Epithelioid Angiosarcoma in the Inguinal Canal Region of an 81-year-old man. Case Report of a Rare Tumor with Challenging Diagnosis and Review of the Literature

Prognostic modalities have long been essential for selecting adjuvant treatment in patients with Gastro Intestinal Stromal Tumor (GIST). The anatomic site of origin is a prognostic factor for GIST; GISTs originating in the small intestine (I-GISTs) have a considerably worse prognosis than GISTs originating in the stomach (S-GISTs). By studying the molecular backgrounds of GISTs with different sites of origin, it may be possible to identify novel prognostic biomarkers. This study aimed to identify prognostic biomarkers for GIST by comparing the molecular backgrounds and prognoses of S-GISTs and I-GISTs. A meta-analysis of 3 studies was performed to identify Differentially Expressed Genes (DEGs) between S-GISTs and I-GISTs. Receiver Operating Characteristic (ROC) analyses were performed for the DEGs, which were then ranked according to the areas under the ROC curves that they achieved. The Kaplan–Meier Method and log-rank test were used to estimate and compare survival curves. Protein-Protein Interaction (PPI) network analysis was performed using the DEGs, to identify hub genes associated with the malignant biological potential of GISTs. Overall, we identified 149 DEGs between S-GISTs and I-GISTs. Comparing I-GISTs with S-GISTs, 89 DEGs were up-regulated and 60 DEGs were down-regulated. Endothelin-3 (EDN3), which was up-regulated in I-GISTs, had the greatest area under the ROC curve of the 149 DEGs. Kaplan–Meier curves showed that high EDN3 expression was associated with significantly shorter disease-free survival in patients with S-GISTs. The EDN3 expression level was higher for high-risk patients with S-GIST than for low-risk patients with S-GISTs. Based on the PPI network of DEGs, EDN3 was identified as a hub gene related to the malignant biological potential of GIST. In summary, our study identified genes that are differentially expressed between S-GISTs and I-GISTs. EDN3 expression may have prognostic value for patients with GIST. Further validation studies of EDN3 are warranted for clinical application.

To determine potential mechanisms by which PpIX-PA (protoporphyrin IX-polyamines; PpIX is coupled with two molecules of spermidine (PpIX-dSd) or spermine (PpIX-dSm)) inhibited prostate cancer cell viability, we studied its effects on mitochondrial membrane potential because alterations in mitochondrial structure and function have been shown to play a crucial role at early stages of apoptosis.

Undifferentiated pleomorphic sarcoma, previously known as malignant fibrous histiocytoma, was one of the most common variant of soft-tissue sarcoma in adults (40 %). It was first recognized as a distinct clinicopathologic entity in the early 1960s as pleomorphic sarcoma. In the head and neck, malignant fibrous histiocytoma is extremely rare and accounts for only 3 % of all undifferentiated pleomorphic sarcomas. We are reporting a large unusual case of undifferentiated pleomorphic sarcoma involving the right submandibular gland in a 60-year-old male patient.

Long bone adamantinoma is a very rare malignant tumor of epithelial origin. In most cases it affects unilateral tibia and fibula, and the definitive treatment is surgical. Distant recurrence is unusual and its systemic treatment has heterogeneous results. We are reporting an unusual case of brain recurrence of tibial adamantinoma and the poor results with systemic treatment.

Background: Liposarcomas in pregnancy are peculiar clinical scenarios that are continuously being reported in the English literature for their rarity, challenges in management and speculations of association between pregnancy and disease kinetics. Most cases reported are with liposarcomas in the retroperitoneum. We here add another case whose lesion is at left thigh with optimal tumor excision and split-thickness skin graft reconstruction to augment both prognosis and aesthetics. A literature review for cases reported after 2000 will be presented.

Method: Case report and literature review.

Results: A 33-year-old female with left thigh tumor noted 1 year prior to her second pregnancy found the lesion growing in size at 18 weeks of gestation. Characteristics of the tumor included soft, elastic, fixed, painless, without discharge or discoloration, and sized about 5x5cm. Myxoid liposarcoma was diagnosed under histological examination after tumor biopsy under local anesthesia. She soon received complete tumor resection with free margins confirmed, followed by split-thickness skin graft reconstruction of the wound to meet cosmetic concerns. She currently continues with her pregnancy uneventfully and no tumor recurrence is observed. A literature search on Pubmed using keywords with sarcoma and pregnancy found 6 entries prior to the current study after year 2000. Patient characteristics, diagnosis modality, pathology histology subtypes, maternal and fetal outcomes are organized and presented.

Conclusion: Liposarcoma in pregnancy is rare but deserves practitioners’ attention, for early detection and proper surgical management could greatly improve disease outcomes. Life-long surveillance after surgery is also important for local recurrence rate is high. Further studies for the interplay of growth hormones and sex hormones during pregnancy and their effects on soft tissue sarcomas are called for, as they might be of valuable treatment or prevention bases.

Background: Patients with a metastatic or locally advanced Soft Tissue Sarcoma (STS) are normally treated with chemotherapy. However, pretreated or vulnerable patients with comorbidities may have difficulties tolerating the intensive intravenous standard regimens. Trofosfomide, a peroral prodrug to ifosfamide, has been described to have promising effects in the treatment of STS. For childhood STS the combination of trofosfamide and etoposide has been used as maintenance therapy, but its utility in the treatment of adult STS has yet to be described.

Methods: A retrospective single center experience comprising of 69 adult patients with advanced STS, treated with Trofosfamide and Etoposide in combination (TE), is presented. The medical records, including pathology and radiology reports, of all patients who initiated TE between May 2002 and September 2015 were reviewed. We present data on duration of treatment, best radiological response and reason for ending treatment and side-effects. The treatment schedule consisted of oral trofosfamide 100 mg (total dose) twice a day from day 1-10, and oral etoposide 50 mg (total dose) twice a day from day 1-10, with a cycle length of 21 days.

Results: Among the 69 patients, the median treatment time was 103 days. A treatment time longer than 90 days were noted for 55.1%, and more than 180 days for 31.9 %. Patients with synovial sarcoma and well differentiated liposarcoma had the longest treatment times. Long treatment times were also noted in patients with other STS histologies. The treatment was well tolerated, regardless of patient age. Hematological toxicities however lead to dose-reductions and supportive measures in more than half of the cases. Three patients were diagnosed with MDS after long treatment times.

Conclusions: The combination of trofosfamide and etoposide is shown to be an effective and well tolerated treatment for adult patients with advanced STS of different histiotypes. TE is a good treatment option for heavily pretreated or vulnerable patients, e.g. caused by comorbidities. The risk for developing secondary cancer after treatment with TE should be considered.

The discovery of the driver mutation BRAF in melanoma has led to the emergence of new therapeutic treatments resulting in prolonged survival. By combining BRAF inhibitors with MEK inhibitors, median Overall Survival (OS) for patients with metastatic disease is approximately 2 years, which is an improvement by nearly a year and a half over previous therapies. Unfortunately, over 90% of patients will ultimately develop resistance to the targeted therapies and experience disease progression. Several mechanisms of resistance have been identified, including mutant BRAF allele amplification, BRAF splice variation, and activation of MEK1/2. These mechanisms are the focus of intensive research as new drugs emerge to potentially overcome resistance. This review focuses on the discovery of the BRAF mutation, the development of combination targeted therapy, the emergence of resistance to these targeted therapies, and new drugs in development to overcome this resistance

Soft tissue sarcomas (STS) are a group of different diseases that differ in presentation, response to therapies and prognosis. Some new interesting approaches are becoming available in the treatment of locally advanced as well as metastatic disease, leading to an improvement of patient’s survival. Neoadjuvant chemotherapy has the aim to limit the extension of surgery and to improve the systemic control of the disease and it is currently widely accepted. In the metastatic setting the modern concept of histology-driven therapy has overcome the universal use of the combination of Antracyclines and Ifosfamide in all subtypes of STS.

Some recent chemotherapic agents such as Trabectidine, Eribuline, or targeted compounds such as Pazopanib, Imatinib, Crizotinib, and Sunitinib have a defined role in some specific STS. Olaratumab, an anti PDGFRα monoclonal antibody, has recently been approved in combination with Doxorubicin as first line treatment in metastatic STS. Second line treatment is now adopted in many patients and leads to PFS and TTP improvement. Now-a-days the role of supportive care to increase the activity and to reduce toxicity of chemotherapy is well recognized.

Conversely, despite biological evidence supporting the role of immunotherapy in STS, adoptive and anti check point inhibitors therapies failed to show any activity and different further approaches are awaited.

Immune checkpoint inhibitors revive pre-existing immune responses that are suppressed in cancer. To restore innate tumour surveillance that is lost in cancer patients, a tumoricidal agent may have synergistic activity with certain immune checkpoint inhibitors. Herein, we report on our clinical experience using two FDA-approved drugs, trabectedin, a marine derived natural alkaloid with pro-apoptosis and immune modulator properties, in combination with nivolumab, a PD-1 immune checkpoint inhibitor, in advanced Soft Tissue Sarcoma (STS). Twenty-eight heavily pre-treated STS patients received trabectedin (1.5 mg/m2 Continuous Intravenous Infusion, CIV, for 24 hours) every 3 weeks, and nivolumab (3 mg/kg IV over 30 minutes) every 2 weeks. Retrospective analysis of safety/toxicity was conducted using the NIH/NCI CTCAE v.4.03. Tumour responses were assessed by RECIST v1.1 and irRECIST. Histologic subtypes in 28 patients include undifferentiated pleomorphic sarcoma (UPS; n=7), myofibroblastic sarcoma (n=1), leiomyosarcoma (n=6), synovial sarcoma (n=4), liposarcoma (n=6), chondrosarcoma (n=2), and Ewing sarcoma (n=2). All patients had metastatic disease and a median of 4 lines of prior chemotherapy. Safety analysis (n=28): Grade 3 treatment emergent adverse events include anaemia (n=2), fatigue (n=1), decreased platelet count (n=1), decreased granulocyte count (n=1) and increased creatine kinase (n=1). Efficacy analysis (n=22): Twenty-two patients were followed for at least 6 months and their results are reported here. There were 4 partial responses (UPS=1, myxoid liposarcoma=1, chondrosarcoma=1, leiomyosarcoma=1), 12 stable disease and 6 progressive disease, with best overall response rate of 18.2%, median progression free survival (PFS) of >45.4 weeks (range: 10->95 weeks), median Overall Survival (OS) of >66.5 weeks (10->95 weeks), 6 month PFS rate of 68.2%, and 6 month OS rate of 95.4%. Taken together, the data suggest that paired administration of trabectedin and nivolumab is safe, and that this chemo-/immuno therapy approach has synergistic activity that can lead to improved clinical outcomes.

Synovial sarcoma is a rare soft tissue cancer occurring more frequently in adolescent and young adults than older people. The primary sites being the joints of the arms and the legs.

A novel Nutrient Mixture (NM) containing green tea extract, ascorbic acid, lysine, and proline exhibited anti-cancer effects in various cancers. In our earlier studies, the NM considerably reduced the tumor weight and tumor burden in synovial sarcoma. Based on the observation, we investigated whether this phenomenon and the anti-cancer effects were due to the induction of apoptosis. Synovial sarcoma cell line SW982 was cultured in complete DME media and the cells were treated with NM at 0-1000 µg/ml concentration. Cell cytotoxicity was measured by MTT assay, morphology by H&E staining, and the apoptosis by Green Caspases. NM showed no significant cytotoxicity at 100 µg/ml, slight toxicity at 500 µg/ml and maximum at 1000 µg/ml. H&E staining at the NM dose of 100 µg/ml showed a few cellular changes characteristic to apoptosis, while significant changes pertaining to apoptosis morphology were observed at 500 and 1000 µg/ml. Live Green Caspases analysis showed cells in early and late apoptosis with increasing doses of NM. Since there are no satisfactory treatments and cures for synovial sarcoma patients and the 5-year survival rate is low (55-75%), we think that addition of NM could add a new option for the patients of synovial sarcoma and deserves further clinical investigation