The radiological spectrum of pulmonary lymphoproliferative disease

Abstract

Pulmonary lymphoproliferative disorders (LPD) are characterised by abnormal proliferation of indigenous cell lines or infiltration of lung parenchyma by lymphoid cells. They encompass a wide spectrum of focal or diffuse abnormalities, which may be classified as reactive or neoplastic on the basis of cellular morphology and clonality. The spectrum of reactive disorders results primarily from antigenic stimulation of bronchial mucosa-associated lymphoid tissue (MALT) and comprises three main entities: follicular bronchiolitis, lymphoid interstitial pneumonia and (more rarely) nodular lymphoid hyperplasia. Primary parenchymal neoplasms are most commonly extranodal marginal zone lymphomas of MALT origin (MALT lymphomas), followed by diffuse large B-cell lymphomas (DLBCLs) and lymphomatoid granulomatosis (LYG). Secondary lymphomatous parenchymal neoplasms (both Hodgkin and non-Hodgkin lymphomas) are far more prevalent than primary neoplasms. Acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL) and post-transplantation lymphoproliferative disorder (PTLD) may also primarily affect the lung parenchyma. Modern advances in treatments for AIDS and transplant medicine are associated with an increase in the incidence of LPD and have heightened the need to understand the range of imaging appearance of these diseases. The multidetector CT (MDCT) findings of LPD are heterogeneous, thereby reflecting the wide spectrum of clinical manifestations of these entities. Understanding the spectrum of LPD and the various imaging manifestations is crucial because the radiologist is often the first one to suggest the diagnosis and has a pivotal role in differentiating these diseases. The current concepts of LPD are discussed together with a demonstration of the breadth of MDCT patterns within this disease spectrum.

Figure 1

Schematic illustration of a classification system for the pulmonary lymphoproliferative disorders (LPDs). AIDS, acquired immune deficiency syndrome; HL Hodgkin lymphoma; MALT, mucosa–associated lymphoid tissue; NHL, non–Hodgkin lymphoma; PTLD, post-transplantation lymphoproliferative disorder.

Figure 2

Multifocal nodular lymphoid hyperplasia in a 30-year-old female. Multidetector CT scan with lung window settings demonstrates a well-circumscibed pulmonary nodule (arrow) with an air bronchogram in the periphery of the right upper lobe. Note the mild surrounding linear opacities indicating focal lymphangitic extension. In addition two smaller nodules (arrowheads) are seen in the right lung. Biopsy of the larger nodule was consistent with nodular lymphoid hyperplasia.

Figure 3

Follicular bronchiolitis. (a) A high-resolution CT demonstrates tiny parenchymal nodules (arrows) and subtle mosaic attenuation in a 56-year-old female with rheumatoid arthritis. There is a mosaic pattern due to small airways disease. The patient presented with progressively worsening shortness of breath. (b) Follicular bronchiolitis in a patient with thymoma. The image shows chronic inflammation of membranous bronchioles (arrows) with reactive lymphoid follicles (arrowheads). Note the normal appearing pulmonary artery (curved arrow) adjacent to an abnormal bronchiole. The intervening lung parenchyma is preserved. Haematoxylin–eosin stain; original magnification ×40.

Figure 4

Lymphoid interstitial pneumonia in a 53-year-old female with Sjogren syndrome. High-resolution CT demonstrates bilateral diffuse ground-glass opacity, cystic airspaces and small nodules (arrows). This was diagnosed with an open lung biopsy.

Figure 5

Lymphoid interstitial pneumonitis. (a) A high-resolution CT in a 52-year-old female with mixed connective tissue disease demonstrates extensive ground-glass opacity with small centrilobular nodules (black arrows) and lung cysts. A bizarrely shaped nodule in the left upper lobe (white arrow) was found to represent an amyloid deposit on percutaneous core biopsy. (b) Histopathological specimen: there is a prominent and diffuse lymphocytic interstitial infiltrate, involving both the airways (thick arrow) and the alveolar septa (thin arrows), which are remarkably thickened. A reactive lymphoid follicle with germinal centre is also noted (asterisk). Haematoxylin–eosin stain; original magnification ×40.

Figure 6

Lymphoid interstitial pneumonitis. A high-resolution CT in a 38-year-old male with human immunodeficiency virus infection demonstrates innumerable small bilateral centrilobular nodules (arrowheads) and patchy ground-glass opacities (arrow) with no lung cysts seen. The diagnosis was confirmed with a transbronchial lung biopsy. There is also a right hilar nodal mass (white arrow).

Figure 7

Lymphoid interstital pneumonitis (LIP) with amyloid. (a) A high-resolution CT scan in a 40-year-old female demonstrates cysts and soft tissue nodules (arrows) in the left lung. The nodule in the lingula contains calcium and was proven on percutaneous core biopsy to represent amyloid. The presence of LIP was confirmed with open lung biopsy. (b) A multidetector CT scan with mediastinal window setting in the same patient demonstrates calcification in two further soft tissue lung nodules (arrows). Such nodules in this context should raise suspicion for coexistent pulmonary amyloidosis.

Figure 8

A thin-section CT scan in a 28-year-old female demonstrating a peribronchial left lower lobe soft tissue mass (black arrow) proven to represent lymphoma. There is a background of ground-glass opacities (black arrowhead) and cysts (white arrow), consistent with coexistent lymphoid interstitial pneumonitis.

Figure 9

Mucosa-associated lymphoid tissue (MALT) lymphoma in a 31-year-old male. The multidetector CT scan demonstrates a large, well-circumscribed soft tissue peripheral mass in the left lung posteriorly (arrow). Percutaneous core needle biopsy demonstrated MALT lymphoma.

Figure 10

Mucosa-associated lymphoid tissue (MALT) lymphoma. A multidetector CT scan in a 43-year-old female demonstrates a wedge-shaped soft tissue opacity with an air bronchogram (arrow) adjacent to the right cardiac border. This was proven to be a MALT lymphoma on percutaneous core biopsy.

Figure 11

Mucosa-associated lymphoid tissue (MALT) lymphoma. A multidetector CT scan in a 40-year-old female demonstrates multiple large bilateral lung nodules (arrows). These were slowly growing on 6-monthly follow-up scans. Biopsy revealed a diagnosis of MALT lymphoma.

Figure 12

(a) Diffuse large B-cell lymphoma in a 32-year-old male. A chest radiograph demonstrates a large opacity in the right middle lobe obscuring the right heart border. (b) A multidetector CT scan in the same patient demonstrates a well-circumscribed right middle lobe mass with central low attenuation, consistent with necrosis (arrow). This was proven on biopsy to represent a primary form of diffuse large B-cell lymphoma.

Figure 13

Lymphomatoid granulomatosis. (a) A chest radiograph in a 37-year-old male demonstrates multiple large bilateral pulmonary nodules with a lower zone predominance. (b) A high-resolution CT in the same patient demonstrates large, irregularly marginated pulmonary nodules. Some of the nodules are coalescent (arrow) and others are of ground-glass opacity, consistent with the “migratory” phenomenon associated with nodules in this disease.

Figure 14

(a) Lymphomatoid granulomatosis. A multidetector CT scan in a 46-year-old male demonstrates multiple pulmonary nodules coalescing in the lower lobes to form larger masses (arrows). Percutaneous core biopsy of the mass-like consolidation in the left lower lobe revealed lymphomatoid granulomatosis. (b) Lymphomatoid granulomatosis histopathological specimen in the same patient: well-demarcated cellular nodule with a central area of necrosis (asterisk). The preserved alveolar parenchyma is shown in the upper part of the image, above the dashed line. Inset shows the angiocentric nature of the lesion. Inset A: infiltration of the intima by lymphoid cells. The muscular wall of the artery is indicated by the arrow. Most of the lymphocytes are small reactive T-cells and atypical B-cells are rare (thin arrows). Haematoxylin–eosin stain; original magnification ×200. Inset B: elastin stain shows the elastic lamina of the artery (arrows). Elastin stain; original magnification ×200.

Figure 15

Secondary pulmonary lymphoma in a 40-year-old male. A chest radiograph demonstrates bilateral parenchymal consolidation with air bronchograms. Note the presence of abnormal paratracheal soft tissue opacity, in keeping with lymphadenopathy. This combination of findings should raise suspicion of lymphoma.

Figure 16

Secondary pulmonary lymphoma. An axial multidetector CT scan in the same patient in Figure 15 demonstrates the mass-like right upper lobe consolidation with air bronchograms (arrow) and this is associated with further bilateral areas of parenchymal involvement. The alveolar pattern of secondary lymphoma is associated with a poor prognosis.

Figure 17

(a) Secondary pulmonary lymphoma. A multidetector CT scan in a 26-year-old male demonstrates a large anterior mediastinal soft tissue mass (arrow) displacing the mediastinal structures posteriorly and abutting the pleura on the left. There is a small left pleural effusion (arrowhead). (b) Integrated fluorodeoxyglucose (FDG) positron emission tomography CT scan in the same patient demonstrates parenchymal extension (arrow) from the large anterior mediastinal mass which demonstrates markedly increased FDG uptake.

Figure 18

Secondary pulmonary lymphoma. A thin-section CT scan in a 63-year-old female demonstrates nodular thickening of interlobular septa in both anterior upper lobes (arrows), consistent with lymphangitic spread of lymphoma. Small bilateral pleural effusions are also seen (arrowheads).

Figure 19

(a) Secondary pulmonary lymphoma in a 42-year-old male with a history of non-Hodgkin lymphoma. Multidetector CT scan demonstrates two peripheral pulmonary masses (arrows). This was confirmed to represent recurrence of non-Hodgkin lymphoma on percutaneous core biopsy. (b) A multidetector CT scan at a different level in the same patient shows cavitation of a recurrent non-Hodgkin lymphoma nodule in the medial basal segment of the right lower lobe (arrow).

Figure 20

Acquired immune deficiency syndrome-related lymphoma: thin-section CT scan in a 49-year-old who is human immunodeficiency virus-positive with a CD4 (cluster of differentiation 4) count of 68 dl^–1 demonstrates a single, well-defined, peripheral large pulmonary nodule (arrow), proven to represent non-Hodgkin lymphoma on percutaneous core biopsy.

Figure 21

Acquired immune deficiency syndrome (AIDS)-related lymphoma. A CT scan in a 36-year-old male with AIDS reveals scattered small pulmonary nodules (arrows) with a focus of chronic left lower lobe consolidation (arrowhead). Biopsy of the consolidation revealed an aggressive non-Hodgkin lymphoma.

Figure 22

Post-transplantation lymphoproliferative disorder. A CT scan in a 14-year-old stem cell transplant recipient demonstrates multiple small lung nodules, many of which are subpleural (arrows). There was also hilar adenopathy, which is not well seen on the lung window setting. This patient presented 7 months post transplant with fever and an intractable infectious mononucleosis-type syndrome.