Cystic Lateral Neck Lesions: Etiologic and Differential Diagnostic Significance in a Series of 133 Patients

Discussion

Patients presenting with cystic neck lesions are relatively rare in the daily work of head and neck specialists. To increase therapeutic efficiency, a central challenge is to anticipate whether the mass represents a branchial cleft cyst or a malignant, particularly metastatic disease.

The two largest studies investigating cystic neck lesions include data from 130 patients and were monocentric (8) and multicentric (9). Further literature includes a review (5) and smaller series and case reports (10, 11). Other reports have different study designs (12). Therefore, this study presents the largest monocentric patient cohort to date of 133 consecutive patients who underwent surgery for a cystic mass. We discuss etiology, diagnostic aspects and clinical features, and present our algorithm to increase diagnostic and therapeutic efficiency.

Pathophysiological aspects. The majority of histological findings in patients presenting with a cystic neck lesion are non-malignant according to this study and the current literature (8, 9). The most frequent diagnosis (59%) in the current study was branchial cleft cyst (Table I). In other series, frequencies of this entity up to 90% were reported (8-10). The second most frequent pathological result was cystic deformed lymph nodes caused by granulomatous infections with tuberculosis. This patient group included migrants from outer European countries younger than 40 years (13). Other non-malignant cystic neck lesions such as Warthin's tumor or thyroid cysts presented as individual cases consistent with the available literature (9, 10).

The malignancy rate in the present study was 31% across all patients and significantly higher than in other investigations with rates between 9.2% and 14.4% (8, 9, 11, 14). In patients older than 40 years, the percentage of malignant findings in the current study was 56%. Other authors reported rates up to 31% (8, 10, 14). Malignant findings were extremely rare in patients under 40 years of age (1.6%). On the other hand, nearly one-third (31/92) of the present cohort with non-malignant findings were older than 40 years. Sira et al. (10) and Seven et al. (15) described a relevant number of papillary thyroid cancer metastases in patients younger than 40 years. In the current study, only one patient with thyroid cancer was found (female aged 79 years). The incidence of malignancy increases in patients older than 40 years (2, 3). The present results highlight the importance of patient age for differential diagnoses of cervical cystic lesions (2, 14). Grönlund et al. discuss a lower critical patient age of 35 years with respect to an increased incidence of HPV-related SCC (9).

The prevailing histological finding in the current study in patients with malignancy was SCC histology (85%). The majority of primary tumors were located in Waldeyer's ring (8, 16). According to the current results, primary carcinoma of the hypopharynx should be included in the search for a primary tumor. Even malignant lymphoma may present as a cystic lesion. Cystic metastases from a primary tumor below the clavicle remain rare exceptions (17). In 15 patients with a histological diagnosis of SCC, no primary tumor was found, even after a meticulous search. These cases were considered as CUPs of an occult primary and were not regarded as branchial cleft cyst carcinoma (18, 19). In our opinion, we agree with former publications that branchial cleft cyst carcinomas either do not exist or are extremely rare (6, 7) (Table I).

Diagnostical aspects. A highly comprehensive history is necessary when patients present with a neck lesion. Anamneses should include infections of the upper aerodigestive tract with enlarged lymph nodes as well as symptoms and habits related to head and neck carcinoma (e.g. pain, dysphagia, smoking and drinking habits). The history should also include typical complaints of tuberculosis and sarcoidosis, and malignant lymphoma.

In the current series, the neck lesion was the first manifestation in most cases of non-malignant (91/92) and malignant (38/41) diseases.

The next steps are the ear, nose and throat examination. The majority of patients presented with a palpable, indolent and sometimes fluctuating cervical mass in level II of 3 to 6 cm. None of our patients had suspicious findings on physical (endoscopic) examination, including flexible endoscopy. While every patient in our series underwent ultrasonography of the head and neck including the thyroid gland, 75% of adult patients older than 40 years were investigated additionally by computed tomographic (CT) or magnetic resonance imaging. For superficial lesions, ultrasound is the first-level imaging study of choice because it is non-invasive, rapid, low-cost, and does not involve exposure to ionizing radiation (20). Using ultrasound to differentiate between non-malignant and malignant cystic lesions can be challenging. Misdiagnosis of malignant neck cysts may delay diagnosis (21). However, use of CT and magnetic resonance imaging may also have difficulties differentiating between non-malignant and malignant cystic lesions (22-24).

In a recent investigation, Abadi et al. identified 14 out of 20 patients with cancer in a retrospective series of 58 patients by positron-emission tomography/CT (25). However, none of our patient underwent such examination.

Fine-needle aspiration biopsy (FNAB) is frequently considered to be of paramount importance when diagnosing neck masses. Depending on personal experiences, FNAB has been associated with false-negative results in cases of malignant diseases when aspiration histology of cystic fluid was free of tumor cells. Discrepancies between FNAB and final histology, which cause time delay in searching for a primary tumor and the onset of therapy, are well documented in literature (5, 8, 9, 14). In our experience, FNAB delays diagnosis of malignant lymphoma. In patients with SCC with false-negative histological results, neck dissections are required in a second setting after definitive histology. Therefore, we do not recommend FNAB when diagnosing cystic neck lesions.

Consequently, our results support the opinion reported in other series that discrimination between a branchial cleft cyst and a malignancy is not possible based on history, clinical examination and radiological imaging including FNAB (5, 8, 9). Histological examination is absolutely required. This algorithm increases therapeutic efficiency.

Therapeutic aspects. The large proportion of malignant findings in the current series emphasize the demand for early biopsy in patients with neck cysts to avoid delaying diagnosis and beginning therapy. Half of the patients (67/133) underwent resection of the neck mass without further procedures. In more than 20% (14/66) of the remaining patients, we found an occult primary tumor of the upper aerodigestive tract by pan-endoscopy. Palpation was of paramount importance when detecting carcinoma of Waldeyer's ring (11/14).

The remaining patients underwent open surgery. The primary objective of our approach is to avoid excision of a cyst before definitive therapy (neck dissection). We believe that the risk of complications and unnecessary radical surgery is increased if definitive surgery is secondary to resection of the neck cyst. Notwithstanding this, others have shown that neck surgery during a second setting does not necessarily result in a poorer outcome (26).

Intraoperative frozen section evaluation was performed in patients with suspected malignancy and without an endoscopically evident tumor in pan-endoscopy. Metastases of SCC were found in 16 out of 40 cases. In six cases, the frozen section was either false-negative or not evaluable (three cases each). According to our experience, intraoperative frozen section evaluation is a reliable method for ruling out malignant histology, e.g. SCC. As a result, neck dissection in a second setting could have been avoided in 30 out of 36 cases. The superior sensitivity of frozen section evaluation in cystic neck lesions compared with FNAB has been demonstrated by Begbie et al. (27).

Moreover, our results outline the need for a second pan-endoscopy with tonsillectomy and mapping biopsies of the tongue base and nasopharynx. In the current study, we performed this procedure after negative pan-endoscopy and proven SCC in the cervical neck cyst. Thereby, five unknown primary tumors were detected.

Patients with metastatic head and neck cancer received postoperative radio- or radiochemotherapy through our practice. When the primary tumor remained occult, additional mucosal dosing of the upper aerodigestive tract excluding the oral cavity was performed (3).

Prognostic aspects. In the current series, HPV status was determined in 50% of those with tonsil cancer and 27% of those with CUP. The association between tumorigenic HPV and cystic morphology of metastasis has been discussed (4). HPV positivity in cancer of Waldeyer's ring, especially tonsillar cancer, has been demonstrated by several authors, while the majority of branchial cleft cysts were proven HPV-negative (8, 28). Therefore, the present results confirm findings of previous reports (24, 29, 30).