyntic glands! . The histochemical staining with PNA and SBA demonstrated a strong reaction.of the luminal membrane and of the secretory canaliculi of the parietal cells!1 in both the polyp and the covering mucosa (Fig. 2 c). Alcian blue positive mucins were observed in the metaplastic goblet cells of the covering mucosa. Most mucous cells of the polyp glands showed a PAS positive-Alcian blue negative staining indicating neutral, gastric type mucopolysaccharides. The lectin-conjugates staining showed the presence of a few glands producing pylorictype mucins (PNA: +/-; WGA: + diffuse, with globules + +; SBA: -) 1 both in the covering mucosa and in the polyp (Fig. 2 d). Most mucous glands of the polyp, however, contained cells producing foveolar-type mucins (PNA: -; WGA: + granular; SBA: +/- diffuse)!' 2. In addition, in the oxyntic glands of the polyp sparse mucous neck cells (PNA: ++; WGA: +; SBA: -? were also detected.

Discussion Our patient presented a solitary pedunculated polyp of the fundic mucosa of the stomach associated with atrophic gastritis and achlorhydria. The polyp revealed a distinctive histological structure, consisting of a submucosal collection of glands with frequent cystic changes in a framework of smooth muscular tissue. Most glands were of the oxyntic (fundic) type but occasionally pyloric type glands were also seen. The former glands showed well represented populations of chief, parietal and EeL endocrine cells, that revealed a remarkable degree of functional differenti-

ation as shown by the specific histochemical and immunohistochemical reactions. This cytological composition coupled with the negative immunohistochemical reaction for pancreatic amylase enabled us to exclude pancreatic heterotopia. We regard our patient's lesion as a specific type of gastric epithelial polyp mainly composed of oxyntic glands which is different from the previously recognized types of polyps with similar glandular composition. Among these types, the most frequent lesion has been reported as fundic glandular cysts5, hamartomatous polyp19, cystic "hamartomatous" gastric polyps16, fundic gland polyposis9, or fundic gland hyperplasia!? This type of polyp, which is composed of fundic glandular micro cysts, is most common in patients with familial adenomatosis coli but may also occur sporadically9. The change appears in the form of multiple lesions, is confined to the mucosa and is associated with an otherwise normal gastric mucosa. All these findings are at variance with those of our patient. The hamartomatous polyps of the oxyntic mucosa associated with the Peutz-Jeghers' syndrome represent another type of polyp containing oxyntic glands. However, these polyps do not extend to the submucosa and' show an exophytic, arborizing pattern of the muscularis mucosae and a prominent foveolar hyperplasia, which were all absent in our case. In addition, no clinical signs or familial history of either Peutz-Jegher's syndrome or familial adenomatosis coli were observed in this patient. Finally, in this context it is pertinent to mention the diffuse cystic glandular malformation of the stomach 10, 13, a pathological condition of the gastric body and fundus showing a very frequent association with gastric adenocarcinoma. With the polypoid lesion of our patient this condition shares the submucosal location and the association with an atrophic gastritis of the overlying fundic mucosa which does not extend to the heterotopic submucosal glands. In contrast to the present polyp, however, the diffuse cystic glandular malformation extends over the entire area of the oxyntic mucosa and has a very s~arse content in well differentiated parietal and chief cells o. A case apparently similar to that described in this paper was recently reported by Hanada et aU. Moreover, additional examples are likely to be included in the group 3 of "solitary gastric folyps in the fundic gland area" described by Hara et al. . Although noting the hamartomatous appearance of the polyp in their case, Hanada et aU considered the lesion as hyperplastic and closely related to the fundic gland polyposis of patients with familial adenomatosis coli. In our opinion, the heterogeneous, complex cytological differentiation of these polyps rather points to a focal developmental disorder, thus justifying the designation hamartoma that we propose.

Acknowledgements This work is supported by grants from the Italian Ministry of Public Education and from the AIRC (Associazione Italiana per la Ricerca sui Cancro).

330 . C. Bordi et al.

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Received May 13, 1986 . Accepted December 16, 1986

Key words: Gastric mucosa - Gastric polyp - Hamartoma - Atrophic gastritis Prof. Cesare Bordi, Istituto di Anatomia Patologica, Universita di Parma, 43100 Parma, Italia