Aggressive mesenteric fibromatosis. Case report.

A 34-year-old man was found to have rectal adenocarcinoma 4 years after diagnosis of mesenteric fibromatosis. Radical excision of the fibromatosis was not feasible and the fibromatous infiltration slowly progressed retroperitoneally, obstructing ureters and colon. Patients with abdominal fibromatosis may be at a risk of developing colonic carcinoma due to coexisting colonic adenomatosis.

Alveolar soft part sarcoma. An immunohistochemical, cytologic and electron-microscopic study and a quantitative DNA analysis.

The type, differentiation and histogenesis of the tumor cells of alveolar soft part sarcoma (ASPS) have been analyzed in a series of ten cases by a light-microscopic, ultrastructural, immunohistochemical and cytologic investigation and quantitative DNA analysis. Four tumors deviated from ordinary ASPS: three were wholly or partly of the so-called pleomorphic variant of ASPS and a fourth tumor showed calcifications of the psammoma body type. The ultrastructural findings and immunohistochemical demonstration of desmin supported the hypothesis of a rhabdomyomatous differentiation and gave no support to epithelial (negative immunoreactions for cytokeratins, epithelial membrane antigen, HMFG-1 and -2, tissue polypeptide antigen (TPA] or neuroectodermal (negative for S-100 protein, glial fibrillary acidic protein, neurofilaments) differentiation. The negative immunoreactions for vimentin and myoglobin and the positive reaction for neuron specific enolase (NSE) do not exclude a rhabdomyomatous differentiation since in rhabdomyosarcomas the undifferentiated rhabdomyoblasts generally contain vimentin and the differentiated tumor cells contain myoglobin and rhabdomyosarcoma has previously been reported as being positive for NSE. The production of external lamina material peripherally in the tumor cell nests and around vessels in the vascular septa was demonstrated both ultrastructurally and by immunohistochemistry using antibodies against collagen IV and laminin. The cytologic appearance in smears obtained by fine-needle aspiration from a case of the pleomorphic variant showed some resemblance to that of a carcinoma. The seven tumors with an ordinary cell appearance were found to show a diploid DNA-distribution at a quantitative analysis performed on paraffin sections, while the three tumors wholly or partly of the pleomorphic type showed an additional tetraploid peak.

Expression of the myc protooncogene in canine rhabdomyosarcoma.

The expression of the protooncogene c-myc in a canine rhabdomyosarcoma was examined. It was found that this highly malignant tumour contained vast quantities of RNA that hybridized with a cDNA probe for c-myc. Restriction fragment length analysis after endonuclease digestion of tumour DNA did not reveal any rearrangements in this gene locus. The potential role of this oncogene in the development of canine rhabdomyosarcoma is discussed.

Induction of 2',5'-oligoadenylate synthetase in freshly separated malignant cells from solid tumors. Variability in the susceptibility of interferon.

The capacity of interferon (IFN) to induce the enzyme 2',5'-oligoadenylate synthetase (2',5'-A synthetase) in malignant cells from freshly explanted solid tumors was investigated. The malignant cells were separated from non-malignant cells by using velocity and density gradient sedimentation as well as adherence on plastic. During the test the cells were usually maintained on an extracellular matrix (ECM) in the wells of a microplate for 24 h. The tumor cells varied in their sensitivity to IFN-induced enhancement of 2',5'-A synthetase. In five out of 28 tumor samples natural alpha-IFN induced no major enhancement in the intracellular levels of 2',5'-A synthetase. The effect was dose-dependent and as little as 0.5 units of alpha-IFN/ml was sufficient to cause an increase in the intracellular levels of this enzyme. Some tumors differed in their susceptibility to alpha-, beta- and gamma-IFN, showing resistance to one IFN-type and sensitivity to the other two. As little as 6 X 10(3) cells/well were required for measuring the induction of 2',5'-A synthetase. Measurement of induction of 2',5'-A synthetase by IFN in vitro could have clinical relevance for pre-treatment testing of the susceptibility of primary tumor cells to IFN.

Comparison of nuclear DNA content in primary and metastatic papillary thyroid carcinoma.

Nuclear DNA values were determined in 40 primary papillary thyroid carcinomas, as well as in 52 corresponding local recurrences and metastases were observed either at the time of diagnosis or up to 20 years later. The patient population consisted of 34 survivors and 6 nonsurvivors. In survivors, both the primary tumors and their recurrences and metastases exhibited a majority of cells with DNA values within the normal diploid region, whereas nonsurvivors showed increased and scattered DNA values. In all cases, the primary tumors and the corresponding recurrences and metastases showed similar DNA distribution patterns even if many years had passed between the detection of the primary tumor and the metastases. The results indicate that in papillary thyroid carcinomas, the DNA distribution patterns in the primary tumor and the corresponding recurrences or metastases are generally similar throughout the entire period of disease.

Biologic considerations and operative strategy in papillary thyroid carcinoma: arguments against the routine performance of total thyroidectomy.

Reasons cited for the routine performance of total thyroidectomy in patients with papillary thyroid carcinoma include: fear of multicentric neoplastic foci causing local recurrence and death; risk of anaplastic transformation of unresected multifocal microscopic carcinoma; toxicity of high-dose radioactive iodine to ablate normal thyroid remnants; and lack of reliable criteria for grading malignancy and identifying patients at high risk. However, autopsy studies have detected microscopic foci of papillary thyroid cancer as incidental findings in up to 24% of patients dead of other diseases. The prevalence of anaplastic transformation of papillary thyroid carcinoma as determined from reports in the literature is less than 1%. A retrospective investigation of 90 patients with papillary thyroid carcinoma derived from the Swedish National Cancer Registry showed no complications from radioiodine ablation of postoperative thyroid remnants in 45 patients. Retrospective analysis of the DNA content of tumors at the time of the initial operation showed a significant difference between a group of 10 patients who died of recurrent and metastatic papillary thyroid carcinoma and a group of 16 patients alive at least 10 years after operation despite distant metastases or recurrent cancer in the thyroid bed and/or cervical lymph nodes. The risk of permanent hypoparathyroidism is higher in patients after total thyroidectomy without apparent improvement in survival rates when compared with less extensive resections. Therefore it is proposed that the criteria for total thyroidectomy in patients with papillary thyroid carcinoma be limited to: tumors that clinically involve both lobes of the thyroid gland, extracapsular spread of cancer requiring enbloc resection, and reoperations where scarring prevents accurate delineation of the extent of the tumor. By differentiating patients at high risk for death from papillary thyroid carcinoma from patients at low risk, the measurement of DNA content may decrease the need for routine total thyroidectomy.

Identification and characterization of non-dividing cell populations in phase II cultures of human glial cells.

It has been reported that cultures of normal cells in phase II contain a non-multiplying cell population, the size of which increases with passage number. In phase II cultures of normal human glial cells we have found two subpopulations of non-proliferating cells, one of which has a characteristic morphology, and differs from the actively dividing cells in a number of respects: (1) they are larger although of various sizes and are well spread over a very large substratum area: (2) they contain a great number of granules showing acid phosphatase activity, being heavy metal positive and displaying the characteristic natural fluorescence of lipofuscin pigment; and (3) they frequently contained a central somewhat irregular nucleus with various numbers of darkly staining nucleolar-like structures. Cytophotometric nuclear DNA measurements of the described "large" cell population show a decreased proportion of diploid cells as compared to their smaller sister cells. Moreover, with increasing passage number, the DNA values for large cells shift towards higher ploidy levels resulting in a scattered aneuploid pattern in the oldest passage. This "large" cell subpopulation consists of between 2% and 3% of all passages and becomes greatly decreased following subcultivation. The other subpopulation of non-dividing cells is generally morphologically similar to the dividers, increases in size with passage number and is the more important in the phase III phenomenon.

Cost effectiveness and cost benefit of vaccination against pneumococcal pneumonia: implications for clinical practice.

The economic techniques of cost-effectiveness and cost-benefit analysis have provided useful insights into the potential advantages of vaccination against pneumococcal pneumonia. They suggest that the cost of vaccinating persons 65 years and older and perhaps younger persons with high risk conditions would be reasonable when compared with the cost of treatment for pneumococcal pneumonia. These findings, together with other considerations, may guide physicians and health care policymakers in deciding which individuals might be expected to benefit from pneumococcal vaccination.

Reoperation for primary hyperparathyroidism.

The reasons for failure of the initial exploration and the results of reoperation were analyzed in 53 patients with a diagnosis of primary hyperparathyroidism, 29 of whom were referred after initial operations elsewhere. Seventy-nine reoperations were performed. Sternotomy was used in 15 patients, and in retrospect was necessary in only 5. There was no operative mortality. The reasons for initial failure were incorrect diagnosis in 6 patients, true recurrence in 4 and persistent disease in 43. Persistence was caused by surgical failure in two thirds and pathology failure in one third. Of 47 patients reoperated on for hyperparathyroidism, 39 (83 percent) were cured, a rate warranting this type of surgery. Analysis of a long-term series of initial operations demonstrates a persistence rate of 5 percent (24 of 461) and a recurrence rate of 1 percent (4 of 461) in this disease. The need for reoperation was les than 1 percent over the recent 5 year period.

The role of fine-needle aspiration cytology in the management of thyroid disease.

Fine-needle aspiration cytology of the thyroid gland is a low-cost office procedure which even in children does not require regional anaesthesia. The method is safe, without appreciable complications or side effects. Since the needling is readily accepted by patients, it can be repeated when necessary. A morphological diagnosis is then rapidly obtainable, and time-consuming and expensive investigations are bypassed. In the hands of experienced cytopathologists, fine-needle biopsy is a reliable means of selecting patients for surgery, thereby reducing the frequency of operations for benign lesions. The cytological report enables the clinician to recognize the conditions which will benefit from non-surgical management, for example colloid goitre, thyroiditis and lymphoma, and also to plan surgical strategy in papillary, medullary and anaplastic giant cell neoplasms. In follicular neoplasms, aspiration biopsy cytology does not permit reliable distinction between adenoma and carcinoma. With combined consideration of aspiration biopsy cytology and scintiscans, however, it is possible to distinguish non-neoplastic from neoplastic follicular proliferation. In cases where cytological study does not give a specific or conclusive diagnosis, broad disease categories such as inflammatory or neoplastic states can be recognized. Even for these patients, therefore, the method can serve as a guide in the further management. In post-therapy follow-up of thyroid neoplasms, aspiration biopsy cytology permits rapid detection of recurrence.

Fine-needle aspiration cytology in thyroid disease.

Fine-needle aspiration biopsy of palpable lesions of the thyroid is a diagnostic method routinely used in several medical centres, but still relatively new in others. Experience has shown that the technical steps involved in this biopsy procedure, that is, palpation, aspiration, smear making, fixation and staining, are critical for good results, and they are therefore reviewed and illustrated. Another prerequisite for the use of aspiration biopsy cytology is a specially interested cytopathologist who is familiar with the methodological aspects, as well as the interpretation of cells in aspirates. A description is given of the different cytological patterns in smears of fine-needle aspirates for clinical thyroid diseases, such as simple and toxic goitre, different types of thyroiditis (acute, subacute and chronic) as well as the various differentiated thyroid neoplasms (follicular, papillary, medullary), anaplastic carcinomas and lymphomas. The limits of cytological diagnosis are indicated and differential diagnostic aspects are discussed. diagnostic accuracy of aspiration biopsy cytology, with particular reference to tumour diagnosis, is high: no false positive diagnoses are made by experienced cytopathologists, whereas false negative tumour diagnosis can occur in about 10 per cent of cases. Such results are the reason for the special position of fine-needle aspiration biopsy among other methods in the diagnostic work-up of patients with thyroid disease.

Transrectal fine-needle aspiration biopsy for cytologic diagnosis and grading of prostatic carcinoma.

In this article, the Karolinska experience of transrectal fine-needle aspiration biopsy of prostatic carcinoma, which now extends over more than twenty years, is evaluated. The cytologic criteria for diagnosing prostatic carcinoma in aspirates are well defined. While accuracy for cytodiagnosis is similar to that of histopathologic diagnosis, fine-needle aspiration is a less traumatic, cheaper procedure compared with histologic biopsy methods. Accuracy depends very much upon the skill of the examiner taking the cell samples and on the alertness of the cytopathologist for possible diagnostic pitfalls. Cytologic grading of prostatic carcinoma into well, moderately, and poorly differentiated types has been shown to be correlated significantly not only to histopathologic grading, but also to clinical stage, response to hormonal therapy and survival. The degree of tumor differentiation is well reproduced by independent observers. Cytochemical parameters, such as DNA measurement, constitute a potential refinement of cytologic grading, especially in moderately differentiated carcinomas. In medical centers with long experience of fine-needle aspiration biopsy, the method has a central role in diagnosis and management of prostatic carcinoma, including posttherapy follow-up.