Primary pulmonary lymphoma (ORPHA:2420)
A rare neoplastic disease defined as a clonal lymphoid proliferation affecting one or both lungs (parenchyma and/or bronchi) in a patient with no detectable extrapulmonary involvement at diagnosis or during the subsequent 3 months. PPL comprises low grade/indolent B cell PPL forms, the most frequent form represented by the marginal B-cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) and other non-MALT low grade lymphomas; and more rarely high-grade B-cell PPL (including diffuse large B cell lymphoma) and lymphomatoid granulomatosis (LYG).
Epidemiology
Primary pulmonary lymphoma (PPL) is very rare and represents only 3-4% of extranodal non-Hodgkin lymphoma (NHL, less than 1% of NHL, and only 0.5-1% of primary pulmonary malignancies. MALT lymphoma represents 85-90% of PPL cases and is the most common type of pulmonary lymphoma. The ratio of male to female patients is close to 1:1.
Clinical description
PPL onset generally occurs in the 5th and 6th decades of life, and very occasionally affects those under 30 years of age. The clinical presentations of PPL are variable and depend on the distinct B-cell histological subtype: Low grade B cell PPL including MALT lymphomas have an indolent presentation while high-grade B-cell PPL and LYG may have an aggressive clinical picture. 50% of patients with MALT lymphoma are asymptomatic at presentation. When present, symptoms are not specific and include coughing, mild dyspnea, chest pain, wheezing, and occasionally hemoptysis. Fever and weight loss are present in less than 25% of cases. Patients with high-grade B-cell PPL usually present respiratory manifestations, fever and weight loss while patients with LYG frequently have brain, kidney and otorhinolaryngeal manifestations.
Etiology
PPL are lymphoproliferative disorders that originate frequently from clonal proliferation of the B cell-lineage, most commonly marginal zone B-cells of MALT of the bronchus. MALT lymphomas are thought to be acquired as a result of chronic antigenic stimulation such as smoking, autoimmune disease, or infection while LYG is associated with Epstein-Barr virus (EBV) infection.
Diagnostic methods
Diagnosis of PPL relies on clinical and radiographic findings which are nonspecific and include solitary nodule, multiple ill-defined nodules, consolidated mass with air bronchograms, pleural effusions, atelectasis, and cavities. Histological examination helps diagnose the type of tumor. Immunohistochemical analysis reveals CD19-CD20+ cells.
Differential diagnosis
Radiological appearance may mimic cryptogenic organizing pneumonia, lymphoid interstitial pneumonia (LIP), diffuse lymphoid hyperplasia, follicular bronchitis and bronchioloalveolar carcinoma. LIP may be associated with PPL in case of autoimmune disease.
Management and treatment
The treatment options include watchful observation for indolent types of PPL, surgery in localized tumors, chemotherapy with or without rituximab if the lesions are diffuse or involve both lungs and radiotherapy for patients with a unique, small lesion.
Prognosis
The prognosis for low grade PPL is good with survival equal to that of the general population. However, survival rate for high grade PPL and LYG can be poorer.

                            Last update: 
                            November 2019


                            - Expert reviewer(s): 
                            Pr Jacques CADRANEL