Diagnosis and management of carcinoma of unknown primary in the head and neck

Abstract

Carcinoma of unknown primary is defined as the histological diagnosis of metastasis without the detection of a primary tumor. In the literature, the incidence of CUP in all patients with a malignant disease is said to be between 3% and 15%. The most frequent histopathological results of CUP metastases are adenocarcinoma, followed by undifferentiated carcinoma and squamous cell carcinoma. In this retrospective investigation the clinical records of 167 patients were studied. All patients had been admitted and treated for cervical CUP at the Department of Otorhinolaryngology of the Grosshadern Clinic from 1979 to 1998. Cervical swelling was the first noted symptom in all cases, followed by pain and dysphagia. The study group comprised 134 men and 33 women with an average age of 55 years at admission. Squamous cell carcinoma (n=123) was the predominant histopathological finding of the cervical lymph nodes. During the 10-year follow-up, a primary tumor was detected in 36 (21.5%) of the 167 initially diagnosed CUP patients. In over 90% of these cases the tumor was localized in the head and neck region. The most frequent origin of the tumor was the tonsilla palatina (n=7). Neck dissection and additional postoperative radiotherapy was performed in 118 (70.7%) of the 167 CUP patients. Primary radiotherapy was the treatment of choice in 28 patients; eight patients received combined radio-chemotherapy as the primary treatment and seven patients were treated with chemotherapy alone. Six patients had no treatment. Comparison of different treatment protocols revealed a significant difference in patient survival: in comparison with primary radiotherapy alone or neck dissection and postoperative radiotherapy, the survival rate improved significantly in patients that received a bilateral tonsillectomy in addition to neck dissection and postoperative radiotherapy. The treatment of choice in patients with cervical CUP should be a surgical procedure including (radical) neck dissection and diagnostic bilateral tonsillectomy followed by postoperative radiation of the cervical lymph drainage. Bilateral tonsillectomy is especially important and is correlated with a significant improvement of the survival rate in CUP patients. Additional postoperative radiation of the entire pharyngeal and laryngeal mucosa should also be considered in order to treat a possible small primary tumor in this region.

Management of lymph node metastases from an unknown primary site to the head and neck (Review)

“…The symptom that commonly prompts initial consultation is a mass in the neck, which accounted for 94% of the 352 patients in the series reported by Grau et al (5), with pain and weight loss reported in only 9 and 7%, respectively. In a series of 167 patients reported by Issing et al (4), the incidence of cervical swelling, pain and dysphagia was 100, 9 and 3.6%, respectively. Typically, the enlarged cervical lymph nodes are located at level II, with bilateral involvement reported in <10% of the cases (2,4,5).…”

“…In a series of 167 patients reported by Issing et al (4), the incidence of cervical swelling, pain and dysphagia was 100, 9 and 3.6%, respectively. Typically, the enlarged cervical lymph nodes are located at level II, with bilateral involvement reported in <10% of the cases (2,4,5). The clinical N classification in the majority of cases is N2, with a median nodal size of 3.5-5 cm (2,5,8) and the time interval between the appearance of cervical mass and diagnosis is 2-5 months (2,4).…”

“…As a clinical entity defined by the exclusion of a primary tumor, the standardized diagnostic work-up includes meticulous medical history and clinical examination using modern diagnostic tools. The estimated incidence of CUP accounts for ~3-9% of all head and neck cancers, with squamous cell histology accounting for 53-77% of the cases (2)(3)(4). Over the last few years, there has been a decrease in the incidence of cervical CUP, due to a more accurate diagnosis of the primary tumor by means of a thorough fibre optic endoscopy of the pharynx and larynx, esophagogastroduodenoscopy, bronchoscopy and advanced imaging technology in the majority of patients (5).…”

Accuracy of Diagnostic Methods for Detection of Head and Neck Primary Origin in Metastatic Neck Mass

“…Dependent on the country, CUP represents 2-8% of the overall malignancies [2] and 3-5% of all solid tumors [3][4][5]. The estimated occurrence of CUP in the head and neck (HNCUP) region varies between 3 and 9%, with histological findings of a squamous cell malignancy in 53-77% of the cases [6][7][8]. The frequency of a subsequent mucosal emergence of the primary site in the head and neck region varies between 4 and 21% percent in the studies reviewed [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28].…”

“…The most frequently encountered primary symptom is a cervical mass due to enlarged lymph nodes (94%) [15], mostly located in level 2 (30-50%), followed by level 1 and 3 (10-20%) and 4 and 5 (5-10%) [2,15]. Bilateral involvement of the neck is reported in less than 10% of the cases [6,8,15,18,19,29,30]. When node metastases are found in levels 1-3, the primary site is suspected to be in the head and neck region.…”