Honeycombing

Lee, Kyung Soo; Han, Joungho; Chung, Man Pyo; Jeong, Yeon Joo

doi:10.1007/978-3-642-37096-0_17

Kyung Soo Lee⁵,
Joungho Han⁶,
Man Pyo Chung⁷ &
…
Yeon Joo Jeong⁸

Part of the book series: Radiology Illustrated ((RADILL))

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Abstract

Pathologically, honeycombing (HC) represents destroyed and fibrotic lung tissue containing numerous cystic airspaces with thick fibrous walls [1] (Fig. 17.1). In addition, HC on pathology is characterized by cysts usually measuring <1 mm, often below the resolution of CT, and therefore not necessarily concordant with macroscopic HC seen on CT images. On thin-section CT (TSCT) scans, the appearance is of clustered cystic air spaces, typically of comparable diameters on the order of 3–10 mm but occasionally as large as 25 mm [2] (Fig. 17.1b). Some researchers may consider HC as a multilayer cluster of cysts with shared walls, but others may recognize a single layer cluster of cysts [3] (Fig. 17.1c).

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Honeycombing with Subpleural or Basal Predominance

Definition

Pathologically, honeycombing (HC) represents destroyed and fibrotic lung tissue containing numerous cystic airspaces with thick fibrous walls [1] (Fig. 17.1). In addition, HC on pathology is characterized by cysts usually measuring <1 mm, often below the resolution of CT, and therefore not necessarily concordant with macroscopic HC seen on CT images. On thin-section CT (TSCT) scans, the appearance is of clustered cystic air spaces, typically of comparable diameters on the order of 3–10 mm but occasionally as large as 25 mm [2] (Fig. 17.1b). Some researchers may consider HC as a multilayer cluster of cysts with shared walls, but others may recognize a single layer cluster of cysts [3] (Fig. 17.1c).

Diseases Causing the Pattern

Cystic structures of HC on transverse CT images consist of either dilated peripheral bronchioles or alveolar ducts, surrounded by several in-folded layers of thickened alveolar septa (a true HC cyst) or tangential view of traction bronchiectasis (TB). In idiopathic pulmonary fibrosis (IPF) and usual interstitial pneumonia (UIP) (Figs. 17.1 and 17.2), cystic structures are mainly composed of true HC cysts in the peripheral portion of the lungs, while most cystic structures in patients with nonspecific interstitial pneumonia (NSIP) (Fig. 17.3) seem to be tangential views of TB [4]. Of course, even in patients with NSIP, main cysts of HC are the true HC cysts as in IPF/UIP. Honeycombing has been reported in up to 40 % of NSIP [5]. HC may be observed in approximately 10 % of patients with asbestosis (Fig. 17.4) along with findings of irregular interlobular septal thickening, intralobular interstitial thickening, subpleural dot-like or branching opacity, and ground-glass opacity (GGO), not to mention of pleural plaques [6].

Distribution

In most diseases, lung abnormalities show lower lung zone and subpleural-distribution predominance. In NSIP, abnormalities may be located along the bronchovascular bundles and may demonstrate subpleural sparing [7].

Clinical Considerations

The identification of HC is essential for making the certain CT diagnosis of UIP and for predicting patient prognosis with fibrotic IIPs [8].

Even in cases of fibrotic idiopathic interstitial pneumonias (IIPs) with little HC, serial CT reveals an increase in the extent of HC and reticulation and a decrease in the extent of GGO. Overall extent of lung fibrosis on the baseline CT examination appears predictive of survival in fibrotic IIPs with little HC [9].

Measuring a fibrotic score (the extent of reticulation plus HC) at TSCT helps predict patient prognosis. In other words, patients with UIP or fibrotic NSIP who have a high fibrotic score determined at thin-section CT and a low DLco level have a high death risk [10].

HC mimickers at CT are paraseptal emphysema and TB of varying severity. NSIP may simulate UIP at CT in the presence of emphysema [11]. Any fibrotic interstitial pneumonia with concurrent emphysema may cause problems in CT interpretation [12].

Key Points for Differential Diagnosis

Diseases	Distribution								Clinical presentations			Others
	Zones								Clinical presentations
	U	M	L	SP	C	R	BV	R	Acute	Subacute	Chronic
IPF/UIP		+	+	+				+			+
NSIP		+	+	+	+		+	+		+	+	Female predominance; subpleural sparing and along BV bundles
Asbestosis		+	+	+				+			+	Exposure history and pleural plaques; with subpleural dot-like or branching opacity and subpleural lines

Note: IPF idiopathic pulmonary fibrosis, UIP usual interstitial pneumonia, NSIP nonspecific interstitial pneumonia, U upper, M middle, L lower, SP subpleural, C central, R random, BV bronchovascular

Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia

Pathology and Pathogenesis

In a typical case, the lungs are shrunken and firm when removed at autopsy or explanted. The lower lobes are most severely affected, with the pleura having a finely nodular “cobblestone” pattern, resembling that of a cirrhotic liver. Pleural fibrosis is uncommon, in contrast to asbestosis. The cut surface of the lung shows fibrosis and a variable degree of “honeycombing,” which is most marked beneath the pleura (Fig. 17.1). The cardinal features of UIP are subpleural and paraseptal predominance, patchy parenchymal involvement, fibrosis leading to loss of architecture, fibroblastic foci adjacent to the established fibrosis indicative of progressive disease, only mild to moderate chronic interstitial inflammation, and an absence of any causal feature such as inorganic dust, granulomas, or accumulations of Langerhans cells [13].

Symptoms and Signs

IPF occurs in middle-aged and elderly adults (median age at diagnosis 66 years, range 55–75 years) [14]. Dry cough and slowly progressive dyspnea on exertion are the cardinal symptoms of IPF. Systemic symptoms, such as fever and weight loss, are rare. Patients may be asymptomatic at the early stage of IPF. Finger clubbing is found in more than 50 % of the patients. Bibasilar fine inspiratory crackle, so-called Velcro-like rale, is heard on chest auscultation.

CT Findings

The characteristic HRCT findings of UIP consist of intralobular lines and honeycombing involving mainly the subpleural regions and lung bases [15] (Figs. 17.1 and 17.2). The intralobular interstitial thickening also results in the presence of irregular interfaces between the lung and pulmonary vessels, bronchi, and pleural surfaces. The bronchioles and bronchi in the areas of fibrosis are often dilated and tortuous (traction bronchiolectasis and bronchiectasis). Parenchymal involvement is typically patchy on HRCT, with areas of normal and markedly abnormal lung often present in the same lobe. Other findings of UIP on HRCT include irregular thickening of interlobular septa and patchy areas of GGO. On HRCT, the overall extent of fibrosis (reticulation and honeycombing) has been consistently shown to correlate with disease severity parameters on pulmonary function tests and prognosis [10]. Recently, the extent of honeycombing at baseline as well as its progression on sequential follow-up CT scan is demonstrated as an important prognostic determinant in patients of fibrotic interstitial pneumonia, including UIP and fibrotic NSIP [9].

CT–Pathology Comparisons

Histologically, UIP shows a variable degree of interstitial inflammation and fibrosis [13]. As disease becomes more severe, alveoli are replaced by fibrous tissue. Contraction of this tissue results in the dilatation of respiratory bronchioles and alveolar ducts, leading to the formation of honeycombing cysts. The intralobular lines reflect the presence of interstitial fibrosis. Interlobular septal thickening reflects the presence of fibrosis in the periphery of the secondary lobules and patchy areas of GGO reflects areas of inflammation or fibrosis. Patchy parenchymal involvement on HRCT reflects histologic features of heterogeneous appearance in which areas of fibrosis with scarring and honeycombing alternate with areas of less affected or normal parenchyma.

Patient Prognosis

IPF is a chronic, progressive, irreversible, and usually fatal lung disease. There is no therapy proven to be effective [16]. Median survival has been reported to be 2–5 years. Lung transplantation remains the last therapeutic option.

Nonspecific Interstitial Pneumonia

Pathology and Pathogenesis

It is a uniform-appearing, cellular interstitial pneumonia characterized by a lymphoplasmacytic infiltrate within the alveolar septa. Varying amounts of fibrosis consisting predominantly of collagen are admixed with the chronic inflammation, and cases can be divided into cellular and fibrotic variants. Patchy intra-alveolar macrophage accumulation and small foci of intraluminal fibrosis resembling BOOP may occur but are always overshadowed by the more extensive interstitial pneumonia [17].

Symptoms and Signs

Cough and dyspnea are the most common symptoms in patients with idiopathic NSIP [14]. The duration of respiratory symptoms is around 6 months, which is shorter than in IPF. Median age of NSIP is 52 years (range 26–73). Finger clubbing can be observed but is less frequent than in IPF.

CT Findings

The most common HRCT findings of NSIP consist of lower lobe, peripherally predominant, and GGO with reticular abnormality, traction bronchiectasis, and lower lobe volume loss [5]. Honeycombing and consolidation are relatively uncommon. The reported prevalence of honeycombing ranges from 0 to 44 % (Fig. 17.3). The HRCT pattern of NSIP may overlap with those of cryptogenic organizing pneumonia (COP), desquamative interstitial pneumonia, and UIP. The parenchymal abnormalities of NSIP, including reticular pattern, traction bronchiectasis, and GGO, may be reversible on follow-up exam. Although differentiation from UIP is very difficult, NSIP is characterized by lack of honeycombing, more GGO, and a finer reticular pattern than UIP. Moreover, in NSIP, relative subpleural sparing [7] or distribution of reticulation along the central bronchovascular bundles is more frequently observed. On recent comparative study of NSIP and UIP at long-term follow-up, 28 % of patients with initial CT findings suggestive of NSIP progressed to features suggestive of IPF/UIP on follow-up CT scans [7].

CT–Pathology Comparisons

Areas of GGO with or without reticular abnormality or traction bronchiectasis on CT correspond histologically to the areas of interstitial thickening caused by varying degrees of interstitial inflammation or fibrosis showing temporal uniformity [18]. The areas of consolidation are related to the areas of COP, foamy cell collections in alveolar spaces or foci of honeycombing in which the cystic spaces are filled with mucus.

Patient Prognosis

Prognosis of idiopathic NSIP is much better than IPF. The 5-year and 10-year survival of the patients with idiopathic NSIP has been reported to be 82.3 and 73.2 %, respectively [14]. Cellular NSIP shows a much better survival than fibrotic NSIP. Corticosteroids with or without immunomodulatory drugs such as azathioprine and cyclophosphamide are the main drugs for the treatment.

Asbestosis

Pathology and Pathogenesis

Asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive amounts of asbestos fibers. Histologically, asbestosis is characterized by discrete foci of fibrosis in the walls of respiratory bronchioles accompanied by asbestos bodies. As the fibrotic process progresses, it extends distally to the alveolar ducts and proximally to the membranous (terminal) bronchioles. The fibrosis also extends radially to involve alveolar septa distant from the respiratory bronchiole. In the most advanced cases, honeycomb fibrosis is present. The hallmark of asbestos exposure is the asbestos body, namely, a rodlike, beaded, or dumbbell-shaped structure with golden-brown coating and a thin, translucent core. Detection of asbestos bodies may be facilitated by the use of iron stains, which impart a deep blue color. Pleural plaques consist of layers of acellular hyalinized collagen, arranged in a “basket weave” pattern, or appear as compact layers of collagen. A mild lymphocytic infiltrate sometimes accompanies the fibrosis [19].

Symptoms and Signs

Clinically, asbestosis manifests as dry cough, dyspnea, fine inspiratory crackles on auscultation, and a restrictive defect in pulmonary function test with or without finger clubbing [15]. Sputum production and wheezing are less common. Patients may be asymptomatic in mild cases.

CT Findings

HRCT with the patient prone is the most sensitive imaging technique to detect asbestosis. Findings in early disease include subpleural dots or branching structures, intralobular lines, thickened interlobular septa, subpleural curvilinear lines, pleura-based irregular small nodules, patchy areas of GGO, and small, cystic spaces [17] (Fig. 17.4). These abnormalities tend to involve mainly the dorsal subpleural regions of lower lobes. Honeycombing is a common finding in advanced-stage disease. On comparative study of asbestosis and IPF, subpleural dot-like or branching opacities, curvilinear lines, band-like opacities, and air trapping are more common in asbestosis, whereas honeycombing, visible bronchioles, and bronchiectasis within consolidation are more common in IPF [6]. However, the presence of parietal pleural thickening in association with lung fibrosis is the most important feature differentiating asbestosis from IPF.

CT–Pathology Comparisons

HRCT-pathology correlation studies have shown that subpleural dots and branching structures correspond to peribronchiolar fibrosis [20]. Extension of fibrous tissue into the parenchyma between affected bronchioles results in pleura-based nodular irregularities. Thickened interlobular septa on HRCT may correspond to the fibrosis of the septa themselves or to fibrosis in the periphery of lobule. GGOs are related to mild alveolar wall fibrosis. In the most severe cases, diffuse interstitial fibrosis leads to parenchymal remodeling and honeycombing.

Patient Prognosis

No specific treatment is available other than prevention of further exposure to asbestos, smoking cessation, and treatment for coexisting chronic obstructive pulmonary disease and cor pulmonale if present. The prognosis of asbestosis is highly variable and depends on the extent of lung involvement. Development of lung cancer or pleural tumor should be closely monitored.