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Advances in Anatomic Pathology May 2021Bone tumors are a rare and heterogeneous group of neoplasms that occur in the bone. The diversity and considerable morphologic overlap of bone tumors with other... (Review)
Review
Bone tumors are a rare and heterogeneous group of neoplasms that occur in the bone. The diversity and considerable morphologic overlap of bone tumors with other mesenchymal and nonmesenchymal bone lesions can complicate diagnosis. Accurate histologic diagnosis is crucial for appropriate management and prognostication. Since the publication of the fourth edition of the World Health Organization (WHO) classification of tumors of soft tissue and bone in 2013, significant advances have been made in our understanding of bone tumor molecular biology, classification, prognostication, and treatment. Detection of tumor-specific molecular alterations can facilitate the accurate diagnosis of histologically challenging cases. The fifth edition of the 2020 WHO classification of tumors of soft tissue and bone tumors provides an updated classification scheme and essential diagnostic criteria for bone tumors. Herein, we summarize these updates, focusing on major changes in each category of bone tumor, the newly described tumor entities and subtypes of existing tumor types, and newly described molecular and genetic data.
Topics: Bone Neoplasms; Chondrosarcoma; Humans; World Health Organization
PubMed: 33480599
DOI: 10.1097/PAP.0000000000000293 -
Nature Reviews. Cancer Oct 2020Epigenetic regulation is critical to physiological control of development, cell fate, cell proliferation, genomic integrity and, fundamentally, transcriptional... (Review)
Review
Epigenetic regulation is critical to physiological control of development, cell fate, cell proliferation, genomic integrity and, fundamentally, transcriptional regulation. This epigenetic control occurs at multiple levels including through DNA methylation, histone modification, nucleosome remodelling and modulation of the 3D chromatin structure. Alterations in genes that encode chromatin regulators are common among mesenchymal neoplasms, a collection of more than 160 tumour types including over 60 malignant variants (sarcomas) that have unique and varied genetic, biological and clinical characteristics. Herein, we review those sarcomas in which chromatin pathway alterations drive disease biology. Specifically, we emphasize examples of dysregulation of each level of epigenetic control though mechanisms that include alterations in metabolic enzymes that regulate DNA methylation and histone post-translational modifications, mutations in histone genes, subunit loss or fusions in chromatin remodelling and modifying complexes, and disruption of higher-order chromatin structure. Epigenetic mechanisms of tumorigenesis have been implicated in mesenchymal tumours ranging from chondroblastoma and giant cell tumour of bone to chondrosarcoma, malignant peripheral nerve sheath tumour, synovial sarcoma, epithelioid sarcoma and Ewing sarcoma - all diseases that present in a younger patient population than most cancers. Finally, we review current and potential future approaches for the development of sarcoma therapies based on this emerging understanding of chromatin dysregulation.
Topics: Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Chromatin; Chromatin Assembly and Disassembly; DNA Methylation; Epigenesis, Genetic; Epigenomics; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Sarcoma
PubMed: 32782366
DOI: 10.1038/s41568-020-0288-4 -
Virchows Archiv : An International... Jan 2020Ewing sarcoma (ES) and Ewing-like sarcomas are highly aggressive round cell mesenchymal neoplasms, most often occurring in children and young adults. The identification... (Review)
Review
Ewing sarcoma (ES) and Ewing-like sarcomas are highly aggressive round cell mesenchymal neoplasms, most often occurring in children and young adults. The identification of novel molecular alterations has greatly contributed to a profound reappraisal of classification, to the extent that the category of undifferentiated round cell sarcoma has significantly shrunk. In fact, in addition to Ewing sarcoma, we currently recognize three main categories: round cell sarcomas with EWSR1 gene fusion with non-ETS family members, CIC-rearranged sarcomas, and BCOR-rearranged sarcomas. Interestingly, despite significant morphologic overlap, most of these entities tend to exhibit morphologic features predictive of the underlying molecular alteration. Ewing sarcoma is the prototype of round cell sarcoma whereas in CIC sarcomas, focal pleomorphism and epithelioid morphology can predominate. BCOR sarcomas often exhibit a spindled neoplastic cell population. NFATC2 sarcoma may exhibit remarkable epithelioid features, and PATZ1 sarcomas often feature a sclerotic background. The differential diagnosis for these tumors is rather broad, and among round cell sarcomas includes alveolar rhabdomyosarcoma, desmoplastic small round cell tumor, poorly differentiated round cell synovial sarcoma, small cell osteosarcoma, and mesenchymal chondrosarcoma. A combination of morphologic, immunohistochemical, and molecular findings allows accurate classification in most cases. A granular diagnostic approach to Ewing sarcoma and Ewing-like sarcomas is justified by significant differences in terms of both response to chemotherapy and overall survival. As all these entities are in part defined by specific fusion genes, a molecular diagnostic approach based on NGS technology should be considered. In consideration of the extreme rarity of many of these tumor entities, referral to expert rare cancer centers or to rare cancer networks represents the best strategy in order to minimize diagnostic inaccuracy, and allow proper patient management.
Topics: Bone Neoplasms; Diagnosis, Differential; Homeodomain Proteins; Humans; Immunohistochemistry; Proto-Oncogene Proteins; RNA-Binding Protein EWS; RNA-Binding Protein FUS; Repressor Proteins; Sarcoma, Ewing
PubMed: 31802230
DOI: 10.1007/s00428-019-02720-8 -
Indian Journal of Otolaryngology and... Dec 2022Mass lesions of the larynx are one of the most common clinical entity which we come across in routine otorhinolaryngology and head neck practice with varied...
Mass lesions of the larynx are one of the most common clinical entity which we come across in routine otorhinolaryngology and head neck practice with varied symptomatology. Among all the mass lesions of the larynx, Epithelial neoplasms constitute up to 97%. Mesenchymal tumours of the larynx constitute only 0.3-1.0% of all the laryngeal tumors. Abundance of cartilage structures in the larynx made it a spot for mesenchymal tumors [chondromas and chandrosacrcomas]. The spectrum of mesenchymal neoplasms can vary from chondromas, chondroblastoma to chondrosarcoma. Here we want to share our experience of a mesenchymal tumour of the larynx. This case is reported for the rarity and ambiguity in diagnosis. Though these are slow-growing tumours with an early presentation, in our case, the patient had a supportive tracheostomy without definitive treatment for more than 2 years. We managed this patient by excising the mass by lateral pharyngotomy with the preservation of larynx followed by successful Decannulation in 20 days.
PubMed: 36742506
DOI: 10.1007/s12070-020-02308-8 -
The Journal of the American Academy of... Jul 2021Chondrosarcoma is the second most common primary bone tumor, with >90% of cases representing the primary conventional subtype. In addition to arising de novo,...
Chondrosarcoma is the second most common primary bone tumor, with >90% of cases representing the primary conventional subtype. In addition to arising de novo, conventional chondrosarcoma can arise secondary to a benign underlying lesion, such as enchondroma or osteochondroma. Symptoms are often characterized by focal, dull, aching pain to the affected region. Grade is a well-recognized prognostic factor in these tumors. Grade I lesions/atypical cartilaginous tumors rarely metastasize, rarely recur, and have a 10-year survival rate of >80%. By contrast, grade III lesions are associated with a poor prognosis with the highest local recurrence rates, a lung metastasis rate of >50%, and a 10-year survival rate of <30%. The standard treatment of high-grade conventional chondrosarcoma is complete surgical resection with wide margin. However, low-grade lesions may be amenable to curettage plus or minus adjuvant local treatment. Conventional chondrosarcoma does not respond to chemotherapy or standard radiation doses. Adjuvant treatment can be beneficial for some subtypes such as chemotherapy for dedifferentiated and mesenchymal chondrosarcoma and radiation additionally for mesenchymal chondrosarcoma. Emerging radiation technologies may also play a useful role in treating tumors in anatomically complex areas such as the spine or pelvis.
Topics: Bone Neoplasms; Chondrosarcoma; Curettage; Humans; Neoplasm Recurrence, Local; Osteochondroma; Prognosis; Retrospective Studies
PubMed: 33595238
DOI: 10.5435/JAAOS-D-20-01188 -
Seminars in Diagnostic Pathology May 2021The SWItch Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex is a large multi-subunit protein assembly that orchestrates chromatin compaction and... (Review)
Review
The SWItch Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex is a large multi-subunit protein assembly that orchestrates chromatin compaction and accessibility for gene transcription in an ATP-dependent manner. As a key epigenetic regulator, the SWI/SNF complex coordinates gene expression, cell proliferation and differentiation, and its biologic functions, in part, antagonize the polycomb repressive complex 2. The mammalian SWI/SNF complex consists of 15 subunits encoded by 29 genes, some of which are recurrently mutated in human cancers, in the germline or sporadic setting. Most SWI/SNF-deficient tumors share common "rhabdoid" cytomorphology. SMARCB1 (INI1) is the subunit most frequently inactivated in soft tissue neoplasms. Specifically, SMARCB1 deficiency is observed as the genetic hallmark in virtually all malignant rhabdoid tumors, and most cases of epithelioid sarcoma and poorly differentiated chordoma. In addition, subsets of myoepithelial carcinoma (10-40%), extraskeletal myxoid chondrosarcoma (20%), epithelioid schwannoma (40%), and epithelioid malignant peripheral nerve sheath tumor (70%) demonstrate SMARCB1 loss. The gene encoding the SS18 subunit is involved in the SS18-SSX rearrangement, which is pathognomonic of synovial sarcoma and indirectly inactivates SMARCB1. Finally, undifferentiated SMARCA4-deficient thoracic sarcomas are defined by SMARCA4 subunit inactivation, leading to SMARCA4 and SMARCA2 loss. Rarely, inactivation of alternate but biologically equivalent key regulators can substitute for canonical subunit deficiency, such as SMARCA4 inactivation in cases of SMARCB1-retained epithelioid sarcoma. This review briefly highlights SWI/SNF complex biologic functions and its roles in human cancer and provides a detailed update on recent advances in soft tissue neoplasms with canonical SWI/SNF complex deficiency, correlating morphologic, genomic, and immunohistochemical findings.
Topics: Chromosomal Proteins, Non-Histone; DNA Helicases; Humans; Immunohistochemistry; Nuclear Proteins; Rhabdoid Tumor; Soft Tissue Neoplasms; Sucrose; Transcription Factors
PubMed: 32646614
DOI: 10.1053/j.semdp.2020.05.005 -
Surgical Pathology Clinics Dec 2021Chondrosarcomas are heterogeneous matrix-producing cartilaginous neoplasms with variable clinical behavior. Subtypes include conventional (75%), dedifferentiated (10%),... (Review)
Review
Chondrosarcomas are heterogeneous matrix-producing cartilaginous neoplasms with variable clinical behavior. Subtypes include conventional (75%), dedifferentiated (10%), clear cell (2%), mesenchymal (2%), and periosteal chondrosarcoma (<1%). Tumor location and primary vs secondary also play a role. In conventional chondrosarcoma, histologic grading (I, II, and III) remains the gold standard for predicting recurrence and metastases. Due to the locally aggressive but overall nonmetastatic behavior, grade I chondrosarcomas (primary and secondary) of long and short tubular bones have been reclassified as atypical cartilaginous tumor. In this review, the pathologic features of malignant cartilage tumors are discussed with updates on recent genetic findings.
Topics: Bone Neoplasms; Cartilage; Chondrosarcoma; Humans
PubMed: 34742483
DOI: 10.1016/j.path.2021.06.005