Clinico-molecular study of dedifferentiation in well-differentiated liposarcoma

Well-differentiated liposarcoma (WD) acquires fully malignant potential when the histological progression named dedifferentiation occurs. This progression is supposed to occur in a time-dependent manner but this is still a debated issue. Clinically, the prediction of dedifferentiation for WD is very important from the therapeutic point of view. To identify genes that are predictive of dedifferentiation and to understand the mechanism of dedifferentiation, we investigated clinical information of 50 cases and studied the gene expression profiles of 36 lipomatous tumors using cDNA microarray. The clinical study showed that the dedifferentiation did not always seem to occur in a time-dependent manner. Interestingly, from the gene expression study, unsupervised hierarchical clustering analysis of well-differentiated lesions obtained from dedifferentiated liposarcoma (DD) cases that were indistinguishable from WD pathologically showed a clearly distinct gene expression pattern from WD. Using the pattern-matching program, 1687 genes including 487 known genes were identified, which discriminated WD cases from well-differentiated lipomatous lesions obtained from DD cases. These results suggest that the dedifferentiation may arise from different types of WD that could be distinguished from gene expression profiling but could hardly be classified by the pathological studies.     

Cytologic features of well-differentiated sclerosing liposarcoma in aspirated samples

The histologic, cytologic and ultrastructural features of two cases of a rare variant of liposarcoma, the well-differentiated sclerosing type, are presented. These tumors are characterized by lipoblasts (in different stages of development), atypical fibroblasts, multinucleated floret cells, lipocytes and delicate, dispersed collagen. The differential diagnosis includes other types of liposarcoma and three benign lipomatous lesions: the pleomorphic lipoma, the atypical lipoma and the spindle cell lipoma. The latter three neoplasms are composed of fibroblasts, lipocytes and coarse collagen and may have typical lipoblastlike or fibroblastic cells. Given the difficulty in distinguishing these lesions, both cytologically and histologically, the clinical presentation and the tumor location become essential in rendering the diagnosis of sclerosing liposarcoma.     

Relationship of hypoxia-inducible factor 1α and p21WAF1/CIP1 expression to cell apoptosis and clinical outcome in patients with gastric cancer

Background

This case report highlights two unusual surgical phenomena: lipoma-like well-differentiated liposarcomas and sciatic hernias. It illustrates the need to be aware that hernias may not always simply contain intra-abdominal viscera.

Case presentation

A 36 year old woman presented with an expanding, yet reducible, right gluteal mass, indicative of a sciatic hernia. However, magnetic resonance imaging demonstrated a large intra- and extra-pelvic fatty mass traversing the greater sciatic foramen. The tumour was surgically removed through an abdomino-perineal approach. Subsequent pathological examination revealed an atypical lipomatous tumour (synonym: lipoma-like well-differentiated liposarcoma). The patient remains free from recurrence two years following her surgery.

Conclusion

The presence of a gluteal mass should always suggest the possibility of a sciatic hernia. However, in this case, the hernia consisted of an atypical lipoma spanning the greater sciatic foramen. Although lipoma-like well-differentiated liposarcomas have only a low potential for recurrence, the variable nature of fatty tumours demands that patients require regular clinical and radiological review.     

Giant dedifferentiated liposarcoma of the right hemifacial area involving the oral cavity

Although liposarcoma is a reasonably common soft tissue sarcoma in adults, its occurrence within the head and neck region is very rare. The following report presents the case of a giant dedifferentiated liposarcoma initially located in the temporal region and then extending to the entire right maxillofacial region. Clinical as well as histopathological features and therapeutic approaches of dedifferentiated liposarcoma are discussed, and a literature review is presented.     

Growth inhibitory effect of quercetin on SW 872 human liposarcoma cells

Adipocytic tumors represent the largest single group of soft tissue tumors. In the present study, we investigated the antiproliferative potential of quercetin in SW 872 human liposarcoma cells. Cell viability was significantly influenced by quercetin treatment in a time- and dose-dependent manner. Flow cytometric analyses of SW 872 human liposarcoma cells exposed to quercetin showed that the increase of apoptotic cells was time- and dose-dependent. The percentages of normal cells were decreased and apoptotic cells (including early apoptotic and late apoptotic) were increased with increasing concentrations of quercetin. Quercetin-induced apoptosis in SW 872 human liposarcoma cells was associated with the loss of mitochondrial membrane potential (DeltaPsi(m)). The apoptosis in SW 872 human liposarcoma cells induced by quercetin was mediated through the activation of caspase-3, Bax, and Bak and then cleavage of PARP and downregulation of Bcl-2. These results demonstrate that quercetin may prevent atypical lipomatous tumors/well-differentiated liposarcomas from mature adipocytic proliferation, which may contribute to its antiproliferative function.     

Cytomorphology of lipomatous tumors of soft tissue

OBJECTIVE: To evaluate the cytomorphologic features of benign and malignant lipomatous tumors of soft tissue on fine needle aspirates (FNA) and determine if the variants of liposarcoma could be identified. STUDY DESIGN: FNA of histologically documented benign (51 cases) and malignant (39 cases) lipomatous tumors were reviewed. Twenty-six of the 51 FNA from lipomas and 34 of the 39 FNA from malignant lipomatous tumors were satisfactory for evaluation. RESULTS: FNA from 26 cases of lipomas were cellular, with lobulated, fibroadipose tissue. Thin and thick capillaries were seen in 92% and 65% of cases, though a chicken wire vascular pattern was seen in only 4 cases (15%). A cytodiagnosis of liposarcoma could be made in 23 cases (88%), and these could be further subtyped into well-differentiated (4 cases), myxoid (8), pleomorphic (4), round cell (3) and liposarcoma, ?type (4). Only 50% of the well-differentiated liposarcomas, 3 of the 10 pleomorphic liposarcomas and 8 of the 17 myxoid liposarcomas were diagnosed as such on FNA. Cytologic diagnosis of the remaining 9 cases of myxoid liposarcoma were pleomorphic liposarcoma (1); liposarcoma, ?type (3); malignant mesenchymal tumor (1); suspicious for malignancy (2); and benign (2). There were no false positives, but there were 3 false negative cases (1 well-differentiated and 2 myxoid liposarcoma). CONCLUSION: Lipomas can be diagnosed readily. Arborizing vessels can be seen in lipomas and should be interpreted with caution. Subclassification of liposarcomas on FNA is possible but not very reliable. Myxoid liposarcomas pose a problem, and aspirates from them can mimic a wide range of morphologic subtypes. The role of FNA in identification of variants of liposarcoma is limited.     

Spontaneous retroperitoneal liposarcoma in a free‐ranging juvenile golden‐headed lion tamarin (Leontopithecus chrysomelas)

Malignant adipocytic neoplasia is rare among nonhuman primates. We report the gross and microscopic features of a retroperitoneal liposarcoma with myxofibrosarcoma‐like dedifferentiation in a free‐ranging juvenile golden‐headed lion tamarin (Leontopithecus chrysomelas). To our knowledge, this is the first report of such tumor subtype in New World primates.     

Localized early mesenteric Castleman's disease presenting as recurrent intestinal obstruction: a case report

Introduction

Pleomorphic adenoma is the most common benign neoplasm of the salivary glands. Extensive lipomatous involvement of the tumor is, however, a very rare finding.

Case report

Herein, a rare case of lipomatous pleomorphic adenoma arising in the parotid gland of a 14-year-old Japanese woman is presented.

Conclusion

This is the sixth case of lipomatous pleomorphic adenoma in the English literature. Recognition of this rare subtype of pleomorphic adenoma is important for clinical diagnosis and management. On CT scan, it may not be detected possibly due to the extensive fatty component.     

Fine needle aspiration biopsy of well-differentiated liposarcoma of the neck in a young female. A case report.

BACKGROUND: Well-differentiated liposarcomas are low grade, nonmetastasizing, malignant neoplasms composed primarily of mature adipose tissue. They are uncommon in the head and neck. CASE: A 24-year-old female presented to the ears, nose and throat clinic for evaluation of a recent, rapidly growing neck mass on the right side. Fine needle aspiration (FNA) biopsy of the mass showed that the smears had fragments of connective tissue with a mixture of mature-appearing fat traversed by bands of fibrous collagen and vessels. Nuclei within the fat and fibrous bands were mildly irregular, hyperchromatic and enlarged, with one or two small nucleoli. Infrequently present but readily identified, lipoblasts were scattered throughout the aspirate smears. A diagnosis of "atypical lipomatous neoplasm" was rendered. Subsequently, the mass was surgically removed. On histologic examination, the tumor was a well-differentiated liposarcoma. CONCLUSION: FNA biopsy of well-differentiated liposarcomas in the head and neck can present difficulties in the classification and diagnosis of this neoplasm.     

Pathology and genetics of adipocytic tumors

Adipocytic tumors are common mesenchymal neoplasms with considerable morphologic and genetic heterogeneity. The fruitful integration of morphology and cytogenetics in the past 15 years has not only enhanced the diagnostic accuracy, but also refined the various pathological classifications and subtypes in these tumors. The current WHO classification includes eleven benign subtypes, one intermediate and five categories of malignant fatty neoplasms with incorporation of relevant genetic findings. Of the benign tumors, lipomas have been extensively analyzed by chromosome banding which has shown that their cytogenetic patterns are heterogeneous. Still aberrations involving 12q13-->q15, 6p23-->p21 and loss of material from 13q are common and consistent findings. Among the malignant tumors, the t(12;16)(q13;p11) resulting in the fusion of DDIT3 and FUS genes is the hallmark of myxoid and round cell liposarcoma and is used as a highly specific and sensitive marker of this entity. The tumor in the intermediate group, atypical lipomatous neoplasm/well-differentiated liposarcoma which poses morphologic challenges due to close histological similarity to benign lipomas shows characteristic supernumerary rings and giant rod chromosomes due to amplification of the 12q14-->q15 region often involving the MDM2 oncogene. This review will focus on the pathological features of the various adipocytic tumors and relevant genetic findings reported in the literature.     

Diagnosis of thymolipoma with fine needle aspiration biopsy. Report of a case initially misdiagnosed as liposarcoma

BACKGROUND: Thymolipomas are the most outstanding mesenchymal mediastinal tumors although they represent only a small percentage of thymic neoplasms. Their histogenesis remains unsolved, and they are usually benign. Fine needle aspiration biopsy (FNAB) has become the method of choice for the study of mediastinal tumors, including thymolipomas. Making the correct diagnosis depends on the availability of all thymic and lipomatous components as well as on the correct application of a differential diagnosis with other lipomatous tumors. CASE: A 24-year-old woman had a 3-month history of coughing with sputum, fever, asthenia, adynamia, headaches and anemia. Physical examination revealed a bilateral pulmonary condensation syndrome. Imaging studies showed a well-defined, large mass occupying both hemithoraxes and the mediastinum. FNAB revealed an admixture of atypical adipocytes, nonneoplasic lymphoid tissue and capillaries with prominent endothelium. An initial diagnosis of well-differentiated liposarcoma was made. A 2.8-kg, encapsulated, yellowish gray mediastinal tumor was surgically removed. Mature adipose tissue intermingled with abundant thymic tissue containing numerous Hassall's corpuscles were seen histologically. Immunohistochemical markers for thymic epithelium, lymphoid tissue and adipocytes were all positive. Thymolipoma was the final diagnosis. The anemia subsided with resection of the tumor, and the patient was disease free 2.5 years after surgery. CONCLUSION: To the best of our knowledge, this is the second report of a thymolipoma studied with FNAB. The criteria for the differential diagnosis between thymolipomas and other lipomatous tumours should be kept in mind.     

Fine needle aspiration diagnosis of lipoblastoma of the parotid region. A case report

BACKGROUND: Lipoblastomas are rare tumors of embryonal fat that occur in infants and children. They are usually located in the extremities and trunk. Two cases in the parotid region have been described. A diagnosis on fine needle aspiration (FNA) specimens has been reported in six cases. CASE: Lipoblastoma of the parotid region occurred in a 6-year-old boy and was diagnosed by FNA. Cytology showed rare lipoblasts and hibernomalike cells in a myxoid background with spindle and stellate mesenchymal cells, mature adipose cells and plexiform capillaries. A 7.0-cm, well-circumscribed mass with lobulated adipose tissue and delicate fibrous bands was resected. Microscopically, it showed a lobulated myxoid stroma, many capillaries, mesenchymal cells, lipoblasts and mature adipose cells. CONCLUSION: Lipoblastoma has to be differentiated from myxoid and lipomatous soft tissue tumors, especially from myxoid liposarcoma, a malignancy that classically affects older individuals and shows pleomorphism, atypical lipoblasts and chromosome-12 translocation. A lipoblastoma diagnosis must be established only after careful consideration of all available clinical, radiologic, cytogenetic and morphologic data.     

Cancer‐associated neochromosomes: a novel mechanism of oncogenesis

Malignant tumours are often characterised by significant rearrangement of the genome. This may be visible in the form of a deranged karyotype with both loss and gain of DNA sequences extending from chromosomal regions to whole chromosomes. In several tumour types, however, gross genomic derangements are minimal, and tumour cells contain one or more additional (supernumerary) chromosomes that may be unrecognisable in terms of a single origin. In this review we term such chromosomes cancer‐associated neochromosomes (CaNCs). In the absence of other identified genomic abnormalities, and because the CaNC is a common feature of the cancer type, it is hypothesised that the genetic alterations required for cell transformation are contained within its structure. In this review, we discuss the potential impact of modern genomic technologies on our understanding of the nature and causes of CaNC formation, which is central to several cancer types, exemplified here by well‐differentiated liposarcoma.     

TEP/TDM au FDG et hibernome : à propos d’un cas

Hibernoma is a rare benign tumour of soft tissue, generally asymptomatic, usually discovered in young adults. It is a form of lipoma that originates from brown adipose tissue. Its diagnosis is based on histology, the main differential diagnoses being lipoma and liposarcoma. Its appearance on FDG PET/CT has being described only in few case reports. We report here the case of a 68-year-old patient with ENT cancer in whom an adipose tumour in the left axilla has been discovered on CT performed for staging. The diagnosis of hibernoma was suggested in the report of FDG PET/CT examination and was consistent with results of other imaging modalities. On MRI, contrast enhancement was observed after gadolinium contrast injection, which was not typical for a lipoma. On PET/CT, the FDG uptake by the adipose tumour was very intense (SUVmax = 16), which is characteristic for hibernoma that derives from brown adipose tissue. Imaging was unable to distinguish between hibernoma and liposarcoma. The diagnosis of benign mixed hibernoma-lipoma was ascertained on histopathology after complete resection of the tumour. Elements favouring hibernoma over liposarcoma are present in this observation: high avidity for FDG (SUVmax > 10) and a fluctuating intensity of uptake, SUVmax of the tumour increasing from 16 to 48 within 16 months in the presented case. A high SUVmax on FDG PET in an adipose tumour on CT seems to be more suggestive of a benign tumour, hibernoma, than of its malignant counterpart, liposarcoma.     

Fine needle aspiration cytology of well-differentiated liposarcoma. A report of two cases

BACKGROUND: Well-differentiated liposarcoma is difficult to diagnose on fine needle aspiration cytology (FNAC) smears and may create considerable diagnostic problems. CASES: Males aged 60 and 45 years presented with a swelling in the groin and retroperitoneal region, respectively. FNAC showed large cells with multilobulated nuclei and mature-looking fat tissue. A soft tissue tumor with bizarre cells was diagnosed cytologically in case 1 and liposarcoma in case 2. Histologically, both cases were diagnosed as well-differentiated sclerosing liposarcoma. CONCLUSION: The cytologic diagnosis of well-differentiated liposarcoma should be done with caution, and the sites should be taken into consideration. Deep-seated tumors with large, bizarre, giant cells should have wide excision as they recur more frequently.     

Fine needle aspiration cytology of a dedifferentiated liposarcoma: report of a case with histologic and immunohistochemical follow-up

BACKGROUND: Dedifferentiation is a histologic progression of a neoplasm from low grade to high grade histology. It occurs in tumors of the retroperitoneum and in those undergoing treatment. This usually occurs in the setting of radiation or chemotherapy or as a spontaneous process over a long period. The features of dedifferentiation can be toward any mesenchymal element of the underlying neoplastic process. CASE: We report the cytologic features of a dedifferentiated liposarcoma arising in a 76-year-old man who had a history of well-differentiated liposarcoma. Papanicolaou- and Diff-Quik-stained smears from a radiologically guided fine needle aspiration biopsy showed a hypercellular sample. The smears showed a mixed population of cells. There were multinucleated, pleomorphic giant cells with abundant cytoplasm, smaller clusters of cells with a high nuclear/cytoplasmic ratio and cells with spindled and elongated nuclear features. The follow-up surgical resection specimen showed a dedifferentiated liposarcoma with strong and diffuse immunoreactivity to vimentin, desmin and CD68 in the large, pleomorphic cells; focal and weak immunoreactivity to smooth muscle actin and S-100 in these cells; and strong and focal immunoreactivity to desmin, smooth muscle actin and muscle-specific actin in the spindle cells. This supports the dedifferentiated components of this tumor to be of fibrohistiocytic and leiomyosarcomatous differentiation. CONCLUSION: Dedifferentiation of a well-differentiated liposarcoma should be entertained in the setting of a mass lesion in the retroperitoneum in patients with prior histories of well-differentiated liposarcoma. The radiologic features of a particular neoplastic process can be very helpful in determining the nature of this process.     

The treatment with differentiation- and apoptosis-inducing agent, vesnarinone, of a patient with oral squamous cell carcinoma

A patient with histopathological recurrent oral cancer with well-differentiated squamous cell carcinoma, was treated with differentiation- and apoptosis-inducing agent, vesnarinone, per os at a dose of 180 mg/day for 56 days and then at a dose of 60 mg/day for 93 days. The vesnarinone administration caused complete remission of the tumour. It has been found by immunohistochemical staining and PCR-SSCP analysis that the recurrent tumour has wild type p53 gene and relative high level of LeY expression as well as DNA fragmentation in the cancer cells, as assessed by nick-end labelling. These findings suggest that the cure of oral squamous cell carcinoma observed in this case might be associated with induction of differentiation and apoptosis of cancer cells by vesnarinone.     

Angiocentric T-cell lymphoma

SUMMARY: The CD20+ variant of angiocentric T-cell lymphoma is an unusual type of T-cell lymphomas that present cystic changes in organs because of ischaemic necroses. The purpose of this study was to describe a case of CD20+angiocentric T-cell lymphoma, discussing its clinical, histopathological and immunohistochemical features, to analyze its proliferation kinetics and to consider its possible relationship to the Epstein-Barr virus (EBV) to understand better the pathobiological nature of the disease. METHODS: The clinical, histopathological, immunohistochemical and single-cell DNA cytophotometric features of the case were analyzed. In addition in situ hybridization was performed to detect EBV. RESULTS: The 24 years old woman was admitted to our Institute because of pain in the abdominal region and weight loss. There were enlarged lymph nodes on the neck, and biopsy was done. Histological diagnosis: angiocentric T-cell lymphoma, CD20+ variant. CD3, CD43, CD45RA and CD45R0 antigens were positive in the atypic lymphoid cells of the tumour and in cells infiltrating the vascular wall. DNA index was 0.8589 (hypodiploid). Tumour cells in G1 phase: 47%, S phase: 45.4%, G2 phase: 7.6%. Combined chemotherapy was administered because of clinical stadium IV/B of malignant lymphoma (5 CHOP-Bleo, CEPP, CEP, CMVE treatment). The disease showed gradual progression and the patient died 14 months after the first symptoms had appeared. CONCLUSIONS: In the last 13 years there were 5 cases of angiocentric T-cell lymphoma at our Institute. The CD20+ variant is rare, its clinical symptoms are special, the prognosis is unfavourable. The cause why we demonstrate this case is to call attention to a new treatment for these patients by immunotherapy using monoclonal antibodies against CD20 antigen.     

Osteolytic skull metastasis with dural involvement from a papillary thyroid carcinoma

Skull metastatic tumors are relatively rare medical entities and originate most often from the lungs, breast or prostate. We report a case of a 76-year-old woman who presented with a bulging, well-circumscribed mass on the right side of the forehead. Neuroimaging of the cranium detected an osteolytic lesion measuring 7 cm in the largest diameter while propagating outwards and intracranially. A thorough medical history revealed that patient had undergone surgery for invasive breast ductal carcinoma and also for a well-differentiated thyroid carcinoma 13 years ago. Considering patients medical history metastatic breast carcinoma was suspected. After a frontal craniotomy the tumour tissue was totally resected. Histological examination revealed metastatic papillary carcinoma characterized by ground-glass nuclei with intranuclear pseudo inclusion and nuclear grooves. We report clinical and neuroradiological features of this uncommon lesion and discussed the differential diagnosis of skull osteolytic lesion together with the treatment management.