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Biomedical subjects

P Klemi

Publications and source records attributed to P Klemi.

At least 55 records · Page 3Linked to original sources

Prognostic value of lymphocyte homing receptor and S phase fraction in non-Hodgkin's lymphoma.

Lymphocyte homing receptors (HRs) mediate lymphocyte binding to high endothelial venules, and control their circulation between the blood and the lymphoid organs. The role of HRs and nuclear DNA content in the spread and prognosis of non-Hodgkin's lymphoma was studied from paraffin-embedded tumor sections of 104 patients followed-up for the minimum of 5 years after the diagnosis. HR expression was analyzed by staining with a monoclonal antibody, Hermes-3, and DNA content by flow cytometry. Ten (10%) lymphomas were HR negative (HR-), 14 (13%) weakly (HR+/-), and 80 (77%) strongly positive (HR+). HR- lymphomas disseminated less often than HR+/- or HR+ lymphomas (P = .03), and their prognosis was more favorable (P = .03), although they often had a large S phase fraction (SPF), indicating a rapid proliferation rate. A large SPF (greater than 12%) was strongly associated with an unfavorable histologic type in Working Formulation (P = .0001) and poor survival (P = .006), whereas DNA aneuploidy was not. The 5-year survival rate corrected for intercurrent deaths was 61% in lymphomas with SPF less than 12% or with HR-, but only 15% if SPF was greater than 12% and HR+ (P less than .0001). In multivariate analysis stage (P less than .001), SPF (P = .002) and HR (P = .003) were the only independent prognostic factors.

Adult↗

Inter-laboratory comparison of DNA flow cytometric results from paraffin-embedded breast carcinomas.

Consecutive sections from 33 paraffin-embedded human breast carcinomas without intratumor heterogeneity were sent for flow cytometric (FCM) DNA analysis in two experienced laboratories. FCM instruments, run conditions, and tumor disaggregation procedures were different in the two laboratories. In four cases (12%) the laboratories reported a different DNA ploidy and DNA index (DI). These variations were due to analytical reasons, differences in the detection rates of near-diploid and tetraploid DIs, not due to interpretation of data or the criteria used for aneuploidy. There was a significant correlation between S-phase fractions (SPF) obtained in the two laboratories (r = 0.90, p less than 0.0001) if only cases with concordant DI were included. Discordant DI usually led to very different SPF values.

Aneuploidy↗

Carcinoma of the breast in children.

Carcinoma of the breast in children is an extremely rare disease, only 44 patients have been reported in the world literature. We report on a case of breast cancer in a 9-year-old girl, who was admitted to the hospital because of a four-month history of a painless mass in the right breast. Clinical examination and mammography resulted in a strong suspicion of malignancy. The histology corresponded to juvenile secretory carcinoma, the histological type without the characteristics of prepubertal cancer cases. Electron microscopy demonstrated intracellular large vacuoles and acini filled with secretory material. The mitotic index was low, the highest measured value was 4 mitotic figures per 10 high power fields corresponding to 2.78 mitotic figures per mm2 of epithelium in the microscope field. Flow cytometry showed that the neoplastic cells were diploid and had a low S-phase fraction. A simple mastectomy including axillary evacuation was performed. No lymph node or distant metastases were found. Postoperative radiation treatment or chemotherapy were not administered. Our patient has been in follow-up for six years without recurrence. In this case simple mastectomy with axillary evacuation seems to have given a cancer-free development into adulthood. Earlier reports have also shown a favourable outcome in these tumours.

Breast↗

Nuclear DNA content as a prognostic factor in T1-2N0 breast cancer.

One hundred fifteen patients with postsurgical stage T1-2N0 breast cancer with the minimum follow-up of 22 years and from a defined population were studied to find reliable prognostic factors predicting long-term survival rate. The 30-year survival rate corrected for intercurrent deaths was 75%, and no deaths of breast cancer occurred after the nineteenth year of follow-up. The 30-year crude survival rate was only 28%, indicating that the great majority of these patients ultimately die of other causes than breast cancer. The nuclear DNA content could be determined by flow cytometry in 95 of the 115 cases, and 52 (55%) of them were nondiploid. DNA ploidy (diploid vs. nondiploid, P = 0.11) did not have a significant influence on long-term survival rate, but cancers with the DNA index less than 1.2 had more favorable prognosis in a univariate analysis than those with the DNA index more than 1.2 (P = 0.02). The most important independent prognostic factor in Cox's multivariate analysis was the presence of lymphatic vessel invasion of cancer cells (P less than 0.001). Several other factors, including histologic grade and type, extent of necrosis, type of tumor margin, age at diagnosis, and primary tumor size could be shown to be of prognostic value in univariate and/or multivariate analyses.

Adult↗

The prognostic significance of nuclear DNA content in invasive breast cancer--a study with long-term follow-up.

The nuclear DNA content of 351 breast carcinomas was determined by flow cytometry from paraffin-embedded tissue to assess the prognostic significance of DNA ploidy, the DNA index (DI) and the S-phase fraction (SPF). The minimum follow-up of the patients was 22 years, and they were all from a defined urban population. DNA ploidy correlated with histological type and grade, mitotic count and nuclear pleomorphism (P less than 0.0001), and also with axillary nodal status (P = 0.0005), tumour necrosis (P = 0.001), primary tumour size (P = 0.03), menopausal status (P = 0.004) and the presence of distant metastases at the time of the diagnosis (P = 0.04). Survival corrected for intercurrent deaths of the patients with a diploid tumour was better than that of the patients with a non-diploid tumour (P = 0.0001, 48% vs 28% at 25 years). SPF had prognostic significance in both axillary node positive and negative patients, but ploidy and DI only in the node negative group, and their significance was greater in post-menopausal than in premenopausal patients. Axillary nodal status, primary tumour size, histological grade and the type of tumour margin circumscription were the most important independent prognostic factors in Cox's multivariate analysis, and SPF had independent prognostic value, whereas ploidy and DI did not. It is concluded that DNA ploidy, DI and SPF have long-term prognostic significance in breast cancer.

Adult↗

A flow cytometric analysis of 23 carcinoid tumors.

Twenty-three carcinoid tumors were investigated from paraffin-embedded tissue with flow cytometry (FCM) in order to correlate the DNA ploidy with clinical variables. DNA aneuploidy was found in ten tumors (45%) and one tumor was classified as tetraploid. Diurnal urinary excretion of 5-hydroxy indolic acetic acid (5-HIAA) was known to be elevated in seven of eight diploid tumors and in four of seven aneuploid carcinoids with distant metastases. Six (55%) of the diploid tumors had not given rise to metastases at the time of diagnosis, compared with three (30%) of the aneuploid tumors. Six of seven patients with an aneuploid tumor and three of five patients with a diploid tumor, observed for at least 10 years, died of the disease. It was concluded that, unlike in earlier studies with static DNA cytometry, DNA aneuploidy is common in human carcinoid tumors and may occur in tumors secreting biogenic amines.

Adult↗

Fluorodeoxyglucose imaging: a method to assess the proliferative activity of human cancer in vivo. Comparison with DNA flow cytometry in head and neck tumors.

Thirteen patients with malignant head and neck tumors were studied before they were treated with (18F) fluorodeoxyglucose (FDG) imaging and DNA flow cytometry (FCM). The nuclear DNA content and the percentage of proliferative cells (S + G2/M) were compared with the FDG uptake; FDG was retained in the primary tumor and/or neck metastasis in all patients. The accumulation of FDG did not correlate with histologic grade of the tumors, but there was a clear correlation (r = 0.86, P less than 0.001) between the proportion of the cells in S + G2/M phases of the cell cycle and the intensity of FDG accumulation. The uptake of FDG by the tumor also correlated with the percentage of S-phase cells (r = 0.82, P less than 0.001). The result suggests that enhanced glucose metabolism, measured by FDG uptake, is associated with the proliferative activity of the tumor. Thus, imaging with FDG may offer a new method to assess the aggressiveness of human cancer growth in vivo.

Aneuploidy↗

Oral biopsy and fine needle aspiration biopsy from subcutaneous fat in diagnosis of secondary amyloidosis.

The reliability of oral biopsy (OB) and fine needle aspiration biopsy from subcutaneous fat (FNAB) in the diagnosis of secondary amyloidosis was compared using the specimens taken from 124 patients, 107 adults and 17 children, suffering from long lasting rheumatoid diseases. 41 of the patients (33.0%) were shown to be positive for amyloidosis with one or both methods. OB was positive in 28, FNAB in 33, and both methods in 20 patients. In addition, rectal biopsy (RB) was positive in 14 out of 43 cases, where it had been taken. In 3 patients, this method was positive for amyloidosis, although OB and FNAB were negative. Thus, the total number of patients positive for amyloidosis in this study was 44 (35.5%). The mean duration time of the disease was significantly longer in the adult and child patient groups with amyloidosis than in those without amyloidosis. The diagnostic sensitivity of OB was 64%, and that of FNAB 75%. The results speak for the use of FNAB as the first choice method in the diagnosis of secondary amyloidosis.

Adipose Tissue↗

Mast cells and IgE in intestinal mucosa in adult atopic dermatitis patients.

Duodenal biopsies from 29 adult atopic dermatitis (AD) patients with multiple positive skin prick test reactions were examined and the results compared with biopsies from 13 non-atopic controls. The duodenal mucosa showed mild inflammatory changes in six out of the 29 patients, but was normal in all the controls. Numerous anti-IgE positive cells, increasing with the severity of AD, were found in the duodenal mucosa in 25 of the 29 AD patients compared with few sporadic positive cells seen in only two out of 13 controls (P less than 0.001). The total serum IgE level showed a significant positive correlation with the number of anti-IgE stained cells in the mucosa (P less than 0.05). No significant differences were found in the total number of toluidine blue stained cells or cells immunoreactive for histamine between patients and controls. However, AD patients who had high numbers of anti-IgE positive cells often had decreased numbers of histamine immunoreactive cells in the mucosa suggesting mast cell degranulation. These findings provide further evidence that also in adult AD patients the gastrointestinal tract may serve as a portal of entry for allergens which may lead to exacerbation of AD.

Adult↗

Influence of cellular DNA content on survival in differentiated thyroid cancer.

Cellular DNA content was measured using a novel flow cytometric method to analyze paraffin-embedded tissue blocks from 125 patients with differentiated thyroid cancer. DNA aneuploidy was found in 20 (24%) of the 82 papillary, 20 (56%) of the 36 follicular, and in four (57%) of the seven medullary carcinomas. Aneuploidy was found to be more common in the elderly (P less than 0.002), in moderately and poorly differentiated carcinomas (P less than 0.004), and in tumors infiltrating beyond the thyroid capsule (P less than 0.03). Patients with an aneuploid tumor had less favorable cumulative survival (P less than 0.0001) than patients with diploid cancer. However, in papillary and follicular carcinomas, multivariate analysis using stepwise Cox model showed age at diagnosis, follicular type, and tumor invasion beyond the thyroid capsule to be more important independent prognostic factors. Increasing probability of DNA aneuploidy with increasing age explains partially why prognosis of differentiated thyroid carcinoma is poor in older patients.

Age Factors↗

Diagnostic aspects of primary tubal malignancy.

Eleven cases of primary tubal malignancy are reported to characterize clinical symptoms and diagnostic procedures. The importance of a yellow vaginal discharge is emphasized as being a diagnostic sign.

Adenocarcinoma, Papillary↗

DNA aneuploidy in follicular adenomas of the thyroid gland.

The nuclear DNA content of 67 follicular adenomas and 7 adenomatous goiters was determined by flow cytometry. The DNA analysis was done with the use of paraffin-embedded tissue, but in 14 cases of follicular adenoma fresh material obtained by fine needle aspiration biopsy was also available. An abnormal DNA stemline was found in 27% (18/67) of the adenomas and in 1 (14%) of the adenomatous goiters. Four (29%) of the 14 adenomas analyzed from fresh samples were aneuploid. In none of the 12 aneuploid or 40 diploid adenomas followed for more than 5 years (mean, 7.2 years) did distant metastases develop after surgical removal of the adenoma. The paraffin blocks of cases with DNA aneuploidy were sectioned subserially at 1-mm intervals, but none of these tumors showed invasion into the capsule or blood vessels. It is concluded that DNA aneuploidy is common in histologically benign follicular adenomas of the thyroid, and that DNA aneuploidy does not appear to be associated with adverse prognosis in follicular adenomas if the tumor is surgically removed.

Adenoma↗

Xanthoma tendinosum in a normolipemic ectodermal dysplasia patient.

A female patient with congenital ectodermal dysplasia is described, who developed xanthoma tendinosum in her hands simulating rheumatoid arthritis. The serum lipids of this patient were normal. Both ectodermal dysplasia and xanthoma tendinosum in a normolipemic patient are rather uncommon and to our knowledge have not been previously reported in one and the same patient.

Adult↗

Ovarian function during and after curative intracavitary high dose-rate irradiation: steroidal output and morphology.

The endocrinological function of the ovary during and after curative intracavitary high dose-rate irradiation has been studied by determining the peripheral plasma levels of P, E1, E2, FSH, LH and PROL in 8 patients aged 37 +/- 7 yr (+/- SD). In addition, the concentrations of E1 and E2 in ovarian venous blood during the estimated ovulatory phase after irradiation were determined. The functional structure of the ovary was studied histochemically using 3 beta-hydroxysteroid dehydrogenase (HSD) and ultrastructurally and histologically with routine methods. The results during and after irradiation were compared to those before irradiation. In addition, 28 postmenopausal patients were used as controls. At the end of the irradiation course, which lasted from the premenstrual to the ovulatory phase, 3 out of 4 patients with cervical carcinoma had normal plasma P levels; the menstrual cycles of these patients was previously ovulatory. The normal P levels as well as a rise in E1 and E2 concentrations indicate ovulation. During the next menstrual cycle these values and the E2/E1 ratio in peripheral venous blood decreased and the levels of FSH and LH rose to the postmenopausal values. In patients with endometrial carcinoma, the menstrual cycle was anovulatory both before and after radiotherapy; in estrogen and gonadotrophin levels, similar changes were observed as in patients having ovulatory cycles. In ovarian venous blood, the E2 plasma levels and the E2/E1 ratios were in both groups significantly higher at the time of the second potential ovulatory phase than the corresponding postmenopausal values. As in the postmenopausal women, both E1 and E2 levels in irradiated patients were higher in ovarian effluent blood than peripherally. The ovarian/cubital E1 ratios did not differ between these groups. For E2, this ratio was, however, significantly higher in irradiated patients than in postmenopausal controls. The morphological findings--both by light and electron microscopy--as well as the enzyme-histochemical studies support the chemical results reflecting a decreased yet significant estrogen production in the ovaries after irradiation.

Adult↗

Malignant thymus tumour progressing into acute leukaemia with non-specific esterase activity.

We describe an 8-year-old girl who presented a massive mediastinal tumour of thymic origin. Surgical excision was unsuccessful. Irradiation treatment (4,500 rad) together with intensive combination chemotherapy resulted in regression of the tumour. After three months, an increase of blasts was observed in the peripheral blood and bone marrow. The terminal phase was characterized by acute leukaemia, which did not respond to chemotherapy. Despite the thymic origin of this malignancy, the blast cells contained non-specific esterase activity as determined by naphthol-AS-acetate as substrate. The NaF-sensitive form of this enzyme is a characteristic of monocytes-macrophages. Other monocyte-macrophage markers were, however, negative. We conclude that the NaF-sensitive naphthol-AS-acetate esterase is not limited to tumours of the monocyte-macrophage system.

Bone Marrow Examination↗

Cytological and functional characterization of three cases of malignant histiocytosis.

This report is a cytological and functional description of 3 cases of malignant histiocytosis (MH). These patients suffered from an intense proliferation of histiocytic cells that occurred predominantly in the bone marrow in 2 cases (the primitive cell type of MH), and in the spleen, liver and intraabdominal nodes in the third patient (the mature cell type of MH). The malignant cells carried the cytological markers typical for the monocyte-macrophage series, e.g., acid phosphatase, NaF-sensitive naphthol-AS-acetate esterase, acid alpha-naphthyl-acetate esterase, lysozyme, and also Fc-IgG-receptors and mouse C3-receptors. Their in vivo phagocytic activity was investigated by ultrastructural studies. In every case, the histiocytic cells phagocytosed Candida albicans in vitro. The proliferative histiocyte compartment differed from that of the mature cells, although these two cell compartments were morphologically indistinguishable in the primitive-cell-type cases of MH. Malignant histiocytes were capable of destroying phagocytosed fungi, but this ability was clearly inferior to that of the mature histiocytes in these 2 cases. The results revealed that most, if not all, monocyte-macrophage characteristics are present in the malignant cells in MH. Nevertheless, the morphological and clinical features seemed to be variable.

Adult↗