Malignant gastrointestinal stromal tumor in

association with Russell body gastritis.

Desislava M. Bozhkova, Maria S. Koleva‐Ivanova, Veselin T. Belovejdov, Dorian I. Dikov
Department of General and Clinical Pathology, Medical University of
Plovdiv, St. George University Hospital, Plovdiv, Bulgaria

Indian Journal of Pathology and MicrobIology ¦ Volume 64 ¦ Special Issue 1 ¦ June 2021
 INTRODUCTION
•Russell bodies (RB), the condensed immunoglobulin (Ig) variants in plasma
cells, are frequently observed in chronic infections, plasma cell dyscrasias, and
autoimmune diseases.

•Small number of RB are often observed in the mucosa in H. pylori gastritis,

but long‐standing overstimulation by H. pylori can result in diffuse infiltration
of plasma cell with RB.

•The term “Russell body gastritis” (RBG) has first been used by Tazawa K et
al. to describe accumulation of RB containing plasma cells in gastric mucosa
with H. pylori infection.
•To date, only four cases of RBG and malignant gastric tumors of epithelial
origin were reported.

•There are no data concerning the association between RBG and

mesenchymal tumors in the literature.

•We report the first case of H. pylori‐associated RBG in peritumoral mucosa

of a malignant gastrointestinal stromal tumor (GIST) with a follow ‐up.

•In addition, in the reported case RBG was associated with coccoid form of
H. pylori.
 CASE HISTORY
•A 60‐year‐old woman presented with abdominal discomfort and a partial
resection of the stomach was performed due to abnormal gastric lesion.
•Macroscopically the gastric fragment was with a length of 5 cm on the
small stomach curvature, 17 cm on the large curvature, and 7 cm thick.
•A nodular tumor formation at the level of the small curvature with
dimensions 6 × 6× 1 cm was observed.
•A fragment of omentum with dimensions 25 × 25 × 1 cm was also
submitted for investigation.
•Histologically a tumor mass was found, composed of spindle cells with
hyperchromatic nuclei, showing 25 mitosis/50 HPF [Figure 1a].
•Immunohistochemically, the tumor cells showed positive expression of c ‐kit
[Figure 1b] and DOG1.

•The final diagnosis was malignant gastrointestinal stromal tumor–spinde

cell histological type, with high risk of progression according to the
classification of Miettinen et al. Lasota, pT3 pN0 staging in TNM (AJCC,
2017).

•There was no evidence of carcinomatous lymphangitis and vascular tumor

embolism. Infiltration of visceral peritoneum was observed. The excision
was complete with longitudinal margins of 3 cm.

•Peritumoral lymph nodes were negative: 15 N‐/15.

Figure 1: (a) Malignant GIST with chronic
gastritis in the adjacent mucosa, HE, ×50. (b) Malignant GIST: Tumor cell with
positive immunohistochemical reaction
for c‐kit, c‐kit ×200
•In the peritumoral mucosa, especially in the fundus, chronic gastritis was
found, rich in RB, so‐called RBG.
•The inflammatory infiltrate was represented by quite a number of plasma
cells and Mott cells with areas consisting entirely of RB [Figure 2a and b].

Figure 2: (a) RB gastritis: Gastric mucosa

densely infiltrated by Russell body‐containing (b) Higher magnification of RB
plasma cells, HE, ×200. gastritis with Mott cells: HE, ×400.
•Several hyperplastic lymphoid follicles were also observed.
•No neutrophilic leucocytes were found.
•In fundic mucosa plasma cells expressed CD79a [Figure 2c], CD138 (data
not shown), kappa [Figure 2d], and IgM lambda [Figure 2e].
•After additional immunohistochemical examination in the area of the
peritumoral mucosa the presence of H. pylori in coccoid form was found
[Figure 2f].
(c) Plasma cells with positive expression (d) Positive immunohistochemical
of CD79a, ×200. reaction in plasma cells with kappa,
×630.
 (e) Positive immunohistochemical (f) Presence of coccoid form of H pylori.
reaction in plasma cells with lambda, IHC Hp, ×200
x630, IgM.
•For the needs of differential diagnosis of RBG and signet ring cell
carcinoma we performed simultaneous PAS staining and cytokeratin
immunostaining.
•RB‐containing plasma cells were PAS positive [Figure 3a] and
cytokeratin AE1/AE3 negative [Figure 3b].
•The first follow‐up gastroscopy with a biopsy was performed 8 months
after the surgical intervention, treatment with immunotherapy, and H.
pylori eradication.
•Normal gastrojejunal anastomosis with focal foveolar hyperplasia was
found.
•The upper 1/3 of the stomach was presented by a normal fundus.

•In cardia the presence of mild inflammatory infiltrate without activity with
single RB and focal intestinal metaplasia without dysplasia (data not
shown) was observed.

•There was no evidence of a tumor process or H. pylori.

•The second and the third follow‐up gastroscopy were performed 4 and 5
years after the surgical intervention, with no evidence of disease.
Figure 3: Russell body‐containing plasma cells are PAS positive (a) and cytokeratin
AE1/AE3 negative (b), ×400
 DISCUSSION
•Since the introduction of the term RBG in the literature were
published 42 cases. 27 of them were associated with H. pylori
infection.
•In the presented case we proved the presence of H. pylori infection by
immunohistochemical staining.
•We found that H. pylori was of coccoid form.
•When exposed to environmental stress conditions, H. pylori is able to
change its morphology from a spiral to coccoid form.
•This form contributes to treatment failures and recurrence.
•The form of H. pylori in RBG was not mentioned in previous studies and
might be an interesting fact for correlation.
•Four cases of total 42 cases of RB gastritis described in the literature were
associated with gastric carcinomas in the adjacent tissues—tree cases of
adenocarcinoma and one of signet ring cell carcinoma.
•Although it is now well established that H. pylori infection predisposes individuals toward gastric adenocarcinoma later in life,
the relationship between RBG and gastric carcinoma remains unclear.
•The significantly higher density of plasma cells containing RB in gastric
biopsies of patients with gastric carcinoma in comparison with patients
without gastric carcinoma led to the statement that these cells could be
important for adenocarcinoma development.
•There are reports that suggest association between the production of
chemokines in tumor cells and the development of RB.
•The association of Helicobacter pylori (HP) with gastritis, gastric dysplasia,
gastric carcinoma, and gastric lymphoma has been previously demonstrated.
•However, the association of HP with GISTs has not been well explored.
•Other studies suggest that gastric GIST arises in cases of nonatrophic or
mildly atrophic gastric mucosa with no prevalence of H. pylori infection.
•The literature analysis showed diverse results—some investigations report
prevalence of H. pylori infection in cases with GIST, while others suggest
no connection between these two entities.
•More studies are needed to establish the association of HP with GISTs.
•In the presented case we proved the presence of H. pylori infection, which
might be in connection with RB gastritis rather than with the malignant
GIST.
•As in our case, larger tumors present with vague abdominal discomfort. The
complications include chronic gastrointestinal bleeding, intestinal
obstruction or altered bowel habits, rarely perforation.
•In one study, a total of 15 cases (15/30) of RBG with polyclonal plasma
cells, containing RB (Mott cells) have been described.
•Our case also showed polyconal proliferation of plasma cells with RB with
uneventful clinical followup.
•The decreased number of Mott cells in the stomach after H. pylori
eradication shows that the factor causing RB formation is H. pylori.
•Future studies are needed to investigate the distinction between RBG with
monoclonal Mott cells and plasmacytoma or mucosa‐associated lymphoid
tissue (MALT)‐lymphoma.
•RBG can be differentiated from MALT lymphoma by the plasmacytic
differentiation with the absence of cytologic atypism, lymphoepithelial
lesions, centrocyte‐like cells, and monocytoid cells.
•Diffuse infiltration of plasma cells with RB in the gastric mucosa requires
differential diagnosis with several diseases.
•Cytokeratin negativity and CD79a and CD138 positivity exclude signet
ring cell carcinoma of the stomach.
•The simultaneous performing of PAS or PAS‐AB staining and cytokeratin
immunostaining in such cases has significant role for setting the correct
diagnosis (unpublished own data).
•Kappa and lambda polyclonal immunoreactive pattern excludes
lymphoplasmacytic lymphoma, plasmacytoma, and monoclonal
gammopathy of undetermined significance.
 CONCLUSION
•Little is known about the connection between RBG and malignant
epithelial or mesenchymal gastric tumors. We report the first case of RBG
in peritumoral mucosa of a malignant GIST.
•The association between RBG and H. pylori infection remains unclear,
although the majority of the reported cases showed H. pylori positivity.
•In our case we presented a rare combination of RBG with coccoid form of
H. pylori.
•Further case reports or large series investigations are required in order to
prove or reject the correlation between RBG and H. pylori infection and
the connection between RBG and stomach malignancies.
THANK YOU