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PubMed2003

Evidence for an association between cutaneous malignant melanoma and lymphoid malignancy: a population-based retrospective cohort study in Scotland.

We analysed the risk of cutaneous malignant melanoma (CM) occurring in patients following a diagnosis of non-Hodgkin's lymphoma (NHL) or chronic lymphatic leukaemia (CLL), and of NHL or CLL subsequently developing in CM survivors. Cohorts of patients with CM, NHL or CLL (index cancer) diagnosed between 1975 and 1997 were identified from the Scottish national cancer registry and followed through the registry for subsequent CM, NHL or CLL. The standardised incidence ratio (SIR) for each cancer was calculated and overall risk, risk in relation to gender and age at diagnosis of the index cancers and time from diagnosis of the index cancer to the diagnosis of the second malignancy were measured. There were 9385 CM patients, 4016 CLL patients and 13 857 NHL patients identified with an index cancer with 56 195, 14 450 and 44 999 person-years of follow-up, respectively. There was an increased risk of both CLL and NHL following a diagnosis of CM (SIR 2.3 and 1.5, respectively) and of CM following a diagnosis of CLL and NHL (SIR 2.3 and 2.1, respectively). The risk was statistically significantly increased for CLL developing in CM patients and for CM occurring in NHL survivors (P<0.05). This study supports an association between CM, CLL and NHL developing in the same patient. Immunosuppression, exposure to ultraviolet radiation and genetic factors may lead to a host environment that is conducive to the development of these malignancies.

Aged↗
PubMed2005

Second primary malignancies after treatment for malignant lymphoma.

To determine the incidence and possible causes of second primary malignancies after treatment for Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL). A cohort of 3764 consecutive patients diagnosed with HL or NHL between January 1970 and July 2001 was identified using the Sheffield Lymphoma Group database. A search was undertaken for all patients diagnosed with a subsequent primary malignancy. Two matched controls were identified for each case. Odds ratios were calculated to detect and quantify any risk factors in the cases compared to their matched controls. Mean follow-up for the cohort was 5.2 years. A total of 68 patients who developed second cancers at least 6 months after their primary diagnosis were identified, giving a crude incidence of 1.89% overall: 3.21% among the patients treated for HL, 1.32% in those treated for NHL. Most common were bronchial, breast, colorectal and haematological malignancies. High stage at diagnosis almost reached statistical significance in the analysis of just the NHL patients (odds ratio = 3.48; P = 0.068) after adjustment for other factors. Treatment modality was not statistically significant in any analysis. High stage at diagnosis of NHL may be a risk factor for developing a second primary cancer.

Case-Control Studies↗
PubMed1999

Malignant peripheral nerve sheath tumor with perineurial cell differentiation (malignant perineurioma).

A unique case of malignant peripheral nerve sheath tumor (MPNST) with perineurial cell differentiation occurring in a 63-year-old woman in a subcutis of the forearm is described. The tumor contained cellular and myxoid areas. The neoplastic cells were fusiform with distinct cell borders. They were arranged in storiform pattern and in wavy parallel cell cords in the cellular areas. Focally, a pleomorphism and mitotic activity (including atypical mitoses) similar to those of malignant fibrous histiocytoma were seen. The myxoid parts contained haphazardly oriented cells and scarce lipoblast-like multivacuolated cells mimicking a liposarcoma. In the differential diagnosis, myxoid liposarcoma, dermatofibrosarcoma protuberans, malignant fibrous histiocytoma and low-grade fibromyxoid sarcoma were considered. Immunohistochemically, perineurial differentiation was indicated by the diffuse expression of epithelial membrane antigen and focal reactivity for CD34. The tumor was negative with antibodies to S-100 protein, Leu-7, CD68 (KP1), vimentin and cytokeratin AE1/AE3. Ultrastructure of tumor cells revealed features of MPNST. No recurrence occurred in the patient during 2 years follow up.

Antigens, CD34↗
PubMed1978

Analysis of malignancy in human cells: malignant and transformed phenotypes are under separate genetic control.

Human cell hybrids derived from malignant HeLa and normal fibroblast parental cells expressed many of the transformed properties of the HeLa parent but their tumor-producing capability was suppressed. Hybrids derived from HeLa/HeLa fusions retained both their transformed and malignant phenotypes. Thus, an apparent separation of the control of the transformed versus malignant phenotype is indicated. Furthermore, several transformed properties--including lack of density-dependent inhibition of growth, lectin agglutination, lowered requirement for serum growth factors, and anchorage independence--are expressed coordinately in the nontumorigenic hybrids. This finding suggests that none of these properties by themselves, or in concert, endows a cell with tumorigenic potential.

Animals↗
PubMed2004

Contribution of flow cytometry to the diagnosis of malignant and non malignant conditions in lymph node biopsies.

In order to assess the contribution of FC to the diagnosis of lymph node disorders we retrospectively compared the pathological and the FC diagnosis made in 118 consecutive lymph node biopsies. Pathological diagnosis included non malignant conditions (n = 43), B-cell Non Hodgkin lymphoma (NHL) (n = 30), T-cell NHL (1 case), carcinoma (n = 18), Hodgkin lymphoma (HL) (n = 15), melanoma (n = 2), chronic myelocytic leukemia (n = 12), miscellaneous non-lymphoid tissues (n = 6) and undetermined conditions (n = 2). Among the 116 assessable samples, FC was in agreement with histology in 102 cases (87.9%; 95%CI = 81-93) which included 38 benign conditions (90%; 95% CI = 77-97%), 29 NHL (96.7%; 95% CI = 83-100), 18 carcinomas (100%; 95% CI = 81-100), and 12 HL (80.0%; 95% CI = 52-96). Discrepancies (14 cases) included 3 HL undiagnosed by FC and 2 granulomatous adenitis with an erroneous FC diagnosis of HL. Finally, a malignant condition was suspected only by FC in 5 cases (1 carcinoma, 2 B-cell and 2 T-cell NHL) and subsequently demonstrated by additional diagnostic procedures. In conclusion, this study confirms that FC performed on fresh lymph node samples is a powerful diagnostic tool in patients with malignant lymphoma. A few cases left undiagnosed by classical pathological analysis can be recognized by FC. Carcinoma is readily identified by FC analysis, while some benign conditions and Hodgkin lymphoma can be misdiagnosed with the use of FC, although the potential of FC to properly recognize HL is improving compared to previously reported studies. FC is a useful adjunct to pathological analysis of lymph node specimens.

Adenocarcinoma↗
PubMed1975

Nonmalignancy of hybrids derived from two mouse malignant cells. II. Analysis of malignancy of LM (TK-) Cl 1D parental cells.

The possibility that Cl 1D cell line, an L-cell line derivative, was a mixture of malignant and nonmalignant cells was investigated because previous experiments showed that some hybrids derived from Cl 1D and tumor cell lines grew in vivo, whereas others apparently did not have that capacity. More highly malignant Cl 1D cells were not selected by animal passage of tumors obtained from inoculation of cultures. The tumor-producing capacity of this line (10%) was greatly increased (81%) in X-irradiated hosts. These observations suggested that the low capacity of Cl 1D cells to grow in vivo did not result from varying degrees of malignancy but mainly from interference of immunogenetic factors between cells and their inbred hosts of origin. Numerous hybrids between tumor and host cells were in all tumors examined.

Animals↗
PubMed1997

Usefulness of a mouse myelin basic protein promoter for gene therapy of malignant glioma: myelin basic protein promoter is strongly active in human malignant glioma cells.

We have searched for suitable promoters to regulate the expression of suicide genes for use in gene therapy. We have shown that the 1.3-kb fragment of the mouse myelin basic protein (MBP) promoter region initiates transcription in mouse glioma cells more efficiently than glial fibrillary acidic protein (GFAP) or myelin proteolipid protein (PLP) promoter. Among three different lengths of the MBP promoter, the shortest (256-bp) core promoter region initiates transcription as efficiently as 650-bp or 1.3-kb MBP promoter lengths in RSV-M glioma cells. To assess the suitability of the MBP promoter for use in clinical trials of malignant glioma gene therapy, we also had to show that it (the 1.3-kb length in this case) is effective in human glioma cells, as well as in murine glioma cells. The activity of the MBP promoter is much higher than that of GFAP or PLP promoter in most human glioma cells, suggesting that the MBP promoter would be best for directing toxic gene expression in gene therapy for patients with malignant glioma. Human glioma cells in which the MBP promoter was strongly active were sensitive to ganciclovir when they were transduced with MBP promoter/herpes simplex virus thymidine kinase gene-bearing retroviruses. In conclusion, retrovirus-targeted gene therapy for malignant glioma using this MBP promoter is a promising candidate for clinical trials.

3T3 Cells↗
PubMed2007

The risk for cutaneous malignant melanoma, melanoma in situ and intraocular malignant melanoma in relation to tobacco use and body mass index.

BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) and melanoma in situ (MIS) has been increasing during the last 50 years. Malignant melanoma (MM) is also the most common intraocular malignancy (IMM). Besides ultraviolet radiation, the cause of these tumours is largely unknown. OBJECTIVES: We designed a study to examine the effect of body mass index (BMI) and tobacco use on the risk for MM and MIS. METHODS: Analyses were performed on a nationwide cohort of 339 802 Swedish construction workers. Exposure information was collected prospectively by questionnaires combined with personal interviews. RESULTS: Follow up yielded a total of 7 663 400 person-years during which 1639 workers developed MM/MIS. The risk for MM/MIS was reduced in current or previous smokers compared with those who had never smoked, both when analysing all smoking tobacco products combined and when analysing cigarette and pipe smokers separately. The risk was further diminished with longer duration of smoking and greater quantity of tobacco smoked. The effect was more evident in CMM/MIS than in IMM. Snuff taking conferred a decreased risk for CMM/MIS, and a BMI over normal weight range conferred an increased risk for CMM. CONCLUSIONS: Tobacco smoking was found to be inversely associated with the risk for CMM and MIS. The mechanism of action is unknown but it has been suggested to be due to the immune suppressive effect that tobacco exerts which would be protective against deleterious immune reactions caused by, for example, the sun. Neither is the mechanism behind the higher risk for CMM due to being overweight known. One hypothesis is that it is an effect of a hormonal imbalance. Further studies are required to elucidate these mechanisms.

Adolescent↗
PubMed1979

Lipid composition of human malignant melanoma tumors at various levels of malignant growth.

The lipid pattern of thirteen human melanoma tumors from various tissues were investigated. In seven of the tumors, an estimate was given about the proportion of malignant melanocytes to the total cell population, and a reverse correlation was determined between the proportion of malignant cells in these tumors and their neutral lipid content. The phospholipids did not show any modification, nor did the cholesterol in the cancerous tissues. The ganglioside pattern was found to be similar in all analyzed samples, with GM3, GM2 and GD3 as major components, although no correlation was found between the malignant level and the ganglioside content of the tumors.

Cholesterol↗
PubMed2006

Seborrhoeic keratosis and malignancy: collision tumour or malignant transformation?

A retrospective study of 813 histological specimens reported as seborrhoeic keratoses included 43 (5.3%) associated with non-melanoma skin cancer. Intraepidermal carcinoma (squamous cell carcinoma in situ) was the most common of these (36). There were five basal cell carcinomas (one with intraepidermal carcinoma also) and two invasive squamous cell carcinomas. No melanomas were reported. Twenty-seven of the intraepidermal carcinomas appeared to arise within the seborrhoeic keratosis as did one of the invasive squamous cell carcinomas. Of these 28 lesions, the head was the most common site. Fourteen were clinically diagnosed as a non-melanoma skin cancer with only nine clinically felt to be a seborrhoeic keratosis. These lesions may represent malignant transformation within the seborrhoeic keratosis. Twelve specimens reported adjacent dual pathologies, with the trunk and limbs the most common sites. Seven were diagnosed clinically as a skin malignancy, whereas three were thought to be solar keratoses. Clinically, the remaining two were seborrhoeic keratoses. The origin of the malignancy in these cases is less obvious and may represent collision tumours. Three curette specimens could not be assessed for architecture.

Adult↗
PubMed1977

Acute myeloblastic leukaemia with marrow fibrosis (malignant myelosclerosis): acute leukaemia or malignant myelosclerosis?

Malignant myelosclerosis has been described as a rare form of acute myeloproliferative disorder characterised by minimal or absent splenomegaly, cytopenias, circulating myeloblasts and diffuse marrow fibrosis, but distinction between this entity and acute myeloblastic leukaemia with marrow fibrosis is difficult. This report describes a 50-year-old man who presented with features similar to those of malignant myelosclerosis but ther terminal stage was characterised by generalised lymphadenopathy, bone tenderness, marked leucocytosis and myeloblastaemia. Post mortem examination showed multiple chloromata consisting of myeloblasts. These findings suggest that malignant myelosclerosis may be but a variant of acute myeloblastic leukaemia and probably should be treated similarly. A possible association between diagnostic medical irradiation and this acute myeloproliferative disorder is discussed.

Acute Disease↗
PubMed1993

Cutaneous histiocytic malignancy. Immunohistochemical re-examination of cases previously diagnosed as cutaneous "histiocytic lymphoma" and "malignant histiocytosis".

True histiocytic lymphoma (THL) and malignant histiocytosis (MH) have been defined by clinical and histologic findings and enzyme histochemistry. We reviewed cases previously diagnosed as cutaneous histiocytic lymphoma (HL) and MH with cutaneous lesions. These cases had been classified as "histiocytic" on the basis of previous enzyme histochemistry profiles of frozen tissue. Cutaneous tumor cells were reevaluated using a panel of immunohistochemical stains in formalin-fixed, paraffin-embedded tissue in correlation with histopathologic examination. The antibodies used in this study were directed against CD45 (leukocyte common antigen [LCA]), CD20 (L26) for B cells, CD3 and CD45RO (UCHL-1) for T cells, CD68 (KP-1) and lysozyme for histiocytes, as well as CD30 (BerH2) for Ki-1 positive cells. On re-evaluation, the seven cases originally classified as HL were reclassified as one case of THL with neoplastic cells positive for CD68 (KP-1) and lysozyme, two cases with immunohistochemical features of Ki-l lymphoma (including one of T-cell lineage), three cases of T-cell lymphoma, and one case of B-cell lymphoma, all associated with variable degrees of reactive histiocytosis. The four cases originally classified as MH were reclassified as two cases of MH and two cases of uncertain lineage. Although rare, histiocytic malignancies do exist. However, the diagnosis of histiocytic malignancy should be made only after careful correlation of atypical tumor cells in histopathologic sections and sections stained immunohistochemically. Erroneous classification of reactive histiocytes as neoplastic histiocytes using only enzyme histochemistry in frozen sections is a pitfall to be avoided.

Adult↗
PubMed1977

DNA synthesis in unstimulated blood lymphocytes of patients with untreated malignant lymphomas or other malignant tumors.

Blood lymphocyte DNA synthesis, as expressed by 24-h uptake of 3H-thymidine in culture of mononuclear peripheral blood leucocytes has been reduced prior to treatment in 18 patients with Hodgkin's disease, 11 with non-leukaemic lymphosarcoma, 13 with reticulosarcoma and 20 with various solid tumors, and compared to 37 normal control subjects.The 3H-thymidine uptake was significantly increased in all the patient groups, but no significant difference existed between them. Increased uptake of 3H-thymidine did not appear to correlate with the degree of dissemination in any of the patient groups or with the presence or absence of general symptoms in malignant lymphoma. It is concluded that increased DNA synthesis in peripheral blood lymphocytes is a feature not limited to Hodgkin's disease, but found in non-Hodgkin's malignant lymphomas and other malignancies to about the same extent.

Cells, Cultured↗
PubMed1992

Toluidine blue and Lugol's iodine application in the assessment of oral malignant disease and lesions at risk of malignancy.

The purpose of the study was to determine if toluidine blue application and counter staining with Logul's iodine would aid in diagnosis of oral dysplastic or malignant lesions. The sensitivity, specificity, and predictive values were studied. Routine use of these tissue stains was found to be sensitive and specific. The use of stains provided better demarcation of oral squamous cell carcinoma and dysplastic changes and assisted in site selection for diagnostic biopsy. The use of toluidine blue and Lugol's iodine can assist in assessment of patients at risk of developing malignant disease and those with lesions that are clinically suspect of dysplasia or malignancy.

Adult↗
PubMed1978

Multicentric primary malignant melanomas of the choroid: two separate malignant melanomas of the choroid and two uveal naevi in one eye.

Two completely separate malignant melanomas of the choroid occurred in 1 eye containing 2 additional uveal naevi. Review of the literature disclosed 7 further patients with unilateral multicentric malignant melanomas of the choroid and 11 bilateral multicentric malignant melanomas of the uvea. General aspects of multicentric primary neoplasia are discussed and an interpretation is attempted.

Choroid Neoplasms↗
PubMed1997

Telomerase activity and in situ telomerase RNA expression in malignant and non-malignant lymph nodes.

AIMS/BACKGROUND: Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant tumours, but is inactive in normal somatic cells except for male germ cells and proliferating stem cells. Thus, the measurement of telomerase activity in tissue samples may provide useful diagnostic and prognostic information. The aim of this study was to determine whether telomerase expression is useful for the detection of occult malignant cells in lymph nodes. METHODS: Telomerase activity was compared with histological findings in 123 surgically removed lymph nodes submitted for routine or frozen section diagnosis. Telomerase activity was measured using a modified, semi-quantitative PCR-based telomeric repeat amplification protocol (TRAP). The assay was adapted for single 5 microns OCT embedded cryostat sections. In either fresh tissues or cryostat sections, normalised activity was linear when compared with protein concentration. Furthermore, using an in situ hybridisation method, the human telomerase RNA (hTR) component was measured in a subset of negative and positive nodes. RESULTS: Most (96%) of the 97 histologically negative nodes expressed low levels of activity (mean value of positive samples = 3.0 units/microgram protein) which may be derived from activated lymphocytes that express telomerase activity. All 26 malignant nodes (17 metastases, nine lymphomas) expressed telomerase (mean value = 17.8 units/microgram protein). The rank order levels between the two groups differed significantly (p = 0.0002). In situ results showed clearly that the hTR was expressed relatively highly in metastatic cancer cells and at lower levels in germinal centres of secondary follicles. CONCLUSIONS: Although expression of telomerase by activated lymphocytes may limit its usefulness, measurement of enzyme activity combined with detection of hTR using in situ hybridisation may assist in the histopathological diagnosis of lymph nodes.

Frozen Sections↗
PubMed2001

Malignant peripheral nerve sheath tumour arising within neurofibroma. An immunohistochemical analysis in the comparison between benign and malignant components.

AIMS: To compare the expression of immunohistochemical variables between benign and malignant components of malignant peripheral nerve sheath tumour (MPNST) arising within neurofibroma. METHODS: Eight cases of MPNST arising within a neurofibroma, associated with neurofibromatosis type 1 (NF1), were studied. The areas of MPNST and neurofibroma were compared immunohistochemically with regard to the expression of proliferative activity (MIB-1), growth factors, p53, bcl-2, neural cell adhesion molecule (N-CAM), and CD34. RESULTS: The expression of transforming growth factor beta 1 (TGF-beta 1), TGF-beta receptor type II, hepatocyte growth factor alpha (HGF-alpha), c-met, p53, and N-CAM was higher in the areas of MPNST than in the neurofibromatous areas in four, five, five, eight, five, and three of the eight cases, respectively. CD34 expression was lower in the areas of MPNST than in the neurofibroma areas in three of the eight cases. CONCLUSIONS: On the basis of these findings, TGF-beta 1, HGF-alpha, and p53 might be involved in the malignant transformation of neurofibroma to MPNST.

Adolescent↗