Our study was designed to determine if the chest radiographic appearance at presentation of the different cell types of lung cancer has changed in the last 30 to 40 years. We wished to reexamine this issue because of a reported increased frequency of adenocarcinoma in both sexes and a higher lung cancer incidence in women since prior reports were published. We do not possess any significant number of original chest radiographs of lung cancer patients from the 1950s and 1960s. Therefore, we compared our series of newly diagnosed lung cancer cases with a widely referenced report from the Mayo Clinic compiled in that time period. Our patient population included 33.6% women, in contrast to 13.7% in the older Mayo Clinic series. The American Cancer Society estimates that 44% of new lung cancer cases in 1996 will occur in women/ Furthermore, in 1992 (the last year of our study), the same source reported that 37% of lung cancer deaths were in women.’ Therefore, our numbers are in accord with current national trends. In contrast to the earlier Mayo Clinic study with 44% squamous cell, our series had adenocarcinoma as the most prevalent cell type at 36%. Squamous cell carcinoma now comprises 28%. Large cell carcinoma (6%) was less frequent than in the Mayo Clinic series (16%), whereas small cell percentage was roughly similar (25% at Marshfield vs 19% at Mayo). Our numbers are comparable to multiple recent reports.’ We believe our series is representative of lung cancer cell type in the United States at the current time. When cell types are analyzed by gender, men show a relative increased frequency of adenocarcinoma compared with historic controls. In women, the increased incidence of all lung cancer cases has been accompanied by a relative increase in squamous cell and small cell carcinoma. In view of the marked increased number of total lung cancer cases in women, there would still be an absolute increase in the number of adenocarcinoma cases diagnosed each year despite its relative decrease in proportion to squamous cell and small cell carcinoma. The cell type showing the most dramatic radiographic change from past series is adenocarcinoma.
There was a marked decrease in frequency of presentation of adenocarcinoma as a peripheral (parenchymal, apical) mass: from 72% at Mayo Clinic to 49% at Marshfield Clinic. Correspondingly, the number presenting as a central mass only (hilar or perihilar) was increased from 6% at Mayo Clinic to 14% at Marshfield Clinic, also a significant change. This latter group had central mass as a solitary abnormality on chest radiograph and most likely represented adenocarcinoma of central origin. Therefore, compared with the prior series, our data suggest a significant change in adenocarcinoma presentation with less peripheral and more central primary tumors. We also showed an increased frequency of central mass plus for adenocarcinoma. However, this group included both the central primary tumors and peripheral tumors with central nodal metastases. It is likely that this reflects both more advanced disease (N1 and N2 nodes) and the increase in tumors of central origin. We are not the first to note a changing radiographic appearance of adenocarcinoma. Woodring and Stell-ing reviewed 100 cases of adenocarcinoma of the lung diagnosed between 1976 and 1982. They found 52% presenting as peripheral mass, with or without hilar involvement. This is comparable to our figure of 49%. They report 13% with hilar mass as the only abnormality, compared to 14% in our study and 6% at Mayo Clinic. Squamous cell carcinoma showed a significant change in a direction opposite to adenocarcinoma: our series had an increased percentage of squamous cell presenting as peripheral masses (43% at Marshfield vs 31% at Mayo).
There was no important difference in squamous cell solitary central masses (17% Marshfield vs 13% Mayo). The increased number in the central mass plus group at Marshfield appears to again represent central nodal metastases. The apparent sites of origin (peripheral vs central) for small cell and large cell carcinoma were unchanged compared with the earlier study. Small cell carcinoma continues to have the highest relative frequency (77%) of central mass at presentation (both primary tumors and lymph nodes). All cell types had an increased frequency of pleural effusion (14 to 30%) compared with the Mayo Clinic data (2 to 5%). Our numbers are similar to those in a series of 417 cases of lung cancer reported in 1966: Cohen and Hossain reviewed chest radiographs at the time of “first hospital admission” and 15% of the chest films had pleural effusion. We did not attempt to determine how many of the effusions in our series were malignant, as there are multiple mechanisms for pleural effusion related to lung cancer (eg, pleural malignancy, atelectasis, lymphatic obstruction). Textbook and review articles continue to state that adenocarcinoma is primarily a peripheral tumor. Diagnosis of Diseases of the Chest by Fraser et al states that “adenocarcinoma usually develops in the periphery/ but does note “some evidence . . . that a central location may be more common than was formerly recognized.” According to a review of lung cancer in Radiologic Clinics of North America2 in 1990, “adenocarcinomas present as a peripheral mass 60 to 70% of the time.” However, this author also notes “recent studies have reported an increased frequency of central involvement.” The Textbook of Respiratory Medicine cites a figure of 71% for adenocarcinoma presenting as parenchymal lung mass. The 1994 MKSAP in the Subspecialty of Pulmonary Medicine and Critical Care4 states that adenocarcinomas have a peripheral location in 65% of cases. These figures are in marked contrast to the 49% we observed in our series. The four sources given above rely on old data in reference to radiographic presentation of cell type. Our study represents a series of lung cancers at presentation in the 1990s and reflects the changing patient demographics and relative incidence of cell types in the last 30 years. We have shown a statistically significant change in the appearance of adenocarcinoma and squamous cell carcinoma compared with the previous era. We also grouped our own cases according to radiographic sites of origin. Peripheral origin included parenchymal and apical masses, whereas central origin consisted of both central masses (including lymph nodes) and obstructive findings without peripheral masses. Our analysis showed no statistically significant difference between adenocarcinoma and squamous cell carcinoma for peripheral vs central origin in the Marshfield Clinic series.
There are a number of potential problems in comparing our current series with older published data. First, the patient selection is different. We analyzed consecutive newly diagnosed lung cancer cases at all stages. Mayo Clinic limited their patients to those undergoing thoracotomy (curative, palliative, or for biopsy) or treated with radiotherapy. We do not know how many patients had a diagnosis by other methods and were not included in their series. Therefore, we almost certainly included more patients with advanced stage disease, as reflected in our higher incidence of pleural effusions and central adenopathy (included in central mass plus group). Second, Mayo Clinic relied principally on stereoscopic PA radiographics, whereas we had both PA and lateral views in most cases. This should increase our accuracy in interpretation. Third, our pathologists used the 1981 World Health Organization system to classify cell types, whereas Mayo Clinic used their own system. Fourth, we had our radiologists read a current series of actual chest radiographs that we compared with published historic data. Ideally, we would like to have had our own series of older radiographs for comparison to ensure consistency of methods, but this was not possible. In summary, we compared data from a widely quoted report of lung cancer radiographic findings in the 1950s and 1960s with a contemporary series of radiographs at presentation. We realize the difficulties in making an exact comparison for reasons given above. Nevertheless, we believe our data present a valid picture of lung cancer at time of diagnosis in the current era. Our conclusions are as follows: As reported elsewhere, women now account for approximately one third of new cases. Adenocarcinoma has surpassed squamous cell as the most frequent cell type. Adenocarcinoma had a significantly different pattern of presentation: peripheral tumors (49%) were less frequent, and central masses (46%) were more frequent than noted earlier (72% peripheral and 17% central masses in the Mayo Clinic series). Squamous cell carcinoma had an increased frequency of peripheral origin (43%) compared with the historic controls (31%). More central masses (61% vs 40%) were also present, representing both central primary sites and lymph node metastasis. There was no statistically significant difference in the proportion of adenocarcinomas (49%) and squamous cell cancers (43%) arising as a peripheral mass. Correspondingly, there was no difference in percent of central origin for adenocarcinoma (46%) and squamous cell (52%) in our series. Radiographic appearance of small cell and large cell carcinomas did not change appreciably. Pleural effusion was present in 24% of lung cancers at time of diagnosis, compared with 4% in the older Mayo Clinic series. Textbook and review articles can no longer rely on data from an earlier period in discussing radiographic presentation of lung cancer. As the incidence of lung cancer has risen and relative frequency of adenocarcinoma has increased, the radiographic presentation of both adenocarcinoma and squamous cell carcinoma has shown a statistically significant change.