Prospective evaluation of unilateral adrenal masses in patients with operable non-small-celliung cancer

Transcription

1 Prospective evaluation of unilateral adrenal masses in patients with operable non-small-celliung cancer Impact of magnetic resonance imaging We designed a prospective study to evaluate the accuracy of magnetic resonance imaging in distinguishing a benign from a malignant adrenal mass in patients with otherwise operable non-small-ceu lung cancer. Methods: Potentially operable non-smail-ceu lung cancer was prospectively staged. If a unilateral adrenal mass was found by computed tomographic scanning, respiratory compensated and cardiac gated thin section magnetic resonance imaging of the adrenal glands was done. One radiologist interpreted the magnetic resonance imaging scan blinded and, on the basis of the relative signal strengths of the Tl- and T2-weighted images, judged whether the adrenal mass was benign or malignant. The patients then underwent a percutaneous needle biopsy of the adrenal mass, if technicady feasible. If the result of the needle biopsy was nondiagnostic or if the biopsy was not feasible, an adrenalectomy through a posterior approach was performed. Results: Twenty-seven patients with a unilateral adrenal mass entered the study-ll men and 16 women whose ages ranged from 42 to 75 years (median 58 years). Four patients had epidermoid and 23 adenocarcinoma of the lung. The clinical locoregional stage was I in 9, II in 1, IlIA in 16, and IIIB in 1. Twenty-five completed the magnetic resonance imaging procedure. Five adrenal masses (19 %) were metastatic non-small-ceu lung cancer (adenocarcinoma = 4, epidermoid = 1~ 22 masses (81 %) were benign (adenoma = 20, hyperplasia = 2). There were no significant differences in age, sex, histologic type, or locoregional stage between those with a benign versus a malignant mass. However, the malignant masses were significantly larger (3.8 ± 1.9 cm; range 2.5 to 7.1; median 3.1) than the benign masses (2.0 ± 0.4 cm, range 1.2 to 2.8; median 2.0) (p < 0.001). Among those having magnetic resonance imaging (n = 25), the technique correctly predicted a malignant mass in the four patients with a histologicauy confirmed metastasis from non-small-ceu lung cancer. However, among the 21 histoiogicauy benign masses, the magnetic resonance imaging was interpreted as benign in 5, malignant in 14, and indeterminate in 2. Therefore, although the faise-negative rate was 0 %, the false-positive rate was 67%. Conclusion: Most adrenal masses in patients with otherwise operable non-small-cell lung cancer are benign. Currently available magnetic resonance imaging methods cannot replace biopsy. (J THORAC CARDIOVASC 1994;107:584-9) SURG Michael Burt, MD, PhD,a Robert T. Heelan, MDb (by invitation), Daniel Coit, MDC (by invitation), Patricia M. McCormack, MD,a Manjit S. Bains, MD,a Nael Martini, MD,a Valerie Rusch, MD,a and Robert J. Ginsberg, MD,a New York, N.Y From the Thoracic Service, Department of Surgery,' the Department of Radiology,b and the Gastric and Mixed Tumor Service, Department of Surgery,C Memorial Sloan-Kettering Cancer Center, New York, N.Y. Read at the Seventy-third Annual Meeting of The American Association for Thoracic Surgery, Chicago, Ill., April 25-28, Address for reprints: Michael Burt, MD, PhD, Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY Copyright 1994 by Mosby-Year Book, Inc /94 $ /6/50934 Adrenal metastases from non-small-cell lung cancer (NSCLC) are common and, in autopsy series, have been reported to occur in 18% to 42% of patients. 1-5 Most authors would agree, therefore, that computed tomographic (CT) scanning of the chest and upper part of the abdomen to include the entire liver and both adrenal glands is indicated in staging of NSCLC.6-12 The difficulty arises when a patient with potentially operable disease is discovered to have a unilaterally enlarged adrenal gland. Data concerning the prevalence 584

2 The Journal of Thoracic and Volume 107, Number 2 Burt et al of adrenal metastases from NSCLC in patients with otherwise operable NSCLC are sparse. In a prospective study Oliver and associates!3 found that 8% of 296 patients with operable NSCLC had a unilaterally enlarged adrenal gland by CT scanning. Among those 23 patients, 6 (26%) had metastatic deposits according to needle biopsy (n = 5) or follow up by CT scan (n = I). At our institution, we found that in 246 patients with otherwise operable NSCLC, 10 patients (4%) had a unilaterally enlarged adrenal gland according to CT scan. All patients underwent biopsy and 4 (40%) were found to have metastases to the adrenal glands.!4 From these two studies, it appears that approximately 4% to 8% of patients with otherwise operable NSCLC will have a unilaterally enlarged adrenal gland, approximately 26% to 40% of which will be cancerous. However, the inverse is much more important: when a patient has an operable NSCLC and a unilateral adrenal mass, the mass should not be considered malignant without further evaluation, because 60% to 74% will ultimately prove to be benign. Recent advances in magnetic resonance imaging (MRI) have led some investigators to suggest that this modality can accurately predict whether an adrenal mass in patients with NSCLC is a metastatic focus or benign. Early studies with 0.35 to 0.5 T superconducting magnets suggested that MRI could distinguish metastatic from benign lesions. ls - Is As more data accumulated with this lower strength magnet, investigators cautioned against relying solely on MRI!9 and recommended biopsy when accurate histologic diagnosis was crucia1. 2o With the development of a more powerful magnet (1.5 T), investigators have again tried to develop MRI criteria to predict whether an adrenal mass is benign or malignant. 21, 22 With the data from our previous prospective study demonstrating that the majority of unilateral adrenal masses in patients with otherwise operable NSCLC were benign,!4 we decided to study the ability of MRI to predict whether an adrenal mass in this group of patients was benign or malignant. Patients and methods With the approval of our institutional review board, we evaluatedall patients with potentially operable NSCLC and a unilaterally enlarged adrenal gland discovered by routine CT scanning of the chest and upper part of the abdomen (to include the adrenal glands). All patients had CT scanning or MRI of the brain and radionuclide bone scanning to rule out other possible sites of metastatic disease. This approach allowed us to stage and evaluate otherwise operable NSCLC accompanied by a unilateral adrenal mass. All patients then underwent MRI scanning of the adrenal glands. Thin-section (5 mm slice), respiratory compensated, cardiac gated MRI of the adrenal glands was performed on a 1.5 T General Electric Signa System (General Electric Com- pany, Fairfield, Conn.). All patients had Tl-weighted axial scans with 192 phase encoding steps obtained with two excitations, as well as T2-weighted axial scans obtained with 128 phase encoding steps with four excitations. Patients also had a third acquisition, typically a Tl-weighted coronal scan. Occasionally, sagittal Tl-weighted scans were obtained. One radiologist (R.T.H.) interpreted the MRI blinded to the histologic result of needle or excisional biopsy. Diagnosis was based on the relative signal strengths of the enlarged adrenal on Tl- and T2-weighted pulsing sequences. On the Tl-weighted scans the signal from the enlarged adrenal gland was compared with the signal from the normal side. On the T2-weighted scans, the signal from the enlarged adrenal gland was compared with that of the liver parenchyma and the normal adrenal gland. If the signal from the abnormal gland was equivalent to that of the normal gland on Tl- and T2-weighted scans and equal to or less intense than normal liver parenchyma on T2-weighted scans, a diagnosis of benign adrenal adenoma or hyperplasia was made. If the abnormal area had more intense signal than the opposite gland (Tl- and T2-weighted scans) or the liver parenchyma (T2-weighted scans), a diagnosis of malignancy was made. The patients then underwent CT-guided percutaneous needle aspiration biopsy of the enlarged adrenal gland, if technically feasible. If the results were nondiagnostic, a second attempt with needle aspiration was done in those patients in whom the radiologist deemed the procedure possible. If no definitive diagnosis was obtained by percutaneous needle aspiration biopsy, or if needle biopsy was not technically feasible, the patient underwent an adrenalectomy through a posterior approach. Differences in frequency data were calculated by Fisher's exact test. Comparisons of means were by Student's t test. Survival was calculated by the method by Kaplan and Meier. Differences in survival were determined by log rank analysis. Significance was defined as p < Results Twenty-seven patients with a unilateral adrenal mass and otherwise operable NSCLC were entered in the study. There were 11 men and 16 women with a median age of 58 years (range 42 to 75 years). Four patients had squamous cell carcinoma and 23 had adenocarcinoma. Among the 27 patients in the study, percutaneous needle aspiration biopsy was deemed not feasible in 7 (26%) because of anatomic constraints and was nondiagnostic in 10 (37%). Of these 17 patients, 16 underwent resection of the adrenal mass through a posterior approach with no complication. One patient with a clinically staged T1 NO adenocarcinoma refused adrenalectomy and underwent lobectomy and radiation therapy for a pathologic T2 Nl adenocarcinoma. He is alive and well 38 months after operation with no change in his 2 cm right adrenal mass by CT scan; the mass is therefore considered to be a benign adrenal adenoma. Of the 16 patients who underwent adrenalectomy, 15 had masses that proved to be benign and 1 malignant. The 1 patient with a metastatic adrenal mass diagnosed by resection had a percutaneous transhepatic needle aspira-

3 5 8 6 Burt et al. The Journal of Thoracic and February 1994 Table I. Characteristics of 27 patients with potentially operable NSCLC and a unilateral adrenal mass All patients (n = 27) Age (yr) Median 58 Range Sex Male 11 (41%) Female 16 (59%) Histology Adenocarcinoma 23 (85%) Squamous cell carcinoma 4 (15%) Side of mass Left 17 (63%) Right 10 (37%) Size of mass (em) Range Median 2.0 Mean ± SD 2.2 ± 1.1 Clinical local stage I 9 (33%) II 1(4%) IlIA 16 (59%) I1IB 1(4%) Benign Metastatic (n = 22) (n = 5) p Value NS (36%) 3 (60%) (64%) 2 (40%) 19 (86%) 4 (80%) (14%) I (20%) 14 (64%) 3 (60%) (36%) 2 (40%) ± ± 1.9 < (32%) 2 (40%) 1(5%) (59%) 3 (60%) I (5%) 0 SD, Standard deviation; NS, not significant. tion biopsy that was initially believed to show benign results. However, when reviewed in light of the resected specimen, what were thought to be benign adrenocortical cells were hepatocytes, and therefore nondiagnostic. Ten patients (37%) had a diagnostic percutaneous needle aspiration biopsy. Of these, 4 had metastatic adrenal masses and 6 had benign masses. Therefore 5 of 27 (19%) adrenal masses in patients with otherwise operable NSCLC were metastases. Of these 5, 4 were adenocarcinoma and 1 was squamous cell carcinoma. Of the 22 benign adrenal masses, 20 (91 % ) were adenomas and 2 (9%) were hyperplasia. The demographic characteristics for all 27 patients are listed in Table I. No significant differences were identified in age, sex, histologic type, side of the mass, or locoregional clinical stage between those with a benign versus a malignant adrenal mass. The size of the adrenal mass was significantly greater in patients with a metastasis to the adrenal gland than patients with a benign adrenal mass (p < 0.001). Of the 22 benign adrenal masses, 7 (32%) were larger than 2 cm. Of the 5 adrenal metastases, no lesion was 2 cm or smaller. Of all adrenal masses (n = 27), 15 were 2 cm or smaller and none were malignant. Of the 12 masses larger than 2 cm, 5 (42%) were malignant and 7 (58%) were benign. All 27 patients underwent MRI scanning of the adrenals, but 2 patients (7%) were unable to complete the study because of claustrophobia. Therefore, MRI data were available for analysis in 25 patients. Of these 25 patients, 4 were considered to have malignant and 21 benign adrenal lesions. MRI scanning correctly predicted a malignant adrenal mass in the 4 patients with a histologically confirmed metastasis from NSCLC. However, MRI was interpreted as benign in 5, as malignant or probably malignant in 14, and as indeterminate in 2 of the 21 histologically benign adrenal masses. From these data the following are calculated {positive [ +] defines metastatic and negative [-] defines benign adrenal masses}: Discussion... MRI(+) 4 SensItlVlty = Biopsy( +) = 4 = 100%.. MRI(-) 5 Speclficlty = B' () = 21 = 24% IOPSY -.. MRI(+) 14 False-posItlve rate = B' () = 21 = 67% IOPSY -. MRI(-) 0 False-negative rate = Biopsy( +) 4 = 0% Adrenal metastases from NSCLC are frequent, ranging from 18% to 42% in autopsy series. 1 - S In patients with otherwise operable lung cancer, unilateral adrenal masses will be found in from 4% to 8% when carefully evaluated by CT scanning. lo, 11 Therefore, most authors recommend a CT scan of the chest and upper part of the

4 The Journal of Thoracic and Volume 107, Number 2 Burt et al Proportion Surviving 1~--~~ , Ben ign (n-28) -+ Metastatic (n-9) p-o ol l------~~ l l------~o o Time (mos) Fig. 1. Survival of 9 patients with a unilateral adrenal metastasis and 28 with a benign adrenal mass. Patients were in operable condition but for the adrenal mass. The survival of those with benign disease was significantly longer than that of those with metastatic disease. abdomen to include both adrenal glands in the evaluation of patients with potentially operable NSCLC. 6 - I2 The study of Silvestri and associates 23 suggested that CT scanning of the adrenal glands was not necessary when staging newly diagnosed patients with bronchogenic carcinoma if initial clinical findings (weight loss, skeletal pain, neurologic examination, hoarseness, hepatomegaly, soft-tissue mass, alkaline phosphatase, or hematocrit) were normal. This study is flawed because it relies only on CT criteria to diagnose an abnormal adrenal gland as metastatic, not on histologic examination. Even studies comparing adrenal metastases by autopsy to CT criteria have demonstrated that CT scanning is inaccurate in determining malignancy, unless there is evidence of disease elsewhere or the adrenal metastasis is large. 24 As this study and our previous study have shown, patients with potentially operable NSCLC must have histologic confirmation of a unilateral adrenal mass, because the majority are benign. On the other hand, the possibility that an adrenal mass could be a metastasis should be considered even in patients with clinical evidence of locoregional stage I disease. One of four patients with adrenal metastases in our previous studyi4 and two offive in the present study were patients with clinical stage I locoregional disease. The importance of the etiology of unilateral adrenal masses in determining prognosis cannot be overemphasized. To evaluate survival more effectively in patients with unilateral benign and metastatic adrenal masses, we combined the survival data from this study (n = 27) with our previous study (n = 10).1 4 In this combined data set, 9 patients had metastatic and 28 benign adrenal masses. Of the 9 patients with adrenal metastases, 6 were treated with cisplatin-based chemotherapy alone and 3 were treated with preoperative cisplatin-based chemotherapy and then underwent pulmonary and adrenal resection. Of the 28 patients with benign adrenal masses, 25 underwent pulmonary resection (5 after cisplatin-based chemotherapy for IlIA disease), 2 received radiation therapy for unresectable tumor and 1 received preoperative chemotherapy but died of sepsis before surgery. The relative frequencies oflocoregional stage were not changed by the addition of the 10 patients from the previous study. The overall survival for those patients with metastatic adrenal masses was significantly less than that of those with benign masses (Fig. 1). We agree with other authors 6 - I2 that patients with potentially operable NSCLC should have CT scanning of the upper part of the abdomen when the chest is being scanned. If during that evaluation a unilateral adrenal mass is discovered as the only evidence of extra thoracic disease, the question arises as to how best to determine whether it is a benign or metastatic lesion. There was early enthusiasm for MRI of the adrenal gland to differentiate benign from metastatic lesions. I5 - I8 When more powerful 1.5 T scanners became available, investigators again began to evaluate their ability to discriminate between benign and metastatic adrenal masses. 2I - 22 In this study, using the best currently available MRI scanning techniques, we were not able to predict consistently whether a unilateral adrenal mass was benign or malignant. Although the sensitivity of MRI to predict a metastatic lesion in this study was 100% and the false-

5 5 8 8 Burt et al. The Journal of Thoracic and February 1994 negative rate 0%, the specificity of 24% and false-positive rate of 67% preclude accepting MRI as a routine method for determining whether an adrenal mass is benign or malignant. Perhaps newer methods, such as in vivo chemical shift MRI, might be able to increase the specificity and decrease the false positivity as indicated by Mitchell and associates. 25 We are currently evaluating this in our population of patients with operable NSCLC. For patients with otherwise operable NSCLC and a unilateral adrenal mass, we recommend percutaneous needle aspiration biopsy. If results of the percutaneous needle aspiration biopsy are nondiagnostic, then the choice must be made to resect the locoregional chest tumor and observe the adrenal mass or to subject the patient to an adrenalectomy, through a posterior approach. If the adrenal mass is 2 cm or smaller, then observation is a viable option, because no adrenal mass 2 cm or smaller in our small series was found to be malignant. However, if the adrenal mass is greater than 2 cm, we would recommend a second attempt at needle biopsy. If the results are nondiagnostic again, adrenalectomy should be advised since 42% of adrenal masses larger than 2 cm were malignant in our series. REFERENCES 1. Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma: analysis of 1000 autopsied cases. Cancer 1950;3: Engleman RM, McNamara WL. Bronchogenic carcinoma: a statistical review of two hundred twenty-four autopsies. J THORAC SURG 1954;27: Matthews MJ. Problems in morphology and behavior of bronchopulmonary malignant disease. In: Israel L, Chahinian AL, eds. Lung cancer: natural history, prognosis, and therapy. San Diego: Academic Press, 1976: Ochsner A, DeBakey M. Carcinoma of the lung. Arch Surg 1941;42: Glomset DA. The incidence of malignant tumors to the adrenals. Am J Cancer 1938;32: Chapman GS, Kumar D, Redmond JIll, Munderloh SH, Gandara DR. Upper abdominal computerized tomography scanning in staging non-small cell lung carcinoma. Cancer 1984;54: Grant D, Edwards D, Goldstraw P. Computed tomography of the brain, chest, and abdomen in the preoperative assessment of non-small cell lung cancer. Thorax 1988;43: Salvatierra A, Baamonde C, Llamas JM, Cruz F, Lopez Pujol J. Extrathoracic staging of bronchogenic carcinoma. Chest 1990;97: Whittlesey D. Prospective computed tomographic scanning in the staging of bronchogenic cancer. J THORAC CARDIO VASC SURG 1988;95: Pagani JJ. Non-small cell lung carcinoma adrenal metastases: computed tomography and percutaneous needle biopsy in their diagnosis. Cancer 1984;53: Nielsen ME, Heaston DK, Dunnick NR, Korobkin M. Preoperative CT evaluation of adrenal gland in non-small cell bronchogenic carcinoma. AJR Am J Roentgenol 1982; 139: Sandler MA, Pearlberg JL, Madrazo BL, Gitschlag KF, Gross SC. Computed tomographic evaluation of the adrenal gland in the preoperative assessment of bronchogenic carcinoma. Radiology 1982;145: Oliver TW Jr, Bernardino ME, Miller JI, Mansour K, Greene D, David W A. Isolated adrenal masses in nonsmall-cell bronchogenic carcinoma. Radiology 1984;153: Ettinghausen SE, Burt ME. Prospective evaluation of unilateral adrenal masses in patients with operable non-smallcell lung cancer. J Clin Oncol1991;9: Reinig JW, Doppman JL, Dwyer AJ, Frank J. MRI of indeterminate adrenal masses. AJR Am J Roentgenol 1986;147: Reinig JW, Doppman JL, Dwyer AJ, Johnson AR, Knop RH. Adrenal masses differentiated by MR. Radiology 1986;158: Glazer GM, Woolsey EJ, Borrello J, et al. Adrenal tissue characterization using MR imaging. Radiology 1986;158: Chang A, GlazerHS, LeeJKT, LingD, Heiken JP.Adrenal gland: MR imaging. Radiology 1987;163: Glazer GM. MR imaging of the liver, kidneys, and adrenal glands. Radiology 1988;166: Chezma JL, Robbins SM, Nelson RC, Steinberg HV, Torres WE, Bernardino ME. Adrenal masses: characterization with T-1 weighted MR imaging. Radiology 1988; 166: Kier R, McCarthy S. MR characterization of adrenal masses: field strength and pulse sequence considerations. Radiology 1989;171 : Baker ME, Blinder R, Spritzer C, Leight GS, Herfken RJ, Dunnick NR. MR evaluation of adrenal masses at 1.5 T. AJR Am J Roentgenol1989;153: Silvestri GA, Lenz JE, Harper SN, Morse RA, Colice GL. The relationship of clinical findings to CT scan evidence of adrenal gland metastases in the staging of bronchogenic carcinoma. Chest 1992; 102: Allard P, Yankaskas BC, Fletcher RH, Parker LA, Halvorsen RA Jr. Sensitivity and specificity of computed tomography for the detection of adrenal metastatic lesions among 91 autopsied lung cancer patients. Cancer 1990; 66: MitchellDG,CrovelloM,MatteucciT,PetersenRO,Miettinen MM. Benign adrenocortical masses: diagnosis with chemical shift MR imaging. Radiology 1992;185: Discussion Dr. Joseph I. Miller (Atlanta, Ga.). The experience at Emory has been roughly the same and the remarks that I would make are mainly by my colleague, Dr. Michael Bernido, in the department of radiology at Emory.

6 The Journal of Thoracic and Volume 107, Number 2 Burt et al We agree that MRI is of very little use in determining benignancy or malignancy in terms of unilateral adrenal masses. The Emory experience has been updated, and in 1989 there were 37 patients with unilateral adrenal masses in otherwise operable lung cancer. In that group we did both Tl- and T2-weighted images and found only a 21% correlation with a T2-weighted image and a 32% correlation with a Tl-weighted image. The false-positive rate, as you have reported, was between 70% and 80%, depending on the method used. In the German literature it is now reported that by gallenium nuclear MRI a 96% correlation can be made histologically. We have not had any experience with that. Have you had any experience with gallenium nuclear MRI? Your fine-needle aspiration rate is extremely low, with 16 of your 27 patients undergoing open adrenalectomy. That seems a very high proportion of patients undergoing adrenalectomy. I would think that with either one your fine-needle aspiration specificity should be at least 85% to 90% in obtaining adrenal tissue on the first pass, and if not, then on a second attempt. In our experience with 37 patients, we only took three to adrenalectomy, and in each of those patients we used an ipsilateral transdiaphragmatic approach. As it happened the lesion was on the same side. In two of those it was a benign adenoma and in one it was a metastatic carcinoma. We did an adrenalectomy and a lobectomy in that one patient, which was otherwise a Tl lesion, and that patient is alive 5 years later. Dr. Burt. With regard to new MRI modalities, our radiologists and others are evaluating chemical shift (fat suppression) MRI. In preliminary work it seems to be more accurate than standard MRI techniques, but of course there will be a group of patients with indeterminate lesions. I agree completely with your comments regarding needle biopsy. Our early experience was a learning curve. Our cytopathologists labeled the initial aspiration biopsy results as nondiagnostic unless they saw abundant benign adrenocortical cells. After we gained experience, if our cytopathologists observed abundant benign adrenocortical cells, they called the tumor a benign adrenal lesion. I agree that a definitive diagnosis should be made by needle aspiration biopsy in 80% of patients. Dr. Mark B. Orringer (Ann Arbor, Mich.). I would like to add some additional information that perhaps would be of use to the members of the Association. When Dr. Gary Glazer was the head of our chest CT imaging unit at Michigan (he is now chairman of radiology at Stanford), he was instrumental in developing some of the basic principles regarding the use of CT scanning in the evaluation of patients with lung cancer; for example, mediastinal lymph nodes greater than 1 cm in size on the CT scan are abnormal and justify the term mediastinal adenopathy. He also pointed out in his studies of our patients with lung cancer undergoing staging with CT scan that this study demonstrates significant abdominal findings that ultimately affect therapy in up to 15% of patients. One of these findings is the discovery of a solitary adrenal mass in which the differentiation of benign disease from a metastasis is essential. At the University of Michigan, one of the most useful tools in resolving this dilemma noninvasively is the radionucleotide NP-59 scan. In the patient with the typical 1 to 3 cm round solitary adrenal lesion on CT scan, if the NP-59 scan is positive, this is presumptive evidence of a benign adrenal lesion. A preliminary report from our radiology department demonstrated excellent correlation between the NP-59 scan findings and the results of CT-guided adrenal aspiration needle biopsy of the nodule. To my knowledge, in subsequent follow-up of our patients, our radiologists have not been wrong in diagnosing a benign adrenal adenoma with their NP-59 scan. In summary, I submit that when the NP-59 scan diagnoses a benign adrenal adenoma after the CT scan has demonstrated an adrenal nodule, it is unnecessary to proceed with more invasive procedures to establish a tissue diagnosis. We have certainly never submitted our patients with lung carcinoma to a preliminary adrenalectomy before proceeding with a pulmonary resection. Dr. Burt. Dr. Glazer from your institution and Dr. Doppman from the National Cancer Institute pioneered MRI of the adrenal glands. Regarding the NP-59 scan and its utility in differentiating benign from malignant adrenal masses, early data have been encouraging. Again, there remains a group of patients with indeterminate lesions by NP-59 scanning. Because documentation of histologic type is critical in this group of patients, we still recommend histologic or cytologic confirmation. Dr. L. Penfield Faber Chicago, Ill.}. Dr. Burt, I would like you to comment on resecting the adrenal gland when metastatic disease is identified. Several papers have discussed resecting solitary metastatic disease of the brain. Why wouldn't resection of solitary metastatic disease of the adrenal gland be just as efficacious? You have two patients with stage I NSCLC and solitary metastatic disease in the adrenal gland. I would appreciate your comment on whether these patients should be considered for resection. Second, should the patient in whom a single metastatic adrenal metastasis develops 1, 2, or 3 years after successful resection of the primary lung cancer be considered for adrenalectomy? Dr. Burt. Dr. Faber, there are three papers describing 12 patients with otherwise operable lung cancer who had resection of an adrenal metastasis. Pooling those 12 patients yields a 40% 5-year survival. However, because we do not know the denominator, I am reluctant to make any recommendations. For the patient with a unilaterally enlarged adrenal gland, which is found to be metastatic, and an operable lung cancer, we currently are evaluating combined modality therapy. Any patient who has an otherwise operable NSCLC and a single site of disease outside the chest receives three cycles of mitomycin, vinblastine sulfate (Velban), and cisplatin and then undergoes resection of both the metastasis and the locoregional tumor. The patient then receives two more cycles of chemotherapy. We have four patients currently receiving that protocol, and it is too soon to make any further comments. Dr. Richard A. Rasmussen (Grand Rapids, Mich.). I had not planned to comment but I will since you mentioned metastasis from lung cancer. We have followed up three cases of lung cancer for at least 15 years, with no recurrence after excision of the secondary cancer to the brain. It is extremely important, in my opinion, to carefully evaluate each patient with lung cancer as to the general physical and mental status before exclusion from surgical consideration by an experienced surgeon, even though metastases have been found. I point out that the first pneumonectomy done by Dr. Evarts A. Graham in 1933 had lymph node involvement. The patient died in 1962 without evidence of cancer, as documented in Ackerman's Surgical Pathology by Juan Rosai, MD (7th ed., St. Louis: CV Mosby, 1989).