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N Mandahl

Publications and source records attributed to N Mandahl.

At least 73 records · Page 4Linked to original sources
PubMed1999

110 subfascial lipomatous tumors. MR and CT findings versus histopathological diagnosis and cytogenetic analysis.

PURPOSE: To evaluate whether liposarcoma, atypical lipomatous tumors and lipoma can be differentiated radiologically. MATERIAL AND METHODS: We have retrospectively analyzed CT and/or MR images of 110 subfascial lipomatous lesions. The amount of fat within the tumors was visually graded from the images as: none, 1-75%, 75-95% or 95-100%. The structure of non-fatty tumor components was compared. The images were compared to histopathology and in 37 cases to cytogenetic findings. RESULTS: Only 4 of 20 liposarcomas contained fat. All 4 lesions, histopathologically diagnosed as atypical lipomatous tumors, contained fat but less than 75% of tumor volume. All lesions with more fat than 75% of tumor volume were histologically diagnosed as lipomas. However, one-third of the karyotyped lipomas had ring chromosomes which are considered typical for atypical lipomatous tumors. CONCLUSION: When a tumor is composed more or less solely of fat, the diagnosis of a lipoma or atypical lipomatous tumor with a phenotype simulating a lipoma can be assumed. When the fat content is less than 75% of the tumor volume or non-fatty nodules are found, biopsies from different tumor components have to be performed to exclude malignancy. When no fat is found, imaging does not help in differentiating lipoma or liposarcoma from other soft tissue tumors.

Adolescent↗
PubMed1999

Analysis of 35 cases of localized and diffuse tenosynovial giant cell tumor: a report from the Chromosomes and Morphology (CHAMP) study group.

The karyotypes of 44 specimens from 35 patients with localized (n = 19) or diffuse (n = 16) tenosynovial giant cell tumors were studied. The majority of cases in both categories (11 of 19 localized; 12 of 16 diffuse) displayed clonal chromosomal aberrations, with a complex karyotype in three cases and a simple chromosomal aberration in the others. No difference in the distribution of karyotypic abnormalities was found between the localized and diffuse form except for trisomies (usually of chromosomes 5 and/or 7), which were more frequent in the diffuse type. The short arm of chromosome 1 (1p11-13) was most frequently rearranged, with 7 of 11 localized and 7 of 12 diffuse lesions affected. These findings indicate that the localized and diffuse forms of tenosynovial giant cell tumor might represent two morphologic manifestations of the same entity. The high frequency of clonal chromosomal abnormalities, with a clustering of structural rearrangements to 1p11-13, suggests that this disease is most likely neoplastic in nature and paves the way to search for gene(s) that might be involved in its development.

Adolescent↗
PubMed1999

Rearrangement of the neoplasia-associated gene HMGIC in synovia from patients with osteoarthritis.

The occurrence of clonal chromosome aberrations in short-term cultures from synovia, osteophytes, and cartilage from patients with osteoarthritis (OA) was recently reported. Among these aberrations, a recurrent involvement of chromosome bands 12q13-15 in structural rearrangements was detected in both synovia and osteophytes. Chromosomal abnormalities of 12q13-15 are frequent among malignant and benign mesenchymal tumors, and it was recently demonstrated that the molecular target in these neoplasms is the HMGIC gene. In this study, we show by fluorescence in situ hybridization that HMGIC was disrupted by rearrangements of 12q15 in synovia from two patients with OA. The finding of HMGIC rearrangement in a lesion that is not traditionally regarded as neoplastic not only widens the spectrum of disorders that may be associated with altered function of this gene, but also provides further support for the notion that genetically rearranged cell populations are part of the OA process.

Aged↗
PubMed1999

Chromosome band 9p21 is frequently altered in malignant peripheral nerve sheath tumors: studies of CDKN2A and other genes of the pRB pathway.

Malignant peripheral nerve sheath tumors (MPNSTs) are frequently associated with the disease neurofibromatosis type 1. Only few recurrent cytogenetic changes have been reported, including rearrangements of the short arm of chromosome 9. By fluorescence in situ hybridization with a centromere 9 probe, and by allelic imbalance studies with seven 9p21-23 markers in nine familial and three sporadic MPNSTs, we found interstitial deletions that supported CDKN2A as a possible target gene. Nine MPNSTs showed aberrations of CDKN2A by Southern blot analyses, and in four of these, expression of CDKN2A could not be detected by Northern blot analysis. No mutations of CDKN2A were identified by sequencing of the coding region, and gene inactivation by promoter methylation was not found. In the 9p allelic imbalance studies, a novel allele was detected at one locus in one tumor. Analyses of additional markers (n = 8) excluded mismatch repair deficiency as an important mechanism in the genesis of these tumors. The tumors were analyzed further for alterations in other candidate cell cycle-associated genes. In total, 11/12 MPNSTs showed DNA changes in one or more of the genes CDKN2A, CDKN2B, RB1, CDK4, MDM2, and CCND2. The present study suggests that disruption of the pRB pathway is common in MPNST, and that dose reduction of CDKN2A is particularly frequent and contributes to MPNST development. Genes Chromosomes Cancer 26:151-160, 1999.

Adolescent↗
PubMed1998

A case of dermatofibrosarcoma protuberans with a ring chromosome 5 and a rearranged chromosome 22 containing amplified COL1A1 and PDGFB sequences.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous tumour of borderline malignancy, the cytogenetic features of which include the translocation t(17;22)(q22;q13) or, more commonly, supernumerary ring chromosomes containing material from 17q22 and 22q13. These rearrangements result in the COL1A1/PDGFB fusion gene. Here, we describe a case of DFSP displaying a ring chromosome 5 together with a large marker chromosome composed of chromosome 22 alphoid DNA, material from distal 12q and amplified COL1A1 and PDGFB sequences. This is the first case of DFSP with multiple copies of COL1A1 and PDGFB not confined to ring chromosomes, showing that DFSP is similar to other borderline malignant mesenchymal tumours, where rings and giant markers are alternative vehicles for amplified material.

Adolescent↗
PubMed1998

Chromosomal abnormalities in two bladder carcinomas with secondary squamous cell differentiation.

Two secondary squamous cell carcinomas of the bladder (i.e., tumors that originated from primary transitional cell carcinomas) were examined cytogenetically. Both tumors showed complex karyotypes with many of the same aberrations that have formerly been described in transitional cell carcinomas. Monosomy 9, trisomy 7, and rearrangements of chromosomes 3, 8, 10, 13, and 17 were common to both tumors. Among other changes that have been implicated in bladder carcinogenesis, an isochromosome for 5p was seen in one tumor and loss of 11p material in the other. Our findings indicate that secondary squamous cell carcinomas of the bladder are karyotypically indistinguishable from advanced transitional cell carcinomas of the same organ. The putative genetic changes that steer the differentiation of the neoplastic epithelium in the direction of squamous cells thus remain unknown.

Aged↗
PubMed1998

Comparison of chromosomal patterns with clinical features in 165 lipomas: a report of the CHAMP study group.

Soft tissue lipomatous tumors are morphologically heterogeneous. Various morphologic features are associated with specific chromosomal patterns and clinical features such as age, sex, and tumor site, location, and size. Simple lipomas are known to be karyotypically heterogeneous, but this has not been correlated with clinicopathological features. In 165 cases of solitary soft tissue lipoma, short-term cultures were analyzed cytogenetically. The karyotypes were divided into the following groups: normal karyotype; 12q13-15 aberrations; 6p rearrangements; 13q rearrangements, 8q11-13 aberrations; ring or giant marker chromosomes or both; other aberrations. The tumors were reexamined morphologically without knowledge of the karyotypic or clinical data. An abnormal chromosomal pattern was observed in 129 of 165 cases (78%): in 75 of 90 (83%) lipomas in the extremities and in 43 of 63 (68%) trunk wall lipomas. Chromosomal aberrations were present in 69 of 90 (77%) subcutaneous tumors and in 59 of 64 (80%) deep tumors. A normal karyotype was twice as frequent in tumors in patients under 30 years of age than in those from older individuals (6 of 16 vs. 30 of 149, 40% resp. 20%). Apart from the finding that normal karyotypes were more common in patients younger than 30 years, there was no significant association between cytogenetic pattern and patient sex or age or tumor localization, size, or depth. The pathogenetic basis and clinicopathologic relevance (if any) of the cytogenetic subtypes among benign lipomas remain unexplained.

Adolescent↗
PubMed1998

Trisomy 3 as the sole karyotypic change in a pediatric immature teratoma.

Cytogenetic analysis of short-term cultured cells from an immature ovarian teratoma of a 9-year-old girl disclosed an extra copy of chromosome 3 as the sole clonal abnormality. The fact that trisomy 3 was previously reported as the only karyotypic change in two ovarian germ-cell tumors--one teratoma NOS and one immature teratoma--suggests that gain of chromosome 3 constitutes an early and pathogenetically important change in a subset of female germ-cell tumors.

Child↗
PubMed1998

Unbalanced chromosomal rearrangements in a metastasizing salivary gland tumor with benign histology.

Benign metastasizing pleomorphic adenoma (BMPA) is a rare tumor of the salivary glands. Despite benign histopathologic features, it can metastasize and is sometimes lethal. No chromosomal data have been reported for this tumor type. We have by chromosome banding and fluorescence in situ hybridization analysis examined the short-term cultures of three skeletal metastases from a BMPA and identified two related hypodiploid clones: 44,XX,dic(3;22)(p11;q13) or der(3)t(3;22)(p11;q?) add(22)(q?),der(9;21)(q10;q10),der(13)t(1;13)(q11;p13)/45,XX,-3,der(9;21 ) (q10;q10),der(13)t(1;13)(q11; p13),?der(22)t(3;22)(q22;q13), +mar. The karyotypic features of this BMPA thus differ from the characteristic cytogenetic findings in pleomorphic adenomas and carcinomas ex pleomorphic adenoma.

Adenoma, Pleomorphic↗
PubMed1998

Cytogenetic analysis of four angiosarcomas from deep and superficial soft tissue.

Angiosarcomas are rare malignant vascular tumors, most commonly found in the skin or superficial soft tissue. We found clonal chromosome aberrations in four short-term cultured angiosarcomas. Two cases were diagnosed as epithelioid angiosarcomas, and one as postmastectomy angiosarcoma. Two of the tumors were deep-seated and two were superficial. Angiosarcomas from deep, soft tissue are extremely rare and have never been cytogenetically investigated before. The chromosome number ranged from hypodiploid to hypertriploid. When the results from the present study were combined with data on the four previously reported cytogenetically aberrant angiosarcomas, the most frequently rearranged chromosomes were 5, 7, 8, 13, 15, 20, 22, and the Y chromosome. Recurrent changes, each found in three of these eight angiosarcomas, were gains of 5pter-p11, 8p12-qter, and 20pter-q12, losses of 7pter-p15 and 22q13-qter, and -Y in two of three men.

Adult↗
PubMed1998

Chromosomal aberrations in a consecutive series of childhood rhabdomyosarcoma.

BACKGROUND AND PROCEDURE: During a 13-year period, 22 children were treated for rhabdomyosarcoma (RMS). In 18 of these patients chromosome analysis was attempted on material from tumor biopsies, fine needle aspiration biopsies and/or bone marrow samples. RESULTS: Clonal chromosome aberrations were detected in 14 cases; 7 of 9 embryonal RMS, 6 of 8 alveolar RMS and in the single case of pleomorphic RMS cytogenetic failures were more frequent in fine needle aspiration biopsies than in tumor biopsies. The characteristic t(2;13) translocation was seen in 2 alveolar RMS but not in any of the other subtypes. In 3 of the embryonal RMS hyperdiploid or hypertetraploid karyotypes with few or no structural rearrangements were seen. In all 3 cases the clinical course was relatively benign, suggesting that certain karyotypic patterns in RMS may be of prognostic significance. CONCLUSIONS: Our results add to the evidence that cytogenetic analysis should be an integral part of the diagnostic examinations of children with RMS.

Adolescent↗
PubMed1998

Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: a report of the CHAMP Study Group. Chromosomes and MorPhology.

With the aim of identifying objective cytogenetic-morphologic correlations, we evaluated 46 pleomorphic soft tissue sarcomas (mainly diagnosed originally as malignant fibrous histiocytomas) with clonal chromosome aberrations both cytogenetically and morphologically as part of an international collaborative study. By detailed histopathologic examination, most cases could be categorized into specific tumor types. Eight sarcomas were diagnosed as lipogenic (4 pleomorphic, 1 combined pleomorphic and myxoid/round cell, and 3 dedifferentiated liposarcomas), 19 as myogenic [11 leiomyosarcomas, 1 rhabdomyosarcoma, 4 myosarcomas not otherwise specified (NOS), and 3 probable myosarcomas NOS], 8 as myxofibrosarcomas, 1 as a malignant peripheral nerve sheath tumor, 1 as malignant mesenchymoma, 1 as extraskeletal osteosarcoma, I as sarcoma resembling proliferative fasciitis, and 7 as pleomorphic sarcomas NOS. In a three-grade system, 10 tumors were grade 2 and 36 were grade 3. The majority had highly complex karyotypes. A total of 24 recurrent abnormalities (defined by their presence in at least five cases) were detected: ring chromosomes, homogeneously staining regions (hsr) and/or double minute chromosomes (dmin), and structural rearrangement of 22 different chromosome bands or regions. The frequency and distribution of the recurrent karyotypic features were uneven. Grade 3 tumors displayed, on average, more aberrations per case than did grade 2 tumors. Nine of the selected abnormalities, including hsr/dmin and rearrangements of 19p13 and 19q13, were found only among the high-grade tumors. When the tumors were subdivided according to lineage of differentiation, the highest frequency of aberrations was seen in pleomorphic sarcomas NOS, followed by myxofibrosarcomas, myogenic sarcomas, and lipogenic sarcomas. None of the selected rearrangements was, however, specific for any of these subgroups. The sole consistent cytogenetic-morphologic association was that all three dedifferentiated liposarcomas had multiple abnormal clones, at least one of which contained supernumerary ring chromosomes. Due mainly to karyotype complexity, it therefore seems unlikely that cytogenetic analysis can assist in the differential diagnostic subclassification of pleomorphic sarcomas, nor was there any clear-cut indication that the karyotypic picture could be used to predict clinical outcome. Although the mean number of recurrent chromosome aberrations was almost twice as high in sarcomas that gave rise to metastases as among those that did not, no particular aberration was restricted to either of the two subgroups.

Adult↗
PubMed1998

Chromosomal organization of amplified chromosome 12 sequences in mesenchymal tumors detected by fluorescence in situ hybridization.

The chromosomal organization of amplified chromosome 12 sequences was studied with fluorescence in situ hybridization in six mesenchymal tumors: two osteosarcomas, one lipoma, two liposarcomas, and one fibrosarcoma. All except the fibrosarcoma contained ring and/or giant marker chromosomes. Amplification of chromosome 12 sequences, demonstrated with whole-chromosome paint in all cases, was confined to ring and giant marker chromosomes in four tumors. In one of the osteosarcomas and in the fibrosarcoma, amplified sequences were added to chromosome 12 and to chromosomes 10, 12, 18, and the Y chromosome, respectively. Hybridizations with single-copy probes demonstrated considerable inter- and intracellular variation in the arrangement of chromosome 12 sequences in ring and marker chromosomes. Amplification of 12q13-15 sequences, predominantly from the HMGIC-MDM2 region, was detected in all cases, but the two osteosarcomas also contained amplification of 12p material. This finding, combined with results from previous studies, indicates that 12p amplification is a feature distinguishing osteosarcomas from adipose tissue tumors. A novel finding was the presence of positive signals for chromosome 12 alpha-satellite sequences in ring and marker chromosomes in four cases. Rod chromosomes carrying amplified material, in particular those that were relatively stable, frequently exhibited chromosome 12 negative terminal segments; two of these, present in two separate cases, were shown by C-banding to contain constitutive heterochromatin. The significant intercellular heterogeneity in the number and structure of rings and giant markers in a subset of mesenchymal tumors could be explained by continuous recombination through breakage-fusion-bridge cycles. If so, this process will continue until broken ends become stabilized, for example by acquisition of telomeric segments from other chromosomes.

Adolescent↗
PubMed1998

Cytogenetics of uterine sarcomas: presentation of eight new cases and review of the literature.

Tissue from 14 uterine tumor samples from eight patients-four with endometrial stromal sarcoma (ESS), two with leiomyosarcoma (ULMS), and two with malignant mixed mesodermal tumor (MMMT)-were investigated cytogenetically after short-term culturing. Clonal chromosome aberrations were found in 12 tumors. One ESS showed a recombination between 7p14 and 17q12, a rearrangement characterizing a subset of ESSs. In our series, chromosomes 1, 6, 7, and 16 were involved in structural aberrations most frequently (four cases each). Net loss of 6q material was found in four cases and bands 11q13, 16q13, and 22q13 were each rearranged in four cases. Among 43 uterine sarcomas, including 12 MMTs, now available for evaluation, some differences in breakpoint distribution among different tumor types were found. Rearrangements of bands 1p32, 3p24, and 10q22 were found exclusively in ULMS, whereas aberrations of bands 6p21, 7p21, and 17q12 were found predominantly in ESS.

Aged↗
PubMed1998

Nonrandom pattern of telomeric associations in atypical lipomatous tumors with ring and giant marker chromosomes.

Atypical lipomatous tumors (ALTs) are cytogenetically characterized by supernumerary ring and giant marker chromosomes. Another common finding in ALT is that the tumor cells are cytogenetically heterogeneous with a variety of mostly nonclonal numerical and structural chromosome aberrations, including telomeric associations. In a series of 48 cytogenetically investigated ALTs, all chromosomal aberrations, clonal as well as nonclonal, were registered. Clonal ring chromosomes were present in 47 cases and giant markers in 11 cases. In 7 cases, 12 clonal telomeric associations were found and 37 cases showed nonclonal associations involving 344 identified telomeres. The telomere associations were nonrandomly distributed, with the telomeres of 11p, 20p, 20q, 9q, 15p, 19q, and 22q being most frequently (8.7-4.1% of all associations) involved; only Xp and Xq were never affected. The pattern of telomeric associations in ALT was compared with literature data on 47 giant cell tumors (880 telomeres), previously reported to show a nonrandom distribution of associations, and 36 sporadic cases of a variety of other human neoplasms (583 telomeres). The analysis indicated that the telomeres of 11p, 19q, and 20q are preferentially involved in associations in several tumor types. Among other structural aberrations in the ALT series, 221 nonclonal and 52 clonal breakpoints were identified, as well as 342 nonclonal and 14 clonal numerical aberrations. The combined data suggest that telomeric associations may predispose to acquired chromosome aberrations in neoplasia.

Adult↗
PubMed1998

Nonrandom numerical chromosome abnormalities in basal cell carcinomas.

Clonal chromosome abnormalities were found in 22 of 23 short-term cultured basal cell carcinomas (BCC) of the skin. The karyotypic abnormalities were nonrandom and in several cases included evidence of clonal evolution. Especially in cultures showing an epithelial growth pattern, simple numerical changes, most commonly +18, +9, +20, +7, and +5, predominated and presumably constitute pathogenetically important aberrations present in the neoplastic parenchyma. Also, several structural rearrangements of chromosome arm 9q were seen, which may be of particular interest against the background that a gene for familial BCC (Gorlin syndrome), the PTCH gene, maps to this region. Finally, most of the clonal aberrations detected in predominantly fibroblast-like cultures are likely to reflect changes acquired by cells of the tumor stroma, which raises the question whether mutations also of this tumor component may play a pathogenetic role in BCC development.

Adult↗
PubMed1998

Complex karyotype in a childhood adrenocortical carcinoma.

Cytogenetic analysis of short-term cultured cells from an 11-cm adrenocortical carcinoma in a 3.5-year-old girl revealed the karyotype 46,XX,inv(9)(p11q12)c/[2]/56-57,XX,+2,+4,+5,+7,+8,inv(9)c,+10,+add (13)(p11), +14,+15,+19,+20,+20,+mar[cp19]. To our knowledge, this is the first description of an abnormal karyotype in a pediatric adrenocortical tumor. Inasmuch as the distinction between benign and malignant adrenocortical tumors is often difficult to make from clinical and histopathologic data alone, the present findings suggest that cytogenetic analysis may be a valuable adjunct in the differential diagnosis.

Adrenal Cortex Neoplasms↗