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Rare Diseases C 13 Non-Neoplastic Pulmonary Lymphoid Lesions

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Rare Diseases C 13 Non-Neoplastic Pulmonary Lymphoid Lesions 964 Thorax 2001;56:964–971 Thorax: first published as 10.1136/thorax.56.12.964 on 1 December 2001. Downloaded from Rare diseases c 13 Series editors: A E Tattersfield, R M du Bois Non-neoplastic pulmonary lymphoid lesions W D Travis, J R Galvin Pulmonary lymphoid lesions encompass a lymphocytic interstitial pneumonia and follicu- spectrum of inflammatory and reactive lesions lar bronchiolitis. However, in this review that are often diYcult to diagnose since they lymphocytic interstitial pneumonia and follicu- are diYcult to diVerentiate from other reactive lar bronchiolitis are regarded separately. and neoplastic entities (box 1). Understanding these lymphoid lesions is complicated by the Intrapulmonary lymph nodes evolution of concepts, criteria, and terminology Intrapulmonary lymph nodes in the periphery over the past few decades. This review will of the lung are usually situated in a subpleural attempt to summarise a historical perspective location or adjacent to interlobular septa.2 In on this subject and present the current one necropsy study they were found in the concepts of pulmonary lymphoid lesions. lungs of 18% of patients.4 This review will focus on the major pulmo- nary non-neoplastic lymphoid lesions which CLINICAL AND RADIOLOGICAL FEATURES include intrapulmonary lymph nodes, follicular They are usually discovered as an incidental bronchitis/bronchiolitis, lymphocytic intersti- radiographic finding in an asymptomatic pa- tial pneumonia, and nodular lymphoid tient.2 Most patients who undergo resection for 1–3 hyperplasia. The terms “lymphocytic inter- intraparenchymal lymph nodes are middle stitial pneumonia” or “diVuse lymphoid hyper- aged or older and have a history of cigarette plasia” have sometimes been used for both smoking and organic dust exposure.2 They may be solitary or multiple. Non-neoplastic PATHOLOGICAL FEATURES + Intrapulmonary lymph node http://thorax.bmj.com/ Grossly, they appear as grey, brown, or black + Follicular bronchiolitis (diVuse lymphoid or MALT hyperplasia) round to oval-shaped nodules beneath the pleura. Histologically, they consist of circum- + Lymphocytic interstitial pneumonia scribed nodules of lymphoid tissue that are not + Nodular lymphoid hyperplasia encapsulated, but usually border on the pleura + Castleman’s disease or interlobular septa (fig 1).2 Germinal centres may be seen but are frequently absent (fig 1). Neoplastic Histiocytes containing dust pigment and/or MALIGNANT LYMPHOMA Non-Hodgkin’s lymphoma birefringent particles are usually present and on September 23, 2021 by guest. Protected copyright. (1) B cell are often prominent. The birefringent particles typically have a needle-like shape and represent + Extranodal marginal zone B cell 2 lymphoma of MALT type silica. According to Kradin and Mark, 50% of surgically resected intrapulmonary lymph + Lymphomatoid granulomatosis nodes contain hyalinised silicotic nodules and + DiVuse large cell lymphoma ectatic lymphatic channels. Based on this + Lymphoplasmacytic lymphoma observation, they speculated that development + Plasmacytoma Department of (2) T cell of intrapulmonary lymph nodes results from Pulmonary and the presence of inorganic dust and lymphatic + Peripheral T cell lymphoma Mediastinal Pathology, obstruction. Armed Forces Institute + Anaplastic large cell lymphoma of Pathology, 6825 N W (3) Special types of lymphoma 16th Street, Bld 54, Rm + Intravascular lymphoma Follicular bronchiolitis M003B, Washington, + Primary eVusion lymphoma Follicular bronchiolitis is also known as hyper- DC 20306-6000, USA Hodgkin’s lymphoma plasia of the bronchial associated lymphoid tis- W D Travis LEUKAEMIC INFILTRATION sue (BALT) or hyperplasia of the mucosal associated lymphoid tissue (MALT), and Department of + Lymphocytic leukaemia, acute and Thoracic Radiology, chronic pulmonary lymphoid hyperplasia. Bienenstock Armed Forces Institute + Non-lymphocytic leukaemia, acute and et al have published several classical studies of of Pathology chronic the BALT.56 They described the lymphoid J R Galvin + Granulocytic sarcoma aggregates along the bifurcation of the bronchi- oles and along the lymphatic routes. The lym- Correspondence to: Dr W D Travis Box 1 Lymphoid lesions of the lung. MALT = phoepithelium was defined as the mucosal epi- travis@afip.osd.mil mucosa associated lymphoid tissue. thelium, which often contained infiltrating www.thoraxjnl.com Non-neoplastic pulmonary lymphoid lesions 965 Thorax: first published as 10.1136/thorax.56.12.964 on 1 December 2001. Downloaded from Figure 1 Intrapulmonary lymph nodes. (A) Intrapulmonary lymph node consisting of a circumscribed, nodular, subpleural mass of lymphoid tissue with hyperplastic lymphoid follicles. (B) Abundant anthracotic pigment is present between the aggregates of lymphoid tissue. lymphocytes and showed attenuation and flat- recurrent pneumonia, or weight loss.89Pulmo- tening. Follicular bronchiolitis results from nary function may show obstruction, restric- antigenic stimulation of the BALT and polyclo- tion, a mixed pattern, or no defect.9 Patients nal lymphoid hyperplasia.5–7 with hypersensitivity syndromes frequently have a peripheral blood eosinophilia.9 CLINICAL AND RADIOLOGICAL FEATURES Chest radiographs show bilateral reticular or Follicular bronchiolitis occurs in several clini- reticulonodular infiltrates.9 One study of high cal settings including collagen vascular disease, resolution CT scans in 12 patients with follicu- immunodeficiency, hypersensitivity disorders, lar bronchiolitis showed bilateral centrilobular and in a variety of non-specific airway centred nodules in all patients and peribronchial inflammatory conditions such as bronchiecta- nodules in almost half of the cases.8 Nodules sis, airway obstruction, and infections.89It can smaller than 3 mm in diameter were present in occur in any of the collagen vascular disorders all patients, but half the patients also had larger but is especially seen in rheumatoid nodules of 3–12 mm diameter. Ground glass arthritis.10–15 BALT hyperplasia has also been opacities were seen in 75% of patients.8 reported in immunodeficiency syndromes such Patients with follicular bronchiolitis typically as AIDS,816 IgA deficiency, Evan’s syndrome have a favourable prognosis. However, Yousem (autoimmune haemolytic anaemia and im- et al9 found that patients under 30 years of age mune thrombocytopenia),17 and common vari- tended to have progressive disease. Treatment 9 able immunodeficiency syndrome. A familial may be directed at the underlying disease or http://thorax.bmj.com/ example of follicular bronchiolitis has been may consist of steroids or azathioprine. Death reported under the term “familial pulmonary associated with disease occurred in only two of nodular lymphoid hyperplasia”.18 19 patients reported by Yousem et al,9 both of Follicular bronchiolitis occurs mostly in whom had collagen vascular disease and devel- adults89 but can also be found in children.919 oped bronchopneumonia. Yousem et al reported a mean age of 44 years (range 6–69) for patients with collagen vascular PATHOLOGICAL FEATURES disease, 16 years (range 1.5–32) for patients Histologically, follicular bronchiolitis consists with immunodeficiency syndromes, and 55 of abundant peribronchiolar lymphoid follicles on September 23, 2021 by guest. Protected copyright. years (range 38–77) for patients with hypersen- (fig 2).9 The lymphoid follicles may be situated sitivity syndromes.9 The typical presenting between bronchioles and pulmonary arteries symptom is progressive shortness of breath and causing compression of the airway lumen, and cough, but some patients may have fever, may also be present along the interlobular septa Figure 2 Follicular bronchiolitis. (A) Hyperplastic lymphoid tissue surrounding the bronchiole. Mild bronchiolar fibrosis is also present. (B) Hyperplastic lymphoid tissue appears to compress the lumen of one bronchiole (centre right). The adjacent bronchioles show marked chronic inflammation. There is mild bronchiolectasis and chronic inflammation of a bronchiole in the surrounding lung parenchyma. www.thoraxjnl.com 966 Travis, Galvin and beneath the pleura. The epithelium of the Thorax: first published as 10.1136/thorax.56.12.964 on 1 December 2001. Downloaded from bronchioles is often infiltrated by lymphocytes. Collagen vascular disease The lymphoid infiltrate is limited to the 21 26 52 peribronchiolar lymphoid follicle or it may +Sjögren’s syndrome +Rheumatoid arthritis53 extend superficially into the surrounding alveo- 54–56 lar interstitium, but it lacks the extensive alveo- +Systemic lupus erythematosus lar septal infiltration of lymphocytic interstitial Other immunological disorders pneumonia. However, there is a continuum of 21 57 lymphoid infiltration between follicular bron- +Autoimmune haemolytic anaemia +Pernicious anaemia58 chiolitis and lymphocytic interstitial pneumo- 21 nia and in some cases this distinction may be +Myasthenia gravis +Hashimoto’s thyroiditis33 somewhat arbitrary. A neutrophilic exudate is 23 present within the bronchiolar lumen in +Primary biliary cirrhosis +Coeliac sprue59 approximately 50% of cases. Secondary ob- 21 25 structive changes such as foamy macrophages +Dysproteinaemia and small foci of organising pneumonia may be seen.9 Follicular bronchiolitis is frequently a Immunodeficiency +AIDS, particularly in children16 60–62 secondary lesion and may be associated with 63 other findings such as bronchiectasis, bronchi- +Common variable immunodeficiency olectasis, bronchiolar fibrosis. or organising Infections pneumonia. 41
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