International Journal of Radiation Oncology*Biology*Physics
Clinical investigation: head and neckCervical lymph node metastases from occult squamous cell carcinoma: cut down a tree to get an apple?☆
Introduction
Cervical nodal metastasis from clinically undetectable primary squamous cell carcinoma (SCC) accounts for 1–2% of head-and-neck malignancies 1, 2, 3, most frequently manifests in the jugulodigastric and mid-jugular lymph nodes 3, 4, and presents both a diagnostic and therapeutic challenge. Routine work-up includes physical examination, biopsy or excision of the enlarged lymph node(s), CT and/or MRI, and panendoscopy with or without random or directed biopsies. Commonly, treatment consists of lymph node dissection and elective irradiation of the putative mucosal sites and bilateral neck, plus supraclavicular, nodes 5, 6, 7. However, unilateral radiotherapy (RT) to the involved side 2, 8, as well as combination of chemotherapy plus comprehensive irradiation 9, 10, have also been proposed.
In the absence of comparative trial results, the optimal treatment strategy remains controversial due to a number of considerations. Briefly, first, the potential gain with comprehensive radiotherapy in controlling the putative primary carcinoma should be weighed against its effect on quality of life resulting from increased acute and persistent morbidity, such as xerostomia. Second, it is possible that a head-and-neck carcinoma detected later in this patient subset is actually a second primary tumor instead of the putative cancer. Finally, the feasibility of reirradiating the head-and-neck region is being recognized should a cancer emerge after ipsilateral radiotherapy. The objective of this review is to evaluate the value of extended diagnostic work-up and to compare the results of comprehensive and volume-restricted RT in this group of patients.
Section snippets
Diagnostic examinations
Physical examination and assessment under anesthesia conducted by experienced otolaryngologists or head and neck surgeons detect primary head-and-neck SCC in over 50% of patients presenting with cervical lymph node metastases (11). Of course, characteristic epidemiologic pattern of such tumors in different parts of the world should be taken into account. CT or MRI may identify suspicious areas guiding biopsy sampling. A recent retrospective analysis by Mendenhall and colleagues on 130 patients
The role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for detecting occult primary tumors
It has been suggested that FDG-PET is more accurate than CT or MRI for staging of both head-and-neck primary tumors and lymph node metastases (15). A study by Stokkel et al. (16) of 68 patients with oral cavity or oropharyngeal SCC examined within 3 weeks of diagnosis showed that clinical examination, chest X-ray, or CT detected second primary tumors in 5 patients (7%) whereas PET detected second aerodigestive tract primary tumors in 11 patients (16%, p = 0.03), along with one thyroid
More recently introduced diagnostic methods
A recent report suggested that laser-induced fluorescence imaging could increase the primary tumor detection rate (26). In a series of 13 patients who underwent conventional assessment, panendoscopy with random biopsies detected 2, whereas fluorescence-guided biopsies detected 5 primary tumors. Despite false-positive results in 8 locations from 4 patients, the number of unnecessary biopsies with fluorescence-guided biopsies was much lower than that of a random biopsy strategy. Considering these
Results of surgery alone
Grau et al. recently reported a series of 277 patients treated with radical intent in 5 cancer centers in Denmark (3). Therapy consisted of radical surgery as the only treatment in 23 (9%), irradiation of the ipsilateral neck in 26 (10%), and radiotherapy to both sides of the neck and the mucosa in 224 patients (81%). The incidence of emerging primary in the head and neck was significantly higher in patients treated with surgery alone than those treated with radiotherapy (5-year actuarial risks
Nodal excision or dissection followed by radiotherapy
Colletier et al. (7) evaluated a series of 136 patients who received radiotherapy after either excisional nodal biopsy (39 patients) or neck dissection (97 patients). The majority of patients (88%) received radiation with comprehensive portals. The mucosal carcinoma emergence rate was 10% (10-year actuarial rate of 14%), the nodal failure rate was 9%, the distant metastases rate 18%, and the 5-year survival rate was 60%. Strojan and Anicin (34) also reported a mucosal primary emergence rate of
Role of chemotherapy
Debaud et al. (4) suggested improved survival by addition of chemotherapy in a report of 41 patients, of whom 16 had one of several chemotherapy regimens before, during, or after radiotherapy. The sample size and heterogeneous disease characteristics did not allow in-depth analysis.
In the series of Kirschner et al. (10) 40 of 64 patients had SCC, 48 underwent nodal resection and comprehensive radiotherapy, and 11 received concurrent chemotherapy (cisplatin and fluorouracil). The primary tumor
Summary
Several clinically relevant issues have been derived from this literature review. The available data show that diagnostic imaging (CT or MRI) plus panendoscopy with or without random biopsies remains the standard work-up of patients presenting with cervical nodal metastasis with no primary tumor detected by physical examination. The role of laser-induced fluorescence imaging in aiding white light panendoscopy to guide biopsy sampling requires further assessment. In the absence of panendoscopy
References (44)
- et al.
The occult head and neck primaryTo treat or not to treat?
Clin Oncol
(1997) - et al.
Cervical lymph node metastases from unknown primary tumours. Results from a national survey by the Danish Society for Head and Neck Oncology
Radiother Oncol
(2000) - et al.
Metastatic carcinoma in the cervical lymph nodes from an unknown primary siteResults of bilateral neck plus mucosal irradiation vs. ipsilateral neck irradiation
Int J Radiat Oncol Biol Phys
(1997) - et al.
Metastatic carcinoma in the cervical lymph nodes from an occult primaryA conservative approach to the role of radiotherapy
Int J Radiat Oncol Biol Phys
(1990) - et al.
Cervical lymph node metastasis from an unknown primaryis a tonsillectomy necessary?
Int J Radiat Oncol Biol Phys
(1997) - et al.
Detection of unknown primary head and neck tumors by positron emission tomography
Int J Oral Maxillofac Surg
(1997) - et al.
18F-FDG whole body positron emission tomography (PET) in patients with unknown primary tumours (UPT)
Eur J Cancer
(1999) - et al.
Metastases to lymph nodes of the head and neck from an unknown primary site
Am J Surg
(1977) - et al.
Cervical nodal metastasis of squamous cell carcinoma of unknown originIndications for withholding radiation therapy
Int J Radiat Oncol Biol Phys
(1992) - et al.
Combined surgery and postoperative radiotherapy for cervical lymph node metastases from an unknown primary tumour
Radiother Oncol
(1998)
Cervical lymph nodes from an unknown primary tumor in 190 patients
Am J Surg
Cervical metastases of occult originThe impact of combined modality therapy
Am J Surg
Radiation treatment of cervical lymph node metastases from an unknown primaryAn analysis of outcome by treatment volume and other prognostic factors
Radiother Oncol
The unknown primary
Diagnosis and management of squamous cell carcinoma of unknown primary tumor site of the neck
Semin Oncol
Metastatic squamous cell carcinoma in cervical lymph nodes from an unknown primary tumorPrognostic factors
Clin Otolaryngol
Postoperative radiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary siteOutcomes and patterns of failure
Head Neck
Metastatic squamous cell carcinoma of an unknown primary localized to the neck
Cancer
Treatment for cervical metastases from an unknown primary (German)
Strahlenther Onkol
Squamous carcinoma presenting as an enlarged cervical lymph node
Cancer
Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site
Head Neck
Occult tonsillar carcinoma in the unknown primary
Laryngoscope
Cited by (165)
Is bilateral radiotherapy necessary for patients with unilateral squamous cell carcinoma of unknown primary of the head and neck region?
2024, Clinical and Translational Radiation OncologyImaging of Neck Nodes in Head and Neck Cancers – a Comprehensive Update
2023, Clinical OncologyCysts of the Neck, Unknown Primary Tumor, and Neck Dissection
2020, Gnepp's Diagnostic Surgical Pathology of the Head and Neck, Third Edition
- ☆
Supported by Research Grants CA-06294 and CA-16672 from the National Cancer Institute, National Institute of Health and the Gilbert H. Fletcher Chair.