Dedifferentiated liposarcoma of the small bowel mesentery presenting as a submucosal mass

Dedifferentiated liposarcoma(DDLPS) is a variant of liposarcoma but with a more aggressive course.It occurs most commonly in the retroperitoneum and rarely in any other anatomical location.We describe a case of DDLPS arising from the small bowel mesentery presenting as submucosal mass of the small bowel.The current case is unusual as the tumor originated from the small bowel mesentery and a dedifferentiated component transmurally invaded the small bowel wall,including the small bowel submucosa.     

伴恶性纤维组织细胞瘤去分化股骨远端脂肪肉瘤一例

Primary intraosseous liposarcoma was a rare and malignant tumor of the skeletal system. It originated from the intraosseous adipose tissue. Since the first case was reported in 1931, there were only do...     

Dedifferentiated chondrosarcoma of the maxilla

A 20-year-old male reported with right-sided facial swelling, epistaxis and right sided proptosis of two months duration. Computerized tomography scan of the face revealed a mass in the right maxillary sinus. The patient underwent surgery and the postoperative histopathology was suggestive of dedifferentiated chondrosarcoma. The present report discusses this rare presentation and the issues in its management.     

Dedifferentiated liposarcoma in the extremity and trunk wall: A multi-institutional study of 132 cases by the Japanese Musculoskeletal Oncology Group (JMOG)

BackgroundDedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined.MethodsClinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study.ResultsA total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm², French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm² and lung metastasis were independent risk factors for disease-specific mortality.ConclusionsThe typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity.     

Dedifferentiated central chondrosarcoma

BACKGROUND: The prognosis for patients who develop dedifferentiation of central chondrosarcoma traditionally has been poor. Because not much has been reported about this rare lesion, many uncertainties remain about prognostic factors. METHODS: In this retrospective study, the clinical, radiographic, and histologic features and the treatments in 123 patients from the Rizzoli Institute were reviewed in an attempt to define which factors may be related to outcome in patients with dedifferentiated central chondrosarcoma. RESULTS: Among 123 patients who were included in this study, 109 patients were treated at the Rizzoli Institute, and 14 patients were seen in consultation. There were 66 males and 57 females, and their average age was 59 years. The femur (62 patients), pelvis (28 patients), and humerus (20 patients) were the most common locations. Radiographically, a soft tissue mass was present in 87% of patients, and a bimorphic pattern was appreciated in 53% of patients. Histologically, the cartilaginous component was considered Grade 1 in 63% of patients and Grade 2 in 37% of patients. In most patients, the dedifferentiated component showed the features of an osteosarcoma (92 patients), followed by fibrosarcoma (19 patients), and malignant fibrous histiocytoma (9 patients). For 101 patients, surgery was a component of their definitive management. In 25 patients, surgery was combined with chemotherapy. The 2-year and 5-year survival rates were 34% and 24%, respectively. The median survival was 13 months (95% confidence interval, 9-17 months). CONCLUSIONS: Metastatic disease at diagnosis, malignant fibrous histiocytoma dedifferentiation, and a high percentage of dedifferentiated component were related to poorer outcomes. There was no statistical evidence of any beneficial effect from adjuvant chemotherapy.     

去分化皮质旁骨肉瘤

目的 探讨去分化皮质旁骨肉瘤(Dedifferentiated parosteal osteosarcoma,dd-POS)的临床特点及其治疗。方法 回顾5例dd-POS的临床、影像和组织学资料,总结出dd-POS的临床病理学特点、治疗及其预后。结果 5例患者中3例分别于术后21个月、25个月和31个月死于肺转移,2例无瘤存活50个月和72个月,其中1例在术后1年局部复发,经再次手术得以控制。结论 虽然dd-POS的诊断最终有赖于组织学检查,但影像资料是早期鉴别高度恶性变区最有效的方法。     

Primary liposarcoma of the mediastinum

Patient. A 62-year-old man presented with effort dyspnea, non-productive cough and weakness of 4 month duration. He had no findings on physical examination.Discussion. Chest X-ray revealed a large mass in the left anterior mediastinum. Computerized tomography of the chest showed a well-delineated homogeneous mediastinal mass with fat-equivalent density and a small pleural effusion. Fiberoptic bronchoscopy revealed narrowing of the left main bronchus, secondary to external compression. The bronchial mucosa was normal and brush cytology was negative. A CT-guided fine needle aspiration (FNA) of the mass yielded fragments of cells embedded in myxoid background material and closely packed atypical lipoblasts, compatible with liposarcoma. The patient underwent a left lateral thoracotomy and margibnal resection of the mass. The histopathological examination confirmed the diagnosis of mixed-type liposarcoma, consisted of myxoid and pleomorphic liposarcoma. Postoperative two-field radiation therapy was delivered to the mediastinum for a total midplane dose of 40 Gy. After a disease-free interval of 8 months the disease recurred in the mediastinum and pleura. Palliative chemotherapy achieved a short duration partial response but the patient succumbed to local recurrence 2 years after the diagnosis.     

Dedifferentiated chondrosarcoma. An ultrastructural study

The light and electron microscopic features of a well-differentiated chondrosarcoma with dedifferentiated foci (dedifferentiated chondrosarcoma) is presented. Ultrastructurally, the cells of the dedifferentiated portion were embedded in a matrix containing numerous short bundles of collagen fibers; these cells showed dilated rough endoplasmic reticulum containing stippled material as well as poorly formed cell junctions and resembled the cells in the cartilaginous component. These findings contrast with those reported previously.     

Dedifferentiated chordoma: a case report

Dedifferentiated chordoma, i.e. chordoma with a sarcomatous component, is a rare bone tumor. This case report is of a dedifferentiated chordoma in the sacrococcygeal region in a 50-year-old male. The patient was initially diagnosed as having a leiomyosarcoma at the first medical consultation, but after the tumor recurred it was proven to be a dedifferentiated chordoma. The primary tumor, which measured 7 x 5 cm, was located in front of the sacrum so as to compress the rectum forward. The resected specimen showed histological features of chordoma, but the presence in some parts of the tumor of spindle-shaped epithelial cells led to a misdiagnosis of leiomyosarcoma. Thirty-six months later, a local recurrent tumor measuring 24 x 17 cm was identified and promptly resected. The recurrent tumor showed features of pleomorphic cell sarcoma mimicking malignant fibrous histiocytoma. In the pleomorphic sarcomatous area, many mitotic figures were seen, and the MIB-1 labeling index was greater than 40%, which was higher than that of the conventional chordoma area. From histological and immunohistochemical examination, the resected tumor was proven to be a dedifferentiated chordoma. This case highlights the importance of careful study of suspected chordoma to allow early identification of sarcomatous components. When we encounter a chordoma with a spindled epithelial component, we need to distinguish this tumor from a dedifferentiated chordoma and other spindle cell sarcomas such as leiomyosarcoma.      

去分化软骨肉瘤的诊断及治疗进展*

去分化软骨肉瘤（DDCS）约占所有软骨肉瘤的10% ,预后极差,5 年生存率不到10% 。好发于股骨、肱骨和骨盆。DDCS是软骨肉瘤中的一个独特类型。典型的特点是分化良好的软骨样成分和高度恶性的间充质细胞来源的肉瘤成分并存、毗邻。DDCS的诊断非常复杂,需要详细的影像学和病理学检查及准确的活检。DDCS去分化成分可以是骨肉瘤、恶性纤维组织细胞瘤,甚至是任何级别的未分化肉瘤成分。约1/3 的X 光片,1/3 的MR,一多半的CT扫描,DDCS表现为典型的“双态”征。最近利用微阵列- 比较基因组杂交技术,发现反复发生的5q14.2~q21.3,6q16~q25.3,9p24.2~q12和9p21.3。染色体缺失更多见于高度恶性的软骨肉瘤（3 级和DDCS）,该差异具有统计学意义。9 号染色体的缺失是DDCS最常见的染色体缺失。早期研究发现DDCS的去分化成分有p53和p53杂合性的丢失现象,进一步研究发现同时伴随Rb基因杂合性的丢失。DDCS的两种成分可出现p16INK 4,FHIT和E-cadherin（上皮型钙黏附蛋白）甲基化的异常。手术切除包括合适足够的外科切缘或根治性的切除,是目前DDCS最主要的治疗手段。化疗效果目前仍然不确定。最近针对软骨肉瘤（包括DDCS）发现了一些新的药物靶标,有些已经进入临床Ⅱ期试验阶段,其中包括Apomab、Perifosine （哌立福新）、Dasatinib（达沙替尼）和多烯紫杉醇联合吉西他滨的联合化疗。同时几个Ⅰ期药物临床试验报告针对DDCS新的有效药物,如组蛋白去乙酰酶抑制剂和血管内皮生长因子反义寡合甘酸。DDCS患者预后极差,预后主要由DDCS中的去分化成分决定。因此,早期诊断、早手术对改善患者的预后非常关键。      

Dedifferentiated parosteal osteosarcoma: the experience of the Rizzoli Institute

BACKGROUND: Dedifferentiated parosteal osteosarcoma (DPOS) is a variant of osteosarcoma in which a high-grade sarcoma coexists with a conventional parosteal osteosarcoma (c-POS), either at presentation (synchronous type) or at the time of recurrence (metachronous type). Only approximately 60 patients have been reported in the literature. The objective of this study was to analyze the clinicopathologic and radiographic features of a relatively large number of patients with DPOS in an attempt to define further the histologic and biologic behavior of this rare entity. METHODS: In a series of 120 patients with parosteal osteosarcoma who were seen at the Rizzoli Institute from 1958 to 2000, the authors identified 29 patients who were diagnosed with DPOS. The authors reviewed the clinical and radiologic features, histologic sections, treatments, and outcomes in this group of patients with DPOS. RESULTS: Twelve patients were male, and 17 patients were female. The patients ranged in age from 15 years to 65 yrs (average, 36 years; median, 32 years). One tumor involved the scapula, one involved the ilium, and another involved the skull. All 26 of the other tumors were located in the long bones (14 in the femur, 5 in the humerus, 3 in the tibia, 3 in the fibula, and 1 in the ulna). In 18 patients, radiographic areas of lucency were seen within an otherwise sclerotic lesion. Histologically, the dedifferentiated component was high-grade osteoblastic osteosarcoma in 14 patients, fibroblastic osteosarcoma in 10 patients, giant cell-rich osteosarcoma in 3 patients, and chondroblastic osteosarcoma in 2 patients. All tumors were Stage IIB, and invasion of the medullary canal was detected in 19 patients (65%). Twenty-eight patients underwent surgery, and 18 of those patients received chemotherapy (5 patients received neoadjuvant chemotherapy, and 13 patients received adjuvant). Nine patients were dead and 20 patients were alive (average follow-up, 107 months; range, from 3 months to 36 years) at the last follow-up. Of the nine patients who died, one patient received no treatment, five patients underwent surgery (with three patients achieving adequate margins) in combination with chemotherapy, and three patients underwent surgery only (with adequate margins achieved). Of the 20 patients who remained alive, 13 patients underwent surgery (with 10 patients achieving adequate margins) in combination with chemotherapy, whereas 7 patients underwent surgery only (all with adequate margins). Seven of the nine patients who died had widespread metastases. One patient died of causes unrelated to the tumor, and another patient died shortly after undergoing resection of a lesion in the skull. CONCLUSIONS: Dedifferentiation occurred in approximately 24% of patients with c-POS. The prognosis for patients with DPOS was better than the prognosis for patients with dedifferentiated central and dedifferentiated peripheral chondrosarcoma.     

Myxoid liposarcoma of the spermatic cord

The clinical and pathological features of one new and eight previously reported myxoid liposarcomas of paratesticular origin were reviewed. This kind of tumor was seen in an older population (average age 64 years), most of whom had scrotal masses of long duration (average 3.3 years). The tumors are large, usually painless, and are frequently misdiagnosed as hydroceles or inguinal hernias. All patients were treated by radical inguinal orchiectomy and are alive with follow-ups of 1-9 years.     

Well-differentiated liposarcoma of the tongue.

Intraoral liposarcomas are rare, with most reported cases being of the myxoid histological type. We present a well-differentiated liposarcoma of the tongue, in a 65-year-old man. The tumour presented lipoblasts in various stages of differentiation, lipocytes in different sizes and shapes, mesenchymal and signet-ring cells. Lipoma, spindle-cell lipoma, myxoma, hibernoma, angiolipoma, fibrolipoma, pseudosarcomatous faciitis and malignant hysticytoma were considered in the diagnosis process. The patient was treated surgically and so far is free of disease.     

未分化及失分化甲状腺癌治疗进展

未分化及失分化甲状腺癌是死亡率较高的内分泌恶性肿瘤,目前尚缺乏有效的治疗手段,寻找新的治疗手段显得尤为迫切.一系列新的治疗方法的出现为未分化及失分化甲状腺癌患者的治疗提供了可能:基因治疗,如通过恢复抑癌基因功能的基因治疗(恢复P53基因功能)或自杀基因导入治疗,抗肿瘤血管形成的基因治疗,钠/碘转运蛋白(NIS)基因介导的放射性碘治疗;诱导分化治疗如:通过维甲酸及组蛋白乙酰化酶抑制剂诱导分化治疗可促进肿瘤细胞的分化,有助于控制肿瘤的发展,而金属蛋白酶抑制剂的应用可控制肿瘤细胞的转移.而手术方式、放化疗方案的改进及综合应用亦可延长甲状腺未分化及失分化癌患者的生存时间.本文就上述新的甲状腺癌的治疗方案做一综述.     

Genomic landscape of liposarcoma

Liposarcoma (LPS) is the most common type of soft tissue sarcoma accounting for 20% of all adult sarcomas. Due to absence of clinically effective treatment options in inoperable situations and resistance to chemotherapeutics, a critical need exists to identify novel therapeutic targets. We analyzed LPS genomic landscape using SNP arrays, whole exome sequencing and targeted exome sequencing to uncover the genomic information for development of specific anti-cancer targets. SNP array analysis indicated known amplified genes (MDM2, CDK4, HMGA2) and important novel genes (UAP1, MIR557, LAMA4, CPM, IGF2, ERBB3, IGF1R). Carboxypeptidase M (CPM), recurrently amplified gene in well-differentiated/de-differentiated LPS was noted as a putative oncogene involved in the EGFR pathway. Notable deletions were found at chromosome 1p (RUNX3, ARID1A), chromosome 11q (ATM, CHEK1) and chromosome 13q14.2 (MIR15A, MIR16-1). Significantly and recurrently mutated genes (false discovery rate < 0.05) included PLEC (27%), MXRA5 (21%), FAT3 (24%), NF1 (20%), MDC1 (10%), TP53 (7%) and CHEK2 (6%). Further, in vitro and in vivo functional studies provided evidence for the tumor suppressor role for Neurofibromin 1 (NF1) gene in different subtypes of LPS. Pathway analysis of recurrent mutations demonstrated signaling through MAPK, JAK-STAT, Wnt, ErbB, axon guidance, apoptosis, DNA damage repair and cell cycle pathways were involved in liposarcomagenesis. Interestingly, we also found mutational and copy number heterogeneity within a primary LPS tumor signifying the importance of multi-region sequencing for cancer-genome guided therapy. In summary, these findings provide insight into the genomic complexity of LPS and highlight potential druggable pathways for targeted therapeutic approach.