Biomedical subjects
Publications and source records attributed to M Akerman.
In five cases of pseudomalignant myositis ossificans a benign diagnosis was suggested by fine-needle aspiration cytology and confirmed by radiographs and the clinical course. Hence, the need of biopsy to exclude malignancy was obviated. The symptoms rapidly resolved in all the patients. Thus, surgery may not be indicated in pseudomalignant myositis ossificans.
In eleven hypertensive patients with renal artery stenosis, the acute renal effects of captopril were investigated using two methods: 1) the Tc99m-DTPA renography with determination of an index of renal perfusion (IP), an index of glomerular filtration (IF) and the ratio of these indices (F/P); 2) the renal hemodynamics obtained by the clearance method using a continuous infusion of I131-hippuran and I125-iothalamate for calculation of renal blood flow (RBF), glomerular filtration rate (GFR) and filtration fraction (FF). The studies were performed before and after captopril treatment. Patients were classified according to the acute response to captopril as responders (R; n = 6) and non responders (NR; n = 5). Results are as follows: (B: basal, C = captopril). (table; see text) These data confirm that captopril produced a significant decrease in F/P and FF in R whereas these indices did not change in NR; it was found that IF and GFR decreased in R whereas IF increased and GFR did not change in NR; a significant correlation was observed between delta IF and delta GFR in R (r = 0.834, p less than 0.05). These results indicate that 1) data obtained before and after captopril by renography and by clearance methods are in good correlation either in Ror in NR patients; 2) Captopril test including renography or renal hemodynamic measurements is useful for selection of R patients.
The clinicopathology of Merkel cell carcinoma (MC) has been evaluated in 17 patients, and its outcome and clinical management in 14 of these. The histopathologic diagnosis was confirmed by electronmicroscopy and/or immunohistopathology. The location of the primary lesions demonstrated a predilection for the skin of the face and the extremities. The primary treatment usually consisted of a wide excision only. Four out of five patients with MC of the face suffered from local and/or nodal relapses, in contrast to only one out of seven patients with primary lesion on the extremities. The three patients treated for local recurrences and/or regional node metastases were alive and disease-free 22-72 months after recurrences. Three patients developed distant metastases. Two of these died within 4 months after initial diagnosis. One patient completely responded to chemotherapy. The high frequency of local recurrences would justify an excision with generous margins, except when the tumour is close to a vital structure. Radiotherapy could in these cases obviate the necessity for extensive operations. If the primary lesion is located on an extremity, regional lymphadenectomy seems only to be necessary whenever nodal involvement is suspected. Node dissection is also recommended for suspected nodes in the face or on the neck, but the guidelines for elective node dissections in these sites are not obvious since the results of salvage therapy were excellent and the location of relapses unpredictable.
Over a period of 3 years in Southern Sweden 35 patients were seen with deep-seated limb sarcomas without metastases, 30 of whom were referred before any operation had been carried out. Thirty seven patients with deep-seated benign lesions were referred during the same period because of suspected malignancy. A preoperative diagnosis considered sufficient for a definitive operation was made from the clinical findings, aspiration cytology and radiographic examination, but without open biopsy, in 59 of these 67 cases. The differentiation between a benign and a malignant tumour was correct in all but one. The extent of excision necessary to achieve adequate margins for a soft-tissue sarcoma can often be reduced if open biopsy is avoided, with preservation of function. We conclude that treatment without open biopsy is possible in the great majority of patients with soft-tissue sarcoma.
A 62-year-old previously healthy woman presented with a centroblastic non-Hodgkin's lymphoma in the thyroid. Chromosome analysis revealed two unrelated clones, 47,XX,+5 and 46,XX,-14,+der(14)t(5;14)(q11;q32). The two clones may reflect a polyclonal origin, or they may be the descendants of the same neoplastically rearranged cell. In the latter case, the clonal aberrations are either secondary to an event detectable only at the molecular level, or one of them is a primary cytogenetic event while the other arose through clonal evolution with loss of the primary aberration. The best candidate for the primary change would be trisomy 5. Trisomy 5 has previously been associated with lymphomas with diffuse, large, noncleaved morphology, a group within the Working Formulation largely equivalent to centroblastic lymphomas in the Kiel classification. Our findings thus support the notion that trisomy 5 may be associated with centroblastic/diffuse, large, noncleaved lymphomas.
Cytogenetic analysis of short-term cultures from two uterine leiomyomas revealed, in addition to the primary abnormality, the reciprocal translocation t(12;14)(q14-15;q23-24), secondary structural changes that in both cases included ring chromosomes and rearrangements of chromosome 1. One tumor had the karyotype 46,XX,r(1)(p34q32),ins(8;9)(q13;q13q22),t(12;14)(q14-15;q23- 24). Massive numerical rearrangements were found in the second leiomyoma, with chromosome numbers ranging from 47 to 92. In spite of this variability, two main cell populations could be discerned, one near-diploid, the other hypotetraploid, with most mitoses having chromosome numbers between 80 and 88. These findings were corroborated by flow cytometry, which revealed two peaks corresponding to DNA indexes of 0.97 and 1.77. The structural abnormalities t(1;1)(p31;q44) and t(12;14)(q14-15;q23-24) were present in all karyotypically abnormal cells, and one or more unidentified ring chromosomes were observed in most of the hypotetraploid mitoses. In no cells were double copies of the t(1;1) and t(12;14) rearrangements detected. The similarity between the secondary changes in the cases reported here suggests that clonal evolution in uterine leiomyoma is nonrandom.
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Short-term cultures from seven soft tissue leiomyosarcomas were investigated cytogenetically. Sufficient mitoses for chromosome analysis were obtained in six cases, four of which had only normal karyotypes. In one tumor, an intramuscular leiomyosarcoma of the lower arm, a variety of nonclonal structural and numerical aberrations were found in two thirds of the metaphases. Another tumor, a subcutaneous leiomyosarcoma of the knee, had clonal abnormalities resulting in the karyotype 46,X,der(X)t(X;4)(:Xq26----cen----Xp22::4q23----4qter) , del(4)(q23)/47,X,der(X)t(X;4),del(4)(q23), + 20. Flow cytofluorometric measurements of the DNA content in the six leiomyosarcomas successfully karyotyped revealed diploid values in five tumors. The leiomyosarcoma displaying numerous nonclonal changes had two cytofluorometric peaks, 1.01 and 1.39, indicating that the metaphases available for cytogenetic study cannot have been fully representative of the tumor stemline.
A Ewing's sarcoma of the thigh in a 9-year-old boy was diagnosed by light microscopy, electron microscopy, and chromosomal analysis performed on fine needle aspirates.
The cytodiagnoses of preoperative fine-needle aspirate smears from 72 histologically proven lipomatous tumors (52 lipomas and 20 liposarcomas of varying type) collected during the 10-yr period 1972-1981 were correlated to the corresponding histopathologic diagnoses. Three out of 52 lipomas were erroneously diagnosed as low-grade malignant liposarcomas, and one out of 20 liposarcomas was falsely diagnosed as a benign soft-tissue tumor. Of the 20 liposarcomas, 15 were cytologically diagnosed as such, and the majority of the myxoid and the pleomorphic liposarcomas were correctly diagnosed as to type. Important differential diagnostic problems were, on one hand, the separation of lipoma with regressive changes and histiocytic reaction and lipoma with chondroid metaplasia from low-grade malignant liposarcoma and, on the other hand, liposarcoma from intramuscular myxoma, myxofibrosarcoma, and malignant fibrous histiocytoma. The differential diagnosis of liposarcoma as opposed to other soft-tissue sarcomas is discussed, and it is concluded that preoperative fine-needle aspiration of lipomatous tumors is of value in the management of these tumors.
The cytogenetic findings in samples from 106 patients with non-Hodgkin lymphomas (NHL), histopathologically classified according to the Kiel classification, have been correlated with survival time. Clonal chromosomal abnormalities were found in 60 patients, and only normal karyotypes in ten. The chromosome analysis of the remaining samples failed. The failures did not differ in survival compared with the cytogenetically successful cases, indicating that this group is not a prognostic entity within NHL. The cytogenetic findings were classified in six ways in order to evaluate the prognostic value of the cytogenetic pattern. Multivariate analysis demonstrated that presence of clonal chromosome abnormalities and the number of aberrations both were important prognostic factors independent of histopathology, whereas, the modal chromosome number, presence of translocations, or unidentified marker chromosomes were not. Some characteristic chromosome abnormalities were correlated with survival time: Patients with a 1p+ marker or +7 had a significantly shorter survival time than patients with normal karyotypes only (NN). Patients with +3, +12, 6q-, i(17q), and t(14;18)(q32;q21) did not differ significantly from the NN group.
At histopathological diagnosis of non-Hodgkin's lymphoma (NHL) the mean number of mitoses in 10 high power fields (X 40) was determined in thin sections (2 micron) and designated 'mitotic index' (MI). In 38 patients the thymidine labelling index (LI) of the lymphoma cells was also determined. There was a close correlation between MIs and LIs (r = 0.81, P less than 0.001) indicating that MI reflects the proliferative activity in NHL. Among 101 patients with NHL classified according to the Kiel nomenclature MIs were generally lower in lymphomas of low grade malignant type than in the high grade malignant lymphomas. The variation of MIs within morphological subgroups was especially pronounced in high grade lymphomas. Only 18 of 49 patients (37%) with MI greater than or equal to 2 have survived for 2 years in contrast to 37 of 52 patients (77%) with MI less than 2 (P = 0.001). For patients with histologically low grade lymphomas and MI greater than or equal to 2.0 the median survival was 23 months and for those with MI less than 2.0 58 months (P = 0.09). Patients with high grade lymphomas and MI greater than or equal to 2.0 had a median survival of 15 months compared to 57 months for those with MI less than 2.0 (P = 0.04). In a multivariate analysis of 50 patients with centroblastic-centrocytic (CB-CC) or centroblastic (CB) lymphomas the importance of different prognostic factors was analysed. Among the variables age, MI, growth pattern (follicular vs. diffuse), cell type (CB-CC vs. CB), clinical stage (I vs. II-IV), initial chemotherapy (active vs. less active) only age and MI gave significant prognostic information. It is concluded that the assessment of mitoses in NHL gives prognostic information in addition to histopathologic classification. The method is simple and the proliferative activity and histopathological diagnosis can be ascertained routinely on the same occasion.
Fine needle aspiration (FNA) cytology is a valuable aid to diagnosis and tumour staging in patients with non-Hodgkin's lymphoma. These tumours are often multicentric and involve sites such as the liver or the spleen which are not easily accessible to surgical biopsy. Particularly with splenic involvement, there is a diagnostic problem of morphologically distinguishing the lymphoma cells in an admixture of normal lymphocytes. Since most lymphomas in adults are of B-cell origin, we studied the diagnostic value of adding a surface immunoglobulin (sIg) light chain analysis to the cytological evaluation of FNAs. B-clonal excess was determined by flow cytometric analysis of the sIg light chain distribution and a monoclonal finding was considered diagnostic of lymphoma. In primary diagnostic procedures the light chain analysis established a diagnosis of lymphoma in 5/14 (36%) aspirates from patients with poorly differentiated tumours. Fine needle aspirates performed as part of staging procedures were morphologically normal or inconclusive in 19 cases; in seven of these (37%) lymphoma involvement was diagnosed by the light chain analysis. Diagnostic precision was enhanced by combining morphological and immunological evaluation of fine needles aspirates in patients with established or suspected non-Hodgkin's lymphoma.
The cytogenetic findings in 70 patients with non-Hodgkin lymphoma have been correlated with tumor histopathology according to the Kiel classification. Certain chromosome aberrations displayed a nonrandom association with the grade of malignancy: 4 lymphomas out of 6 with 1p+, 5 out of 7 with del(6)(q15), 7 out of 11 with 14q+, and 5 out of 8 with +18 belonged to the high grade malignancy group, whereas 9 lymphomas out of 10 with t(14;18) were low grade malignant. Two aberration types were closely associated with specific histopathologic subtypes: t(14;18) occurred in 7 cases out of 10 in centroblastic/centrocytic (cb/cc) follicular lymphomas, and 5 cases out of 6 with i(17q) were cb or cb/cc. Although less striking, there was a tendency for del(6)(q15) to occur in cb or cb/cc lymphomas (4 cases out of 7), in contrast to only 1 case out of 5 with the more distal deletion del(6)(q21).
Cytogenetic analysis was attempted in 20 patients with Hodgkin's disease. No mitoses were found in 2 cases, normal metaphases in 7, and normal metaphases with nonclonal aberrations in 7. Of the 4 cases with clonal aberrations, one had +16 as the sole change, whereas the remaining tumors had multiple numerical and structural changes.
Preoperative fine-needle aspirates of 25 soft tissue tumors and four bone tumors were used for cytodiagnosis and flow cytometric DNA ploidy analysis. The results were compared with the histopathologic diagnosis and flow cytometric DNA ploidy analysis on tissue samples after surgery. There was good agreement between the cytodiagnoses and histopathologic diagnoses with regard to benign tumor or sarcoma. There was good agreement between the ploidy determinations in aspirates and tissue samples in 20 out of the 26 tumors that could be analyzed. Aneuploid cell populations were found in 13 tumors cytologically classified as sarcoma and in one tumor classified as unspecified malignant tumor. These 14 tumors also showed aneuploid cell populations in the tissue samples and were histologically diagnosed as high-grade malignant sarcomas. The combined evaluation of preoperative cytodiagnosis and DNA ploidy on aspirates may give valuable prognostic information.
Primary localized non-Hodgkin's lymphomas (NHL) of the thyroid are rare. The data presented are derived from 819 consecutive patients with NHL and six patients with anaplastic thyroid carcinomas of small cell type investigated and treated at our department between 1970 and 1981. The present analyses are based on the 19 patients, who were found to have localized primary thyroid lymphomas. Four of these patients were initially considered to have undifferentiated small cell carcinomas of the thyroid but revealed to be lymphomas at re-examination supplemented with immunohistopathologic staining. Prognosis has been evaluated with regard to initial stage, histopathology according to the Kiel classification and therapy. Median follow-up was 5 years. The crude survival was 77% 5 years after diagnosis. This was not significantly less (4.2%) than the overall-survival in an age- and sex-matched population, despite the majority of patients having tumours which were locally advanced, often with spread to regional lymph nodes, and in many cases a histology showing a high-grade malignancy according to Kiel classification. The excellent prognosis in the current study compared to other studies is probably mainly attributed to more extensive staging procedures. The biologic behaviour supports the hypothesis that these lymphomas represent lymphomas of mucosa associated lymphoid tissue (MALT). According to present results anaplastic thyroid carcinoma of small cell type must be extremely rare.
The European Organization for Research on Treatment of Cancer (EORTC) Thyroid Cancer Cooperative Group presented a prognostic index in 1979 that included all histologic groups of thyroid carcinomas, and was based on a multivariate analysis of 507 patients with a median follow-up of 40 months. The current report not only uses a multivariate analysis to study the clinical validity and reproducibility of this index on case material consisting of 226 differentiated thyroid carcinomas with a considerably long follow-up (11 years), but also it investigates possible prognostic factors, other than those proposed by the EORTC. Three EORTC variables could be reproduced as important: age at diagnosis, locally advanced disease, and distant metastases. Of the additional histopathologic variables tested, microscopic tumor invasion beyond thyroid capsule (pT4) and marked cellular atypia (MCA) proved to be significant. When the effect of the age-correlated tumor factors pT4 and MCA of differentiated thyroid carcinomas were taken into consideration, age alone lost its prognostic importance as a guide for treatment.