Pancreatic Lymphoma

Pancreatic lymphoma is lymphoma involving the pancreas, either primary (disease confined to the pancreas and peripancreatic nodes) or secondary (spread from nodal or other extranodal disease). It is a treatable condition that can mimic pancreatic carcinoma.

Primary pancreatic lymphoma is under 0.5% of pancreatic malignancies and under 1% of extranodal lymphomas. Most cases are diffuse large B-cell lymphoma (about 80%), and follicular lymphoma is next. The mean age is 55 to 65 years, with a male predominance. Secondary involvement is more common than primary.

It is more frequent in immunosuppressed patients (HIV, transplant). Five year survival in large B-cell disease is about 50% to 60% with chemotherapy.

Pathophysiology.

Malignant lymphocytes infiltrate the pancreatic head (most often) and peripancreatic nodes, producing a bulky mass with limited involvement of the duct, because the tumour infiltrates rather than invades.

Abdominal pain, weight loss, jaundice (less frequent than with carcinoma), nausea, palpable mass, B symptoms (fever, night sweats), acute pancreatitis and bowel obstruction.

Red flags.

• B symptoms with a pancreatic mass.
• Rapidly enlarging mass.
• Lymphadenopathy or splenomegaly.
• Tumour lysis features (raised urate, potassium and creatinine).

Imaging (CT and magnetic resonance imaging) shows a bulky, homogeneous, hypodense mass in the pancreatic head, often over 6 cm, without main pancreatic duct dilatation, vascular encasement or atrophy. Lactate dehydrogenase is raised and CA 19-9 is usually normal. Core biopsy by endoscopic ultrasound with flow cytometry and immunohistochemistry (CD20, CD10, BCL2, BCL6, Ki-67) confirms the diagnosis. Stage with positron emission tomography-CT and bone marrow examination. Test for HIV, hepatitis B and C.

Differential diagnosis.

• Pancreatic ductal adenocarcinoma.
• Autoimmune pancreatitis.
• Pancreatic neuroendocrine tumour.
• Acinar cell carcinoma.
• Metastasis.
• Peripancreatic lymphadenopathy of other cause.

Chemotherapy is the treatment, not surgery. Reserve resection for diagnostic uncertainty or complications. Treat obstructive jaundice by endoscopic stenting only when needed, since response to chemotherapy relieves obstruction.

• R-CHOP every 21 days for 6 cycles: rituximab 375 mg/m2 IV on day 1, cyclophosphamide 750 mg/m2 IV on day 1, doxorubicin 50 mg/m2 IV on day 1, vincristine 1.4 mg/m2 IV on day 1 (capped at 2 mg) and prednisolone 100 mg orally on days 1 to 5; maximum lifetime doxorubicin 450 to 550 mg/m2; monitor blood counts before each cycle, echocardiography at baseline and by cumulative dose, liver and renal function, tumour lysis and neuropathy; reduce doxorubicin and vincristine in hepatic impairment (raised bilirubin), delay for neutrophils under 1.0 x 10^9/L and reduce cyclophosphamide in severe renal impairment.
• Allopurinol (tumour lysis prophylaxis): 300 mg orally once daily starting 1 to 2 days before treatment for 7 to 10 days; maximum 600 mg daily; monitor urate, creatinine and rash; reduce to 100 to 200 mg daily when creatinine clearance is under 30 mL/min.
• Rasburicase (high tumour burden): 0.2 mg/kg IV over 30 minutes once daily for up to 5 days; maximum 5 days; monitor urate (sample on ice) and for haemolysis; avoid in glucose-6-phosphate dehydrogenase deficiency.
• Entecavir (hepatitis B core antibody positive, as prophylaxis): 0.5 mg orally once daily from before chemotherapy until 12 months after; maximum 0.5 mg daily; monitor liver function and viral load; give 0.5 mg every 48 hours when creatinine clearance is 30 to 49 mL/min.

Add central nervous system prophylaxis in high risk patients by haematology decision, and radiotherapy for residual bulky disease in selected cases.

Monitoring. Positron emission tomography-CT after 3 to 4 cycles and at the end of treatment; clinical and laboratory review every 3 months for 2 years.

Referral and escalation. Haematology oncology urgently; endoscopy for biliary drainage if cholangitis occurs.