Use of Chest Radiography in the Initial Evaluation of Patients With Localized Melanoma FREE

THE MAJORITY of patients with melanoma present with local disease (American Joint Committee on Cancer [AJCC] stages I and II) with a 5-year survival rate of approximately 80%.^{1 - 2} These data indicate that 20% of patients with stages I and II disease have occult distant metastases at the time of diagnosis. In an attempt to detect these occult lesions, an initial staging evaluation is often performed on patients newly diagnosed as having melanoma. While a detailed medical history taking and physical examination are essential for this purpose, there are few data to support the use of screening studies such as chest x-ray films,^{3 - 7} computed tomographic (CT) scans,^{8 - 9} liver-spleen scans,^{3 - 6 ,10 - 12} bone scans,^{3 - 6 ,10 - 11} and brain scans^{3 - 6 ,10 - 12} in asymptomatic patients. Despite this, the initial workup for patients with localized melanoma often includes multiple diagnostic studies, most frequently chest radiography. This may be due to the ease of ordering and performing the test and because the lung is the most common visceral site for metastases.^{7 ,13} We performed a retrospective analysis to evaluate the use of chest x-ray films in the initial screening evaluation of patients with localized melanoma.

The University of Michigan melanoma database in Ann Arbor was retrospectively reviewed for 1982 to 1993 to evaluate the initial staging workup and follow-up of 1032 consecutive asymptomatic patients presenting with in situ and stages I and II melanoma. The AJCC stages I and II represent local disease with Breslow depth of 1.50 mm or less and more than 1.50 mm, respectively. Stage III represents regional disease and stage IV, distant disease.¹

Standard workup of all patients included a medical history taking and physical examination. All pathologic specimens were reviewed at the University of Michigan by dermatopathologists and evaluated for level of invasion according to Breslow depth and Clark level when possible. Patients were classified according to the AJCC staging system based on findings of the clinicopathologic evaluation. Chest radiography was performed in the majority of patients (85%). Hematologic studies, such as complete blood cell counts and liver function tests, were not routinely performed and then only at the discretion of the attending physician.

Of the patients studied, 876 (85%) of 1032 had initial staging chest radiography performed. In the other 156 patients, patient refusal, pregnancy, or lack of a radiography order at the discretion of the attending physician accounted for the lack of test results. A chest x-ray film was considered initial if performed within 6 months of melanoma diagnosis.

A suspicious chest x-ray film was defined by abnormalities or findings that were suggestive of, or could not be distinguished from, metastatic melanoma by the radiologist. The most common findings considered suspicious included multiple or solitary nodules, an opacity, pleural thickening, a prominent hilum, or an interstitial pattern of disease. Follow-up of suspicious findings involved obtaining a previous chest x-ray film for comparison or ordering a second chest x-ray film or a chest CT scan. Repeated x-ray films or CT scans were obtained on an average within 4 months of the initial study (range, 1-33 months).

Long-term follow-up data were available in 685 (66%) of all patients (Table 1). Lack of all available data was attributable to return of patients to referring physicians and loss of patients to follow-up, in general.

The study population consisted of 53% male and 47% female patients with an average age of 50 years (range, 1.5-98 years). Nearly all patients were white (99%) (Table 2). The majority of tumors (57%) were of the superficial spreading type and occurred most commonly on the trunk. Six hundred nine patients (59%) were classified as having stage I disease and 303 (29%) as having stage II. Seventy-three (7%) represented cases of melanoma in situ and 47 (5%) could not be staged because the depth of invasion could not be determined accurately because of tumor extending to the deep margins following a shave biopsy or misorientation of the biopsy specimen (Table 3). Forty-six (5%) of the 876 patients suitable for study analysis had melanoma in situ, 543 (62%) had stage I disease, 218 (25%) had stage II disease (Breslow depth, 1.5-4.0 mm), 40 (5%) had stage II disease (Breslow depth, >4.0 mm), and 29 (3%) had unknown thickness invasive melanoma.

One hundred thirty (15%) of the 876 patients had suspicious findings on the chest x-ray film, necessitating further evaluation. Additional evaluation included a comparison with previous chest x-ray films, a second chest x-ray film, or a chest CT scan. In 35 patients, a combination of these follow-up studies or multiple repeated tests were necessary to definitively confirm the nature of the abnormal findings. In 128 of these 130 patients, the follow-up evaluation found the pulmonary abnormalities to have resolved, remained stable, or clearly represented benign disease, thus confirming the absence of lung metastases. In 1 patient no radiographic follow-up evaluation was documented, but clinically the patient remained free of disease several years after the suspicious findings on the chest x-ray film. In only 1 patient did repeated studies suggest the presence of lung metastasis. This individual was a 45-year-old white man with a melanoma, Breslow depth of 2.94 mm and Clark level IV, on his back. The initial chest x-ray film revealed a solitary nodule. Repeated chest x-ray film and CT scan indicated enlargement of the nodule and hilar adenopathy. Analysis of a lung biopsy specimen confirmed the nodule to be metastatic melanoma.

Silent pulmonary metastasis was found in only 1 (0.1%) of 876 patients. No metastatic lung disease was detected in cases of melanoma in situ and stage I disease, while lung metastasis was found in 1 (0.4%) of 258 patients with stage II disease. Overall, the frequency of false-positive results was 15%.

Of the group with long-term follow-up data available, 30 developed lung metastases and 2 developed a primary lung cancer. Metastases were detected between 4 months and 9 years after initial diagnosis (average, 2.8 years). Seventeen cases of lung metastases were found in patients with initial negative findings on chest x-ray films and 5 were found in patients with initial suspicious findings on chest x-ray films.

Melanoma may disseminate to any organ system. The most common sites of dissemination in decreasing frequency are the skin, lymph nodes, lungs, liver, brain, bone, and gastrointestinal tract.^{14 - 16} Clearly, a certain number of patients initially diagnosed as having localized melanoma will develop distant metastases. Tumor thickness measured in millimeters remains the strongest predictor of the risk of metastasis. ^{17 - 28} In a collaborative study, Balch et al² reported the average 5-year survival rate for patients with stages I and II melanoma to be 79%. This suggested that at least 20% of patients with localized melanoma have occult distant metastases at the time of initial diagnosis. Based on these results, patients diagnosed as having primary localized melanoma often undergo exhaustive evaluations in search of metastatic disease.

In general, imaging studies are used in the initial evaluation of patients with melanoma for the purpose of detecting and diagnosing metastatic disease. The demonstration of distant metastases will not only affect prognosis but also significantly alter treatment. Evaluation of the lung by chest radiography remains one of the most frequently ordered studies for staging patients with melanoma. This may be because the lung is one of the most common visceral sites of spread and a chest radiograph is relatively inexpensive, low risk, widely available, and easy to perform.

Several studies have evaluated the use of various diagnostic tests in the initial evaluation of patients with primary cutaneous melanoma. Khansur et al⁴ evaluated 72 patients with localized melanoma using various combinations of chest x-ray film, radionuclide scans of the brain, bone, and liver, head CT scan, and upper gastrointestinal tract series. No metastatic disease was detected in the 72 patients with clinically localized disease; however, 9 false-positive test results, including 2 false-positive chest x-ray films, were found. Ardizzoni et al⁵ performed initial staging chest radiography on 116 asymptomatic patients diagnosed as having melanoma; 93 had only local disease. Results of all studies in patients with localized disease were normal. Ninety patients with primary localized melanoma were studied by Zartman et al⁶ using chest radiography in addition to other blood and imaging studies. All patients were asymptomatic and had unremarkable findings on physical examination. Findings from all chest x-ray films were within normal limits. In addition, 209 patients are reported in the literature with localized melanoma initially evaluated with a myriad of brain, bone, and liver or spleen scans. ^{10 ,12 ,29} None detected unsuspected metastasis. The false-positive rate was 16% in 1 study.²⁹ Collectively, these studies do not support the use of chest radiography, radionuclide scans, or CT scans in the initial evaluation of patients with localized melanoma.

When melanoma metastasizes to the lungs, it usually appears as multiple small foci.^{30 - 32} Since the resolution of plain films is usually limited to lesions of 1 cm or greater,³³ these tests have limited capacity to detect metastases smaller than this. Computed tomography of the chest has been shown to be superior to chest radiography in the detection of metastatic disease in high-risk patients.^{33 - 34} However, in low-risk patients its use is minimal. Buzaid et al⁸ studied the role of CT scans in the staging evaluation of 151 patients with melanoma AJCC stages I through III. Of 124 patients with localized disease, only 1 had unsuspected metastasis. This patient had a scalp melanoma of 6.6 mm in Breslow depth with a clinically undetected cervical node found on a CT scan of the head. No chest CT scans demonstrated silent pulmonary metastasis. However, false-positive results were found in 17% of cases.

The retrospective nature of this study precludes us from commenting with certainty on the available long-term data. Patients evaluated in a multidisciplinary clinic in a tertiary care hospital are often seen once and returned to referring physicians without follow-up readily available. Patients may also fail to follow-up once the melanoma has been removed. According to our data, the majority of cases in which lung metastases were eventually detected occurred in patients with initial negative chest x-ray films. However, of those with initial negative chest x-ray films 2.3% developed lung metastases and of those with initial suspicious false-positive chest x-ray films 3.8% developed lung metastases. This suggests that lung metastases occur more frequently in patients with suspicious false-positive radiographs. It is possible that these metastases were present at initial diagnosis and were not detected because of limitations of the nature, performance, and reading of chest x-ray films. Lack of availability of initial chest x-ray films for review in these cases prevents definitive conclusions. Given the limited nature of our follow-up data in terms of patient numbers and length, the ultimate use of these data is unclear. A lengthy prospective study would eliminate this difficulty.

Our results, based on large patient numbers, support the notion that initial screening chest radiography screening in asymptomatic patients presenting with stage I and intermediate thickness (1.5- to 4.0-mm) stage II melanoma is highly unlikely to detect silent pulmonary metastasis, thus suggesting that it may be neither useful nor cost-effective.^{4 - 6 ,35} Additionally, the high false-positive rate of 15% led to costly investigations and contributed to an increase in the patient anxiety's level. Of greatest importance is a thorough medical history taking and physical examination. Conclusions based on retrospective analysis are useful to define prospective studies for definitive conclusions.

Accepted for publication November 24, 1997.

Reprints: Timothy M. Johnson, MD, Department of Dermatology, University of Michigan, 1910 Taubman Center, Box 0314, Ann Arbor, MI 48109-0314 (e-mail: timjohn@umich.edu).