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Fifty human B-cell lymphomas have been studied with regard to surface markers (surface immunoglobulins (sIg) and complement receptors (CR)), capping of sIg, and relative amounts of sIg by single-cell flow cytometry. The results show that these lymphomas can be subdivided into distinct immunological subsets. Whereas one histological subgroup (lymphocytic) consisted of only one immunological subtype, others were heterogeneous with regard to immunological subtypes. This was most striking in nodular lymphomas of germinal centre cell origin (centroblastic/centrocytic). Our studies provide further evidence for the existence of a large number of subsets in the B-cell compartment of the immune system. sIgD was only found in association with sIgM. The relative amounts of sIgD varied, especially in nodular lymphomas. A discrepancy between capping of sIgM and sIgD was also found in some lymphomas belonging to this group. These findings together with other observations suggest that sIgD plays a role in B-cell maturation and differentiation events taking place in germinal centres and becomes lost during this process. A close association was found between the presence of CR and capping of sIgM but not capping of sIgD or sIgG. Nodular lymphomas expressing sIgG only, lacked CR. These findings suggest that CR may become lost during maturation and differentiation processes also taking place in germinal centres. Lymphoplasmacytoid lymphomas, which show morphological evidence of differentiation towards plasma cells, could be subdivided into three immunological subsets, indicating that plasma cell maturation may take place from different subsets of B cells. [ABSTRACT FROM AUTHOR]

Background: The Norwegian Radium Hospital's sarcoma group is a multidisciplinary group with a leading role in the diagnosis and treatment of bone and soft tissue sarcomas in Norway., Material and Methods: From 1980 through 1999, 1,355 patients with soft tissue sarcoma and 458 patients with bone sarcoma were treated. In a retrospective analysis of trends over time, patients were allocated to consecutive five-year periods., Results: Patient characteristics were relatively stable, but there was an increasing proportion of soft tissue sarcomas being referred without prior surgery. Treatment principles have remained unchanged, with surgery with or without radiotherapy dominating in soft tissue sarcoma and surgery with or without chemotherapy in bone sarcoma. The amputation rate for bone sarcoma has fallen from 78% to 17%, and survival has increased significantly for both soft tissue and bone sarcoma patients., Interpretation: The results indicate significant improvements in the quality of treatment of soft tissue and bone sarcoma. More resources for treatment and organizational development of a multidisciplinary group may contribute to improved quality of care.

Background: Medullary thyroid cancer may be inherited dominantly. Germline mutations in the RET oncogene which code for a receptor tyrosine kinase cause MEN2. Thyroidectomy is recommended in family members who carry a mutation., Material and Methods: We have thyroidectomized four children from three families, 12, 10, 7 and 6 years old, because of germline mutations., Results: The 12-year-old had developed a minimal medullary cancer with microscopic lymph node metastases; the others showed variable degrees of C-cell hyperplasia. The mutations were located on exon 10 (C620F) in the two patients from one family, on exon 11 (C634R) in the second family and on exon 14 (V804M) in the third family. In the families with the codon 620 and codon 634 mutations, only medullary thyroid cancer has been diagnosed. In the family with the codon 804 mutation, the index patient has been operated for a pheochromocytoma. The longterm clinical course seems more favorable in the family with the codon 620 mutation than in the two other families. With knowledge of the family mutations, we found that two out of nine family members we previously have thyroidectomized following calcitonin testing did not carry the family mutation., Interpretation: Genetic diagnostic is a safe and reliable predictive test for familial medullary thyroid cancer and should be carried out in any individual with this cancer. Thyroidectomy is recommended in gene carriers at the age of six.

Fibrosarcoma is a rare tumour in children. The potential of malignancy has been questioned. We present three cases of fibrosarcoma in children . The follow-up periods range from 10 to 37 years. The first patient had pulmonary metastases at the time of diagnosis in 1958. The primary tumour in fossa ischio-rectalis was resected in 1960. Lung metastases were resected in 1960 and 1989. Radiotherapy was given in 1992. He is still alive with metastases 37 years after the first manifestation of disease. The second patient had a primary tumour and several local recurrences in the mandible. He is alive without evidence of disease 4 years after resection of pulmonary metastases and 21 years after resection of the primary tumour. The third patient has no signs of recurrence or metastatic spread 10 years after a wide excision of subcutaneous tumours of the left upper arm. The cases demonstrate a special tumour-entity of low-grade malignancy, which show a good prognosis and a wide spectrum of biological behaviour.

Of 103 patients with high-grade osteosarcoma, 27% had tumours localized outside the extremities. Non-extremity patients were significantly older at diagnosis than patients with extremity tumours (median 38 vs. 17 years). More than 90% of patients with extremity tumours received adequate treatment (aggressive chemotherapy plus at least marginal surgery), compared with only 25% of patients with non-extremity tumours. Failure of adequate treatment was due to inoperable tumour, intralesional surgery and age preventing aggressive chemotherapy. There was a highly significant difference in both local tumour control and overall survival, both favouring patients with extremity tumours. Within the extremity tumour group, patients who were treated in prospective multicentre trials had a significantly better outcome than non-trial patients. Our results show that the fraction of patients with high-grade tumours that fall outside trials designed for 'classical osteosarcoma' may be larger than is usually acknowledged, and that the results reported for the classical group are by no means representative of the whole patient population. Improved and new treatment approaches are needed for patients with non-extremity tumours, particularly in the older age groups.

Pulmonary lymphangioleiomyomatosis is a rare disease with a haphazard proliferation of smooth muscle throughout the lung. Little knowledge about the disease, its clinical presentation and the diagnostic methods used may be a reason for underdiagnosing the disease. In Ostfold county, Norway, with only 250,000 inhabitants, we have seen four patients with this disease in the last few years. The diagnosis was based on histological examination of transbronchial biopsy material in three patients who underwent bronchoscopy the presence of lymphangioleiomyomatosis was not recognized at the initial pathological examination. The disease can be misinterpreted as fibrosis at histological examination. Specific procedures for detecting smooth muscle can be used, eradicating the need for open lung biopsy. Transbronchial biopsy is a valid and useful method for confirming the diagnosis of lymphangioleiomyomatosis. High resolution CT has also shown to be an important diagnostic tool. We emphasize the importance of raising the question of lymphangioleiomyomatosis with the pathologist when this rare, but probably underdiagnosed disease, is suspected by the clinician.

The authors present a retrospective analysis of 59 chondrosarcoma patients treated at the Norwegian Radium Hospital during the period 1981 to 1993. 31 patients were admitted with untouched tumour, seven after fine needle cytology and 20 after open biopsy or partial excision. One patient had recurrent local disease. Only 20% of the tumours were of high grade malignancy. 51 patients were treated by surgery. Reconstructions were performed in 16 patients, using allografts or endoprostheses. Amputations were performed in six cases and wide excision in 12 cases. In these 18 patients local recurrence appeared in one case, and two developed lung metastases. Only one of the 18 patients operated by amputation or wide excision has since died from chondrosarcoma. Marginal excisions were performed in 26 cases. Nine of these patients developed a local recurrence, five developed metastases and three have died. Six patients had partial excisions. Postoperative radiotherapy was given to one patient only. Five of the six are alive. In one case, the quality of the margins could not be evaluated. A total of 45 of the 51 patients treated for the primary tumour by surgery are alive. The median observation time is four years. Treatment of nonmetastatic chondrosarcoma should be surgical. Chondrosarcoma patients show wider variations in age, localization of tumour and tumour growth rate than patients with other bone sarcomas. Although wide excisions provide the best local control of any grade of malignancy, the mutilation or risk involved may be so great that some patients may benefit from marginal or even partial excision.

Medullary thyroid cancer may be autosomal dominantly inherited. Calcitonin is a very sensitive tumour marker in medullary thyroid cancer. It is essential to measure calcitonin in first grade relatives of these patients, in order to expose familial incidents of subclinical disease. In 55 patients with medullary thyroid cancer and no history of familial disease, nine close relatives with elevated calcitonin were identified in four different families. Eight of these nine have been thyroidectomized. Five were found to have medullary thyroid cancer, one had definite C-cell-hyperplasia, and two had equivocal C-cell hyperplasia. The last two, had elevated basal serum calcitonin-levels were increased, but with no further increase after intravenous pentagastrin bolus injection. Thyroidectomy did not modify these results and DNA-analysis may be necessary to draw a conclusion about the hereditary situation of these patients.

In 98 follicular thyroid carcinoma patients with a follow-up of 10-32 years, 10-year survival varied in subgroups from 15.5-63.4%. Survival with encapsulated primary tumors was 46.7%, compared to 26.9% in widely invasive tumors, and varied from 59.9-35.8% with growth pattern. In patients younger than 60 years of age at diagnosis 10-year survival was 68% of expected survival, compared to 32% in patients older than 60. Patients treated after 1970 had an improved survival of 24.2%. Thirty-one patients had previous thyroid operations for benign lesions. Review of histopathologic slides and medical records demonstrated follicular adenomas in 17 cases, and overlooked carcinomas in 11. Calculating survival from the first surgical intervention improved reported 10-year survival by 14.5%. Papillary carcinoma patients matched for age and sex had significantly better 10-year survival.

From 1979-89, 211 women with cancer mammae were irradiated at the Norwegian Radium Hospital after breast-conserving surgery performed at different hospitals in Norway. 181 of these patients were called in for re-examination to check the procedures for treatment and the cosmetic results. Only 37% of the patients had undergone mammography prior to surgery and 48% of the patients had had two or more operations before the irradiation. The cosmetic results were not very satisfactory in 45% of the patients. Reduced cosmesis was mainly due to less than optimal surgery. We propose better standardisation of the treatment programme for breast preservation. Optimal results require close collaboration between radiologists, surgeons, oncologists and pathologists. The treatment must be organized in a way that facilitates this collaboration.

A total of 15 patients with advanced nonseminomatous testicular cancer underwent 2 sequential operations (4 in 1 patient) to remove residual masses after cisplatin-based combination chemotherapy. All patients had normal human chorionic gonadotropin and alpha-fetoprotein levels but persistent radiographic masses after chemotherapy. The operations included retroperitoneal lymph node dissection in 13 patients, thoracotomy in 15, hepatic resection in 3 and craniotomy in 1. Histological comparison of the specimens resected during post-chemotherapy operations 1 and 2 demonstrated different patterns in 7 of 15 patients. Of these 7 patients 4 had less favorable pathological features in the specimen removed during the second procedure. Residual malignant tumor or mature teratoma was found in at least 1 site in 12 of the 15 patients and only 3 had complete necrosis or fibrosis in both specimens examined. These data indicate the favorable impact of excising all post-chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer. However, in patients with no teratomatous elements in the testicular tumor and complete necrosis or fibrosis in the initial post-chemotherapy operation specimen the probability of complete necrosis or fibrosis in remaining tumors appears to be high.

Impairment of vocal cord function is a threat to patients with thyroid carcinoma; either due to the tumor having infiltrated the larynx or the recurrent nerve, or to accidental damage to the laryngeal nerves during thyroid surgery. We have reviewed 1,245 patients' records which were filed under the diagnosis of thyroid carcinoma at Det Norske Radiumhospital from 1956 to 1978. Pareses of vocal cords were noted in 465 patients (37.3%) during the course of their illness. In 135 patients (10.8%) the pareses were due to infiltration by the tumor, most commonly seen in anaplastic carcinoma. In 267 patients (21.4%) the pareses followed surgery; planned resections of the recurrent nerves were performed in 48 patients (3.9%). Transient pareses with normal vocal cord movements within months were experienced in 137 cases (11%). Permanent paralysis caused accidentally during surgery was seen in 82 patients, representing 6.6% of all patients and 4.7% of the surgically exposed nerves. We stress the need for pre- and postoperative evaluation of vocal cord movement as an aid to future diagnosis and optimal surgical planning.

Cell suspensions were obtained from biopsy tissue from 149 patients with B cell lymphomas and analysed with regard to DNA-synthesis as assessed by 3H-thymidine uptake, response to therapy and survival. The 3H-thymidine uptake was significantly increased in lymphomas of high versus low grade malignancy (p = 0.0001), in patients with stage I and II versus stage III and IV (p = 0.014), and in patients with general symptoms (p = 0.0025) as opposed to asymptomatic cases. The complete response rate was significantly higher in patients with increased thymidine uptake than in those with low uptake, 26/51 (51%) cases versus 24/83 (29%) cases, respectively (p = 0.014). 55 patients with increased 3H-thymidine uptake survived for significantly shorter times than (94 patients) with low uptake (p = 0.0056). Furthermore, a markedly larger group of high-risk patients was identified by the 3H-thymidine assay than by histopathology alone, 55 cases versus 23 cases, respectively. Among the patients (126 cases) with low grade tumours, those with increased 3H-thymidine uptake (40 cases) had poorer outcome than those with low uptake (86 cases) (p = 0.045). The data suggest that DNA-synthesis in this study, as assessed by 3H-thymidine uptake, is an independent indicator of survival in NHL. Furthermore, it may be a useful parameter in laying down guidelines for therapy in B cell neoplasms, especially in low grade tumours.

The hemocytometer leukocyte adherence inhibition technique was used to study cell-mediated immuno-activity of patients with lung cancer. KCl extracts (3.5 M) from the lung cancer cell line Calu-1 and the breast cancer cell line MCF-7 were used as antigens. Of 138 patients with lung cancer, 85% showed a positive response against the Calu-1 antigen. The response was independent of the histological type of the tumor and was the same among untreated patients, patients undergoing different types of treatment and patients who died within 3 months after blood collection. Twenty-five percent of the untreated lung cancer patients also reacted against the breast cancer antigen. Among lung cancer patients undergoing different types of treatment, 36% reacted while 50% of the patients who died within 3 months after blood collection reacted against the breast cancer antigen.

Two cases of adenocarcinoma in columnar epithelium-lined oesophagus are reported. Two discrete carcinomas were found in one case, and areas of epithelial atypia were demonstrated in regions devoid of tumour in both. Similar observations in the literature together with statistical evidence indicate that Barrett's oesophagus should be regarded as a premalignant condition. Its clinical implications are outlined.

The presence of oestrogen receptors was studied in 105 human breast carcinomas using monoclonal antibodies (Abbott ER-ICA kit). The oestrogen receptors of neoplastic cells were semiquantitatively measured and correlations were made to receptor values determined by a dextran-coated charcoal (DCC) steroid binding assay and to histological grade. Immunoreactive cells were found in about 2/3 of the tumours. Usually only a fraction of the cells within each tumour were immunoreactive, and the staining intensity varied among different cells. In general, well differentiated tumours had a greater proportion of immunoreactive cells than poorly differentiated ones. In most cases (65/98) a good agreement was found between the ER-ICA method and the DCC assay. However, in 33 cases discrepancies were demonstrated.

Previous work has shown that parameters of cell activation studied on lymphoma biopsies can be used to discriminate between low-grade and high-grade non-Hodgkin's lymphomas and to predict prognosis in the low-grade malignancy group alone. We have now examined expression of several activation antigens and indicators of DNA synthesis in 29 patients with low-grade malignant B-cell lymphomas at the time of primary diagnosis and later at relapse and/or tumour progression. At both times, the level of 4F2 antigen expression examined by flow cytometry on cells in suspension as well as the number of Ki67 antigen-positive cells examined by immunohistochemistry were predictive of patient survival. DNA synthesis estimated by (3H-TdR) thymidine incorporation was of prognostic value at the second biopsy only. These parameters were more sensitive than histological demonstration of morphological transformation in secondary high-grade lymphomas in identifying high-risk patients at repeated biopsy. We propose that Ki67 or 4F2 expression or a marker of DNA synthesis (such as 3H-TdR incorporation or labelling index) should be evaluated when repeated biopsies are performed, in order to select patients for whom aggressive chemotherapy may be considered.

Serum thyroglobulin (Tg) radioimmunoassay and 131I whole-body scintigraphy were performed in 134 patients with previous total thyroidectomy for differentiated thyroid carcinoma. Distant spread was found in 46 patients (34%), 42 of whom had serum Tg greater than 10 micrograms/l. Accumulation of 131I in metastases was seen in 39 patients. Serum Tg in patients with iodine-accumulating metastases was significantly higher in follicular than in papillary carcinoma. Scintigraphy showed thyroid tissue remnant and no metastases in 60 patients. Serum Tg was elevated in 19 of these patients and normal in 41. The respective mean uptake of 131I in these two groups was 3.8% and 1.15% of the administered dose (p less than 0.002), indicating that ablation of normal thyroid tissue is important to avoid misinterpreting Tg findings. Scintigraphy performed after 131I in therapeutic doses of 4.5 GBq gave no information additional to that in scans after only 40 MBq 131I. The latter dose thus is adequate for depicting iodine-accumulating metastases. For diagnostic purposes, therefore, a 131I dose of 40 MBq is recommended.