Gastric lymphoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Mazia Fatima, MBBS [2]

Overview

Primary gastric lymphoma is cancer derived from lymphocytes (a type of white blood cell) that originates in the stomach^[1]

Most common cause of primary gastric lymphoma is mucosa-associated lymphoid tissue (MALT) gastric lymphoma and diffuse large B-cell lymphoma (DLBCL) of the stomach.These account for 90% of all diagnosed cases. Lymphomas originating outside the lymph nodes are referred to as extra nodal lymphoma. Primary gastric lymphoma is the most common type of extra nodal lymphoma.

Primary gastric Lymphoma is a rare condition.^[2] Gastric lymphoma accounts for less than 15% of gastric malignancies and about 2% of all lymphomas. Most of the primary gastric lymphomas are B cell non-Hodgkin lymphoma(NHL) .

Primary Gastric Lymphoma

Endoscopic image of gastric MALT lymphoma taken in body of stomach in patient who presented with upper GI hemorrhage. Appearance is similar to gastric ulcer with adherent clot.

Clinical presentation

Primary gastric lymphoma commonly affects the elderly patients with peak incidence in the sixth decade of life^[3] and presenting symptoms include epigastric pain, early satiety, fatigue and weight loss.

Diagnosis

These lymphomas are often difficult to differentiate from gastric adenocarcinoma. The lesions are usually ulcers with a ragged, thickened mucosal pattern on contrast radiographs.

The diagnosis is typically made by biopsy at the time of endoscopy. Several endoscopic findings have been reported, including solitary ulcers, thickened gastric folds, mass lesions and nodules. As there may be infiltration of the submucosa, larger biopsy forceps, endoscopic ultrasound guided biopsy, endoscopic submucosal resection, or laparotomy may be required to obtain tissue.

Imaging investigations including CT scans or endoscopic ultrasound are useful to stage disease. Hematological parameters are usually checked to assist with staging and to exclude concomitant leukemia. An elevated LDH level may be suggestive of lymphoma.

Histopathology

The majority of gastric lymphomas are non-Hodgkin's lymphoma of B-cell origin. These tumors may range from well-differentiated, superficial involvements (MALT) to high-grade, large-cell lymphomas.

Other lymphomas involving the stomach include mantle cell lymphoma and T-cell lymphomas which may be associated with enteropathy; the latter usually occur in the small bowel but have been reported in the stomach.

Risk Factors

Risk factors for gastric lymphoma include the following:

Helicobacter pylori ^[4]
Long-term immunosuppressant drug therapy
HIV infection

Differential Diagnosis

Gastric lymphoma must be differentiated from conditions with similar presentation like:^[5]^[6]^[7]^[8]^[9]^[10]^[11]^[12]^[13]

Disease	Cause	Symptoms									Diagnosis	Other findings
		Pain			Nausea & Vomiting	Heartburn	Belching or Bloating	Weight loss	Loss of Appetite	Stools	Endoscopy findings
		Location	Aggravating Factors	Alleviating Factors	Nausea & Vomiting	Heartburn	Belching or Bloating	Weight loss	Loss of Appetite	Stools	Endoscopy findings
Acute gastritis	H. pylori NSAIDS Corticosteroids Alcohol Spicy food Viral infections Crohn's disease Autoimmune diseases Bile reflux Cocaine use Breathing machine or ventilator Ingestion of corrosives	Epigastric pain	Food	Antacids	?	?	?	-	?	Black stools	Pangastritis or antral gastritis Erosive (Superficial, deep, hemorrhagic) Nonerosive (H. pylori)	-
Chronic gastritis	H. pylori Alcohol Medications Autoimmune diseases Chronic stress	Epigastric pain	Food	Antacids	?	?	?	?	?	-	H. pylori gastritis Atrophy Intestinal metaplasia Lymphocytic gastritis Enlarged folds Aphthoid erosions	-
Atrophic gastritis	H. pylori Autoimmune disease	Epigastric pain	-	-	?	-		?	?	-	H. pylori Mucosal atrophy Autoimmune Mucosal atrophy	Iron deficiency anemia Autoimmune gastritis diagnosis include: Antiparietal and anti-IF antibodies Achlorhydria and hypergastrinemia Low serum cobalamine
Crohn's disease	Autoimmune disease	Abdominal pain	-	-	-	-	-	?	?	Chronic diarrhea often bloody with pus or mucus Rectal bleeding	Mucosal nodularity with cobblestoning Multiple aphthous ulcers Linier or serpiginous ulcerations Thickened antral folds Antral narrowing Hypoperistalsis Duodenal strictures	Fever Fatigue Anemia (pernicious anemia)
GERD	Lower esophageal sphincter abnormalities Hiatal hernia Abnormal esophageal contractions Prolonged emptying of stomach Gastrinomas	Epigastric pain	Spicy food Tight fitting clothing	Antacids Head elevation during sleep	? (Suspect delayed gastric emptying)	?	-	-	-	-	Esophagitis Barrette esophagus Strictures	Other symptoms: Dysphagia Regurgitation Nocturnal cough Hoarseness Complications Esophagitis Strictures Barrette esophagus
Peptic ulcer disease	H. pylori Smoking Alcohol Radiation therapy Medications Zollinger-ellison syndrome	Epigastric pain sometimes extending to back Right upper quadrant pain	Duodenal ulcer Pain aggravates with empty stomach Gastric ulcer Pain aggravates with food	Antacids Duodenal ulcer Pain alleviates with food	?	?	-	-	-	Black stools	Gastric ulcers Discrete mucosal lesions with a punched-out smooth ulcer base with whitish fibrinoid base Most ulcers are at the junction of fundus and antrum 0.5-2.5cm Duodenal ulcers Well-demarcated break in the mucosa that may extend into the muscularis propria of the duodenum Found in the first part of duodenum <1cm	Other diagnostic tests Serum gastrin levels Secretin stimulation test Biopsy
Gastrinoma	Associated with MEN type 1	Abdominal pain	-	-	? (suspect gastric outlet obstruction)	?	-	-	-	Black stools	Useful in collecting the tissue for biopsy	May present with symptoms of GERD or peptic ulcer disease Associated with MEN type 1 Diagnostic tests Serum gastrin levels Somatostatin receptor scintigraphy CT and MRI
Gastric Adenocarcinoma	H. pylori infection Smoked and salted food	Abdominal pain	-	-	?	?	?	?	?	Black stools, or blood in stools	Esophagogastroduodenoscopy Multiple biopsies are taken to establish the diagnosis	Other symptoms Dysphagia Early satiety Frequent burping
Primary gastric lymphoma	H. pylori infection	Abdominal pain Chest pain	-	-	-	-	-	?	-	-	Useful in collecting the tissue for biopsy	Other symptoms Painless swollen lymph nodes in neck and armpit Night sweats Fatigue Fever Cough or trouble breathing

Treatment

The predominant therapy for diffuse large B-cell lymphomas of the stomach is chemotherapy.</ref>. Second line therapy for MALT lymphomas is usually chemotherapy with a single agent, and complete response rates of greater than 70% have gain been reported ^[14].

Chemotherapy includes treatment with CHOP with or without rituximab. The mainstay of therapy for MALT lymphomas is antibiotic treatment to eradicate H.pylori. Regression is seen in about 60% of cases with eradication therapy alone. Single drug chemotherapy is recommended as a second line therapy for MALT lymphomas and is associated with a complete resolution of symptoms in greater than 70% cases. In case of complications like gastric outlet obstruction, the recommended treatment is subtotal gastrectomy followed by post-operative.

References

Fauci, et al. Harrison's Principles of Internal Medicine,16th Ed.

Notes

↑ Dawson IMP, Cornes JS, Morrison BC. Primary malignant lymphoid tumours of the intestinal tract. Br J Surg. 1961;49:80-89.
↑ Aisenberg AC. Coherent view of non-Hodgkin's lymphoma. J Clin Oncol. 1995;13:2656-2675.
↑ Thirlby RC. Gastrointestinal lymphoma: a surgical perspective. Oncology (Huntingt). 1993;7:29-32.
↑ NEJM article
↑ Sugimachi K, Inokuchi K, Kuwano H, Ooiwa T (1984). "Acute gastritis clinically classified in accordance with data from both upper GI series and endoscopy". Scand J Gastroenterol. 19 (1): 31–7. PMID 6710074.
↑ Sipponen P, Maaroos HI (2015). "Chronic gastritis". Scand J Gastroenterol. 50 (6): 657–67. doi:10.3109/00365521.2015.1019918. PMC 4673514. PMID 25901896.
↑ Sartor RB (2006). "Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis". Nat Clin Pract Gastroenterol Hepatol. 3 (7): 390–407. doi:10.1038/ncpgasthep0528. PMID 16819502.
↑ Sipponen P (1989). "Atrophic gastritis as a premalignant condition". Ann Med. 21 (4): 287–90. PMID 2789799.
↑ Badillo R, Francis D (2014). "Diagnosis and treatment of gastroesophageal reflux disease". World J Gastrointest Pharmacol Ther. 5 (3): 105–12. doi:10.4292/wjgpt.v5.i3.105. PMC 4133436. PMID 25133039.
↑ Ramakrishnan K, Salinas RC (2007). "Peptic ulcer disease". Am Fam Physician. 76 (7): 1005–12. PMID 17956071.
↑ Banasch M, Schmitz F (2007). "Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors". Wien Klin Wochenschr. 119 (19–20): 573–8. doi:10.1007/s00508-007-0884-2. PMID 17985090.
↑ Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM (2005). "Gastric adenocarcinoma: review and considerations for future directions". Ann Surg. 241 (1): 27–39. PMC 1356843. PMID 15621988.
↑ Ghimire P, Wu GY, Zhu L (2011). "Primary gastrointestinal lymphoma". World J Gastroenterol. 17 (6): 697–707. doi:10.3748/wjg.v17.i6.697. PMC 3042647. PMID 21390139.
↑ Hammel P et al. Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression. J Clin Oncol 1995 Oct;13(10):2524-9.

Template:Gastroenterology Template:Tumors

Template:WikiDoc Sources

[1] Dawson IMP, Cornes JS, Morrison BC. Primary malignant lymphoid tumours of the intestinal tract. Br J Surg. 1961;49:80-89.

[2] Aisenberg AC. Coherent view of non-Hodgkin's lymphoma. J Clin Oncol. 1995;13:2656-2675.

[3] Thirlby RC. Gastrointestinal lymphoma: a surgical perspective. Oncology (Huntingt). 1993;7:29-32.

[4] NEJM article

[pmid6710074-5] Sugimachi K, Inokuchi K, Kuwano H, Ooiwa T (1984). "Acute gastritis clinically classified in accordance with data from both upper GI series and endoscopy". Scand J Gastroenterol. 19 (1): 31–7. PMID 6710074.

[pmid25901896-6] Sipponen P, Maaroos HI (2015). "Chronic gastritis". Scand J Gastroenterol. 50 (6): 657–67. doi:10.3109/00365521.2015.1019918. PMC 4673514. PMID 25901896.

[pmid16819502-7] Sartor RB (2006). "Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis". Nat Clin Pract Gastroenterol Hepatol. 3 (7): 390–407. doi:10.1038/ncpgasthep0528. PMID 16819502.

[pmid2789799-8] Sipponen P (1989). "Atrophic gastritis as a premalignant condition". Ann Med. 21 (4): 287–90. PMID 2789799.

[pmid25133039-9] Badillo R, Francis D (2014). "Diagnosis and treatment of gastroesophageal reflux disease". World J Gastrointest Pharmacol Ther. 5 (3): 105–12. doi:10.4292/wjgpt.v5.i3.105. PMC 4133436. PMID 25133039.

[pmid17956071-10] Ramakrishnan K, Salinas RC (2007). "Peptic ulcer disease". Am Fam Physician. 76 (7): 1005–12. PMID 17956071.

[pmid17985090-11] Banasch M, Schmitz F (2007). "Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors". Wien Klin Wochenschr. 119 (19–20): 573–8. doi:10.1007/s00508-007-0884-2. PMID 17985090.

[pmid15621988-12] Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM (2005). "Gastric adenocarcinoma: review and considerations for future directions". Ann Surg. 241 (1): 27–39. PMC 1356843. PMID 15621988.

[pmid21390139-13] Ghimire P, Wu GY, Zhu L (2011). "Primary gastrointestinal lymphoma". World J Gastroenterol. 17 (6): 697–707. doi:10.3748/wjg.v17.i6.697. PMC 3042647. PMID 21390139.

[14] Hammel P et al. Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression. J Clin Oncol 1995 Oct;13(10):2524-9.

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