Lipomatous tumours of soft tissues: an update

This review summarizes the clinicopathological features of recently characterized variants of lipomatous tumours of soft tissue, attempts to deal with some difficult conceptual issues relating to adipocytic neoplasms and aims to provide an update on cytogenetic aspects of fatty tumours. Myolipoma is a rare benign neoplasm, occurring most frequently in adults in the deep soft tissue of the abdomen or retroperitoneum, and is composed of irregularly admixed mature adipose and smooth muscle tissues. Chondroid lipoma represents an unusual benign lesion occurring mainly in adult females subcutaneously or in deep soft tissue; it is easily mistaken for myxoid liposarcoma or extraskeletal myxoid chondrosarcoma. Spindle-cell liposarcoma is a variant of well-differentiated liposarcoma quite commonly found in subcutaneous tissue of the shoulder region and upper limbs and is composed of relatively bland-appearing spindle cells mixed with a well-differentiated liposarcomatous component. Recently there has been considerable debate about classification of lipomatous tumours. The term atypical lipoma was proposed for a group of well-differentiated non-metastasizing liposarcomas arising in surgically amenable soft tissues and for deep-seated atypical adipocytic neoplasms that show variation in adipocytic size and atypical stromal cells but lack lipoblasts. However, these neoplasms recur repeatedly and may dedifferentiate and thereby acquire metastatic potential. We use the diagnosis atypical lipoma with caution and propose to use the terms well-differentiated liposarcoma and atypical lipoma interchangeably. The relationship between myxoid and round-cell liposarcoma, which constitutes the morphological spectrum of a single entity, has been clarified but there remain considerable problems in defining likely clinical behaviour. The recent advances in cytogenetic characterization and classification of lipomatous tumours, which is already proving to be of diagnostic importance, are reviewed, and the genetic importance of the distinct chromosomal translocation in myxoid/round cell liposarcoma is briefly discussed.     

Diffuse angiomatosis of the extremities presenting as a sarcoma

Diffuse angiomatosis of the extremities is a rare condition characterized by extensive or multifocal benign mass-forming vascular lesions involving multiple tissue planes; histologically, adipose and fibrous tissue are admixed with vascular elements that vary from capillary proliferations to large vessels that are often structurally abnormal. Although diffuse angiomatosis most likely represents a hamartomatous form of arteriovenous malformation, it behaves clinically as a benign but slowly progressive and unresectable neoplasm. We describe a case of diffuse angiomatosis of the lower extremity that presented clinically as a soft-tissue sarcoma.     

Intramuscular myxoma with fibrous dysplasia: A report of two cases with a review of the literature

Two cases are reported of a rare association of intramuscular myxoma with fibrous dysplasia in a 70 and 40 year old Japanese woman, respectively. One of them had a solitary intramuscular myxoma, and the other patient suffered from two intramuscular tumors that had been initially misdiag-nosed as myxoid liposarcoma. Only 24 cases of this kind of association have been recorded in the literature. This association should be taken into consideration to avoid inappropriate treatment, when cases of myxoid soft tissue tumor with a bone lesion are encountered.     

Liposarcoma: new entities and evolving concepts

Liposarcoma is the most common soft tissue sarcoma and accounts for approximately 20% of all mesenchymal malignancies. In the last decade, the results of several studies have led to the delineation of new variants as well as to the introduction of new concepts, mainly as a result of the fruitful interactions between genetics and pathology. Spindle cell liposarcoma represents an uncommon variant of well-differentiated liposarcoma. It tends to occur in adults and often involves the subcutaneous soft tissue. However, from the observation of a larger number of cases, the anatomic distribution of spindle cell liposarcoma seems to be comparable to that of the other well-differentiated liposarcoma subtypes. Spindle cell liposarcoma tends to recur locally and may dedifferentiate. Morphologically it is composed of a fairly bland neural-like spindle cell proliferation set in a fibrous and/or myxoid background and is associated with an atypical lipomatous component. Great debate has been generated by the introduction of the term atypical lipoma to emphasize the fact that well-differentiated liposarcoma shows risk of local recurrence but no potential for metastasis. In our opinion well-differentiated liposarcoma and atypical lipoma should be considered synonyms that describe lesions identical both morphologically and kayotypically. Dedifferentiated liposarcoma is a distinct type of liposarcoma in which transition from low-grade to high-grade nonlipogenic morphology within a well-differentiated liposarcoma is observed. The transition usually occurs in an abrupt fashion; however, in rare cases it can be more gradual. Recently, it also has been proposed that dedifferentiated liposarcoma should be further classified into low and high grade. Dedifferentiated liposarcoma rarely exhibits heterologous (most often myoid) differentiation. A peculiar "neural-like whorling pattern" of dedifferentiation also has been described recently. Surprisingly, the clinical outcome of dedifferentiated liposarcoma is less aggressive that in other high-grade pleomorphic sarcomas but genetic as well as molecular data exist that may partiallyjustify such a discrepancy. Myxoid and round cell liposarcoma, even if still classified by the World Health Organization as two distinct subtypes, share both clinical and morphologic features. Lesions combining both patterns are very frequent and wide agreement exists in considering round cell liposarcoma as the high-grade counterpart of myxoid liposarcoma. Furthermore, myxoid and round cell liposarcoma share the same characteristic chromosome change. Albeit rare, it has been recently shown that liposarcoma indeed can occur as a primary skin lesion. It often presents clinically as a dome-shaped or polypoid lesion that, histologically, most frequently shows high-grade morphologic features but carries a comparatively good prognosis. Considering currently available data, the most logical classification of liposarcoma is into three main groups: (1) well-differentiated liposarcoma (including adipocytic, sclerosing, inflammatory, spindle-cell, and dedifferentiated variants), characterized by ring or long markers chromosomes derived from the long arm of chromosome 12; (2) myxoid and round cell (poorly differentiated myxoid) liposarcoma, characterized in most cases by a reciprocal translocation t(12;16)(q13;p11); and (3) pleomorphic liposarcoma, characterized by complex karyotypes.     

Myxoid liposarcoma and pleomorphic liposarcoma: cyto-histological correlations

Myxoid liposarcoma and pleomorphic liposarcoma: cito-histological correlations. A correlative cytologic and histologic study of a myxoid liposarcoma of the shoulder in a 72 year-old man and a pleomorphic liposarcoma observed in the retroperitoneum of a 84 year-old woman, are presented. A preoperative FNAB cytology performed in both cases showed necrotic material containing spindle-stellate shaped cells, interspersed in a myxoid matrix, with rare classical monovacuolated lipoblasts and fragments of plessiform vessels were seen in the first and scattered pleomorphic and multinucleated cells, with prominent nucleoli and numerous atypical mitosis in the second. A malignant mesenchimal spindle-cells tumor, with myxoid matrix and pleomorphic cells, consistent with liposarcoma, respectively were suspected. Gross and histological specimens confirmed the cytological suspect. Authors discuss main cyto-histological differential diagnoses of myxoid tumors, and point out the importance and a correct differentiation between myxoid liposarcoma and intramuscular myxoma. The cytologic appearance of pleomorphic liposarcoma is similar to histologic type and therefore the problem of a differential diagnosis with soft tissue tumors is analogous. When mono or plurivacuolated lipoblasts are absent, differential diagnosis between pleomorphic histiocytoma and liposarcoma is impossible. Nevertheless this is not a important problem at cytological level because both tumors have a had prognosis and must be treated with radical surgery. Definition of correct histologic type will be more suitable on histologic specimens.     

Dedifferentiated myxoid liposarcoma: a clinicopathological study suggesting a closer relationship between myxoid and well-differentiated liposarcoma

Myxoid/round cell liposarcoma is arguably the commonest type of liposarcoma occurring in the extremities and may show gradual progression from low-grade, pure myxoid liposarcoma to high-grade round cell liposarcoma. Rarely myxoid/round cell liposarcoma is associated with areas of well-differentiated or pleomorphic liposarcoma (mixed liposarcoma). We describe the clinicopathological features of three unusual myxoid/round cell liposarcomas which showed morphological features of de novo dedifferentiation. All patients were male and were aged 66, 70 and 76 years, respectively. One lesion each arose in the retroperitoneum, inguinal region and peritoneal cavity. Histologically, in one case the myxoid/round cell component was juxtaposed to a high-grade non-lipogenic component resembling non-pleomorphic storiform 'malignant fibrous histiocytoma' ('MFH'), one case showed a combination of myxoid liposarcoma and a high-grade myxofibrosarcoma-like component (so-called myxoid 'MFH'), and in the third case, a well-differentiated myxoid liposarcoma with a discontinuous micronodular pattern of dedifferentiation was seen. Follow-up information of 30, 28 and 26 months revealed two recurrences each in two patients. These patients died of postoperative pulmonary embolism and abdominal haemorrhage, respectively; systemic metastases were not noted. These cases demonstrate that myxoid/round cell liposarcoma can show, albeit very rarely, histological features of dedifferentiation. Cases like these, combined with the occurrence of mixed-type liposarcoma (well-differentiated/myxoid liposarcoma) and the vicinity of chromosomal regions involved by specific karyotypic aberrations in these tumours, suggest that myxoid/round cell liposarcoma and well-differentiated liposarcoma (including its dedifferentiated variant) are more closely related in biological terms than is generally believed.     

Lipomatous tumours

Adipocytic neoplasms are among the most common mesenchymal neoplasms. In the last decade, some new entities have been delineated and new concepts introduced. Myolipoma is a benign lesion composed of mature adipocytic tissue intermingled with smooth muscle fibers. Clinically it usually arises in the abdomen, retroperitoneum or abdominal wall of adults. Chondroid lipoma is a deeply seated benign lesion located in the limbs, trunk and head and neck region of adult females. Microscopically it is composed by an admixture of mature adipocytes, eosinophilic chondroblast-like cells and lipoblasts set in myxochondroid background. Spindle cell liposarcoma represents a rare variant of well-differentiated (WD) liposarcoma with tendency to recur locally. Morphologically it is composed of a neural-like spindle cell proliferation associated with an atypical lipomatous component. The fact that WD liposarcoma shows a risk of local recurrence but no potential for metastasis has led to the introduction of the term atypical lipomatous tumour. Well-differentiated liposarcoma and atypical lipoma however, should be considered synonyms. De-differentiated liposarcoma is characterised by the transition from low grade to high grade non-lipogenic morphology within a WD liposarcoma. Heterologous differentiation is seen in about 5% of cases and, a distinctive neural-like whorling pattern of de-differentiation has been recently described. Surprisingly, the clinical behaviour of de-differentiated liposarcoma is less aggressive than in other high grade pleomorphic sarcomas, at least in part as a consequence of peculiar genetic as well as molecular mechanisms. Myxoid and round cell liposarcoma, even if still classified by the World Health Organisation as two distinct subtypes, represent both morphologically and cytogenetically a spectrum of myxoid adipocytic neoplasia. Considering currently available data, liposarcoma can be classified into three main groups: 1) WD liposarcoma (including adipocytic, sclerosing, inflammatory, spindle cell and de-differentiated variants), characterised by ring or long marker chromosomes derived from chromosome 12; 2) myxoid and round cell liposarcoma, characterised in most cases by a reciprocal translocation: t(12; 16)(q13; p11); and 3) pleomorphic liposarcoma, characterised by complex karyotypes.     

Myxoid liposarcoma: a case report of a sentinel metastasis to the parotid gland with molecular confirmation

Myxoid liposarcoma is a subtype of liposarcoma with a predilection for the deep soft tissues of the extremities that accounts approximately for 10% of all adult soft tissue sarcomas. We report a case of a metastatic myxoid liposarcoma to the parotid gland, with fine-needle aspiration cytology correlation and molecular characterization. The lesion was diagnosed in a 53-year-old Hispanic male who presented with a left posterior thigh mass. A core needle biopsy established the diagnosis of myxoid liposarcoma. The patient underwent limb-sparing, wide local excision of the malignancy and later presented with an initial metastatic lesion to the parotid gland. The diagnosis of metastatic myxoid liposarcoma was rendered by fine-needle aspiration cytology with cell block preparation, and molecular confirmation. Although myxoid/round cell liposarcomas are classically described as having minimal pleomorphism on cytologic material, we encountered significant pleomorphism in our case. Therefore, a diagnosis of myxoid/round cell liposarcoma should still be a diagnostic consideration even if markedly pleomorphic cells are seen in fine-needle aspiration biopsies.     

Pleomorphic lipoma: a tumour simulating liposarcoma

Pleomorphic lipoma or giant-cell lipoma is a recently recognized entity affecting predominantly elderly and middle-aged men. The neck, shoulder region and back are the sites of predilection. The clinical setting is similar to that seen with spindlecell lipoma. The lesion is characterized by an intricate mixture of mature fibrous tissue, adipose tissue and myxoid tissue interspersed with cellular foci. Most characteristic of the latter are a variety of giant cells and especially the 'floret' giant-cells, so named because of the arrangement of their nuclei which is reminiscent of the petals of a flower. The pleomorphism of the lesion frequently leads to misdiagnosis as liposarcoma. Criteria for the differentiation from the various types of liposarcoma are discussed. The possible relationship of pleomorphic lipoma to some of the 'atypical lipomas' described in the recent literature is analysed. The pleomorphic lipoma is a benign lesion of subcutaneous tissue which must be sharply differentiated from sarcomas. Some of the liposarcomas alleged in the literature to have originated within a pre-existing lipoma possibly represented pleomorphic lipomas. Pleomorphic lipoma is an entity which must be added to the growing number of pseudosarcomatous lesions of soft tissue.     

Cytomorphological features of combined myxoid and round cell liposarcoma--a case report

Fine needle aspiration cytology plays an important role in the preoperative assessment of soft tissue neoplasms. In a 40-year-old man presenting with a large soft tissue mass in the posterior aspect of thigh a diagnosis of myxoid liposarcoma was suggested on FNAC. Scrape smears of the excised mass showed an additional finding of round cell component. Histopathology confirmed combined myxoid and round cell liposarcoma (grade 2), which behaves aggressively when compared to pure myxoid liposarcoma.     

The ultrastructure of liposarcoma. A study of 10 cases.

An ultrastructural study of 10 liposarcomas is reported. Four of the liposarcomas were wholly or predominantly of well-differentiated, lipoma-like or fibrosing type, 3 of myxoid type, 2 of round cell type and 1 pleomorphic type. The well-differentiated, lipoma-like liposarcomas showed cells with a few, large lipid droplets, few organelles and a peripherally located, fairly large nucleus, The well-differentiated liposarcomas of fibrosing type revealed mostly spindle-shaped, fibroblast-like cells, with abundant rough endoplasmic reticulum and inconspicuous lipid inclusions, surrounded by collagen. One well-differentiated liposarcoma contained an area which was similar to brown adipose tissue and hibernoma. The spindle and stellate shaped cells of the myxoid liposarcomas showed abundant rough endoplasmic reticulum and large smooth-membraned vacuoles filled with moderately dense amorphous material, which appeared to be extruded extracellularly by rupture of the vacuoles. Cytoplasmic lipid droplets were seen in most cells but were much less prominent than in the well-differentiated lipoma-like liposarcomas. Ultrastructurally there were many similarities between the myxoid and round cell liposarcoma, indicating a close relationship between the two types. The pleomorphic liposarcoma revealed cells with one or more large, irregular nuclei, numerous large vacuoles after dissolved lipids, abundant dilated cisternae of rough endoplasmic reticulum and rounded, electron-dense bodies corresponding to PAS-positive hyalin globules seen in the light microscope. The ultrastructural study suggests that the variegated cellular appearance of the different subtypes of liposarcoma reflects the wide cellular spectrum seen during the differentiation of adipose tissue and supports the view that all liposarcomas histogenetically represent a single entity.     

Intramuscular dendritic fibromyxolipoma: Myxoid variant of spindle cell lipoma?

Dendritic fibromyxolipoma (DFML) is an uncommon, recently described, benign soft tissue lesion that shares many clinical and pathological features with myxoid variants of spindle cell lipoma (SCL). As described, DFML is distinguished from SCL by the presence of dendritic cytoplasmic processes, abundant keloidal collagen and a prominent, often plexiform vascular pattern. We describe the first known reported case of an intramuscular DFML that occurred in the right shoulder region of a 73-year-old man. The tumor displayed the typical histopathological features of DFML but also included foci of chondroid metaplasia, a previously unreported finding. This report also discusses the differential diagnosis, particularly distinguishing DFML from SCL and myxoid liposarcoma. In view of the similarities in many clinical and pathological features between SCL and DFML, we speculate that DFML probably represents an unusual variant of myxoid SCL.     

眼眶原发性脂肪肉瘤附1例报道并文献复习

目的：了解眼眶内原发性脂肪肉瘤的临床及理特点。方法：Ｒ列荆棘人原发性脂肪肉瘤并复习文献中２１例，进行综合讨论，结果：脂肪肉瘤临床表现为眶内占位和貌似急性上的局部红、肿、痛，无特征性的症状；病理分析４型，文献中以不论了多见；次为分化主菜细胞为主型及多型性各１例，分型不详２例；本例为分化良好型为主伴有圆形脂母细胞及多型怀脂母细胞成分。结论：眶内原发性脂肪肉瘤罕见，以粘液样型多见，其他３型也有发生，临床     

An unusual lesion of the mediastinum: angiomatosis or diffuse hemangioma

Angiomatosis are rare benign vascular lesions representing almost 4% of vascular tumours in children and adolescent. These lesions occur in soft tissue and are clinically extensive, covering large parts of the body in a continuous pattern. Limbs are classically involved. The incidence is high in childhood and adolescence. The authors report an original case of angiomatosis or diffuse haemangioma located in the anterosuperior part of the mediastinum in a 17 year old girl. The patient consulted for increasing dyspnoea starting two years earlier. At medical imaging, calcified tumoral mass measuring 60 mm situated in the anterosuperior mediastinum was objectivated. The mass did not involve bony nor chondral structure. Teratoma or thymoma was suspected. At operation the whole tumor was resected with adherent pericardium. At histological examination, the lesion showed the presence of vascular structures inside fibro muscular and fatty tissue mixed with multiple nerve sections. In the lesion, venous walls were remarkably thick and sometimes picked or surrounded by multiple micro vessels. A Hamartomatous or proliferative origin may be discussed. The multiple components supports a hamartomatous origin, especially because of the unexpected presence of nervous elements. A proliferative process trapping preexisting vascular and nervous elements may be also considered. Furthermore, the lesion may represent a diffuse mesenchymatous proliferation as suggested by the presence of adipose tissue or glomic cells. Additional studies based on cytogenetics could surely improve the understanding of this lesion.     

Fine-needle aspiration cytology findings in a case of aggressive angiomyxoma: A case report and review of the literature

Aggressive angiomyxomas are uncommon but distinct soft-tissue neoplasms occurring predominantly in the pelvis and peritoneum of females, but they have occasionally been reported in association with inguinal hernias in males. Histologically, these neoplasms are characterized by a proliferation of spindle- or stellate-shaped cells widely separated by loose myxoid stroma in which is dispersed a prominent vascular component. The vascular component is comprised of large, thick-walled vessels that generally do not show an arborizing pattern. Mitotic activity has been exceedingly low in the cases reported. Because of their occurrence within the groin, these lesions may undergo fine-needle aspiration (FNA). Cytologic examination of this material will reveal hypocellular smears containing scattered spindle cells with bipolar cytoplasmic processes, as well as bland stellate cells. The nuclei are fusiform to oval with a bland chromatin pattern. The stromal cells lie in a background of watery myxoid material. While specific diagnosis by FNA is not possible, the recognition of this cytologic appearance should exclude lymphoproliferative processes as well as metastatic disease from the differential diagnosis. Careful attention to cytologic detail should also help exclude certain other myxoid neoplasms, especially myxoid liposarcoma. Once the myxoid stromal nature of the proliferation is recognized, a differential diagnosis of myxoid lesions can be considered along with a recommendation for open biopsy to establish the definitive diagnosis. Diagn. Cytopathol. 16:425–429, 1997. © 1997 Wiley-Liss, Inc.     

Focal divergent chondrosarcomatous differentiation in a primary pleomorphic liposarcoma and expression of transforming growth factor beta

A rare case of primary pleomorphic liposarcoma of the thigh with a myxoid component, in which divergent differentiation to a well-differentiated chondrosarcoma was focally present, is described. Presence of heterologous elements has mainly been recognized in the context of dedifferentiated liposarcomas. Few cases of benign mesenchymal tissue have also been reported in well-differentiated and myxoid liposarcomas, while divergent sarcomatous differentiation in liposarcomas appears to be also rare in the absence of dedifferentiation. Positive immunostaining of transforming growth factor-beta, which seems to play a role in the formation of bone and cartilage, was demonstrated in our case. Review of the existing literature on the subject has been carried out.     

Undifferentiated myxoid lipoblastoma with PLAG1 gene rearrangement in infant

ObjectivesTo analyze the clinicopathologic feature, diagnosis and differential diagnosis of undifferentiated myxoid lipoblastoma in infant.MethodsThe study included 2 cases of undifferentiated myxoid lipoblastoma in infant according to the molecular genetic diagnosis. The relevant clinicopathologic feature was investigated.ResultsWe describe 2 cases of undifferentiated myxoid lipoblastoma in infant. The both large circumscribed masses are located in deep soft tissue. Unlike most lipoblastoma, lobulated appearance was not obvious in one case and completely absent in another. The both cases presented prominent myxoid change with a plexiform vascular pattern. There were some spindle-shaped or stellate mesenchymal cells, while no any mature adipocytes. The initial suggestion of case 1 was myxoid liposarcoma, and case 2 was aggressive angiomyxoma. However, few S-100 positive lipoblasts suggested the origin of the tumor. FISH analysis using a PLAG1 break apart probe confirmed a PLAG1 rearrangment. The final diagnosis was undifferentiated myxoid lipoblastoma.ConclusionsThe undifferentiated myxoid lipoblastoma is a very rare tumor in infant. Histologically, prominent myxoid change, a plexiform vascular pattern and lacking of mature adipocytes make it indistinguishable from myxoid liposarcoma, PMMTI and aggressive angiomyxoma. The S-100 positive lipoblasts and genetic rearrangement of PLAG1 helps in confirming the diagnosis. Even if there were no mature adipocytes, myxoid lipoblastoma was still a diagnosis that can not be ignored in myxoid tumors in children.     

Mixed-type liposarcoma: clinicopathological, immunohistochemical, and molecular analysis of a case arising in deep soft tissues of the lower extremity

A rare case of mixed-type liposarcoma arising in deep soft tissue of the right thigh of a 45-year-old female patient is reported. The neoplasm was completely excised and was composed of an irregular admixture of areas of atypical lipomatous tumor/well-differentiated liposarcoma of the lipoma-like subtype with areas of myxoid/round cell liposarcoma. An amplification of the MDM2 and CDK4 genes respectively in the atypical lipomatous tumor/well-differentiated liposarcoma areas was detected by fluorescence in situ hybridization (FISH) analysis, and translocations of the CHOP and FUS genes were detected by FISH analysis in the myxoid/round cell liposarcoma areas.     

Validation of immature adipogenic status and identification of prognostic biomarkers in myxoid liposarcoma using tissue microarrays

Myxoid liposarcoma displays variably aggressive behavior and responds poorly to available systemic therapies. Expression profiling followed by tissue microarray validation linked to patient outcome is a powerful approach for validating biological mechanisms and identifying prognostic biomarkers. We applied these techniques to independent series of primary myxoid liposarcomas in an effort to assess markers of adipose differentiation in myxoid liposarcoma and to identify prognostic markers that can be efficiently assessed by immunohistochemistry. Candidate genes were selected based on analysis of expression profiles from 9 primary myxoid/round liposarcomas and 45 other soft tissue tumors, and by reference to publicly available data sets. Protein products were validated on an adipose neoplasm tissue microarray, including 32 myxoid liposarcomas linked to patient outcome. Results were scored visually and correlated with clinical outcome by Kaplan-Meier and Cox regression analyses. In the study, by examining expression patterns of several lipogenic regulatory gene products, an immature adipogenic status was verified in myxoid liposarcomas. We also found that expression levels of the ret proto-oncogene, insulin-like growth factor 1 receptor, and insulin-like growth factor 2 correlate with poor metastasis-free survival, supporting a role for ERK/MAPK and PI3K/AKT pathways in clinically aggressive myxoid liposarcomas.