Otto Ljungberg

Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial.

STUDY OBJECTIVE--To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN--Birth year cohorts of city population separately randomised into study and control groups. SETTING--Screening clinic outside main hospital. PATIENTS--Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS--Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT--Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS--All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS--In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS--Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.

Occult thyroid carcinoma at autopsy in Malmö, Sweden

Thorough examination of complete thyroid glands from 500 consecutive autopsies in a Swedish population revealed 43 primary thyroid carcinomas (8.6%). Thirty‐two were papillary, seven follicular, and four medullary. All but three follicular carcinomas were less than 1 cm and clinically unsuspected. The prevalence of occult papillary carcinoma did not differ significantly between men and women and there was no definite increase in frequency with age in the age groups studied (40–90 years).

Oxyphil tumors of the thyroid: follow-up of 42 surgical cases.

Histopathologic and clinical follow-up data on 42 patients observed 2-20 years after operations for oxyphil neoplasms of the thyroid are presented. In eight patients histologic signs of malignancy were found but only two patients showed a clinically malignant course with development of distant metastases. The results do not indicate that oxyphil thyroid neoplasms are especially prone to assume a malignant course with the mode of treatment applied. Our policy is to remove any differentiated epithelial thyroid neoplasm with at least lobectomy. Total thyroidectomy is reserved for cases with capsular penetration, blood vessel invasion and/or metastases.

Breast tomosynthesis: Accuracy of tumor measurement compared with digital mammography and ultrasonography.

Background: Mammographic tumor size measurement can be difficult because breast structures are superimposed onto a two-dimensional (2D) plane, potentially obscuring the tumor outline. Breast tomosynthesis (BT) is a 3D X-ray imaging technique in which low-dose images are acquired over a limited angular range at a total dose comparable to digital mammography (DM). These low-dose images are used to mathematically reconstruct a 3D image volume of the breast, thus reducing the problem of superimposed tissue. Purpose: To investigate whether breast cancer size can be more accurately assessed with breast tomosynthesis than with digital mammography and ultrasonography (US), by reducing the disturbance effect of the projected anatomy. Material and Methods: A prototype BT system was used. The main inclusion criterion for BT examination was subtle but suspicious findings of breast cancer on 2D mammography. Sixty-two women with 73 breast cancers were included. BT, DM, and US sizes were measured independently by experienced radiologists without knowledge of the pathology results, which were used as reference. Results: The tumor outline could be determined in significantly more cases with BT (63) and US (60) than DM (49). BT and US size correlated well with pathology (R=0.86 and R=0.85, respectively), and significantly better than DM size (R=0.71). Accordingly, staging was significantly more accurate with BT than with DM. Conclusion: The study indicates that BT is superior to DM in the assessment of breast tumor size and stage.

A compound follicular‐parafollicular cell carcinoma of the thyroid: A new tumor entity?

An unusual thyroid carcinoma is described, showing structural, histochemical and radioimmunologic features of both a follicular and a parafollicular cell carcinoma. Radioimmunoassay revealed high levels of thyroglobulin in the patients serum and in extracts from metastatic tumor tissue. Immunoreactive thyroglobulin was demonstrated histochemically in tumor cells. On scanning, pulmonary metastases showed uptake of 131I. Somatostatin and neurotensin immunoreactivity was also revealed histochemically in the tumor and a large proportion of the neoplastic cells were argyrophil. Serum calcitonin level was normal and no immunoreactive calcitonin was found in tumor tissue by radioimmunoassay or histochemically. Light microscopy showed cribriform patterns suggestive of follicular carcinoma as well as solid areas reminiscent of medullary carcinoma. Electron microscopy revealed two types of tumor cells. One type had electron dense granules resembling secretory granules characteristic of polypeptide hormone and/or monoamine producing endocrine cells. The other type had no such granules but showed a prominent vesicular rough endoplasmic reticulum similar to that seen in neoplastic follicular cells. The results suggest two alternative possibilities regarding the histogenesis of the tumor. One would be a mixed neoplasm, resulting from a coincidental malignant change in both follicular and parafollicular thyroid cells. The other, more likely alternative would be that the tumor cells are derived from a common stem cell with the potentiality of differentiating into both follicular and parafollicular adult cells. The finding that both thyroglobulin and somatostatin or neurotensin immunoreactivity occurred together in some tumor cells supports the latter possibility and suggests that at least some follicular and parafollicular cells may have a common precursor origin.

Immunohistochemical evidence of peptide hormones in endocrine tumors of the rectum

Twenty‐five endocrine tumors of the rectum (rectal carcinoids) were examined immunohistochemically for various pancreatic and gut neurohormonal polypeptides. Twenty‐one of the tumors were found to contain cells displaying pancreatic polypeptide (PP), glucagon, somatostatin, insulin, substance P, enkephalin or β‐endorphin immunoreactivity. At least 11 of the tumors contained more than one peptide hormone. In some of the tumors PP cells made up the major cell population, in others the glucagon cells constituted the majority. Only four of the tumors contained 5‐hydroxytryptamine. Rectal endocrine tumors seem unique among gut endocrine tumors in that they may store immunoreactive enkephalin, β‐endorphin and even insulin. None of the patients displayed the carcinoid syndrome; symptoms were usually vague and uncharacteristic. In many cases the tumor was found at routine examination.

Medullary thyroid carcinoma and phaeochromocytoma: a familial chromaffinomatosis.

Coexistence of thyroid cancer and phaeochromocytoma was first reported by Eisenberg and Wallerstein in 1932 ; since then some 20 cases have been described (Williams, 1965). In most of these cases the thyroid cancer was of the rare medullary type with amyloid in the stroma (Hazard, Hawk, and Crile, 1959). The familial occurrence of thyroid cancer and phaeo chromocytoma has also recently been reported (Nourok, 1964 ; Schimke and Hartmann, 1965 ; Ljungberg, 1966). We have found this combination in a number of cases and have had the opportunity of examining a family several members of which had both types of tumour associated with multiple cutaneous tumours resembling fibromas ; one of them also had caf?-au lait-like skin spots. The results of xhis investigation are presented below.

Occult papillary thyroid carcinoma in the young and the aged.

Thorough examination of complete thyroid glands from the autopsies of 218 people 50 years of age or younger, and 212 persons older than 80 years of age in a Swedish population showed that occult papillary thyroid carcinoma occurred in much the same frequency (about 7%) in the ages from the second decade. The youngest person with the lesion in question was 17 years of age. The prevalence of occult papillary thyroid carcinoma did not differ significantly between men and women. The tumors of the women were on an average larger than those of the men, and the tumors in the old were on an average larger than those in the young.

Antro-pyloric gastrinoma associated with pancreatic nesidioblastosis and proliferation of islets

An adenoma in the antropyloric mucosa of a patient with recurrent duodenal ulcers was identified by immunofluorescence as a gastrinoma. Resected pancreatic tissue showed greatly increased numbers of islets and ducts. Insulin and glucagon cells were revealed by immunofluorescence not only in the islets but also in the duct epithelium. Signs suggesting neoformation of islets from the duct epithelium were observed.

Neurohormonal Peptides in Endocrine Tumors of the Pancreas, Stomach, and Upper Small Intestine: I. An Immunohistochemical Study of 27 Cases

Preliminary observations have indicated the existence of characteristic spectra of gastroenteropancreatic (GEP) neurohormonal peptides in endocrine tumors arising in foregut, midgut, and hindgut derivatives. In order to further explore this feature of GEP endocrine neoplasms, islet cell tumors from 14 patients were studied, as were endocrine tumors of the stomach, duodenum, and upper jejunum from 6, 5, and 2 patients, respectively. All tumors were examined immunohistochemically with antisera raised against islet hormones [insulin, somatostatin, glucagon, pancreatic polypeptide (PP)], peptides of the gastrin family [gastrin, cholecystokinin (CCK)], peptides of the secretin family [secretin, vasoactive intestinal peptide (VIP)], and substance P, neurotensin, leu-enkephalin, beta-endorphin, motilin, calcitonin, and ACTH. In addition, an ultrastructural investigation was made. Whenever possible, the immunohistochemical observations were correlated with the clinical manifestations and with the results of radioimmunochemical determination of GEP neurohormones in the blood. The pattern of immunoreactive neurohormonal peptides and the clinical picture were those to be expected in endocrine tumors arising in foregut derivatives. Some principles are proposed for the classification of GEP endocrine tumors on the basis of their histopathologic growth pattern, their spectrum of neurohormonal peptides, and their clinical manifestations.