Chromosomal evolution and tumor progression in a myxoid liposarcoma

A myxoid liposarcoma showed macroscopic, histologic, and cytogenetic heterogeneity. In one of three myxoid nodules and in the surrounding lipoma-like tumor tissue, the translocation t(12;16)(g13;p11), known to be specific for myxoid liposarcoma, was found as the sole chromosomal abnormality. In the other two nodules, additional rearrangements involving chromosomes 1, 12, and 16 were found. These aberrations were probably secondary to the primary t(12;16), and are cytogenetic evidence of clonal evolution. The complex chromosome aberrations were present in those tumor parts that had more malignant histology, indicating that the acquisition of secondary chromosomal aberrations parallels the histologic manifestations of tumor progression.     

The utility of fluorescence in situ hybridization (FISH) in the diagnosis of myxoid soft tissue neoplasms

Diagnosing myxoid soft tissue neoplasms can be challenging because of overlapping histologic features. Distinct chromosomal translocations have been identified in several myxoid sarcomas, including t(12;16)(q13;p11) FUS-DDIT3 in myxoid liposarcoma, t(7;16)(q34;p11) FUS-CREB3L2 in low-grade fibromyxoid sarcoma, and t(9;22)(q31;q12) EWSR1-NR4A3 in extraskeletal myxoid chondrosarcoma. These recurrent chromosomal alterations are attractive targets for diagnostic studies. To that end, dual-color, break-apart fluorescence in situ hybridization (FISH) probes spanning the genomic regions of EWSR1 (22q12), DDIT3 (12q13), and FUS (16p11) (Vysis, Downer's Grove, IL) were evaluated in formalin-fixed, paraffin-embedded tissues from myxoid neoplasms, including intramuscular myxoma (n=10), myxoid liposarcoma (n=18), low-grade fibromyxoid sarcoma (n=10), extraskeletal myxoid chondrosarcoma (n=13), and myxofibrosarcoma (n=8). Of the myxoid liposarcomas, 18/18 cases had a rearrangement of the DDIT3 gene, with 17/18 (94.4%) showing both DDIT3 and FUS gene rearrangements. A FUS gene rearrangement was identified in 7/10 (70%) of low-grade fibromyxoid sarcomas, with no changes involving EWSR1 or DDIT3. An EWSR1 translocation was seen in 6/13 (46.2%) of extraskeletal myxoid chondrosarcomas, without changes in DDIT3 or FUS genes. The remaining neoplasms studied showed no rearrangements involving DDIT3, FUS, or EWSR1 genes. In conclusion, interphase FISH using DDIT3 and FUS probes identifies the characteristic translocation in myxoid liposarcoma. FUS and EWSR1 probes are useful in confirming the diagnosis of low-grade fibromyxoid sarcoma and extraskeletal myxoid chondrosarcoma, respectively. The specificity of the probes is documented as none of the non-translocation-associated myxoid tumors showed genomic abnormalities with the probes tested. FISH is capable of providing specific ancillary information useful in this often difficult differential diagnosis.     

Histologic subtype and margin of resection predict pattern of recurrence and survival for retroperitoneal liposarcoma

OBJECTIVE: The aim of this study was to determine the pattern of recurrence and prognostic significance of histologic subtype in a large series of patients with primary retroperitoneal liposarcoma. SUMMARY BACKGROUND DATA: Classification of liposarcoma into subtypes, based on morphologic features and cytogenetic aberrations, is now widely accepted. Previous studies have shown that high histologic grade and incomplete gross resection are the most important prognostic factors for survival in patients with retroperitoneal sarcoma and suggest that patients with liposarcoma have a 3-fold higher risk of local recurrence compared with other histologies. METHODS: A prospective database was used to identify 177 patients with primary retroperitoneal liposarcoma treated between July 1982 and June 2002. Histology at primary presentation was reviewed by a sarcoma pathologist and subtyped into 4 distinct groups according to strict criteria. The influence of clinicopathological factors on local recurrence, distant recurrence, and disease-specific survival was analyzed. RESULTS: Of 177 patients with primary retroperitoneal liposarcoma operated on for curative intent, 99 (56%) presented with well-differentiated, 65 (37%) with dedifferentiated, 9 (5%) with myxoid, and 4 (2%) with round cell morphology. The tumor burden was determined by the sum of the maximum tumor diameters. The median tumor burden was 26 cm (5-139). Median follow-up time for 92 (52%) surviving patients was 37 (mean, 0.5-192) months. Multivariate analysis showed that dedifferentiated liposarcoma subtype was associated with a 6-fold increased risk of death compared with well-differentiated histology (P < 0.0001). In addition to histologic subtype, incomplete resection (P < 0.0001), contiguous organ resection (excluding nephrectomy; P = 0.05), and age (P = 0.03) were important independent prognostic factors for survival in retroperitoneal liposarcoma. Retroperitoneal dedifferentiated liposarcoma was associated with an 83% local recurrence rate and 30% distant recurrence rate at 3 years. CONCLUSIONS: The histologic subtype and margin of resection are prognostic for survival in primary retroperitoneal liposarcoma. Dedifferentiated histologic subtype and the need for contiguous organ resection (excluding nephrectomy) was associated with an increase risk of local and distant recurrence. Nephrectomy may be needed to achieve complete resection, but has no measurable influence on disease specific survival.     

Myxoid liposarcoma of the ankle: a case report

Myxoid liposarcoma occurs predominantly in the deep soft tissues of the extremities, and tends to metastasize to a wide range of soft tissue or bone locations. We report a case of myxoid liposarcoma arising in the ankle of a 19-year-old man. A diagnosis of myxoid liposarcoma was made by open biopsy, and a wide resection requiring plastic surgical reconstruction was performed. Cytogenetic analysis of the resected tumor exhibited a reciprocal translocation t(12;16)(q13;p11) as the sole anomaly, which is found in more than 90% of myxoid liposarcoma cases. The patient had no evidence of local recurrence or metastasis within 7 years of follow-up. Although myxoid liposarcoma is rare in the ankle, it should be considered in the differential diagnosis of a painless soft tissue mass in this region.     

Chromosomal changes in soft-tissue sarcomas. A new diagnostic parameter

A cytogenetic study was performed on short-term cultures from fresh surgical specimens obtained from 41 patients with soft-tissue sarcomas of various histologic origins. The results demonstrated that myxoid liposarcomas (five tumors) were associated with a specific translocation between chromosomes 12 and 16 and that synovial sarcomas (six tumors) were associated with a specific translocation between the X chromosome and chromosome 18. These chromosomal data have been used to differentiate myxoid liposarcoma from other myxoid tumors exhibiting a non-characteristic histologic picture, as well as to ascertain the diagnosis of synovial sarcoma in undifferentiated soft-tissue sarcomas. The results to date indicate that identification of specific chromosomal changes in sarcomas may provide a new diagnostic criterion for these tumors and possibly improve prognostication with regard to survival and response to treatment.     

Phosphatemia is related to chromosomal aberrations of parathyroid glands in patients with hyperparathyroidism

BACKGROUND AND AIMS: It has been well documented that gene and DNA alterations occur frequently in benign primary parathyroid adenomas as well as in parathyroid glands with secondary hyperplasia. However, it has not been shown whether a correlation exists between somatic DNA aberrations and clinical data. METHODS: We analyzed the frequency of chromosomal aberrations in adenomas obtained from 25 patients with primary hyperparathyroidism (pHPT) and 60 parathyroid nodules from 20 uremic patients with secondary hyperparathyroidism (sHPT). The relation of chromosomal aberrations to parathyroid hormone, as well as calcium and phosphate serum concentrations, was assessed. Allelic changes were evaluated by microsatellite allelotyping using 105 polymorphic markers. RESULTS: Somatic chromosomal aberrations were found in 23 out of 25 adenomas, in hyperplastic lesions from 16 out of 20 patients. In pHPT as well as in sHPT a positive correlation was found between the number of chromosomal alterations and serum phosphate concentration (tau=0.270, p=0.05; and tau=0.362, p=0.03, respectively). Only in pHPT was a negative correlation of borderline significance between serum parathormone (PTH) and number of aberrated chromosomes noticed (tau=-0.258, p=0.07). There was no correlation between the number of DNA changes and serum concentration of calcium or tumor volume. CONCLUSION: Hyperphosphatemia may increase the risk of specific and random chromosomal aberrations due to increasing proliferation rate of parathyroid cells in patients with sHPT.     

Liposarcomas of the mediastinum and thorax: a clinicopathologic and molecular cytogenetic study of 24 cases, emphasizing unusual and diverse histologic features

Liposarcoma rarely occurs in the mediastinum, and most reports predate the current genetically based classification system. We report the clinicopathologic and molecular genetic features of a series of thoracic liposarcomas identified over a 60-year period. Twenty-four confirmed cases were reclassified using the most recent World Health Organization classification. Fluorescent in situ hybridization for CPM amplification and/or DDIT3 rearrangement was performed on selected cases. The 24 cases occurred in 13 men and 11 women (mean age, 53 y; range, 15 to 73 y) and arose in all mediastinal compartments. All subtypes were encountered with 8 well-differentiated liposarcomas, 6 dedifferentiated liposarcomas (3 of 6 confirmed CPM+), 7 pleomorphic liposarcomas (2 of 7 confirmed CPM-, 1 of 7 confirmed DDIT3-), 2 myxoid liposarcomas, and 1 unclassifiable liposarcoma (CPM- and DDIT3-). Unusual histologic features included myxoid well-differentiated liposarcoma mimicking myxoid liposarcoma (2 cases), lipoleiomyosarcoma (1 case), dedifferentiated liposarcoma with "meningothelial"-like dedifferentiation, differentiated myxoid liposarcoma mimicking well-differentiated liposarcoma (CPM-), and pleomorphic liposarcoma with epithelioid and myxoid change. Follow-up information was available for 19 patients (mean, 55 mo; range, 8 to 252 mo). Outcome was strongly associated with histologic subtype, with death from disease occurring in 1 of 6 well-differentiated, 1 of 4 dedifferentiated, 5 of 7 pleomorphic, and 2 of 2 myxoid liposarcomas. The mediastinum shows a preponderance of uncommon subtypes and unusual morphologic variants. Correct classification has important implications, with most patients with well-differentiated/dedifferentiated liposarcoma having a protracted clinical course, in contrast to the more rapid disease progression seen in patients with myxoid and pleomorphic liposarcoma.     

Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases

One-hundred-eleven cases of histopathologically atypical or malignant lipomatous lesions in the somatic soft tissue and retroperitoneum were studied. These consisted of 48 differentiated fatty neoplasms of the somatic soft tissues (DFT-S), 21 fatty neoplasms of the retroperitoneum (DFT-R), 33 myxoid liposarcomas from various sites and nine pleomorphic liposarcomas. DFT-S were defined as lipomatous lesions composed of mature fat and containing atypical stromal cells or lipoblasts. In the somatic soft tissues, this group included lesions that would be classified using published criteria as "atypical lipoma", "pleomorphic lipoma", "well-differentiated lipoma-like liposarcoma", and "sclerosing liposarcoma". All of the DFT-R met previously published criteria for "well differentiated liposarcoma" or "sclerosing liposarcoma". We found no consistent histologic differences between the DFT-S and DRT-R. No pure "round cell" liposarcomas were encountered although many myxoid liposarcomas had "round cell" areas. Follow-up data were available in 80 cases (72%) with a mean follow-up period of over 7 years. Among the DFT-S there were no uncontrollable recurrences, distant metastases, or tumor-related deaths. The depth of the neoplasm correlated with the tendency for local recurrence; no neoplasms primary in the subcutis recurred; 29% of the tumors recurred when they originated in the deep soft tissues or within the muscle. None of the recurrent tumors demonstrated "dedifferentiation." DFT-R had a recurrence rate of 67% and, although there were no distant metastases, nine patients (43%) died of tumor. Five retroperitoneal tumors dedifferentiated but did not metastasize. In light of this experience, we believe that the term "atypical lipoma" is warranted for the DFT-S and "well differentiated liposarcoma" is an appropriate label for the DFT-R. The overall mean survival for the 52 cases of liposarcoma (excluding DFT-S) was 13.6 years. The mean survival in "well differentiated liposarcoma" (11.25 years) was between that for myxoid liposarcoma (16.25 years) and that for pleomorphic liposarcoma (7 years). Six patients (29%) with myxoid liposarcoma developed local recurrences and 6 patients (29%) developed distant metastases and died. Metastasis was always associated with a round cell (or pleomorphic) component with increased numbers of mitotic figures in either the primary tumor or a local recurrence.     

Lipoblastoma and liposarcoma in children: an analysis of 9 cases and a review of the literature

Objectives

To review the experience at a children’s hospital of lipoblastoma and liposarcoma and to identify any factors that would differentiate one type of tumour from the other.

Design

A retrospective case series.

Setting

British Columbia’s Children’s Hospital a tertiary-care pediatric centre.

Patients

All patients with a pathological diagnosis of lipoblastoma and liposarcoma recorded over 12 years.

Main outcome measures

The frequency of lipoblastoma and liposarcoma, identified from biopsy specimens of pediatric adipose tumours. The clinical, pathological and cytogenetic variables between lipoblastoma and liposarcoma.

Results

One hundred and forty-nine adipose tumours were recorded. Seven (4.7%) were lipoblastomas and 2 (1.3%) were liposarcomas. All tumours presented as asymptomatic, slow-growing, soft-tissue masses. The children with lipoblastoma tended to be younger, but 29% were over 3 years of age. The liposarcoma patients were aged 9 and 14 years. One liposarcoma was of myxoid type and the other was a round cell variant. Karyotypes were reported for 1 lipoblastoma and 1 liposarcoma. The myxoid liposarcoma karyotype was 46,XY,t(12;16)(q13;p11), and the lipoblastoma was reported as 46,XY,der(8)?t(8q;?),+mar.

Conclusions

Lipoblastoma is an unusual childhood neoplasm and liposarcoma is very rare in children. Both tumours may present in a similar fashion, and differentiating them histologically can be difficult. Age cannot be relied upon to accurately predict their behaviour. The tumour karyotype is very helpful in differentiating these neoplasms.     

A case of retroperitoneal liposarcoma

A case of retroperitoneal liposarcoma is reported. A 42-year-old woman was admitted to our hospital with the complaint of a palpable mass in her left abdomen. Intravenous pyelography, barium enema and an ultrasonogram revealed a huge left abdominal tumor. At operation, a huge yellow-brownish tumor found in the retroperitoneal space, was completely removed. The tumor was 32 x 24 x 12 cm and weighed 4,075 g. Histologically, it was a myxoid liposarcoma. Three courses of adjuvant chemotherapy (cis-platin) were administered. The postoperative course was uneventful and the patient has been free of disease for 16 months.     

Unique cytological features and chromosome aberrations in chondroid lipoma: a case report based on fine-needle aspiration cytology, histopathology, electron microscopy, chromosome banding, and molecular cytogenetics.

Chondroid lipoma is a rare, benign tumor that may mimic soft-tissue sarcoma clinically. Its histopathologic features may resemble hibernoma, myxoid liposarcoma, myxoid chondrosarcoma, and other lipomatous or chondroid neoplasms. In this study, a chondroid lipoma was analyzed by fine-needle aspiration cytology, histopathology, electron microscopy, chromosome banding, and metaphase fluorescence in situ hybridization. The results demonstrate that chondroid lipoma exhibits a characteristic pattern by fine-needle aspiration cytology, including a mixture of benign adipose tissue with lipoblastlike cells, and chondroblastlike cells with a fibrochondroid matrix. Cytogenetically, a three-way rearrangement between chromosomes 1, 2, and 5 was found, together with an 11;16 translocation with a breakpoint in 11q13, approximately 1 Mb proximal to the MEN1 region shown to be rearranged frequently in hibernoma. The presence of a karyotype of low complexity, but without any of the genetic aberrations characteristic for other types of soft-tissue tumors, indicate that chondroid lipoma develops along a unique pathogenetic pathway.     

Low-grade pulmonary myxoid liposarcoma

Primary pulmonary liposarcoma is extremely rare. There are only 12 cases reported in the literature. We presented a case of low-grade primary pulmonary myxoid liposarcoma, which was diagnosed and underwent surgery in our clinic. The diagnosis was established after imaging investigations (X-ray and CT), histologic and immunohistochemical examinations. The patient was followed up one year after the operation.     

Predictive value of progression-associated chromosomal aberrations for the prognosis of meningiomas: a retrospective study of 198 cases

OBJECT: The goal of this study was to determine whether in meningiomas cytogenetic findings are suitable as a predictive parameter relevant to prognosis. METHODS: Between 1992 and 1998 at the Department of Neurosurgery, Saarland University, 198 patients underwent surgery to resect meningiomas. The meningiomas were investigated cytogenetically and the patients were followed up for a mean period of 33 months. On the basis of the cytogenetic findings, the meningiomas were subdivided into four groups: Group 0 meningiomas displayed a normal diploid chromosome set; Group 1 tumors were found to have monosomy 22 as the sole cytogenetic aberration; Group 2 tumors were markedly hypodiploid meningiomas with loss of additional autosomes in addition to monosomy 22; and Group 3 meningiomas had deletions of the short arm of a chromosome 1, as well as additional chromosomal aberrations including loss of one chromosome 22. One hundred ninety-eight patients in whom tumor resections were determined to be Simpson Grade I or II could be followed up after complete tumor extirpation. In 20 patients, one or several recurrences were documented during the period of observation. The tumors were classified according to their different, but mostly uniform chromosomal aberrations. Recurrences were found in six (4.3%) of 139 tumors in Groups 0 and 1 and in two (10.5%) of 19 tumors in Group 2; the highest rate of recurrence was found in 12 (30%) of 40 tumors in Group 3. This supports the notion that the deletion of the short arm of one chromosome 1 is an important prognostic factor in meningiomas. The results of this study document a significant correlation between histological grade (p < 0.0001), location (p < 0.0001), and recurrences of meningiomas (p < 0.0001) (significance determined using chi-square tests). CONCLUSIONS: The cytogenetic classification of meningiomas provides a significant contribution to the predictability of tumor recurrence and is, therefore, a valuable criterion for the neurosurgeon's postoperative management protocol.     

Liposarcoma with radiologically biphasic patterns

Liposarcoma is a one of the common soft tissue sarcomas, and is estimated to represent 16–18% of sarcomas in adults. According to the World Health Organization, this tumor is mainly classified into five subtypes: well-differentiated, dedifferentiated, myxoid/round, pleomorphic and mixed-type. Previous papers have reported that radiological information for liposarcoma is correlated with the radiological and histopathological findings. In liposarcoma, when biphasic patterns composed of a lipogenic tumor with a sarcomatous appearance are found on radiological examination of computed tomography and/or magnetic resonance imaging, dedifferentiated liposarcoma, defined as a “malignant adipocytic neoplasm showing transition from atypical lipomatous tumor/well-differentiated liposarcoma to non-lipogenic sarcoma of variable histological grade”, is usually considered.     

Giant cardiac metastasis of myxoid liposarcoma causing cardiac tamponade; report of a case

We report a very rare case of cardiac metastasis of myxoid liposarcoma. A 55-year-old man presented with dyspnea. Two and a half years ago, he underwent resection of myxoid liposarcoma in the left thigh. Magnetic resonance imaging (MRI) revealed a giant tumor occupying the pericardiac cavity and pressing the heart and consequently causing cardiac tamponade. The patient underwent surgery through a left thoracotomy approach. The pericardiac cavity was filled with a giant tumor with a stalk from the right ventricle and 2 small nodules on the main pulmonary artery. He was relieved from the symptom: however, he had a recurrence of the tumor at the same site 5 months after the operation. He underwent surgery for the removal of the second tumor; however, he died 49 days after the operation. Although cardiac metastasis is a very rare condition, its awareness is essential for careful long-term follow-up for the early detection of a metastatic cardiac liposarcoma after the resection of the primary tumor.     

Primary mediastinal liposarcoma: clinicopathologic analysis of 24 cases

Liposarcomas are rare in the mediastinum. Here, we report the clinicopathologic features of 24 cases of mediastinal liposarcoma. Patients included 13 males and 11 females, with an age range of 3 to 72 years (median 58). Nine tumors were located in the anterior mediastinum, 7 in the posterior mediastinum, 1 in the superior mediastinum, and the precise location was not specified in 7 cases. Of the anterior mediastinal tumors, 3 appeared to arise from the thymus. Tumors were well-circumscribed, multinodular masses and ranged in size from 2.2 to 61 cm in greatest dimension (median 16 cm). Histologic examination revealed that most of the cases were well-differentiated liposarcomas (10), followed by dedifferentiated liposarcomas (8), pleomorphic liposarcomas (4), and myxoid liposarcomas (2). Of the pleomorphic liposarcomas, 2 had areas that resembled myxofibrosarcoma with atypical hyperchromatic spindle cells in a myxoid stroma, but the focal presence of lipoblasts confirmed the diagnoses. Clinical follow-up was obtained in 15 cases (range 1 to 59 mo; median 26). Complete surgical excision was attempted in 13 patients; however, local recurrence was common (5 cases), including 1 patient whose tumor recurred twice. Eleven patients were alive with no evidence of disease at last follow-up (5 well-differentiated, 5 dedifferentiated, and 1 myxoid liposarcoma). Two patients developed distant metastases (dedifferentiated and pleomorphic liposarcoma). One patient was alive with disease (pleomorphic liposarcoma), and 2 died of disease (pleomorphic and dedifferentiated liposarcoma). Overall, mediastinal liposarcomas appear to be similar, in clinicopathologic terms, to liposarcomas arising in the retroperitoneum.     

Primary omental liposarcoma presenting as an incarcerated inguinal hernia

Herein, we present a case of primary liposarcoma of the omentum found in an incarcerated inguinal hernia in a 52-year-old male patient. The patient was admitted to our hospital in June 2000 with sudden onset of left-sided abdominal and groin pain of 12 hours duration with a large, irreducible inguinal hernia. This was not associated with nausea or vomiting. An emergency operation was performed, and in the hernia sac the tumor, arising from the greater omentum, was found. After we opened the transversal fascia and peritoneum, the tumor was resected with a block of the greater omentum, and hernioplasty was performed using Shouldices method. The histopathological diagnosis of resected tumor showed myxoid type liposarcoma. In the English medical literature, omental liposarcoma has never before been reported as the content of a hernia sac.     

Aspectos histopatológicos iniciales de la hiperplasia benigna de próstata: nódulos mixo-inflamatorios

ObjectivesInfiltration of benign prostatic hyperplasia (BPH), nodular prostatic hyperplasia (NPH) or prostatic adenoma by mononuclear cells, predominantly lymphocytes, is a common finding in surgical specimens. The biological significance of this infiltration, very similar to chronic inflammation, is unknown, but it is suspected as being related to the pathogenesis and progression of the BPH. The identity and number of the infiltrating cells is not well known. The objectives of the present study were: 1) to describe in more detail the histologic pattern of early lesions BPH, that is “myxoid” nodules. 2) to count and locate these myxoid nodules and to analyse the possible influence of age 3) and describe the patterns of mononuclear cell infiltration in BPH.Materials and methodsOne hundred and seventy-three specimens of BPH tissue were reviewed. These samples were processed routinely for histological examination and immunohistochemical examination was performed in selected cases in order to further define the cellular composition of the described lesions. The immunohistochemical stains were performed automatically. Vimentin, specific smooth muscle actin an desmin were use to show the stromal cells and CD₃, CD₂₀ and CD₆₈ monoclonal antibodies were used to quantify the populations of T-lymphocytes, B-lymphocytes and macrophages, respectively.The number of myxoid nodules identified in each patient was counted and the maximum and minimum diameter measured. These data have been compared in two groups of patients, those younger than 57 years and those over 80. Statistical analysis has been performed with SPSS 13.0. Student′s t test was used for bivariate analysis and Pearson's r for correlation.ResultsInterstitial infiltration involving T and B lymphocytes with less macrophages was a constant finding of the early nodules of BPH.The bivariate analysis with Student's t has shown a statistically significant difference between the mean number of myxoid nodules (p=0.02), significantly lower in the younger patients. Although we have found differences between the mean diameters of the smallest and the largest nodules in both groups, these differences did not reach statistical significance. We have not shown any significant correlation between the number of nodules and the patient age (p=0.11) in the Pearson's r correlation.ConclusionInflammatory cells and myxoid nodules are a constant finding in BPH surgical samples. The mean number of myxoid nodules is significantly lower in younger patients. Interstitial distribution is the most common pattern of mononuclear cell infiltration. B and T-cell lymphocytes are the most frequently found inflammatory cells in early myxoid nodules.