Jonas
T. Johnson,
MD
A Surgeon
Looks
at
S
Squamous cell carcinoma is the most commonly encountered malignant neoplasm of the upper aerodigestive tract. The most important factor that influences therapeutic outcome is the development of metastasis to the cervical lymph nodes. Traditionally, assessment and staging have been based on clinical evaluation. Studies of clinicopathologic correlation have demonstrated that both the sensitivity and the specificity of the clinical examination findings are unsatisfactorily low in that false-negative rates may be 15%-25% while false-positive rates may be similarly high. The clinician is caught in the position of having to overtreat many patients to avoid undertreating a few. The rapid advances in imaging technology introduced in the past decade have greatly affected our ability to identify cervical metastatic disease. With improved technology and increased experience, patients can be better characterized individually according to the status of the cervical lymph nodes so that therapeutic intervention can be appropriately designed.
Index
terms:
20.373,
Head
Lymphatic Mouth,
system, neoplasms, 263.373 272.373
neoplasms,
neck
276.375
262.373
#{149} Nasopharynx,
Pharynx,
#{149}
#{149} State-of-art
262.373
271.373
neoplasms,
#{149} Tonsils,
neoplasms, reviews
#{149} Tongue,
neoplasms,
262.373
Radiology
1990;
‘From
and ber 23.
Ear
8, 1989; Address EDITOR’S
the-art review gists in areas CRSNA
175:607-610
of Otolaryngology,
the Department
Hospital
of Pittsburgh,
revision reprint
requested requests
NOTE-Dr
articles of interest 1990
Johnson
intended to the
Suite
500,
December to the author. is a surgeon.
to capture practicing
203
QUAMOUS
University
of Pittsburgh
Lothrop
St. Pittsburgh,
29; revision His
Lymph
cell carcinoma is the most common malignant neoplasm encountered on the mucosal surfaces of the upper aerodigestive tract. This epithelial lesion is closely associated with the abuse of tobacco and alcohol products (1). Cellular atypia and dysplasia commonly exist for some period before invasive carcinoma is recognized. Invasion of the submucosa and adjacent soft tissues progresses at a variable rate and is commonly associated with the development of cervical metastases to the draining lymph nodes. While it is commonly stated that the presence of cervical lymph node metastases is associated with a statistically significant negative effect on prognosis, there does not currently exist a precise way to identify and quantitate microscopic cervical metastatic disease. The TNM staging system of the American Joint Committee on Cancer has been developed as a working tool for clinicians (2). Unfortunately, even the most current TNM staging system is based largely on the surface dimensions of the primary lesions encountered. This seems to ignore the fact that a number of recently reported clinical studies have convincingly demonstrated that the depth of tumor invasion is closely associated with the development of cervical metastases and, eventually, with prognosis (3-5). It is widely held that the risk of cervical metastasis is site specific (ie, the incidence of metastatic disease varies with the site in the head and neck) (6). For example, the frequency
neoplasms,
neoplasms,
#{149}
neoplasms, 26.373,
and
Larynx,
30.373
Cervical
article
the perspectives radiologist.
received
School PA
January
is one
in a small
of surgeons,
of Medicine,
15213.
19, 1990; series
clinicians,
Received
accepted of solicited
and
Eye
DecemJanuary state-of-
patholo-
Nodes’ of metastatic disease in patients with carcinoma of the glottic larynx is unusually low (50%) (9,10). Unfortunately, this approach depreciates the fact that all patients with invasive squamous cell carcinoma of the head and neck are at some finite risk for the development of metastatic disease. Be that as it may, patients with metastatic disease remain potentially curable, and every effort should be made to identify and treat patients with cervical lymph node metastasis. The essential element in the initial evaluation of the patient with squamous cell carcinoma of the head and neck has been the physical examination. Assessment of cervical metastatic disease is based on the clinician’s ability to detect with palpation the presence of metastatic deposits. Unfortunately, the ability of the physician to detect cervical metastasis is limited. Microscopic deposits may escape detection. It is estimated, for instance, that it takes 1 billion malignant cells to produce a mass of 1 cm3 (ii). Even then, the ability of the clinician to detect these lesions is based in part on the muscular development of the neck, the specific location of the lymph node, and the experience of the examiner. Unfortunately, other methods previously employed to detect cervical metastases have been only partially successful and have not achieved widespread use. This includes the use of ultrasound and radionuclide scans. Contrast lymphangiography has been suggested for the study of the cervical lymph system (12), but this technique has not been widely embraced. Lymphangiography is an invasive procedure that is tedious at best and is not technically possible in many cases due to difficulties in the cannulization of the cervical lymph vessels, which may be tiny, fragile, or 607
tortuous. To date, a monoclonal antibody that is useful in the detection of squamous cell carcinoma of the head and neck has not been identified. Clinical assessment of the status of the cervical lymph nodes is maccurate. The rate of false-negative diagnoses has been variously reported. Bocca et al (13) treated 407 patients with squamous carcinoma of the supraglottic larynx. Almost all patients underwent bilateral cervical lymphadenectomy (either functional or classic radical neck dissection). In the group of patients judged to have no evidence of metastatic disease preoperatively, 12% were found to have histologic evidence of disease. Conversely, a false-positive rate of 35% was encountered, in that 22 of 62 patients judged to have palpable nodes demonstrated no histologic evidence of disease. Nason et al (14) reviewed the data on 209 patients treated for squamous cell carcinoma of the floor of the mouth, in whom surgery was the single curative modality. In 17% of the patients with early-stage disease, histologic evidence of involvement of the lymph nodes was discovered during elective neck dissection. Another 10% of patients who did not undergo elective neck dissection subsequently developed recurrence in the cervical lymph nodes. In this series of over 200 patients, the frequency of falsenegative clinical diagnosis was 29%. In another study, Snyderman et al (15) retrospectively reviewed the data on a group of patients with squamous cell carcinoma of the supraglottic larynx. Twenty percent of the patients with no palpable adenopathy were found to have metastatic disease at histologic assessment of neck dissection specimens. The prognostic importance of cervical metastasis has been demonstrated by Whitehurst and Droulias (16), who reviewed the charts of 150 patients with squamous cell carcinoma of the oral tongue treated with surgery alone. The overall survival rate was 67.9%. The authors noted that partial glossectomy was effective for control of local disease in 92.7% of cases. When cervical lymph node involvement was noted, the survival rate dropped to 31%. In an effort to further refine the understanding of the prognostic importance of metastatic disease, Johnson et al (17) reviewed the records of 349 patients treated with radical neck dissection for squamous cell carcinoma of the head and neck. The patients were evaluated according to 608
#{149} Radiology
histologic findings in the neck dissection specimen. Three groups were identified: patients with no evidence of cervical metastasis, patients with cervical metastasis limited to the lymph nodes, and patients with extracapsular spread of tumor. In 129 patients (37%) there was no evidence of cervical metastasis. Of the 203 remaining patients, 1 18 (58%) demonstrated extracapsular spread of tumor associated with cervical metastasis. The frequency of extracapsular spread in patients with stage III tumors and positive node findings was 50%. Extracapsular spread was found in 66% of node-positive patients with stage IV disease. The histologic demonstration of extracapsular spread had a statistically significant impact on survival (17). Patients with cervical metastasis limited to the lymph nodes had a survival rate similar to that of patients with no evidence of cervical metastasis. In contrast, the 2-year survival rate of patients who had evidence of extracapsular spread was reduced by approximately 50%. In a select group of patients treated with surgery plus postoperative radiation therapy, 105 patients were available for evaluation. This included 44 patients with no extracapsular spread, of whom 32 (73%) survived 2 years or longer with no evidence of recurrent disease. In contrast, only 25 of 61 patients (49%) with extracapsular spread showed no evidence of recurrent disease (P < .03). When these patients were evaluated according to stage, there was no statistically significant difference in survival rate between patients with stage III disease and patients with stage IV disease. These data seem to support the argument that the histologic status of the cervical lymph nodes is a more subtle prognostic indicator than is the stage assigned in the TNM system as it currently exists. Other factors that influence the prognostic importance of cervical adenopathy include bilateral involvement and fixation of nodes. Stell (18) reviewed the data on 1,726 previously untreated patients with squamous cell carcinoma of the head and neck. Bilateral mobile cervical adenopathy (N2c in the TNM system) was noted in 64 patients (3.7%). In this group, the i-year survival rate was 44%. In contrast, 128 patients (7.4% of the entire group) had unilateral fixed adenopathy; 30% of those patients survived 1 year. Of the 24 patients in whom bilateral adenopathy involved one or more fixed nodes, only one patient (4%) survived 1 year. These
data emphasize the prognostic significance of bilateral adenopathy, while serving to reinforce the observation that fixed adenopathy is associated with extremely poor prognosis. It should be noted that “fixation” is a clinical term, which does not necessarily correlate with the histologic findings. The majority of fixed nodes have massive soft-tissue invasion. Clinically speaking, fixation may have a variety of interpretationsfixation to the sternomastoid muscle, skin fixation, involvement of the great vessels, and even fixation of the skull base and transverse processes of the cervical vertebrae. The uniform definition of nodal fixation presented such a problem for physicians that the term “fixed” was deleted from the staging system in the 1978 revision of the American Joint Committee on Cancer manual (2). When discussing therapy for patients with squamous cell carcinoma that originated on the mucosal surfaces of the upper aerodigestive tract, one must consider the potential for cervical metastases. Carcinomas in some sites, such as the glottic larynx, the lip, and the sinonasal tract, rarely metastasize (
T. Johnson,
MD
A Surgeon
Looks
at
S
Squamous cell carcinoma is the most commonly encountered malignant neoplasm of the upper aerodigestive tract. The most important factor that influences therapeutic outcome is the development of metastasis to the cervical lymph nodes. Traditionally, assessment and staging have been based on clinical evaluation. Studies of clinicopathologic correlation have demonstrated that both the sensitivity and the specificity of the clinical examination findings are unsatisfactorily low in that false-negative rates may be 15%-25% while false-positive rates may be similarly high. The clinician is caught in the position of having to overtreat many patients to avoid undertreating a few. The rapid advances in imaging technology introduced in the past decade have greatly affected our ability to identify cervical metastatic disease. With improved technology and increased experience, patients can be better characterized individually according to the status of the cervical lymph nodes so that therapeutic intervention can be appropriately designed.
Index
terms:
20.373,
Head
Lymphatic Mouth,
system, neoplasms, 263.373 272.373
neoplasms,
neck
276.375
262.373
#{149} Nasopharynx,
Pharynx,
#{149}
#{149} State-of-art
262.373
271.373
neoplasms,
#{149} Tonsils,
neoplasms, reviews
#{149} Tongue,
neoplasms,
262.373
Radiology
1990;
‘From
and ber 23.
Ear
8, 1989; Address EDITOR’S
the-art review gists in areas CRSNA
175:607-610
of Otolaryngology,
the Department
Hospital
of Pittsburgh,
revision reprint
requested requests
NOTE-Dr
articles of interest 1990
Johnson
intended to the
Suite
500,
December to the author. is a surgeon.
to capture practicing
203
QUAMOUS
University
of Pittsburgh
Lothrop
St. Pittsburgh,
29; revision His
Lymph
cell carcinoma is the most common malignant neoplasm encountered on the mucosal surfaces of the upper aerodigestive tract. This epithelial lesion is closely associated with the abuse of tobacco and alcohol products (1). Cellular atypia and dysplasia commonly exist for some period before invasive carcinoma is recognized. Invasion of the submucosa and adjacent soft tissues progresses at a variable rate and is commonly associated with the development of cervical metastases to the draining lymph nodes. While it is commonly stated that the presence of cervical lymph node metastases is associated with a statistically significant negative effect on prognosis, there does not currently exist a precise way to identify and quantitate microscopic cervical metastatic disease. The TNM staging system of the American Joint Committee on Cancer has been developed as a working tool for clinicians (2). Unfortunately, even the most current TNM staging system is based largely on the surface dimensions of the primary lesions encountered. This seems to ignore the fact that a number of recently reported clinical studies have convincingly demonstrated that the depth of tumor invasion is closely associated with the development of cervical metastases and, eventually, with prognosis (3-5). It is widely held that the risk of cervical metastasis is site specific (ie, the incidence of metastatic disease varies with the site in the head and neck) (6). For example, the frequency
neoplasms,
neoplasms,
#{149}
neoplasms, 26.373,
and
Larynx,
30.373
Cervical
article
the perspectives radiologist.
received
School PA
January
is one
in a small
of surgeons,
of Medicine,
15213.
19, 1990; series
clinicians,
Received
accepted of solicited
and
Eye
DecemJanuary state-of-
patholo-
Nodes’ of metastatic disease in patients with carcinoma of the glottic larynx is unusually low (50%) (9,10). Unfortunately, this approach depreciates the fact that all patients with invasive squamous cell carcinoma of the head and neck are at some finite risk for the development of metastatic disease. Be that as it may, patients with metastatic disease remain potentially curable, and every effort should be made to identify and treat patients with cervical lymph node metastasis. The essential element in the initial evaluation of the patient with squamous cell carcinoma of the head and neck has been the physical examination. Assessment of cervical metastatic disease is based on the clinician’s ability to detect with palpation the presence of metastatic deposits. Unfortunately, the ability of the physician to detect cervical metastasis is limited. Microscopic deposits may escape detection. It is estimated, for instance, that it takes 1 billion malignant cells to produce a mass of 1 cm3 (ii). Even then, the ability of the clinician to detect these lesions is based in part on the muscular development of the neck, the specific location of the lymph node, and the experience of the examiner. Unfortunately, other methods previously employed to detect cervical metastases have been only partially successful and have not achieved widespread use. This includes the use of ultrasound and radionuclide scans. Contrast lymphangiography has been suggested for the study of the cervical lymph system (12), but this technique has not been widely embraced. Lymphangiography is an invasive procedure that is tedious at best and is not technically possible in many cases due to difficulties in the cannulization of the cervical lymph vessels, which may be tiny, fragile, or 607
tortuous. To date, a monoclonal antibody that is useful in the detection of squamous cell carcinoma of the head and neck has not been identified. Clinical assessment of the status of the cervical lymph nodes is maccurate. The rate of false-negative diagnoses has been variously reported. Bocca et al (13) treated 407 patients with squamous carcinoma of the supraglottic larynx. Almost all patients underwent bilateral cervical lymphadenectomy (either functional or classic radical neck dissection). In the group of patients judged to have no evidence of metastatic disease preoperatively, 12% were found to have histologic evidence of disease. Conversely, a false-positive rate of 35% was encountered, in that 22 of 62 patients judged to have palpable nodes demonstrated no histologic evidence of disease. Nason et al (14) reviewed the data on 209 patients treated for squamous cell carcinoma of the floor of the mouth, in whom surgery was the single curative modality. In 17% of the patients with early-stage disease, histologic evidence of involvement of the lymph nodes was discovered during elective neck dissection. Another 10% of patients who did not undergo elective neck dissection subsequently developed recurrence in the cervical lymph nodes. In this series of over 200 patients, the frequency of falsenegative clinical diagnosis was 29%. In another study, Snyderman et al (15) retrospectively reviewed the data on a group of patients with squamous cell carcinoma of the supraglottic larynx. Twenty percent of the patients with no palpable adenopathy were found to have metastatic disease at histologic assessment of neck dissection specimens. The prognostic importance of cervical metastasis has been demonstrated by Whitehurst and Droulias (16), who reviewed the charts of 150 patients with squamous cell carcinoma of the oral tongue treated with surgery alone. The overall survival rate was 67.9%. The authors noted that partial glossectomy was effective for control of local disease in 92.7% of cases. When cervical lymph node involvement was noted, the survival rate dropped to 31%. In an effort to further refine the understanding of the prognostic importance of metastatic disease, Johnson et al (17) reviewed the records of 349 patients treated with radical neck dissection for squamous cell carcinoma of the head and neck. The patients were evaluated according to 608
#{149} Radiology
histologic findings in the neck dissection specimen. Three groups were identified: patients with no evidence of cervical metastasis, patients with cervical metastasis limited to the lymph nodes, and patients with extracapsular spread of tumor. In 129 patients (37%) there was no evidence of cervical metastasis. Of the 203 remaining patients, 1 18 (58%) demonstrated extracapsular spread of tumor associated with cervical metastasis. The frequency of extracapsular spread in patients with stage III tumors and positive node findings was 50%. Extracapsular spread was found in 66% of node-positive patients with stage IV disease. The histologic demonstration of extracapsular spread had a statistically significant impact on survival (17). Patients with cervical metastasis limited to the lymph nodes had a survival rate similar to that of patients with no evidence of cervical metastasis. In contrast, the 2-year survival rate of patients who had evidence of extracapsular spread was reduced by approximately 50%. In a select group of patients treated with surgery plus postoperative radiation therapy, 105 patients were available for evaluation. This included 44 patients with no extracapsular spread, of whom 32 (73%) survived 2 years or longer with no evidence of recurrent disease. In contrast, only 25 of 61 patients (49%) with extracapsular spread showed no evidence of recurrent disease (P < .03). When these patients were evaluated according to stage, there was no statistically significant difference in survival rate between patients with stage III disease and patients with stage IV disease. These data seem to support the argument that the histologic status of the cervical lymph nodes is a more subtle prognostic indicator than is the stage assigned in the TNM system as it currently exists. Other factors that influence the prognostic importance of cervical adenopathy include bilateral involvement and fixation of nodes. Stell (18) reviewed the data on 1,726 previously untreated patients with squamous cell carcinoma of the head and neck. Bilateral mobile cervical adenopathy (N2c in the TNM system) was noted in 64 patients (3.7%). In this group, the i-year survival rate was 44%. In contrast, 128 patients (7.4% of the entire group) had unilateral fixed adenopathy; 30% of those patients survived 1 year. Of the 24 patients in whom bilateral adenopathy involved one or more fixed nodes, only one patient (4%) survived 1 year. These
data emphasize the prognostic significance of bilateral adenopathy, while serving to reinforce the observation that fixed adenopathy is associated with extremely poor prognosis. It should be noted that “fixation” is a clinical term, which does not necessarily correlate with the histologic findings. The majority of fixed nodes have massive soft-tissue invasion. Clinically speaking, fixation may have a variety of interpretationsfixation to the sternomastoid muscle, skin fixation, involvement of the great vessels, and even fixation of the skull base and transverse processes of the cervical vertebrae. The uniform definition of nodal fixation presented such a problem for physicians that the term “fixed” was deleted from the staging system in the 1978 revision of the American Joint Committee on Cancer manual (2). When discussing therapy for patients with squamous cell carcinoma that originated on the mucosal surfaces of the upper aerodigestive tract, one must consider the potential for cervical metastases. Carcinomas in some sites, such as the glottic larynx, the lip, and the sinonasal tract, rarely metastasize (
