Identification of Nodular Gastritis among Patients Diagnosed with Lymphofollicular Gastritis on a Gastric Biopsied Specimen

Young Jung Kim; Sun-Young Lee; Sang Pyo Lee; Jeong Hwan Kim; In-Kyung Sung; Hyung Seok Park; Chan Sup Shim; Hye Seung Han

doi:10.4166/kjg.2018.71.3.143

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Kim, Lee, Lee, Kim, Sung, Park, Shim, and Han: Identification of Nodular Gastritis among Patients Diagnosed with Lymphofollicular Gastritis on a Gastric Biopsied Specimen

Original Article

Korean J Gastroenterol 2018;71(3):143-152.

Published online: 4 October 2018

DOI: https://doi.org/10.4166/kjg.2018.71.3.143

Identification of Nodular Gastritis among Patients Diagnosed with Lymphofollicular Gastritis on a Gastric Biopsied Specimen

Young Jung Kim, Sun-Young Lee, Sang Pyo Lee, Jeong Hwan Kim, In-Kyung Sung, Hyung Seok Park, Chan Sup Shim, Hye Seung Han¹

¹Departments of Internal Medicine and Pathology, Konkuk University School of Medicine, Seoul, Korea

Correspondence to: Sun-Young Lee, Department of Internal Medicine, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea. Tel: +82-2-2030-7747, Fax: +82-2-2030-7748, E-mail: sunyoung@kuh.ac.kr

Received 27 November 2017 Accepted 29 December 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

Nodular gastritis (NG) is a well-known endoscopic finding observed in patients with a Helicobacter pylori infection, which may lead to invasive gastric cancer. Lymphofollicular gastritis consists of lymphoid follicles or lymphoid cell aggregates, and is common in children. The aim of this study was to identify patients with NG from those in whom gastric biopsied specimens showed lymphoid follicles and lymphoid cell aggregates.

Methods

Subjects, whose gastric biopsy specimens showed lymphoid follicles or lymphoid cell aggregates, were included in this study. The inclusion criterion was that they underwent a serum pepsinogen assay on the day of upper gastrointestinal endoscopy. NG was diagnosed if the endoscopy findings revealed regular-sized, multiple, colorless subepithelial nodules.

Results

Among 108 subjects who showed lymphoid follicles or lymphoid cell aggregates, 13 (12.0%) revealed NG on endoscopy, and all these subjects showed positive Giemsa staining. Patients diagnosed with NG were younger (p=0.012) and showed a female pre-dominance (p=0.001) compared to those without NG. The mean serum pepsinogen levels were higher (p=0.001) and lymphoid fol-licle-dominant subjects were more common (p<0.001) in the NG subjects than in those without NG. Logistic regression analysis revealed a younger age (p=0.041) and female gender (p=0.002) to be significant independent risk factors for NG.

Conclusions

NG should be distinguished from lymphofollicular gastritis because only 12% of patients showing gastric biopsy findings of lymphoid follicles and lymphoid cell aggregates demonstrated NG on endoscopy. NG is an endoscopic finding that is more common in women and in the younger population, irrespective of the biopsy findings and gastric secretory ability.

Keywords: Gastritis, Lymphocyte, Lymphoid tissue

References

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Fig. 1.

Lymphoid follicle-dominant type. (A) On the upper gastrointestinal endoscopic findings, multiple 2 mm-sized, colorless subepithelial nodules were noticed. The findings were consistent with nodular gastritis of the small-granular type. (B) On the endoscopic findings, multiple 5 mm-sized, flat subepithelial nodules can be seen on the antrum. These findings are consistent with nodular gastritis of the large-nodular type. (C) On the gastric biopsied specimen of (A) taken from the proximal antrum, lymphoid follicles with prominent germinal centers were noticed with few lymphoplasma cell infiltration (H&E stain, ×40). The mucosa was expanded by prominent germinal centers reaching up to the superficial layer of the lamina propria. (D) On the gastric biopsied specimen of (B) from the proximal antrum, two lymphoid follicles were noticed with few lymphoid cell aggregates. The germinal centers were smaller and deeper than the first case (H&E stain, ×40).

Fig. 2.

Lymphoid cell aggregate-dominant type. (A) The endoscopic findings of the antrum are consistent with nodular gastritis of the small-granular type. (B) The endoscopic findings are consistent with nodular gastritis of the large-nodular type. (C) On the biopsied specimen of (A), diffuse lymphoplasma cell infiltration can be observed as lymphoid cell aggregates (H&E stain, ×40). Infiltrated lymphoplasma cells on the superficial layer of the lamina propria are expanding the nodular mucosa. (D) On the biopsied specimen of (B) from the antrum, lymphoid cell aggregates can be seen on the deeper layer of lamina propria without a germinal center (H&E stain, ×40).

Table 1.

Baseline Characteristics of the 108 Subjects Whose Gastric Biopsy Specimens Showed Lymphoid Follicles or Lymphoid Cell Aggregates

Variables	Total (n=108)	Nodular gastritis+ & Giemsa+ (n=13)	p-value (vs. 83 Giemsa+)	Nodular gastritis- & Giemsa+ (n=83)	p-value (vs. 12 Giemsa)	Nodular gastritis- & Giemsa (n=12)	p-value (vs. 13 nodular gastritis)	p-value^a
Age (year-old)	49.6±9.3	46.3±11.0	0.288	49.1±8.5	0.007	56.6±10.0	0.023	0.012
Female gender	48 (44.4)	12 (92.3)	<0.001	30 (36.1)	0.362	6 (50)	0.030	0.001
Body mass index (kg/m²)	24.3±4.0	24.0±4.6	0.819	24.2±4.0	0.483	25.1±3.8	0.503	0.747
Comorbidity	23 (21.3)	2 (15.4)	0.726	20 (24.1)	0.290	1 (8.3)	0.531	0.394
Hypertension	15 (13.9)	1 (7.7)	0.684	13 (15.7)	0.687	1 (8.3)	0.740	0.209
Diabetes mellitus	8 (7.4)	2 (15.4)	0.240	5 (6.0)	0.566	1 (8.3)	0.531	0.564
Cardiovascular disease	8 (7.4)	0 (0)	0.593	8 (9.6)	0.590	0 (0)	−	0.235
Recent medication	18 (16.7)	4 (30.8)	0.221	12 (14.5)	0.560	2 (16.6)	0.645	0.341
Aspirin	6 (5.6)	2 (15.4)	0.186	4 (4.8)	0.577	0 (0)	0.480	0.240
NSAID	6 (5.6)	1 (7.7)	0.447	3 (3.6)	0.118	2 (16.6)	0.593	0.221
Hormone replacement	5 (4.6)	1 (7.7)	0.447	3 (3.6)	0.423	1 (8.3)	0.740	0.727

Values are presented as mean±standard deviation or n (%).

NSAID, nonsteroidal anti-inflammatory drug.

^a Differences between the three groups were analyzed using analysis of variance with Bonferroni correction for the continuous variables and Chi-square test with Bonferroni correction for the categorical variables.

Table 2.

Serum Pepsinogen Assay, Endoscopy, and Gastric Biopsy Findings according to the Presence of Nodular Gastritis and Helicobacter pylori Infection

Variables	Nodular gastritis+ & Giemsa+ (n=13)	p-value (vs. 83 Giemsa+)	Nodular gastritis- & Giemsa+ (n=83)	p-value (vs. 12 Giemsa)	Nodular gastritis- & Giemsa (n=12)	p-value (vs. 13 nodular gastritis)	p-value^a
Pepsinogen I (ng/mL)	74.3±28.9	0.379	68.4±21.2	<0.001	43.4±16.6	0.004	0.001
Pepsinogen II (ng/mL)	21.9±9.1	0.439	19.8±8.7	<0.001	10.3±4.3	0.001	0.001
Pepsinogen I/II ratio	3.5±0.8	0.393	3.9±1.5	0.045	4.9±2.3	0.049	0.062
Background gastric mucosa		<0.001		0.294		<0.001	<0.001
Normal finding	0 (0)		15 (18.1)		0 (0)
Nodular gastritis	13 (100.0)		0 (0)		0 (0)
Erosive gastritis	0 (0)		15 (18.1)		4 (33.3)
Metaplastic gastritis	0 (0)		11 (13.3)		1 (8.4)
Chronic atrophic gastritis	0 (0)		42 (50.5)		7 (58.3)
Coexisting erosive esophagitis	1 (7.7)	0.652	6 (7.2)	0.021	4 (33.3)	0.160	0.034
Coexisting peptic ulcer disease	0 (0)	0.588	7 (8.4)	0.590	0 (0)	−	0.324
Dominant pathology		0.340		0.001		0.001	<0.001
Lymphoid follicles	11 (84.6)		58 (69.9)		2 (16.7)
Lymphoid cell aggregations	2 (15.4)		25 (30.1)		10 (83.3)

Values are presented as mean±standard deviation or n (%).

Table 3.

Main Pathology Findings of 13 Nodular Gastritis Patients

Pathology finding	Endoscopy finding	Subject	PG I (ng/mL)	PG II (ng/mL)	PG I/II ratio	Other findings
Lymphoid follicle-dominant	Small-granular type	F/25	111.1	21.4	5.2	−
		F/33^a	61.1	18.0	3.4	Follow-up tests after 48 months
		F/53	35.7	11.8	3.0	−
		F/41	75.3	18.0	4.2	−
		F/47	57.7	18.5	3.1	−
	Large-nodular type	M/36	67.0	20.2	3.3	−
		F/48^a	68.3	28.3	2.4	Follow-up tests after 13 months
		F/53	70.1	27.4	2.6	−
		F/55^a	70.4	20.6	3.4	Follow-up tests after 49 months
		F/59	152.1	47.6	3.2	DM
		F/60	69.6	19.5	3.6	DM, HTN, erosive esophagitis
Lymphoid cell	Small-granular type	F/37	51.8	11.7	4.4	−
aggregates-dominant	Large-nodular type	F/55	75.4	21.1	3.6	−

F, female; M, male; PG, pepsinogen; DM, diabetes mellitus; HTN, hypertension.

^a Three subjects were followed up using serum pepsinogen assay and upper gastrointestinal endoscopy. All of them showed persistent Helicobacter pylori infection with regression of nodules.

Table 4.

Pathology and Endoscopy Findings of 12 Subjects without a H. pylori Infection

Pathology finding	Endoscopy finding	Subject	PG I (ng/mL)	PG II (ng/mL)	PG I/ II ratio	Other findings
Lymphoid	Erosive gastritis	F/57 ^a	66.1	10.6	6.2	Follow-up tests after 58 months
follicle-predominant	Chronic atrophic gastritis	M/39	50.9	11.0	4.6	−
Lymphoid cell	Erosive gastritis	F/47	38.1	8.2	4.7	−
aggregate-predominant		F/54	23.7	21.0	1.1	NSAIDs
		F/57	58.2	12.2	4.8	Hormone replacement therapy
	Chronic atrophic gastritis	M/62	16.1	14.1	1.1	NSAIDs
		F/66	38.3	7.0	5.5	−
		F/69 ^a	35.4	5.3	6.6	Follow-up tests after 24 months
	Chronic atrophic gastritis &	M/41	68.8	7.9	8.7	−
	erosive esophagitis	M/63 ^a	43.1	11.8	3.9	DM, HTN, H. pylori eradication
						history, Follow-up tests after
						12 months
		M/68	27.7	7.2	3.8	−
	Metaplastic gastritis &	M/56	53.9	7.0	7.7	−
	erosive esophagitis

F, female; M, male; PG, pepsinogen; NSAID, nonsteroidal anti-inflammatory drug; DM, diabetes mellitus; HTN, hypertension; H. pylori, Helicobacter pylori.

^a Three subjects were followed up using serum pepsinogen assay and upper gastrointestinal endoscopy. Neither nodular gastritis nor positive Giemsa staining was found at the follow-up tests. One subject (M/63) still showed lymphoid cell aggregates at the follow-up endoscopic biopsied specimen taken from the antrum.

Table 5.

Characteristics of the Subjects s according to the Pathology Findings

Variables	Lymphoid follicle-predominant (n=71)	Lymphoid cell aggregate-predominant (n=37)	p-value
Age (year-old)	48.9±9.1	51.1±9.6	0.231
Female gender	31 (43.7)	17 (45.9)	0.821
Body mass index (kg/m²)	24.3±4.0	24.3±4.3	0.960
Pepsinogen I (ng/mL)	68.0±23.4	63.1±22.6	0.298
Pepsinogen II (ng/mL)	19.6±9.0	17.9±8.7	0.373
Pepsinogen I/II ratio	3.8±1.2	4.2±2.1	0.265
Background gastric mucosa			0.492
Normal endoscopy finding	11 (15.5)	4 (10.8)
Nodular gastritis	11 (15.5)	2 (5.4)
Erosive gastritis	11 (15.5)	8 (21.6)
Chronic atrophic gastritis	30 (42.2)	19 (51.4)
Metaplastic gastritis	8 (11.3)	4 (10.8)
Gastric ulcer	4 (5.6)	1 (2.7)	0.502
Duodenal ulcer	2 (2.8)	0 (0)	0.785
Erosive esophagitis	7 (9.9)	4 (10.8)	0.877

Values are presented as mean±standard deviation or n (%).

Table 6.

Independent Risk Factors for the Presence of Nodular Gastritis

Significant variables	Odds ratio	95% confidence interval	p-value
Old age	0.901	0.816–0.996	0.041
Male gender	0.025	0.002–0.261	0.002
Pepsinogen I level	1.002	0.996–1.041	0.896
Pepsinogen II level	1.030	0.929–1.141	0.578
Pathology finding
Lymphoid follicle-predominant	2.629	0.464–14.889	0.275
Lymphoid aggregate-predominant	1
Coexisting erosive esophagitis	0.244	0.016–3.799	0.314

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