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PubMed2005

The relative distribution of oncogenic types of human papillomavirus in benign, pre-malignant and malignant cervical biopsies. A study with human papillomavirus deoxyribonucleic acid sequence analysis.

The aim of the present investigation was to define the spectrum of oncogenic types of human papillomavirus (HPV) present in benign, pre-malignant (low-grade and high-grade squamous intraepithelial lesions, LSIL and HSIL) and malignant cervical lesions. The study comprises 215 HPV-positive biopsies, analysed with PCR, followed by sequence analyses of the HPV DNA. Fifeteen oncogenic types of HPV were identified. In 170 benign or pre-maligant alterations, the most common being HPV 16 (51%), HPV 31 (8%), HPV 18 (7%) and HPV 45 (6%). HPV 33, 35, 51, 56, 58, 66, and 70 occurred in about 1-4%. The prevalence of HPV 39, 52, 56, 59 and 73 was <1%. All the observed types of HPV, except 39 and 52, occurred in SIL lesions. The most common oncogenic HPV types (16 and 18), occurring in 45 invasive squamous carcinomas, comprised 76 per cent of the tumours, whereas less frequent HPV types (31, 33, 52, 56, 67, 70 and 73) were each found in about 2-4%. Double HPV infections were not observed. In conclusion, a total of 15 different oncogenic HPV types were identified, of which 13 types were present in pre-malignant cervical lesions and 9 in malignant lesions. This information may have some relevance when HPV analyses are considered as an adjunct to the organised screening of cervical cancer and for those working with the development of HPV vaccines for the prevention of cervical cancer.

Adult↗

PubMed1988

Malignant angioendotheliomatosis--a true lymphoma: a case of intravascular malignant lymphomatosis studied by southern blot hybridization analysis.

Malignant angioendotheliomatosis is a rare, systemic, usually fatal disease characterized by a massive proliferation of large, bizarre-looking mononuclear cells within small and medium-sized blood vessels. The histogenesis of the neoplastic cells has been the subject of long-standing controversy since the disease's initial description. Early investigators concluded that the entity represented a neoplasm of endothelial cells, but recently others have suggested that it is of lymphoid origin. We studied a case of malignant angioendotheliomatosis by Southern blot hybridization analysis which showed clonal rearrangements of the immunoglobulin heavy-chain gene strongly suggesting a B-lymphocyte origin. Our results provide additional evidence that malignant angioendotheliomatosis is an intravascular malignant lymphomatosis.

Aged↗

PubMed2004

Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation (malignant triton tumor) with balanced t(7;9)(q11.2;p24) and unbalanced translocation der(16)t(1;16)(q23;q13).

Malignant peripheral nerve sheath tumors (MPNST) with skeletal muscle differentiation are termed malignant triton tumors. A case of malignant triton tumor arising in a patient without signs of neurofibromatosis with two consistent chromosomal abnormalities is described. The first was of a balanced translocation between the long arm of chromosome 7 and the short arm of chromosome 9. The second was an unbalanced rearrangement between chromosomes 1 and 16, leading to partial trisomy for the long arm of chromosome 1 and partial monosomy for the long arm of chromosome 16. Review of previous reports on chromosomal abnormalities in malignant triton tumors revealed consistent abnormalities involving chromosome 1, regardless of the presence or absence of neurofibromatosis. This finding may relate to the observed poor prognostic outcome in this type of sarcoma. Also unique to our case is the translocation involving 7q and 9p, both regions may play a role in MPNST.

Cell Differentiation↗

PubMed1990

Multiple primary malignancies in patients with malignant tumours of the nasal cavities and paranasal sinuses.

The incidence of multiple primary malignancies (MPM) was analysed in 1297 patients with malignant tumours of the nasal cavities and paranasal sinuses. The patients were followed for a minimum of six years or until death. The incidence of MPM was 3.4 per cent (44/1297) which is lower in patients with malignant tumours of other regions in the upper aerodigestive tract. Five of the 44 patients had second malignancies within previously irradiated areas. There was a difference between the proportion of histologies occurring in irradiated tissues compared with the overall 1297 patients. This finding suggests that radiotherapy may induce a second cancer.

Humans↗

PubMed2002

Malignant peripheral nerve sheath tumor with perineurial differentiation: "malignant perineurioma".

BACKGROUND: Although benign tumors derived from the nerve sheath perineurial cell have been described from a variety of anatomic sites and are known to be a component of a number of benign neoplasms, malignant nerve sheath tumors of perineurial origin are exceedingly uncommon. METHODS: We report an unusual case of a 70-year-old male who presented with a rapidly growing mass of the left arm, subsequently shown to be a malignant nerve sheath tumor with perineurial differentiation. A brief microscopic differential diagnosis and review of the literature are discussed. RESULTS: Histologic sections show a partially circumscribed tumor of atypical spindle cells arranged in sweeping fascicles embedded in a myxoid matrix with focal whorling. Nuclear pleomorphism was evident among scattered typical and atypical mitotic figures (mean mitotic index of 7/10 high-power fields). The immunophenotypic profile consisted of only vimentin and epithelial membrane antigen (EMA) positivity, while antibodies to S-100, CD34, smooth muscle actin, and pankeratins were negative. Ultrastructural features included spindle cells with long cytoplasmic processes invested by interrupted basal lamina and pinocytotic vesicles, consistent with perineurial differentiation. CONCLUSIONS: While the histogenic source of the benign perineurioma, the perineurial cell has only rarely been described in conjunction with malignant tumors. All cases to date have shown EMA-positive and S-100-negative atypical spindled cells arranged in fascicles embedded in a myxoid matrix. In addition to immunohistochemistry, ultrastructural examination may be necessary to support the diagnosis. The diagnostic differential includes melanoma, spindle cell squamous cell carcinoma, atypical fibroxanthoma, leiomyosarcoma, and conventional malignant peripheral nerve sheath tumor, most commonly of Schwannian differentiation. Recognizing perineurial differentiation is important since few cases have been reported to date and the biological potential of these neoplasms is not known.

Aged↗

PubMed1999

Frequent allelic loss of the RB, D13S319 and D13S25 locus in myeloid malignancies with deletion/translocation at 13q14 of chromosome 13, but not in lymphoid malignancies.

In order to identify a commonly deleted region of 13q14 on chromosome 13, we performed fluorescence in situ hybridization (FISH) on 17 patients with myeloid malignancies and 12 patients with lymphoid leukemia/lymphoma who exhibited either deletion or translocation at 13q14. Three cosmid probes (RB, D13S319 and D13S25) hybridizing to sequences on 13q14 were used. Fourteen of the 17 patients with myeloid malignancies (82.4%) exhibited allelic loss at the RB, D13S319 and D13S25 locus, whereas only three of the 12 patients with lymphoid malignancies (25.0%) exhibited loss within these loci. These three patients had chronic lymphocytic leukemia (CLL). Six, two and one of the remaining nine lymphoid leukemia/lymphoma patients had breakpoints centromeric to the RB gene, telomeric to D13S25 and within the D13S319 locus, respectively. A high frequency of allelic loss was found using these probes in patients with myeloid malignancies, compared to in patients with leukemia in the lymphoid origin, except CLL patients. These results indicate that loss of the RB gene itself or a region between RB and D13S319, which includes commonly deleted loci, may play an important role in myeloid leukemogenesis.

Adult↗

PubMed2001

Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts).

Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) and conventional malignant melanoma may demonstrate significant morphologic overlap at the light microscopic and ultrastructural level. Consequently, the clinically relevant distinction between primary clear cell sarcoma and metastatic melanoma in the absence of a known primary cutaneous, mucosal or ocular tumour may occasionally cause diagnostic problems. A balanced translocation, t(12;22)(q13;q13), which can be detected, amongst others, using the reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization (FISH), has been identified in a high percentage (50-75%) of clear cell sarcomas and is presumed to be tumour specific. Whether this chromosomal rearrangement is present in malignant melanoma has, to date, not as yet been studied by molecular genetic or molecular cytogenetic techniques. Using RT-PCR and FISH, a series of metastases from 25 known cutaneous melanomas and 8 melanoma cell lines (5 uveal and 3 cutaneous) were screened for the t(12;22)(q13;q13) translocation. Primers for RT-PCR were chosen based upon published breakpoint sequences. The Cosmids G9 and CCS2.2, corresponding to the 5' region of EWS and 3' region of ATF-1 respectively, were used as probes. The translocation was not identified in any of the melanomas or melanoma cell lines analysed in this study; in contrast this translocation was identified in 3 out of 5 clear cell sarcomas using these techniques. This allows distinction between translocation positive cases of clear cell sarcoma and malignant melanoma at a molecular genetic level. Consequently, in diagnostically challenging cases, this represents a valuable tool for the clinicopathologic differentiation between these two entities, with an important impact on patient management and prognosis.

Chromosomes, Human, Pair 12↗

PubMed2001

A 6 year prospective analysis of the diagnosis of malignant melanoma in a pigmented-lesion clinic: even the experts miss malignant melanomas, but not often.

We investigated whether the pigmented-lesion clinic (PLC) run by the Department of Plastic and Reconstructive Surgery at Frenchay Hospital was effective in making and excluding the diagnosis of malignant melanoma, by looking at the pattern of referrals over time, the number of melanomas excised and melanomas in which the diagnosis was delayed or missed. We also investigated whether the PLC was having an effect on the thicknesses of melanomas excised. All 9968 patients attending the PLC between 1 January 1993 and 31 December 1998 were included in the study and 586 malignant melanomas were diagnosed; 24.7% of excisions led to the diagnosis of malignant melanoma. Seven invasive melanomas and two lentigo malignas were missed. There was one histological false negative. The PLC has a sensitivity of 98.5% and specificity of 89.2% for the diagnosis of melanoma; the negative predictive value is 99.9%. The PLC is effective in rapidly making or excluding the diagnosis of malignant melanoma, but has had no effect on the average thickness of melanomas excised over the 6 year study period.

Adult↗

PubMed2006

Pre-malignant and malignant cervical pathologies among inert and copper-bearing intrauterine contraceptive device users: a 10-year follow-up study.

OBJECTIVES: The aim of the study was to compare the incidence of pre-malignant and malignant cervical conditions during a period of 10 years of use of inert (Szontagh) and copper-bearing IUCDs. METHODS: Candidates were parous women requesting intrauterine contraception regardless of the previous IUCD use and having no contraindications. Follow-ups were scheduled at 1, 6, and 12 months after insertion, and annually thereafter. Colposcopy and cytological evaluation were performed at insertion and at yearly follow-ups. For comparison of the two groups and the different follow-up periods (at the end of each ordinal year), net and gross cumulative lifetable rates were calculated. Statistical differences were measured by chi-squared test, and were regarded as significant at P <or= 0.05. RESULTS: The total number of insertions was 3536 and 13,518 for inert and copper devices, respectively, and the maximum cumulative woman months of use (CWMU) at 10 years for the two groups were 163,567 and 492,836, respectively. There were no statistically significant differences in the life table rates of terminations for suspected cervical pre-malignant and malignant conditions between the groups at the end of each ordinal year. CONCLUSION: The copper-bearing intrauterine contraceptive devices are not associated with a significantly higher risk of cervical cancer compared to the inert IUCDs.

Adult↗

PubMed1998

Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma.

Malignant pleural mesothelioma is a fatal neoplasm that is unresponsive to standard modalities of cancer therapy. We conducted a phase I dose-escalation clinical trial of adenoviral (Ad)-mediated intrapleural herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) gene therapy in patients with mesothelioma as a model for treatment of a localized malignancy. The goals of this phase I trial were to assess the safety, toxicity, and maximally tolerated dose of intrapleural Ad.HSVtk, to examine patient inflammatory response to the viral vector, and to evaluate the efficiency of intratumoral gene transfer. Twenty-one previously untreated patients were enrolled in this single-arm, dose-escalation study with viral doses ranging from 1 x 10(9) plaque-forming units (pfu) to 1 x 10(12) pfu. A replication-incompetent recombinant adenoviral vector containing the HSVtk gene under control of the Rous sarcoma virus (RSV) promoter-enhancer was introduced into the pleural cavity of patients with malignant mesothelioma followed by 2 weeks of systemic therapy with GCV at a dose of 5 mg/kg twice a day. The initial 15 patients underwent thoracoscopic pleural biopsy prior to, and 3 days after, vector delivery. The last six patients underwent only the post-vector instillation biopsy. Dose-limiting toxicity was not reached. Side effects were minimal and included fever, anemia, transient liver enzyme elevations, and bullous skin eruptions, as well as a temporary systemic inflammatory response in those receiving the highest dose. Strong intrapleural and intratumoral immune responses were generated. Using RNA PCR, in situ hybridization, immunohistochemistry, and immunoblotting, HSVtk gene transfer was documented in 11 of 20 evaluable patients in a dose-related fashion. This study demonstrates that intrapleural administration of an adenoviral vector containing the HSVtk gene is well tolerated and results in detectable gene transfer when delivered at high doses. Further development of therapeutic trials for treatment of localized malignancy using this vector is thus warranted.

Adenoviruses, Human↗

PubMed1991

The presence of dysplastic nevus remnants in malignant melanomas. A population-based study of 551 malignant melanomas.

We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi.

Adult↗

PubMed1985

Malignant peripheral nerve-sheath tumors (malignant schwannomas). An immunohistochemical study of 29 cases.

Twenty-nine cases of malignant schwannoma consisted of three groups; 11 tumors associated with von Recklinghausen's disease (group I), nine tumors arising grossly from nerve trunks (group II), and 11 tumors so diagnosed basically on the histologic features (group III). Using the immunoperoxidase methods, the tumors were investigated with regard to S-100 protein, keratin, and epithelial membrane antigen (EMA). Approximately one-third of the cases (10 of 29) were devoid of S-100 positive cells and the remaining two-thirds (19 of 29) contained positive cells, with variable frequencies. The number of S-100 positive cells differed, depending largely on the presence or absence of neurofibroma-like areas in the tumor. The positive cells were rarely found in the group III tumors, which were neither associated with von Recklinghausen's disease nor connected to nerve trunks, even when their histologic features were unequivocal. Certain specific organoid structures in the tumor, such as neuroid or tactoid ones, were positive for S-100 protein. In one of the two malignant epithelioid schwannomas, the tumor cells were strongly positive for S-100 protein, thereby suggesting melanocytic differentiation. This tumor was interpreted as a melanocytic malignant schwannoma rather than a malignant melanoma, based in part on the fact that the overlying epidermis was uninvolved in this patient with von Recklinghausen's disease. True epithelial differentiation in one case of glandular schwannoma was verified by the positive stain of EMA along the inner surface of the glandular element.

Adolescent↗

PubMed1995

Malignant mesonephric neoplasms of the uterine cervix. A report of eight cases, including four with a malignant spindle cell component.

Eight mesonephric adenocarcinomas of the uterine cervix, four of which had a malignant spindle-cell component, occurred in women aged 34 to 71 (median 43, mean 54.5) years, bringing to 14 the number of cervical mesonephric carcinomas in the literature. The tumors with a malignant spindle-cell component ("malignant mesonephric mixed tumors") are, with one possible exception, the first reported examples at this site. The patients, almost all of whom presented with vaginal bleeding, underwent hysterectomy; five also had a pelvic lymph node dissection. The tumors were all stage IB, although microscopic lymph node metastases were found in two cases. Gross examination revealed an invasive cervical mass in each case. On microscopic examination, seven tumors were adjacent to mesonephric hyperplasia, which in five cases was florid and focally atypical; in the remaining case, occasional non-neoplastic mesonephric tubules were found only within the tumor. The adenocarcinomas typically exhibited a variety of patterns, including a ductal pattern resembling endometrioid adenocarcinoma, a small tubular pattern, a retiform pattern, a solid pattern, and a sex-cord-like pattern. These disparate patterns frequently caused diagnostic difficulty. The spindle-cell component generally resembled endometrial stromal sarcoma or a nonspecific spindle-cell sarcoma; one tumor also contained multiple foci of osteosarcoma and another, a single chondroid focus. Immunohistochemical staining for a variety of antigens failed to reveal a distinctive profile, although all the carcinomas were immunoreactive for vimentin. Follow-up in six cases revealed three patients to be alive without evidence of recurrence at postoperative intervals of 2 to 3 years. Recurrent tumor developed in a fourth patient 1 year after hysterectomy; she was treated with chemotherapy and was alive and free of disease at 2 years. Another patient had intra-abdominal recurrences (including liver metastases) at 9 and 11 years and was alive with tumor at 13 years. Death at 8.5 months in a final patient was probably due to an independent stage IIc ovarian clear-cell carcinoma. These and prior observations in the literature suggest that malignant mesonephric tumors of the cervix may be more indolent than their müllerian counterparts, from which they should be distinguished. Mesonephric carcinomas in this site should also be distinguished from florid mesonephric hyperplasia, with which they are usually associated.

Adult↗

PubMed1994

Malignancy-related ascites and ascitic fluid "humoral tests of malignancy".

A large number of ascitic fluid tests, e.g., fibronectin and cholesterol, have been proposed as helpful in detecting malignancy as the cause of ascites. Unfortunately, these "humoral tests of malignancy" are nonspecific. Although the ascitic fluid concentrations of these proteins or protein-bound substances tend to be quite high in patients with peritoneal carcinomatosis and low in the setting of cirrhotic ascites, the problem is that patients with tuberculous peritonitis, cardiac ascites, pancreatitis ascites, etc. usually have values in the malignancy range, i.e., false-positive results. This can lead to an extensive search for a nonexistent tumor, with confusion and anxiety for patient and physician. The cytology is the single best test to order when peritoneal carcinomatosis is suspected; its sensitivity approaches 100%. However, peritoneal carcinomatosis is only one of several mechanisms by which tumors can cause ascites. No one test can be expected to detect tumors as the cause of these diverse mechanisms of ascites formation. The serum-ascites albumin gradient is a helpful test in classifying ascitic fluid specimens into portal-hypertension-related and non-portal-hypertension-related categories. An elevated serum alpha-fetoprotein test can be useful in raising suspicion of hepatocellular carcinoma. Careful analysis of ascitic fluid, without measurement of "humoral tests of malignancy," combined with information obtained from the history and physical examination, usually lead to an accurate diagnosis of the cause of ascites.

Ascites↗

PubMed1995

Adipose tissue concentrations of dioxins and dibenzofurans in patients with malignant lymphoproliferative diseases and in patients without a malignant disease.

Concentrations of dioxins (PCDD) and dibenzofurans (PCDF) were analysed in adipose tissue from seven patients with malignant lymphoproliferative diseases and 12 surgical patients without a malignant disease. All cases in the first group had reported potential exposure to PCDD and PCDF. Of the analysed congeners significantly higher concentrations of 1,2,3,7,8-pentachlorodioxin, 1,2,3,6,7,8-hexachlorodioxin, and 2,3,4,7,8-pentachlorodibenzofuran were found in the cases with lymphoproliferative diseases compared with the patients in the other group. Higher mean concentration of 2,3,7,8-TCDD was also found in the first group but not significantly so. Toxic equivalents of PCDD and PCDF were significantly higher in the first group (mean 64.7 pg/g, range 19.9-187) than in the second group (mean 29.7 pg/g, range 12.9-53.4). Even if the cases with lymphoproliferative diseases in this case series were potentially exposed to PCDD/PCDF in contrast to the other group, the observed differences may be of may be of interest in relation to the aetiology of these malignancies. Immunosuppression increases the risk for malignant lymphoproliferative diseases, and PCDD/PCDF have established immunotoxic properties.

Adipose Tissue↗

PubMed1987

The risk of malignant melanoma, internal malignancy and mortality in xeroderma pigmentosum patients.

Mortality and malignancy were studied in a series of 32 patients with xeroderma pigmentosum presenting during the period 1950-84. Twenty-nine of the patients were followed to the end of 1984 using the National Health Service Central Register, and hospital case records and correspondence with referring physicians; three patients had incomplete follow-up. Three of the patients developed malignant melanoma during follow-up, but none developed internal malignancy. Two males and one female died [standardized mortality ratio (SMR) = 971, P less than 0.05, for males; SMR = 1931, not significant, for females]. All three deaths were from non-malignant causes: severe neurological involvement with terminal infection. This high mortality from neurological complications in xeroderma pigmentosum patients contrasts with previously reported mortality, particularly from actinic-induced cutaneous tumours.

Adolescent↗

PubMed1986

Ferritins in malignant and non-malignant lymphoid cells.

Lymphoid cells from peripheral blood, thymus, malignant and non-malignant lymph nodes were analysed for ferritin content using radioimmunoassays specific for the 'acidic' H-subunit-rich and for 'basic' L-subunit-rich isoferritins, and the data were compared with the immunological characteristics of the cells. All tissues with high proportion of T or 'null' cells contained the lowest concentration of L-subunit-rich isoferritins, while the H-subunit-rich forms increased from low levels in the quiescent peripheral blood lymphocytes (PBL), to higher values in the immature and proliferating thymocytes and lymphoblasts, malignant or not. B-cell lymphomas contained concentrations of both ferritin types higher than those found in PBL. No significant difference was found in the isoferritin concentrations between non-malignant lymph nodes and tissues involved in Hodgkin's disease. These findings indicate that maturation stage, proliferative status and anatomical localization affect isoferritin expression in lymphoid cells.

Ferritins↗

PubMed1993

The adnexal mass: benign or malignant? Evaluation of a risk of malignancy index.

OBJECTIVE: To validate a risk of malignancy index incorporating menopausal status, serum CA 125 level and pelvic ultrasound features in the pre-operative diagnosis of ovarian cancer. DESIGN: A retrospective observational study. SETTING: Department of Obstetrics and Gynaecology, The Royal London Hospital. SUBJECTS: One hundred and twenty-four women admitted consecutively to the gynaecology department for surgical exploration of an adnexal mass. MAIN OUTCOME MEASURES: The sensitivities and specificities of menopausal status, serum CA 125 level and ultrasound features, in isolation and combined (the risk of malignancy index (RMI)), for diagnosing ovarian cancer. RESULTS: Tested on a new population of women, the RMI retained the high sensitivity for diagnosing ovarian cancer seen in the original report describing its derivation. The specificity, however, was lower. The study confirmed that the RMI is more accurate than the individual criteria in diagnosing ovarian cancer, and was comparable with other scoring systems. CONCLUSIONS: The risk of malignancy index is a simple scoring system for ovarian cancer. Application of the risk of malignancy index in clinical practice may provide a rational basis for specialist referral of patients with ovarian cancer before diagnostic surgery.

Antigens, Tumor-Associated, Carbohydrate↗