|Year : 2022 | Volume
| Issue : 3 | Page : 69-72
Clinicopathological Profile of Primary Gastric Lymphoma - A Retrospective and Observational Study
Ritu Mehta1, Rashmi Yadav2, Naveen Chawla3
1 Department of Pathology, AFMC, Pune, Maharashtra, India
2 Department of Pathology, Indian Railways, Raipur, Chhattisgarh, India
3 DGMS(N), IHQ MoD(N), New Delhi, India
|Date of Submission||20-Dec-2020|
|Date of Acceptance||01-Mar-2021|
|Date of Web Publication||01-Jul-2022|
(Dr) Ritu Mehta
Department of Pathology, AFMC, Pune - 411 040, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Primary gastric lymphoma (PGL) accounts for <15% of all the gastric malignances and <2% of all the lymphomas. Although they can involve any part of gastric tract, however, stomach is predominantly involved. Clinically, it is difficult to diagnose gastric lymphoma as it does not present with specific symptoms. Materials and Methods: It was a retrospective study carried out from July 16 to July 20. Patient's data were obtained from clinical record sheets. Histopathological examination was performed followed by panel of immunohistochemistry with leukocyte common antigen, CD 3, CD138, CD10, CD5, CD79a, CD20, Bcl-2, Bcl-6, Cyclin D1, and Ki-67. Further subtyping of gastric NHL was done using immunohistochemistry. Results: A total of 30 patients of PGL were included in the study. There were 23 males and 7 females, with M:F of 3.1:1. The mean age of presentation was 53 years. Abdominal pain and dyspepsia were common symptoms at presentation. Gastric antrum was the common site of involvement. Diffuse large B-cell lymphoma germinal center type was the most common histological variant seen in the present study. Helicobacter pylori was seen in 9 cases (30%) cases. Majority of patients were diagnosed in Stage II and III. Conclusion: PGL clinically is difficult to diagnose because of its nonspecific symptoms. Endoscopic examination should be done in such patients. All these suspicious patients should undergo biopsy examination of the lesion.
Keywords: Diffuse large B-cell lymphoma, MALToma, primary gastric lymphoma
|How to cite this article:|
Mehta R, Yadav R, Chawla N. Clinicopathological Profile of Primary Gastric Lymphoma - A Retrospective and Observational Study. J Mar Med Soc 2022;24, Suppl S1:69-72
| Introduction|| |
Primary gastric lymphoma (PGL) is uncommon and accounts for <4% of all gastric malignancies as stomach mucosa lacks lymphoid tissue. However, it is common site for metastasis of the lymphomas that originate else were. Gastrointestinal tract involvement is seen in 5%–20% of all Non-Hodgkin's lymphoma. The incidence of PGL has been rapidly increasing in the past two to three decades.
Although both T and B cell lymphoma can occur in gastrointestinal tract. B-cell lineage lymphoma accounts for 90% of all gastric lymphoma. Site-specific predilection is seen in these as mucosa-associated lymphoid tissue (MALT) lymphoma is seen in stomach, mantle cell lymphoma in duodenum and enteropathy-associated T-cell lymphoma in jejunum.
PGL most commonly affects patients who are in 5th decade of their life. However, with increasing incidence, it is now also seen in young patients with 2nd decade of life.,
Males have three times more chances than females to be affected
There are various risk factors associated with pathogenesis of PGL such as Helicobacter pylori infections, HIV, EBV, campylobacter Jejuni, and Human T-cell lymphotropic virus.,
There are certain other diseases too which are commonly associated with PGL like celiac disease. As PGL often present with nonspecific symptoms and mimic gastritis and peptic ulcer, it is very difficult to make timely diagnosis.
Secondary involvement of stomach by NHL should always be ruled out before starting treatment. Dawson's diagnosing criteria are used in differentiating PGL from secondary involvement of gastrointestinal tract by Non-Hodgkin's lymphoma. These criteria include (1) absence of peripheral lymphadenopathy at the time of presentation; (2) lack of enlarged mediastinal lymph nodes; (3) total and differential white blood cell count should be normal; (4) predominantly bowel disease with only lymph nodes obviously affected in the immediate vicinity; and (5) no hepatic or splenic involvement.
| Materials and Methods|| |
A retrorespective study was carried out at tertiary care hospital from December 2015 to July 2020. Thirty cases of PGL were included in the study. Patients presenting with GI symptoms or predominant tumor in the gastrointestinal tract based on Lewin et al. definition were included in the study. Non-Hodgkin's lymphoma patients with secondary involvement of gastrointestinal tract were not included in the study. The sample size was not calculated as PGL is relatively rare lymphoma and adequate sample size was not possible. Relevant clinical details were retrieved from clinical records. Upper GI endoscopy and gastric biopsy were done in all cases. Biopsies were fixed in 10% formalin. Hematoxylin and eosin (H and E) staining was done on paraffin-embedded tissues. The histopathological slides were reviewed. Giemsa stain for detection of H. pylori was done in all cases. Immunohistochemistry was done on poly L-lysine-coated slides. Antigen retrieval was done in pressure. Avidin-Biotin peroxidase technique was used. The relevant IHC markers done were leukocyte common antigen, CD3, CD20, CD79a, CD10, Bcl-2, Bcl-6, CD5, Cyclin D1, CD138, and Ki-67. Positive controls were run with immunohistochemistry. Based on immunohistochemical results subtyping of lymphoma was done. Bone marrow examination for staging of lymphoma was done in all cases. Chest X-ray, and computed tomography scan of the chest, abdomen, and pelvis were also done up as staging workup [Figure 1].
| Results|| |
Totally 30 cases of PGL were studied. There were 23 male and 7 female, with M:F of 3.1:1. The mean age at diagnosis was 53 years. Various symptoms at presentation were as abdominal pain, dyspepsia, weight loss and hematemesis. Abdominal pain and dyspepsia were common presenting complaints as shown in [Table 1].
Various sites of involvement were antrum (16), body (8), diffuse lesions (5), fundus (1). The staging at the time of diagnosis is shown in [Table 2].
The endoscopic examination showed ulcerated lesions in 08 (27%) cases, diffuse gastric thickening in 13 (43.34%) cases, and gastric erosion in 09 (30%) cases. The frequencies of different histological subtypes of PGL are listed in [Table 3].
Subtyping of tumors were done based on immunohistochemical findings [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e, [Figure 2]f, [Figure 2]g, [Figure 2]h. DLBCL germinal center type showed immunopositivity for CD20 and CD10. DLBCL non germinal center type showed immunopositivity for CD20, while tumor cells were negative for CD10 and BCL6. MALToma (mucosa-associated lymphoid tissue lymphoma) showed immunopositivity for CD 20 and CD79a, CD5, CD 10, CD 23, cyclin D1 were negative. The most common symptom at presentation in our study was abdominal pain accounting for 43% of the cases followed by hematemesis, dyspepsia, and weight loss. Mean age of presentation was 53 years. Males were affected more in our study. The most common site of involvement was gastric antrum followed by body of the stomach, diffuse involvement of stomach, and fundus. The gastroscopic findings ranged from gastric ulcers, diffuse thickening and gastric erosions. The most common histological type was diffuse large cell lymphoma [Figure 2]. The 13 cases were of germinal center type of DLBCL. Ten cases were of nongerminal center type DLBCL. Seven cases were of MALToma. H. pylori was positive in 9 cases. Out of these 9 cases 6 cases were of MALToma and remaining 3 cases were of DLBCL. Adjuvant chemotherapy comprising of RCHOP and radiotherapy was given to all patients. H. pylori treatment comprising of Capsule amoxicillin, tablet clarithromycin, and tablet pantoprazole was given to 9 patients showing positivity for H. pylori. Response to treatment was evaluated by repeat endoscopy after completion of 3 and 6 cycles.
|Figure 2: (a) CD 20 positive in neoplastic cells. (b) Cyclin D1 negative in neoplastic cells. (c) BCL6 Positive in neoplastic cells. (d) MUM 1 negative in neoplastic cells. (e) Ki 67 nearly 100% positive. (f) BCL2 negative in neoplastic cells. (g) C-myc Positive in neoplastic cells. (h) CD 10 Positive in neoplastic cells|
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| Discussion|| |
Our understanding of PGLs has been improved greatly in recent decades with the advanced use of morphological, immunohistochemical studies.
Advancement in the morphological, immunohistochemical studies has drastically improved the understanding of PGLs. Malignant lymphoma of the stomach can be primary or secondary. Stomach is primarily affected by Non-Hodgkin's lymphoma. Immunophenotypically, PGLs are of B-cell origin. DLBCL and MALT lymphoma are the most common subtype of B-cell lymphoma. Rarely mantle cell lymphoma can present as PGL. T cell lymphomas well as Hodgkin's lymphoma are very rare in the stomach. Although stomach can be secondarily involved any lymphoma. The most common histological lymphoma seen in stomach is MALT lymphoma. PGL commonly affect people in their 5–6 decade. In the present study, mean age of presentation was 53 years. In our study, males were affected more. It is in accordance with other available studies. Approximately 70 % of the cases are associated with H. Pylori associated gastritis. Eradication of H. Pylori leads to regression of the tumor in significant number of tumor . Gastric MALT lymphomas are also associated with hepatitis C, HIV and autoimmune diseases. H. pylori infection was seen in 30% of patients in our study as compared with other studies which reported 75% by Shukla et al., 44% by Arora et al. and 85% by Delchier et al. Low prevalence of H. pylori was noted in our study compared to other studies. This could be due to non availability of immunohistochemistry and serological tests for H. pylori. Diagnosis of H. pylori was made on H&E and Geimsa stain. Three patients DLBCL patients showed H. pylori positivity. These cases might have transformed from low-grade lymphoma to a high grade DLBCL. Diffuse large B-cell lymphoma was the most common histologic type seen in our study, which was similar to other studies from India and other parts of the world. Primary gastric DLBCL is characterized by proliferation of large sized atypical lymphoid cells which causes gastric glandular destruction as well as destruction of lymphoid follicles. MALT lymphoma was the second most common lymphoma seen in our study. It is seen commonly in antrum as polypoidal mass or ulcerating lesions. Microscopically, the gastric mucosa is infiltrated by small to medium sized monomorphic population of atypical lymphoid cells. Lymphoepithelial lesions defined as glandular destruction by three or more lymphoid cells are also seen. It is difficult to differentiate MALT lymphoma from heavy chronic inflammatory infiltrate. Lymphoepithelial lesion can be seen in acute gastritis mainly EBV-associated gastritis but glandular destruction will not be seen in inflammatory conditions. Immunohistochemistry along with molecular study is the main stay of diagnosis. The atypical lymphoid cells will show immunoreactivity for B-cell markers such as CD20 and CD 79a. Cyclin D1, CD5, CD10, Bcl2, and CD 23 will be negative which will rule out low grade lymphoma such as follicular and small cell lymphoma. Translocation t (11; 18) (q21;21) is associated with MALT lymphomas. Gastric lymphomas are classified according to Musshoff's modification of Ann Arbor staging. In the present study, most cases were diagnosed in stage IIE and stage III. This could be due to delayed presentation of patients because of nonspecific symptoms.
Prognosis depends on the stage and grade of the disease. The role of surgery prior to chemotherapy is still controversial. PGL are highly chemosensitive. Chemotherapy combined with anti-CD20 monoclonal antibody achieves higher complete response rate and more than 80% are long-term survival. Patients with advanced stage or high grade tumors are treated with surgery, adjuvant chemotherapy, and radiotherapy. Regular follow-up with endoscopic are required after completion of treatment to see recurrences.
Limitation of study
Only 30 cases of PGL were included in the study. Larger sample size would have given better insight into clinicopathological profiles of PGL. Immunohistochemistry is the gold standard for detecting H. pylori. It should always be accompanied with serological tests. IHC and serological tests for H. pylori were not done in present study and diagnosis was made only on histopathological examination.
| Conclusion|| |
PGL is the most common extranodal non-Hodgkin's lymphoma and represents a wide spectrum of disease, ranging from indolent low-grade marginal zone lymphoma or MALT lymphoma to aggressive diffuse large B-cell lymphoma. The PGL is a relatively rare cancer and easily misdiagnosed due to its unspecific symptoms of the digestive tract. PGL has a variable clinical presentation and a wide differential diagnosis. Due to the rarity of PGL, many aspects of this neoplasm are still controversial. Early diagnosing is a key for treatment of PGL. Early endoscopic examination, histopathological examination along with immunohistochemistry should be done. Better insight into the etiology of the disease along with immunohistochemistry and molecular studies can lead to the better understanding and early treatment of the disease.
We would like to thank the Department of Pathology, INHS Asvini.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]