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Alterations in kinase genes such as NTRK1/2/3, RET, and BRAF underlie infantile fibrosarcoma (IFS), the emerging entity 'NTRK-rearranged spindle cell neoplasms' included in the latest WHO classification, and a growing set of tumors with overlapping clinical and pathological features. In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other kinase gene-altered spindle cell neoplasms affecting both pediatric and adult patients. Follow-up periods for 16 patients ranged in length from 10 to 130 months (mean 38 months). Six patients were treated with targeted therapy, achieving a partial or complete response in five cases. Overall, three cases recurred and one metastasized. Eight patients were free of disease, five were alive with disease, and two patients died. All cases showed previously reported morphological patterns. Based on the cellularity and level of atypia, cases were divided into three morphological grade groups. S100 protein and CD34 were at least focally positive in 12/22 and 14/22 cases, respectively. Novel PWWP2A::RET, NUMA1::RET, ITSN1::RAF1, and CAPZA2::MET fusions, which we report herein in mesenchymal tumors for the first time, were detected by RNA sequencing. Additionally, the first uterine case with BRAF and EGFR mutations and CD34 and S100 co-expression is described. DNA sequencing performed in 13 cases uncovered very rare additional genetic aberrations. The CNV profiles showed that high-grade tumors demonstrate a significantly higher percentage of copy number gains and losses across the genome compared with low- and intermediate-grade tumors. Unsupervised clustering of the tumors' methylation profiles revealed that in 8/9 cases, the methylation profiles clustered with the IFS methylation class, irrespective of their clinicopathological or molecular features. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Fibrossarcoma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias de Tecidos Moles , Adulto , Humanos , Criança , Receptor trkA/genética , Proteínas Proto-Oncogênicas B-raf/genética , Recidiva Local de Neoplasia/genética , Fibrossarcoma/genética , Fibrossarcoma/patologia , Neoplasias de Tecidos Moles/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Proteínas de Fusão Oncogênica/genéticaRESUMO
AIMS: Spindle-cell/sclerosing rhabdomyosarcomas (SS-RMS) are clinically and genetically heterogeneous. They include three well-defined molecular subtypes, of which those with EWSR1/FUS::TFCP2 rearrangements were described only recently. This study aimed to evaluate five new cases of SS-RMS and to perform a clinicopathological and statistical analysis of all TFCP2-rearranged SS-RMS described in the English literature to more comprehensively characterize this rare tumour type. METHODS AND RESULTS: Cases were retrospectively selected and studied by immunohistochemistry, fluorescence in situ hybridization with EWSR1/FUS and TFCP2 break-apart probes, next-generation sequencing (Archer FusionPlex Sarcoma kit and TruSight RNA Pan-Cancer Panel). The PubMed database was searched for relevant peer-reviewed English reports. Five cases of SS-RMS were found. Three cases were TFCP2 rearranged SS-RMS, having FUSex6::TFCP2ex2 gene fusion in two cases and triple gene fusion EWSR1ex5::TFCP2ex2, VAX2ex2::ALKex2 and VAX2intron2::ALKex2 in one case. Two cases showed rhabdomyoblastic differentiation and spindle-round cell/sclerosing morphology, but were characterized by novel genetic fusions including EWSR1ex8::ZBTB41ex7 and PLOD2ex8::RBM6ex7, respectively. In the statistical analysis of all published cases, CDKN2A or ALK alterations, the use of standard chemotherapy and age at presentation in the range of 18-24 years were negatively correlated to overall survival. CONCLUSION: EWSR1/FUS::TFCP2-rearranged SS-RMS is a rare rhabdomyosarcoma subtype, affecting predominantly young adults with average age at presentation 34 years (median 29.5 years; age range 7-86 years), with a predilection for craniofacial bones, rapid clinical course with frequent bone and lung metastases, and poor prognosis (3-year overall survival rate 28%).
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Rabdomiossarcoma , Fatores de Transcrição , Adulto Jovem , Criança , Humanos , Adulto , Adolescente , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hibridização in Situ Fluorescente , Estudos Retrospectivos , Fatores de Transcrição/genética , Proteína EWS de Ligação a RNA/genética , Rabdomiossarcoma/genética , Rabdomiossarcoma/patologia , Fusão Gênica , Biomarcadores Tumorais/genética , Proteínas de Ligação a RNA/genética , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética , Proteínas de Ligação a DNA/genéticaRESUMO
Chordoma is a rare malignant tumor with notochordal differentiation, usually affecting the axial skeleton of young patients. We report a case of a high-grade epithelioid tumor involving the synovium and soft tissues of the knee in a 74-year-old male patient. The preliminary biopsy was inconclusive, but a diagnosis of metastatic clear-cell carcinoma of unknown origin was suggested. However, imaging studies did not reveal any primary lesions. The resection specimen consisted of nests and sheets of oval to polygonal cells with discernible cell borders, clear or lightly amphophilic cytoplasm, and round to oval nuclei with occasional well-visible eosinophilic nucleoli. Rare atypical mitoses, necrotic areas, and bizarre nuclei were noted. The biopsy and resection specimens underwent a wide molecular genetic analysis which included methylation profiling. The DKFZ sarcoma classifier assigned the methylation class chordoma (dedifferentiated) with a calibrated score of 0.96, and additionally, a loss of SMARCB1 locus was noted in the copy number variation plot. To verify these findings, T-brachyury and SMARCB1 immunostaining was performed afterward, showing diffuse nuclear positivity and complete loss in the tumor cells, respectively. To assess the prevalence of T-brachyury immunopositivity among SWI/SNF-deficient tumors and to evaluate its specificity for poorly differentiated chordoma, we analyzed a series of 23 SMARCB1- or SMARCA4-deficient tumors, all of which were negative. After incorporating all the available data, including the absence of any morphological features of conventional chordoma, the case was diagnosed as poorly differentiated chordoma. As illustrated herein, the utilization of methylation profiling in the diagnostic process of some carefully selected unclassifiable soft tissue neoplasms may lead to an increased detection rate of such extremely rare soft tissue tumors and enable their better characterization.
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Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain lineage. Insulinoma-associated protein 1 (INSM1) has recently been described as a highly specific and sensitive immunohistochemical marker for EMC. The goal of this study was to evaluate the diagnostic significance of INSM1 immunohistochemistry in EMC. Furthermore, correlations between molecular and morphological findings were performed. Sixteen of 17 EMC cases were stained with the INSM1 antibody. Tumors with at least 5% INSM1-positive cells and any staining intensity were considered positive. Molecular testing was successfully performed in 12/17 cases. The immunohistochemical analysis detected 13 INSM1-positive (81%) and 3 INSM1-negative tumors (19%). The extent of the staining was classified as 1+ in 7 cases (44%), 2+ in 2 cases (13%), 3+ in 2 cases (13%) and 4+ in 2 cases (13%). Intensity of immunostaining was weak in 5 cases (31%), moderate in 2 cases (13%) and strong in 6 cases (38%). Molecular assays revealed 8 EWSR1::NR4A3 positive tumors (67%), 2 TAF15::NR4A3 positive tumors (17%), 1 TCF12::NR4A3 positive tumor (8%) and 1 NR4A3 positive tumor (8%) in which no other gene alteration was identified. Two of them, namely TCF12 positive and one TAF15 positive tumors, were highly cellular and partially associated with pseudopapillary architecture. Our study found that moderate/strong expression of INSM1 in more than 25% of tumor cells was present in only 31% of cases. Thus, the diagnostic utility of INSM1 is rather low. Two morphologically unique cases of non-EWSR1 rearranged EMC with an extremely rare pseudopapillary growth pattern are also reported.
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Condrossarcoma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Receptores de Esteroides , Sarcoma , Humanos , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Condrossarcoma/diagnóstico , Condrossarcoma/genética , Sarcoma/genética , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Proteínas Repressoras/genética , Proteínas de Ligação a DNA/genética , Receptores de Esteroides/genética , Receptores dos Hormônios Tireóideos/genéticaRESUMO
GLI1 fusions involving ACTB, MALAT1, PTCH1 and FOXO4 genes have been reported in a subset of malignant mesenchymal tumors with a characteristic nested epithelioid morphology and frequent S100 positivity. Typically, these multilobulated tumors consist of uniform epithelioid cells with bland nuclei and are organized into distinct nests and cords with conspicuously rich vasculature. We herein expand earlier findings by reporting a case of a 34-year-old female with an epithelioid mesenchymal tumor of the palate. The neoplastic cells stained positive for S100 protein and D2-40, whereas multiple other markers were negative. Genetic alterations were investigated by targeted RNA sequencing, and a PTCH1-GLI1 fusion was detected. Epithelioid mesenchymal tumors harboring a PTCH1-GLI1 fusion are vanishingly rare with only three cases reported so far. Due to the unique location in the mucosa of the soft palate adjacent to minor salivary glands, multilobulated growth, nested epithelioid morphology, focal clearing of the cytoplasm, and immunopositivity for S100 protein and D2-40, the differential diagnoses include primary salivary gland epithelial tumors, in particular myoepithelioma and myoepithelial carcinoma. Another differential diagnostic possibility is the ectomesenchymal chondromyxoid tumor. Useful diagnostic clues for tumors with a GLI1 rearrangement include a rich vascular network between the nests of neoplastic cells, tumor tissue bulging into vascular spaces, and absence of SOX10, GFAP and cytokeratin immunopositivity. Identifying areas with features of GLI1-rearranged tumors should trigger subsequent molecular confirmation. This is important for appropriate treatment measures as PTCH1-GLI1 positive mesenchymal epithelioid neoplasms have a propensity for locoregional lymph node and distant lung metastases.
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Mioepitelioma , Neoplasias das Glândulas Salivares , Neoplasias de Tecidos Moles , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Mioepitelioma/patologia , Palato Mole/patologia , Proteínas S100 , Neoplasias de Tecidos Moles/patologia , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismoRESUMO
The knowledge of clinical features and, particularly, histopathological spectrum of EWSR1-PATZ1-rearranged spindle and round cell sarcomas (EPS) remains limited. For this reason, we report the largest clinicopathological study of EPS to date. Nine cases were collected, consisting of four males and five females ranging in age from 10 to 81 years (average: 49 years). Five tumors occurred in abdominal wall soft tissues, three in the thorax, and one in the back of the neck. Tumor sizes ranged from 2.5 to 18 cm (average 6.6 cm). Five patients had follow-up with an average of 38 months (range: 18-60 months). Two patients had no recurrence or metastasis 19 months after diagnosis. Four patients developed multifocal pleural or pulmonary metastasis and were treated variably by surgery, radiotherapy, and chemotherapy. The latter seemed to have little to no clinical benefit. One of the four patients was free of disease 60 months after diagnosis, two patients were alive with disease at 18 and 60 months, respectively. Morphologically, low, intermediate, and high-grade sarcomas composed of a variable mixture of spindled, ovoid, epithelioid, and round cells were seen. The architectural and stromal features also varied, resulting in a broad morphologic spectrum. Immunohistochemically, the following markers were most consistently expressed: S100-protein (7/9 cases), GFAP (7/8), MyoD1 (8/9), Pax-7 (4/5), desmin (7/9), and AE1/3 (4/9). By next-generation sequencing, all cases revealed EWSR1-PATZ1 gene fusion. In addition, 3/6 cases tested harbored CDKN2A deletion, while CDKN2B deletion and TP53 mutation were detected in one case each. Our findings confirm that EPS is a clinicopathologic entity, albeit with a broad morphologic spectrum. The uneventful outcome in some of our cases indicates that a subset of EPS might follow a more indolent clinical course than previously appreciated. Additional studies are needed to validate whether any morphological and/or molecular attributes have a prognostic impact.
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Biomarcadores Tumorais/genética , Fatores de Transcrição Kruppel-Like/genética , Proteína EWS de Ligação a RNA/genética , Proteínas Repressoras/genética , Sarcoma/genética , Neoplasias de Tecidos Moles/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Criança , Europa (Continente) , Feminino , Fusão Gênica , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Sarcoma/química , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/química , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Resultado do Tratamento , Estados UnidosRESUMO
Dermatofibrosarcoma protuberans is a quite rare local aggressive tumor of dermis and subcutis, revealing characteristic morphology and chromosomal translocation (17; 22)(q21;q13) with gene fusion COL1A1-PDGFB. The tumour almost never metastasizes and complete excision signs an excellent prognosis. Approximately in 10% of cases, dermatofibrosarcoma undergoes a fibrosarcomatous transformation associated with metastatic disease and worse prognosis. In this paper, we refer a case of a male patient with subcutaneous tumor in back region, in which the small biopsy lead to diagnosis of a spindle cell sarcoma. However, only the histopathological examination of the entire tumor in the material from the radical surgery detected the dermatofibrosarcoma protuberans with fibrosarcomatous transformation. Both components of the tumor showed the characteristic genetic alteration. Identification of fibrosarcomatous component within the DFSP matters in prognosis. Distinction between fibrosarcoma arising within the dermatofibrosarcoma protuberans and fibrosarcoma arising de novo is of therapeutic consequence: the patients with metastatic or inoperable DFSP with fibrosarcomatous transformation may profit form imatinib treatment.
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Dermatofibrossarcoma , Fibrossarcoma , Neoplasias Cutâneas , Dermatofibrossarcoma/tratamento farmacológico , Dermatofibrossarcoma/patologia , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/patologia , Humanos , Mesilato de Imatinib/uso terapêutico , Masculino , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Translocação GenéticaRESUMO
35-year-old woman suffered prolonged pain in the left shoulder, where an aggressively growing tumor of the proximal humerus was revealed thereafter. The lesion caused massive osteolysis of the metaepiphysis with cortical disruption, but no soft tissue extension was evident. Given the unsatisfactory effect, the ongoing neoadjuvant chemotherapy was prematurely ceased and the resection 13 cm long segment of bone with modular prosthesis replacement followed. Histologically, clear-cut malignant tumor with both the presence of numerous reactive osteoclast-like giant cells and geographic structural deposition of chondroid matrix bore a close resemblance to chondroblastoma. Dominant cellular composition formed solid mosaic clusters of large, atypical, frequently binucleated cells with voluminous eosinophilic cytoplasm. Impressive nuclear pleomorphism was accentuated by both the grooving and atypical mitotic figures. Thorough sampling disclosed limited, but sharply contrasting parts, where biphasic arrangement of small uniform stromal elements together with regularly distributed, reactive osteoclasts suggested putative precursor giant cell lesion. Except the osteoclasts, all matrical and stromal cells were strongly SOX9 and D2-40 positive; in contrary desmin, SATB2, S100 and p63 yielded completely negative results. Detected H3F3A c.103G>T mutation in exon 2 finally established true nature of that peculiar neoplastic proliferation and lead to descriptive term of primary chondroblastoma-like malignant giant cell tumor. In the setting of all the microscopic variability, histogenesis and complex differential diagnosis of skeletal (malignant) giant cell lesions, there are discussed e.g. aggressive/malignant chondroblastoma, chondroblastoma-like osteosarcoma or giant cell-rich osteosarcoma and practical impact of specific mutational analysis results as well.
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Neoplasias Ósseas , Condroblastoma , Tumores de Células Gigantes , Proteínas de Ligação à Região de Interação com a Matriz , Osteossarcoma , Adulto , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/cirurgia , Condroblastoma/complicações , Condroblastoma/diagnóstico , Condroblastoma/cirurgia , Feminino , Tumores de Células Gigantes/complicações , Tumores de Células Gigantes/diagnóstico , Tumores de Células Gigantes/cirurgia , Humanos , Úmero , Osteossarcoma/complicações , Osteossarcoma/diagnóstico , Osteossarcoma/cirurgia , Fatores de TranscriçãoRESUMO
Myositis ossificans (MO) and fibro-osseous pseudotumor of digits (FOPD) are localized, self-limiting bone-producing pseudosarcomatous lesions characterized by nodular fasciitis-like proliferation and osteoid and immature woven bone production, which may eventually develop into more mature lamellar bone. Traditionally, MO and FOPD were thought to be of reactive, non-neoplastic nature. USP6 gene rearrangement was recently reported as a consistent finding in MO and FOPD, thus expanding the spectrum of transient, USP6-rearranged neoplasms. COL1A1 was described as the fusion partner of USP6 in a subset of MO cases, but the fusion partners of USP6-rearranged FOPD have not been uncovered so far. Initially, we carefully reviewed all 27 cases of MO/FOPD from our archives, documenting the remarkable morphological overlap between both lesions. Sixteen cases were seen in consultation, and our review was requested to rule in or rule out tentative diagnoses by referring pathologists. Malignant diagnosis (osteosarcoma) was suggested by the submitting pathologists in 3 cases, whereas 7 cases were sent by the referring pathologists to "rule out sarcoma." In the following step, using next-generation sequencing, we confirmed the COL1A1-USP6 rearrangement in 5/7 cases of MO and found the same abnormality in 4/5 of FOPD. Overall, 9 of the 12 analyzable cases (75%) of MO and FOPD harbored this gene fusion. The presence of COL1A1-USP6 gene rearrangement in MO/FOPD links these lesions to other USP6-driven tumors and represents a very useful supportive marker, which may help to avoid overdiagnosis of MO/FOPD as a sarcoma.
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Colágeno Tipo I/genética , Rearranjo Gênico/genética , Doenças Musculoesqueléticas/genética , Miosite Ossificante/genética , Ubiquitina Tiolesterase/genética , Adulto , Doenças Ósseas/genética , Criança , Pré-Escolar , Cadeia alfa 1 do Colágeno Tipo I , Diagnóstico Diferencial , Extremidades , Fasciite/genética , Fasciite/patologia , Feminino , Fibroblastos/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/patologia , Miosite Ossificante/patologiaRESUMO
INTRODUCTION: Secretory breast carcinoma (SBC) is a rare breast tumor which accounts for < 0.15% of all breast cancers. It was originally described as a juvenile breast carcinoma, occurring in young children and adolescent women. SBC is associated with a characteristic balanced translocation, t(12;15), that creates aETV6-NTRK3 gene fusion. PRESENTATION OF CASE: A 52-year-old Caucasian woman had palpable lump in her right breast. After breast imaging examination (BI-RADS 4b) and preoperative core-needle biopsy with suspicion of SBC a breast conserving therapy was performed. The diagnosis of SBC was confirmed through immunohistochemistry and cytogenetic examination of the tumor. The patient is now 22 months postsurgery and remains diseasefree. DISCUSSION: Recent studies reported that the disease occurs at a later age than previously recognized, and is associated with good long-term survival. In breast imaging it may mimic a benign tumor. Immunohistochemistry and cytogenetic analysis of the tumor are crucial for confirmation of SBC. CONCLUSION: There is no consensus with regard to the best treatment strategy for patients with SBC. Breast conserving therapy with sentinel lymph nodes biopsy is at present the first choice treatment. Further research for a specific NTRK3 tyrosine kinase inhibitor could lead to the discovery of a new targeted treatment of this tumor.
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The term "idiopathic calcifying tenosynovitis" (ICT) refers to a clinically and radiologically defined syndrome of pain and tendinous calcifications, most often involving the shoulder joint. A distinctive subset of ICT cases, termed "tenosynovitis with psammomatous calcifications" (TPC), occurs in the distal extremities and shows characteristic morphology, in particular psammomatous calcifications. As only 14 cases have been reported to date, TPC remains poorly recognized by both pathologists and clinicians. Twenty-three well-characterized cases of TPC along with all available radiologic and clinical information, including follow-up, were collected. Cases occurred in 21 females and 1 male (1 patient of unknown sex), aged 16 to 75 years (mean: 41), and almost exclusively involved the fingers and toes, except for one case in the elbow and one in the knee joint. The lesions ranged from 2 to 30 mm in size (mean: 10 mm). Pain was the most common presenting symptom (12/16 patients). A history of trauma or repetitive activity was present in 6 of 15 patients. None of the individuals was known to have disorders in calcium or phosphate metabolism. Radiographic studies showed a nonspecific, calcified mass. Typical morphologic features of TPC were invariably present, with degenerating tendinous tissue containing psammomatous calcifications, surrounded by a variably cellular, CD68/CD163/CD4-positive histiocyte-rich granulomatous host reaction. HUMARA assay in one case showed a polyclonal pattern. Clinical follow-up (19 patients; mean: 5.2 y; range: 1 to 14 y) showed no local recurrences. In this, the largest study of TPC to date, we confirm striking predilection of this distinctive pseudoneoplasm for the fingers and toes of young to middle-aged women. TPC should be rigorously distinguished from other forms of ICT, which typically involve large, proximal joints, and show simply dystrophic calcification involving tendinous tissues, and from tumoral calcinosis, which also involves large joints and often is associated with calcium and/or phosphate abnormalities. TPC appears to be related to trauma and/or repetitive activity and is cured with simple excision.
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Calcinose/patologia , Tenossinovite/patologia , Adolescente , Adulto , Idoso , Extremidades/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The literature is reviewed regarding of a rare molecularly defined group of sarcomas with rearrangement of both CIC and BCOR genes, which were originally placed into the EWSR1wt Ewing-like category. Personal experience with three cases demonstrating difficulties of this issue is added. Both groups of lesions differ not only by age and topography, but also vary in both the prognostic and the predictive parameters. CIC-rearranged tumors are very aggressive and almost never occur in the skeleton; in contrary, the BCOR-rearranged ones are predominantly bone tumors in young males behaving even better than classical Ewing sarcoma. From the morphologic point of view, it turned out to be a salient finding that these types of neoplasm might leave canonical morphotype of small blue round cell sarcoma. Instead of it, they are not uncommonly characterized as a relatively uniform spindle cell proliferation with prevailing myxoid transformation deserving much broader differential diagnosis. Our three cases reports display difficulties in reaching the correct diagnosis even by implementing sophisticated molecular techniques in routine practice. Notwithstanding of exhaustive molecular assays used, one may still encounter a lesion where original descriptive term Ewing-lie sarcoma remains uncorrected.
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Rearranjo Gênico , Sarcoma de Ewing , Sarcoma de Células Pequenas , Neoplasias de Tecidos Moles , Biomarcadores Tumorais , Humanos , Masculino , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/genética , Sarcoma de Células Pequenas/diagnóstico , Sarcoma de Células Pequenas/genética , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genéticaRESUMO
Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumor of subcutaneous tissue characterized by slow infiltrative growth. The tumor occurs in patients of all ages, with the highest frequency occurring between the second and the fifth decades of age. Genetically, DFSP is characterized by a reciprocal translocation t(17;22)(q22;q13), or more often, as a supernumerary ring chromosome involving chromosomes 17 and 22. Standard treatment of a localized tumor is surgical excision with wide margins. In the present study, a case report of a 43-year-old woman with a growing tumor in the left breast is discussed. The patient underwent breast-conserving surgery. Histological and cytogenetic examinations of the tumor resulted in a diagnosis of DFSP. The clinical and morphological characteristics of the tumor, in addition to the treatment options, were also evaluated.
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Presented is a case of 59-year-old woman with longstanding neck pain who has been promptly operated for spinal cord compression. Imaging studies disclosed ill-defined cervical paravertebral soft tissue mass at the level of vertebra C5/6 abutting left-sided intervertebral joint and destroying neighboring both vertebral arch and processus spinosus. Submitted specimen was interpreted as a possible metastatic skeletal process by clinicians and referring pathologist favored diagnosis of giant cell tumor/osteoclastoma of the bone. Microscopic features were consistent with giant cell lesion where uniform mononuclear mosaic stromal component dominated the unevenly distributed loose clusters of osteoclast-like giant cells frequently imparting appearance of peculiar pseudoalveolar spaces. Additionally, alternating geographic xanthomatous and densely hyalinized/ osteoid-like zones with speckled, coarsely granular haemosiderin pigment completed the variegated structural composition. The tumor infiltrated adjacent striated muscles; either original bone structures and/or extracellular matrix deposits were not identified. Immunohistochemical stains with p63, SATB2, desmin, EMA, clusterin and S100protein turned out to be completely negative. FISH analysis revealed no rearrangement of CSF1 gene. The diagnosis of the diffuse tenosynovial giant cell tumor was rendered.
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Vértebras Cervicais/patologia , Cervicalgia/patologia , Neoplasias de Tecidos Moles/patologia , Sinovite Pigmentada Vilonodular/patologia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Descompressão Cirúrgica , Feminino , Humanos , Pessoa de Meia-Idade , Cervicalgia/diagnóstico por imagem , Cervicalgia/cirurgia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/cirurgia , Sinovite Pigmentada Vilonodular/diagnóstico por imagem , Sinovite Pigmentada Vilonodular/cirurgia , Resultado do TratamentoRESUMO
The authors present five cases of periosteal osteosarcoma located in the femur (4) and tibia (1) in children and young adults (1 female and 4 males) with an age range of 9 - 23 years (mean age 15 years). Radiographs in all cases showed a broad-based soft tissue mass attached to the cortex with periosteal reaction and in two of them cortical disruption with extensive medullary involvement. Follow-ups were available in four cases (range 11 - 73 months) and revealed pelvic metastasis after 15 months with ultimately rapid dissemination and death in a 9-year-old girl and metastasis to the humerus after 13 months in a 15-year-old boy. The former tumor widely extended into the medullary cavity and an amputation was carried out, the latter had a pure juxtacortical position and an en block resection was performed; both of them were treated with chemotherapy. All the lesions displayed distinctive structural patterns combining a large island of tumorous cartilage and hypocellular, bland-looking myxoid mesenchymal stroma with abrupt transition between both components. Contrary to conventional osteosarcoma, the delicate flocculent osteoid deposits were produced by innocuous stromal cells lacking apparent atypia. They were strictly situated outside the prevailing chondroid areas and disclosed sometimes only after a meticulous search. Immunohistochemical detection of SATB2, S100protein and D2-40 assisted effectively not only in recognition of the real stromal histogenetic derivation, but also in distinction of true differentiation of a heavily mineralized extracellular matrix. Molecular analysis revealed no IDH1/2 mutation in four examined cases. Regardless of unique low-grade morphology in rare periosteal osteosarcoma, an aggressive therapeutical approach similar to conventional osteosarcoma is justified, particularly in the case of a medullary extension.
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Neoplasias Ósseas/patologia , Osteossarcoma/patologia , Periósteo/patologia , Adolescente , Criança , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Sebaceous carcinoma of the breast is an exceedingly rare neoplasm. Little is known about the behavior and prognosis of this type of breast cancer. We report clinical, histological and immunohistochemical features of four cases of breast carcinoma with prominent (at least 50%) sebaceous differentiation. The tumors occurred in four women, aged 25-66, and were composed of cords, lobules and solid sheets of tumor cells with sebaceous differentiation, comprising 50-90% of the tumor mass. The second component consisted of cells with non-vacuolated cytoplasm, present mostly around the periphery of the lobules, or which formed separate tumor sheets with no evidence of sebaceous differentiation and were indistinguishable from a classical ductal carcinoma. Immunohistochemically, three tumors expressed hormone receptors; all cases were HER2-negative and had retained expression of the DNA mismatch repair proteins. Three patients had axillary lymph node metastases, and two patients had distant metastases: one in the liver, lung and bones, and one in the mediastinal and supraclavicular lymph nodes. One patient died 28 months after diagnosis, indicating that mammary sebaceous carcinoma is a potentially aggressive neoplasm. In contrast to extraocular cutaneous sebaceous carcinomas, mammary sebaceous carcinoma is probably unrelated to Muir-Torre syndrome. It should be differentiated from morphologically similar but biologically distinct lipid-rich carcinoma.
Assuntos
Neoplasias da Mama/patologia , Carcinoma/patologia , Neoplasias das Glândulas Sebáceas/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Biópsia , Neoplasias Ósseas/secundário , Neoplasias da Mama/química , Neoplasias da Mama/terapia , Carcinoma/química , Carcinoma/secundário , Carcinoma/terapia , Diferenciação Celular , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Metástase Linfática , Pessoa de Meia-Idade , Neoplasias das Glândulas Sebáceas/química , Neoplasias das Glândulas Sebáceas/terapia , Fatores de Tempo , Resultado do TratamentoRESUMO
We describe 23 cases of high-grade myxoinflammatory fibroblastic sarcoma (MIFS). The patients were 15 women and 8 men, with the age ranging at the time of diagnosis from 39 to 93 years (mean, 64.3 years; median, 66 years). Follow-up was available for 18 patients, of whom 9 developed metastatic disease; 7 of these died. Most tumors showed a predilection for the soft tissues of the extremities, with 14 cases involving the lower limb and 5 the upper extremity. However, in both sites, the acral parts were affected in only 1 case each. Of the 4 remaining tumors, 2 were found in axilla, 1 was found in sacral area, and 1 developed in the scar on the breast, 14 years after previous excision of a mammary carcinoma and subsequent local irradiation. The tumor size ranged from 1.3 cm to as much as 30 cm in the largest dimension with a mean size of 8.3 cm. Histologically, the tumors were characterized by occurrence of 3 types of characteristic cells, including (1) lipoblast-like cells with an ample, distended, mucin-filled cytoplasm compartmentalized by a variable number of intracytoplasmic septa, thus remotely resembling soccer balls; (2) large, polygonal, bizarre ganglion-like cells similar to those seen in the Hodgkin disease, also called Reed-Sternberg-like cells. Within an ample, deeply eosinophilic cytoplasm, there was an oval nucleus with vesicular chromatin and a large, inclusion-like nucleolus. Binucleated, multinucleated, or more pleomorphic forms of these cells were also present; (3) cells with emperipolesis of variable sizes, ranging from very inconspicuous neoplastic cells containing only one to a few engulfed cells to conspicuous large ones having many inflammatory cells, usually polymorphonuclear leukocytes admixed with various numbers of some lymphoid cells, within the cytoplasm. Quite often, we found elements that combined the histologic features of all the above 3 characteristic tumor cell types. In 2 tumors, we found an additional undifferentiated spindle cell sarcoma component, whereas in another tumor, a chondrosarcomatous moiety was evident. For comparison, we studied 10 cases of pleomorphic hyalinizing angiectatic tumor (PHAT) of soft tissues. Based on the identification of morphological changes typical for MIFS within most of the cases of PHAT, we suggest that most cases of PHAT represent examples of MIFS merely having hyaline ectatic vessels.
Assuntos
Fibrossarcoma/patologia , Mixossarcoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Condrossarcoma/metabolismo , Condrossarcoma/patologia , Ciclina D1/metabolismo , Feminino , Fibrossarcoma/metabolismo , Seguimentos , Humanos , Hialina/metabolismo , Imuno-Histoquímica , Inflamação/metabolismo , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Mixossarcoma/metabolismo , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologiaRESUMO
The authors present a unique case of small cell variant of clear cell sarcoma of soft parts in a 42-year old woman. The tumor originally arose in the right flank of the soft tissues and ultimately developed both a local recurrence and multiple distant skin metastases two years and ten months thereafter. Nonspecific morphology of small blue round cell tumor was preserved at all microscopically verified sites and initially led to the spectrum of erroneous diagnoses such as an extraskeletal myxoid chondrosarcoma, Ewing sarcoma as well as malignant melanoma. The distinctive features of clear cell sarcoma such as fascicular nested growth pattern, spindling, clear cell change and/or eosinophilic cytoplasm were not disclosed even by extensive sampling. Immunohistochemically, the tumor expressed only S100protein and HMB45; all other markers (CD99, FLI1, cytokeratins, EMA) were completely negative. The molecular analysis carried out in one of the cutaneous metastases revealed translocation t(12;22) (EWSR1-ATF1) and ultimately led to the correct diagnosis of unusual Ewing-like clear cell sarcoma. Discussed is the implementation of molecular tests in routine diagnostics considering the existence of both histologically and biologically different tumors with an identical pathogenic molecular background.