We performed a retrospective study of 859 patients with papillary thyroid cancer, who had received their primary treatment at the Mayo Clinic during the period 1946 through 1970. The maximal follow-up was 39 years. All but 2 patients underwent a thyroid operation; 319 (37%) had metastatic cervical nodes. Of the 800 patients without distant metastatic lesions on initial examination who underwent a potentially curative surgical procedure, postoperatively 7% had nodal metastatic lesions, 6% had a local tumor recurrence, and 5% had a distant metastatic lesion. In patients who had intrathyroidal tumors initially, postoperative local recurrences or distant metastatic lesions resulted in a 10-year cancer mortality of 17 and 41%, respectively; in those with extrathyroidal tumors, postoperative recurrences were associated with significantly higher death rates. Death from thyroid cancer was highly associated with the following factors: age more than 50 years, male sex, tumor size, tumor grade, initial extent of disease, and absence of Hashimoto's disease. Earlier studies of Mayo patients treated between 1926 and 1960 described no deaths due to thyroid cancer in patients with occult tumors (1.5 cm or less). Four such patients were identified among our 859 patients; all had been examined and treated after 1961. To date, 56 (6.5%) of the 859 patients have died as a result of papillary thyroid cancer. In this study, in which 16% of patients underwent total thyroidectomy and 3% had radioiodine ablation, the overall mortality observed at 30 years was only 3% above that expected.

Undifferentiated (anaplastic) thyroid carcinoma is a highly aggressive neoplasm which may simulate microscopically a variety of soft tissue sarcomas. The three major subtypes are spindle cell, giant cell, and squamoid. Electron microscopic examination and immunocytochemical stain for cytokeratin are the most useful special techniques to document the epithelial nature of the tumor. Undifferentiated small-cell carcinoma is a term to be discarded. Nearly all tumors so designated in the past are malignant lymphomas, small-cell variants of medullary carcinomas, or poorly differentiated (insular) carcinomas. Poorly differentiated (insular) carcinoma is a thyroid malignant tumor characterized by the formation of solid nests and small follicles, a monotonous growth of small cells of follicular derivation, mitotic activity, necrosis, and peritheliomatous formation. Immunocytochemically, it is negative for calcitonin and positive for thyroglobulin. It is a clinically aggressive neoplasm, which metastasizes to both regional lymph nodes and distant organs. It is probably analogous to the tumor described by Langhans in 1907 as "wuchernde Struma."

Sputum cytologic testing has been applied in the screening of high-risk individuals for presymptomatic lung cancer. This same screening procedure sometimes identifies patients with upper respiratory tract cancers and thereby may permit earlier treatment. Patients enrolled in the Mayo Lung Project undergo sputum cytologic and chest roentgenographic screening at four-month intervals and are compared with matched controls who are not intensively screened. Experience to date indicates an incidence rate of approximately 1 per 1,000 per year of cancer in the upper respiratory and alimentary passages among males more than 45 years old who are heavy cigarette smokers. This compares with a rate of approximately 4 per 1,000 per year of lung cancer. Recognition of early cancer of the upper respiratory tract is an additional benefit of screening for lung cancer. Since cigarette smoking represents an etiologic agent common to both upper and lower respiratory tract cancers, tumors should be searched for in both sites in this high-risk population.

During the past 10 years, 54 patients, all men, were found to have roentgenographically occult lung cancer. The mean age was 61 years (range 45 to 76 years). All patients had abnormal findings on sputum cytologic study (carcinoma in 41 patients and squamous cell atypia in 13). The cancer was localized by bronchoscopy in all patients (range one to five examinations, mean 1.5). Seventy-five percent of the tumors were localized within 169 days of the abnormal sputum cytologic examination. Pulmonary resection for cure was performed in all patients: lobectomy in 38, pneumonectomy in nine, and bilobectomy in seven. Operative mortality was 5.6% (three patients). Fifty-eight cancers were resected, all squamous cell carcinomas (two had a component of large cell cancer). Tumor TNM classification (AJC) was TIS N0 M0 in 19 patients, T1 N0 M0 in 25, T1 N1 M0 in five, T2 N1 M0 in four, and T3 N0 M0 in one. Overall 5 year actuarial survival rate (lung cancer deaths only) was 90%. Five-year survival rate for the 44 patients with TIS N0 M0 and T1 N0 M0 neoplasms was 91%. Currently, 21 patients have died, but only 10 of lung cancer. Subsequent additional lung cancer developed in 12 patients (22%). Eleven of these patients had a second primary squamous lung cancer, six of which again were occult. We conclude that patients with occult lung cancer have a strong likelihood of long-term survival if treated early. Close surveillance is indicated because of the high incidence of a second primary lung cancer.

Mesothelioma, even of the pleura alone, is a ubiquitous pathological designation. The diffuse variety is associated with an ominous prognosis. The localized mesothelioma generally has been assumed to be benign. A review of tumors from 60 patients with localized pleural mesothelioma seems to justify separation into benign (52 patients) and malignant (eight patients) variants. Histologic criteria are used primarily to make this division. No single clinical feature allowed preoperative predictability concerning benignity or malignancy, although extrathoracic osteoarthropathy was seen only with benign lesions (20 percent), usually those greater than 7 cm. Follow-up periods of as long as 24 years revealed recurrent tumor in only two of the 58 patients with benign lesions and revealed a survival curve identical to that of the general population. All of the patients with the malignant variety had recurrence or metastasis, and all but one were dead within 2 years of the initial operation. One patient died of tumor complications after 9 years. More aggressive local resection is indicated for the malignant variant.

Of 53 patients who had hyperparathyroidism assocated with multiple parathyroid gland enlargement, 39 (74%) had primary hyperparathyroidism without clinical or laboratory evidence of associated endocrine gland dysfunction, 2 had documented familial primary hyperparathyroidism, and 12 had hyperparathyroidism as part of the multiple endocrine neoplasia syndrome. When last studied, 31 of the 39 patients with nonfamilial hyperparathyroidism had normal serum calcium levels, 3 had permanent hypoparathyroidism, 2 had recurrent hyperparathyroidism, and 3 were lost to follow-up. The two patients with familial hyperparathyroidism were treated by removal only of enlarged parathyroid glands, and in each, hyperparathyroidism recurred. Five patients with multiple endocrine neoplasia, type 1, were treated by removal only of enlarged parathyroid glands, and hyperparathyroidism recurred in four. Four patients with multiple endocrine neoplasia, type 1, were treated by removal of three or more parathyroid glands, and there were no instances of recurrent hyperparathyroidism. In one patient, permanent hypoparathyroidism developed. Three patients with multiple endocrine neoplasia syndrome, type 2, had total parathyroidectomies as a part of thyroidectomy for medullary thyroid carcinoma. In each patient, permanent hypoparathyroidism developed. When primary hyperparathyroidism occurs in the absence of a definite history of polyendocrine or familial disease, only the glands that are definitely enlarged should be removed, and normal-appearing glands should be tagged rather than risk the possibility of permanent hypoparathyroidism that may attend routine subtotal parathyroid gland excision.

The 40-year incidence trends of bronchogenic carcinoma in Olmsted County, Minnesota, are presented and analyzed. The incidence in men has risen rapidly with each decade. During the last decade this increase was due to an increase of the rate among men over 65, rates in men under 65 appearing to have plateaued. The incidence in women increased for the first time in the decade 1965 to 1974. During the period 1935 through 1974, rates for all cell types increased in men, with that for squamous cell carcinoma increasing most. In women the recent overall increase was due mainly to an increase of adenocarcinoma, which has been the predominant cell type in women throughout. Among all cases together the 5-year survivorship was 11%, which comprised 24% for squamous cell carcinoma, 11% for large cell carcinoma, 12% for adenocarcinoma, and 0 for small cell carcinoma.

A pulsating lavage irrigation system was employed during diagnostic bronchoscopy in patients with suspected bronchogenic carcinoma to facilitate collection of specimens for cytologic examination. No untoward effects were observed, and good quality samples of exfoliated cells were recovered. This method also might have application in the management of patients with suppurative lung disease or retained secretions and in situations in which a large volume of lavage solution is desired.

The Mayo Lung Project has been established to assess the effectiveness of close surveillance in reducing the death rate from bronchogenic carcinoma. Candidates for study are high-risk patients (men, aged 45 or older, smoking at least one pack of cigarettes daily) with life expectancy of at least 5 years. A lung-health questionnaire, chest roentgenogram, and 3-day pooled specimen of sputum provide the basic information. Candidates with positive test results receive appropriate treatment. Those whose initial data are negative are randomized into either a close-surveillance (participant) group or a control group. Participants are restudied every 4 months. Controls receive whatever medical care they ordinarily would, but no regular restudy except annual follow-up by letter. This routine will extend over 5 years or more, and tracing 5 to 10 years further. Lung-cancer death rates in the two groups will be compared. Preliminarily, it appears such programs can be incorporated into private group practices.

To evaluate the trends relative to incidence of Hashimoto's thyroiditis and Graves' disease from 1935 through 1967, records of all diagnosed cases occurring in residents of Rochester, Minnesota, were identified through the facilities of the Rochester-Olmsted County epidemiologic program. During those 33 yr, 246 cases of Hashimoto's thyroiditis and 256 cases of Graves' disease were diagnosed in the subject population. The average annual incidence rates per 100,000 for Hashimoto's thyroiditis for females increased from 6.5 (1935–1944) to 21.4 (1945–1954) to 67.0 (1955–1964) to 69.0 (1965–1967). There was no indication that the incidence of Graves' disease changed in any significant or consistent pattern during the 33 yr. The average annual rate for females was 36.8/100,000/yr for all age groups; the rate was highest among women 20–39 yr old.

Dockerty, Malcolm B.; Parkhill, M.; Dahlin, David C.; Woolner, Lewis B.; Soule, Edward H.; Harrison, Edgar G. Jr.

To evaluate the trend of thyroid cancer from 1935–65, inclusive, reports of all diagnosed cases occurring in bona fide residents of Olmsted County, Minnesota, were identified and reviewed. There were 46 acceptable cases of thyroid cancer (group 1). The average annual incidence rates (age-adjusted to the 1950 U.S. white population) increased from 1.7 to 3.1 to 3.6/100,000 population in 1935–44, 1945–54, and 1955–65. The increase, most marked between the first and second decades, is not statistically significant. There has probably been an upward trend, but it is believed to reflect an increasing awareness of the problem and improved diagnostic capabilities for thyroid cancer in the community. The age range was 11–91 years and the median age was 50 years. The female-to-male ratio was 3:1. In addition, 21 patients (18 females and 3 males) had “occult,” grade 1, papillary carcinoma of less than 1.5 cm in diameter without evidence of regional metastasis (group 2). These lesions are considered innocuous and relatively benign in the absence of clinical evidence of metastasis to cervical nodes. In 16 of the 21 cases, the diagnosis was made between 1955 and 1965. If these occult lesions were included, the age-adjusted incidence rates/100,000 population increased significantly from 2.2 to 3.7 to 6.1, respectively, in the 3 periods. The increased recognition of these occult lesions, particularly since 1955, is believed to account for this upward trend. If the increased exposure to diagnostic irradiation, radioactive fallout, and other environmental radiation has significantly affected the incidence of the thyroid cancer in adults, our survey procedure is not sufficiently sensitive to detect the effect. If the Olmsted County data were extrapolated to the population of the United States, based on the group-1 cases during 1955–65, we would expect about 7,000 persons in the country to develop clinically identifiable thyroid cancer each year.