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Ann Thorac Surg 1996;62:338-341
© 1996 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Lung Cancer Staging: The Value of Ipsilateral Scalene Lymph Node Biopsy Performed at Mediastinoscopy

Department of Surgery, Thoracic Service, Memorial Sloan-Kettering Cancer Center, New York, New York

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. The accurate preoperative staging of lung cancer remains an essential element in its proper treatment. In most centers, N3 disease contraindicates an operative approach, despite the advent of combined modality therapy. Although it is used to confirm palpable supraclavicular disease, routine scalene lymph node biopsy to stage nonpalpable disease has been abandoned.

Methods. From January 1991 to July 1995, 408 cervical mediastinoscopies were performed by a single surgeon for the staging of lung cancer. In those patients eligible for induction therapy, when N2 or N3 disease was strongly suspected or identified, ipsilateral scalene lymph node biopsy was performed through the same cervical incision using the mediastinoscope to reach the scalene fat pad.

Results. Eighty-one patients underwent this additional staging procedure. There was minimal morbidity and no deaths. Of these 81 fully staged patients, primary tumor histology was non-small cell in 95.1%. Thirty-nine patients were staged as N2 after standard mediastinoscopy. Of these, 6 (15.4%) harbored occult nonpalpable supraclavicular lymph node disease as well. Nineteen patients were staged as N3-contralateral after standard mediastinoscopy. Of these, 13 (68.4%) had occult supraclavicular disease as well. Of all 58 patients with superior mediastinal nodal involvement identified by standard mediastinoscopy, 19 (32.8%) also harbored occult scalene lymph node disease, rendering them ineligible for our induction therapy protocols. Scalene positive primary tumors were all centrally located (visualizable by flexible bronchoscopy) (19 of 19) and were uniformly of nonsquamous origin.

Conclusions. We believe that this technique is a valuable extension to standard cervical mediastinoscopy and can be used in N2 or N3 staged patients with central, nonsquamous tumors before considering a combined modality therapeutic approach that includes operation. Through its use, more accurate staging before initiation of therapy and elimination of those patients who may derive no benefit from an aggressive surgical approach may be possible.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Despite the advent of combined modality therapy, the identification of N3 disease (contralateral-mediastinal or supraclavicular lymph node involvement) may contraindicate a surgical approach. Although invaluable in staging the superior mediastinum, standard cervical mediastinoscopy will not routinely evaluate the status of the supraclavicular scalene lymph nodes. Although initially used to confirm palpable supraclavicular disease, the routine use of scalene lymph node biopsy in nonpalpable disease has been abandoned.

In a series of 81 patients undergoing mediastinoscopy, when N2 or N3 disease was strongly suspected or identified and a combined modality approach including operation was being considered, we performed ipsilateral scalene lymph node biopsies through the same cervical incision using the mediastinoscope to reach the scalene fat pad.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
In our clinic, most patients undergo an extensive metastatic survey and mediastinoscopy before definitive treatment planning. Needle biopsy of any palpable supraclavicular abnormalities is performed in the clinic, and if the results are inconclusive, open scalene lymph node biopsy is performed. Only those without evidence of extrathoracic metastasis are staged invasively with cervical mediastinoscopy. For this study, when N2 or N3-contralateral disease was discovered by frozen section at mediastinoscopy or strongly suspected because of lymph node appearance, and a multimodality treatment regimen including surgical resection was being considered, we used the mediastinoscope to obtain ipsilateral scalene lymph node biopsy specimens as well.

Technique
Through a 2- to 3-cm transverse suprasternal incision, sharp dissection in the midline was performed, separating the cervical strap muscles and incising the pretracheal fascia. Digital dissection into the superior mediastinum and a standard cervical mediastinoscopy were then completed [1]. Routinely, biopsy was performed of two ipsilateral mediastinal, one contralateral mediastinal, and the subcarinal nodal stations. Through the same incision, the mediastinoscope was then withdrawn along the anterior tracheal wall to the thoracic inlet. Posterolateral and superior rotation of the mediastinoscope tip behind the ipsilateral carotid sheath and into the supraclavicular fossa was then performed. By gentle dissection of the medial aspect of the scalene fat pad through the mediastinoscope, a single ipsilateral scalene lymph node was teased free and then removed (Fig 1).

View larger version (38K): [in this window] [in a new window]   Fig 1. . Technique of mediastinoscopic scalene lymph node biopsy (see text).

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Morbidity and Mortality
This additional staging procedure was associated with very limited morbidity (one superficial wound infection, one wound hematoma) and no mortality. It required only a few additional minutes of operative time.

Patient and Primary Tumor Characteristics
Of 408 cervical mediastinoscopies performed by a single surgeon (R.J.G.), 81 were in patients (50 male, 31 female) who also underwent mediastinoscopic ipsilateral scalene lymph node biopsies. These patients represented a heterogeneous population with a mean age of 60.5 ± 10.3 years (range, 40 to 82 years). Smoking history was 40.3 ± 30.8 pack-years. Tumor size averaged 5.3 ± 2.9 cm (range, 0.9 to 15 cm). Right-sided primary tumors (70 of 81, 86.4%) were more common than left-sided ones (11 of 81, 13.6%) because left-sided primary tumors with superior mediastinal-paratracheal lymph node involvement were usually deemed inoperable, and therefore were not considered for this additional staging procedure. On final pathologic review, primary tumor histology was non-small cell in 95.1% (adenocarcinoma in 48, squamous in 14, large cell in 12, and poorly differentiated in 3). The remainder were small cell (4 patients).

Results of Combined Staging Procedures
Of the 81 patients undergoing the combined procedure, 23 had negative standard cervical mediastinoscopy results (staged N0-N1). Of these, none had occult scalene lymph node involvement. Fifty-eight of the 81 patients undergoing the combined procedure were ultimately proven to have superior mediastinal nodal involvement (N2, n = 39, N3-contralateral, n = 19) by standard mediastinoscopy. Of these, 19 (32.8%) had occult nonpalpable scalene lymph node metastasis. Of 39 patients identified to have ipsilateral mediastinal nodal involvement (N2), 6 (15.4%) harbored occult ipsilateral scalene nodal disease. Of 19 patients with both ipsilateral (N2) and contralateral (N3) mediastinal nodal involvement documented by standard mediastinoscopy, 13 (68.4%) also harbored occult ipsilateral scalene lymph node metastasis.

Examination of the patterns of lymph node involvement revealed that of the patients with occult scalene lymph node disease, 14 of 19 (73.7%) had upper paratracheal lymph node involvement (level 2) as well. Of the 6 N2-staged patients, 2 exhibited a "skip pattern" (involvement of the ipsilateral scalene fat pad without documented level 2 involvement).

Comparison of Scalene-Negative and Scalene-Positive Patients
We compared the demographics and tumor characteristics of the scalene-negative group (n = 62) and the scalene-positive group (n = 19) (Table 1). There were no statistically significant differences in patient age (p = 0.533), sex predominance (p = 0.141), or primary tumor size (p = 0.657). There were more right-sided primary tumors in the scalene-negative group (p = 0.0187). There were also differences in location and histologic origin of the primary tumors. When one defines central lesions as those within the view of a flexible bronchoscope, the scalene-negative group comprised both central (37 of 62, 59.7%) and peripheral lesions (25 of 62, 40.3%). Conversely, all scalene-positive tumors were central lesions (19 of 19, 100%) (p = 0.001). The histologic origin of scalene-negative tumors was either squamous (14 of 62, 22.6%) or nonsquamous (48 of 62, 77.4%), whereas all scalene-positive tumors were nonsquamous (19 of 19, 100%; p = 0.0001).

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Increasingly, multidisciplinary treatment protocols are being used for the treatment of locally advanced lung cancer. Recent phase II and phase III treatment protocols [2–9] extensively screened potential patients for metastatic disease and used cervical mediastinoscopy to stage the mediastinal lymph nodes. We describe a technique for improving the staging accuracy of standard cervical mediastinoscopy. In our experience, ipsilateral scalene lymph node biopsies performed in the same setting as standard cervical mediastinoscopy can greatly expand the findings of the standard approach and identify those patients with supraclavicular N3 disease.

Excision of the scalene lymph nodes as an aid in diagnosing intrathoracic lesions was reported by Daniels in 1949 [10]. Others adopted this technique widely for the staging of lung cancer [11], as well as for a variety of other malignancies [12, 13]. In an autopsy study, Agliozzo and Reingold [14] documented scalene lymph node metastasis in 18 of 49 patients (37.5%) with lung carcinoma. Of these, 10 lesions (55.6%) were less than 1.0 cm in size and nonpalpable. Others attempted to define the incidence of occult malignancy in nonpalpable scalene lymph nodes. Palumbo and Sharpe [15] reported occult malignancy in 11% of nonpalpable scalene nodes, whereas Brantigan and colleagues [16] found a 23.8% positivity rate. In a recent study, Bernstein and associates [17] detected only a 3.5% incidence. These wide-ranging results may be due to differences in patient population, primary tumor stage, location or histology, and surgical technique. Few studies have assessed both supraclavicular and superior mediastinal nodal involvement. We have shown a strong positive correlation between superior mediastinal and scalene lymph node involvement. All patients with negative standard cervical mediastinoscopy results (staged N0-N1) when evaluated for scalene nodal involvement were found to be free of occult cervical metastasis. Of those with N2 involvement by standard cervical mediastinoscopy, 15.4% harbored nonpalpable microscopic scalene nodal disease. In most cases, N3-contralateral involvement foreboded scalene nodal involvement as well (68.4%).

Primary tumor location and histologic type were important factors. All of the tumors associated with occult scalene nodal disease were centrally located (p = 0.001) and of nonsquamous histology (p = 0.0001). Over 50% of centrally placed, nonsquamous primary tumors with mediastinal involvement demonstrated occult supraclavicular disease. Schatzlein and co-workers [18] also found that central tumor location and nonsquamous histology were important factors in scalene nodal involvement. Hence, the low 3.5% incidence of involvement reported by Bernstein and associates [17] may be due to the preponderence of early-stage tumors in this study (only 10 patients [19.2%] had N2 disease documented by preoperative mediastinoscopy or Chamberlain procedure) and the relatively high percentage of patients (41.1%) with squamous histology. In our series, biopsy was only performed on single scalene lymph nodes. It is possible that one could further increase diagnostic yield by performing bilateral scalene lymph node biopsies or complete scalene fat pad excisions. The higher incidence of positive nodes (23.8%) reported by Brantigan and colleagues [16] may be attributable in part to the routine performance in that study of bilateral open scalene fat pad excisions. They found that in nonpalpable scalene lymph nodes, ipsilateral biopsy detected 73% of occult metastases, whereas contralateral biopsy identified an additional 27%.

Numerous phase II and a few phase III trials have evaluated a multimodality approach that includes operation to treat locally advanced lung cancer [2–9]. A few [5–8] have included IIIb patients (T4 with or without N3-contralateral or N3-scalene) in aggressive neoadjuvant treatment protocols. Some encouraging early results have been demonstrated for both the IIIa and IIIb subgroups, with apparently little survival difference between these groups (3-year survival 27% and 24%, respectively; p = 0.81) [7]. Subset analysis of the IIIb subgroup, however, seems to highlight important prognostic factors. Those staged IIIb on the basis of T4 involvement and who were non-N2 had a more favorable median survival compared with all others in the IIIb subgroup (28 months versus 13 months). Conversely, among 27 patients with N3 disease, none of the patients with N3-contralateral disease were alive at 2 years. The vast majority (89%) of recurrences in this study [7] involved distant metastasis. Our finding that the majority (68.4%) of those with N3-contralateral disease also harbor occult supraclavicular metastasis, and presumably other unidentified sites of disease, may help explain their poor survival. These patients clearly represent a much poorer prognostic group without evidence of benefit from a surgical approach.

Recent results of positron emission tomography staging suggest that this new noninvasive modality may identify those patients with superior mediastinal and supraclavicular involvement [19–21]. Histologic confirmation of these findings should be sought. The combined modalities of standard cervical mediastinoscopy, extended cervical mediastinoscopy [22], and mediastinoscopic scalene lymph node biopsy seem well suited for this role.

When N2 or N3 disease is encountered at mediastinoscopy, scalene lymph node biopsy will identify occult supraclavicular disease in a substantial proportion of patients with central, nonsquamous tumors and may be of value before considering such patients for a combined modality approach that includes operation.

Addendum
Since the presentation of this report, 2 patients have suffered transient bilateral vocal cord paresis, presumably due to intraoperative injury to both recurrent laryngeal nerves during mediastinoscopy and scalene lymph node biopsy. Neither patient required further therapy (eg, tracheostomy), but a 48-hour hospital admission was necessary in each case. Close attention to anatomic details as depicted in Figure 1 is essential.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Presented at the Poster Session of the Thirty-second Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Jan 29–31, 1996.

Address reprint requests to Dr Ginsberg, Department of Surgery, Thoracic Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

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