Biomedical subjects

G Tallini

Publications and source records attributed to G Tallini.

At least 37 records · Page 2Linked to original sources

PubMed2000

Cytogenetic, clinical, and morphologic correlations in 78 cases of fibromatosis: a report from the CHAMP Study Group. CHromosomes And Morphology.

Whether fibromatoses are neoplastic or reactive lesions has long been controversial and the relationship, if any, between the superficial and deep forms (desmoid tumors) are poorly understood. Clinical, pathologic, and cytogenetic data of 78 cases of fibromatosis were analyzed and correlated with each other. The results demonstrate that clonal chromosome aberrations are a common feature of this entity, being present in 46% of desmoid tumors, although less frequent in the superficial types (10%). In the deep-seated extra-abdominal fibromatoses, trisomies 8 and 20 and loss of 5q material were the only recurrent features. No correlation between +8 and local recurrence was found. Our findings provide additional evidence for the neoplastic nature of fibromatoses.

Adult↗

PubMed2000

Cytogenetic-morphologic correlations in aneurysmal bone cyst, giant cell tumor of bone and combined lesions. A report from the CHAMP study group.

Aneurysmal bone cyst and giant cell tumor of bone are relatively rare bone tumors that sometimes coexist. We examined the karyotypes of 3 aneurysmal bone cysts, 12 giant cell tumors, and 3 combined lesions. All aneurysmal bone cysts showed involvement of chromosome segments 17p11-13 and/or 16q22. In addition, in 1 of the 3 giant cell tumors with secondary aneurysmal bone cyst, both chromosome bands were rearranged as well, albeit not in a balanced translocation. Seven out of 12 giant cell tumors were characterized by telomeric associations. One giant cell tumor showed a dup(16)(q13q22), suggesting the presence of a (minor) secondary aneurysmal bone cyst component, despite the absence of histological proof. Our results, combined with literature data further substantiate that segments 16q22 and 17p11-13 are nonrandomly involved in at least some aneurysmal bone cysts, irrespective of subtype (primary, secondary, intra/extraosseous, solid or classic). These findings strongly suggest that some aneurysmal bone cysts are true neoplasms. In addition, telomeric associations are the most frequent chromosomal aberrations in giant cell tumor of bone, the significance of which remains elusive. In combined giant cell tumor/aneurysmal bone cyst each component seems to retain its own karyotypic abnormality.

Adolescent↗

PubMed2000

Cytogenetic evidence of clonality in cutaneous benign fibrous histiocytomas: a report of the CHAMP study group.

AIMS: Cutaneous benign fibrohistiocytic tumours are among the most common soft tissue lesions. Their biological nature, in particular whether they are neoplastic or reactive, has long been disputed. Some morphological subtypes can be confused with sarcoma. Since available karyotypic data in these lesions are scarce, this study was undertaken to determine whether their cytogenetic analysis might demonstrate clonality and might help in differential diagnosis. METHODS AND RESULTS: Thirteen karyotyped benign cutaneous fibrous histiocytomas (BFH) were morphologically reassessed and classified as ordinary BFH (eight cases), cellular BFH (four cases), and one ankle-type lesion. Five cases (38%) showed clonal cytogenetic changes, although the aberrations varied and did not correlate with histological subtypes. Karyotypic aberrations were more common in cellular BFH (3/4) than in the ordinary BFH (2/8). CONCLUSIONS: The demonstration of clonal chromosome abnormalities, in at least some cases, supports the neoplastic nature of cutaneous BFH. The karyotypic changes identified are different from those in dermatofibrosarcoma, with which cellular BFH is often confused histologically.

Adolescent↗

PubMed2000

Epstein-Barr virus RNA detection and glandular differentiation in nasopharyngeal carcinoma: report of 2 cases.

Most tumors arising in the nasopharynx are either squamous cell carcinoma or so-called undifferentiated carcinoma of the nasopharyngeal type. Primary adenocarcinomas of the nasopharynx are rare, and glandular differentiation in undifferentiated carcinoma of the nasopharyngeal type has not been reported to date. We report 2 cases of undifferentiated carcinoma of the nasopharyngeal type that show distinct glandular differentiation by light microscopy, histochemistry, immunohistochemistry, and ultrastructure. Both tumors showed equal positivity for Epstein-Barr virus latent membrane protein and in situ hybridization for Epstein-Barr virus genome in the undifferentiated areas of the tumor and those featuring glandular differentiation.

Adenocarcinoma↗

PubMed2000

Dysregulation of HMGIC in a uterine lipoleiomyoma with a complex rearrangement including chromosomes 7, 12, and 14.

Uterine lipoleiomyomas are extremely rare tumors consisting of a mixture of mature adipocytes and smooth muscle cells. Using G-banding and FISH, we characterized a complex rearrangement involving chromosomes 7, 8, 10, 11, 12, and 14 in one of these tumors. The region 14q23-24 was inserted into the long arm of the derivative chromosome 12, between the 3' end of HMGIC and 7q21-22, another region often rearranged in uterine leiomyomas. Other portions of chromosomes 12 and 14 were involved in derivative chromosomes 7, 11, 12, and 14. A chromosome 8 was involved in a three-way rearrangement including the derivative 7, a ring chromosome 10, and a small derivative chromosome 8 bearing segments of chromosomes 10 and 11. No abnormality of chromosome 5 was detected, in contrast to two previously reported cytogenetic analyses of uterine lipoleiomyoma. The consistent finding of chromosomes 12 and 14 on different derivatives indicates that the t(12;14) was a primary event. In addition, immunohistochemical studies showed that HMGI-C was aberrantly expressed in this tumor. These observations suggest that uterine lipoleiomyomas have a pathogenetic origin similar to that of typical leiomyomas. Genes Chromosomes Cancer 27:209-215, 2000.

Aged↗

PubMed2000

FRA-1 expression in hyperplastic and neoplastic thyroid diseases.

fra-1 gene overexpression has been shown to represent a general event in thyroid cell transformation in vitro and in vivo. Moreover, inhibition of FRA-1 protein synthesis by stable transfection with a fra-1 antisense construct significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role of the fra-1 gene product in the process of cellular transformation. In the attempt to define the potential use of FRA-1 protein detection in the diagnosis of thyroid diseases, we analyzed Fra-1 expression by a combination of immunohistochemistry and reverse transcription-PCR (RT-PCR) assay in 174 samples of thyroid nodules (22 nodular hyperplasias, 102 follicular adenomas, 34 papillary carcinomas, 12 follicular carcinomas, and 4 anaplastic carcinomas) representative of the spectrum of thyroid tumor pathology. FRA-1 protein was abundant in all of the carcinoma samples (50/50, 100%), with an intense staining in the nucleus and the cytoplasm. Positive staining was also found in most of the adenomas (90 of 102; 88%), but in this case, the staining was restricted to the nucleus. Similar results were obtained from the analysis of thyroid goiters; however, the number of positive cases is lower than adenomas (8 of 22; 36%); moreover, the staining was not observed in all of the cells. Conversely, no FRA-1 protein was detectable in 12 normal thyroid tissue samples used as controls. RT-PCR analysis confirmed a higher fra-1 expression in papillary and follicular carcinomas compared with goiters and adenomas. fra-1 expression was also analyzed on 10 fine needle aspiration biopsy (FNAB) samples by RT-PCR. fra-1-specific mRNA was detected in seven of the eight FNABs corresponding to thyroid nodules that were eventually diagnosed as adenomas (three of four) and carcinomas (four of four) after surgery. Conversely, no fra-1 gene expression was observed in two FNABs derived from normal thyroid. Further studies are required before suggesting FRA-1 protein detection as a useful tool for the diagnosis of hyperplastic and neoplastic disorders of the thyroid gland.

Biopsy, Needle↗

PubMed1999

Frequent mutation and nuclear localization of beta-catenin in anaplastic thyroid carcinoma.

Beta-catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both E-cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless pathway. Stabilization of beta-catenin followed by nuclear translocation and subsequent T-cell factor/lymphoid-enhancing factor-mediated transcriptional activation has been proposed as an important step in oncogenesis. Stabilization may occur through activating mutations in exon-3 at the phosphorylation sites for ubiquitination and degradation of beta-catenin. Immunohistochemical subcellular localization of beta-catenin and mutational analysis of exon-3 of the beta-catenin gene by single-strand conformational polymorphism followed by DNA sequencing was performed on 37 samples from 31 patients with anaplastic thyroid carcinoma. Immunofluorescent staining showed nuclear localization in 15 (42%) of the 36 samples examined. Nucleotide sequencing of mobility shifts detected by single-strand conformational polymorphism revealed somatic alterations in 19 (61%) of the 31 patients analyzed. We conclude that mutations in beta-catenin are common in anaplastic thyroid cancer and that they may activate transcription, as illustrated by frequent nuclear localization of the protein. These findings support the idea that beta-catenin acts as an oncogene and contributes to the highly aggressive behavior of this tumor.

Amino Acid Sequence↗

PubMed1999

Prostatic carcinoma cell migration via alpha(v)beta3 integrin is modulated by a focal adhesion kinase pathway.

The highly invasive human prostate cancer PC3 cell line was found to express the alpha(v)beta3 integrin; in contrast, the noninvasive LNCaP prostate cancer cell line did not express alpha(v)beta3. PC3 cells adhered to and migrated on vitronectin (VN), an alpha(v)beta3 ligand expressed in mature bone where prostate cancer cells preferentially metastasize. In contrast, LNCaP cells did not adhere to or migrate on VN. Analysis of primary human prostate cancer cells isolated from 16 surgical specimens, showed that these cells expressed alpha(v)beta3, whereas normal prostate epithelial cells did not. In addition, only primary prostate cancer cells adhered to and migrated on VN. The role of alpha(v)beta3 in mediating prostate epithelial cell migration was confirmed using LNCaP cell transfectants expressing beta3 (beta3-LNCaP). Exogenous expression of alpha(v)beta3 induced LNCaP cells to adhere to and migrate on VN. In response to alpha(v)beta3 engagement, increased tyrosine phosphorylation of focal adhesion kinase (FAK), a signaling molecule activated by integrins and able to modulate cell migration, was detected. Transfection of FAK-related nonkinase, known to compete with FAK for its correct localization and phosphorylation, caused inhibition of beta3-LNCaP cell migration, specifically on VN. These data indicate that de novo expression of alpha(v)beta3 integrin in prostate cancer cells generates a migratory phenotype that is modulated by a FAK signaling pathway. This study points to alpha(v)beta3 as potential target in prostate cancer cell invasion and metastasis.

Cell Adhesion Molecules↗

PubMed1999

Correlation between clinicopathological features and karyotype in spindle cell sarcomas. A report of 130 cases from the CHAMP study group.

Soft-tissue tumors have proved to be a fruitful area for the identification of reproducible cytogenetic aberrations, especially among pediatric round-cell sarcomas and lipomatous tumors. Thus far, however, data regarding sarcomas of monomorphic spindle cell type have been limited and somewhat disappointing, with the notable exception of synovial sarcoma. As part of an ongoing international collaborative study, 130 karyotyped spindle-cell sarcomas were reviewed and classified histologically, without knowledge of the clinical and karyotypic data, with the aim of identifying objective correlations between morphology, karyotype, and clinical parameters. Clonal chromosomal abnormalities were identified in 82 cases studied (63%), but only in the group of synovial sarcomas was there clear correlation between the cytogenetic findings, in the form of a consistent t(X;18)(p11;q11), and morphology. Among leiomyosarcomas (41 cases) and malignant peripheral nerve sheath tumors (MPNSTs; 27 cases) as well as in individual examples of rarer entities, there was a general tendency for karyotypic complexity associated with frequent loss or rearrangement of chromosome arms 1p, 10p, 11q, 12q, 17p, and 22q. Rearrangements of 17q (the region of the NF1 gene) were seen in 9/27 (33%) of MPNSTs. Among nine cases of solitary fibrous tumor (in which previous cytogenetic data are very limited) no consistent aberrations were identified. We conclude that, with the exception of synovial sarcoma, most spindle-cell sarcomas share with pleomorphic sarcomas the tendency for karyotypic complexity. There was no indication (in most of these lesions) that detectable cytogenetic aberrations could either facilitate their diagnosis or help to determine prognosis. There is a clear need to further study and understand the significance of multiple chromosomal abnormalities in this group of mesenchymal neoplasms with the particular goal of determining their role in the process of tumor development.

Adolescent↗

PubMed1999

Downregulation of p27KIP1 and Ki67/Mib1 labeling index support the classification of thyroid carcinoma into prognostically relevant categories.

The cyclin-dependent kinase inhibitor p27KIP1 has been proposed as a valuable prognostic indicator for a variety of human neoplasms. Immunohistochemical reactivity for p27KIP1 and the proliferation marker Ki67/Mib1 were investigated in 90 thyroid carcinomas of follicular cell origin. The neoplasms were divided into three prognostic groups on the basis of their morphologic features: group 1, well-differentiated papillary or follicular carcinomas with favorable pathologic features (43 papillary carcinomas and 4 minimally invasive follicular carcinomas); group 2, papillary or follicular carcinomas with unfavorable pathologic features (21 poorly differentiated carcinomas and 2 papillary carcinomas, tall cell variant); and group 3, undifferentiated, or anaplastic, carcinomas. p27KIP1 expression (p = 0.007) and Ki67/Mib1 labeling index (p = 0.02) showed a strong correlation with the subdivision of the thyroid carcinomas in the three prognostic groups with a significant linear trend for tumors with low p27KIP1 (p = 0.002) and high Ki67/Mib1 labeling index (p = 0.005) to segregate into the unfavorable categories (groups 2 and 3). Low p27KIP1 expression, but not cellular proliferation, was related to adverse prognostic factors, such as large tumor size (p = 0.03) and extrathyroidal extension (p = 0.01), but the correlation was not independent of the subdivision in the three groups. Low p27KIP1 expression (p = 0.03) and high proliferative rate (p = 0.02) were associated with poor survival, reflecting the close association between patient morbidity and mortality rates and tumor differentiation. No significant association could be seen between p27KIP1 or cellular proliferation and clinicopathologic parameters (e.g., age, sex, tumor size, extrathyroidal extension, vascular invasion, lymph node metastases, distant metastases, tumor stage, and survival rate) within any of the groups, or the histologic diagnosis of papillary versus follicular carcinoma irrespective of their degree of differentiation. Modulation of p27KIP1 and cellular proliferation patterns in thyroid carcinoma correlate with tumor differentiation and support the morphologic classification of thyroid carcinoma into prognostically relevant categories.

Adenocarcinoma, Follicular↗

PubMed1999

Biliary tract obstruction secondary to mycosis fungoides: a case report.

Mycosis fungoides is a cutaneous T-cell lymphoma that can disseminate to multiple organs. We report a patient who presented with obstructive jaundice caused by isolated involvement of the extrahepatic biliary tree by mycosis fungoides. Initially, endoscopic examinations and biopsies of the biliary tree and liver failed to reveal a cause for the obstructive symptoms. Finally, surgical resection of the gallbladder and extrahepatic ducts was performed. Examination revealed a dense, mixed lymphocytic infiltrate with atypical cells within the mucosa. Gene rearrangement studies confirmed the presence of a monoclonal T-cell population. The pattern of the gene rearrangement in the biliary tree was identical to that found in a previous skin biopsy that showed mycosis fungoides. Although liver involvement by mycosis fungoides is not uncommon, disease isolated to the extrahepatic biliary tree has not previously been reported. This case should alert clinicians and pathologists to yet another cause of obstructive jaundice.

Adult↗

PubMed1999

p27(kip1) acts as a downstream effector of and is coexpressed with the beta1C integrin in prostatic adenocarcinoma.

Integrins are a large family of transmembrane receptors that, in addition to mediating cell adhesion, modulate cell proliferation. The beta1C integrin is an alternatively spliced variant of the beta1 subfamily that contains a unique 48-amino acid sequence in its cytoplasmic domain. We have shown previously that in vitro beta1C inhibits cell proliferation and that in vivo beta1C is expressed in nonproliferative, differentiated epithelium and is selectively downregulated in prostatic adenocarcinoma. Here we show, by immunohistochemistry and immunoblotting analysis, that beta1C is coexpressed in human prostate epithelial cells with the cell-cycle inhibitor p27(kip1), the loss of which correlates with poor prognosis in prostate cancer. In the 37 specimens analyzed, beta1C and p27(kip1) are concurrently expressed in 93% of benign and 84%-91% of tumor prostate cells. Forced expression of beta1C in vitro is accompanied by an increase in p27(kip1) levels, by inhibition of cyclin A-dependent kinase activity, and by increased association of p27(kip1) with cyclin A. beta1C inhibitory effect on cell proliferation is completely prevented by p27(kip1) antisense, but not mismatch oligonucleotides. beta1C expression does not affect either cyclin A or E levels, or cyclin E-associated kinase activity, nor the mitogen-activated protein (MAP) kinase pathway. These findings show a unique mechanism of cell growth inhibition by integrins and point to beta1C as an upstream regulator of p27(kip1) expression and, therefore, a potential target for tumor suppression in prostate cancer.

Adenocarcinoma↗

PubMed1999

Frequent chromosomal DNA unbalance in thyroid oncocytic (Hürthle cell) neoplasms detected by comparative genomic hybridization.

Thyroid oncocytic (Hürthle cell) neoplasms represent a distinct subset of follicular thyroid tumors characterized by abnormal accumulation of mitochondria, whose chromosomal abnormalities have never been systematically analyzed. We have used comparative genomic hybridization to investigate chromosomal DNA alterations in 11 thyroid oncocytic tumors (7 adenomas and 4 carcinomas). Unbalanced chromosomal DNA profiles were detected in 6 of 7 adenomas and 3 of 4 carcinomas, numerical chromosomal aberrations being the dominant feature. Comparative genomic hybridization findings are compatible with two separate groups of tumors with karyotypic abnormalities, one characterized by multiple chromosomal gains with polysomy of chromosomes 5 and 7, the other by loss of chromosome 2. Pathologic and clinical features were similar in the two groups with no difference observed between adenomas and carcinomas. Activating H-, K-, or N-Ras mutations are commonly detected in follicular adenomas and carcinomas of the thyroid gland. However, Ras mutational analysis demonstrated that only one of the tumors in this series, an oncocytic carcinoma with a balanced karyotype, had activating Ras mutations (at codon 13 of K-Ras). The lack of Ras mutations in the 9 oncocytic neoplasms exhibiting chromosomal aneuploidy indicates that numerical chromosomal abnormalities are independent of activating Ras mutations in oncocytic tumors.

Adenoma, Oxyphilic↗

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

HMGI(Y) and HMGI-C dysregulation: a common occurrence in human tumors.

HMGI(Y) and HMGI-C are members of a distinct family of "high mobility group" (HMG) proteins that are nonhistone chromatin-associated proteins initially characterized by high electrophoretic mobility in polyacrylamide gels (hence the acronym HMG). Recent studies have shown that HMGI(Y) and HMGI-C are important elements with a role in the regulation of chromatin structure and function. Like other HMG proteins they are responsible for the correct three-dimensional configuration of protein-DNA complexes and therefore play a key role in important cellular processes such as DNA transcription. Aberrant HMGI(Y) and HMGI-C expression generally correlates with a malignant tumor phenotype. However, HMGI(Y) and HMGI-C dysregulation, as a result of specific chromosomal rearrangements, is also being identified in a variety of common benign mesenchymal tumors such as lipomas and uterine leiomyomas making HMGI(Y) and HMGI-C genes probably the most commonly rearranged genes in human neoplasms. While a precise definition of the HMGI(Y) and HMGI-C role in tumor initiation and progression is still missing, it is likely that future investigations will contribute valuable insights to the understanding of human neoplasia.

Female↗

PubMed1998

Detection of high mobility group I HMGI(Y) protein in the diagnosis of thyroid tumors: HMGI(Y) expression represents a potential diagnostic indicator of carcinoma.

Hyperplastic or neoplastic proliferative lesions of thyroid follicular epithelium consist of a spectrum, ranging from nodular hyperplasia to undifferentiated (anaplastic) carcinoma, and usually present as palpable thyroid nodules. Thyroid nodules are a common occurrence in the general population, but only a small proportion of them are eventually diagnosed as carcinoma. The difficulty in objectively identifying those thyroid nodules that are malignant to avoid unnecessary surgery, combined with the range and effectiveness of the available therapeutic options in those patients who do, indeed, have thyroid carcinoma, has prompted the search for tumor markers and prognostic indicators. The high mobility group I (HMGI) proteins represent a class of nuclear proteins involved in the regulation of chromatin structure and function. HMGI(Y), one of the members of this class, is expressed at high levels during embryogenesis and in malignant tumors but at generally low levels in normal adult human tissues. Previous work on a limited number of thyroid samples suggested that the detection of the HMGI(Y) proteins may provide a clinically useful diagnostic tool. To verify this assumption, we analyzed HMGI(Y) expression by a combination of immunohistochemistry and reverse transcription-PCR in 358 thyroid tissue samples that were representative of the spectrum of thyroid tumor pathology. HMGI(Y) was detectable in 18 of 19 follicular carcinomas, 92 of 96 papillary carcinomas, and 11 of 11 undifferentiated (anaplastic) carcinomas but in only 1 of 20 hyperplastic nodules, 44 of 200 follicular adenomas, and 0 of 12 normal tissue samples. The correlation between HMGI(Y) expression and a diagnosis of carcinoma was highly significant (P < 0.0001). We also prospectively collected and analyzed for HMGI(Y) expression by immunohistochemistry and reverse transcription-PCR in 12 fine needle aspiration biopsies from 10 patients who subsequently underwent surgical removal of a solitary thyroid nodule. HMGI(Y) was detectable only in the four fine needle aspiration biopsies, corresponding to the thyroid nodules that were definitively diagnosed as carcinomas after surgery (two follicular carcinomas and two papillary carcinomas). The remaining eight samples (six follicular adenomas and two samples consisting of normal follicular cells) were negative. The findings of this study confirm the differential expression of HMGI(Y) in thyroid neoplasia and indicate the HMGI(Y) protein as a potential marker for thyroid carcinoma.

Adenocarcinoma, Follicular↗

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

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↗