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Case report Blizzard Sign as a specic endobronchial ultrasound image for ground glass opacity: A case report Shinji Sasada, M.D. Ph.D. * , Takehiro Izumo, M.D. Ph.D., Christine Chavez, M.D., Takaaki Tsuchida, M.D. Ph.D. Department of Endoscopy, Respiratory Endoscopy Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan Keywords: Endobronchial ultrasound with a guide sheath Ground glass opacity Peripheral pulmonary lesion Blizzard Sign abstract We report a case of lung adenocarcinoma presenting as pure ground glass opacity (GGO) and diagnosed by bronchoscopy with the use endobronchial ultrasound with a guide sheath (EBUS-GS). The lesion was indistinguishable by real-time uoroscopy but simultaneous endobronchial ultrasound scanning of the involved lung segment showed a hyperechoic shadow that was subtly more intense than a typical snowstorm appearance when scanning normal alveolar tissue. Transbronchial biopsy from this area revealed adenocarcinoma with lepidic growth. On hindsight, it was the aforementioned ultrasound pattern that helped us decide the sampling site for EBUS-GS guided TBB when uoroscopy was equivocal. We hypothesize that this pattern is specic for GGO and we name it the Blizzard Sign. Ó 2014 The Authors. Published by Elsevier Ltd. Introduction Transbronchial biopsy (TBB) with the aid of radial endobron- chial ultrasound (R-EBUS) had long been demonstrated to have a good diagnostic performance for peripheral pulmonary lesions (PPL) [1]. Almost 10 years ago, Kurimoto et al. introduced endo- bronchial ultrasound with a guide sheath (EBUS-GS) to augment TBB [2] and indeed, the overall diagnostic yield for PPLs increased to 70 percent [3]. A lung adenocarcinoma that presents as ground glass opacity (GGO) on computed tomography (CT) screening is often detected these days [4], but majority of the patients either undergo surgical resection or are observed without denitive diagnosis. However, diagnostic bronchoscopy for GGO lesions, especially the pure type without a solid component, is not commonly performed because most respiratory physicians recognize that GGO cannot be visual- ized on uoroscopy or is undetectable by EBUS. In fact, several studies on bronchoscopic diagnosis of solid pulmonary nodules have already been published but only a few studies on GGO were reported [5]. Performing EBUS-GS for TBB of GGO is a challenging matter. To the best of our knowledge, an EBUS nding that represents a ground glass process is still unknown. In this case report, we describe the specic EBUS ndings for GGO and highlight the importance of obtaining large pieces for denitive diagnosis. Case presentation The representative case is that of an 81-year old female, non- smoker, with a 35 mm pure ground glass opacity (GGO) in the right lower lobe that was incidentally seen on computed to- mography (CT) scan of the chest (Fig. 1A) but was indistinct on chest radiograph (Fig. 1B). The endobronchial route was carefully planned prior to bronchoscopy using 1-mm cross-sectional CT scan images and the topographical location of the target lesion on the coronal plane was mapped out on chest tomosynthesis. The patient underwent diagnostic bronchoscopy (1T260, Olympus) using radial EBUS (UM-S20-20R, Olympus) with large type GS (K- 203, Olympus). Fluoroscopy was used concomitantly with endo- bronchial ultrasound scanning to nd the target. During the initial attempt, it was difcult to distinguish the mass on uo- roscopy (Fig. 2A) and ultrasound signals only generated a snow- storm appearance that was ascribed as normal lung tissue (Fig. 2B). But we were certain that we were in the intended lung segment so the ultrasound probe was inserted more distally. At this point, a subtle but noticeable enhancement and increase in Abbreviation: AIS, adenocarcinoma in situ; CT, computed tomography; EBUS, endobronchial ultrasound; EBUS-GS, endobronchial ultrasound with a guide sheath; GGO, ground glass opacity; MIA, minimally invasive adenocarcinoma; PPL, peripheral pulmonary lesion; TBB, transbronchial biopsy. * Corresponding author. Tel.: þ81 3 3542 2511; fax: þ81 3 3542 3567. E-mail address: [email protected] (S. Sasada). Contents lists available at ScienceDirect Respiratory Medicine Case Reports journal homepage: www.elsevier.com/locate/rmcr http://dx.doi.org/10.1016/j.rmcr.2013.11.003 2213-0071 Ó 2014 The Authors. Published by Elsevier Ltd. Respiratory Medicine Case Reports 12 (2014) 19e21 Open access under CC BY-NC-ND license. Open access under CC BY-NC-ND license.

Respiratory Medicine Case Reports · two incidence screenings in the National Lung Screening Trial. N Engl J Med 2013;369:920e31. [5] IzumoT, Sasada S, Chavez C, Nagai Y, Kitagawa

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Page 1: Respiratory Medicine Case Reports · two incidence screenings in the National Lung Screening Trial. N Engl J Med 2013;369:920e31. [5] IzumoT, Sasada S, Chavez C, Nagai Y, Kitagawa

lable at ScienceDirect

Respiratory Medicine Case Reports 12 (2014) 19e21

Contents lists avai

Respiratory Medicine Case Reports

journal homepage: www.elsevier .com/locate/rmcr

Case report

Blizzard Sign as a specific endobronchial ultrasound image for groundglass opacity: A case report

Shinji Sasada, M.D. Ph.D. *, Takehiro Izumo, M.D. Ph.D., Christine Chavez, M.D.,Takaaki Tsuchida, M.D. Ph.D.Department of Endoscopy, Respiratory Endoscopy Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

Keywords:Endobronchial ultrasound with a guidesheathGround glass opacityPeripheral pulmonary lesionBlizzard Sign

Abbreviation: AIS, adenocarcinoma in situ; CT, coendobronchial ultrasound; EBUS-GS, endobronchiasheath; GGO, ground glass opacity; MIA, minimally inperipheral pulmonary lesion; TBB, transbronchial bio* Corresponding author. Tel.: þ81 3 3542 2511; fax

E-mail address: [email protected] (S. Sasada)

http://dx.doi.org/10.1016/j.rmcr.2013.11.0032213-0071 � 2014 The Authors. Published by Elsevier

a b s t r a c t

We report a case of lung adenocarcinoma presenting as pure ground glass opacity (GGO) and diagnosedby bronchoscopy with the use endobronchial ultrasound with a guide sheath (EBUS-GS). The lesion wasindistinguishable by real-time fluoroscopy but simultaneous endobronchial ultrasound scanning of theinvolved lung segment showed a hyperechoic shadow that was subtly more intense than a typicalsnowstorm appearance when scanning normal alveolar tissue. Transbronchial biopsy from this arearevealed adenocarcinoma with lepidic growth.

On hindsight, it was the aforementioned ultrasound pattern that helped us decide the sampling site forEBUS-GS guided TBB when fluoroscopy was equivocal. We hypothesize that this pattern is specific forGGO and we name it the Blizzard Sign.

� 2014 The Authors. Published by Elsevier Ltd. Open access under CC BY-NC-ND license.

Introduction

Transbronchial biopsy (TBB) with the aid of radial endobron-chial ultrasound (R-EBUS) had long been demonstrated to have agood diagnostic performance for peripheral pulmonary lesions(PPL) [1]. Almost 10 years ago, Kurimoto et al. introduced endo-bronchial ultrasound with a guide sheath (EBUS-GS) to augmentTBB [2] and indeed, the overall diagnostic yield for PPLs increasedto 70 percent [3].

A lung adenocarcinoma that presents as ground glass opacity(GGO) on computed tomography (CT) screening is often detectedthese days [4], but majority of the patients either undergo surgicalresection or are observed without definitive diagnosis. However,diagnostic bronchoscopy for GGO lesions, especially the pure typewithout a solid component, is not commonly performed becausemost respiratory physicians recognize that GGO cannot be visual-ized on fluoroscopy or is undetectable by EBUS. In fact, severalstudies on bronchoscopic diagnosis of solid pulmonary noduleshave already been published but only a few studies on GGO werereported [5].

mputed tomography; EBUS,l ultrasound with a guidevasive adenocarcinoma; PPL,psy.: þ81 3 3542 3567..

Ltd. Open access under CC BY-NC-ND

Performing EBUS-GS for TBB of GGO is a challenging matter.To the best of our knowledge, an EBUS finding that represents aground glass process is still unknown. In this case report, wedescribe the specific EBUS findings for GGO and highlight theimportance of obtaining large pieces for definitive diagnosis.

Case presentation

The representative case is that of an 81-year old female, non-smoker, with a 35 mm pure ground glass opacity (GGO) in theright lower lobe that was incidentally seen on computed to-mography (CT) scan of the chest (Fig. 1A) but was indistinct onchest radiograph (Fig. 1B). The endobronchial route was carefullyplanned prior to bronchoscopy using 1-mm cross-sectional CTscan images and the topographical location of the target lesion onthe coronal plane was mapped out on chest tomosynthesis. Thepatient underwent diagnostic bronchoscopy (1T260, Olympus)using radial EBUS (UM-S20-20R, Olympus) with large type GS (K-203, Olympus). Fluoroscopy was used concomitantly with endo-bronchial ultrasound scanning to find the target. During theinitial attempt, it was difficult to distinguish the mass on fluo-roscopy (Fig. 2A) and ultrasound signals only generated a snow-storm appearance that was ascribed as normal lung tissue(Fig. 2B). But we were certain that we were in the intended lungsegment so the ultrasound probe was inserted more distally. Atthis point, a subtle but noticeable enhancement and increase in

license.

Page 2: Respiratory Medicine Case Reports · two incidence screenings in the National Lung Screening Trial. N Engl J Med 2013;369:920e31. [5] IzumoT, Sasada S, Chavez C, Nagai Y, Kitagawa

Fig. 1. A. Computed tomography scan of the chest shows pure ground glass opacity on segment 8 of the right lung. B. On chest radiograph (PA view), note that the area corre-sponding to right lung segment 8 does not clearly define an abnormality.

Fig. 2. A. Real-time fluoroscopy image of the chest during endobronchial ultrasound scanning. B. Initial endobronchial ultrasound scanning through the right B8bi showed a whitishacoustic shadow that represented normal air-filled alveoli. EBUS image shown is on a 2 mm scale. C. The Blizzard Sign. When the endobronchial ultrasound probe was insertedfurther and more distally, there was a subtle but noticeable increase in the intensity and radius of the whitish acoustic shadowmore than 1 cm from the center of the EBUS image. D.Real-time fluoroscopy image during transbronchial biopsy using forceps and guide sheath (K-203 kit, Olympus).

S. Sasada et al. / Respiratory Medicine Case Reports 12 (2014) 19e2120

area of the snowstorm appearance was seen (Fig. 2C). Aftermarking this location of the GS on fluoroscopy, seven TBB sampleswere obtained using a dedicated biopsy forceps with guide sheathkit (Fig. 2D). Histopathologic examination of the 3rd to the 7thconsecutive biopsy specimens revealed adenocarcinoma withlepidic growth (Fig. 3). The patient was staged as T2aN0M0 butrefused further treatment.

Discussion

In this case report, the EBUS image of the pure GGO lesion wasan ill-defined signal that was more intense than the snowstormappearance of normal lung tissue. Using this as a confirmation ofthe desired GS location, we were able to successfully diagnose thetumor by TBB. When lesions in the lung adenocarcinoma spectrum

have a ground glass component, majority of the lesions arepathologically classified as either one of the following: adenocar-cinoma in situ (AIS), minimally invasive carcinoma (MIA), andlepidic predominant adenocarcinoma [6]. Based on our pre-liminary, unpublished data, 80% (12 out 15) of patients with GGO,who were diagnosed by EBUS-GS and surgically confirmed as AIS,MIA, or lepidic predominant adenocarcinoma, had EBUS findingsthat were similar to this report. The average number of specimensthat we obtained in this series and what we also recommend is atleast five.

We observed that this EBUS pattern for GGO has several char-acteristics. First, the change in the ultrasound signal from normallung tissue to the ground glass area is similar to a whiteout, albeitsubtle. Second, this signal traverses an area that is greater than thatof normal alveolar tissue. Based on our experience, the radius from

Page 3: Respiratory Medicine Case Reports · two incidence screenings in the National Lung Screening Trial. N Engl J Med 2013;369:920e31. [5] IzumoT, Sasada S, Chavez C, Nagai Y, Kitagawa

Fig. 3. Photomicrographs of the Hematoxylin & Eosin staining of a transbronchial biopsy specimen from a pure ground glass opacity show adenocarcinoma with lepidic growth. A(�100); B (�400).

S. Sasada et al. / Respiratory Medicine Case Reports 12 (2014) 19e21 21

the probe to the periphery of the acoustic shadow is usually morethan 1 cmwhile that of the surrounding normal lung parenchyma isless than 1 cm. Third, the character of the signals are generallymorecoarse compared to the typical snowstorm appearance. We desig-nated the name Blizzard Sign for this combination of characteristicsas a specific EBUS finding for GGO.

GGO patterns on CT scan are divided into pure, heterogeneous,or mixed type. In mixed type GGO, the solid component is generallydetected on EBUS scanning as a well-defined signal with hyper-echoic dots. The ground glass attenuation usually surrounds theperiphery of the lesion and demonstrates the Blizzard Sign justdescribed.

In this case, definitive diagnosis was successfully obtained fromseven TBB specimens by using the usual 1.8 mm biopsy forcepsincluded in the K-203 Guide Sheath Kit (Olympus). We underscorethe importance of using this biopsy forceps, particularly for pureGGO, to preserve the structural integrity of the tissues. We supposethat doing so would facilitate a more comprehensive histopatho-logic examination of the ground glass tissue sample, especially foridentifying AIS or MIA, which often exhibit weak cellular atypia.Most physicians commonly use small guide sheath kit (K-201)when approaching peripheral lesions but from our experience itoften fails to provide adequate amount of tissues. A usual 1.8 mmbiopsy forceps with large guide sheath (K-203) is favored inobtaining the desired quality of specimens compared to the smallone.

In conclusion, Blizzard Sign on EBUS was found to be useful fordetecting GGO, especially the pure type, during bronchoscopy evenif the lesion was not visualized by fluoroscopy.

Ethical issues

This study was approved by the hospital’s Institutional ReviewBoard and Ethics Committee; informed consent was sought fromthe patients.

Acknowledgment

We thank Koji Tsuta and Yukio Watanabe for pathological ex-aminations. This work was supported by The National CancerCenter Research and Development Fund (25-A-12).

References

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[2] Kurimoto N, Miyazawa T, Okimasa S, Maeda A, Oiwa H, Murayama M, et al.Endobronchial ultrasonography using a guide sheath increases the ability todiagnose peripheral pulmonary lesions endoscopically. Chest 2004;126:959e65.

[3] Wang Memoli JS, Nietert PJ, Silvestri GA. Meta-analysis of guided bronchoscopyfor the evaluation of the pulmonary nodule. Chest 2012;142:385e93.

[4] Aberle DR, DeMello S, Berg CD, Black WC, Brewer B, Church TR, et al. Results oftwo incidence screenings in the National Lung Screening Trial. N Engl J Med2013;369:920e31.

[5] Izumo T, Sasada S, Chavez C, Nagai Y, Kitagawa M, J Torii, et al. The value of chesttomosynthesis in locating a ground glass nodule (GGN) during endobronchialultrasonography with a guide sheath: a case report. J Thorac Dis 2013;5:E75e7.

[6] Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al.International association for the study of lung cancer/American thoracic soci-ety/European respiratory society international multidisciplinary classificationof lung adenocarcinoma. J Thorac Oncol 2011;6:244e85.