Dedifferentiated Liposarcoma of the Deep (Paralaryngeal) Soft Tissue: Lessons Learnt from a Case with a Partly Deceptively Benign Appearing Dedifferentiated Component

We present a case (female, 61 years of age) of dedifferentiated liposarcoma of the deep, cervical (paralaryngeal) soft tissue with a significant myxoid component and characteristic immunohistochemical (strong and diffuse expression of p16, mdm2 and cdk4 in both the well differentiated liposarcomatous and dedifferentiated components) and molecular genetic findings (MDM2-gene amplification on fluorescence in situ hybridization). The myxoid component which was present in the well differentiated liposarcomatous component gave the tumor atypical radiological features. The case presented initial diagnostic difficulties, mainly because of the bland histomorphological appearance of the limited biopsy material from the sampled non-lipogenic, dedifferentiated component. The dedifferentiated part of the tumor turned out to harbor significant heterogeneity with regards to cellularity, cytomorphology and proliferative activity.     

Dedifferentiated melanomas: Morpho-phenotypic profile,genetic reprogramming and clinical implications

Phenotypic plasticity of malignant melanoma is a well-known phenomenon. Several translational studies and small case series have reported this clinical and biological entity, particularly in metastatic melanoma, showing frequent aberrant expression of non-melanocytic differentiation markers of different lineages, posing remarkable challenges due to several alternative differential diagnoses including undifferentiated carcinoma and sarcomas. When melanoma loses its typical morpho-phenotype by routinely used diagnostic immunohistochemical markers, it is defined as “dedifferentiated melanoma”. Historically, this process was closely related to diagnostic interpretative difficulties. In recent years, however, dedifferentiation has been increasingly recognized as an important biological phenomenon that demonstrates the phenotypic and genetic plasticity of melanoma, and specifically the non-irreversibility of the multistep cancerogenesis. Furthermore, dedifferentiation emerged as a general hallmark of cancer evolution and a common denominator of cross-resistance to both targeted and immunotherapy. In this review, we summarize the histopathological features, the genetic and epigenetic bases underlying the dedifferentiated phenotype in melanomas and provide additional support that dedifferentiation is a mechanism of resistance to immunotherapy and targeted therapy.     

Dedifferentiated liposarcoma of the rectum: A case report

Liposarcoma is one of the most common soft tissue sarcomas found in adults, and it usually occurs in the retroperitoneum and the extremities. Here, we describe a case of dedifferentiated liposarcoma originating from a well-differentiated liposarcoma of the mesorectum that presented as a protruding mass in the rectal lumen. Hartmann’s operation with total mesorectal excision was performed and the tumor was removed radically. No management guidelines are currently available for liposarcoma of the rectum. We propose that complete surgical resection be required for the treatment of rectal liposarcoma and that a long-term detailed follow up is necessary.     

去分化脂肪细胞与脂肪来源干细胞体内成脂能力比较的初步研究

目的 通过比较去分化脂肪细胞(dedifferentiated adipocytes,DA)与脂肪来源干细胞(adipose-derived stem cells,ASCs)在体内的成脂分化能力,为脂肪组织工程筛选出成脂效率高的种子细胞.方法 取健康女性脂肪抽吸术的抽吸物,使用酶消化法获取成熟脂肪细胞及脂肪来源干细胞,采用天花板贴壁法培养成熟脂肪细胞使其去分化,获取去分化脂肪细胞,各取第3代细胞进行实验.将两种细胞分别与纤维蛋白胶(fibrin glue,FG)支架体外混合培养,光镜及扫描电镜检测细胞与支架的相容性;DiI荧光染料标记细胞,将DiI标记过的细胞支架复合物(DA-FG组,去分化脂肪细胞-支架,n=8;ASCs-FG组,脂肪来源干细胞-支架,n=8)以及空白支架(空白FG组,n=8)注射于裸鼠皮下.术后8周将新生组织取出,进行大体观察和湿重测定,HE染色、H染色和油红"O"染色后进行组织学观察、纤维化比率测定以鉴定新生物的性质、来源.结果 成熟脂肪细胞经天花板贴壁法培养后变为长梭形成纤维细胞状,即去分化脂肪细胞,脂肪来源干细胞呈长梭形.细胞-支架复合物体外培养3 d后光镜及扫描电镜检测发现细胞在支架上生长良好.术后8周DA-FG、ASCs-FG组裸鼠背部皮下均有新生组织块形成,经检测后证实其为成熟脂肪块并来源于植入的种子细胞,DA-FG组新生物平均湿重大于ASCs-FG组,平均纤维化比率则低于ASCs-FG组;空白FG组无新生组织形成,支架被降解吸收.结论 去分化脂肪细胞与脂肪来源干细胞均可作为种子细胞在裸鼠皮下构建出脂肪组织,较之脂肪来源干细胞,去分化脂肪细胞构建出的组织块具有湿重大,纤维化比率低的优点.     

脂肪来源细胞在缺血性心脏病中的应用

 脂肪来源细胞（褐色脂肪来源细胞、脂肪干细胞和去分化脂肪细胞）可分化成心肌样细胞,移植后可改善心梗后心功能,降低心室重塑,有可能成为最有潜力的治疗缺血性心脏病的干细胞来源。     

Dedifferentiated Chondrosarcoma: An Ultrastructural Study of Two Cases, with Immunocytochemical Correlations

The clinicopathologic features of two cases of dedifferentiated chondrosarcoma (DCS) are presented, in which anaplastic components showed the electron microscopic features of malignant fibrous histiocytoma, as well as immunoreactivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Rare cells also displayed S100 protein in high-grade areas of the primary tumors, but a pulmonary metastasis lacked this determinant. These findings could be interpreted as reflecting a retained potential for primitive chondrogensis in primary DCS, which may be lost in its metastases. In all other respects, this tumor appears to assume the morphological and immunocytochemical attributes of a fibrohistiocytic neoplasm.     

Atypical lipomatous tumor/well-differentiated liposarcoma of the extremity and trunk wall: Importance of histological subtype with treatment recommendations

Background This study defines the behavior and classification of atypical lipomatous tumors (ALT) and well-differentiated liposarcomas (WDLS) of the extremity and trunk. Methods A total of 91 well-differentiated lipomatous tumors of the extremity and trunk were identified from a soft tissue tumor database between July 1982 and June 2001. A soft tissue pathologist, blinded to prior diagnosis and clinical outcome, reviewed histology. Those composed predominantly of mature adipose tissue with scattered atypical stromal cells and scant lipoblasts or fibrosis were ALTs. Tumors with lipoblast but <25% fibrosis were termed lipoma-like WDLS, and those with >-25% fibrosis were identified as sclerosing WDLS. Clinical factors were analyzed to assess effects on local recurrence-free survival (LRFS). Results Histological review identified 34 ALTs and 57 WDLSs. Of the WDLSs, 29 were lipoma-like and 28 were sclerosing. Five-year and 10-year LRFS were 100%±0% and 78%±9%, respectively. Factors evaluated were age, sex, tumor site, tumor size, histology, presentation status, margin status, and adjuvant radiotherapy. Positive resection margins and sclerosing histology were associated with reduced LRFS. Dedifferentiation was observed in three tumors (3%) Conclusions Lipoma-like WDLSs and ALTs share similar histological features and favorable behavior. Margin-positive sclerosing WDLSs have a 10-year LRFS of only 17% and should undergo function-preserving re-excision when possible, or adjuvant radiotherapy.     

Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of a dedifferentiated chondrosarcoma

We investigated a dedifferentiated chondrosarcoma of a 61-year-old woman with an osteosarcomatous high-grade component for p53 alteration. The low-grade cartilaginous and the high-grade osteosarcomatous components of the tumor were macrodissected and evaluated separately by immunohistochemistry and molecular biology. We used PCR-SSCP analysis and direct sequencing to screen exons 4–8 for p53 mutations. The p53 intron 1-polymorphism was investigated for loss of heterozygosity. A functionally relevant p53 missense mutation in codon 193 of exon 6 (A-to-T transversion) with loss of wild-type allele was detected only in the dedifferentiated component. Using the monoclonal antibody DO-1, immunohistochemistry failed to show p53 overexpression. This evidence of p53 mutation may be regarded as at least a co-factor that ”switched” the preexisting low-grade conventional chondrosarcoma to a highly malignant dedifferentiated tumor. Received: 24 August 1999 / Accepted: 9 November 1999     

维甲酸诱导失分化型甲状腺癌的观察

应用全反式维甲酸(ATRA)诱导失分化型甲状腺癌(dDTC)患者,5例患者(5/9,55.6%)ATRA诱导有效;5例患者(5/8,62.5%)131I治疗获益.3例患者(3/12,25.O%)因神经系统的不良反应,不能耐受而放弃ATRA诱导.ATRA是诱导dDTC分化的有效方法,可以提高dDTC病灶的摄碘能力,但使用中应关注ATRA的不良反应.