Pathology Of Soft Tissue Tumors Research Articles

Soft Tissue and Bone Tumor Diagnostics: Harnessing the Power of Molecular Techniques.

Since the introduction of new molecular techniques, the diagnostic landscape of soft tissue and bone tumors has expanded greatly over the past few years. The use of new molecular techniques has led to the identification of new genetic alterations and, therefore, to a better understanding of tumorigenesis, tumor detection and classification. Furthermore, methylation profiling has emerged as a classification tool for soft tissue and bone tumors. Molecular pathology also plays an important role in the determination of patient prognosis and in the identification of targets that can be used for targeted therapy. As a result, molecular pathology has gained a more prominent role in the daily practice of the surgical pathologist. This review delves into various molecular techniques applied in the surgical pathology of soft tissue and bone tumors. It highlights their applications through the analysis of five specific cases.

Pathology of soft tissue tumours

Pathology of soft tissue tumours

[Advances in clinical and molecular pathology of soft tissue tumors].

软组织肿瘤亚型众多，且肉瘤性病变恶性程度高、预后差，给临床诊治带来巨大挑战。随着以二代测序为代表的高通量分子检测手段的开展和应用，基于分子异常的软组织肿瘤新病种也在不断涌现，以往一些分化不明或未分化的肿瘤经过二代测序也得到了重新认识，软组织肿瘤的分类基础正在从形态学分类转向分子分类，在协助病理诊断、临床治疗策略制定和生物学行为预测等方面具有重要价值。.

The contribution of Juan Rosai to the pathology of soft tissue tumors.

SummaryThe conceptual evolution in the field of soft tissue tumor pathology has been mostly driven by a relatively small group of individuals that includes giants of the past and the present such as James Ewing, Raffaele Lattes, Arthur Purdy Stout, Franz Enzinger, Sharon Weiss, Lennart Angervall, Harry Evans, Marku Miettinen, and Christopher Fletcher. Juan Rosai, not only exerted an immense impact on surgical pathology in general, but in consideration of his unique talent in identifying novel clinicopathologic entities, has also contributed remarkably to current understanding of mesenchymal neoplasms. The creation of desmoplastic small round cell tumor certainly ranks among his most relevant efforts, although he actually put his mark on a broad variety of soft tissue lesions, including vascular neoplasms. It would be impossible to include in a single article all the entities that he created or contributed to refine; therefore, this review is limited to a selection of what we believe represent true milestones.

[Focus on the classification and molecular pathology of soft tissue tumors].

[Focus on the classification and molecular pathology of soft tissue tumors].

Soft tissue pathology for the radiologist: a tumor board primer with 2020 WHO classification update.

Radiologists serve an important role in the diagnosis and staging of soft tissue tumors, often through participation in multidisciplinary tumor board teams. While an important function of the radiologist is to review pertinent imaging and assist in the differential diagnosis, a critical role is to ensure that there is concordance between the imaging and the pathologic diagnosis. This requires a basic understanding of the pathology of soft tissue tumors, particularly in the case of diagnostic dilemmas or incongruent imaging and histologic features. This work is intended to provide an overview of soft tissue pathology for the radiologist to optimize participation in multidisciplinary orthopedic oncology tumor boards, allowing for contribution to management decisions with expertise beyond image interpretation.

Pediatric soft tissue tumor pathology: A happy morpho-molecular union

Since its foundation by remarkably talented and insightful individuals, prominently including Pepper Dehner, pediatric soft tissue tumor pathology has developed at an immense rate. The morphologic classification of tumoral entities has extensively been corroborated, but has also evolved with refinement or realignment of these classifications, through accruing molecular data, with many derivative ancillary diagnostic assays now already well-established. Tumors of unclear histogenesis, classically morphologically undifferentiated, are prominent amongst pediatric sarcomas, however, the classes of undifferentiated round- or spindle-cell-tumors-not-otherwise-specified are being dismantled gradually with the identification of their molecular underpinnings. Within recent years, for example, numerous subcategories of 'Ewing-like' round cell sarcoma have emerged. Such advances have provided the basis for novel diagnostic and prognostic sub-classifications. Efforts at defining cell- or lineage-of-origin for several tumor types have produced interesting insights especially for rhabdomyosarcoma. The remarkably early onset of pediatric sarcomas defies the theory necessitating stochastic accumulation of several somatic mutations for cancer development and indeed, these tumors may be remarkably genomically stable, often belying their aggressive nature. Much is coming to light recently regarding the role of epigenetic modifications in the evolution of these sarcomas. Indeed the morphologic features of embryonal tumors generally (not just sarcomas) may be highly reminiscent of arrested differentiation, and given the tight epigenetic regulation of cell fate determination and cell identity maintenance, a theory of epigenetically-driven oncogenesis sits easily with these tumors. The age-delimited distinct biologies of 'pediatric' and adult GIST are intriguing, particularly, the SDH-deficient 'pediatric' form, driven by a metabolic defect, but resulting in epigenetic dysregulation with genome-wide DNA methylation changes. There is little doubt that many of the gaps in our understanding of pediatric sarcoma biology will be filled by a deeper appreciation of the role of dysregulated epigenetics including chromatin biology, perhaps best exemplified in malignant rhabdoid tumor. The field of pediatric soft tissue tumor pathology grows ever more interesting. Importantly though, it must be emphasized, that none of this progress could have occurred, or indeed continue, without the initial step of accurate diagnosis, founded solidly on morphology - thank you Pepper for your unparalleled contributions to this field! The opportunity to be your apprentice for five years has been a bigger and more positive influence than words can express.

Soft tissue tumor pathology: New diagnostic immunohistochemical markers

Recent insights into the pathogenesis of various soft tissue tumors, along with the identification of recurrent molecular alterations characteristic of specific tumor types, have resulted in the development of many diagnostically useful immunohistochemical markers. In some cases, expression of these markers is significantly associated with distinctive clinical and histologic features, which may impart prognostic or predictive information. This review outlines new diagnostic immunohistochemical markers in soft tissue tumor pathology, emphasizing their utility in clinical practice and potential pitfalls, molecular correlates and clinical associations.

Histopathological diagnostic discrepancies in soft tissue tumours referred to a specialist centre: reassessment in the era of ancillary molecular diagnosis.

Introduction. Soft tissue tumour pathology is a highly specialised area of surgical pathology, but soft tissue neoplasms can occur at virtually all sites and are therefore encountered by a wide population of surgical pathologists. Potential sarcomas require referral to specialist centres for review by pathologists who see a large number of soft tissue lesions and where appropriate ancillary investigations can be performed. We have previously assessed the types of diagnostic discrepancies between referring and final diagnosis for soft tissue lesions referred to our tertiary centre. We now reaudit this 6 years later, assessing changes in discrepancy patterns, particularly in relation to the now widespread use of ancillary molecular diagnostic techniques which were not prevalent in our original study. Materials and Methods. We compared the sarcoma unit's histopathology reports with referring reports on 348 specimens from 286 patients with suspected or proven soft tissue tumours in a one-year period. Results. Diagnostic agreement was seen in 250 cases (71.8%), with 57 (16.4%) major and 41 (11.8%) minor discrepancies. There were 23 cases of benign/malignant discrepancies (23.5% of all discrepancies). 50 ancillary molecular tests were performed, 33 for aiding diagnosis and 17 mutational analyses for gastrointestinal stromal tumour to guide therapy. Findings from ancillary techniques contributed to 3 major and 4 minor discrepancies. While the results were broadly similar to those of the previous study, there was an increase in frequency of major discrepancies. Conclusion. Six years following our previous study and notably now in an era of widespread ancillary molecular diagnosis, the overall discrepancy rate between referral and tertiary centre diagnosis remains similar, but there is an increase in frequency of major discrepancies likely to alter patient management. A possible reason for the increase in major discrepancies is the increasing lack of exposure to soft tissue cases in nonspecialist centres in a time of subspecialisation. The findings support the national guidelines in which all suspected soft tissue tumour pathology specimens should be referred to a specialist sarcoma unit.

Selected topics in the pathology of epithelioid soft tissue tumors

Epithelioid morphology, mimicking carcinoma, is a key or defining feature of several soft tissue tumors and may be seen in a wide variety of other tumors. This review will focus on those tumors defined at least in part by their epithelioid morphology, in particular epithelioid sarcoma, epithelioid malignant peripheral nerve sheath tumor, and sclerosing epithelioid fibrosarcoma. The role of loss of the SMARCB1 tumor-suppressor gene in the pathogenesis of these epithelioid soft tissue tumors will be discussed, as will their differential diagnosis with non-mesenchymal tumors, in particular carcinoma and melanoma.

Annual Review Issue: Soft Tissue Tumour Pathology

HistopathologyVolume 64, Issue 1 p. 1-1 Editorial Annual Review Issue: Soft Tissue Tumour Pathology Jason L Hornick, Jason L HornickSearch for more papers by this authorD Chas Mangham, D Chas ManghamSearch for more papers by this author Jason L Hornick, Jason L HornickSearch for more papers by this authorD Chas Mangham, D Chas ManghamSearch for more papers by this author First published: 10 December 2013 https://doi.org/10.1111/his.12335Citations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume64, Issue1January 2014Pages 1-1 RelatedInformation

A current perspective on the role for molecular studies in soft tissue tumor pathology

Soft tissue sarcomas represent an heterogenous group of malignancies. They represent a diagnostic challenge, and their accurate classification impact over treatment options. Sarcomas, similarly to hematologic neoplasm, often harbor relatively specific genetic aberrations, the recognition of which can be used to improved diagnostic accuracy. This review will focus on the clinical relevance of molecular analysis in soft tissue sarcomas, trying to elucidate its role as a diagnostic tool as well as a potential prognostic/predictive marker.

Die neue WHO-Klassifikation und aktuelle Ergebnisse in der Weichteiltumorpathologie

The new World Health Organization (WHO) classification presents a comprehensive description of soft tissue tumors which was published in book format at the beginning of 2013. Changes have been made relating to the allocation of known entities, e.g. undifferentiated sarcomas are formed into a new group and are not longer assigned to the so-called fibrohistiocytic tumors and new subgroups were incorporated, such as nerve sheath tumors and gastrointestinal stroma tumors which were previously included in the tumor classification of other organ systems. This development is important from the practical point of view as most of relevant soft tissue tumors are now summarized and can be found in a single book. This is also related to the rapid increase in knowledge of the genetics and cell biology of soft tissue tumors. At present there is considerable progress in tumor pathology illustrated by the fact that important new findings have been published after completion of the classification, such as those related to the identification of the recurrent NAB2-STAT6 gene fusion in solitary fibrous tumors and the detection of frequent mutations in the promoter of the hTERT gene in malignant melanoma. In this report some new findings and clinically relevant aspects of soft tissue tumor pathology will be presented.

Updates on pathology of soft tissue tumors

在过去的几年中,学者们在发现软组织肿瘤新病种、报道新亚型、深化分子遗传学研究和拓展靶向治疗等方面也取得了较大的进展,不仅给软组织肿瘤的病理诊断和研究带来了新的机遇,也带来了新的挑战.在当下临床各学科都在强调个体化诊治的大背景下,软组织肿瘤的诊治也需要包括外科、肿瘤(内)科、影像诊断科和病理科等在内的多个学科的共同参与,其中病理医师在多学科诊治(multidisciplinary treatment,MDT)模式中的作用至关重要.病理诊断将成为结合形态学、免疫组织化学和分子病理的综合性诊断,不仅仅要作出疾病的诊断,还要为个体化治疗提供充分的信息。

Molecular Pathology of Soft Tissue Tumours: New Insights and Applications

Soft tissue tumours are a heterogeneous group of neoplastic lesions that arise from mesenchymal cells. Classification of these tumours has historically been based on morphology with ancillary histochemical and immunohistochemical techniques. Improved cytogenetic studies and advances in molecular genetics have led to increased understanding of the pathology and classification of these tumours. Genetically, soft tissue tumours can be divided into four categories. These include tumours with reciprocal translocations and otherwise simple karyotypes, tumours with characteristic amplifications, tumours with specific driver mutations, and those with complex karyotypes associated with chromosomal instability. Knowledge of these genetic abnormalities and application of molecular diagnostic techniques such fluorescence in situ hybridisation and mutation screening in histopathological practice is currently driving a revolution in how these tumours are diagnosed and managed.

Soft Tissue Tumour Pathology

HistopathologyVolume 61, Issue s1 p. 214-219 Free Access Soft Tissue Tumour Pathology First published: 30 August 2012 https://doi.org/10.1111/j.1365-2559.2012.04359_25.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume61, Issues1Special Issue: XXIXth Congress of the International Academy of Pathology, 30 September - 5 October 2012, Cape Town, South AfricaOctober 2012Pages 214-219 RelatedInformation

The clinical impact of molecular techniques on diagnostic pathology of soft tissue and bone tumours

Molecular techniques have become quite crucial for diagnostic histopathology. Their application in sarcomas, both in bone as well as in soft tissue, have been quite successful. Being sarcomas quite rare and diagnostically challenging, the use of ancillary molecular diagnostic tools is quite useful. Furthermore, thanks to the results of previous and ongoing research, specific genetic alterations are found to be strongly associated with several distinct mesenchymal lesions. Molecular techniques allow: 1. better disease definition and therefore more accurate diagnostics, 2. identification of molecular predictive and prognostic markers, 3. unravelling novel molecular targets for more specific therapeutic approach and eventual drug development. The pathologist has a crucial role: 1. in selecting the adequate materials for these analyses, 2. choosing the adequate technology for the given questions and 3. in integrating the results of these analyses with the clinico-pathological features to render a final diagnosis. Here we review the major applications of this approach and discuss its use and limits.

Soft Tissue Tumors

In recent years, new tumor entities have been described and previously known tumor types have undergone a reassessment. This article offers an overview of recent developments in the classification and interpretation of soft tissue tumors. Selective review of publications from 1990 until 2008 from the literature database of the Consultation and Referral Center for Soft Tissue Tumors in Jena. The current status of the classification and morphological diagnosis of these tumors is described. The description of the biological behavior of soft tissue tumors has become more detailed with the introduction of two intermediate categories ("intermediate, locally aggressive" and "intermediate, rarely metastasizing"). There have also been some changes in terminology. Previously established terms such as "malignant fibrous histiocytoma" or "hemangiopericytoma" will be used much less often in future, because these tumor types have been reinterpreted. The WHO recommends that highly differentiated liposarcoma be renamed "atypical lipomatous tumor." Molecular diagnostic techniques have become firmly established as an ancillary diagnostic method. The importance of molecular tumor characterization for individually tailored therapy is already becoming clear. Optimal diagnosis is the prerequisite for effective therapy and can be achieved only with state-of-the-art knowledge of the pathology of soft tissue tumors.

Pathology of soft‐tissue tumors: Daily diagnosis, molecular cytogenetics and experimental approach

This article reviews problems in diagnostic pathology and molecular cytogenetics of soft-tissue tumors. Also discussed are the origin of soft-tissue sarcomas and the molecular basis of effective target therapy for sarcomas. Molecular cytogenetic analysis of tumor-specific chromosomal translocations and associated fusion gene transcripts offers a useful adjunct to the diagnosis of soft-tissue tumors, but recent studies have indicated a growing number of fusion gene variations in each tumor type. In pleomorphic sarcoma/malignant fibrous histiocytoma, the alternative lengthening of telomeres (ALT) mechanism may result in formation of anaphase bridges and marked nuclear pleomorphism. The histogenesis of soft-tissue sarcomas has been a matter of controversy. In the present experimental model using s.c. injection of 3-methylcholanthrene in C57BL/6 mice pretreated with bone marrow-transplantation from green fluorescent protein (GFP)-positive green mice, the bone marrow-derived mesenchymal stem cells as well as the tissue-resident mesenchymal cells in the peripheral soft tissues are possible originators of sarcomagenesis. Little is known about a molecular basis of target therapy for sarcomas. Platelet-derived growth factor-BB (PDGF-BB) enhances the invasive activity of malignant peripheral nerve sheath tumor (MPNST) cells through platelet-derived growth factor receptor (PDGFR) phosphorylation, whereas imatinib mesylate inhibited such activity, suggesting that targeting PDGFR-beta may result in the establishment of novel treatment for MPNST. In addition, emmprin is a transmembrane glycoprotein on tumor cells that stimulates peritumoral fibroblasts to produce matrix metalloproteinases (MMP), playing a crucial role in tumor progression, invasion and metastasis. The MMP upregulation mechanism mediated by tumor-associated emmprin may be a potentially useful target in anti-tumor invasion therapy for sarcomas.

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.