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M Dictor

Publications and source records attributed to M Dictor.

At least 37 records · Page 2Linked to original sources

Cytogenetic analysis of inverted nasal papillomas and demonstration of genetic convergence during in vitro passaging.

Three inverted nasal papillomas were cytogenetically investigated after short-term culture. Two of the cases were characterized by a single abnormal clone with t(1;8)(p36;q11) and trisomy 7, respectively, whereas the third papilloma showed extreme cytogenetic heterogeneity: of 852 analyzed cells, 329 belonged to 36 unrelated clones, 344 had non-clonal changes, and 179 had a normal chromosome constitution. The polyclonal papilloma was further analyzed during in vitro passage of 3 lines (L1-L3) cultured independently since initiation of the primary cultures and found to have 6, 16 and 6 unrelated clones at analysis of primary cultures. At passage 1, each line was further subdivided into 2 sub-lines (L1A and B, L2A and B, and L3A and B), which were cultured separately until the cells spontaneously stopped dividing. After 4 to 7 passages, each sub-line was dominated (83-98% of the cells) by a single clone. The cell populations that took over the cultures were the same within each set of sub-lines (A and B lines), demonstrating that clonal overgrowth in vitro is not random. The difference in clonal selection among the L1-L3 lines further shows that genetic convergence during in vitro growth in stable conditions is dependent not only on the clones' ability to adapt to the culture conditions, but also on the nature of the neighboring cells with which they collaborate and compete.

Aged↗

Correlation between p53 mutation and cyclin D1 amplification in had and neck squamous cell carcinoma.

Mutations in the p53 tumour suppressor gene and amplification of the cyclin D1 (CCND1) oncogene have been commonly reported in various malignancies. In the present study of 39 squamous cell carcinomas of the head and neck, p53 mutations were manifest in 11 (28%) of the cases, whereas CCND1 amplification was seen in 6 (16%) of 37 analysed tumours. The 10 mutations occurring in coding sequences of p53 were found in exon 5 (4 cases), exon 6 (3 cases),f and exon 8 (3 cases). No mutation was found in exon 7. Eight of the 10 exon nucleotide substitutions were missense mutations and two were nonsense mutations. All six tumours with CCND1 amplification also had p53 mutations, while an additional five tumours manifested p53 mutations in the absence of CCND1 amplification. There was a statistically significant positive correlation between these two gene alterations. This raises the possibility that mutation of p53 precedes CCND1 amplification in carcinogenesis.

Adult↗

Human herpesvirus 8 and Kaposi's sarcoma.

In the last 2 years, the discovery that the suspected causative agent of Kaposi's sarcoma (KS) is a new gamma-herpesvirus, called human herpesvirus type 8 (HHV8) or Kaposi's sarcoma-associated herpesvirus (KSHV), has been followed by studies showing it to be a sine qua non of all clinical forms of KS and a specific marker for KS in the differential diagnosis of angioproliferative lesions. Reports that the virus is ubiquitous have been based on the polymerase chain reaction and appear to be contradicted by serological studies of blood donors and patients with acquired immunodeficiency syndrome (AIDS)-related and classical KS. Further serological surveys and the application of molecular probes in histological sections should resolve the issue. The recent descriptions of KSHV RNA molecules and several viral mimickers of human cytokines offer the chance to map the viral latent-lytic cycle and will change the direction of cytokine research in KS. These discoveries suggest that the increase of endemic classical KS noted in Nordic countries before the AIDS epidemic was due to spread of KSHV by unknown routes. The aggregate data should force a paradigm shift away from the notion that human immunodeficiency virus infection has a necessary role to play in AIDS-KS other than as a cause of progressive immunodeficiency.

Diagnosis, Differential↗

The surgical pathologist in a client/server computer network: work support, quality assurance, and the graphical user interface.

Cympathy is a relational client/server database application designed to integrate the departmental work flow in anatomic pathology, segment information appropriately, and allow flexible interaction with standalone microcomputer programs. The database resides in a minicomputer server connected to 40 client microcomputers. Patient histories on consultation requests are scanned and maintained as bitmapped files; all information is stored on fixed disks. Client microcomputers use a graphical interface to update a patient-related status bar and retrieve any of the nearly 40 data entry tables for accessioning, ordering special stains and studies, block and slide production, reports, gross and microscopic findings, evaluation of analyses, Systematized Nomenclature in Medicine (SNOMED) coding, conference scheduling, logging of borrowed materials, queries, and specialized functions such as electron microscopy, including indexes for blocks, grids, and photonegatives. The application radically reduces the need for administrative personnel. Cympathy allows major refinements in the method of composing, distributing, and storing report information. Quality assurance protocols can be expanded to relate the frequency and quantification of microscopic findings retrieved in a structured query to the individual pathologist for a given type of specimen and diagnosis. Such queries can extend output to include the number of blocks and slides and all analyses, services, and procedures applied to each case. Debiting is automated through a flexible dependence on SNOMED codes, analyses, and number of slides generated. Any number of structured queries can be written and saved within Cympathy, addressed directly to the database server, or composed in microcomputer programs linked to the database by open database connectivity drivers. Within Cympathy, query results are output in a fixed table format, which can be expanded to include, for example, tabulations of gross and microscopic findings and analysis results. The application offers the opportunity for research and quality assurance in anatomic pathology without the need for hard copy output.

Databases, Factual↗

Epidemiology of Kaposi's sarcoma in the Nordic countries before the AIDS epidemic.

Based on data from the Nordic cancer registries, time-related trends in incidence of Kaposi's sarcoma (KS) were analysed in four ethnically similar populations before the AIDS epidemic. Data were available for different time periods in Denmark (1970-79), Sweden (1958-79), Finland (1953-79) and Norway (1953-79). KS was more common among men than among women aged 60 years or more, whereas no differences were observed for younger persons. The incidence of KS differed significantly between the four countries (P = 0.0001); Sweden having the highest and Denmark the lowest rates. Similarly, regional differences in incidence were observed within Sweden, rates being higher in the northern than in the southern areas (Ptrend = 0.002). Overall, in Nordic men the world standardised incidence rose from 0.5/1,000,000 person-years in the period 1953-57 to 1.8/1,000,000 person-years in 1978-79; in Nordic women, the corresponding rates were 0.2/1,000,000 person-years and 0.8/1,000,000 person-years respectively. The rate of increase was similar in Sweden, Finland and Norway (P = 0.14), whereas the short period of observation in Denmark precluded precise assessment of time-related incidence trends. These observations cannot be explained by registrational procedures or known risk factors for KS, and argue that environmental factors play an important role in the development of the disease.

Acquired Immunodeficiency Syndrome↗

Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) DNA in Kaposi's sarcoma lesions, AIDS Kaposi's sarcoma cell lines, endothelial Kaposi's sarcoma simulators, and the skin of immunosuppressed patients.

We used the polymerase chain reaction on 63 tissue specimens of histologically staged classic Kaposi's sarcoma (KS) from 40 patients, 14 specimens from 14 acquired immune deficiency syndrome (AIDS)-KS cases (all from the same geographic area over a 10-year period), and peripheral blood mononuclear cells from 1 of the non-AIDS KS patients to amplify a specific 210-bp genomic sequence of the newly discovered KS-associated herpesvirus (KSHV). Also tested were 86 benign and malignant endothelial lesions, which potentially simulated each KS histological stage and were further matched by age approximation and by sex with a classical KS specimen. The lesions included hemangioma, lymphangioma, pyogenic granuloma, and angiosarcoma. KSHV was also sought in multiple well characterized vascular endothelial cell lines from AIDS-KS lesions and in 20 mainly cutaneous benign and malignant lesions from 15 immunosuppressed transplant patients. Overall, 92% of KS tissue specimens, representing 88% of classical KS and 100% of AIDS-KS patients, and in addition the sample of peripheral blood mononuclear cell DNA, were positive as visualized on ethidium bromide gels and confirmed by Southern blot hybridization (only 1 case was negative on gell visualization but positive on Southern blot), thus confirming the close association of KSHV with KS of different clinical forms. None of the various other endothelial lesion, skin lesions in immunosuppressed patients, or AIDS-KS endothelial cell lines contained amplifiable KSHV DNA, which indicates that reactivation of KSHV is not present in the skin lesions of immunosuppressed patients and probably is not a ubiquitous agent that secondarily infects proliferative endothelium. The absence of amplifiable virus DNA in the cultured endothelium of KS suggests that the stimulus for angioproliferation originates in another host cell or under conditions not reproduced in culture. The polymerase chain reaction is a specific and sensitive means of verifying KS in the differential diagnosis of angioproliferative lessons.

Acquired Immunodeficiency Syndrome↗

Sinonasal T-cell lymphoma in the differential diagnosis of lethal midline granuloma using in situ hybridization for Epstein-Barr virus RNA.

"Lethal midline granuloma" of the upper airways generally encompasses T-cell lymphoma and Wegener's granulomatosis in Western populations. Treatment and outcome for each is different, but their pathological distinction may not always be possible on routine biopsy specimens. Within a defined population between 1947 and 1994, we found 12 cases of primary sinonasal T-cell lymphoma, all with a CD20-, CD3+ immunophenotype in paraffin sections. We studied the occurrence of the Epstein-Barr virus RNA EBER1 using colorimetric in situ hybridization (ISH) with an oligoprobe. All available biopsy specimens from each patient were hybridized to detect the presence of EBER1 in relation to the phase of lymphoma progression. In addition, ISH was performed on 23 cases of nonspecific rhinitis and 10 cases of Wegener's granulomatosis to determine the specificity of the method in the differential diagnosis of inflammatory/ulcerative lesions. In ten cases of lymphoma, initial biopsy specimens showed the early phase with minimal lymphocytic atypia ("polymorphic reticulosis"). Four of these (including one recurrence) had been missed by experienced pathologists, resulting in a diagnostic delay of 2 to 8 yr. The remaining two cases were in the late phase, i.e., malignant grade atypia was apparent in the initial biopsy specimen, and neither was misdiagnosed as being benign. All hybridizable lymphoma sections, regardless of phase of development, gave a strong ISH signal easily detected at low magnification in 50 to 100% of tumor cells. Scattered positive cells were usually present even in necrotic areas. In contrast, no case of Wegener's granulomatosis or nonspecific rhinitis produced a true hybridization signal. We conclude that a negative EBER1 ISH provides strong evidence against T-cell lymphoma in the differential diagnosis of lethal midline granuloma in our population. Conversely, a strong ISH signal for EBER1 in immunohistochemically determined T-cell infiltrates within sinonasal tissues provides strong support for the presence of lymphoma.

Adolescent↗

Karyotypic features of malignant tumors of the nasal cavity and paranasal sinuses.

Cytogenetic analysis of short-term cultures from 6 tumors of the nasal cavity and paranasal sinuses--one esthesioneuroblastoma, 2 adenocarcinomas and 3 squamous-cell carcinomas (SCC)--revealed clonal chromosome aberrations in all cases. The esthesioneuroblastoma had a complex hyperdiploid karyotype. None of the aberrations was similar to those previously described in short-term cultures or established cell lines from esthesioneuroblastomas. The 2 adenocarcinomas had complex karyotypic changes, which in both cases included rearrangements of bands 9p22 and 14q11. One SCC had 5 unrelated pseudodiploid clones, 1 displayed a highly complex karyotype, including rearrangement of band 11q13, and 1 had simple karyotypic changes with loss of 6q material and gain of 3q. These findings are similar to those described in head-and-neck SCC at other sites.

Adenocarcinoma↗

Tetraploidization and progressive loss of 6q in a squamous cell carcinoma of the parotid gland.

Cytogenetic analysis of short-term cultures from a squamous cell carcinoma (SCC) of the parotid gland revealed one clone with loss of the Y chromosome only, as well as three related subclones: 91,XXYY,add(6)(q21), -11,t(11;22)(q13;q11),ins(15;?)(q22;?)[cp5+ ++]/91,XXYY,add (6)(q21), -11,add(11)(p11), ins(15;?)(q22;?),der(22)t(11;22)(p11;q11)[2]/91,XXYY,add(6)(q11), -11,add(11)(p11),ins(15;?)(q22;?),der(22) t(11;22)(p11;q11) [cp4]. The finding of only one copy of all structurally rearranged chromosomes in a near-tetraploid karyotype indicates that tetraploidization was an early event in tumorigenesis. Rearrangements, in particular deletions, of 6q have previously been associated with adenoid salivary gland malignancies. Our finding of progressive 6q loss with clonal evolution, combined with the fact that 6q deletions were also seen in the two previously reported SCCs of the salivary glands, indicate that loss of genetic information from this chromosome arm is characteristic for most types of salivary gland carcinomas, irrespective of their histologic differentiation.

Aged↗

Incidence and prognostic significance of t(14;18) translocation in follicle center cell lymphoma of low and high grade. A report from southern Sweden.

BACKGROUND: The t(14;18)(q21;q32) is the most common recurrent genetic defect in follicle center cell lymphoma (FCC). Conflicting reports exist in regard to a possible prognostic significance for the translocation. PATIENTS AND METHODS: In a single center, 102 patients with either low-grade (n = 50) or high-grade (n = 52) FCC (Kiel classification) and a median follow-up of 82 months were retrospectively studied to determine survival in relation to t(14;18) as shown by either PCR of the bcl-2 rearrangement in paraffinized tissue or karyotype analysis. RESULTS: t(14;18) was detected in 30 of 50 (60%) low-grade FCC and in 12 of 52 (23%) high-grade FCC. The presence of the t(14;18) was not related to morphologic bone marrow involvement or other clinical parameters, but it was related to age: in low-grade FCC, patients with t(14;18) were an average of 17 years younger (p = 0.002) than those without the translocation. In the group with high-grade histology, 30% survived beyond 60 months regardless of t(14;18) status (p = 0.92). Patients with low-grade histology and t(14;18) fared better than those without, irrespective of age (p = 0.01). No significant difference in disease-free survival related to t(14;18) was found in either low- or high-grade FCC. CONCLUSIONS: The incidence of t(14;18) is in accord with that of other European reports. T(14;18) does not define a prognostic subset of high-grade FCC, but is significantly correlated with a better survival in low-grade FCC. The association of t(14;18) with younger age and indolent lymphoma is perplexing in light of recent findings of an age-related increase in t(14;18) in normal subjects.

Adult↗

Major basement membrane components in Kaposi's sarcoma, angiosarcoma and benign vascular neogenesis.

Recent cell biologic studies have emphasized the importance of the basement membrane (BM) and its molecular components in angiogenesis. We immunostained 60 angioproliferative lesions (angiosarcoma, sclerosing hemangioma of skin, pyogenic granuloma, capillary hemangioma, lymphangioma, glomangioma and granulation tissue) and 23 cases of Kaposi's sarcoma (KS) for the major macromolecular components laminin, collagen type IV, fibronectin and heparan sulfate proteoglycan (HSPG). Normal structures served as aggregate controls in each group, and semiquantitative scoring reflected the degree of consistency of staining about blood and lymphatic endothelium and vascular sheath (pericyte/smooth muscle) within and peripheral to each lesion. Benign and reactive vasoproliferations consistently maintained immunoreactivity for each BM component around endothelium and sheath components of blood vessels. Angiosarcoma showed from 20 to more than 60% less consistent immunoreactivity by comparison, although the score variances were greater than for non-malignant lesions. Staining about blood vessel endothelium was both strong and consistent among histologic stages in KS with the exception of HSPG, which was weakly immunoreactive in all stages. Marked selective HSPG loss was characteristic only of KS and normal lymphendothelium, and in the light of evidence for a role for HSPG in the assembly and maintenance of BM, suggests that reduced HSPG may be responsible for the loss of ultrastructural integrity of perivascular BM in both.

Basement Membrane↗

Determination of nonendemic nasopharyngeal carcinoma by in situ hybridization for Epstein-Barr virus EBER1 RNA: sensitivity and specificity in cervical node metastases.

After time-consuming and costly investigations, patients with neck metastases from an occult primary often receive unnecessarily large radiation volumes to treat a possible origin in the nasopharynx. In this study a colorimetric antisense Epstein-Barr early ribonucleoprotein 1 (EBER1) oligonucleotide probe specific for Epstein-Barr virus RNA was hybridized in situ to metastatic tissue obtained from 18 nasopharyngeal, 54 oral and pharyngeal, and 12 occult carcinomas derived from an unselected population. All 16 nonkeratinizing nasopharyngeal carcinomas (NPCs) were positive for EBER1. Both cases of keratinizing NPC and all 54 other metastases were negative. A single positive case of occult carcinoma indicated its origin from NPC. In retrospect, 7 patients with occult carcinoma had received unnecessary treatment with irradiation to the nasopharynx. Nasopharyngeal carcinoma appears to be a less common origin of occult carcinoma than previously considered. In the proper clinicopathologic context EBER1 in situ hybridization (EBER1-ISH) allows exclusion of NPC with a high degree of accuracy. Thus unnecessarily large radiation volumes and their adverse sequelae may be reduced in the treatment of occult carcinoma. Conversely, a positive result of ISH allows exclusion of further extensive diagnostic procedures.

Adolescent↗

Characteristic karyotypic features in lacrimal and salivary gland carcinomas.

Short-term cultures from 12 non-squamous cell carcinomas (NSCCs) of the head and neck were cytogenetically investigated. Three tumours were acinic cell carcinomas, two adenoid cystic carcinomas, three mucoepidermoid carcinomas, two carcinomas in pleomorphic adenoma, and two adenocarcinomas. Clonal chromosome aberrations were detected in all but one adenocarcinoma. Including our data, a total of 40 head and neck NSCCs with clonal aberrations have been described. Deletions of the long arm of chromosome 6 are the most common aberrations (11/40 cases); they have been detected in all types of NSCC except carcinoma in pleomorphic adenoma. Two aberrations seem to be closely associated with tumour type: t(6;9)(q21-24;p13-23), which has been seen in three of 11 adenoid cystic carcinomas (in two as the sole aberration), and structural rearrangements of 8q12-13, which have been detected in three of four carcinomas in pleomorphic adenoma.

Adenocarcinoma↗

Endothelial transdifferentiated phenotype and cell-cycle kinetics of AIDS-associated Kaposi sarcoma cells.

The nature of Kaposi sarcoma (KS) (vascular malignancy vs. discordant angiogenesis) and lineage of the progenitor cell remain unclear. Therefore, AIDS-KS enzyme isolate cultures were prepared from excised skin lesions. Endothelial marker positivity for Factor VIII related antigen (F8RAg), Ulex europaeus agglutinin (UEA), and angiotensin-converting enzyme (ACE) were determined by fluorescence microscopy (FM) and flow cytometry (FCM). DNA cell-cycle analysis was performed using FCM. KS lesions showed large thick-walled channels (F8RAg and UEA strongly +), narrow vascular slits and thin-walled lakes (F8RAg and UEA weakly +), and non-prominent spindle cells (F8RAg and UEA almost uniformly negative). KS cultures yielded heterogenous populations of spindle, stellate, and flattened endothelial-like cells, displaying positivity for F8RAg (64 +/- 3%; mean +/- SE), UEA (40 +/- 9%), and ACE (81 +/- 9%). When injected subcutaneously in the nude mouse these cells failed to produce tumors. During contact inhibition induced quiescence, KS cultures exhibited a high G2M (18 +/- 3%) compared to non-KS (7 +/- 4%; p < 0.04), evidence of an altered proliferative potential consistent with a transdifferentiated or transformed phenotype.

Acquired Immunodeficiency Syndrome↗

Myofibromatosis-like hemangiopericytoma metastasizing as differentiated vascular smooth-muscle and myosarcoma. Myopericytes as a subset of "myofibroblasts".

A thyroid hemangiopericytoma that was resected in a 5-year-old boy recurred insidiously in the larynx 8 years later. Marked cicatricial mucosal inflammation prevented a definitive pathologic diagnosis of recurrence until a nodule grew to obstruct the airway 15 years after initial surgery. After excision of the nodule, a larger sarcomatous metastasis was discovered in the upper esophagus and resected, but the patient eventually succumbed to widespread disease at the age of 20 years. The original tumor contained atypical pericytes and bundles of hyalinizing smooth muscle abutting on "staghorn vessels," a pattern similar to infantile myofibromatosis. Desmin immunostaining was negative in the pericytes but positive in smooth-muscle cells dispersed singly as well as in bundles. Both elements reacted strongly for vimentin and the alpha-isoform of actin (alpha-SMA) found in normal smooth muscle and pericytes. A third cell type showing dendritic processes and immunoreactivity for all three antigens was interpreted as a myopericyte. Spindled cells in multiple subsequent mucosal biopsy specimens stained retrospectively also positive for these antigens. Large bundles of vascular smooth muscle surrounded by radiating myocytes characterized the occluding laryngeal nodule. In the esophageal metastasis, which showed no histologic features typical of hemangiopericytoma, numerous mitotically active, small, vimentin+, desmin+, alpha-SMA+ cells often maintained shortened processes and tended to form nodular aggregates about capillaries. Single rows of pericytes accreted to endothelial tubes. Ultrastructurally, some cells contained myofilaments and irregular dense material or showed rare cell junctions and variable investment by a basal lamina.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

Moderately differentiated neuroendocrine carcinoma (atypical carcinoid) of the supraglottic larynx. A report of two cases including immunohistochemistry and aspiration cytology.

Moderately differentiated neuroendocrine carcinoma of the larynx is morphologically distinct from the classic carcinoid and small-cell carcinoma. It is composed of medium to large polyhedral cells with an insular, trabecular, or acinar growth pattern, variable pleomorphism, and a tendency to metastasize to skin and bone. We describe the clinicopathological features of the tumor in two patients in whom tumor dissemination resulted in death 13 and 33 months after diagnosis. Both tumors occurred above the glottis and metastasized to bone but not to regional tissues. In one case, the diagnosis was confirmed when the aspiration cytological specimen from a rib lesion suggested a neuroendocrine carcinoma resembling medullary thyroid cancer (triangular cytoplasm, double nuclei, and fine red cytoplasmic granules on May-Grünwald-Giemsa staining). Both tumors were originally misdiagnosed as squamous cell carcinoma, as acinic cell cancer, or as suggesting metastasis of melanoma. Immunohistochemistry gave strong reactivity in both for chromogranin A and calcitonin, although the serum level of calcitonin, determined in one case, was normal.

Aged↗

HIV in pregnant women and their offspring: evidence for late transmission.

To assess the role of maternal viraemia in vertical transmission of HIV and the extent to which viraemia occurs during the various stages of pregnancy, we have attempted to detect human immunodeficiency virus (HIV) in 44 pregnant HIV-1 infected women during 47 pregnancies (30 continued, 17 aborted) and in 30 children and 12 fetuses. Infectious HIV was detected at some time during pregnancy in 59% of women from plasma and in 83% from either peripheral blood mononuclear cells or plasma. HIV was not isolated from any of the newborn babies (0/27) at birth. The mothers had a significantly higher frequency of viraemia during pregnancy than their children had by 6 months of age (p = 0.002); by this time HIV was recovered from 5 (26%) of 19 infants. HIV was not detected by virus isolation, in-situ hybridisation, or polymerase chain reaction (PCR) in 10 fetuses; the other 2 fetuses were positive either by in-situ hybridisation or by PCR but neither result could be confirmed in a second organ or by the other methods of detection. The findings show that there is no consistent spread of HIV across the placenta during maternal viraemia, and indicate that in most cases transmission occurs close to or at delivery.

Female↗