Clin J Gastroenterol DOI 10.1007/s12328-015-0554-2

CASE REPORT

Case of pharyngeal cancer not detected during preoperative transoral endoscopy with narrow band imaging Kunihiro Tsuji • Hisashi Doyama • Hiroyoshi Nakanishi • Kenichi Takemura • Hideki Moriyama • Makoto Sakumoto Sho Tsuyama • Hiroshi Kurumaya



Received: 21 December 2014 / Accepted: 24 January 2015 Ó Springer Japan 2015

Abstract We herein report a case of pharyngeal cancer that was not detected during preoperative transoral endoscopy with narrow band imaging (NBI). A 61-year-old female was referred to our hospital for further evaluation of a pharyngeal lesion. Endoscopy revealed a small, elevated lesion, approximately 7 mm in size, at the right pyriform sinus. We performed endoscopic resection to remove this lesion under general anesthesia based on the biopsy results. Intraoperatively, we detected another tumor in the left oropharyngeal wall with Lugol staining after insertion of a curved laryngoscope. Although this lesion was C20 mm in diameter, we were unable to detect it during preoperative transoral endoscopy with NBI and white light imaging. We performed endoscopic treatment for this lesion 2 months later. The pathological diagnosis was pharyngeal cancer; the lesion had low vascularity. This case report provides an example of false-negative endoscopy with NBI. Although transoral endoscopy with NBI has improved the early diagnosis of superficial squamous cell carcinomas of the

K. Tsuji (&)  H. Doyama  H. Nakanishi  K. Takemura Department of Gastroenterology, Ishikawa Prefectural Central Hospital, 2-1 Kuratukihigashi, Kanazawa, Ishikawa 920-8530, Japan e-mail: [email protected] H. Moriyama Department of Digestive Surgery, Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan M. Sakumoto Department of Otolaryngology, Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan S. Tsuyama  H. Kurumaya Department of Diagnostic Pathology, Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan

head and neck, pharyngeal cancers that are less vascular may be missed with NBI. Keywords False negative  Gastrointestinal endoscopy  Head and neck cancer  NBI  Pharyngeal cancer

Introduction Transoral upper gastrointestinal (GI) endoscopy with narrow band imaging (NBI) has been reported to improve the early diagnosis of superficial squamous cell carcinomas of the head and neck (H&N) compared with white light imaging (WLI) [1], and this modality is now widely used in clinical practice [2]. The endoscopic diagnosis and curative treatment of pharyngeal cancer have become a reality [3, 4]. The development of synchronous and metachronous squamous cell carcinoma in the esophagus or head and neck region can be attributed to ‘‘field cancerization,’’ a concept first proposed by Slaughter in 1953. In this process, environmental carcinogens, such as tobacco and alcohol, may induce malignant transformation in a field of mucosa affected by premalignant disease [5]. Among patients with H&N cancer, synchronous and metachronous malignancies most commonly affect mucosal sites in the head and neck, lung, and esophagus. With the use of NBI, pharyngeal cancer is detected at a high frequency in these high-risk groups. However, the complicated structure of most H&N lesions and the presence of the gag reflex can make endoscopic examination difficult. We previously reported that transoral endoscopy yields poorer results in the cancerprone pyriform sinuses and postcricoid area [6]. Additionally, we have often encountered cases of pharyngeal

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cancer during endoscopic treatment that were not detected prior to the procedure. This report describes a case of pharyngeal cancer that was not detected during preoperative transoral endoscopy with NBI and WLI.

Case report A 61-year-old female underwent endoscopy for surveillance after previous treatment for esophageal cancer and H&N cancer. Past medical history was as follows: she had been treated for esophageal cancer by surgical resection 5 years ago. She had also been treated for tumors of the oropharynx posterior wall and epiglottis by laser ablation 4 years previously, then treated for tongue cancer by surgical resection 3 years ago. Physical examination revealed no abnormalities, and laboratory findings were within normal limits. Endoscopy revealed a small, elevated lesion, approximately 7 mm in size at the right pyriform sinus (Fig. 1a–c). An endoscopic biopsy taken from this lesion revealed presumptive squamous carcinoma, so we performed endoscopic resection to remove the lesion under general anesthesia. Intraoperatively, we detected a tumor in the left wall of the oropharynx with the use of Lugol dye after the insertion of a curved laryngoscope (Fig. 2a–d). Although this lesion was C20 mm in diameter, we were unable to detect it during Fig. 1 a A small elevated lesion was revealed at the right pyriform sinus during preoperative examination. b Narrow band imaging (NBI) showed a brownish area in the right pyriform sinus. c On magnified observation, this lesion exhibited brownish intervascular epithelium and abnormal microvessels with dilatation

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preoperative transoral endoscopy with NBI. We endoscopically resected the right pyriform sinus tumor as scheduled, and we decided to choose the treatment strategy for the tumor in the left oropharyngeal wall based on the biopsy results. Histopathology revealed presumptive squamous carcinoma, so we scheduled its removal for 2 months later. At that time, although we attempted to detect the squamous carcinoma with transoral endoscopy using NBI and WLI under general anesthesia (after the insertion of a curved laryngoscope), we were unable to detect the lesion with these techniques. We performed endoscopic submucosal dissection of the lesion. Because of technical difficulties, the tumor was removed in two pieces (Fig. 3a). The pathological diagnosis was pharyngeal cancer. The vertical margins of the resected specimen were negative for neoplasia; the lateral margins were unclear, because it was not an en bloc resection. This lesion was less vascular in comparison with typical pharyngeal cancer (Fig. 3b, c). The patient was discharged 18 days after endoscopic resection. Although we did not perform additional treatment, the patient has not experienced recurrence since the procedure, now over 2 years ago. Preoperative endoscopic examination Preoperative endoscopy was performed using a magnifying endoscope (GIF-H260Z; Olympus Medical Systems,

Clin J Gastroenterol Fig. 2 a The left wall of the oropharynx was not lusterous, and part of it was whitish. However, it was difficult to detect it as a cancerous lesion with white light imaging. b The cancerous lesion in the left wall of the oropharynx was detected with Lugol staining during the intraoperative examination. c The lesion is not observed as a brownish area with intraoperative narrow band imaging. d A typical vessel was not observed with magnified narrow band imaging

Fig. 3 a The left oropharyngeal wall lesion was removed in two pieces. b Microscopic findings: squamous cell carcinoma was observed. The pathological border of normal mucosa and cancer is indicated by the blue arrow. c Microscopically, this oropharyngeal cancer had low vascularity

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Clin J Gastroenterol Fig. 4 a CD34-stained browncolored blood vessels in oropharyngeal cancer of this case. Intraepithelial brown-colored vessels were hardly observed. b CD34-stained brown-colored blood vessels in hypopharyngeal cancer of this case. Many intraepithelial brown-colored vessels were observed

Tokyo, Japan) with a soft hood attachment (MAJ-1990 for GIFH260Z; Olympus Medical Systems). Prior to the procedure, the patient was given 100 ml of water containing 20,000 units of pronase (Kaken Pharmaceutical, Tokyo, Japan), 1 g of sodium bicarbonate, and 10 ml of dimethylpolysiloxane (20 mg/ml; Horii Pharmaceutical Industries, Osaka, Japan). The subject also inhaled three to four puffs of lidocaine (Xylocaine Pump Spray 8 %; AstraZeneca, Osaka, Japan) for pharyngeal anesthesia. She was placed in the left lateral decubitus position. Endoscopic examination was performed while the patient was under conscious sedation with midazolam. The pharynx was assessed at the beginning of the examination, and standard esophagogastroduodenoscopy was performed at the end. Operative endoscopic examination and treatment Endoscopic observation just before treatment was performed with the GIF-H260Z. Endoscopic examination and resection were performed under general anesthesia with the patient resting in the supine position as described above. The patient underwent tracheal intubation to minimize aspiration of Lugol as well as unexpected movement during the procedure. An adequate working area was created by the otolaryngologist by lifting the larynx with a curved laryngoscope. We observed the pharyngeal area by WLI and NBI, followed by staining with Lugol. Pathologic evaluation Histological diagnoses were made according to the World Health Organization criteria [7]. Evaluation of tumor invasion and macroscopic classification was made according to the general rules for clinical studies on head and neck cancer by the Japanese Society for Head and Neck Cancer [8].

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Discussion This report describes a case of cancer in the oropharyngeal mucosa that was not detected during preoperative evaluation with transoral endoscopy using NBI. There are some differences between preoperative and operative endoscopic examinations. However, in this case, we were unable to detect the lesion during operative transoral endoscopy with NBI, so we attribute the operative identification of the lesion to the use of Lugol as opposed to other differences between the procedures. Lugol has been established as the gold standard technique for detecting superficial pharyngeal cancers. However, it cannot be used preoperatively because the mucosal irritation caused by Lugol can result in its aspiration into the airway. Because it is simple and associated with fewer complications, NBI is used as an alternative technique, and this modality has improved the early diagnosis of superficial squamous cell H&N carcinomas [1]. There have been some reports suggesting that NBI can be used instead of Lugol staining for esophageal examination [9, 10]. However, no reports have suggested that NBI can be used in place of Lugol for H&N lesions. The low vascularity of this lesion as demonstrated on histopathology was considered to be the reason that we could not detect it with NBI. We compared the oropharyngeal cancer and hypopharyngeal cancer of this case using CD34 stains, which are vascular markers that the pathologist can use to help identify vascular invasion (Fig. 4a–b). As shown in Fig. 4, the oropharyngeal cancer in this case had clearly low vascularity compared to hypopharyngeal cancer. NBI is an optical technology that maximizes visualization of the microvascular architecture of the epithelium, so it is difficult to detect lesions with less microvascular hyperplasia using this modality. So far, we have encountered three cases of pharyngeal cancer during endoscopic treatment that were not previously detected. Although the hypopharynx was the most frequent primary

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location for preoperative lesions, two of the three undetected cancers were located in the side wall of the oropharynx. The other was located in the right pyriform sinus. Because the characteristics of such lesions have not been clarified, further studies are necessary to address this issue. In conclusion, our case report suggests a limitation of observation with NBI in the pharyngeal region. As it is currently necessary for us to use NBI for preoperative examination of the pharyngeal mucosa, we should carefully examine the pharynx during surgery using Lugol after the curved laryngoscope has been inserted. Close patient follow-up is prudent after endoscopic resection of superficial lesions. Disclosures Conflict of Interest: Kunihiro Tsuji, Hisashi Doyama, Hiroyoshi Nakanishi, Kenichi Takemura, Hideki Moriyama, Makoto Sakumoto, Sho Tsuyama and Hiroshi Kurumaya declare that they have no conflict of interest. Human/Animal Rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5). Informed Consent: Informed consent was obtained from this patient for being included in the study.

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References 1. Muto M, Minashi K, Yano T, et al. Early detection of superficial squamous cell carcinoma in the head and neck region and

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Case of pharyngeal cancer not detected during preoperative transoral endoscopy with narrow band imaging.

We herein report a case of pharyngeal cancer that was not detected during preoperative transoral endoscopy with narrow band imaging (NBI). A 61-year-o...
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