-
Acta Cytologica 2022Small round cell sarcomas (SRCSs) account for most solid malignancies in the pediatric age group and are a part of group of malignant tumors characterized by... (Review)
Review
BACKGROUND
Small round cell sarcomas (SRCSs) account for most solid malignancies in the pediatric age group and are a part of group of malignant tumors characterized by heterogenous clinical presentation and overlapping microscopic features of small, round, primitive cells. In addition to the recently established certain genetically defined subset of undifferentiated round cell sarcomas of soft tissue and bone, this group of sarcomas include desmoplastic small round cell tumor, poorly differentiated synovial sarcoma, alveolar rhabdomyosarcoma, mesenchymal chondrosarcoma, and small cell osteosarcoma. Although, those entities share clinical and cytomorphologic features and cannot be unequivocally classified based on clinical presentation and morphology alone. Most of SRCSs characterizes of particular patterns of protein expression or genetic changes and ancillary tests remain necessary to confirm or rule out a specific diagnosis. Subtle but occasionally distinctive cytologic features narrows the number of differential diagnoses and helps to select appropriate ancillary tests necessary for the final diagnosis. Thus, when adequate fine needle aspiration (FNA) biopsy specimen is combined with ancillary tests, a specific histologic diagnosis can be made in almost all cases. However, due to complex cytologic features of SRCS as well as various quality and diversity of FNA smears, there are cases in that cytologic features which do not entirely match the known diagnostic criteria.
SUMMARY
The aim of this review was to summarize cytomorphologic criteria and to present rare and divergent cytological features of SRCSs. Careful assessment of clinical presentation, cytological features, immunohistochemical patterns, and molecular alternations is necessary for an accurate diagnosis. Knowing of rare and divergent microscopic findings that does not fit with the known cytological criteria will help to avoid misdiagnosis.
KEY MESSAGES
The role of FNA biopsies diagnosing soft tissue and bone tumors has been increasing because of the ability of ancillary tests to assist in the diagnosis of specific tumors. SRCSs may be diagnosed accurately in cytology specimens. Access to clinical and radiographic presentation, utility of ancillary tests, understanding complexity of cytological features, and awareness of the rare cytologic findings that differ from that of the established diagnostic criteria are essential to make correct diagnosis.
Topics: Biopsy, Fine-Needle; Bone Neoplasms; Child; Diagnosis, Differential; Humans; Sarcoma; Soft Tissue Neoplasms
PubMed: 35417916
DOI: 10.1159/000524260 -
International Journal of Oncology Sep 2022Rhabdomyosarcoma (RMS) is a highly aggressive soft tissue malignancy that predominantly affects children. The main subtypes are alveolar RMS (ARMS) and embryonal RMS...
Rhabdomyosarcoma (RMS) is a highly aggressive soft tissue malignancy that predominantly affects children. The main subtypes are alveolar RMS (ARMS) and embryonal RMS (ERMS) and the two show an impaired muscle differentiation phenotype. One pathway involved in muscle differentiation is WNT signaling. However, the role of this pathway in RMS is far from clear. Our recent data showed that the canonical WNT/β‑Catenin pathway serves a subordinate role in RMS, whereas non‑canonical WNT signaling probably is more important for this tumor entity. The present study investigated the role of WNT5A, which is the major ligand of non‑canonical WNT signaling, in ERMS and ARMS. Gene expression analysis showed that WNT5A was expressed in human RMS samples and that its expression is more pronounced in ERMS. When stably overexpressed in RMS cell lines, WNT5A decreased proliferation and migration of the cells as demonstrated by BrdU incorporation and Transwell migration or scratch assay, respectively. WNT5A also decreased the self‑renewal capacity and the expression of stem cell markers and modulates the levels of muscle differentiation markers as shown by sphere assay and western blot analysis, respectively. Finally, overexpression of WNT5A can destabilize active β‑Catenin of RMS cells. A WNT5A knockdown has opposite effects. Together, the results suggest that WNT5A has tumor suppressive functions in RMS, which accompanies downregulation of β‑Catenin.
Topics: Cell Differentiation; Cell Line; Humans; Rhabdomyosarcoma; Wnt Signaling Pathway; Wnt-5a Protein; beta Catenin
PubMed: 35796028
DOI: 10.3892/ijo.2022.5392 -
Frontiers in Oncology 2022Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases...
BACKGROUND
Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases and altogether account for ~20% of all soft tissue sarcomas (STS) and bone sarcomas. The Italian Sarcoma Group has recently performed a non-interventional, retrospective TrObs study with data from 512 anthracycline-pretreated patients with advanced multiple STS histologies and treated with trabectedin (Palmerini, 2021; ClinicalTrials.gov Identifier: NCT02793050).
METHODS
A analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety.
RESULTS
Thirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6).
CONCLUSIONS
Trabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.
PubMed: 36568164
DOI: 10.3389/fonc.2022.1042479 -
JPMA. the Journal of the Pakistan... Sep 2022Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma, making 50% of all diagnosed cases. It is a complex disease that has the potential to arise from...
Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma, making 50% of all diagnosed cases. It is a complex disease that has the potential to arise from any tissue of the body except the bones. There are four types of rhabdomyosarcoma; embryonal, botryoidal, alveolar and pleomorphic. [18F]-FDG PET-CT plays a vital role in staging, response evaluation and follow-up of the disease. Due to significant morbidity and mortality with high-risk disease, proper staging is of paramount importance. Staging of rhabdomyosarcoma depends on tumour localization, infiltration of local structures by the primary tumour, nodal involvement, and presence of visceral metastases. Without timely intervention, rhabdomyosarcoma progresses at an exponential speed.
Topics: Child; Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Tomography, X-Ray Computed; Neoplasm Staging; Positron-Emission Tomography; Rhabdomyosarcoma; Radiopharmaceuticals
PubMed: 36281001
DOI: 10.47391/JPMA.22-96 -
Head and Neck Pathology Sep 2017Head and neck rhabdomyosarcoma occurs frequently in children and adolescents, and has been well studied in that population. In contrast, it is rare in adults and is not...
Head and neck rhabdomyosarcoma occurs frequently in children and adolescents, and has been well studied in that population. In contrast, it is rare in adults and is not as well characterized clinically and pathologically. Seven cases of adult rhabdomyosarcoma occurring in head and neck were retrieved from the archives of Department of Pathology and Division of Oral Pathology at University of Washington. Radiologic findings and clinical history, as well as pathologic findings from hematoxylin and eosin slides and immunohistochemistry for myogenic markers were reviewed. A total of seven cases of rhabdomyosarcoma (two embryonal, three alveolar and two pleomorphic subtype) were reviewed. Patient ages ranged from 18 to 57 years (median 21 years). Classic and unique histologic features for each subtype, including post-treatment morphologic changes, were identified. Clinical follow-up information was available for 4 patients. 3 of 4 patients experienced recurrence, including two with distant metastasis. One patient died of disease progression 41 months after presentation. Head and neck rhabdomyosarcoma in adults can manifest both classic and unique histologic features for each subtype. In addition, recurrence and distant metastasis were observed, suggesting aggressive clinical behavior regardless of subtype.
Topics: Adolescent; Adult; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Rhabdomyosarcoma; Young Adult
PubMed: 27896667
DOI: 10.1007/s12105-016-0771-0 -
Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study.Cancer Medicine Aug 2018Five-year overall survival (OS) of localized RMS exceeds 70% in children (<18) but is very poor in adult patients. We analyzed the outcome and prognostic factors (PF) of... (Review)
Review
Five-year overall survival (OS) of localized RMS exceeds 70% in children (<18) but is very poor in adult patients. We analyzed the outcome and prognostic factors (PF) of a national series of adult patients with RMS in a large study. The study population consisted of two different cohorts: a retrospective cohort (157 adult patients treated in 13 reference centers between 05/1981 and 02/2010) and the prospective cohort (292 patients with RMS diagnosed and treated between 01/2010 and 12/2014 in France) included in the NetSarc database. A descriptive analysis of patients' characteristics and prognostic factors was conducted on both series which were compared. In the retrospective series, histological subtypes were embryonal (E-RMS) for 21% of patients, alveolar (A-RMS) for 35% of patients, and "adult-type" P-RMS (pleomorphic, spindle cell RMS, not otherwise specified) (P) for 44% patients. This distribution significantly differed in the prospective cohort: A-RMS: 18%; E-RMS: 17%; and P-RMS 65%. With a median follow-up of 8.5 years, 5-year OS for localized RMS and advanced RMS (with nodes and/or metastases) was 43% and 5%, respectively, (P < 0.0001), and median OS was 51, 33, and 16 months for E-RMS, A-RMS, and P-RMS, respectively, in the retrospective cohort. The median OS was less than 40 months for the prospective nationwide cohort for the entire population. In a multivariate analysis of the retrospective study, independent prognostic factors for OS were A-RMS, R0 resection, and adjuvant radiotherapy (RT). For localized RMS, age and use of pediatric chemotherapy (CT) regimen are independent prognostic factors. Adult patients with RMS have a poorer overall survival than pediatric patients, and survival varies considerably across histological subtypes.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Female; France; Humans; Male; Middle Aged; Patient Outcome Assessment; Prognosis; Public Health Surveillance; Retrospective Studies; Rhabdomyosarcoma, Embryonal; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 29956493
DOI: 10.1002/cam4.1374 -
Sarcoma 2022Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma for which subsets of patients have longstanding unmet clinical needs. For example, children with...
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma for which subsets of patients have longstanding unmet clinical needs. For example, children with alveolar rhabdomyosarcoma and metastases at diagnosis will experience only 8% disease-free 5-year survival for nonlocalized unresectable recurrent disease. Hence, development of novel therapeutic strategies is urgently needed to improve outcomes. The Plexin-Semaphorin pathway is largely unexplored for sarcoma research. However, emerging interest in the Plexin-Semaphorin signaling axis in pediatric sarcomas has led to phase I cooperative group dose-finding clinical trials, now completed (NCT03320330). In this study, we specifically investigated the protein expression of transmembrane receptor Plexin-B2 and its cognate SEMA4C ligands in clinical RMS tumors and cell models. By RNA interferences, we assessed the role of Plexin-B2 in cell growth and cell migration ability in selected alveolar and embryonal RMS cell model systems. Our results affirmed expression of Plexin-B2 across human samples, while also dissecting expression of the different protein subunits of Plexin-B2 along with the assessment of preferred Semaphorin ligands of Plexin-B2. Plexin-B2 knockdown had positive or negative effects on cell growth, which varied by cell model system. Migration assayed after Plexin-B2 knockdown revealed selective cell line specific migration inhibition, which was independent of Plexin-B2 expression level. Overall, these findings are suggestive of context-specific and possibly patient-specific (stochastic) role of Plexin-B2 and SEMA4 ligands in RMS.
PubMed: 35570846
DOI: 10.1155/2022/9646909 -
BMJ Case Reports Jul 2021This is the case of a parameningeal alveolar rhabdomyosarcoma (ARMS) in a 13-year-old boy who presented with painless loss of vision in the right eye, but very few other...
This is the case of a parameningeal alveolar rhabdomyosarcoma (ARMS) in a 13-year-old boy who presented with painless loss of vision in the right eye, but very few other physical signs. The ARMS diagnosis was confirmed with imaging and molecular characterisation of the tumour. Despite tolerating the initial chemotherapy and radiotherapy regimens, there was leptomeningeal recurrence and the patient unfortunately passed away. Parameningeal ARMS occurs in an area of the body, which leads to a wide variety of possible presenting symptoms, creating a long list of differentials that can delay treatment. This tumour subtype has a poor prognosis, and due to the location of the tumour around vital structures in the head, treatment toxicities must be taken into account. This highlights the necessity for having a strong index of suspicion for this tumour in atypical presentations in children, and the necessity for prompt treatment to prevent leptomeningeal disease from occurring.
Topics: Adolescent; Child; Family; Head and Neck Neoplasms; Humans; Male; Meningeal Neoplasms; Neoplasm Recurrence, Local; Rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal
PubMed: 34266827
DOI: 10.1136/bcr-2021-243267 -
Pediatric Blood & Cancer Sep 2021Rhabdomyosarcoma (RMS) is characterized by the expression of the myogenic regulatory protein MYOD1. Histologic types include alveolar, embryonal (ERMS), and spindle cell...
BACKGROUND/OBJECTIVES
Rhabdomyosarcoma (RMS) is characterized by the expression of the myogenic regulatory protein MYOD1. Histologic types include alveolar, embryonal (ERMS), and spindle cell sclerosing RMS (SRMS). SRMS harbors MYOD1 mutations in a subset of adult cases in association with poor prognosis.
DESIGN/METHODS
To study the level of MYOD1 protein expression and its clinical significance, we have analyzed variable numbers of pediatric (<18 years of age) and adult (age range ≥18 to 35 years) ERMS and SRMS cases for presence or absence of MYOD1 immunoreactivity in correlation with clinical outcome and MYOD1 L122R mutations.
RESULTS
Lack of MYOD1 immunoreactivity, identified in 23.8% of nonalveolar RMS (non-ARMS) cases, was more prevalent in SRMS (44%) than ERMS (17.2%) and was significantly associated with low overall survival and unfavorable tumor sites (p < .05). Lack of MYOD1 immunoreactivity was not associated with MYOD1 L122R mutations, which were identified in 3/37 (8%) cases including only two of 31 (6.5%) pediatric cases, one of 11 or 9% pediatric SRMS, and one case of infant ERMS.
CONCLUSION
These studies highlight the prognostic role of MYOD1 in non-ARMS. Lack of MYOD1 immunoreactivity is associated with poor prognosis in ERMS and SRMS. MYOD1 gene mutations are generally infrequent in pediatric RMS. Although mutations are predominant in SRMS, they may exceptionally occur in infantile ERMS.
Topics: Adolescent; Adult; Child; Humans; Infant; Mutation; MyoD Protein; Prognosis; Rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal; Young Adult
PubMed: 33913590
DOI: 10.1002/pbc.29085 -
Clinical Cancer Research : An Official... Sep 2022Placental growth factor (PlGF) and its receptor neuropilin 1 are elevated in malignant embryonal tumors and mediate tumor progression by promoting cell proliferation,...
PURPOSE
Placental growth factor (PlGF) and its receptor neuropilin 1 are elevated in malignant embryonal tumors and mediate tumor progression by promoting cell proliferation, survival, and metastasis. TB-403 is a blocking monoclonal antibody against PlGF that inhibits tumor growth and increases survival in orthotopic medulloblastoma models.
PATIENTS AND METHODS
We conducted a phase I, open-label, multicenter, dose-escalation study of TB-403 in pediatric subjects with relapsed or refractory cancers. The study involved four dose levels (20 mg/kg, 50 mg/kg, 100 mg/kg, 175 mg/kg) using a 3 + 3 dose-escalation scheme. Subjects received two doses of TB-403 (days 1 and 15) per cycle. After cycle 1, temozolomide or etoposide could be added. The primary objective was to determine the maximum tolerated dose (MTD) of TB-403 monotherapy during a dose-limiting toxicity assessment period. The secondary and exploratory objectives included efficacy, drug pharmacokinetics, and detection of pharmacodynamic biomarkers.
RESULTS
Fifteen subjects were treated in four dose levels. All subjects received two doses of TB-403 in cycle 1. Five serious treatment-emergent adverse events were reported in 3 subjects, but MTD was not reached. While no complete nor partial responses were observed, 7 of 11 relapsed subjects with medulloblastoma experienced stable disease, which persisted for more than 100 days in 4 of 7 subjects.
CONCLUSIONS
TB-403 was safe and well tolerated at all dose levels. No MTD was reached. The results look encouraging and therefore warrant further evaluation of efficacy in pediatric subjects with medulloblastoma.
Topics: Antibodies, Monoclonal, Humanized; Brain Neoplasms; Cerebellar Neoplasms; Child; Female; Humans; Maximum Tolerated Dose; Medulloblastoma; Neuroblastoma; Placenta Growth Factor; Rhabdomyosarcoma, Alveolar; Sarcoma, Ewing
PubMed: 35833850
DOI: 10.1158/1078-0432.CCR-22-1169