Unusual Presentation of Ewing’s Sarcoma

Unusual Presentation of Ewings SarcomaD.V.Prasad1, Sanjay Mulay2, Krishna Badgire 3, *Abhinav S.Jadhav4, Deepak Datrange5, Sagar Jawale6, Arun alex7ABSTRACTEwings sarcoma is a broad(prenominal)ly malignant, polish cell tumour of uncertain origin. It is the sixth most common malignant neoplasm of bone. It must be distinguished from chronic osteomyelitis and other malignant round cell tumors corresponding lymphoma, metastatic neuroblastoma and small cell osteosarcoma. Most patients are amid 10 to 25years old rarely patients are younger than age 5 years and erstwhile(a) than age 40 years. We report a 55 years female who presented with swelling over discipline shoulder with pain and unfitness to move right shoulder later diagnosed as Ewings sarcoma of proximal part of humerus right side. The earlier diagnosis at this age may help in split management of the condition and prevent further complications and have better prognosis.KEY WORDS Ewings sarcoma, Primitive neuroectodermal tumor (PNET), Ewing family of tumors (EFT), round cell tumor.INTRODUCTIONEwings sarcoma is a highly malignant, round cell neoplasm of uncertain origin. It is the sixth most common malignant tumor of bone 1. Most patients are between 10 to 25years old rarely patients are younger than age 5 years and older than age 40 years. The present report is about rare presentation of Ewings sarcoma in a 55 years old female who presented with swelling over right shoulder with severe pain and inability to move right shoulder.CASE REPORTA55 years old female, housewife, was presented with progressive swelling over right shoulder and difficulty in shoulder movements. chunk was accompanied with severe pain which increased gradually over a period of 6 months.On examination, she was an average built female with swelling over right shoulder and upper part of right sleeve. Swelling was of 25x20cm size. It was a solitary swelling with local rise of temperature over swelling. Swelling was tender and prot ean in consistency. It was a non-mobile swelling. Redness and prominent superficial veins were visible over swelling over right shoulder and upper part of arm (Fig.1). Her haemoglobin levels were decreased and she had elevated erythrocyte sedimentation rate (ESR). Her renal function tests and liver function tests were towards lower normal range.X-ray right shoulder with arm shows round lytic lesion in head and upper part of humerus (Fig.2). MRI of right shoulder joint was suggestive of a 8.76.76.5 cm well defined, lobulated, expansile, lytic, lesion involving head and proximal shaft of right humerus, causing thinning and erosion of the cortex with breach at few places and narrow zone of transition, adjacent soft tissue extensions with dropsy and moderate right shoulder joint effusion. These findings are suggestive of Neoplastic mass involving proximal humerus with pathological fractures (Fig. 3)Histopathology report shows sheets of small round cells with hyperchromatic nuclei, con densed chromatin and meager eosinophilic cytoplasm with vaculisations with unremarkable bony trabeculae (Fig.4). Immuno-histochemistry is suggestive of Vimentin, CD99, S 100 positive and AE1/AE3 focally positive. Cytology report was suggestive of cytomorphological features positive for malignancy (Fig.5).Fig. 1 clinical photograph of patient showing right shoulder swelling. Fig.2X-ray right shoulder showing round lytic area in upper end of humerus.Fig. 3 MRI right shoulder T1W,T2W and STIR images showing expansile, lobulated, lytic lesion involving head and proximal part of humerus.Fig.4 Microscopic picture (40X) showing sheets of small round cells with hyperchromatic nuclei, condensed chromatin and panty eosinophilic cytoplasm.Fig.5 Cytology report showing cytomorphological features positive for malignancyDISCUSSIONIn 1918 Arthur Purdy intrepid described a tumor composed of small round cells with rose windows in Ulnar nerve 2, later on it became known as Primitive neuroectoderma l tumor (PNET). James Ewing described a tumor of diaphysis of long bone composed of undifferentiated cells and the tumor was radiosensitive 3. Earlier Ewings sarcoma (ES) PNET were described as two separate entities, but in 1975 Angervall and Enzinger described unnecessaryskeletal tumor resembling to ES 4and Jaffe et al. wrote an article on the neuroectodermal tumor of bone in 1984 5. Now it is known that ES and PNET show similar translocations and are considered to be ends of histological spectrum of Ewings family of tumors (EFT). outline of molecular techniques not only provided better understanding of biology but also help in developing better techniques in diagnosis and equivalently potential treatment.EpidemologyEFT comprises 5 to 10 % of total bone tumors and is the 2nd most common tumor of childhood 6. It occurs predominantly in young adults and children and shows a polished predilection for males 7.75% cases are seen between 10 to 25 years age of life. Youngest case r eported so far was of 4.5 months old 8 and oldest case reported was 61 years old. Infancy cases are to be differentiated from metastatic neurofibroma.SitesIn 55% long bones it is usually diaphyseal lesion but also metaphyseodiaphyseal lesion chiffonier be seen. Flat bone (pelvis and ribs) involvement can also be seen. Less common sites of occurance are skull, vertebra and scapula.Presentation of Ewings sarcomaPain, Swelling and fever are the presenting symptoms. X-ray shows permeative pattern of bone involvement (boundary between uninvolved bone and area of bone destruction and bone is broad, vague imperceptible). All types of periosteal reactions seen like onion peel, moth eaten, honey combed, fine and reticulated 1.BiopsyIdeally core biopsy is done, if repeated attempts of core biopsy fails open biopsy is done. FNAC not recommended in case of Ewings sarcoma. Frozen section studies opted in selected cases only as freezing of tissue distorts the morphology. Fixation of tissue is d one in 10% formalin. Inadequate fixation leads to loss of antigen, so inconclusive results on immunohistochemistry and also causes autolysis and degeneration of DNA thus making molecular abstract difficult. Ratio of specimen to formalin is 110.HistologyIt is prototype of small round cell tumor growth. It is composed of sheets of small cells with increased nuclear to cytoplasm ratio. Cytoplasm is scanty, eosinophilic, and detected by periodic acid Schiff (PAS), contains glycogen and diastase degradable. Occasional rosette formation are seen and frequently undergoes necrosis and residual viable cells show perithetiomatous or perivascular distribution.EFT tumor cells can be large with irregular nuclear tissue layer and prominent nucleoli 9. EFT cells show membrane expression of CD99 /MIC 2 on immunohistochemistry 10. Antibody against FLI-1 is seen in nucleus of tumor cells which is specific for diagnosis of EFT 11. Tumor cells may show nerve cell specific enolase (NSE), synaptophysin and s-100 protein.Family of EFT includes -1)non hodgekins lymphoma 2)rhabdomyosarcoma 3)synovial sarcoma 4)messenchymal chondrosarcoma 5)desmoplastic small round cell tumor (DSRCT) 6)retinoblastoma.False positive cd99 screening is seen in other cases as well hence CD99, FLI1 and NSE to be positive for diagnosis of EFT/PNET.Molecular geneticsTranslocation t (1122) (q24q22) is seen in 85 % cases. Fusion of EWS gene on 22q12 with FLI-1 on 11q24 results in chimeric fusion reproduction EWS-FLI1 12. EWS-FLI1 induces insulin like growth factor (IGF-1). Phospholipase D2 (PLD2) and Protein tyrosine phosphatase 1 (PTPL1) are expressed in increased levels. Thus tumor cells escape from apoptosin and growth inhibition.Therapeutic targetsEWS-FLI1 fusion is to be targeted and split. Monoclonal antibodies against IGF -1 are being tried as it is associated with EFT growth 13 and PLD 2, PTPL1 are other conceivable candidates as both are highly expressed in EFT 14.Chemotherapy in ESThere is no univer sally accepted staging. American joint committee on cancer (AJCC) suggests that primary bone or extra skeletal Ewings sarcoma may be included with their respective bone or soft-tissue sarcoma staging (STS) systems 15. Although AJCC staging includes metastatic disease and tumor size great or less than 8 cm nodal status and grade are irrelevant for ES because it rarely spreads by lymph nodes and by definition of ES is high grade tumor 15. Most of centers use presence or absence of metastasis at the time of diagnosis, as main tool for planning the treatment.Prognostic factors 1) tumor site and size 2) age and gender 3) serum LDH levelsES in distal extremity has better prognosis than proximal extremity. ES in aboriginal location (pelvis) has worst prognosis 16 17 18. Tumor volume 100-200ml- large tumor has bad prognosis. Girls have better prognosis than boys 18. Increased serum LDH levels at time of diagnosis with large tumor with metastatic disease has worse prognosis. Metastasis in lungs alone has prognosis better than metastasis in extra-pulmonary sites. Patient with minimal tumor or no residual tumor after preoperative chemotherapy incline towards better prognosis.Evolution of chemotherapy Adjuvant therapy Vincristine + Actinomycin D + Cyclophosphamide (VAC).Intergroup Ewings sarcoma take apart (IESS) VAC + doxorubicin. IESS trial II demonstrated that intermittent high doses of VAC + doxorubicin was superior to continuous moderate dose therapy with this agents 19.VAC+ doxorubicin alternating with Ifosfamide and Eloposide (IE) has better prognosis. There is no use of dose intensification.Current tendencyAlternating cycles of VAC IE every 3 weeks for 48 weeks with local control at 9-12 weeks 20 is to be administered. There is no role of dose compression (decrease in duration of cycles).There is some role of stem cell in preliminary stage of management.Local therapySurgical resection with or without limb salvage followed by radiation sickness and then chemo therapy is given.Chemotherapy remains back bone of the T/t for Ewings sarcoma, local T/t with surgery /or radiotherapy has important role in management of ES. The outcome of management is better in localized ES as compared to elusive outcome in metastatic disease or local recurrence.This case is presented in view of rarity to increase suspicion index for the presence of Ewings sarcoma. Early detection of Ewings sarcoma as chemotherapy and radiotherapy can limit further damage and progression of the disease can be done.REFERENCESJoseph M. Mirra, Piero Picci Ewings sarcoma In Bone tumors- clinical, radiologic, and pathologic correlations, volume two, Lea Febiger, Philadelphia, London1989, pp. 1088-1094.Stout AP. A tumor of the ulnar nerve. 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