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Liposarcomas. A histogenetic approach to the classification of adipose tissue neoplasms.

A series of atypical lipomas, well-differentiated/dedifferentiated liposarcomas, and myxoid/round cell liposarcomas were examined by light and electron microscopy in order to understand better the marked variation in histologic growth patterns exhibited by adipose tissue neoplasms. We found that they were composed of a mixture of adipocytes and nonfat-storing mesenchymal cells or were predominantly made up of only one of these cell types. From these and other published observations, we feel that 1) myxoid/round cell liposarcomas are composed of adipocytes; 2) spindle cell lipomas, atypical lipomas, and well-differentiated liposarcomas are composed of a mixture of the two cell types; and 3) the dedifferentiated regions of well-differentiated liposarcomas are composed of nonfat-storing mesenchymal cells. The basic structural differences of the two cell types and the quantitative variations when they occur in mixtures seem to account for the marked variations in neoplastic growth patterns.

Adipose Tissue↗

An unusual neoplasm of adipose tissue in a rat.

The light microscopic features of a spontaneous neoplasm of adipose tissue from a rat were suggestive of a mixed liposarcoma with a myxoid matrix. However, ultrastructurally, the cell characteristics were those of a hibernoma. These characteristics included cells containing lipid droplets of variable size, numberous pleomorphic mitochondria and close apposition to blood vessels. Lipofuscin granules and subplasmalemmal condensations were not observed ultrastructurally.

Adipose Tissue↗

Immunoreactivity for the human hematopoietic progenitor cell antigen (CD34) in lipomatous tumors.

The human hematopoietic progenitor cell antigen (CD34) recently was shown to react with a variety of nonhematopoietic tissues and their tumors, including vascular endothelium, dendritic interstitial fibroblastic cells, and endoneurial cells as well as with the neoplastic cells in a variety of mesenchymal neoplasms of unknown etiology, such as Kaposi's sarcoma, dermatofibrosarcoma protuberans, epithelioid sarcoma, gastrointestinal stromal tumors, and solitary fibrous tumors. Additionally, it has been claimed that normal adipocytes may also react with this antibody. We studied a series of 90 lipomatous lesions to examine the pattern of immunoreactivity of the CD34 antigen in adipose tissue neoplasms. The study included 14 lipomas, 19 angiolipomas, 4 atypical lipomas, 18 spindle cell lipomas, 3 renal angiomyolipomas, 1 intramuscular lipoma, and 31 liposarcomas. Immunostains identified a network of CD34+ spindle cells admixed with the adipose tissue elements in all cases of lipoma, angiolipoma, angiomyolipoma, intramuscular lipoma, and well-differentiated lipoma-like liposarcoma. Additionally, the spindle cell component in all cases of spindle cell lipoma were strongly positive for this antigen. Atypical, stellate spindle cells and multinucleated "floret" cells in all cases of atypical lipoma as well as in six of 12 cases of well-differentiated lipoma-like liposarcoma of deep soft tissue were also positive for CD34. Scattered spindle cells in all cases of myxoid liposarcoma and in one case of round cell liposarcoma, as well as the sarcomatous component in one case of "dedifferentiated" liposarcoma, were strongly positive for this antigen. The round cells in myxoid liposarcoma and round cell liposarcoma, the signet-ring and multivacuolated lipoblasts in well-differentiated liposarcoma, and the pleomorphic atypical cells in pleomorphic liposarcoma were uniformly negative. The results of this study appear to indicate that lipomatous tumors may harbor a population of CD34+ interstitial dendritic spindle cells. Overgrowth or clonal expansion of this dendritic cell subpopulation may account for the development of spindle cell lipomas and for the spindle cell component in some cases of "dedifferentiated" liposarcoma.

Antigens, CD34↗

Characteristic chromosome abnormalities and karyotype profiles in soft tissue tumors.

Characteristic chromosome abnormalities and karyotype profiles are emerging for the soft tissue tumors. The notable findings are summarized in the Table 1. Within the broad range of solid tumors, it is certainly the soft tissue tumors in which the most spectacular success has occurred with regard to neoplasia-associated chromosome abnormalities. Cytogenetic studies of soft tissue tumors have been encouraged by the early and growing supporting interest of pathologists and clinicians concerned with soft tissue tumors. However, when one considers the variety of types and subtypes of benign and malignant soft tissue tumors, the number that has been so far characterized by a specific chromosome change is still very small. But, as we attempt to demonstrate in this report, these data should be viewed as paradigms for the importance of cytogenetic investigations in solid tumors. Cytogenetic studies of solid tumors are of more than clinical interest. Cytogenetic studies allow molecular investigations of the chromosomal breakpoints. They allow the search to proceed for genes involved in the chromosomal changes, providing a better knowledge of the malignant transformation process. In addition, the fruits of the combined efforts in cytogenetic and molecular technologies, from which has come "molecular cytogenetics," will let us recognize more conveniently, more quickly and, hopefully, less expensively the well-characterized diagnostic chromosome markers in tumor cells. Thus, we may be able to reach the goal of incorporating cytogenetics into standard diagnostic procedures for solid tumors, as has been achieved with hematological malignancies. Molecular cytogenetics including fluorescent in situ hybridization (FISH) technology promises to bring soft tissue tumor cytogenetics into regular diagnostic armamentaria and concurrently speed research into the basis of soft tissue tumors.

Chromosome Aberrations↗

Mesenchymal, non-meningothelial tumors of the central nervous system.

The spectrum of non-meningothelial mesenchymal tumors that may arise within the central nervous system is presented, based on the current classification of soft tissue tumors. Among malignant types, hemangiopericytoma, rhabdomyosarcoma, mesenchymal chondrosarcoma, and malignant fibrous histiocytoma are the most frequent ones. Rare tumor entities are mentioned. As in soft tissue sarcomas, diagnosis is mainly based on light and electron microscopy, while immunohistochemistry can improve accuracy of diagnosis.

Central Nervous System Neoplasms↗

Coexistence of spindle cell lipoma and ordinary lipoma.

We report a patient with a spindle cell lipoma on the nape and three ordinary lipomas on the abdomen and extremities. The coexistence of spindle cell lipoma and ordinary lipoma in a single patient is rare. Abundant CD34-positive spindle cells and mast cells were found in the spindle cell lipoma, but in the ordinary lipomas, only a small number of CD34-positive spindle cells were found in the interstitial connective tissue and no mast cells were seen. Because mast cells are known to stimulate mesenchymal cell proliferation and collagen production, mast cell infiltration may be a trigger for the proliferation of CD34-positive spindle cells, leading to the conversion of ordinary lipoma into spindle cell lipoma.

Antigens, CD34↗

Mesenchymal tumours of the thorax: CT findings and pathological features.

Mesenchymal tumours of the thorax are uncommon and may originate from the muscle, bone, cartilage, vessel, nerves, fat and fibrous tissue. These tumours occur at different sites including the lung, pleura, mediastinum or chest wall. Mesenchymal tumours tend to show protean and non-specific imaging characteristics. However, in some instances, the imaging characteristics of the tumour may allow a specific diagnosis to be made, such as with lipoid or vascular tumours.

Adolescent↗

Oncogenic osteomalacia: localization of underlying peripheral mesenchymal tumors with use of Tc 99m sestamibi scintigraphy.

OBJECTIVE: To highlight a strategy for potential detection of mesenchymal tumors in oncogenic malacia, as illustrated by 3 cases. METHODS: Three case reports are presented in which successful localization of the offending neoplasm was accomplished by using whole-body Tc 99m sestamibi scanning. Alternative localization techniques are also reviewed. RESULTS: Oncogenic osteomalacia occurs infrequently and is caused by neoplasms that secrete phosphatonins, substances that interfere with proximal tubular resorption of phosphorus and can result in phosphaturia, hypophosphatemia, reduced 1,25-dihydroxyvitamin D concentration, and osteomalacia. Removal of the underlying neoplasm results in complete resolution of all biochemical, pathologic, and physical manifestations of this disorder, as shown in our 3 patients. Because the neoplasms are small and can occur in any tissue compartment, they are difficult to localize, a feature that often results in therapeutic failure. CONCLUSION: We conclude that use of whole-body Tc 99m sestamibi scanning may be an appropriate and cost-effective initial strategy for the localization of peripheral phosphatonin-secreting tumors.

Aged↗

Fibrous lipoblastoma with 8q11.2 abnormality.

A 3-month-old African American female infant had a rapidly growing lipoblastoma with a prominent fibrous component in the soft tissue of the left lateral knee, which recurred at 10 months. Cytogenetic analysis revealed deletion of 8(q11.2q13) with a 19(q12q13.3) insertion at that site, confirming that this is closely related to the conventional lipoblastoma. The presence of multivacuolated lipoblasts and the staining characteristics (no staining for CD99, CD34, or smooth muscle actin) distinguish this from the recently described lipofibromatosis.

Chromosome Aberrations↗

Genetic and molecular abnormalities in tumors of the bone and soft tissues.

BACKGROUND: Malignant transformation requires the accumulation of multiple genetic alterations such as chromosomal abnormalities, oncogene activation, loss of tumor suppressor genes, or abnormalities in genes that control DNA repair and genomic instability. Sarcomas are a heterogeneous group of malignant mesenchymal tumors of difficult histologic classification and strong genetic predisposition. This article provides a comprehensive review of the cytogenetic abnormalities observed in bone and soft-tissue tumors, emphasizing known downstream molecular changes that may play a role in oncogenesis. METHODS: The database of the National Library of Medicine was searched for literature relating to genetic and molecular mechanisms in sarcomas in general and in each of the main tumor entities. RESULTS: Recent techniques in chromosome analysis and molecular cytogenetics have improved our ability to characterize genetic changes in mesenchymal tumors. Some changes are so characteristic as to be virtually pathognomonic of particular histologic types, while others are complex, difficult to characterize, and of unknown relevance to pathogenesis. The implications to the cell of some of these abnormalities are now being recognized. CONCLUSIONS: The study of sarcomas will benefit from the information derived from genetic studies and translational research. The human genome project and new methodologies, such as computer-based DNA microarray, may help in the histogenetic classification of sarcomas and in the identification of molecular targets for therapy.

Bone Neoplasms↗

Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas.

Caveolae are plasma membrane microdomains that have been implicated in the regulation of several intracellular signaling pathways. Previous studies suggest that caveolin-1, the main structural protein of caveolae, could function as a tumor suppressor. Caveolin-1 is highly expressed in terminally differentiated mesenchymal cells including adipocytes, endothelial cells, and smooth muscle cells. To study whether caveolin-1 is a possible tumor suppressor in human mesenchymal tumors, we have analyzed the expression using immunohistochemistry in normal mesenchymal tissues, 22 benign and 79 malignant mesenchymal tumors. Caveolin-1 was found to be expressed in fibromatoses, leiomyomas, hemangiomas, and lipomas at high levels comparable to normal mesenchymal tissues. The expression of caveolin-1 was slightly reduced in four of six well-differentiated liposarcomas and strongly reduced or lost in three of three fibrosarcomas, 17 of 20 leiomyosarcomas, 16 of 16 myxoid/round cell/pleomorphic liposarcomas, five of eight angiosarcomas, 15 of 18 malignant fibrous histiocytomas, and eight of eight synovial sarcomas. The immunohistochemical findings were confirmed by Western blot analysis in a number of tumors. High levels of both the 24-kd [alpha]- and the 21-kd [beta]-isoform of caveolin-1 were detected in the nontumorigenic human fibroblast cell line IMR-90. In contrast, in HT-1080 human fibrosarcoma cells, caveolin-1 is strongly down-regulated. We show that the [alpha]-isoform of caveolin-1 is potently up-regulated in HT-1080 cells by inhibition of the mitogen-activated protein kinase-signaling pathway with the specific inhibitor PD 98059, whereas the specific inhibitor of DNA methylation 5-aza-2'-deoxycytidine only marginally up-regulates caveolin-1. In addition, re-expression of caveolin-1 in HT-1080 fibrosarcoma cells potently inhibited colony formation. From these we conclude that caveolin-1 is likely to act as a tumor suppressor gene in human sarcomas.

Blotting, Western↗

Caveolin expression is common among benign and malignant smooth muscle and adipocyte neoplasms.

The caveolins belong to a newly described group of membrane-scaffolding proteins. Their presence in benign endothelial cells has been used to discriminate benign from malignant vascular neoplasms. The extent of caveolin expression in cutaneous mesenchymal neoplasms has not yet been evaluated, and thus the diagnostic utility of these antibodies is not yet known. In our study, we immunohistochemically examined a spectrum of tumors derived from smooth muscle and adipocytes for caveolin expression. We found that both benign and malignant smooth muscle tumors and tumors comprised of adipocytes expressed caveolins. The presence of this protein in a range of mesenchymal neoplasms is important to know about as this decreases the reported specificity of a positive finding. It is doubtful that caveolin down-regulation contributes to the pathogenesis of liposarcomas and leiomyosarcomas. This finding also may suggest a common origin between endothelial cells and other mesenchymal cells.

Adipocytes↗

MDM2+/CDK4+/p53+ oral liposarcoma: case report and review of the literature.

Although liposarcoma is one of the most common soft tissue sarcomas, its location in the oral cavity is very rare. To our knowledge, only 43 cases of liposarcoma originating in the oral tissues have been reported in the English-language literature. In this article, we report a case of well-differentiated liposarcoma affecting the cheek of a 28-year-old man and review the oral liposarcoma literature. Immunohistochemical analysis of the tumor revealed an MDM2+/CDK4+/p53+ immunophenotype that is consistent with the immunohistochemical profile of well-differentiated liposarcoma originating in other areas of the body. Quantitative polymerase chain reaction analysis of the DNA levels of the MDM2 (human homologue of the murine double-minute type 2), CDK4 (cyclin-dependent kinase 4), and SAS (sarcoma amplified sequence), genes was performed, revealing only SAS gene amplification. The possibility of misdiagnosis of oral liposarcoma because of its sometimes inconspicuous clinical and microscopic features is emphasized. Careful pathologic examination of liposarcoma is essential for discrimination from benign adipose tissue neoplasms and for precise histologic classification, both of major prognostic significance. Possible implications of molecular and cytogenetic analysis for unraveling the pathogenesis and determining the prognosis of liposarcoma are discussed.

Adult↗

Adenomyolipoma of the uterus: a case report.

Adenomyolipoma of the uterus is a rare, benign, polypoid lesion considered to be of hamartomatous origin or represent an unusual type of benign Müllerian mixed tumour with a heterologous element. The authors present a case of uterine adenomyolipoma and discuss its pathogenesis. A 62-year-old woman complained of lower abdominal pain and postmenopausal bleeding. Imaging techniques revealed a solid ovarian mass and a polypoid intrauterine lesion. The frozen section diagnosis of the ovarian mass was a thecoma. A total hysterectomy and bilateral salpingo-oophorectomy were performed. On gross examination a pedunculated, polypoid lesion of 7x4.5x3cm was found in the uterine cavity. Microscopically, the polypoid lesion contained both epithelial and mesenchymal elements. The epithelial elements were endometrial glands of various size, formed by proliferative endometrial cells. The mesenchymal elements were composed of endometrial stroma, smooth muscle and mature adipocytes. Both the epithelial and the mesenchymal elements showed a benign appearance, were intermingled with each other and periglandular stromal condensation was absent. The lesion had an irregular surface. Microscopic diagnosis was an adenomyolipoma. The peculiar shape and microscopic features of this lesion suggested that it was a variant of benign Müllerian mixed tumour.

Actins↗

Chimeric TLS/FUS-CHOP gene expression and the heterogeneity of its junction in human myxoid and round cell liposarcoma.

Myxoid liposarcomas have a unique and specific t(12;16)q13;p11) chromosomal translocation. The breakpoint has recently been identified and shown to involve the TLS/FUS gene on chromosome 16 and the CHOP gene on chromosome 12. This translocation causes fusion of these genes resulting in the expression of a novel chimeric TLS/FUS-CHOP message. Using the polymerase chain reaction with primer sets derived from sequences of TLS/FUS and CHOP cDNAs, we could amplify three types of the fusion transcripts from seven of seven samples of myxoid and round cell liposarcomas. In six of the seven positive samples, two kinds of chimeric messenger RNAs were found that have been reported previously. However, the last sample had a novel chimeric message that had an extra sequence of 33 bp derived from the TLS/FUS gene. Thus, it was shown that these fusion transcripts had a varying extent of the sequence of TLS/FUS gene incorporated at the site of the fusion. However, the TLS/FUS-CHOP fusion transcripts were not detected in two pleomorphic liposarcomas or in three myxoid variants of malignant fibrous histiocytomas. Our findings indicate that in liposarcomas TLS/FUS-CHOP fusion transcripts have variations at the junction of chimeric messages, which was the case for Ewing's sarcoma. Detection of the chimeric message by reverse transcription polymerase chain reaction was also suggested to be a useful approach for the diagnosis of myxoid and round cell liposarcomas that have (12;16) translocation, and for distinguishing them from pleomorphic liposarcoma and myxoid variant of malignant fibrous histiocytomas.

Adult↗

[Tumors of the mesentery. Apropos of 102 cases].

One hundred and two mesenteric tumours or masses are reported, and their histologic, clinical and therapeutic aspects are described: 28 cystic tumours, 38 mesenchymatous and 3 neurogenic tumours, 27 miscellaneous tumours, including 17 lymphomas, 2 hematomas and lymphoid or inflammatory masses. Seventy-four patients presented with an abdominal mass, 41 with pain and 28 with acute abdominal syndrome, including 16 with intestinal obstruction. Ultrasonography and computerised tomography were performed in 31 patients, RMI in 8 patients: these investigations are useful in establishing the diagnosis but surgical exploration and biopsies remain necessary for the pathology. One hundred and one patients required operation: 45 biopsies with 5 by-passes, and 56 resections, 32 localized tumour resections and 24 extended to the small bowel. Radiotherapy and chemotherapy have little or no effect.

Adolescent↗

The relationship between dietary fat, adipose tissue composition, and neoplasms of the breast.

Dietary fat has been implicated in the development of carcinoma of the breast. Because of the difficulties in obtaining accurate dietary histories, we analyzed subcutaneous adipose fatty acids to compare the quality of fat intake in three groups of patients undergoing investigations for breast masses. These included carcinoma (n = 37, avg. age 54 yrs.), fibroadenoma (n = 27, age 31 yrs.), and other types (n = 21, age 50 yrs.). Subjects in the carcinoma group were heavier, although they were not obese. A one-way analysis of variance of nine adipose fatty acids and their derived ratios [polysaturates:saturates (P:S)] did not show any systematic differences in the three groups. The quality of dietary fat does not appear to be associated with the development of neoplasia of the breast in this population, which consumes a diet of a high P:S ratio.

Adenofibroma↗