Small Nodules

Small Nodules with Centrilobular Distribution

Definition

Small nodules, usually less than 10 mm in diameter, are regarded to be centrilobular when the nodules are separated from pleural surfaces or the interlobular septa by a distance of several millimeters, usually centered 4–10 mm from the pleural or fissural surfaces or from interlobular septa [1, 2]. They are frequently associated with centrilobular branching nodular structures, thus forming the so-called tree-in-bud sign (Figs. 18.1 and 18.2) (see also Chap. 9). The small nodules represent lesions involving the small airways. However, vascular lesions involving the arterioles and capillaries may simulate the centrilobular small nodules and branching nodular structures (vascular tree-in-bud sign) [1, 3, 4] (Fig. 18.3).

Fig. 18.1 Cystic fibrosis in a 21-year-old woman. Lung window image of CT scan (2.5-mm section thickness) obtained at level of azygos arch shows well-defined (arrows) and poorly defined (arrowheads) tree-in- bud sign in both upper lobes. Also note mucus plugging (open arrows) in medium-sized airways

Diseases Causing the Pattern

The diseases manifesting small nodules of centrilobular distribution or tree-in-bud signs include infectious bronchiolitis including Haemophilus influenzae pneumonia and Mycoplasma pneumoniae pneumonia [5] (Fig. 18.4), bronchogenic dissemination of pulmonary tuberculosis [6, 7] or the nodular bronchiectatic form of nontuberculous mycobacterial (NTM) pulmonary disease [8, 9] (Fig. 18.5), diffuse panbronchiolitis (DPB) [10] (Fig. 18.6), subacute hypersensitivity pneumonitis, follicular bronchiolitis [11] (Fig. 18.7) or bronchus-associated lymphoid tissue lymphoma [12], and cystic fibrosis [13].

Vascular tree-in-bud sign may be seen in pulmonary tumor embolism [3] or localized lymphangitic carcinomatosis (Figs. 18.3 and 18.8), foreign-body-induced necrotizing vasculitis or necrotizing pulmonary vasculitis in systemic lupus erythematosus [4, 6], and localized pulmonary lymphatic metastasis [14].

Distribution

In infectious bronchiolitis and DPB, the small nodules or tree-in-bud signs show middle and lower lung zone predominance. In particular, the small nodules in DPB depict symmetric and subpleural distribution along with bronchiectasis [10]. They are random and patchy in distribution in bronchogenic dissemination of tuberculosis, hypersensitivity pneumonitis, and follicular bronchiolitis or bronchus-associated lymphoid tissue lymphoma or follicular bronchiolitis. Right middle lobe and lingular division of the left upper lobe are typical location of nodular bronchiectatic form of nontuberculous mycobacterial pulmonary disease. Other lobes such as right upper lobe and both lower lobes may have lesions of tree-in-bud signs (pathologic cellular bronchiolitis). The lesions of bronchiectasis and cellular bronchiolitis (tree-in- bud signs) in the disease are asymmetrically distributed, differently from DPB [8, 9].

Fig. 18.2 Infectious bronchiolitis showing tree-in-bud signs in a 3-year-old boy. (a) Lung window image of CT scan (5.0-mm section thickness) obtained at level of liver dome shows tree-in-bud signs (arrows) in both lower lobes. Also note bronchiectasis (open arrows) in bottom of right middle lobe and lingular division of left upper lobe. (b) Low-magnification (×10) photomicrograph of surgical biopsy specimen obtained from right lower lobe demonstrates bronchiolocentric

(arrows) dense inflammatory cell (cellular) infiltration. (c) Highmagnification (×100) photomicrography exhibits more clearly bronchiolocentric (arrows) dense inflammatory cell infiltration. (d) High-magnification (×200) photomicrograph discloses thickened bronchiolar wall with dense lymphoplasma cell infiltration and expansion of subepithelial connective tissue. Br bronchiole

In tumor thrombotic microangiopathy, necrotizing vasculitis, and localized lymphatic metastasis, the vascular tree-in- bud sings demonstrate lower lung zone and subpleural predominance.

Clinical Considerations

Chronic maxillary sinusitis is usually associated with DPB. Follicular bronchiolitis is a kind of lymphoproliferative disease. Therefore, the disease is frequently associated with

rheumatoid arthritis, mixed collagen vascular disorders, autoimmune disorders, or acquired immunodeficiency syndrome [11]. Patient diagnosis of cystic fibrosis may be confirmed with positive chloride sweat test in all cases. As in DPB, maxillary sinusitis is frequently associated and the sinusitis may be used as a surrogate model for gene therapy [15].

Pulmonary tumor thrombotic microangiopathy is infrequently seen in a patient with gastric cancer [16], ovarian cancer, or lung invasive adenocarcinoma. In tumor thrombotic microangiopathy, hypoxemia is severe and patient complains of progressive dyspnea.