Alveolar soft tissue sarcoma

Clinical and morphological manifestations of alveolar soft tissue sarcoma (ASTS) are presented on the basis of 19 examinations performed by the authors and data available in the literature. ASTS has been found to be more common in young women and to be usually located in the thick layers of the proximal parts of the extremities. The tumor generally shows slow growth and late occurrence of metastases. It has been demonstrated that ASTS has an organoid structure, namely alveolar grouping of cells, abundance of capillaries, and its cells contain PAS-positive inclusions. In atypical ASTS, the prognosis has been found to be less favourable. The crystalloid inclusions that are absent in other soft tissue neoplasms are a characteristic ultrastructural sign of ASTS. The genesis of ASTS remains controversial but it cannot be ruled out that it is related to the elements of the APUD-system.     

New therapeutic targets in soft tissue sarcoma

Soft tissue sarcomas are an uncommon and diverse group of more than 50 mesenchymal malignancies. The pathogenesis of many of these is poorly understood, but others have begun to reveal the secrets of their underlying mechanisms. With considerable effort over recent years, soft tissue sarcomas have increasingly been classified on the basis of underlying molecular alterations. In turn, this has allowed the development and application of targeted agents in several specific, molecularly defined, sarcoma subtypes. This review will focus on the rationale for targeted therapy in sarcoma, with emphasis on the relevance of specific molecular factors and pathways in both translocation-associated sarcomas and in genetically complex tumors. In addition, we will address some of the early successes in sarcoma-targeted therapy as well as a few challenges and disappointments in this field. Finally, we will discuss several possible opportunities represented by poorly understood, but potentially promising new therapeutic targets, as well as several novel biological agents currently in preclinical and early phase I/II trials. This will provide the reader with the context for understanding the current state of this field and a sense of where it may be headed in the coming years.     

Intranuclear filaments in a soft tissue sarcoma

Intranuclear filaments aggregating into rodlike structures were found in cells of an undifferentiated soft tissue sarcoma in a child. Similar structures have been uncommonly described in human neoplasms, and uncertainties exist concerning the nature of the inclusion bearing cells in previous reports. The filaments were found to be resistant to mild trypsin digestion. Review of the pertinent literature indicates that these structures may represent the structural manifestation of a highly specialized functional state, rather than a degenerative phenomenon or an artifact. A certain selectivity of occurrence has also been noted. It is therefore plausible to speculate that intranuclear filaments may eventually constitute a morphologic criterion of interest for new tumor classifications.     

Cutaneous sporotrichosis presenting as soft tissue sarcoma

Sporotrichosis is not an uncommon disease. Lymphocutaneous involvement is the common characteristic but systemic dissemination from the primary skin lesion has been observed. The disease is progressive but spontaneous resolution, in rare instances, has been observed. Multiple, fungating, ulcerated, tumorous cutaneous lesions, fixed to the underlying tissue, often pose a difficult diagnostic problem, as in this case. The disease has been frequently related to occupational exposure to plant life, but handling of infected animals may be a source of infection in rare instances.     

Recommendations for the reporting of soft tissue sarcoma

 The Association of Directors of Anatomic and Surgical Pathology has developed recommendations for the surgical pathology reporting of common malignant tumors. The recommendations for soft tissue sarcomas are reported herein. Received: 14 August 1998 / Accepted: 9 November 1998     

臀大肌下间隙软组织肉瘤屏障切除术相关问题探讨

目的　探讨臀大肌下间隙软组织肉瘤屏障切除术可行性和并发症的防治。 方法　⑴对3具6侧成人臀部标本的臀肌筋膜、臀大肌下间隙各壁组成、臀上动脉、坐骨神经出盆处进行解剖观察。⑵对15例臀部软组织肉瘤屏障切除术的治疗结果进行分析。 结果　（1）臀大肌下间隙各壁的肌肉、肌腱、韧带、筋膜对软组织肉瘤生长具有屏障作用。（2）臀上动脉出盆处并不游离,在坐骨大孔内缘1 cm左右有一层致密的纤维结缔组织包绕固定臀上动脉。（3）坐骨神经与梨状肌下孔之间间隙较疏松,表面有一层脂肪组织。（4）15例病例,术后随访6~36个月,平均24个月,12例无瘤生存,2例出现转移而死亡,1例复发后放弃治疗。所有病人术后均出现程度不等的下肢跛行。3例臀上血管损伤出血,咬除部分髂骨骨质结扎止血。 结论 （1）屏障切除术适用于臀大肌下间隙软组织肉瘤;（2）臀上动脉的损伤可以通过切除部分髂骨骨质进行结扎止血。     

Unravelling undifferentiated soft tissue sarcomas: insights from genomics

Undifferentiated pleomorphic sarcoma now falls under the broader rubric of undifferentiated soft tissue sarcoma (USTS) in the 2020 World Health Organization classification of bone and soft tissue tumours. These rare cancers remain a diagnosis of exclusion, and show genomic complexity manifesting as extreme forms of aneuploidy and genetic rearrangement. This review covers some of the recent advances in the diagnosis and treatment of USTS based on genomic sequencing, cancer evolution and heterogeneity studies, and immunotherapy. We highlight the critical role that pathologists have to play in the diagnosis and treatment of patients with USTS, viewed through the lens of the hallmarks of cancer.     

Metastases of malignant melanoma simulating soft tissue sarcoma

Summary Metastases of cutaneous malignant melanoma (MM) of ordinary type can resemble various types of soft tissue sarcoma light microscopically to a degree which has not been previously recognized. Twenty-one cases are described, in which the tumours were originally diagnosed as a soft tissue sarcoma. Seven tumours were predominantly of blue and spindle-cell, fascicular type, resembling malignant peripheral nerve sheath tumour and at times monophasic synovial sarcoma. Ten tumours which were of fascicular and predominantly storiform type, and included uni- and multi-nuleated pleomorphic cells resembled malignant fibrous histiocytoma. Due to the presence of multivacuolated lipoblast-like tumour cells, 2 of these 10 tumours resembled pleomorphic liposarcoma. One had a predominantly myxoid and hypocellular appearance and 5 additional tumours included such areas. The diagnoses were revised after ultrastructural examination with the demonstration of melanosomes in 13 of 16 studied cases and the immunohistochemical demonstration of positivity using anti-S-100 protein antibodies and the anti-melanoma antibody NKI/C3 in all cases. The anti-melanoma antibody HMB 45 gave a positivity in 9 of 21 cases. Light microscopically, sparse amounts of melanin were noted in 7 tumours using the Whartin-Starry technique. Eleven tumours occurred at sites close to major lymph node groups and in 9 of these cases, lymphoid tissue was associated with the tumours, suggesting that they represented lymph node metastases. Following a review of the patients' clinical histories and renewed clinical examination, primary cutaneous MM was demonstrated in 10 of 21 patients and in 1 case an MM in regression was detected. The origin of the 10 tumours without a detected primary is discussed, including the possibility of an overlooked primary, spontaneous regression of a primary and a de novo origin from lymph nodes and soft tissues.Case 2 presented by one of us (L. Angervall) at the Slide Seminar on Soft Tissue Tumors with Special Emphasis on Modern Techniques (Chairman: F.M. Enzinger), Symposium Management of Soft Tissue and Bone Sarcomas, European Organisation for Research on Treatment of Cancer (EORTC), Utrecht, The Netherlands, June 1984Case 1 presented by one of us (L.-G. Kindblom) at the Soft Tissue Tumors Slide Seminar (Chairmen: L. Angervall and J. Costa), The XII European Congress of Pathology, Porto, Portugal, September 1989     

The role of genetic testing in soft tissue sarcoma

Soft tissue tumours represent a heterogeneous group of mesenchymal lesions and their classification continues to evolve as a result of incorporating advances in cytogenetic and molecular techniques. In the last decade traditional diagnostic approaches were supplemented with a significant number of reliable molecular diagnostic tools, detecting tumour type-specific genetic alterations. In addition, the successful application of some of these techniques to formalin-fixed paraffin-embedded tissue made it possible to subject a broader range of clinical material to molecular analysis. Thus, molecular genetics has already become an integral part of the work-up in some tumours, such as paediatric small blue round cell tumours, which demonstrate characteristic translocations. Several lines of evidence suggest that sarcomas can be divided into two major genetic groups: (i) sarcomas with specific genetic alterations and usually simple karyotypes, such as reciprocal chromosomal translocations (e.g. FUS-DDIT3 in myxoid liposarcoma) and specific oncogenic mutations (e.g. KIT mutation in gastrointestinal stromal tumours); and (i) sarcomas with non-specific genetic alterations and complex unbalanced karyotypes. Some of these genetic abnormalities, including chromosomal numerical changes, translocations, gene amplifications or large deletions can be apparent at the cytogenetic level (karyotyping, fluorescence in situ hybridization), while others, such as small deletions, insertions or point mutations, require molecular genetic techniques (polymerase chain reaction and sequence analysis). This review focuses on the applicability of genetic testing in the diagnosis and prognosis of soft tissue sarcomas, and gives a realistic appraisal of the ancillary role of molecular techniques, including its advantages and limitations.     

Surgical margins in soft tissue sarcoma of the extremities

Negative surgical margins (R0 resection) play a key role in the prevention of local recurrences of soft tissue sarcoma of the extremities in the multimodal therapy concept. The prognostic relevance for long-term survival is still under dispute. Despite the fact that numerous recommendations and guidelines have existed for over 100?years, strong evidence-based data from prospective randomized studies are still not available today. These studies should include parameters like tumor localization, subtype and biological aggressiveness. Recommendations as to surgical therapy diverge considerably. They range from amputation and compartment resection to centimetre and millimetre surgical margins. The present article analyses currently available data and definitions and discusses the impact on functional restriction, lymph drainage, local recurrence and the perioperative irradiation field. In the absence of surgical standards, it is doubtful whether existing studies and multicenter trials currently underway are valid. Close co-operation between surgeon and pathologist is imperative to further substantiate the significance of histological examinations and resection margins.     

Cell marker studies in undifferentiated soft tissue sarcoma.

100 cases of undifferentiated soft tissue sarcomas were studied using cell markers by immunoperoxidase technique with DAB as substrate. Vimentin, Desmin, Myoglobin, Actin, Keratin, Epithelial Membrane Antigen, S-100 protein, F VIII R Ag, A1 Antitrypsin, A1 Antichymotrypsin, Collagen-IV and UEA-1 lectin were used as markers. Fibrosarcoma was consistently positive for Vimentin and Collagen-IV. The undifferentiated Rhabdomyosarcoma showed strong and consistent positivity for Vimentin Actin and Myoglobin. Desmin positivity was the hallmark of leiomyosarcoma, whereas the malignant schwannomas were identified by their S-100 positivity. This marker along with A1AT and A1ACT reactivity was of great use in the identification of malignant fibrous histiocytoma. Angiosarcoma/malignant haemangioendothelioma could be identified with great accuracy by their strong positivity for F VIII RAg and UEA-1 lectin. Other miscellaneous sarcomas also could be identified by their specific reactivity to the markers used. We consider immunohistochemistry to be an important and essential adjunct to routine stains in the diagnosis of undifferentiated soft tissue sarcomas.     

软组织肉瘤染色体易位机制研究进展

软组织肉瘤种类繁多 ,形态各异 ,长期以来一直是病理诊断中的难点。细胞遗传学研究相继发现多种软组织肉瘤存在特征性的染色体易位。这些染色体易位引起相应染色体上的基因发生断裂 ,并形成新的融合基因 ,且编码融合蛋白 ,融合基因的检测已成为诊断这些肿瘤的敏感的分子手段(表 1) [1] 。目前的研究主要集中于这些融合蛋白功能的研究上 ,大多数融合蛋白属于融合性转录因子或辅助因子 ,在特定肿瘤的发生中可能起重要作用。软组织肉瘤染色体易位发生机制的研究尚少 ,有一些问题尚待阐明 ,如染色体易位的发生是随机的还是有内在规律 ?发生易位…     

Human DNA damage checkpoints and their relevance to soft tissue sarcoma

Soft tissue sarcoma (STS) is a malignant neoplasm, arising in mesenchymal tissues, that is difficult to treat clinically because it can be highly resistant to chemo-radiotherapy. At present, the mechanism of that resistance remains unclear. Cell cycle checkpoints engender strict control of cell proliferation, arresting the cell cycle to provide time for repair or apoptosis when DNA damage is induced by unprogrammed extrinsic events. These pathways involve at least two checkpoints: one at the G1/S transition and one at the G2/M transition. The p53 gene, which is mutated in several malignant tumors, plays an important role in DNA repair at the G1/S transition; however, there is little information on the G2/M checkpoint in STS. In the present study, several proteins (phospho-p53, -cdc25, -cdc2, -Chk1 and -Chk2) involved in checkpoint pathways were investigated using immunohistochemistry in STS specimens. Most STSs maintain a well-preserved G2/M checkpoint despite the loss of the G1/S checkpoint (phospho-p53: 4.9% (2/41); -cdc25: 41% (17/41); -cdc2: 61% (25/41); -Chk1: 29% (12/41); -Chk2: 46% (19/41)). Furthermore, in a postoperative chemotherapy case the number of cells positive for phospho-cdc25 and -Chk2 was higher in a recurrent tumor than in the primary tumor (n = 7, P  = 0.046 < 0.05, Wilcoxon signed-ranks test). These findings indicate that the G2/M checkpoint pathway is well preserved and might contribute to the chemotherapeutic resistance associated with STS.