Honeycombing on CT; its definition, pathologic correlation, and future direction of its diagnosis

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Abstract

Honeycombing on CT is the clue for the diagnosis of usual interstitial pneumonia (UIP) and its hallmark. According to the ATS-ERS-JRS-ALAT 2010 guideline, the patients with honeycombing on CT can be diagnosed as UIP without surgical biopsy. On CT scans, it is defined as clustered cystic airspaces, typically of comparable diameters of the order of 3–10 mm, which are usually subpleural and have well-defined walls. Pathologically, honeycombing consists of both collapsing of multiple fibrotic alveoli and dilation of alveolar duct and lumen Although the definition of honeycombing seems to be strict, recognition of honeycombing on CT is various among each observer Because typical honeycombing is frequently observed in the patients with UIP, we should judge clustered cysts as honeycombing when a diagnosis of UIP is suspected.

Introduction

Honeycombing on CT is the clue for the diagnosis of usual interstitial pneumonia (UIP) and its hallmark [1], [2]. Diagnostic criteria in recent ATS-ERS-JRS-ALAT guideline of idiopathic pulmonary fibrosis (IPF) is as follows; (1) Exclusion of other known causes of interstitial lung disease (e.g. domestic and occupational environmental exposures, connective tissue disease, and drug toxicity). (2) The presence of a UIP pattern on high resolution computed tomography (HRCT) in patients not subjected to surgical lung biopsy. (3) Specific combinations of HRCT and surgical lung biopsy pattern in patients subjected to surgical lung biopsy. In this guideline, UIP pattern on CT is defined as the abnormalities which have following all four features; (1) subpleural, basal predominance, (2) reticular abnormality, (3) honeycombing with or without traction bronchiectasis and (4) absence of features listed as inconsistent with UIP pattern [3]. Namely, according to this guideline, the patients with honeycombing on CT can be diagnosed as UIP without surgical biopsy.

Honeycombing on CT indicate poor prognosis not only in patients with UIP [4], [5] but also in non-specific interstitial pneumonia (NSIP) [6], [7]. Recently, new drugs for UIP have been developed [8], [9]. Although they are strictly applied to IPF/UIP, the number of patients with IPF diagnosed by surgical biopsy is not so large. Thus, importance of determination of honeycombing on CT has been increasing in the daily clinical practice for IPF/UIP. The purpose of this review is four-fold; (1) to reconfirm the definition of honeycombing on CT, (2) to demonstrate CT-pathologic correlation of honeycombing, (3) to describe both pitfalls and limitations of detection of honeycombing on CT, and (4) to show the future directions of diagnosis of honeycombing on CT.

Section snippets

Definition of honeycombing on CT and its history

At first, let us review the history and changes of the definition of honeycombing. One recent review article described the history of the definition of honeycombing in detail and we would like you to read through it [10].

The term “honeycomb lung” first appeared in 1949 in a study by Oswald and Parkinson [11]. The study included Langerhans cell histiocytosis (LCH), lymphangioleiomyomatosis (LAM), and some chronic interstitial pneumonias (Fig. 1). Oswald and Parkinson defined that honeycomb lung

Radiologic pathologic correlation of honeycombing

At first, “progress from intralobular reticular opacity to honeycombing” is mentioned In relatively early stage, fibrosis shows intralobular reticular opacity on CT. Admixture of dilatation of terminal airway and periacinar fibrosis correspond to intralobular reticular opacities on CT (Fig. 2) [18]. If airway dilatation and collapsing of fibrotic alveoli progress, the areas cause honeycombing (Fig. 3) [18].

Pathologically, honeycombing consists of both collapsing of multiple fibrotic alveoli and

Honeycombing vs. traction bronchiectasis

Confluence of traction bronchiectasis sometimes, especially in basal segments, looks like real honeycombing on CT. Of course, as previously mentioned, tangential view of traction bronchiectasis is one of components of honeycombing cysts. Confluence of traction bronchiectasis is the one of hallmarks of end-stage fibrosing NSIP [20], [21]. Thus, the discrimination of confluence of traction bronchiectasis from honeycombing on CT is clue for the differentiation of fibrosing NSIP from UIP, How can

Limitations of diagnosis of honeycombing on CT

Although the definition of honeycombing seems to be strict, recognition of honeycombing on CT is various among each observer [23]. Watadani et al. reported that agreement of honeycombing judgment is not so good (k value ranges from 0.4 to 0.7) among expert radiologists, board-certified chest radiologists and chest physicians [23]. Why does such variability of understanding of honeycombing happen? There are three major reasons. First, the diseases to which are applied the term “honeycombing”

Future directions of diagnosis of honeycombing on CT

Considering present situation of diagnosis of honeycombing and recent our study [23], we would like to submit following proposals.

  • (1)

    Because typical honeycombing is frequently observed in the patients with UIP, we should judge clustered cysts as honeycombing when a diagnosis of UIP is suspected. However, please note other diseases than UIP can show honeycombing on CT.

  • (2)

    Not only multi layered clustered cysts but also single layered ones should be diagnosed as honeycombing because the most important

Conflict of interest

All authors do not have any financial and personal relationships with other people or organisations that could inappropriately influence (bias) our work.

Acknowledgements

This article is supported by a grant to the Diffuse Lung Diseases Research Group from the Ministry of Labor, Health and Welfare of Japan. We would also like to thank the following researchers for providing images and/or joining reading session: Drs. Yoshikazu Inoue, Arata Azuma, Hiroyuki Taniguchi, Kingo Chida, Minoru Kanazawa, Sakae Homma, Tetsuo Yamaguchi, Takashi Ogura, Hitoshi Tokuda, Yoshio Taguchi, and Kazuya Ichikado, of the Diffuse Lung Diseases Research Group of the Ministry of Health,

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