Clinicopathological Features And Prognosis of Primary Pulmonary Rhabdomyosarcoma In The Middle-Aged And Elderly: A Case Report And Literature Review

Background: Primary pulmonary rhabdomyosarcoma（PPRMS）in the middle-aged and elderly is a very rare event with only a few cases published. To date, only thirty-five cases of PPRMS in the middle-aged and elderly have been published. However, the analyses on clinicopathological characteristics and prognosis of PPRMS in the middle-aged and elderly have not been performed.Case presentation: We report an additional case of PPRMS in the middle-aged and elderly.Conclusions: PPRMS in the middle-aged and elderly was a highly malignant soft tissue tumor with obvious gender characteristics and significant age distribution. Pleomorphic rhabdomyosarcoma (RMS) was the most common subtype, with poor prognosis and significantly prolonged survival time after surgical resection.

A CASE REPORT OF A YOUNG MAN WITH ABDOMINAL MASS: HUNT FOR DIAGNOSIS

Introduction: Extraskeletal Ewing sarcoma/PNET is a small round cell sarcoma showing gene fusions of EWSR1-FLI1. A 28-year-old male patient presented with right ank pain and low gr Case Report: ade fever since 15 days. On examination: a mass was palpable in the right hypochondrium. Provisional diagnosis of Liver abscess has been made. USG abdomen shows features cystic lesion in the liver with internal septation ?Liver abscess /Hydatid cyst. Intraoperatively, tumor was seen attached to upper pole of kidney. Since tumor was large, it was ruptured intraoperatively and debulking surgery has been done. Under microscopy, tumor was arranged in sheets with intervening stroma showing desmoplastic reaction. Perivascular pseudorosettes are seen. The diagnosis of malignant small round cell tumor has been given. On immunohistochemistry, tumor cells are positive for Vimentin, CD99, NKX2.2 , FLI1, Neurolaments, Synaptophysin with focal immunoreactivity for EMA, Pancytokeratin. Final diagnosis was EXTRASKELETAL EWING SARCOMA/PNET. Discussion: Extra-skeletal Ewing sarcoma/PNET is malignant soft tissue tumor seen in chest wall, thigh, paravertebal region etc. Retroperitoneum is a least common site. Most common presentation is swelling in the soft tissue with compressive symptoms. Histologically, it is composed of undifferentiated small round cells. Conclusion: Clinical examination and radiological ndings leads to ambiguous diagnosis in Ewing sarcoma/PNET. Hence proper histopathological study is essential for nal diagnosis.

Embryonal Rhabdomyosarcoma with Posttherapy Cytodifferentiation and Aggressive Clinical Course

Rhabdomyosarcoma is the most common soft tissue sarcoma in children and adolescents. Embryonal rhabdomyosarcoma (ERMS), its most common subtype, is a malignant soft tissue tumor with morphologic and immunophenotypic features of embryonic skeletal muscle. The histologic findings in ERMS typically include a range of differentiation in rhabdomyoblasts from primitive to terminally differentiated forms, and the latter become more prominent after chemotherapy-induced cytodifferentiation. Several reports have shown therapy-related cytodifferentiation to portend a good prognosis in ERMS. We discuss the case of a pediatric patient who presented with ERMS of the orbit. Although her tumor showed extensive posttreatment cytodifferentiation and several other good prognostic clinicopathologic factors, it pursued an aggressive course, resulting in early metastasis and death. This case represents an unusual course and may be instructive as to the clinicopathologic features impacting prognostication, and ultimately the biology, of this aggressive family of tumors.

Synovial Sarcoma in Children, Adolescents, and Young Adults: A Report From the Children's Oncology Group ARST0332 Study

PURPOSE Synovial sarcoma (SS) is the second most common malignant soft tissue tumor in children. ARST0332 evaluated a risk-based treatment strategy for young patients with soft tissue sarcoma designed to limit therapy for low-risk (LR) disease and to test neoadjuvant chemoradiotherapy for unresected higher-risk disease. METHODS Newly diagnosed patients with SS age < 30 years were assigned to four treatment arms based on disease features: A (surgery only), B (55.8 Gy radiotherapy [RT]), C (ifosfamide and doxorubicin [ID] chemotherapy plus 55.8 Gy RT), and D (neoadjuvant ID and 45 Gy RT, then surgery and RT boost based on margins followed by adjuvant ID). Patients treated in Arms A and B were considered LR, arms C and D without metastases as intermediate-risk (IR), and those with metastases as high-risk (HR). RESULTS Of the 146 patients with SS enrolled, 138 were eligible and evaluable: LR (46), IR (71), and HR (21). Tumors were 80% extremity, 70% > 5 cm, 70% high-grade, 62% invasive, 95% deep, and 15% metastatic. Treatment was on arm A (29.7%), B (3.6%), C (16.7%), and D (50%). There were no toxic deaths and four unexpected grade 4 adverse events. By risk group, at a median follow-up of 6.8 years, estimated 5-year event-free survival was LR 82%, IR 70%, and HR 8%, and overall survival was LR 98%, IR 89%, and HR 13%. After accounting for the features that defined risk category, none of the other patient or disease characteristics (age, sex, tumor site, tumor invasiveness, and depth) improved the risk stratification model. CONCLUSION The risk-based treatment strategy used in ARST0332 produced favorable outcomes in patients with nonmetastatic SS relative to historical controls despite using RT less frequently and at lower doses. The outcome for metastatic SS remains unsatisfactory and new therapies are urgently needed.

Clinical characteristics of patients with undergoing unplanned excisions of malignant soft tissue tumors

Introduction Malignant soft tissue tumors are rare tumors representing <1% of all malignancies. As these tumors are rare, it is not uncommon that malignant soft tissue tumor excision is performed without the required preoperative imaging, staging, or wide resection margins for sarcomas. The purpose of this study was to investigate the characteristics of patients with undergoing unplanned excisions. Risk factors for tumor recurrence and mortality in patients treated with unplanned excisions were also analyzed. Methods Forty-nine patients who underwent unplanned excision at other hospitals and additional wide excision at our hospital between January 2002 and December 2018 were identified. Among them, 42 patients with follow-up for more than 1 year were included in this retrospective study. The relationships between sex, age, tumor depth, histological grade, location, size, surgical margin at additional wide excision, residual tumor, reconstruction, kind of hospital where the primary excision was done (sarcoma vs non-sarcoma center), preoperative examination, chemotherapy, radiation therapy, and oncological outcomes were statistically analyzed. Results Mean patient age was 57.3 years (15–85 years) and the mean observation period was 72.5 months (14–181 months). This analysis showed 53.8% tumors that underwent unplanned excisions were small (<5 cm) and 70.7% tumors were superficial. Multivariate analysis revealed that a positive margin during additional wide excision was significantly associated with a lower 5-year LRFS ( p < 0.01). Conclusion Most of the tumors underwent unplanned excisions were small (<5 cm) and superficial. Surgeons should be aware that a positive margin during additional wide excision is an independent risk factor for local recurrence.

Accumulation of genome-wide somatic loss of heterozygosity (LOH) as a prominent feature of advanced malignant soft tissue tumors and association with the BRCAness status, suppression of immune responses, and lower survival rates.

11533 Background: Malignant soft tissue tumor is a rare cancer with few therapeutic options. Recent genomic analysis revealed widespread CNA and the cumulative burden of cancer-related pathogenic germline mutations/variants, their clinical and therapeutic significance were unknown. Methods: We recruited 155 patients with advanced malignant soft tissue tumors (135 female and 20 male, mean age 51 at analysis, 100 LMS, 19 LPS, 4 ESS, 3 UPS, 3 AS, 3 MPT, 3 GIST and others) with confirmed metastasis/recurrence and information on familial cancer burden. Whole exome sequencing was performed in both blood and tumor samples as described in 2018ASCO. The copy number of BRCA2 gene was determined by the MLPA method. Tumor immune microenvironment was assessed by immunohistochemistry. The MSI status was analysed by PCR. Results: We analyzed the LOH status in 595 COSMIC genes and found that genome-wide accumulation of somatic LOH of polygenic germline mutations/variants. Patients with more than 33% LOH genes (n=102) in the total of somatic and LOH mutations showed significantly lower OS rates compared with those (n=53) with less LOH genes (5-year survival rates; 49 vs 75%, p=0.010), which constitute 78% of LMS (n=78/100) and 26% of LPS (n=5/19). Total of 41 patients (26%, n=41/155) including 33 LMS (33%, n=33/100) showed LOH in the BRCA2 locus with hemizygous VUS. Those patients with BRCA2 LOH (n=41) showed significantly lower OS rates compared with those without BRCA2 LOH (n=114) (5-year survival rates; 43 vs. 64%, p=0.019). Neither TMB nor the MSI status was associated with LOH. In contrast, accumulation of somatic LOH (mean LOH values of 71.7 vs. 15.7%) was clearly and negatively associated with CD8+T-cell immune infiltrates (T-cells; 44±23 vs 555±180/mm2, n=7, p=0.016), CD20+B-cell accumulation in tertiary lymphoid structures (TLS) (TLS; 0.57±0.43 vs. 20.1±6.1/tumor, n=7, p=0.008) and low levels of neutrophil-to-lymphocyte ratio (NLR) (NLR; 3.63±0.45 vs. 1.71±0.17, n=7, p=0.002), hallmarks of the immunological response to tumors. Conclusions: This study suggests that in advanced malignant soft tissue tumors, accumulation of genome-wide LOH of germline mutations/variants is associated with the BRCAness status and suppression of the immune responses to tumors, and thus influences therapeutic response and survival of the patients.

Adult Primary Pineal Alveolar Rhabdomyosarcoma With FOXO1 Gene Rearrangement and OLIG2 Expression: a Case Report and the Literature Review

Introduction: Alveolar rhabdomyosarcoma (ARMS) is a common malignant soft tissue tumor in child and adolescents. When diagnosed in adults, it is an aggressive, often fatal disease. Intracranial ARMS in adults is rare, especially in the pineal region. Case presentation: A 36-year-old Chinese man presented with a 3-month history of dizziness and 1-month history of headache and unsteady walking. Magnetic resonance imaging of the brain revealed a pineal region lesion with obstructive hydrocephalus. He received ventricular-abdominal shunt and endoscopic-assisted pineal lesion resection.The tumor appears as a solid sheet-like growth of medium-sized round or oval cells with map-like necrosis and some rhabdomyoblasts. Immunohistochemical test revealed that tumor cells were diffusely positive for desmin, myogenin, MyoD1, ALK and CD56. Notably, the tumors were diffusely positive for OLIG2. Fluorescence in situ hybridization confirmed the FOXO-1 gene rearrangement. The final diagnosis of the present case is ARMS of the pineal gland. Conclusions: We presented an extremely rare case of primary ARMS in adult pineal region particularly with expression of OLIG2 and confirmed by PAX3/7-FOXO1 fusion gene detection.

ACTA1 is inhibited by PAX3-FOXO1 through RhoA-MKL1-SRF signaling pathway and impairs cell proliferation, migration and tumor growth in Alveolar Rhabdomyosarcoma

Background Alveolar Rhabdomyosarcoma (ARMS) is a pediatric malignant soft tissue tumor with skeletal muscle phenotype. Little work about skeletal muscle proteins in ARMS was reported. PAX3-FOXO1 is a specific fusion gene generated from the chromosomal translocation t (2;13) (q35; q14) in most ARMS. ACTA1 is the skeletal muscle alpha actin gene whose transcript was detected in ARMS. However, ACTA1 expression and regulation in ARMS have not been well investigated. This work aims to explore the expression, regulation and potential role of ACTA1 in ARMS. Results ACTA1 protein was detected in the studied RH30, RH4 and RH41 ARMS cells. ACTA1 was found to be inhibited by PAX3-FOXO1 at transcription and protein levels by employing western blot, luciferase reporter, qRT-PCR and immunofluorescence assays. The activities of ACTA1 gene reporter induced by RhoA, MKL1, SRF, STARS or Cytochalasin D molecule were reduced in the presence of overexpressed PAX3-FOXO1 protein. CCG-1423 is an inhibitor of RhoA-MKL1-SRF signaling, we observed there was a synergistic effect between this inhibitor and PAX3-FOXO1 to suppress ACTA1 reporter activity. Furthermore, PAX3-FOXO1 overexpression decreased ACTA1 protein level and knockdown of PAX3-FOXO1 by siRNA enhanced ACTA1 expression. In addition, both MKL1 and SRF, but not RhoA were also found to be inhibited by PAX3-FOXO1 gene at protein levels and increased once knockdown of PAX3-FOXO1 expression. The association between MKL1 and SRF in cells was decreased accordingly with ectopic expression of PAX3-FOXO1. However, the distribution of MKL1 and SRF in nuclear or cytoplasm fraction was not changed by PAX3-FOXO1 expression. Finally, we showed that ACTA1 overexpression in RH30 cells could inhibit cell proliferation and migration in vitro and impair tumor growth in vivo compared with the control groups. Conclusions ACTA1 is inhibited by PAX3-FOXO1 at transcription and protein levels through RhoA-MKL1-SRF signaling pathway and this inhibition may partially contribute to the tumorigenesis and development of ARMS. Our findings improved the understanding of PAX3-FOXO1 in ARMS and provided a potential strategy for the treatment of ARMS in future.

Synovial sarcoma of the spine: A case report and review of the literature

Background: Synovial sarcoma (SS) of the spine is a rare malignant soft-tissue tumor, and there are few reported cases. The aim of this paper is to report a rare case of spinal SS involving the paraspinal muscles, and to review all such cases reported in the literature. Case Description: In this paper, we report a rare case of spinal SS involving the paraspinal muscles in a 12-year-old girl. The patient underwent surgical excision of the mass with adjuvant radiation and chemotherapy. At the 1-year follow-up, there was no evidence of local tumor recurrence, and the patient’s symptoms had improved. In addition, we identified and reviewed 33 reported cases of SS involving the spine. Conclusion: Due to the limited number of reported cases in the literature, it is difficult to predict the outcomes of spinal SS. Further, different treatment modalities have been used to treat spinal SS. However, most of the reported cases had poor outcomes. Therefore, prospective multi-center studies are needed to further investigate the treatment strategies and outcomes for patients with spinal SS.