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2.
Clin Nucl Med ; 49(5): 434-437, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557577

RESUMO

ABSTRACT: We present a new, extremely rare nonmyxoid cellular variant of extraskeletal myxoid chondrosarcoma. Although diagnosis is radiologically and pathologically challenging, FDG PET/CT and MRI accurately showed the malignancy and high tumor density. A 52-year-old woman complained of a left dorsal mass, which presented inhomogeneous intermediate signals on T2-weighted images, with diffusion restriction, strong enhancement, and increased accumulation of FDG (SUV max , 5.2). Although biopsy was inconclusive, a highly malignant tumor was suspected radiologically. The resected specimen was histologically diagnosed as extraskeletal myxoid chondrosarcoma by detection of EWSR1::NR4A3 fusion using fluorescence in situ hybridization.


Assuntos
Condrossarcoma , Fluordesoxiglucose F18 , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Hibridização in Situ Fluorescente , Condrossarcoma/diagnóstico por imagem , Imageamento por Ressonância Magnética
3.
Rev Esp Patol ; 57(2): 141-145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599736

RESUMO

Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour with a high local and distant metastasis rate and limited response to chemotherapy. Meckel's diverticulum is the most frequent congenital anomaly, and it is associated with a considerable risk of malignant transformation. In this case report, we describe a 50-year-old female patient with a history of extraskeletal myxoid chondrosarcoma of the lower limb and metastasis to the forearm who went to the emergency department with abdominal pain. The investigations revealed a caecal volvulus. A lesion in the middle third of the ileum was incidentally discovered and removed during surgery. Pathology examination revealed a Meckel's diverticulum adenocarcinoma, with metastasis of extraskeletal myxoid chondrosarcoma. Resection was complete; however, the patient had diffuse metastatic pulmonary disease and died eight months later due to disease progression. This mechanism of tumour-to-tumour metastasis is described in other locations, but, regarding the Meckel's diverticulum, this is a unique situation, previously unreported in the literature.


Assuntos
Adenocarcinoma , Condrossarcoma , Divertículo Ileal , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Feminino , Humanos , Pessoa de Meia-Idade , Divertículo Ileal/complicações , Divertículo Ileal/diagnóstico , Divertículo Ileal/cirurgia , Íleo/patologia , Adenocarcinoma/patologia , Progressão da Doença , Condrossarcoma/complicações
4.
Pathol Res Pract ; 256: 155240, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492357

RESUMO

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms constituting less than 2% of all soft tissue tumors. They typically originate in the thoracic cavity, mainly in the pleura, but can also occur in other various sites such as lung parenchyma, pericardium, and bronchus. In this study, a 49-year-old non-smoking female with a history of allergies presented to our pulmonary clinic with a chronic cough. An explorative bronchoscopy revealed an intrabronchial mass in the left superior bronchi, and a 68 Ga-DOTATOC positron emission computed tomography suggested a carcinoid tumor. Subsequent pulmonary segmentectomy unveiled a well-circumscribed polypoid lesion diagnosed as a low-grade bronchus SFT through histopathological and immunohistochemical assessments. The patient was asymptomatic after surgical excision and showed no other lesion during the 6-month follow-up. The endobronchial location of SFT is uncommon, with only a few reported cases in the literature, underscoring the necessity of considering various differential diagnoses, including carcinoid, mucoepidermoid carcinoma, endobronchial pleomorphic adenoma, hamartoma, leiomyoma, and metastasis, depending on location and imaging features. This report underscores the importance of careful histological and immunohistochemical evaluation in understanding and appropriately stratifying the risk associated with polypoid lesions.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias de Tecidos Moles , Tumores Fibrosos Solitários , Humanos , Feminino , Pessoa de Meia-Idade , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/patologia , Diagnóstico Diferencial , Neoplasias de Tecidos Moles/diagnóstico , Brônquios/patologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/diagnóstico
5.
Genes Chromosomes Cancer ; 63(3): e23227, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38517106

RESUMO

AIMS: Kinase fusion-positive soft tissue tumors represent an emerging, molecularly defined group of mesenchymal tumors with a wide morphologic spectrum and diverse activating kinases. Here, we present two cases of soft tissue tumors with novel LTK fusions. METHODS AND RESULTS: Both cases presented as acral skin nodules (big toe and middle finger) in pediatric patients (17-year-old girl and 2-year-old boy). The tumors measured 2 and 3 cm in greatest dimension. Histologically, both cases exhibited bland-looking spindle cells infiltrating adipose tissue and accompanied by collagenous stroma. One case additionally displayed perivascular hyalinization and band-like stromal collagen. Both cases exhibited focal S100 staining, and one case had patchy coexpression of CD34. Targeted RNA-seq revealed the presence of novel in-frame MYH9::LTK and MYH10::LTK fusions, resulting in upregulation of LTK expression. Of interest, DNA methylation-based unsupervised clustering analysis in one case showed that the tumor clustered with dermatofibrosarcoma protuberans (DFSP). One tumor was excised with amputation with no local recurrence or distant metastasis at 18-month follow-up. The other case was initially marginally excised with local recurrence after one year, followed by wide local excision, with no evidence of disease at 10 years of follow-up. CONCLUSIONS: This is the first reported case series of soft tissue tumors harboring LTK fusion, expanding the molecular landscape of soft tissue tumors driven by activating kinase fusions. Furthermore, studies involving a larger number of cases and integrated genomic analyses will be warranted to fully elucidate the pathogenesis and classification of these tumors.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Proteínas de Fusão Oncogênica , Neoplasias Cutâneas , Neoplasias de Tecidos Moles , Adolescente , Criança , Feminino , Humanos , Masculino , Antígenos CD34/metabolismo , Biomarcadores Tumorais/genética , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Receptores Proteína Tirosina Quinases , Neoplasias Cutâneas/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Proteínas de Fusão Oncogênica/genética , Cadeias Pesadas de Miosina/genética , Miosina não Muscular Tipo IIB/genética
6.
Int J Mol Sci ; 25(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339014

RESUMO

Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is necessary for differential diagnosis. EWSR1 is a 'promiscuous' gene that can fuse with many different partner genes, defining different entities among a broad range of mesenchymal neoplasms. Molecular testing of EWSR1 translocation traditionally relies on FISH assays with break-apart probes, which are unable to identify the fusion partner. Therefore, other ancillary molecular diagnostic modalities are being increasingly adopted for accurate classification of these neoplasms. Herein, we report three cases with rare GFs involving EWSR1 in undifferentiated mesenchymal neoplasms with uncertain differential diagnoses, using targeted RNA-seq and confirming with RT-PCR and Sanger sequencing. Two GFs involved hormone nuclear receptors as 3' partners, NR4A2 and RORB, which have not been previously reported. NR4A2 may functionally replace NR4A3, the usual 3' partner in extraskeletal myxoid chondrosarcoma. The third GF, EWSR1::BEND2, has previously been reported in a subtype of astroblastoma and other rare entities, including a single case of a soft-tissue tumor that we discuss in this work. In conclusion, our findings indicate that the catalogue of mesenchymal neoplasm-bearing EWSR1 fusions continues to grow, underscoring the value of using molecular ancillary techniques with higher diagnostic abilities in the routine clinical setting.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Proteínas de Fusão Oncogênica , Proteína EWS de Ligação a RNA , Neoplasias de Tecidos Moles , Humanos , Proteínas de Ligação a Calmodulina/genética , Condrossarcoma/genética , Proteínas de Fusão Oncogênica/genética , Proteína EWS de Ligação a RNA/genética , Proteínas de Ligação a RNA/genética , Sarcoma/patologia , Neoplasias de Tecidos Moles/genética
7.
J Pathol ; 263(1): 61-73, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38332737

RESUMO

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.


Assuntos
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/genética
8.
Am J Surg Pathol ; 48(5): 588-595, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38357912

RESUMO

Nasal chondromesenchymal hamartoma (NCMH) is a rare benign polypoid mesenchymal tumor arising in the nasal cavity and/or paranasal sinuses. Recognizing these sporadic, rare lesions is crucial, as surgical complete removal of the mass is the common treatment approach. This retrospective study analyzed the demographics, symptoms, and imaging data of 9 patients diagnosed with NCMH between January 2017 and June 2023, possibly representing the largest single-center adult case cohort to date. Diagnostic techniques included nasal endoscopy, CT/MRI scan, immunohistological studies, and morphologic comparisons. Pathologic specimens were subjected to Sanger sequencing of exons 24 and 25 of DICER1. The average age of 9 cases was 24.4 years, and the oldest was 55 years. Four of the patients were children, ranging from 1 year old to 11 years old, with an average of 4.5 years. Nasal congestion is the most common registered symptom. Endoscopic findings showed that most patients had smooth pink neoplasms or polypoid masses in the nasal meatus. Radiologic scanning revealed soft-tissue density masses that occupied the nasal cavity. Histologically, the characteristic structure of NCMHs is immature cellular cartilage nodules and mature cartilage nodules distributed in a loose mucoid matrix. Five of the 9 patients had somatic DICER1 missense mutations. Four of the patients with DICER1-mutated NCMH exhibited a p.E1813 missense hotspot mutation. We also report a case of a rare p.P1836H missense mutation. The detected DICER1 somatic mutations provide compelling evidence of an association with the DICER1 tumor family. We emphasize the importance of pathologic consultation and the need for pathologists to accumulate experience in NCMH diagnosis to avoid misdiagnosis.


Assuntos
Hamartoma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Doenças Nasais , Criança , Lactente , Adulto , Humanos , Adulto Jovem , Estudos Retrospectivos , Doenças Nasais/genética , Doenças Nasais/diagnóstico , Doenças Nasais/patologia , Cavidade Nasal/patologia , Hamartoma/genética , Hamartoma/patologia , Ribonuclease III/genética , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Mutação , RNA Helicases DEAD-box/genética
9.
Surg Pathol Clin ; 17(1): 1-12, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38278599

RESUMO

Superficial CD34-positive fibroblastic tumor is a mesenchymal neoplasm of "intermediate malignancy" recently included in the fifth edition of the World Health Organization classification of soft tissue and bone tumors. In this review, we summarize the current knowledge on this rare entity with a special focus on its clinicopathological features, morphologic spectrum, and differential diagnosis. We also provide data regarding recent discoveries on its molecular profile and discuss its prognosis and management.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias de Tecidos Moles , Humanos , Antígenos CD34 , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/diagnóstico , Diagnóstico Diferencial , Biomarcadores Tumorais
10.
Surg Pathol Clin ; 17(1): 105-118, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38278600

RESUMO

Perivascular epithelioid cell tumors (PEComas) are a heterogenous group of mesenchymal neoplasms with a mixed myomelanocytic immunophenotype. PEComa-family tumors include angiomyolipoma, lymphangioleiomyomatosis, and a large category of rare neoplasms throughout the body that are now classified under the umbrella term "PEComa." This review focuses on recent advances in the clinicopathological and molecular features of PEComas, with an emphasis on PEComas that originate in soft tissue.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias de Células Epitelioides Perivasculares , Humanos , Biomarcadores Tumorais/genética , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/patologia
11.
PET Clin ; 19(2): 217-229, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38184453

RESUMO

The past 25 years have seen significant growth in the role of positron emission tomography/computed tomography (PET/CT) in musculoskeletal oncology. Substantiative advances in technical capability and image quality have been paralleled by increasingly widespread clinical adoption and implementation. It is now recognized that PET/CT is useful in diagnosis, staging, prognostication, response assessment, and surveillance of bone and soft tissue sarcomas, often providing critical information in addition to conventional imaging assessment. As individualized, precision medicine continues to evolve for patients with sarcoma, PET/CT is uniquely positioned to offer additional insight into the biology and management of these tumors.


Assuntos
Neoplasias Ósseas , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Sarcoma , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Tomografia por Emissão de Pósitrons , Estadiamento de Neoplasias
12.
Clin Nucl Med ; 49(3): 260-261, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38271245

RESUMO

ABSTRACT: Ovarian myxoid chondrosarcoma is a rare and aggressive tumor. We present 18 F-FDG PET/CT findings of ovarian myxoid chondrosarcoma. The images not only demonstrated a pelvic mass with increased FDG uptake, but also a mass with increased FDG uptake in the right lower abdominal wall. Ovarian malignancy with abdominal wall metastases was suspected. An extraskeletal myxoid chondrosarcoma was diagnosed histopathologically after the mass excision.


Assuntos
Condrossarcoma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Humanos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Condrossarcoma/diagnóstico por imagem
13.
Ann Diagn Pathol ; 68: 152242, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38039617

RESUMO

SMARCB1/INI1-deficient soft tissue tumors with epithelioid and myxoid features are diverse and mainly include soft tissue myoepithelial tumor, extraskeletal myxoid chondrosarcoma, and the recently described myoepithelioma-like tumor of the vulvar region and myxoepithelioid tumor with chordoid features. Because of their overlapping features, the accurate diagnosis and classification of these tumors are often challenging. Herein, we report two unique cases of SMARCB1/INI1-deficient soft tissue neoplasm with epithelioid and myxoid features occurring in male paratesticular region. The first case was a 52-year-old man presented with an intermittent painful left paratesticular mass for 1 year. The second case was a 41-year-old man presented with a painless paratesticular mass on the right side for 3 months. Both patients underwent an orchiectomy. After 6 and 26 months of follow-up, both were alive with no evidence of recurrence or metastasis. In both cases, the tumor was relatively well-demarcated and showed monomorphic round to epithelioid cells arranged in a nested, trabecular, reticular, and corded pattern, setting in a myxohyalinized and vascularized matrix. The tumor cells showed relatively uniform round nuclei with vesicular chromatin and variably prominent nucleoli. No rhabdoid cells were identified. Mitoses numbered 3 and 2 per 10 high-power fields. Tumor necrosis or lymphovascular invasion was absent. Immunohistochemically, both tumors expressed epithelial membrane antigen (focal), calponin (focal), and CD99. SMARCB1/INI1 expression was deficient in both cases. In addition, case 1 diffusely expressed pan-cytokeratin, and case 2 diffusely expressed CD34 and synaptophysin. Molecular genetically, case 1 showed SMARCB1 homozygous deletion as detected by fluorescence in-situ hybridization (FISH), and case 2 demonstrated SMARCB1 copy number deletions by next-generation sequencing and SMARCB1 monoallelic deletion by FISH. Both cases lacked EWSR1 rearrangements by FISH. The overall clinicopathologic profiles of the two cases made it difficult to classify them as one of the established categories of SMARCB1/INI1-deficient mesenchymal tumors. Our study further expands the clinicopathologic and molecular spectrum of SMARCB1/INI1-deficient epithelioid and myxoid neoplasms and highlights the challenges to diagnose these tumors.


Assuntos
Condrossarcoma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias de Tecidos Moles , Humanos , Masculino , Pessoa de Meia-Idade , Adulto , Homozigoto , Deleção de Sequência , Proteína SMARCB1/genética , Condrossarcoma/patologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/diagnóstico , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Biomarcadores Tumorais
14.
Mod Pathol ; 37(2): 100386, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37992966

RESUMO

Mesenchymal tumors with GLI1 fusions or amplifications have recently emerged as a distinctive group of neoplasms. The terms GLI1-altered mesenchymal tumor or GLI1-altered soft tissue tumor serve as a nosological category, although the exact boundaries/criteria require further elucidation. We examined 16 tumors affecting predominantly adults (median age: 40 years), without sex predilection. Several patients had tumors of longstanding duration (>10 years). The most common primary site was soft tissue (n = 9); other sites included epidural tissue (n = 1), vertebra (n = 1), tongue (n = 1), hard palate (n = 1), and liver (n = 1). Histologically, the tumors demonstrated multinodular growth of cytologically uniform, ovoid-to-epithelioid, occasionally short spindled cells with delicate intratumoral vasculature and frequent myxoid stroma. Mitotic activity ranged from 0 to 8 mitoses/2 mm2 (mean 2). Lymphovascular invasion/protrusion of tumor cells into endothelial-lined vascular spaces was present or suspected in 6 cases. Necrosis, significant nuclear pleomorphism, or well-developed, fascicular spindle-cell growth were absent. Half demonstrated features of the newly proposed subset, "distinctive nested glomoid neoplasm." Tumors were consistently positive for CD56 (n = 5/5). A subset was stained with S100 protein (n = 7/13), SMA (n = 6/13), keratin (n = 2/9), EMA (n = 3/7), and CD99 (n = 2/6). Tumors harbored ACTB::GLI1 (n = 15) or PTCH1::GLI1 (n = 1) fusions. The assays used did not capture cases defined by GLI1 amplification. We also identified recurrent cytogenetic gains (1q, 5, 7, 8, 12, 12q13.2-ter, 21, and X). For patients with available clinical follow-up (n = 8), half were disease free. Half demonstrated distant metastases (lungs, bone, or soft tissue). Of cases without follow-up (n = 8), 2 were known recurrences, and 1 was presumed metastasis. Our results imply a more aggressive biological potential than currently reported. Given the possibility for metastasis and disease progression, even in cytologically bland, nested tumors, close clinical surveillance, akin to that for sarcoma management, may be indicated. The term GLI1-altered mesenchymal tumor with malignant potential is proposed.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Proteína GLI1 em Dedos de Zinco/genética , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Proteínas S100 , Sarcoma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise
15.
Genes Chromosomes Cancer ; 63(1): e23197, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37642440

RESUMO

Calcified chondroid mesenchymal neoplasms represent a distinct, and recently recognized, spectrum of tumors. To date most cases have been reported to be characterized by FN1 gene fusions involving multiple potential tyrosine kinase partners. Following incidental identification of a tumor morphologically corresponding to calcified chondroid mesenchymal neoplasm, but with a PDGFRA::USP8 gene fusion, we undertook a retrospective review to identify and characterize additional such cases. A total of four tumors were identified. Each was multilobulated and composed of polygonal-epithelioid-stellate cells with a background of chondroid matrix containing distinctive patterns of calcification. Targeted RNA sequencing revealed an identical PDGFRA (exon 22)::USP8 (exon 5) gene fusion in each case. Subsequent immunohistochemical staining confirmed the presence of PDGFRα overexpression. In summary, we report a series of four tumors within the morphologic spectrum of calcified chondroid mesenchymal neoplasms. In contrast to prior reports, these tumors harbored a novel PDGFRA::USP8 gene fusion, rather than FN1 rearrangement. Our findings expand the molecular diversity of these neoplasms, and suggest they are united through activation of protein kinases.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias de Tecidos Moles , Humanos , Proteínas Tirosina Quinases/genética , Fusão Gênica , Receptores Proteína Tirosina Quinases/genética , Neoplasias de Tecidos Moles/genética , Biomarcadores Tumorais/genética , Endopeptidases/genética , Ubiquitina Tiolesterase/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética
16.
Histopathology ; 84(3): 451-462, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37988282

RESUMO

AIMS: NTRK-rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a "fibrosarcoma-like" morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan-TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements. The aim of this study was to characterize pan-TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan-TRK immunohistochemistry to distinguish NTRK-rearranged sarcoma from its mimics. METHODS AND RESULTS: A total of 473 gynaecological mesenchymal tumours (461 without known NTRK fusions and 12 NTRK-rearranged sarcomas) were selected. Pan-TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan-TRK positive tumours was performed by RNA sequencing or fluorescence in situ hybridization (FISH). Of the 12 NTRK-rearranged sarcomas, 11 (92%) exhibited diffuse (≥70%) cytoplasmic pan-TRK staining with moderate/marked intensity, while the other was negative. Eleven (2.4%) additional tumours also exhibited pan-TRK immunohistochemical expression: three low-grade endometrial stromal sarcomas, seven high-grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of NTRK rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal/multifocal (<70%) pan-TRK cytoplasmic staining with weak/moderate intensity. CONCLUSION: Even though pan-TRK immunohistochemical expression is not entirely sensitive or specific for NTRK-rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate/strong intensity, unlike its mimics. Pan-TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and/ or S100. Ultimately, the diagnosis requires molecular confirmation.


Assuntos
Neoplasias do Endométrio , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Sarcoma do Estroma Endometrial , Sarcoma , Neoplasias de Tecidos Moles , Feminino , Humanos , Biomarcadores Tumorais/genética , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Proteínas de Fusão Oncogênica/genética , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia , Receptor trkA
17.
Genes Chromosomes Cancer ; 63(1): e23203, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37724942

RESUMO

Spindle cell mesenchymal neoplasms are a diverse and often challenging diagnostic group. While morphological impression is sufficient for some diagnoses, increasingly immunohistochemical and even molecular data is required to render an accurate diagnosis, which can lead to the characterization of new entities. We describe five cases of novel mesenchymal neoplasms with rearrangements in the NCOA2 and NCOA3 genes partnered with either CTCF or CRTC1. Three tumors occurred in the head and neck (palate, auditory canal), while the other two were in visceral organs (lung, urinary bladder). All cases occurred in adults (range 33-86) with a median age of 42 and fairly even sex distribution = (male-to-female = 3:2). Morphologically, they had similar features consisting of monotonous, bland spindle to ovoid cells with fascicular and reticular arrangements in a myxohyaline to collagenous stroma. However, immunophenotypically they had essentially a null phenotype, with only two tumors staining partially for CD34 and smooth muscle actin. Targeted RNA sequencing detected in-frame CTCF::NCOA2 (one case), CRTC1::NCOA2 (two cases), and CTCF::NCOA3 (two cases) fusions. Treatment was surgical resection in all cases. Local recurrence and/or distant metastases were not observed in any case (median follow-up, 7.5 months; range, 2-19 months). Given their morphologic, immunohistochemical, and molecular similarities, we believe that these cases may represent an emerging family of low-grade NCOA2/3-rearranged fibroblastic spindle cell neoplasms.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias de Tecidos Moles , Adulto , Humanos , Masculino , Feminino , Fibroblastos/patologia , Sequência de Bases , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Fenótipo , Biomarcadores Tumorais/genética , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Coativador 2 de Receptor Nuclear/genética
18.
Genes Chromosomes Cancer ; 63(1): e23200, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37698344

RESUMO

High-mobility group AT-hook 2 (HMGA2) is rearranged in various types of mesenchymal tumors, particularly lipomas. HMGA2 is also co-amplified with mouse double minute 2 (MDM2) in well-differentiated liposarcoma/dedifferentiated liposarcoma (WDLPS/DDLPS). We report a case of relapsed DDLPS with a novel in-frame fusion between HMGA2 and KITLG, which encodes the ligand for KIT kinase, a critical protein involved in gametogenesis, hematopoiesis, and melanogenesis. The HMGA2 breakpoint is in intron 3, a commonly observed location for HMGA2 rearrangements, while the KITLG breakpoint is in intron 2, leading to a fusion protein that contains almost the entire coding sequence of KITLG. By immunohistochemical staining, tumor cells expressed KIT and showed phosphorylated MAPK, a major KIT downstream target. We suggest an oncogenic mechanism that involves the overexpression of KITLG caused by its rearrangement with HMGA2, leading to the constitutive activation of KIT kinase. While MDM2 amplification was observed in both the primary tumor and the relapsed tumor, the HMGA2::KITLG was only present in the relapsed tumor, indicating the role of HMGA2::KITLG in disease progression.


Assuntos
Lipoma , Lipossarcoma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Humanos , Animais , Camundongos , Lipossarcoma/genética , Lipossarcoma/patologia , Lipoma/genética , Lipoma/patologia , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Amplificação de Genes
19.
Int J Gynecol Pathol ; 43(1): 56-60, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37668341

RESUMO

NTRK gene fusions are part of a paradigm shift in oncology, arising as one of the main genomic alterations with actionability in the so-called "agnostic setting." In gynecologic pathology, the recent description of uterine sarcoma resembling fibrosarcoma and with NTRK rearrangements ( NTRK -rearranged uterine sarcoma) highlights the importance of recognizing clinicopathological cues that can lead to genomic profiling. Herein, we report the case of a 43-year-old woman presenting with vaginal bleeding and pelvic mass. Histopathology of the tumor showed moderately atypical spindle cells arranged in long fascicles reminiscent of fibrosarcoma, along with immunohistochemical positivity for S100, CD34, and pan-tropomyosin receptor kinase. This prompted RNA-sequencing and the finding of a rare EML4::NTRK3 fusion. Clinical, histologic, and molecular findings are described, in addition to discussions regarding differential diagnoses and possible implications of the findings in clinical practice.


Assuntos
Fibrossarcoma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias Pélvicas , Sarcoma , Neoplasias de Tecidos Moles , Neoplasias Uterinas , Humanos , Feminino , Adulto , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia , Fibrossarcoma/diagnóstico , Neoplasias de Tecidos Moles/patologia , Fusão Gênica , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Proteínas de Fusão Oncogênica/genética , Rearranjo Gênico
20.
Ann Diagn Pathol ; 67: 152200, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37666011

RESUMO

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor that is mainly seen in middle-aged women. PEComa originating in the ureter is extremely rare it is unclear whether they display typical clinical and radiographic features seen elsewhere. Herein, we report findings from 2 cases of primary PEComa of the ureter that we classified as malignant. Case 1: A 45-year-old woman was admitted to the hospital with intermittent distension in her waist. After appropriate imaging, the right ureter and right kidney were excised under general anesthesia. The tumor measured 1.4 cm. Microscopically, the tumor displayed infiltrative growth, >2 mitoses per 10 high power fields (HPF), necrosis, and lympho-vascular invasion. Case 2: A 30-year-old woman was admitted to the hospital due to hematuria 20 days duration. The left ureter and left kidney were ultimately excised under general anesthesia. The tumor measured 2 cm. Microscopically, the tumor showed infiltrative growth and >2 mitoses/10 HPF. Our cases were diagnosed as malignant PEComa. No disease recurrence was observed in either of the two patients during the postoperative follow-up period. Malignant primary ureteral PEComa is very rare. The clinical manifestations are not specific, and it is usually misdiagnosed as a malignant neoplasm on imaging. Therefore, its diagnosis requires pathological examination and immunohistochemical analysis of the sampled or resected tumor. Treatment requires a complete surgical resection and regular clinical follow-up.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias de Células Epitelioides Perivasculares , Ureter , Humanos , Pessoa de Meia-Idade , Feminino , Adulto , Ureter/patologia , Recidiva Local de Neoplasia , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/cirurgia , Neoplasias de Células Epitelioides Perivasculares/patologia
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