Histiocytis Sarcoma-Targeted Therapy: Novel Therapeutic Options? A Series of 4 Cases
Authors: Schlick Konstantin , Pichler Martin , Reitter Sonja , Neumeister Peter , Hoefler Gerald , Beham-Schmid Christine , Linkesch Werner , Strunk Dirk , Aigelsreiter Ariane 
Published: October 2019

Abstract
Abstract 5005
Case 1: A 23-year old man presented with a newly diagnosed Histiocytic Sarcoma (HS) of the neck. Tracheotomy had to be performed due to a massive swelling of the neck and pharynx. Chemotherapy was initiated in combination with local irradiation therapy with the aim of stabilization of the fulminate disease course.To gain further insight in the tumour's biology an extensive immunohistochemistry exploration was done. A positive reaction with antibodies (AB) against PDGFRalpha and VEGFR2 and VEGFR3 was detected with variable staining intensities and number of tumor cells. According to this marker profile the tyrosinkinase inhibitor Imatinib and the immunomodulating agent thalidomide were added to the chemotherapy regimen. The therapy regime of both agents, which can only be applied orally, could only partially be followed due to the massive pharyngeal mass and repeated emesis. After two cycles of chemotherapy the patient showed progressive disease and succumbed to fulminant pericardial effusions and progressive disease.
Case 2: A 53-years old female with a history of exogenous allergic asthma bronchiale was admitted to a hospital. CT scan was performed and the presumption diagnosis of pneumonia was made. Due to thickened pleura with suspect pericardial infiltrations the differential diagnosis of mesothelioma was reported and a video assisted thoracoscopy with biopsies were obtained. Immunohistochemistry was positive for EGFR, PDGFRalpha, PDGFRbeta, and VEGFA20. Two cycles of an experimental therapy regime containing Imatinib and Bevacizumab, combined with chemotherapy were applied. Restaging imaging studies showed a stable tumour load in the CT and PET scans. The patient could be discharged under continuation of daily imatinib therapy and bevacizumab every 14 days. Five months later the patient showed progressive disease and succumbed.
Case 3: A 48-year old male patient presented with a newly diagnosed HS of the right upper leg. Tumour tissue could not be removed in sano due to infiltration of the surrounding fat tissue. Seven months later the patient was hospitalised again with a local recurrent tumor. According to the literature two cycles of chemotherapy for extramedullary myeloid leukaemia was applied and the patient was discharged in a complete remission. Seven months later the patient developed severe back pain and a biopsy of the spine was taken. Histology reported metastasis of HS. A polychemotherapy was applied coming up with a no change course of the disease. An immunohistochemical workup showed a positive reaction with antibodies against EGFR, PDGFRalpha PDGFRbeta and VEGFC1. A Bevacizumab monotherapy was applied for three times, however showing no response. Finally, the patient died due to progressive disease.
Case 4: A 68-year old female was admitted to hospital after diagnosis of a HS of the intestinal tract. A tumor of the terminal ileum of six cm in greatest diameter had been surgically removed in sano. Five weeks later the patient presented with pathologically enlarged mediastinal and abdominal lymph nodes in CT scan. Progressive disease was confirmed by a PET scan. An immunohistochemical workup showed a positive reaction with AB against PDGFRalpha, PDGFRbeta, VEGFR2 and VEGFR3 An experimental treatment approach of two cycles with a combination of Bevacizumab and chemotherapy was applied. In addition a low dose maintenance therapy with Sorafenib 2×400mg daily was administered due to pancytopenia. Therapy had to be discontinued after one month due to elevation of pancreatic enzymes. A restaging CT scan showed no pathological enlarged lymph nodes and a PET scan, two months after initiation of therapy, revealed a complete metabolic remission. Five months later on control revaluation remission was stable by CT and PET scan. Nowadays, almost two years later, the patient is still in an ongoing complete remission without any further therapy.

Disclosures:
No relevant conflicts of interest to declare.