Gastric lymphoma

# Overview
Primary gastric lymphoma is cancer derived from lymphocytes (a type of white blood cell) that originates in the stomach. Most common cause of primary gastric lymphoma is mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL) of the stomach. Primary gastric lymphoma may be classified according to histology into MALT lymphoma and DLBCL. MALT lymphoma can be further divided into H. pylori positive MALT lymphoma and H. pylori negative MALT lymphoma. DLBCL can be divided into 3 subgroups germinal-center B-cell-like, activated B-cell-like, primary mediastinal DLBCL. The exact pathogenesis of primary gastric lymphoma is not fully understood. Common symptoms of primary gastric lymphoma include epigastric discomfort, anorexia, weight loss, nausea associated with or without vomiting, occult gastrointestinal bleeding, early satiety. Less common symptoms include ever and night sweats. Patients with primary gastric lymphoma usually appear normal. Vital signs are within normal limits unless there is complication. Physical examination of patients with primary gastric lymphoma is usually remarkable for palpable mass and peripheral lymphadenopathy. Gastric lymphoma must be differentiated from conditions with similar presentation like acute gastritis, chronic gastritis, atrophic gastritis, Crohn's disease, gastroesophageal reflux disease, peptic ulcer disease, gastrinoma and gastric adenocarcinoma. Primary gastric lymphoma commonly affects elderly patients in the fifth or sixth decade of life. Primary gastric lymphoma is more prevalent in men than in women. Risk factors for gastric lymphoma include Helicobacter pylori, long-term immunosuppressant drug therapy, HIV infection. The majority of patients with primary gastric lymphoma present with nonspecific symptoms in the 5th decade of life. Early clinical features include epigastric pain, nausea, and vomiting. If left untreated, patients with gastric lymphoma may progress to develop anorexia, weight loss, and early satiety. Common complications of gastric lymphoma include perforation, hemorrhage, and obstruction. Prognosis is generally good, and complete remission can be achieved after 6-8 rounds of chemotherapy or following surgery. Upper gastrointestinal endoscopy with biopsy is the gold standard test for the diagnosis of gastric lymphoma. Laparotomy and laparoscopy should be performed when the patient presents with complications such as perforation or obstruction. An endoscopic ultrasound (EUS) will help assess the depth of lymphoma invasion and involvement of perigastric nodes. MALT lymphoma presents as superficial spreading or diffuse infiltrating lesion whereas diffuse large B cell lymphoma has a typical mass forming lesion appearance on endoscopic ultrasound. 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. There are no established measures for the primary and secondary prevention of gastric lymphoma.

# Classification
Primary gastric lymphoma may be classified according to histology into the following subtypes:
- B-cell lymphomas are of two main types:
MALT lymphoma
DLBCL (diffuse large B-cell lymphoma)
- MALT lymphoma
- DLBCL (diffuse large B-cell lymphoma)
- MALT lymphoma can be further divided into:
H. pylori positive MALT lymphoma
H. pylori negative MALT lymphoma
- H. pylori positive MALT lymphoma
- H. pylori negative MALT lymphoma
- DLBCL can be divided into 3 subgroups based on the gene expression:
Germinal-center B-cell-like
Activated B-cell-like
Primary mediastinal DLBCL
- Germinal-center B-cell-like
- Activated B-cell-like
- Primary mediastinal DLBCL

# Pathophysiology
- The exact pathogenesis of primary gastric lymphoma is not fully understood.
- Primary gastric lymphoma is cancer derived from lymphocytes (a type of white blood cell) that originates in the stomach.
- Most common cause of primary gastric lymphoma is mucosa-associated lymphoid tissue (MALT) 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.
- Most of the MALT lymphomas have an associated history of H.pylori infection. Chronic inflammation associated with H.pylori can cause T and B cell proliferation that increases the risk of malignant transformation.
In case of DLBCL, antibiotic eradication therapy for H.pylori has shown to result in complete remission of lymphoma highlighting the role of H.pylori in the pathogenesis.
- HBV plays a role in the pathogenesis of B-cell NHL, evidenced by an increased risk of developing NHL in HBsAg positive patients.

## Histopathology
Most of the gastric lymphomas are predominantly non-Hodgkins lymphoma of B-cell origin. Primary gastric lymphoma can vary from being well-differentiated, low-grade lymphomas to high grade or large cell lymphomas.

# Symptoms
Common symptoms of primary gastric lymphoma include:
- Epigastric discomfort
- Anorexia
- Weight loss
- Nausea associated with or without vomiting
- Occult gastrointestinal bleeding
- Early satiety
Less common symptoms include:
- Fever
- Night sweats

# Physical Examination

## Appearance of the Patient
- Patients with primary gastric lymphoma usually appear normal.

## Vital signs
Vital signs are within normal limits unless there is complication.

## Abdominal Examination
- Physical examination of patients with primary gastric lymphoma is usually remarkable for palpable mass and peripheral lymphadenopathy.

# Differential Diagnosis
Gastric lymphoma must be differentiated from conditions with similar presentation like acute gastritis, chronic gastritis, atrophic gastritis, Crohn's disease, gastroesophageal reflux disease, peptic ulcer disease, gastrinoma and gastric adenocarcinoma :

# Demographics
- Primary gastric lymphoma commonly affects elderly patients in the fifth or sixth decade of life.
- Primary gastric lymphoma is more prevalent in men than in women.

# Risk Factors
Risk factors for gastric lymphoma include the following:
- Helicobacter pylori
- Long-term immunosuppressant drug therapy
- HIV infection

# Natural History, Complications and Prognosis

## Natural History
- The majority of patients with primary gastric lymphoma present with nonspecific symptoms in the 5th decade of life.
- Early clinical features include epigastric pain, nausea, and vomiting.
- If left untreated, patients with gastric lymphoma may progress to develop anorexia, weight loss, and early satiety.

## Complications
- Common complications of gastric lymphoma include perforation, hemorrhage, and obstruction.

## Prognosis
- Prognosis is generally good, and complete remission can be achieved after 6-8 rounds of chemotherapy or following surgery.

# Diagnosis
- Upper gastrointestinal endoscopy with biopsy is the gold standard test for the diagnosis of gastric lymphoma.
- Laparotomy and laparoscopy should be performed when the patient presents with complications such as perforation or obstruction.
- Findings on upper gastrointestinal endoscopy suggestive of gastric lymphoma:
Mucosal erythema
A mass or polypoid lesion with or without ulceration
Benign-appearing gastric ulcer
Nodular lesion
Thickened, cerebroid gastric folds
- Mucosal erythema
- A mass or polypoid lesion with or without ulceration
- Benign-appearing gastric ulcer
- Nodular lesion
- Thickened, cerebroid gastric folds
- An endoscopic ultrasound (EUS) will help assess the depth of lymphoma invasion and involvement of perigastric nodes.
- MALT lymphoma presents as superficial spreading or diffuse infiltrating lesion whereas diffuse large B cell lymphoma has a typical mass forming lesion appearance on endoscopic ultrasound.
- 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.

## MRI
Findings of Gastric lymphoma on MRI includes:
- Irregularly thickened mucosal folds
- Irregular submucosal infiltration
- Annular constricting lesion
- Exophytic tumor growth
- Retroperitoneal lymphadenopathy.

# Treatment
- The predominant therapy for diffuse large B-cell lymphomas of the stomach is chemotherapy.
- Second line therapy for MALT lymphomas is usually chemotherapy with a single agent, and complete response rates of greater than 70% have been observed.
- 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.

# Prevention

## Primary Prevention
Proper treatment of Helicobacter pylori, can prevent MALT lymphoma.

## Secondary Prevention
There are no established measures for the secondary prevention of gastric lymphoma.