Serum vitamin E and risk of cancer among Finnish men during a 10-year follow-up.

The association between serum alpha-tocopherol levels and the subsequent incidence of cancer was investigated in a longitudinal study of 21,172 men initially aged 15-99 years in six geographic areas in Finland. The baseline examination was conducted in 1968-1972, and during the follow-up of 6-10 years, 453 cancers were diagnosed. The serum alpha-tocopherol levels were measured from stored serum samples from these men and from 841 male controls, matched for municipality and age, who did not develop cancer during the follow-up. The mean levels of serum alpha-tocopherol among the cancer cases and controls were 8.02 and 8.28 mg/liter, respectively. A high serum alpha-tocopherol level was associated with a reduced risk of cancer. The relative risk of cancer in persons in the two highest (threshold 8.70 mg/liter) quintiles of serum alpha-tocopherol was 0.64 (95 per cent confidence interval = 0.49-0.85) in comparison with those in the three lowest quintiles. The association was strongest for the combined group of cancers unrelated to smoking and varied between subgroups of the study population as well as between different cancers. The association persisted when adjusted for serum cholesterol, serum vitamin A, serum selenium, and various confounding factors. It also persisted when subjects with possible signs of cancer at the time when the blood samples were drawn or with cancers diagnosed during the first two years of follow-up were excluded. These findings agree with the hypothesis that high vitamin E intake protects against cancer.

Sinus histiocytosis with massive lymphadenopathy. A nodal and extranodal proliferation of S-100 protein positive histiocytes?

Four cases of sinus histiocytosis with massive lymphadenopathy (SHML) from Finland were studied clinically and immunohistologically. Three patients had histologically verified extranodal manifestations that often caused the most prominent clinical symptoms. Upper respiratory tract obstruction resulting from SHML lesions was present in two cases, multiple bone lesions in one case, and skin lesions in one case. Clinical remission was observed in all cases, but the course was often protracted. Immunohistochemical studies revealed S-100 protein and alpha-1-antichymotrypsin (ACT) positivity in most large pale cytoplasmic histiocyte-like cells in all cases, whereas lysozyme was not present in these cells. Sinus cells in ordinary sinus histiocytosis were constantly positive for ACT and variably positive for lysozyme and were generally negative for S-100 protein. The large histiocyte-like cells in SHML resemble interdigitating reticulum cells and Langerhans' cells in their S-100 protein positivity but differ from these cells by morphologic characteristics and the presence of alpha-1-antichymotrypsin, a marker constantly seen in ordinary histiocytes. These results suggest that SHML is a proliferative condition of histiocyte-related cells, which share some properties of histiocytes and some of interdigitating reticulum cells. Further studies are necessary to clarify the nature of the peculiar histiocyte-like cells in SHML.

Do the predictions for cancer incidence come true? Experience from Finland.

The observed occurrence of cancer in Finland in 1980 was compared with that predicted by extrapolation of the trends in cancer incidence by site in 1957 to 1968. The predictions had been constructed as 90% confidence intervals. Of the mutually exclusive 33 incidence predictions, 22 (67%) included the observed incidence rate. The incidence rate was successfully predicted for intestinal, pancreatic, and urinary cancers, as well as for lymphomas, whereas incidence forecasts concerning cancers of the lung, breast, and cervix uteri, and melanomas of the skin did not come true. The incidence of male lung cancer did not increase as was expected, breast cancer incidence increased even more than expected, and the decrease in the incidence of cervical cancer was steeper than expected. Because of failure in the population forecast, only 55% of the predictions (90% confidence intervals) for the numbers of new cancer cases included the observed number. For administrative purposes it would be important for the predictions to come true. On the other hand, the successes or failures of the predictions related to specific cancers may be used to study the effect of changes in etiologic factors, diagnostic methods, or the definition of cancer, as well as the effect of mass screening or other intervention measures upon the cancer incidence. Extrapolation as a method of forecasting cancer incidence is adequate as far as the control of random error is concerned when only short-term forecasts, ranging from 5 to 10 years, are needed.

Multiple cancer--an epidemiologic exercise in Finland.

The material of the Finnish Cancer Registry from 1953-79 (279,745 cancer patients, 774,518 person-yr at risk) was analyzed for the occurrence of multiple cancer. There were 5,871 new primary cancers in the series (excluding the first 12 mo from diagnosis of the first cancer). A positive association between cancers with similar etiology could be demonstrated, e.g., between cancers of the lip, larynx, and lung (smoking) and between cancers of the breast and endometrium (hormones, reproductive history). Clustering of different risk factors resulted, e.g., in an excess risk of colon cancer among female breast cancer patients (risk factors in both cancers are prevalent particularly in higher-social classes). Differences in the distribution of the risk factors resulted in risk deficits, e.g., low relative risk of lung cancer among male colon cancer patients (the prevalence of smoking was highest in the lower-social classes and the prevalence of risk factors in colon cancer was highest in the higher-social classes). The risk of leukemia was increased among patients with cancers of the breast, endometrium, and thyroid (possibly due to irradiation). There was a high relative risk of salivary gland cancer among patients with skin cancer other than melanoma or basal cell carcinoma in both sexes. The relative risk of a new primary cancer decreased with increasing age at diagnosis of the first cancer. The length of follow-up was positively associated with the relative risk of many cancers, although this finding was not as consistent as that with age.

Undifferentiated and poorly differentiated carcinoma.

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."

Sauna, dust and migration as risk factors in lung cancer among smoking and non-smoking males in Finland.

To study possible causes of the high lung cancer incidence among Finnish males, the Finnish Cancer Registry and the Cancer Registry of Norway in 1962 performed a population survey covering smoking habits, occupational and residential history and, in Finland, sauna habits. The cohort of 4,475 Finnish men has now been followed up for incidence of lung cancer in 1964-1979. The relative importance of 3 factors--sauna baths, occupational exposure to dust, and migration to urban areas--was studied in different smoking categories. Among smokers of greater than or equal to 25 g/day, takers of frequent saunas (more than once a week) displayed some excess risk (RR 1.7). In smokers an increased risk was also found among those exposed to dust (RR 1.3), and those who had migrated to urban areas (RR 1.8, when compared to native urban population). Dust exposure and migration factors act synergistically with smoking. Migration was the only factor apart from smoking to show a substantial population-attributable risk, which amounted to 10%.

Breast tumors with a solid and uniform carcinoid pattern. Ultrastructural and immunohistochemical study of two cases.

Two cases of breast tumors with a uniform solid carcinoid pattern and argyrophilic dense-core granules were analyzed by immunohistochemistry in order to compare their characteristics with known features of other carcinoid tumors and ordinary breast carcinomas. The tumors were positive for keratin-type intermediate filaments, neuron-specific enolase and alpha-chain of human chorion gonadotropin but negative for vimentin and S-100 protein. Laminin was found only in a rim between tumor cell islands and stroma but not among the cells. It is concluded that these tumors are histologically, ultrastructurally and immunohistochemically similar to other carcinoid tumors. The present results suggest that both breast carcinoids and carcinomas may have a common precursor in the mammary secretory unit.

The cancer registry in cancer control.

The sole justification for a cancer registry is that use is made of its data. The information stored and produced by a cancer registry forms the scientific basis for planning and organization of the treatment and prevention of cancer in the community. Its data can also be used in the testing of various hypotheses concerning the aetiology and biology of malignant neoplasms and it may also give rise to various new hypotheses.

Hodgkin's disease, lymphocytic predominance nodular. Increased risk for subsequent non-Hodgkin's lymphomas.

Fifty-one cases of Hodgkin's disease, of lymphocytic predominance type, nodular subtype (HDLPN) were singled out from three sources: lymph nodes originally diagnosed as malignant lymphoma, nodes suspected of lymphoma and nodes suspected of toxoplasmosis. Two thirds of the 51 patients were men, and the median age was 42 years. The disease was characteristically unilocular and cervical and axillary nodes were most often involved. Local recurrences were common (in 13 cases). Oncological treatment (irradiation, cytostatics, or both) was given to 20 patients, whereas 31 patients remained untreated as the original histological diagnosis was not malignant. Despite the lack of treatment, the prognosis was good. Relative actuarial survival for the whole material was 93% at five years and 80% at ten years. During follow-up, five patients developed a diffuse large-celled non-Hodgkin's lymphoma 4-11 years after the onset of HDLPN. The majority of the subsequent lymphomas cannot be therapy-induced as only one of these patients had previously been treated (irradiated). Transition to other types of Hodgkin's disease was observed only in two cases. It is concluded that HDLPN is a clinicopathological entity with a good prognosis, but that it may sometimes change into a more malignant lymphoma of the Hodgkin's or non-Hodgkin's type.

Risk indicators of breast and cervical cancer on ecologic and individual levels.

Ecologic and individual risk indicators were derived from the population censuses of Finland Cancer Registry. The years covered in the study were 1955-1974 for the ecologic analysis and 1971-1975 for the analysis on individuals. The incidence of both diseases was high in an urban environment with high standard of living. The individuals with high risk of breast cancer were of high socioeconomic status and were well educated, whereas cervical cancer was common among women of low socioeconomic status and with less education. Conceptually similar indicators used on both the ecologic and individual levels characterize different aspects of risk; for example, a woman with a low standard of living in a well-to-do environment has a high risk of cervical cancer.

The desmoid tumor. I. Incidence, sex-, age- and anatomical distribution in the Finnish population.

We have (1) estimated the incidence of desmoid tumor (DT) in the Finnish population, and (2) defined statistically four major age components of the DT with different biological properties. The incidence of the DT, based on admissions to four separate hospitals and on the number of pathological biopsy specimens analyzed at the Central Pathological Laboratory of Helsinki University, is 2.4-4.3 new cases per 10(6) inhabitants per annum. Statistical analysis demonstrated four major age components where the site of the tumor and/or sex of the patient were non-randomly distributed: "juvenile" DT, a predominantly extra-abdominal desmoid tumor of the female sex; "fertile" DT, a nearly exclusively abdominal DT of fertile females; "menopausal" DT, a predominantly abdominal tumor where the sex ratio approaches one:one; and "senescent" DT, where abdominal and extra-abdominal varieties are equally frequently encountered and where the sex ratio of the affected patients is one:one.

Teaching and continuing education in pathology.

Pathology is both a clinical and pre-clinical subject, a bridge between the clinical disciplines and the basic sciences. The teaching of organ pathology should be given to a major extent during the first clinical year, and only part of it should be integrated with the clinical courses, e.g., pediatric pathology and dermatopathology. The knowledge obtained from pathology courses provides a foundation for continuing education throughout the physician's professional life. Continuing education of academic pathologists includes activities of professional societies, following scientific journals, attending congresses and symposia, both national and international, sabbaticals, and shorter visits to other pathological laboratories. Continuing education of hospital pathologists should follow the same lines. In addition, the professional societies and academic pathologists should arrange courses and slide seminars especially for hospital pathologists. Hospital administrators should be informed about the importance of continuing education.

Incidence of different morphological types of thyroid cancer in the Nordic countries.

In order to determine the incidence of different morphological types of thyroid cancer in the Nordic countries, all cases of thyroid cancer reported to the national cancer registries of Finland, Iceland, Norway and Sweden over periods ranging from 1 to 14 years were re-examined (a total of 706 cases) by one or two pathologists from each country. The age-adjusted incidence rate for Iceland was clearly higher than those for the other Nordic countries. The rate for Finland was the lowest, and a five-fold difference was seen between Iceland and Finland. The differences in the incidence rates applied to all age groups and to both sexes. The differences also concerned all histological types and were more pronounced for papillary and medullary carcinomas. In papillary carcinoma, an almost 10-fold difference was found between Finland and Iceland. The causes of the differences are not known. There has been and probably still is some endemic goitre in Finland, Norway and Sweden, but no endemic goitre occurs in Iceland. Thus, no positive association was found between the presence of endemic goitre and the risk of follicular carcinoma. There was a marked negative association between endemic goitre and the risk of papillary carcinoma.