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1.
Genes Chromosomes Cancer ; 62(10): 581-588, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37057757

RESUMEN

Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain differentiation predominantly arising in deep soft tissue. Its conventional morphologic appearance manifests as a relatively well-circumscribed, multilobular tumor composed of uniform short spindle-to-ovoid primitive mesenchymal cells with deeply eosinophilic cytoplasm arranged in anastomosing cords within abundant myxoid matrix. The genetic hallmark of EMC has long been considered to be pathognomonic gene rearrangements involving NR4A3, which when fused to TAF15, often have high-grade morphology with increased cellularity, moderate to severe cytologic atypia, and rhabdoid cytomorphology. Herein, we describe two cases of EMC with TAF15::NR4A3 fusion that appear morphologically distinct from both conventional and high-grade EMC. Both cases had an unusual biphasic appearance and showed diffuse positivity for p63, mimicking myoepithelial tumors. DNA methylation profiling demonstrated that both cases clearly cluster with EMC, indicating that they most likely represent morphologically distinct variants of EMC. The clinical significance and prognostic impact of this morphologic variance remains to be determined. Molecular testing, including DNA methylation profiling, can help to confirm the diagnosis and avoid confusion with mimics; it adds another layer of data to support expanding the morphologic spectrum of EMC.

2.
Mod Pathol ; 36(11): 100301, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37567448

RESUMEN

Adamantinoma-like Ewing sarcoma (ALES) has traditionally been considered a variant of Ewing sarcoma because it generally harbors EWSR1::FLI1 fusions despite showing diffuse positivity for keratins and p40. However, it has become increasingly recognized that different tumors can have identical translocations, including shared fusions between carcinomas and sarcomas, raising questions as to whether ALES might represent a separate entity. Using methylation profiling, we further explored the relationship between Ewing sarcoma and ALES. The archives of multiple institutions were searched for candidate cases of ALES. DNA methylation profiling was performed and results were compared to corresponding data from conventional Ewing sarcoma. Twelve cases of ALES (5 previously reported) were identified in 10 men and 2 women (aged 20-72 years; median age, 41.5 years). Cases included tumors arising in the parotid gland (3), sinonasal cavity (2), submandibular gland (2), thyroid gland (1), neck (1), gingiva (1), hypopharynx (1), and mandible (1). Histologic review consistently showed sheets and nests of basaloid cells within a fibromyxoid or hyalinized stroma. All tumors were positive for at least 1 keratin and CD99 expression, whereas all 10 cases tested were positive for p63 or p40; S100 protein expression was noted in 2 cases. Cases harbored either EWSR1::FLI1 fusions (n = 6), FUS::FLI1 fusions (n = 1), and/or EWSR1 rearrangements (n = 6). Methylation profiling was successful in 11/12 cases evaluated. Unsupervised clustering and dimensionality reduction (Uniform Manifold Approximation and Projection) of DNA methylation data revealed a distinct methylation cluster for all 11 cases, including the tumor with the FUS::FLI1 fusion, which clearly segregated them from the conventional Ewing sarcoma. Follow-up (n = 11, 1-154 months) revealed that 4 patients experienced recurrence and 6 developed metastatic disease. ALES demonstrates a distinct methylation signature from conventional Ewing sarcoma. This finding adds to the distinctive immunoprofile of ALES, suggesting that these 2 tumors should be considered distinct entities rather than histologic extremes of the same disease.


Asunto(s)
Adamantinoma , Sarcoma de Ewing , Sarcoma , Masculino , Humanos , Femenino , Adulto , Sarcoma de Ewing/genética , Sarcoma de Ewing/patología , Adamantinoma/genética , Adamantinoma/patología , Metilación de ADN , Proteína EWS de Unión a ARN/genética , Sarcoma/genética , Reordenamiento Génico , Proteínas de Fusión Oncogénica/genética
3.
Semin Diagn Pathol ; 40(4): 238-245, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37147159

RESUMEN

The diagnosis of mesenchymal neoplasms arising in the superficial soft tissue can be challenging as some entities are rare and show overlapping features. Moreover, the spectrum of mesenchymal tumours has expanded recently to include potential new entities, some of which have been described after the 5th edition of the World Health Organisation (WHO) classification of soft tissue and bone tumours published in 2020. In the skin and superficial soft tissue, tumours of epidermal, melanocytic and appendageal origin are more commonly encountered than mesenchymal neoplasms. However, specific entities from the latter category can occasionally express epithelial markers on immunohistochemistry, some of them in a strong and diffuse manner. It is therefore crucial to be aware of diagnostic pitfalls when encountering cytokeratin positivity in superficial soft tissue neoplasms. This article provides an overview on the differential diagnosis of these mesenchymal tumours that can sporadically occur also in the skin, including myoepithelial neoplasms, epithelioid sarcoma, keratin positive giant cell tumour of soft tissue / xanthogranulomatous epithelial tumour, superficial CD34-positive fibroblastic tumour / PRDM10-rearranged soft tissue tumour, and perineurioma.


Asunto(s)
Neoplasias Óseas , Sarcoma , Neoplasias Cutáneas , Neoplasias de los Tejidos Blandos , Humanos , Inmunohistoquímica , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias Óseas/patología , Biomarcadores de Tumor
4.
Skeletal Radiol ; 51(5): 957-970, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34562125

RESUMEN

Giant cell tu mour accounts for up to 5% of all bone tumours and malignant giant cell tumour arises in < 10% of cases, representing sarcomatous transformation. Primary malignant giant cell tumour of bone occurs when sarcomatous tissue is observed within conventional giant cell tumour histologically on initial presentation. Secondary malignant giant cell tumour of bone occurs in a region of previously treated giant cell tumour, with most cases arising due to prior radiotherapy. Malignancy in giant cell tumour of bone does not have any unique clinical or imaging features compared to conventional aggressive disease. Historically, malignant giant cell tumour of bone has a poor prognosis which is worse in cases of secondary malignancy. This article aims to present the clinical, pathological and imaging features of MGCTB based on a review of the literature and illustrated by examples from our experience.


Asunto(s)
Neoplasias Óseas , Tumor Óseo de Células Gigantes , Sarcoma , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patología , Tumor Óseo de Células Gigantes/diagnóstico por imagen , Tumor Óseo de Células Gigantes/patología , Humanos
5.
Skeletal Radiol ; 51(6): 1189-1199, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34714386

RESUMEN

OBJECTIVE: To determine whether MRI can distinguish atypical cartilaginous tumour/grade 1 peripheral/periosteal chondrosarcoma (ACT/Gd1 PP-CS) from high-grade peripheral/periosteal chondrosarcoma (HG-PP-CS) or dedifferentiated peripheral/periosteal chondrosarcoma (DD-PP-CS). MATERIALS AND METHODS: Retrospective review of patients diagnosed between January 2007 and December 2020 who had undergone resection of PP-CS. Data collected included age, sex, and skeletal location. Histological tumour grades based on surgical resection were classified as ACT/grade 1 PP-CS, HG-PP-CS, or DD-PP-CS. A variety of MRI features were reviewed independently by 2 musculoskeletal radiologists blinded to final diagnosis and compared between the 3 groups. For statistical analysis, HG-PP-CS and DD-PP-CS were combined. RESULTS: Fifty-eight patients fulfilled the inclusion criteria, 31 (53%) males and 27 (47%) females with a mean age at diagnosis of 46.1 years (range 11-83 years), 14 (24%) of whom had an underlying diagnosis of diaphyseal aclasis. Forty-one (70.7%) cases were peripheral and 17 (29.3%) periosteal, 38 (66%) involving the flat bones, 15 (26%) the major long bones, 3 (5%) the spine, and 2 (3%) the bones of the hands and feet. Final histology revealed 33 (57%) ACT/Gd1-PP-CS, 18 (31%) HG-PP-CS, and 7 (12%) DD-PP-CS. Periosteal tumours were 16 times more likely to be HG/DD-CS compared to peripheral tumours (p < 0.001). Intra-medullary tumour extension was predictive of HG/DD-CS (p = 0.004) for both tumour types, while cap thickness (p = 0.04) and a diffuse cap type (p = 0.03) were differentiating features of low-grade and high-grade peripheral CS. DISCUSSION: A variety of features can help differentiate low-grade from high-grade peripheral/periosteal CS, the most significant being origin from the bone surface.


Asunto(s)
Neoplasias Óseas , Condrosarcoma , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/patología , Huesos/patología , Niño , Condrosarcoma/diagnóstico por imagen , Condrosarcoma/patología , Femenino , Humanos , Hiperplasia/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Columna Vertebral/patología , Adulto Joven
6.
Skeletal Radiol ; 50(8): 1491-1511, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33410967

RESUMEN

Rare primary bone sarcomas are challenging entities both radiologically and pathologically. These include the diagnoses of spindle cell sarcoma (leiomyosarcoma, fibrosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor), pleomorphic liposarcoma, and undifferentiated pleomorphic sarcoma. The radiographic and cross-sectional imaging features of each of these tumors are presented, along with current key pathological concepts. Frequently non-specific, the radiological appearances must be correlated with all clinical and pathological information available to enable an accurate diagnosis.


Asunto(s)
Fibrosarcoma , Leiomiosarcoma , Liposarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Sarcoma/diagnóstico por imagen
7.
Skeletal Radiol ; 50(10): 1921-1940, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33787962

RESUMEN

The non-Langerhans cell histiocytoses (N-LCH) represent a group of rare diseases with different clinical presentations and imaging features to classical LCH. While there is a long list of entities, only few present with musculoskeletal soft tissue and osseous manifestations alongside the more commonly reported systemic findings. Erdheim-Chester disease (ECD) is typically seen in adults as bilateral and symmetrical long bone osteosclerosis. Rosai-Dorfman disease (RDD) is more commonly seen in children and young adults with bone involvement usually being a manifestation of extra-nodal disease. Primary osseous RDD is very rare, with both displaying rather non-specific imaging features of an expansile lucent lesion with or without an extra-osseous component. Juvenile xanthogranuloma (JXG) is a benign disorder typically seen in very young children. The most common imaging manifestation is a dermal or sub-dermal soft tissue mass. This article reviews the musculoskeletal imaging appearances of the commoner N-LCH.


Asunto(s)
Enfermedad de Erdheim-Chester , Histiocitosis de Células de Langerhans , Histiocitosis Sinusal , Preescolar , Diagnóstico por Imagen , Enfermedad de Erdheim-Chester/diagnóstico por imagen , Humanos , Cintigrafía
8.
Skeletal Radiol ; 50(10): 1963-1980, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33792747

RESUMEN

Myxoid liposarcoma (MLS) accounts for approximately 30% of all liposarcomas. The majority are intermediate-grade tumours, but the presence of >5% round cell component renders it a high-grade sarcoma with subsequent poorer outcome. MLS most commonly arises in the lower extremities, has a predilection for extra-pulmonary sites of metastatic disease, and is recognized to be radiosensitive. The purpose of the current article is to review the role of MRI in the management of MLS, including the characteristic features of the primary tumour, features which help to identify a round cell component and thus determine prognosis, the role of whole-body MRI for evaluation of extra-pulmonary metastatic disease, and the utility of MRI for assessing treatment response. The MRI differential diagnosis of MLS is also considered.


Asunto(s)
Liposarcoma Mixoide , Liposarcoma , Adulto , Humanos , Liposarcoma Mixoide/diagnóstico por imagen , Extremidad Inferior , Imagen por Resonancia Magnética , Pronóstico , Estudios Retrospectivos
9.
Pathology ; 55(3): 324-328, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36707318

RESUMEN

Cemento-osseous dysplasia (COD) belongs to the spectrum of benign fibro-osseous lesions occurring exclusively in the tooth-bearing areas of the jaws. Depending on site and extent of involvement, periapical, focal and florid subtypes can be distinguished that share an identical histomorphology. Most cases are asymptomatic and follow a self-limited course requiring no specific treatment. Over time, lesions progressively mineralise while the cellularity decreases. However, the molecular pathogenesis of COD, has not yet been explored. We analysed a series of 31 COD samples by targeted sequencing and detected pathogenic hotspot mutations involving the RAS-MAPK signalling pathway in 5/18 evaluable cases (28%). The mutations were found in the BRAF, HRAS, KRAS, NRAS, and FGFR3 genes. Our findings suggest that COD is driven by RAS-MAPK activation; however, the mechanism underlying the spontaneous growth arrest typically occuring in most of the lesions remains elusive.


Asunto(s)
Tumores Odontogénicos , Humanos , Mutación , Transducción de Señal , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas ras/metabolismo
10.
Pathology ; 55(5): 621-628, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37225644

RESUMEN

Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive tumour of soft tissue and bone that is defined by an underlying and highly specific fusion transcript involving HEY1 and NCOA2. Histologically, the tumours show a biphasic appearance consisting of an undifferentiated blue and round cell component as well as islands of highly differentiated cartilage. Particularly in core needle biopsies, the chondromatous component can be missed and the non-specific morphology and immunophenotype of the round cell component can cause diagnostic challenges. We applied NKX3.1 immunohistochemistry which was recently reported as a highly specific marker as well as methylome and copy number profiling to a set of 45 well characterised MCS cases to evaluate their potential diagnostic value. Methylome profiling revealed a highly distinct cluster for MCS. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. NKX3.1 immunohistochemistry showed positivity in 36% of tumours, the majority of which was rather focal and weak. Taken together, NKX3.1 expression showed a low sensitivity but a high specificity in our analysis. Methylome profiling on the other hand represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. Furthermore, it can aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.


Asunto(s)
Neoplasias Óseas , Condrosarcoma Mesenquimal , Humanos , Condrosarcoma Mesenquimal/diagnóstico , Condrosarcoma Mesenquimal/genética , Condrosarcoma Mesenquimal/patología , Inmunohistoquímica , Epigenoma , Huesos/patología , Diferenciación Celular , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/genética , Neoplasias Óseas/patología
11.
J Pathol Clin Res ; 9(6): 464-474, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37555357

RESUMEN

Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma).


Asunto(s)
Neoplasias Óseas , Querubismo , Condroblastoma , Tumor Óseo de Células Gigantes , Granuloma de Células Gigantes , Humanos , Querubismo/diagnóstico , Querubismo/genética , Querubismo/patología , Granuloma de Células Gigantes/diagnóstico , Granuloma de Células Gigantes/genética , Granuloma de Células Gigantes/patología , Condroblastoma/diagnóstico , Condroblastoma/genética , Condroblastoma/patología , Metilación de ADN , Células Gigantes/patología , Tumor Óseo de Células Gigantes/diagnóstico , Tumor Óseo de Células Gigantes/genética , Tumor Óseo de Células Gigantes/patología , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Maxilares/patología
12.
Front Oncol ; 12: 954717, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35875137

RESUMEN

The craniofacial skeleton is a highly complex and specialized anatomic region containing and protecting the brain and sensory organs. Bone sarcomas arising here comprise a heterogeneous group of tumours, some of which differ in their biological behaviour compared to their peripheral counterparts. The reasons for this seem to lie, at least partially, in the embryonal development of the craniofacial bones. For reaching the correct diagnosis as the cornerstone of optimal personalised treatment planning, a multidisciplinary team of specialists, including pathologists, radiologists, oncologists, and head and neck surgeons needs to be involved. The most common tumours arising in the craniofacial bones are bone-forming tumours, cartilage-forming tumours, fibro-osseous lesions, giant cell-rich lesions, and notochordal tumours. While morphology remains the backbone for the diagnosis, the last decade has witnessed tremendous advances in the molecular characterization of tumours, and molecular testing is increasingly becoming a part of the diagnostic process. The integration of these new molecular markers into the diagnostic approach has undoubtedly increased the diagnostic accuracy and objectivity, and holds great promise to also identify new therapeutic targets for precision medicine in the future. Examples include HEY1-NCOA2 in mesenchymal chondrosarcoma, IDH1/2 mutations in chondrosarcoma and TFCP2 rearrangements in rhabdomyosarcoma. In this article, key clinical, histological and molecular features of malignant bone tumours arising in the craniofacial region are discussed, with a special focus on the differential diagnosis and prognostic considerations.

13.
Front Oncol ; 12: 1086677, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36578930

RESUMEN

Mesenchymal chondrosarcoma is a rare and aggressive sarcoma subtype with high risk for distant metastases and poor prognosis. Currently NCCN- and ESMO-Guidelines recommend using Ewing sarcoma protocols as standard treatment. Nevertheless, in localized disease overall 5-year survival rates are below 50% whereas in metastatic spread median progression-free survival rates of only 5 months can be expected. Here we present a patient with metastatic osseous spread of mesenchymal chondrosarcoma that showed a sustained clinical improvement and a good partial response on imaging over a period of one year when treated with the multi-tyrosine kinase inhibitor cabozantinib. Although we cannot explain the exact mechanism underlying this treatment effect, tumors with similar genetic patterns might respond to the same therapy as well.

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