The role of cytogenetics in the classification of soft tissue tumours

 Soft tissue tumours represent a heterogeneous group of mesenchymal lesions, and their classification is the subject of continuous debate. Chromosome analysis, molecular cytogenetics and molecular assays may become increasingly useful in diagnosis, and this review summarises advances in the cytogenetic characterisation and classification of soft tissue tumours. Among the group of fibrous lesions, superficial fibromatosis exhibits trisomy 8. This genomic change is also observed in desmoid fibromatosis in association with trisomy 20. Trisomy 11 is the most frequently observed chromosomal aberration in congenital fibrosarcoma. Dermatofibrosarcoma protuberans and giant cell fibroblastoma share a translocation t(17;22), which supports the concept of the existence of a common differentiation pathway. Adipose tissue tumours is the group in which integration of genetics and pathology has been most fruitful. Ordinary lipomas cytogenetically show an abnormal karyotype in about half the cases. Genomic changes of the 11q13 region are observed in hibernoma. Lipoblastoma exhibits a specific 8q rearrangement in 8q11-q13. Loss of material from the region 16q13-qter and 13q deletions are observed in spindle cell/pleomorphic lipomas. The well-differentiated liposarcoma/atypical lipoma group is characterised karyotypically by the presence of one extra ring and/or extra giant chromosome marker. Myxoid and round cell liposarcoma share the same characteristic chromosome change: t(12;16)(q13;p11) in most cases. In the group of smooth muscle lesions most data are derived from uterine leiomyomas, which can be subclassified cytogenetically into seven different types. Half of all leiomyomas are chromosomally normal; the other half have one of six possible consistent chromosome changes. Alveolar rhabdomyosarcoma is characterised cytogenetically by two variant translocations t(2;13)(q35;q14) and t(1;13)(p36;q14). Among tenosynovial tumours, the localised type of giant cell tumour of tendon sheath exhibits two different karyotypic changes. One involves 1p11 in a translocation with chromosome 2 or with another chromosome. A second type involves 16q24. Synovial sarcoma is characterised cytogenetically by a translocation occurring between chromosome 18 and presumably two adjacent loci on the X chromosome. In neural tumours, abnormalities of chromosome 22 have been reported in benign schwannomas and perineuriomas. Malignant peripheral nerve sheath tumours exist in two main forms: sporadic and associated with the NF-1 syndrome. Karyotypes are very complex, but chromosomes 17q and 22q are very often involved. Clear cell sarcoma is characterised cytogenetically and molecularly by a translocation t(12;22)(q13;q12). The Ewing’s sarcoma/peripheral neuroectodermal tumour category shows a central karyotypic anomaly represented by the translocation t(11;22). The two variants t(21;22) and t(7;22) are found in some cases. Among cartilaginous lesion, the most frequently described anomaly is the t(9;22)(q22;q12) in extraskeletal myxoid chondrosarcoma. Intra-abdominal desmoplastic small round cell tumour is characterised by a t(11;22)(p13;q12). Received: 5 February 1997 / Accepted: 24 February 1997     

Rheumatoid arthritis and membranoproliferative glomerulonephritis: an unusual case

SUMMARY: Renal involvement is not uncommon in rheumatoid arthritis (RA). Many RA patients have renal dysfunction either secondary to the drugs used to treat arthritis or because of the chronic inflammation. Renal pathologies have often included amyloidosis, drug-related renal disease and mesangial glomerulonephritis. However, membranoproliferative glomerulonephritis has only been rarely reported. We report a case of rheumatoid arthritis associated with membranoproliferative glomerulonephritis that rapidly progressed to end-stage renal disease.     

Clonal chromosomal changes in juxta-articular myxoma

 Cytogenetic analysis of a juxta-articular myxoma revealed two distinct cytogenetically abnormal cell populations: inv(2)(p15q36) and +7, t(8;22)(q11–12; q12–13). These clonal chromosomal changes, the first to be reported in this tumour type, suggest that at least some juxta-articular myxomas are neoplastic rather than reactive in nature. Received: 8 June 1998 / Accepted: 17 August 1998     

5q — syndrome in a child

A boy aged 8 years, 10 months presented with refractory anemia. Bone marrow investigation revealed monolobular megakaryocytes. Cytogenetic analysis showed a clonal abnormality: 46, XY, del(5)(q14q32). This is the youngest individual ever reported with this disorder. A year after diagnosis, while on treatment with human recombinant erythropoietin, the bone marrow showed an excess of blasts. No bone marrow donor could be found. Transformation to acute myelomonocytic leukemia occurred 3 months later. In spite of intensive chemotherapy, the child died of progressive disease with massive splenomegaly and jaundice. The case illustrates that the 5q- syndrome can occur de novo in children. The outcome in this child was poor, which may reflect a difference from the adult 5q- syndrome or may possibly be related to the erythropoietin the child received.     

Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group.

Soft tissue tumors commonly show cytogenetic abnormalities, some of which are tumor specific. Lipomatous tumors represent the largest category of soft tissue neoplasms, and numerous karyotypic aberrations have been identified. However, clear-cut correlation between morphology and karyotype has not been undertaken on a systematic basis in a double-blind setting. The morphological features and histological diagnosis of 178 lipomatous neoplasms were reviewed independently without knowledge of the clinical data. The consensus diagnoses were then correlated with the clinical findings and compared with the tumors' karyotypes, using G-banded preparations from short-term cultures. The data were collated by a multicenter collaborative group of pathologists, geneticists, and surgeons. Clonal chromosomal abnormalities were identified in 149 cases studied (84%) and, to a large extent, the karyotype correlated with the morphological diagnosis. Specifically, 26 (96%) of 27 myxoid liposarcomas and its poorly differentiated variants showed a t(12;16); 29 (78%) of 37 atypical lipomatous tumors (including 5 dedifferentiated cases) showed ring chromosomes; 74 (80%) of 93 subcutaneous and intramuscular lipomas had karyotypic aberrations affecting mainly 12q, 6p, and 13q; 7 of 8 spindle cell and pleomorphic lipomas had aberrations of 16q; 3 lipoblastomas showed 8q rearrangements; and 2 hibernomas showed 11q abnormalities. We conclude that cytogenetic abnormalities are common in lipomatous tumors, correlate reliably with morphological sub-type in many cases, and can be of diagnostic value in histologically borderline or difficult cases.     

Chromosome abnormalities in benign prostatic hyperplasia

We combined conventional cytogenetic analysis and fluorescence in situ hybridization of short-term cultures of 28 samples from benign prostatic hyperplasia. Lou of the Y chromosome was the most common chromosome change, followed by trisomy 7. Trisomy 7, however, may be unrelated to the origin of benign prostate hyperplasia, in which the only and not very specific change seems to be the loss of the Y chromosome. Genes Chrom Cancer 9:227-233 (1594). © 1994 Wiley-Liss, Inc.     

Ring chromosome 6 as the only change in a thymoma

Cytogenetic analysis of a thymoma showed the presence of a ring chromosome 6 as the sole chromosome abnormality. © 1993 Wiley-Liss, Inc.     

Leiomyoma cells with 12q15 aberrations can be transformed in vitro and show a relatively stable karyotype during precrisis period

Tumor cells from three uterine leiomyomas showing translocations involving 12q14-15 were transformed by transfection using the "early regions" of the SV40 genome. The cells had a higher proliferative capacity, were able to form colonies in soft agar, and showed an increased growth potential. Karyotype analyses of these transformed leiomyoma cells showed that the cells had retained the initial t(12;14) and t(12;15).     

Intramuscular mixed tumour with clonal chromosomal changes

 A case of an entirely intramuscular mixed tumour occurred in an 82-year-old man, who presented with a large mass in the region of the right triceps muscle. A lobulated tumour was seen, with plump, round epithelioid cells embedded in a chondromyxoid stroma. Immunohistochemical examination showed strong S100 protein and pancytokeratin positivity in most of the tumour cells. Cytogenetic analysis revealed complex clonal chromosomal changes: 47, XY, +i (2) (q10), –15, der (17)t(15;17) (q11; p12), +r. Differential diagnosis against extraskeletal myxoid chondrosarcoma (EMC) may be problematic, particularly in an incisional biopsy. Chromosomal analysis can be very helpful in solving this problem, since EMC shows a specific reciprocal chromosome translocation characterised as t (9;22) (q22–31) (q11–12). Received: 8 July 1998 / Accepted: 22 September 1998