RESUMO
Undifferentiated sarcomas characterized by a primitive monomorphic round to spindle cell phenotype and often non-specific immunoprofile remain difficult to subclassify outside molecular analysis. The increased application of RNA sequencing in clinical practice led to significant advances and discoveries of novel gene fusions that furthered our understanding and refined classification of otherwise undifferentiated neoplasms. In this study, we report an undifferentiated round to spindle cell sarcoma arising in the femur of a 34-year-old female. The round to spindle tumor cells were arranged in short fascicles, with focal rosette formation, within a hyalinized stroma. The tumor immunoprofile included diffuse reactivity for CD99, SATB2, and TLE1 and patchy positivity for Cyclin D1, Keratin AE1/AE3, synaptophysin, and chromogranin. Other markers, such as EMA, SMA, desmin, S100, ERG, and WT1, were negative. Fluorescence in situ hybridization analysis for EWSR1 gene alterations showed a break-apart signal and targeted RNA sequencing revealed an EWSR1::SSX3 gene fusion. The patient received neoadjuvant chemotherapy followed by surgery and subsequently relapsed in less than a year with lung metastasis. Larger series are needed to determine if this fusion defines a novel subset of undifferentiated tumors or represents a genomic variant of already existing primitive round cell sarcoma categories, such as Ewing sarcoma or synovial sarcoma.
Assuntos
Sarcoma de Ewing , Sarcoma , Neoplasias de Tecidos Moles , Feminino , Humanos , Adulto , Hibridização in Situ Fluorescente , Sarcoma/genética , Sarcoma/patologia , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Fatores de Transcrição/genética , Neoplasias de Tecidos Moles/genética , Fusão Gênica , Biomarcadores Tumorais/genética , Proteínas de Fusão Oncogênica/genética , Proteína EWS de Ligação a RNA/genéticaRESUMO
Very long fusiform gram-negative bacilli were observed after Gram staining of amniotic fluid from a 36-year-old multigravida woman. At 24 hours, pure, abundant growth of smooth, gray, only slightly convex catalase-positive and oxidase-negative colonies measuring about 2 mm were observed. Growth was greater in anaerobic than in aerobic conditions. The bacterium was identified as Leptotrichia trevisanii by matrix-assisted laser desorption ionization time of flight mass spectrometry. Ampicillin and gentamicin were prescribed for chorioamnionitis, and vaginal prostaglandins were administered to terminate the pregnancy. The patient remained afebrile throughout 48 hours and was discharged. Microscopic examination of the placenta revealed severe acute chorioamnionitis with a maternal inflammatory response and abundant bacillary-shaped microorganisms. To our knowledge, this isolate constitutes the first reported case of chorioamnionitis caused by L. trevisanii.
Assuntos
Corioamnionite/microbiologia , Infecções por Fusobacteriaceae/microbiologia , Leptotrichia/isolamento & purificação , Complicações na Gravidez/microbiologia , Adulto , Ampicilina/administração & dosagem , Antibacterianos/administração & dosagem , Feminino , Infecções por Fusobacteriaceae/tratamento farmacológico , Gentamicinas/administração & dosagem , Humanos , Leptotrichia/efeitos dos fármacos , Leptotrichia/genética , Leptotrichia/fisiologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Poor long-term survival in localized high-risk soft tissue sarcomas (STSs) of the extremities and trunk highlights the need to identify new prognostic factors. CXCR4 is a chemokine receptor involved in tumor progression, angiogenesis, and metastasis. The aim of this study was to evaluate the association between CXCR4 expression in tumor tissue and survival in STSs patients treated with neoadjuvant therapy. CXCR4 expression was retrospectively determined by immunohistochemical analysis in serial specimens including initial biopsies, tumors post-neoadjuvant treatment, and tumors after relapse. We found that a positive cytoplasmatic expression of CXCR4 in tumors after neoadjuvant treatment was a predictor of poor recurrence-free survival (RFS) (p = 0.003) and overall survival (p = 0.019) in synovial sarcomas. We also found that positive nuclear CXCR4 expression in the initial biopsies was associated with poor RFS (p = 0.022) in undifferentiated pleomorphic sarcomas. In conclusion, our study adds to the evidence that CXCR4 expression in tumor tissue is a promising prognostic factor for STSs.
RESUMO
AIMS: Benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumours occur either sporadically or are related to neurofibromatosis (NF). The mechanisms involved are well known in NF-related tumours, but still remain unclear in sporadic cases. Somatic BRAF and KRAS mutations represent the most frequent genetic events in melanocytic neoplastic lesions. Because melanocytes and Schwann cells both derive from neural crest cells, we hypothesized that BRAF and KRAS mutations might influence BPNST and MPNST development. METHODS AND RESULTS: BRAF exon 15 and KRAS exons 2 and 3 polymerase chain reaction (PCR) sequencing was performed in formalin-fixed/paraffin-embedded samples of 99 BPNST and MPNST, related and non-related to NF types 1 and 2. Oncogenic BRAF V600E mutations were found in four of 40 schwannomas (including one acoustic neuroma) and one of 13 MPNST, not associated with NF. A KRAS G12S mutation was also evident in one sporadic schwannoma. CONCLUSION: Our findings suggest that RAS pathway activation due to BRAF V600E and KRAS mutations is an important event in a subset of peripheral nerve sheath tumours not related to NF.
Assuntos
Mutação , Neoplasias de Bainha Neural/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Bainha Neural/patologia , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas p21(ras)RESUMO
INTRODUCTION: The effectiveness of trabectedin for the treatment of leiomyosarcoma and liposarcoma (commonly referred to as L-sarcomas) has been widely evidenced in clinical trials and real-world studies. Nevertheless, available literature on non-L-sarcomas is less abundant. The objective of the present study is to evaluate the effectiveness and safety of trabectedin in a cohort of patients with non-L-sarcomas in the real-world setting. METHODS: This retrospective, observational study included 34 patients who received trabectedin in the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) between October 2013 and July 2020. RESULTS: The most frequent histologic subtypes were undifferentiated spindle cell/pleomorphic sarcoma (n = 11, 32.4%), synovial sarcoma (n = 6, 17.7%), myxofibrosarcoma (n = 5, 14.7%), and malignant peripheral nerve sheath tumor (n = 4, 11.8%). The mean number of cycles with trabectedin was 5.5 (range 2-28). Three patients achieved partial response (8.8%) and eight patients showed stable disease (23.5%). The objective response rate and disease control rate were 8.8% (95% confidence interval (CI), 95% CI 1.9-23.7) and 32.4% (95% CI 17.4-50.5), respectively. Overall, progression-free survival was 2.9 months (95% CI 2.1-3.4). The overall survival was 7.3 months (95% CI 4.7-12.8). The most common trabectedin-related grade 3 adverse events were observed in 10 patients (26.5%), mostly being neutropenia (14.7%) and elevated transaminases (5.9%), whereas one patient (2.9%) reported grade 4 febrile neutropenia that required hospitalization. CONCLUSIONS: The findings of this real-life study consistently support that trabectedin is an effective and safe option for the treatment of patients with non-L-sarcoma after failure of anthracyclines and ifosfamide, or in patients who are unsuited to receive these agents.
Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Tetra-Hidroisoquinolinas , Adulto , Antineoplásicos Alquilantes/efeitos adversos , Dioxóis/efeitos adversos , Humanos , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/patologia , Tetra-Hidroisoquinolinas/uso terapêutico , Trabectedina/uso terapêuticoRESUMO
Neoadjuvant chemotherapy based on anthracyclines and ifosfamide for high-risk soft tissue sarcomas (STS) of the extremities and trunk is a controversial treatment option. There are substantial interindividual differences in clinical outcomes in patients treated with neoadjuvant chemotherapy. The aim of this study was to evaluate, as biomarkers, polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, or drug targets and their association with toxicity and survival in STS patients treated with neoadjuvant chemotherapy. We analysed variants in genes involved in anthracycline metabolism (ABCB1, ABCC2, NQO1, CBR3, and SLC22A16) and in ifosfamide catabolism (ALDH1A1) in 79 treated patients. Two genes showed significant association after adjusted multivariate analysis: ABCC2 and ALDH1A1. In patients treated with anthracyclines, ABCC2 rs3740066 was associated with risk of febrile neutropenia (p = 0.031), and with decreased overall survival (OS) (p = 0.024). ABCC2 rs2273697 was associated with recurrence-free survival (RFS) (p = 0.024). In patients treated with ifosfamide, ALDH1A1 rs3764435 was associated with RFS (p = 0.046). Our pharmacogenetic study shows for the first time that variants in genes regulating the metabolism of neoadjuvant chemotherapy may be helpful to predict toxicity and survival benefit in high-risk STS treated with neoadjuvant chemotherapy. Further validation studies are needed to establish their clinical utility.
RESUMO
Paciente mujer de 60 años, en seguimiento por historia familiar de cáncer de mama y ovario, en la que se detectaron implantes tumorales peritoneales y depósitos de mucina en serosa apendicular. Los implantes peritoneales fueron diagnosticados de carcinoma seroso tipo ovárico/peritoneal con inmunofenotipo característico, siendo la mucina acelular. Se realizaron estudios de mutación de KRAS y BRAF mediante PCR que demostró la presencia de mutación GD12 únicamente en el componente mucinoso, lo que permitió mostrar la existencia de una doble neoplasia. La cirugía posterior confirmó la existencia sincrónica de un adenocarcinoma mucinoso apendicular y un carcinoma seroso peritoneal. Creemos que este caso permite ilustrar que la incorporación de los estudios moleculares en la actividad asistencial del patólogo puede aportarnos información adicional con valor diagnóstico (AU)
A 60 year old female with a family history of ovarian and breast cancer underwent a follow-up laparoscopic exploration which revealed peritoneal implants and mucinous deposits on the appendicular surface. The peritoneal implants were diagnosed as serous carcinoma with a characteristic immunophenotype, while the mucinous material was acellular. KRAS and BRAF mutation studies with PCR showed a GD12 mutation in the mucinous component only, suggesting the presence of a synchronous carcinoma. Subsequent cytorreductive surgery confirmed the presence of an infiltrating appendicular mucinous adenocarcinoma, synchronous with the peritoneal infiltrating serous carcinoma. We believe that this case, where the different immunohistochemical and molecular profiles allowed a correct diagnosis of two independent neoplasms, emphasizes the value of molecular studies in routine diagnostic procedure (AU)
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Adenocarcinoma Mucinoso/patologia , Cistadenocarcinoma Seroso/patologia , Biópsia , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias/patologia , Imuno-Histoquímica/métodos , Patologia/métodos , Terapia Neoadjuvante/métodosRESUMO
Introduction. Teratomas comprise only 3.5% of germcell tumors. We report a case of a 1-month-old girl whowas diagnosed with a large retroperitoneal thoracoabdominalteratoma.Case report. Her presenting features included an expandingabdominal girth, failure to thrive and progressiverespiratory distress. An abdomen X-Ray showed calcifications,and alpha-fetoprotein levels were moderately elevated.Additional studies included abdomen US, CT and MRI,which showed a large abdominal mass adjacent to thegreat vessels with an hour-glass shaped intrathoracic extension,and an anteriorly displaced right hydronephrotickidney. The surgical intervention was performed using acombined abdominal and transdiaphragmatic approach.Pathology showed immature teratoma.Discussion. A transdiaphragmatic surgical approachmay be very useful in scenarios where the great vessels areinvolved and the mass extends into the chest. In our case,this approach was very successful, allowing for a completeresection without resulting in phrenic paralysis. The rightkidney, which was displaced and hydronephrotic at diagnosis,has remained with low function. The patient iscurrently being followed every three months with imagingstudies and alpha-fetoprotein levels (AU)
Introducció. Els teratomes retroperitoneals representennomés el 3.5% dels tumors de cèl·lules germinals. Presentemel cas duna lactant dun mes de vida amb un granteratoma retroperitoneal toracoabdominal dret.Cas clínic. Lactant que ingressa al mes de vida tramesapel seu pediatre per simptomatologia de distensió abdominalprogressiva, estancament pondoestatural, posiciódopistòtons de cap i tronc i dificultat respiratòria. La radiografiadabdomen mostra calcificacions. Els nivells dalfafetoproteïnavan ser moderadament elevats per ledatde la pacient. Lecografia, la tomografia i la ressonànciamagnètica mostraven una gran massa abdominal en relacióamb els grans vasos i una hidronefrosi dreta dun ronyóde localització anterior amb visualització duna imatgedelevació del diafragma interpretada com a secundària ala compressió per la tumoració. La complicada reseccióquirúrgica es va dur a terme per abordatge abdominali transdiafragmàtic perquè la tumoració tenia un doblecomponent toracoabdominal en rellotge de sorra.Comentari. Labordatge transdiafragmàtic pot ser útilen situacions especials quan hi estan implicats els grans vasosi, a la vegada, hi ha un component toràcic. No sha produïtparàlisi frènica. Només el ronyó dret que tenia una alteracióen la morfologia i la localització i una hidronefrosiimportant en la intervenció, persisteix amb una baixa funció.Com que es tractava dun teratoma immadur, cada tresmesos es controlen estrictament els nivells dalfafetoproteïnai es repeteixen les tècniques dimatge ecogràfiques (AU)