Clinical investigation: head and neck
Cervical lymph node metastases from occult squamous cell carcinoma: cut down a tree to get an apple?

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Abstract

Purpose: To review the value of extended diagnostic work-up procedures and to compare the results of comprehensive or volume-restricted radiotherapy in patients presenting with cervical lymph node metastases from clinically undetectable squamous cell carcinoma.

Methods and Materials: A systematic review was undertaken of published papers up to May 2000.

Results: Positron emission tomography (PET) has an overall staging accuracy of 69%, with a positive predictive value of 56% and negative predictive value of 86%. With negative routine clinical examination and computerized tomography (CT) or magnetic resonance imaging (MRI), PET detected primary tumors in 5–25% of patients, whereas ipsilateral tonsillectomy discovered carcinoma in about 25% of patients. Laser-induced fluorescence imaging with panendoscopy and directed biopsies showed some encouraging preliminary results and warrants further study. All together, the reported mucosal carcinoma emergence rates were 2–13% (median, 9.5%) after comprehensive radiotherapy and 5–44% (median, 8%) after unilateral neck irradiation. The corresponding nodal relapse rates were 8–45% (median, 19%) and 31–63% (median, 51.5%), and 5-year survival rates were 34–63% (median, 50%) and 22–41% (median, 36.5%), respectively. Retrospective single-institution comparisons between comprehensive and unilateral neck radiotherapy did not show apparent differences in outcome. Prognostic determinants for survival are the N stage, number of nodes, extracapsular extension, and histologic grade. No data were found to support the benefit of chemotherapy in this disease.

Conclusion: Physical examination, CT or MRI, and panendoscopy with biopsies remain the standard work-up for these patients. Routine use of PET or laser-induced fluorescence imaging cannot be firmly advocated based on presently available data. Although combination of nodal dissection with comprehensive radiotherapy yielded most favorable results, its impact on the quality of life should be recognized, and the confounding effects of patient selection for various treatment modalities on therapeutic outcome cannot be ruled out. A randomized trial comparing the therapeutic value of comprehensive vs. volume-limited radiotherapy is being considered.

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

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