Ultrasonography in the Diagnosis and Follow-up of Nasopharyngeal Carcinoma

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1 C A S E R E P O R T Ultrasonography in the Diagnosis and Follow-up of Nasopharyngeal Carcinoma Yi-Lun Tseng, Li-Jen Liao* We present a case with an initial presentation of smooth nasopharyngeal mucosa and vague left upper neck swelling. Palpation-guided fine-needle aspiration was performed initially, but the specimen was inadequate and showed only blood. Ultrasound-guided fine-needle aspiration of the lymph node was conducted, and cytology suggested metastatic carcinoma. In addition, computed tomography with detailed endoscopic examination and biopsy of the nasopharynx finally confirmed nasopharyngeal carcinoma. Serial change of the malignant lymph node after irradiation was followed by ultrasound and disappeared on the third month after radiotherapy. Our experiences with this case highlight the benefits of ultrasound-guided fine-needle aspiration for clinically vague neck masses, in avoiding unnecessary and harmful open biopsies in the diagnosis of nasopharyngeal carcinoma patients. KEY WORDS fine-needle aspiration, nasopharyngeal carcinoma, ultrasound J Med Ultrasound 2009;17(4): Introduction Nasopharyngeal carcinoma (NPC) is more common in Asia than in other parts of the world. The incidence rate is about per 100,000 person-years in Southeast Asia, while in Western countries it is less than 1 per 100,000 person-years [1]. The etiology of NPC is multifactorial, and common causes include viral, genetic, and environmental factors. The most common clinical presentation of patients with NPC consists of cervical lymphadenopathy, followed by nasal, aural and neurological symptoms. However, the clinical symptoms may be subtle and thus are easily missed at early stages. Neck node metastasis is also a common presentation of NPC and other head and neck cancers. The treatment for NPC and that for other head and neck cancers are quite different. Radiotherapy is the therapy of choice for NPC; an operation on the neck is unnecessary for most NPC patients. NPC is associated with high mortality if it is not diagnosed early and treated correctly. Symptom duration is associated with the degree of invasion and the prognosis of NPC [2]. The diagnosis of NPC usually depends on direct visualization of the nasopharyngeal tumor, followed by confirmation by histological examination. If there is no remarkable tumor at the nasopharyngeal roof, it is difficult to Received: December 17, 2008 Accepted: February 27, 2009 Department of Otolaryngology, Far Eastern Memorial Hospital, Taipei, Taiwan. *Address correspondence to: Li-Jen Liao, Department of Otolaryngology, Far Eastern Memorial Hospital, 21, Section 2, Nan-Ya South Road, Pan Chiao, Taipei 220, Taiwan. liaolj@ntu.edu.tw Elsevier & CTSUM. All rights reserved. J Med Ultrasound 2009 Vol 17 No 4 207

2 Y.L. Tseng, L.J. Liao diagnose accurately. Hence, the diagnosis of NPC is often delayed and involves open biopsies of neck lymph nodes, which, in many cases, are unnecessary. It is well recognized that ultrasound is important in the evaluation of neck lumps. When combined with fine needle aspiration (FNA), ultrasound, with its high sensitivity (89 98%), specificity (95 98%) and accuracy (95 97%), is an ideal initial investigational tool for cervical lymphadenopathy [3,4]. We report a case of NPC who initially presented with a vague neck node and a smooth nasopharynx. In this report, we highlight the benefits of ultrasoundguided fine-needle aspiration (US-FNA) for clinically vague neck masses, in obtaining better specimens and avoiding unnecessary open biopsies in the diagnosis of NPC patients. (Fig. 1), and there was only a vague left upper neck mass. Fine-needle aspiration was performed by palpation in an out-patient clinic; however, the specimen was inadequate and showed only blood. He was referred for US-FNA, using Gray scale and power Doppler sonography (Philips ATL HDI-3500; Bothel, WA, USA) with a 5 12-MHz broad-band linear array transducer. Ultrasound showed a homogeneous hypoechoic lymph node with hilar vascularity at the left upper jugular area (Fig. 2A), which Case Report A 43-year-old male patient noticed a left upper neck swelling, which had persisted for 2 weeks. He denied a cigarette smoking habit or a family history of head and neck malignancy. Previously, he had no symptoms of nasal obstruction, epistaxis, hearing impairment or headache. Physical examination did not show anything remarkable in the nasopharynx Fig. 1. Nasopharyngoscopic examination showed unremarkable Rosenmüller fossa. Biopsy from left Rosenmüller fossa (arrow) showed an undifferentiated non-keratinizing carcinoma. A B Fig. 2. (A) Initial ultrasound showed a solitary homogeneous hypoechoic lymph node ( cm in dimension, S/L ratio = 0.59) in the upper jugular area on the left side. The node was beneath the sternocleidomastoid muscle (S). The margin (+) between the lymph node and the adjacent tissue is clear. Echo-guided fine-needle aspiration was performed and cytology showed metastatic carcinoma. (B) The axial view of the computed tomography scan at the nasopharyngeal level showed bilaterally smooth nasopharynx. However, the left side Rosenmüller fossa (arrow) showed mild swelling compared with the right side. 208 J Med Ultrasound 2009 Vol 17 No 4

3 Ultrasound in the Diagnosis and Follow-up of NPC was in level II of the neck. The boundary of the lymph node and the adjacent muscle was intact. The short to long axes (S/L) ratio of the lymph node was 0.59 ( cm in minimal and maximal axial diameters). After informed consent was obtained, US-FNA was conducted, and cytology was suggestive of metastatic carcinoma. The tentative diagnosis was an unknown primary carcinoma. Neck computed tomography was conducted in the assessment of this patient, and the axial view with contrast enhancement showed smooth nasopharynx, and a mild swelling over the left Rosenmüller fossa (Fig. 2B). Results of US-FNA cytology and computed tomography led us to examine the nasopharynx, and a nasopharyngeal biopsy finally proved the presence of an undifferentiated non-keratinizing carcinoma. There was no distant metastasis after completion of cancer staging (TNM Classification of Malignant Tumours: T1N1M0). The patient underwent concurrent chemo-radiotherapy, and the neck node subsided after therapy. Follow-up ultrasound of the neck at 1 month after radiotherapy showed a regression in size and a change in shape ( cm in diameter, ratio of 0.38) of the neck node. The echogenicity was increased compared with the pre-radiotherapy sonographic appearance. The node was completely regressed 3 months after the completion of irradiation. Discussion NPC is a tumor arising from the mucosal epithelium of the nasopharynx. Three subtypes of NPC are recognized in the World Health Organization classification [5]: (1) squamous cell carcinoma, typically found in the older adult population; (2) non-keratinizing carcinoma; and (3) undifferentiated carcinoma, which is more common in endemic areas and more responsive to radiotherapy [6,7]. Radiation therapy is the mainstay of treatment and not surgery, which is the first choice of therapy for other head and neck cancers. Therefore, it is important to differentiate malignant nodal disease from nasopharyngeal and other cancers. Most NPC is located at the lateral nasopharyngeal recess, called the Rosenmüller fossa. Symptoms related to the primary tumor can include otitis media, hearing loss and cranial nerve palsies. A large growth may produce nasal obstruction or bleeding. Cervical lymphadenopathy is the initial presentation in many patients; the nodal metastatic rate has been shown to be 60 90% at the time of initial diagnosis [8]. The diagnosis of NPC is often delayed and involves a biopsy of the neck lymph nodes, which is often unnecessary, especially if the nasopharyngeal lesion is subtle. Hence, early stage NPC is one of the most difficult diseases to diagnose. Not only is the post-nasal space inaccessible to examination, it is frequently occupied by a normal lympho-epithelium lining, which is difficult to differentiate from NPC. Also, given its frequent atypical presentation, it is not surprising that the diagnosis is missed or delayed [9]. Delay in diagnosis correlates with the degree of invasion and stage of NPC [2]. This is undesirable, as the delay in treatment of NPC carries a poor prognosis. The diagnosis of NPC usually depends on visualization of the nasopharyngeal tumor and pathological evidence. Despite advances in endoscopic examination, tumors may still evade detection due to the submucosal spread of the tumor, or a very small primary tumor. As a result, a normal appearing nasopharynx does not rule out NPC. In this patient, left upper neck swelling was found, but other local findings in the nasopharynx and ears were unremarkable. Hence, it was difficult to make a quick diagnosis in this patient. An FNA of cervical lymph nodes can aid in the diagnosis of occult NPC. Unfortunately, the FNA in the out-patient clinic did not obtain an adequate specimen. According to a previous report [10], a clinician-guided FNA of cervical lymph nodes had a higher nondiagnostic rate compared with US-FNA (21.5% vs. 3.4%). Under the guidance of ultrasound, aspiration over the target lymph node can be visualized. Therefore, US-FNA cytology offers more reliable specimens for these patients. The presence of a dissociated or mixed architectural pattern of large, J Med Ultrasound 2009 Vol 17 No 4 209

4 Y.L. Tseng, L.J. Liao anaplastic cells and naked nuclei accompanied by an abundant lymphoid component in cytology is suggestive of undifferentiated NPC [11]. The result of US-FNA cytology in this patient allowed us to avoid performing an open biopsy of the neck. Various sonographic findings have been used for predicting malignancy of the lymph node. The ratio of short and long axial diameters (S/L ratio) of the node is the most valuable factor [12]. A lymph node with a round configuration (S/L ratio of more than 0.55) leads to a suspicion of malignancy. However, the diagnosis of lymph node lesions cannot depend solely on ultrasound findings. Ultrasound combined with FNA cytology will enhance the accuracy of the evaluation of neck nodes [13]. US-FNA has some limitations; retropharyngeal nodes, micrometastases, and lymph nodes smaller than 4 mm cannot be evaluated with US-FNA [4]. It is also difficult to differentiate benign disease from lymphoma by cytomorphology [14]. Open biopsy is still necessary when a diagnosis of malignant lymphoma is suspected. Ultrasound-guided core needle aspiration (US- CNB) is another investigational method; it provides a higher specific diagnostic rate and greater accuracy compared with US-FNA [15]. However, the sensitivity and specificity did not differ significantly between the two methods. US-FNA is still the best choice for initial assessment of head and neck lesions. The indication for US-CNB is when repeated failures in US-FNA have been observed. The initial ultrasound in this patient showed a round hypoechoic lymph node (S/L ratio of 0.59), while the follow-up ultrasound of the node showed a more echogenic ovoid node (S/L ratio of 0.38) at 1 month after radiotherapy. The lymph node regressed 3 months after radiotherapy. This is consistent with the fact that a round-shaped lymph node is a predictor of malignancy [12] and that a residual node may persist up to 3 months following radiotherapy for NPC [16]. Radiotherapy for NPC is effective, and an open biopsy of the metastatic lymph node in NPC is not necessary for diagnosis. In conclusion, US-FNA cytology can assist in the evaluation of vague neck lumps with unremarkable local otolaryngological findings, and can help clinicians avoid unnecessary open biopsies in the diagnosis of NPC patients. References 1. Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol 2002;12: Sheng L, Shui Y, Shen L, et al. Effect of patientrelated delay in diagnosis on the extent of disease and prognosis in nasopharyngeal carcinoma. Am J Rhinol 2008;22: Baatenburg de Jong RJ, Rongen RJ, et al. Ultrasoundguided fine-needle aspiration biopsy of neck nodes. Arch Otolaryngol Head Neck Surg 1991;117: Knappe M, Louw M, Gregor RT. Ultrasonographyguided fine-needle aspiration for the assessment of cervical metastases. Arch Otolaryngol Head Neck Surg 2000;126: Shanmugaratnam K, Chan SH, de-the G, et al. Histopathology of nasopharyngeal carcinoma: correlations with epidemiology, survival rates and other biological characteristics. Cancer 1979;44: Marks JE, Phillips JL, Menck HR. The National Cancer Data Base report on the relationship of race and national origin to the histology of nasopharyngeal carcinoma. Cancer 1998;83: Lo KW, To KF, Huang DP. Focus on nasopharyngeal carcinoma. Cancer Cell 2004;5: Glastonbury CM. Nasopharyngeal carcinoma: the role of magnetic resonance imaging in diagnosis, staging, treatment, and follow-up. Top Magn Reson Imaging 2007; 18: Leong JL, Fong KW, Low WK. Factors contributing to delayed diagnosis in nasopharyngeal carcinoma. J Laryngol Otol 1999;113: Robinson IA, Cozens NJ. Does a joint ultrasound guided cytology clinic optimize the cytological evaluation of head and neck masses? Clin Radiol 1999;54: Viguer JM, Jimenez-Heffernan JA, Lopez-Ferrer P, et al. Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma. Diagn Cytopathol 2005;32: Takashima S, Sone S, Nomura N, et al. Nonpalpable lymph nodes of the neck: assessment with US and 210 J Med Ultrasound 2009 Vol 17 No 4

5 Ultrasound in the Diagnosis and Follow-up of NPC US-guided fine-needle aspiration biopsy. J Clin Ultrasound 1997;25: Bruneton JN, Roux P, Caramella E, et al. Ear, nose, and throat cancer: ultrasound diagnosis of metastasis to cervical lymph nodes. Radiology 1984;152: Roh JL, Lee YW, Kim JM. Clinical utility of fine-needle aspiration for diagnosis of head and neck lymphoma. Eur J Surg Oncol 2008;34: Kraft M, Laeng H, Schmuziger N, et al. Comparison of ultrasound-guided core-needle biopsy and fineneedle aspiration in the assessment of head and neck lesions. Head Neck 2008;30: Ahuja A, Ying M, Leung SF, et al. The sonographic appearance and significance of cervical metastatic nodes following radiotherapy for nasopharyngeal carcinoma. Clin Radiol 1996;51: J Med Ultrasound 2009 Vol 17 No 4 211