Snowball-like appearance on radial endobronchial ultrasonography in a patient with invasive mucinous adenocarcinoma.

Invasive mucinous adenocarcinoma (IMA), which is a relatively rare lung adenocarcinoma, is considered a high-grade subtype and is associated with a poor prognosis. IMA is difficult to diagnose by computed tomography because it requires differentiation from inflammatory diseases, such as atelectasis, infectious pneumonia, and organizing pneumonia. Thus far, no reports of radial endobronchial ultrasonography (EBUS) findings in IMA have been published. This article presents a case of IMA with a characteristic shadow, snowball-like appearance on radial EBUS in a 67-year-old Japanese man.

Introduction

Invasive mucinous adenocarcinoma (IMA) is categorized as a subtype of invasive lung adenocarcinoma according to the 2015 World Health Organization Classification of Lung Cancers. Computed tomography (CT) findings of IMA are used to classify IMA into the solitary/pneumonic types, and the frequency of the pneumonic type has been reported to be 25% [1]. The pneumonic type of IMA is difficult to differentiate from inflammatory diseases, such as atelectasis, infectious pneumonia, and organizing pneumonia [2]. No reports of radial endobronchial ultrasonography (EBUS) findings in IMA have been published thus far. Here, we report a case of IMA with a characteristic shadow, snowball‐like appearance on radial EBUS.

Case Report

A 67‐year‐old Japanese male and current smoker had hypertension, diabetes mellitus, and old myocardial infarction, which was treated by percutaneous coronary intervention and anticoagulant therapy. He presented to our hospital with a complaint of sputum. The patient's chest X‐ray showed consolidation in the left middle lower lung field. CT scans revealed consolidation with CT angiogram in the S3 and lingular segments of the left lung (Fig. 1A), and positron emission tomography‐CT demonstrated abnormal accumulation at the same site. Sputum culture and sputum cytology were both negative. The serum levels of carcinoembryonic antigen and Sialyl Lewis X‐i were slightly elevated to 9.4 ng/mL (normal range: 0–5.0 ng/mL) and 52 U/mL (normal value: ≤38 U/mL), respectively. The serum levels of squamous cell carcinoma antigen and cytokeratin 19 fragment (CYFRA) were normal. Then, either lung cancer including IMA or bacterial pneumonia or organizing pneumonia was suspected. On flexible bronchoscopy, radial EBUS performed in the B4 bronchus of the left lung showed an unusual finding: snowball‐like hyperechoic nodules floating on a hypoechoic background (Fig. 1B). We performed bronchial wash and bronchial brushing within the lesion. The cytological specimens were not malignant. Then, the left upper lobe was surgically resected and ND2a‐1 was performed. The section contained many various‐sized cancer foci in the entire lobe. Thin mucinous and fibrinous exudates were seen in the alveolar spaces (Fig. 2A). Microscopic findings showed cancer cells with large columnar cytoplasm containing abundant intracytoplasmic mucin and proliferation of cells with small round‐to‐oval basal nuclei in a lepidic pattern (Fig. 2B). Periodic acid–Schiff (PAS)–Alcian blue staining showed neutral mucin in their cytoplasm (Fig. 2C). Immunohistochemically, cancer cells were positive for cytokeratin‐7 (CK7) and MUC5AC; weakly positive for CK20 and MUC6; and negative for thyroid transcription factor 1, Napsin A, and p53 (Fig. 2D). The patient was diagnosed with primary pulmonary IMA (left upper lobe, 15 × 6 cm, T3N0M0 stage IIB). Molecular analysis of the tumour for epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) rearrangement, and PD‐L1 expression was negative. Molecular analysis for KRAS mutation was not performed. After post‐operative adjuvant chemotherapy, the disease recurred two years later, and although the patient was administered additional chemotherapy, he died.

Figure 1

Image inspection on admission. (A) Enhanced computed tomography (CT) shows consolidation with the CT angiogram sign in the S3 and lingular segments of the left lung. (B) Radial endobronchial ultrasonography performed in the B4 bronchus of the left lung showed snowball‐like hyperechoic nodules (indicated by arrow heads) floating on a hypoechoic background.

Figure 2

Pathological findings of the resected left upper lung. (A) The gross specimen revealed many various‐sized cancer foci in the entire lobe and thin mucinous and fibrinous exudates in the alveolar spaces. (B) Microscopic findings revealed cancer cells with large columnar cytoplasm and abundant intracytoplasmic mucin as well as proliferation of cells with small round‐to‐oval basal nuclei in a lepidic pattern (haematoxylin and eosin staining, 10×). (C) Neutral mucin in their cytoplasm (periodic acid–Schiff–Alcian blue staining, 10×). (D) Cancer cells were positive for cytokeratin‐7 (CK7, 20×).

Discussion

IMA represents 3–5% of all lung adenocarcinomas, is considered a high‐grade subtype, and is associated with a poor prognosis [3]. Therefore, early diagnosis and treatment of IMA are important. Findings included a homogeneous area with low attenuation, within which were enhanced branching pulmonary vessels (the CT angiogram sign) on contrast‐enhanced CT, which has been reported to suggest IMA [4]. However, similar findings are observed in bacterial pneumonia, metastatic lung cancer, malignant lymphoma, pulmonary infarction, and pulmonary oedema. IMA is often diagnosed by surgical resection. Because benign inflammatory diseases are differential diagnoses, it is important to obtain findings suggestive of cancer before surgery.

Kutimoto et al. reported that EBUS allows visualization of the internal structure of peripheral pulmonary lesions, and this information partially contributes to the histological evaluation of the lesion [5]. To our knowledge, no study on EBUS findings of IMA has been published thus far. In our case, a distinctive echo image with snowball‐like hyperechoic nodules floating on a hypoechoic background was observed. By comparing the EBUS and pathological findings, we can speculate that the snowball‐like nodules represented mucin in the cytoplasmic spaces. Although this is a rare observation, these EBUS findings are believed to strongly suggest the pneumonic type of IMA.

Disclosure Statement

Appropriate written informed consent was obtained for publication of this case report and accompanying images.

Author Contribution Statement

Data curation: Takeshi Kawaguchi, Daisuke Himeji, Kiichio Beppu, Kousuke Marutsuka. Project administration: Takeshi Kawaguchi. Visualization: Takeshi Kawaguchi. Writing—original draft: Takeshi Kawaguchi. Writing—review and editing: Takeshi Kawaguchi, Daisuke Himeji, Kiichio Beppu, Kousuke Marutsuka.