Extrarenal retroperitoneal angiomyolipoma: description of a case and review of the literature

A case of retroperitoneal extrarenal angiomyolipoma is described. The patient, a 61-year-old woman, presented with a large retroperitoneal lipomatous mass. Histologically, it consisted of lipomatous tissue. Focally, there was interstitial and perivascular proliferation of bland oval and epithelioid cells with a large, eosinophilic or clear cytoplasm. Immunohistochemically, these elements were positive for smooth muscle actin and HMB-45. The literature on retroperitoneal extrarenal angiomyolipoma is briefly reviewed. It is important that the pathologist recognize this lesion, even when it is located in the retroperitoneum outside the kidney, and differentiate it from a liposarcoma.     

Massive retroperitoneal angiomyolipoma. A lesion that may be confused with well-differentiated liposarcoma

A benign massive retroperitoneal lipomatous tumor is described. The tumor, from a 72-year-old woman with increasing abdominal girth, consisted of a mixture of mature lipocytes, smooth muscle cells, and thick-walled medium-size blood vessels. Although the tumor focally involved the uterine serosa, suggesting the possible diagnosis of uterine leiomyoma with fatty change, the authors think that, because the bulk of the tumor was located in the retroperitoneum and because the tumor contained characteristic thick-walled blood vessels from which smooth muscle cells radiated, this tumor would be best classified as a retroperitoneal angiomyolipoma. Although both angiomyolipomas and leiomyomas with fatty change presenting as large retroperitoneal tumors are rare, and therefore are not well-recognized by surgical pathologists, they are benign and must be distinguished from liposarcomas.     

Dedifferentiated liposarcoma of the cheek

Liposarcomas of the head and neck region are rare; only a few cases have been reported to arise in the cheek or buccal mucosa. Dedifferentiated liposarcoma has rarely been reported in the head and neck region and, to the best of our knowledge, this is the first reported case of dedifferentiated liposarcoma of the cheek. Dedifferentiated liposarcoma is a mixed histologic subtype defined by the association of an atypical lipomatous tumor or well-differentiated liposarcoma and a nonlipogenic sarcoma. The patient was a 61-year-old man who presented with a soft-tissue mass of the left cheek and a presumptive diagnosis of salivary neoplasm based on a fine needle aspiration. The tumor was excised and consisted histologically of an atypical lipomatous tumor/well-differentiated liposarcoma composed a well-differentiated lipomatous neoplasm with atypical cells and rare lipoblasts. The tumor recurred in the same location 5 months after surgery. The recurrent tumor was primarily composed of a nonlipogenic spindle sarcoma with focal rhabdomyoblastic differentiation associated with areas of an atypical lipomatous tumor/well-differentiated liposarcoma.     

A case of retroperitoneal lipoleiomyoma

We report a case of lipoleiomyoma which arose in retroperitoneum and presented with progressively distended abdomen in a 56-yr-old woman. The tumor was well encapsulated and consisted of two components, benign smooth muscle cells and mature adipose tissue without any atypia. It is likely to be mistaken as extrarenal angiomyolipoma, well-differentiated liposarcoma and leiomyoma with fatty change. We review the histologic characteristics of previously reported myolipoma and describe essential points of differential diagnosis.     

Fine-needle aspiration cytology of well-differentiated inflammatory liposarcoma: a case report with histologic follow-up

Inflammatory liposarcoma is an unusual variant of well-differentiated liposarcoma. We report on the fine-needle aspiration (FNA) cytology findings of a retroperitoneal well-differentiated inflammatory liposarcoma from a 63-yr-old white female. The smears showed numerous dispersed inflammatory cells, with the majority being reactive lymphoid cells and plasma cells. There were scattered, large, atypical cells containing multiple or hyperlobated nuclei with coarse chromatin and abundant ill-defined cytoplasm. The large atypical cells, as well as the inflammatory cells, were also found within the fibrous tissue fragments. The follow-up surgical resection of the tumor demonstrated a well-differentiated inflammatory liposarcoma with coexistent dedifferentiated areas and lipoma-like, well-differentiated liposarcoma. With the appropriate anatomic and radiographic settings, the FNA cytology findings of abundant, reactive inflammatory cells and scattered, large, atypical tumor cells that are CD15-, CD30-, and cytokeratin-negative are highly suggestive of a well-differentiated inflammatory liposarcoma.     

Paratesticular liposarcoma with smooth muscle differentiation mimicking angiomyolipoma

AIMS: To discuss the differential diagnosis of a case of well-differentiated liposarcoma which had areas resembling angiomyolipoma-a feature which, to our knowledge, has not been reported previously. METHODS AND RESULTS: A tumour in the paratesticular region had apparently been present for 40 years, but had grown recently. A fat component containing lipoblasts was admixed with areas resembling angiomyolipoma, i.e. desmin positive, but HMB45-negative smooth muscle proliferation with atypia and thick-walled blood vessels devoid of elastin. CONCLUSION: The diagnosis of liposarcoma, rather than angiomyolipoma with adipose atypia, in this case is based on the fact that smooth muscle differentiation is documented in liposarcoma, lack of HMB45 staining and recent clonality studies which suggest that the fat in angiomyolipoma is not neoplastic.     

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.     

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.     

Histologically low-grade dedifferentiated liposarcoma of the retroperitoneum

A low-grade dedifferentiated liposarcoma in the retroperitoneum of a 52-year-old woman is described. The excised specimens contained six nodules of lipoma-like well-differentiated liposarcoma and a nodule of dedifferentiated liposarcoma. The latter was composed predominantly of loosely arranged, benign-appearing spindle cells and fat cells. A small number of cells with irregularly shaped nuclei were scattered. There were no mitotic figures. The fat cells showed slight variation of size and shape, and a few multivacuolated lipoblasts were found. The spindle cell areas occupied approximately 60% of the tumor. The stroma was somewhat fibrous and myxoid and no dense collagenous matrix was found. The stroma vascularity was not prominent. Immunohistochemically, the spindle cells were positive for vimentin but negative for S-100 protein, desmin, muscle actin, and alpha-smooth muscle actin. Follow up for 5 months showed no evidence of recurrence or metastasis. The tumor, in which the benign-appearing spindle cell component was predominant, was considered to be a low-grade dedifferentiated liposarcoma. Close and long-term follow up is required. In retroperitoneal lipoma-like well-differentiated liposarcomas, spindle cell components like the present tumor, which represent dedifferentiation, should not be overlooked.     

Does parosteal liposarcoma differ from other atypical lipomatous tumors/well-differentiated liposarcomas? A molecular cytogenetic study using combined multicolor COBRA-FISH karyotyping and array-based comparative genomic hybridization

Parosteal adipocytic tumors of the bone are extremely rare. As a result, (cyto-) genetic data on this entity are essentially lacking. In the literature there is debate as to whether these lesions should be classified according to the criteria used in soft-tissue tumor pathology, or if they should be considered a separate bone tumor entity. Here we present a 68-year-old male patient with a tumor in his right upper leg diagnosed as parosteal atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLS) on the basis of clinico-radiologic and pathologic findings. Molecular cytogenetic investigations using combined binary ratio labeling fluorescence in situ hybridization and array comparative genomic hybridization showed abnormalities, which are in accordance with the histologic appearance of an atypical lipomatous tumor/well-differentiated liposarcoma. Therefore, on the basis of these molecular cytogenetic investigations, we conclude that parosteal liposarcoma is not a separate entity but should be categorized within the spectrum of soft-tissue ALT/WDLS.     

Dedifferentiated liposarcoma with extensive lymphoid component

An unusual variant of dedifferentiated liposarcoma with extensive lymphocytic component is described. A 71-year-old patient suffered from a relapse of an atypical lipomatous tumor/well-differentiated liposarcoma with early micronodular (low-grade) dedifferentiation, which had been resected 4 years before. The relapse revealed features of a dedifferentiated liposarcoma with spindle-cell, partly pleomorphic dedifferentiation and osseous metaplasia. Clearly separated from the spindle-cell areas, an extensive homogeneously dense lymphoid (lymphocytic) tumor-component was evident, with relative abrupt transition to the well-differentiated liposarcoma component. Using immunohistochemistry and PCR, the lymphoid ("lymphoma-like") infiltrate proved to be a polyclonal lymphocytic proliferation. Fluorescence in situ hybridization (FISII) analysis revealed no signs of MDM2- and CDK4-gene amplification in the lymphoid areas, although within this mononuclear lymphoid population, large polymorphic nuclei displayed an amplified number of MDM2/CDK4 gene copies, indicating the presence of truly dedifferentiated tumor cells within the lymphoid component. The results favor a reactive lymphocytic infiltration versus a neoplastic one, which might be caused for example by chemoattractive agents. An extensive lymphoid "overgrowth" must be considered within the spectrum of unusual variants and in the differential diagnosis of dedifferentiated liposarcoma.     

Dedifferentiated liposarcoma with peculiar meningothelial-like whorling and metaplastic bone formation

Dedifferentiated liposarcoma with peculiar meningothelial-like whorling pattern and metaplastic bone formation (DDLMB) is an unusual morphologic entity that is characterized by an atypical lipomatous tumor/well-differentiated liposarcoma with epithelioid or spindle cells concentrically arranged into meningothelial-like “whorls,” and mature bone trabeculae rimmed by reactive osteoblasts. We recently experienced 2 cases of DDLMB, one in a 64-year–old male patient with a painless right groin mass and another in a 42-year–old female patient with a painless right abdominal mass. The size of the tumors was 3.5 and 18 cm; and the tumors were located in the right scrotal sac and retroperitoneum in case 1 and case 2, respectively. Under the initial clinical diagnosis of cord lipoma in case 1 and high-grade sarcoma in case 2, the masses were removed. The cut surfaces of the masses were well circumscribed with encapsulation, red-tan, firm, and multinodular. Microscopically, the tumors consisted of atypical lipomatous tumor/well-differentiated liposarcoma with meningothelial-like whorls and metaplastic bone formation in both cases. In addition, the first case showed focal areas of paraganglioma-like pattern; and the second case showed pleomorphic high-grade sarcoma with low-grade myxofibrosarcoma-like areas. Immunohistochemically, the tumor components with meningothelial-like pattern and paraganglioma-like pattern in DDLMB were positive for vimentin and CD56 and negative for pancytokeratin, epithelial membrane antigen (EMA), desmin, and smooth muscle actin. Characteristically, the paraganglioma-like area was immunoreactive for S-100 protein, with a “dot-like” staining pattern. The patient additionally underwent radical orchiectomy in case 1. Review of the literature revealed that only 34 cases of DDLMB have been reported. One case of dedifferentiated liposarcoma with a predominant paraganglioma-like pattern has also been reported in the literature. To our knowledge, case 1 represents the first report of DDLMB with paraganglioma-like pattern. A brief literature review was made with focus on the morphologic variations of DDLMB.     

Myolipoma of the retroperitoneum

A case of retroperitoneal myolipoma is reported. A 55-year-old woman with the main complaint of an abdominal mass was admitted to Teikyo University Hospital, Tokyo, Japan. Retroperitoneal liposarcoma was suspected based on magnetic resonance imaging, and the tumor was resected. The resected tumor was well encapsulated and 30 x 15 x 8 cm in size. Histologically, it consisted of mature adipose cells and smooth muscle cells. Neither nuclear atypia nor mitosis was observed in either component. The tumor was pathologically diagnosed as myolipoma of the retroperitoneum. Retroperitoneal myolipoma is often misdiagnosed radiologically as liposarcoma because the overwhelming majority of large retroperitoneal tumor containing fat is liposarcoma, however, the clinical course of myolipoma is quite different from that of liposarcoma. Although myolipoma is very rare, pathologists should consider it in the differential diagnosis of fat-containing retroperitoneal masses.     

Atypical lipomatous tumor in a 14-year-old patient: distinction from lipoblastoma using FISH analysis

Liposarcomas are rare in young age. We present the rare case of an atypical lipomatous tumor (synonym: well-differentiated lipoma-like liposarcoma) in a 14-year-old girl with the differential diagnosis of lipoblastoma which was excluded by fluorescence in situ hybridization (FISH) analysis. The tumor presented as a soft tissue mass at the dorsal part of the right thigh measuring up to 18 cm. Microscopically the lesion consisted of atypical adipocytes with hyperchromatic nuclei and additional multivacuolated lipoblasts. Interphase dual-color FISH performed with chromosome 8 centromeric and YAC164H5 (mapping to exons 2-5 of the PLAG1 gene) probes revealed no rearrangement of PLAG1 oncogene or polysomy of chromosome 8. Additional FISH using an MDM2 gene probe and an BAC534N15 probe (containing sequences specific for the CDK4 gene) showed amplification of the CDK4 gene. These findings indicate that this tumor was no lipoblastoma but an atypical lipomatous tumor, which is of clinical relevance. In young individuals the distinction between lipoblastoma and liposarcoma is often impossible by light microscopy alone. This case shows that FISH can serve as a decisive tool in the differential diagnosis of lipoblastoma and lipoma-like liposarcoma apart from its role in distinction between lipoblastoma and myxoid/round cell liposarcoma.     

Atypical spindle cell lipoma: a clinicopathologic,immunohistochemical, and molecular study emphasizing its relationship to classical spindle cell lipoma

We studied a series of spindle cell lipomas arising in atypical sites and showing unusual morphologic features (which we called atypical spindle cell lipoma) to assess if these lesions have the same chromosomal alterations as classical spindle cell lipoma but different from those found in atypical lipomatous tumor/well-differentiated liposarcoma. We investigated alterations of different genes in the 13q14 region and the amplification status of the MDM2 and CDK4 genes at 12q14-15 by multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) analysis. In the atypical spindle cell lipomas, MLPA revealed deletions in the two nearest flanking genes of RB1 (ITM2B and RCBTB2) and in multiple important exons of RB1. In contrast, in classical spindle cell lipomas, a less complex loss of RB1 exons was found but no deletion of ITM2B and RCBTB2. Moreover, MLPA identified a deletion of the DLEU1 gene, a finding which has not been reported earlier. We propose an immunohistochemical panel for lipomatous tumors which comprises of MDM2, CDK4, p16, Rb, which we have found useful in discriminating between atypical or classical spindle cell lipomas and other adipocytic neoplasms, especially atypical lipomatous tumor/well-differentiated liposarcoma. Our findings strengthen the link between atypical spindle cell lipoma and classical spindle cell lipoma, and differentiate them from atypical lipomatous tumor/well-differentiated liposarcoma.     

Lipomatous tumors of the anterior mediastinum with muscle differentiation: a clinicopathological and immunohistochemical study of three cases

Three cases of primary lipomatous tumors of the anterior mediastinum with prominent muscle differentiation are presented. The patients were two women and one man between the age of 52 and 68 years. All patients presented with progressive shortness of breath. Radiographically, all patients demonstrated anterior mediastinal tumors which were surgically resected. In two cases, the gross findings were those of circumscribed tumors, while one lesion was described as an ill-defined and unencapsulated neoplasm. Histologically, two cases corresponded to a well-differentiated liposarcoma, while the third was a thymolipoma. Extensive areas of smooth muscle were identified in one of the liposarcomas, while the other contained areas of mature skeletal muscle. The thymolipoma displayed a prominent myoid component. Immunohistochemical studies for muscle markers including smooth muscle actin, desmin, and myoglobin showed positive staining in the corresponding components. Follow-up information showed that one patient with liposarcoma died 60 months after initial diagnosis, while the other two patients remain alive and well 16 and 36 months after diagnosis, respectively. The current cases highlight the spectrum of muscle differentiation that can be seen in adipose tumors of the anterior mediastinum and also emphasize the difficulty that such a diagnosis can pose when confronted with limited mediastinoscopic biopsies.     

Primary retroperitoneal spindle cell liposarcoma: Pathological and immunohistochemical findings

Spindle cell liposarcoma (SCLS) is presently regarded as a rare variant of well‐differentiated liposarcoma (WDLPS), which has the potential for aggressive clinical behavior. WDLPS occurs most frequently in the limbs and retroperitoneum. The most common site of SCLS occurrence is the upper limbs or shoulder girdle. Herein we report the first case of primary retroperitoneal SCLS. A 60‐year‐old Japanese man presented with a right inferior abdominal mass. Complete excision of the mass displayed a yellowish spherical tumor with a well‐circumscribed appearance measuring 98 × 95 mm. Pathological examination of the tumor revealed a neural‐like spindle cell proliferation set in a fibrous background that was associated with an atypical lipomatous component, which usually included lipoblasts. Mitotic cells were scarce. Immunohistochemical analysis demonstrated that lipoblasts were S100 positive, spindle cells were CD34 positive, and both spindle cells and lipoblasts were MDM2 negative. The Ki‐67 labeling index was <2%. At one year follow up, the patient was alive without local recurrence or metastasis. Although the proliferative activity of this tumor did not indicate strong malignancy, retroperitoneal liposarcoma generally has a poor prognosis. Accumulation of cases of SCLS is necessary to facilitate a more accurate evaluation of the pathology and clinical behavior of this tumor.     

Well-differentiated and dedifferentiated liposarcomas

Atypical lipomatous tumor or well-differentiated liposarcoma (ALT-WDLPS) and dedifferentiated liposarcoma (DDLPS) share the same basic genetic abnormality characterized by a simple genomic profile with a 12q14–15 amplification involving MDM2 gene. These tumors are the most frequent LPS. This paper reviews the molecular pathology, general clinical and imaging features, histopathology, new diagnostic tools, and prognosis of ALT-WDLPS and DDLPS.     

Retroperitoneal dedifferentiated liposarcoma with osteosarcomatous components: a case report

We report a rare case of recurrent retroperitoneal dedifferentiated liposarcoma with osteosarcomatous components. An 82-year-old male diagnosed with recurrent retroperitoneal liposarcoma underwent a tumor resection. Histologically, osseous matrix with osteoid and mature hyaline cartilaginous tissues with high cellularity were observed in a fibrous background through most of the tumor, and scattered MDM2- and CDK4-positive atypical hyperchromatic stromal cells were detected surrounding the dedifferentiated areas. Dedifferentiation occurs in up to 10% of well-differentiated liposarcomas, frequently resembling a malignant fibrous histiocytoma-like pleomorphic sarcoma. In contrast, divergent differentiation with osteosarcomatous components is considered to be extremely rare.     

Sensitivity of MDM2 amplification and unexpected multiple faint alphoid 12 (alpha 12 satellite sequences) signals in atypical lipomatous tumor

This study assessed whether analysis of MDM2 copy number by fluorescence in situ hybridization (FISH) would help distinguish lipomas from atypical lipomatous tumors, otherwise referred to as well-differentiated liposarcomas, using a commercially available MDM2 FISH kit. 227 lipomatous and 201 non-lipomatous tumors were analyzed to assess its sensitivity and specificity. Of 178 mature lipomatous tumors, 86 were classified histologically as lipoma and 92 as atypical lipomatous tumor. Two of the lipomas harboring MDM2 amplification were reclassified as atypical lipomatous tumors. Overall, 13 atypical lipomatous tumors did not reveal MDM2 or CDK4 amplification, although this was reduced to 12 following analysis of multiple slides. Three of these cases revealed very occasional tumor cells harboring high-level MDM2 amplification, two had a dedifferentiated component, and MDM2 amplification was detected when one tumor recurred. The remaining six cases exhibited reactive/inflammatory features and were reclassified as lipomas. The findings indicate that MDM2 amplification is 93.5% sensitive for diagnosing atypical lipomatous tumor. A total of 2 of the 20 dedifferentiated liposarcomas failed to reveal MDM2 amplification. All atypical lipomatous tumors measured >10?cm, two dedifferentiated liposarcoma presented de novo at <10?cm, and ～50% of lipomas measured >10?cm. Spindle cell lipomas, lipoblastomas, hibernomas and pleomorphic liposarcomas did not reveal MDM2 amplification. Of 201 non-lipomatous tumors, eight revealed MDM2 amplification or multiple faint alphoid 12 signals and were reclassified as dedifferentiated liposarcoma. Multiple faint alphoid 12 signals were observed in nine tumors from seven patients, an observation not previously reported on paraffin sections: these included four atypical lipomatous tumors, and three dedifferentiated liposarcomas, one previously diagnosed as a myxofibrosarcoma, all of which also revealed amplification of CDK4, although two lacked MDM2 amplification. MDM2 FISH test is a useful adjunct to histology for distinguishing lipoma from atypical lipomatous tumor. The limitations of molecular genetic tests must be known before introducing them into a clinical service.