Auris Nasus Larynx 39 (2012) 298–300
Contents lists available at SciVerse ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Diagnosis of congenital cervical cysts using carcinoembryonic antigen levels in cyst fluid Ujimoto Konomi a,*, Ryoji Tokashiki a, Tomoyuki Yoshida b, Akira Shimizu a, Kiyoaki Tsukahara b, Mamoru Suzuki a a b
Department of Otolaryngology, Tokyo Medical University School of Medicine 6-7-1, Nishi-shinjyuku, Shinjyuku-ku, Tokyo #160-0023, Japan Department of Otolaryngology, Head and Neck Surgery, Tokyo Medical University Hachiouji Medical Center, Tokyo, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 19 April 2011 Accepted 11 July 2011 Available online 14 March 2012
Objective: To investigate whether carcinoembryonic antigen (CEA) levels in the fluid of median or lateral cervical cysts can improve diagnosis. Methods: Cyst fluid CEA levels in 10 cases of median cervical or lateral cervical cysts based on pathological diagnoses (congenital cervical cyst group) were measured. These results were compared with the CEA levels of the control group comprising 10 cases of other head and neck cyst disorders. Results: The CEA levels in nine out of ten cases in the congenital cervical cyst group were 10,000 ng/mL. The CEA level in the remaining case was 8290 ng/mL. In contrast, the CEA levels were low in the control group (>1000 ng/mL). The optimal cut-off level between these groups was 8290 ng/mL in the receiver operating characteristic curve (p < 0.01). Conclusion: Cyst fluid CEA levels may assist in the diagnosis of median and lateral cervical cysts. ß 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords: Carcinoembryonic antigen (CEA) Lateral cervical cyst Branchial cleft cyst Median cervical cyst Congenital cyst Diagnosis
1. Introduction Pre-surgery neck cyst lesions are usually diagnosed by clinical symptoms or imaging findings. In many cases, an accurate diagnosis is obtained by histopathology after surgically removing the cyst [1]. Few studies have reported that patients with congenital cervical cysts, such as median and lateral cervical cysts, exhibit high levels of carcinoembryonic antigen (CEA) [2,3]. However, these reports did not compare CEA levels with other cyst disorders or include additional clinical tests. In the present study, we measured cyst fluid CEA levels in 10 patients who were diagnosed with median or lateral cervical cysts based on pathologic findings, and compared these results with cyst fluid CEA levels in 10 patients with other head and neck cyst disorders, to determine the usefulness of cyst fluid CEA levels in diagnosing cervical cyst disorders. 2. Subjects Subjects were selected from patients who visited our hospital between 2001 and 2007. Inclusion criteria consisted of median or lateral cervical cysts based on a pathologic diagnosis after surgical removal of the cyst. The 10 cases in the congenital cervical cyst
* Corresponding author. Tel.: +81 3 3342 6111; fax: +81 3 3346 9275. E-mail address:
[email protected] (U. Konomi). 0385-8146/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2011.07.005
group (5 male and 5 female; mean age, 33.5 years; age range, 10– 73 years) included a median cervical cyst (n = 1) and lateral cervical cysts (n = 9). The control group consisted of patients with other head and neck cyst disorders; these cases were not confirmed by pathologic findings. The 10 cases in the control group (8 male and 2 female; mean age, 39.8 years; age range, 18– 84 years) included oropharyngeal cysts (n = 2), a lymphocele (n = 1), a parotid cyst (n = 1), a ranula (n = 1), a squamous cell carcinoma (n = 1), a congenital maxillary cyst (n = 1), and thyroid cysts (n = 3). 3. Methods 3.1. Sampling of cyst fluid We sampled cyst fluid from patients with suspected median or lateral cervical cysts, and cyst fluid from patients with head and neck cysts was used as a control. Cyst fluid was collected transdermally by fine-needle aspiration using a 21-gauge needle with a syringe. Sampling was performed before or during surgery. 3.2. Measurement of cyst fluid CEA levels We determined cyst fluid CEA levels by enzyme immunoassay (EIA) immediately after collecting fluid. The normal level of serum CEA was <5.0 ng/mL using this assay. We could easily measure CEA levels in the congenital cervical cyst group. In the control group,
[(Fig._1)TD$IG]
U. Konomi et al. / Auris Nasus Larynx 39 (2012) 298–300
299
CEA levels were difficult to measure in some cases with high viscosity of the cyst fluid. We could determine approximate values in such cases by diluting the cyst fluid, but these cases were excluded in the present study. 3.3. Definitive diagnosis Definitive diagnoses for all median and lateral cervical cyst cases were based on pathologic findings after surgical removal. 3.4. Statistical analysis CEA levels of the congenital cervical cyst group were compared with the control group, and analyzed using the cut-off value determined by the receiver operating characteristic (ROC) curve. Fig. 1. Carcinoembryonic antigen levels in cysts.
4. Results 4.1. Congenital cervical cyst group
5. Discussion
As shown in Table 1, cyst fluid CEA levels were markedly increased in all cases. The case with the lowest CEA level reached 8290 ng/mL, and three cases revealed a CEA level 100,000 ng/mL. The mean CEA level was 60,768.3 ng/mL (range 8290–131,000 ng/ mL).
In 1965, Gold and Freedman [4] reported CEA as an antigen that is specific to digestive system carcinomas and the embryonic digestive system. Subsequently, various cancer cells were also shown to produce CEA. Presently, CEA is one of the most commonly used tumor markers, and determination of CEA levels is a very important supplemental test for the definitive diagnosis of various cancers and also for use as an index after treatment. CEA is expressed at relatively high levels in stomach, colon, biliary, lung, ovarian, and breast cancers. Thus, CEA levels are useful for diagnosis, assessment of therapeutic effects, and follow-up observation after surgical treatment [5]. CEA is a membrane-bound glycoprotein (comprising approximately 60% saccharide by mass) with a molecular weight of about 180,000 Da. It is extensively produced by mucosa types such as oral, intestine, gastric, respiratory and biliary mucosae. In normal mucosa, CEA is present only on the luminal surface of mucosal epithelial cells, but not on the basal part of the mucosa. Thus, CEA is
4.2. Control group As shown in Table 2 and Fig. 1, cyst fluid CEA levels were <1000 ng/mL in all cases (range 0.8–733 ng/mL). The mean CEA level was 171.8 ng/mL, which was significantly lower than that in the congenital cervical cyst group. 4.3. Statistical analysis The optimal cut-off level between the two groups was 8290 ng/ mL in the ROC curve (p < 0.01).
Table 1 Congenital cervical cyst group. Case
Clinical diagnosis
Pathology results
Gender (F/M)
Age (year)
CEA (ng/ml)
1 2 3 4 5 6 7 8 9 10
Cervical cyst Cervical cyst Cervical cyst Cervical cyst Cervical cyst Cervical cyst Cervical cyst Cervical cyst Median cervical cyst Cervical cyst
Lateral cervical cyst Lateral cervical cyst Lateral cervical cyst Lateral cervical cyst Lateral cervical cyst Lateral cervical cyst Lateral cervical cyst Lateral cervical cyst Thyroglossal duct cyst Lateral cervical cyst
F M M F F M F F M M
19 18 49 19 10 18 44 16 69 73
131,000 128,900 122,000 55,000 47,776 38,500 36,100 23,717 16,400 8290
Table 2 Control group. Case
Clinical diagnosis
1 2 3 4 5 6 7 8 9 10
Oropharyngeal cyst Oropharyngeal cyst Cervical cyst Parotid cyst Ranula Cervical cyst Congenital maxillary cyst Thyroid cyst Thyroid cyst Thyroid cyst
Pathology results Epithelial cyst Lymphocele Ranula Squamous cell carcinoma
Thyroid cyst
Sex (F/M)
Age (year)
CEA (ng/ml)
M M f f M M M M M M
37 48 21 84 18 58 28 30 26 48
247 178 4.5 190 53.7 733 192 0.8 0.6 118
300
U. Konomi et al. / Auris Nasus Larynx 39 (2012) 298–300
not usually in contact with blood, lymph, or tissue fluid; it is present in blood only when the cell polarity is disturbed by cancerous tissue or inflammation [3]. Various disorders are associated with increased serum CEA, including hepatitis, cirrhosis, pancreatitis, obstructive jaundice, pulmonary tuberculosis, chronic respiratory disorders, inflammatory bowel disease, thyroid disorders, aging, smoking, diabetes, and renal failure. The cut-off value for serum CEA by chemiluminescence immunoassay (CLIA) or EIA methods is 5.0 ng/L. For benign disorders such as inflammation, the cut-off value is 10 ng/mL. However, no standard value has been established for cyst fluid CEA levels. Although serum sampling is most commonly used for determining CEA levels, plasma, pleural effusion, ascites, and secretory fluid (e.g., breast fluid and bile) are also analyzed to diagnose metastasis. CEA levels can also increase in branchial cyst fluid. Immunostaining revealed the presence of CEA-producing cells in the stratified squamous epithelium of cyst internal mucosa [6,7], which produce CEA as CEA-producing mucosae in other regions. We speculate that this is why CEA accumulates in cyst fluid. Few reports about cyst fluid CEA levels exist, and many of them are case reports [8]. Yamamoto et al. [3] reported increased CEA, squamous cell carcinoma (SCC) antigen, and CA19-9 levels in median and lateral cervical cysts; however, they did not use these results for clinical applications or for comparison with a control group. In the present study, we demonstrated that cyst fluid CEA levels in the congenital cervical cyst group were significantly elevated compared with those of the control group. The only one median cervical cyst case was included in the congenital cervical cyst group. This is because the median cervical cyst should be further studied as a cyst group that demonstrates high CEA level. Although determination of the cyst fluid CEA level is not the only minimally invasive diagnostic examination for cervical cyst disease, it may become an important supplemental diagnostic test, especially in difficult-to-diagnose cases [9]. In the rare case of a cervical cyst showing rapid growth and possessing a solid component by imaging findings, thyroglossal or branchial cancer should be considered. In this case, surgical treatment and pathological diagnosis should be prioritized over the cyst fluid CEA level [10]. Additionally, positron emission tomography (PET) is necessary for the pre-operative diagnosis of malignant cysts. Other cases, including lymph node metastasis of pharyngeal and thyroid cancers, are often difficult to distinguish. However, aspiration cytology is important when malignancy is suspected, because malignant cells cannot always be detected. Clinically, examining cyst fluid CEA levels may potentially assist in the diagnosis of cyst disease. Table 2 displays cases in which CEA was found to be useful. When patients refuse surgical removal of the cervical cyst, cytological analysis and cyst fluid CEA levels can be determined from fluid that is drained by fine-needle aspiration. If CEA levels are markedly high, congenital cervical cysts may be
suspected and can be easily determined by follow-up observation. Furthermore, when a malignant tumor is suspected, based on imaging examination and cytological analysis, cyst fluid CEA levels can determine whether the tumor is a primary branchial cancer or metastasized cancer. CEA levels may also be applicable to cyst disorders in the parotid gland and auricular region because first branchial cleft cysts sometimes appear in this area. For these cysts, we can distinguish between first branchial cysts and other disorders by determining cyst fluid CEA levels before surgery. If a branchial cyst is suspected, surgery using the fistula procedure can be considered in advance. Therefore, analysis of cyst fluid CEA levels may become an essential tool for neck cysts that are difficult to diagnose, and useful for deciding the timing of surgery. 6. Summary Analysis of cyst fluid CEA levels is useful for the diagnosis of congenital cervical cysts (median and lateral cervical cysts). This examination may be potentially useful for differential diagnosis of neck cysts and deciding the timing of surgery. Conflict of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. References [1] Shanker L, Khan A, Cheung G. Differential diagnosis of neck spaces. In: Shanker L, Khan A, Cheung G, editors. Head and neck imaging. New York, NY: McGrawHill; 1998. p. 43–52. [2] Hirota J, Maeda Y, Ueta E, Osaki T. Immunohistochemical and histologic study of cervical lymphoepithelial cysts. J Oral Pathol Med 1989;18:202–5. [3] Yamamoto M, Tsuji M, Yamada K, Taniguchi H, Kim YH, Fukuda K, et al. Cyst fluid levels of carcinoembryonic antigen, carbohydrate antigen 19-9, squamous cell carcinoma antigen, and amylase in thyroglossal duct and branchial cleft cysts. Surg Today 2001;31:477–81. [4] Gold P, Freedom SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med 1965;122:467–81. [5] Sheahan K, O’Brien MJ, Burke B, Dervan PA, O’Keane JC, Gottlieb LS, et al. Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies. Am J Clin Pathol 1990;94:157–64. [6] Regauer S, Gogg-Kamerer M, Braun H, Beham A. Lateral neck cysts—the branchial theory revisited. A critical review and clinicopathological study of 97 cases with special emphasis on cytokeratin expression. APMIS 1997;105: 623–30. [7] Golledge J, Ellis H. The aetiology of lateral cervical (branchial) cysts: past and present theories. J Laryngol Otol 1994;108:653–9. [8] Tokuchi Y, Ukita H, Tsuneta Y, Nishiura Y, Takahashi W, Kawai T, et al. Bronchogenic cyst with high carbohydrate antigen 19-9 in the cyst fluid and the serum. Intern Med 1998;37:86–90. [9] Androulakis M, Johnson JT, Wagner RL. Thyroglossal duct and second branchial cleft anomalies in adults. Ear Nose Throat J 1990;69:318–22. [10] Khafif RA, Prichep R, Minkowitz S. Primary branchiogenic carcinoma. Head Neck 1989;11:153–63.