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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 12  |  Issue : 3  |  Page : 172-176

Ewing's sarcoma: A rare case report


Department of Oral Pathology, Narayana Dental College and Hospital, Nellore, Andhra Pradesh, India

Date of Submission07-May-2021
Date of Acceptance29-Jul-2021
Date of Web Publication17-Sep-2021

Correspondence Address:
Dr. Vandana Raghunath
Department of Oral Pathology, Narayana Dental College and Hospital, Chinthareddypalem, Nellore - 524 003, Andhra Pradesh
India
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DOI: 10.4103/srmjrds.srmjrds_37_21

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  Abstract 

Ewing's sarcoma is an uncommon malignancy, constituting 4%–10% of the entire malignant osseous tumors involving children and young people. Rarely does it affect the facial bones, and added to its nonspecific presentation, its diagnosis remains challenging. Its occurrence is <3% in the head-and-neck region, with the mandible being frequently affected. It belongs to the ES family of tumors, shows rapid growth, and has a greater propensity for metastasis. ES of the jaws either presents as a primary or as a metastatic deposit. We report one such rare clinical and histological scenario of a primary ES of the mandible in a girl, of 8 years of age, whose clinical presentation mimicked that of an odontogenic tumor/cyst. Tumor cells were positive for CD99 and vimentin which confirmed the diagnosis. This report is to showcase the importance of early diagnosis in such rarely occurring aggressive tumors. It further facilitates appropriate therapy to achieve local control, prevent metastasis, and systemic eradication.

Keywords: Ewing's sarcoma, immunohistochemistry, mandible


How to cite this article:
Ratna Jerusha J F, Raghunath V, Reginald B A, Reddy B S, Kamal F, Reddy S. Ewing's sarcoma: A rare case report. SRM J Res Dent Sci 2021;12:172-6

How to cite this URL:
Ratna Jerusha J F, Raghunath V, Reginald B A, Reddy B S, Kamal F, Reddy S. Ewing's sarcoma: A rare case report. SRM J Res Dent Sci [serial online] 2021 [cited 2021 Dec 4];12:172-6. Available from: https://www.srmjrds.in/text.asp?2021/12/3/172/326209




  Introduction Top


Ewing's sarcoma (ES) belongs to the Ewing's family of tumors (EFT) and represents 4%–10% of primarily occurring osseous tumors. Children and youngsters are primarily affected, and a trivial prevalence is noted in males. The long bones and pelvis are commonly affected. It is unusual in the head-and-neck region, and the mandible is frequently involved compared to the maxilla. Both the diagnosis and treatment of ES are challenging, as jaw lesions may pose clinically as inflammatory, traumatic, or cystic lesions, and often do not form a part of the differential diagnosis for radiolucent jaw lesions due to their rarity.[1],[2]

The origin of this tumor remains contentious. It is predicted to originate from endothelial or neural elements or from undeveloped reticulum or undifferentiated marrow cells. Both osseous and extraosseous types of ES belong to the EFT. The other variants included are large cell/atypical ES, adamantinoma type, primitive neuroectodermal tumors (PNET or ES/PNET), and Askin tumor of the thoracopulmonary area.[3] Peripheral PNETs (pPNETs) are seen outside the central nervous system. They develop from the wandering embryonal cell population belonging to the neural crest.[3] Immunohistochemistry and molecular assays for chromosomal translocation help differentiate from similar-looking small cell tumors with round blue-colored cells. Hence, they remain the mainstay of diagnosis.

ES is a malignant bone and soft-tissue tumor composed of small round cells showing the least differentiation histologically. It is destructive with a high predisposition for metastasis. This accounts for the high mortality. By the time the patients report, clinically apparent metastatic disease is noted in approximately 20%–25% of cases, and despite early intervention, approximately 20% have left out with a 5-year chance of survival.[2] A case of primary ES of the mandible affecting a girl child of 8 years is presented to alert the clinicians about the clinical and histopathological spectrum of this rare tumor and the need for an early diagnosis.


  Case Report Top


An 8-year-old girl reported to the Department of Oral Medicine and Radiology with painful, slow-growing enlargement of 2-month duration in the left lower posterior jaw region. The swelling had progressively grown out to reach the present size. There was no history of trauma. Her past medical/dental narration was insignificant.

Extraoral examination revealed asymmetry in the left lower third of the face owing to the enlargement. It had developed over 2 months, was firm to hard, nontender, and measured 4 cm × 3 cm. The inferior mandibular border appeared intact.

Intraoral examination showed swelling about the lingual aspect of the left mandibular 36 tooth region, of 3 cm × 2 cm, intact, firm, nonpulsatile, mildly tender, and with well-defined borders. The buccal cortical plate exhibited slight expansion with obliteration of the vestibule [Figure 1]. A solitary, enlarged, unilateral, movable, and firm left submandibular lymph node was noted. Orthopantomograph revealed a well-defined multilocular radiolucency posterior to the roots of 36 with displacement of the crown of unerupted 37 tooth, anterosuperiorly [Figure 2]. Fine-needle aspiration cytology was performed, which yielded very little serosanguinous fluid. Cytosmear showed few scattered squamous epithelial cells, inflammatory cells, and red blood cells. The lesion was provisionally diagnosed as an infected odontogenic tumor/cyst. The patient had increased levels of serum alkaline phosphatase. Increased levels of C-reactive proteins were also noted apart from anemia, leukocytosis, and increased erythrocyte sedimentation rate.
Figure 1: Intraoral photograph showing a slight expansion of cortical plate with obliteration of the buccal vestibule in the posterior region

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Figure 2: Orthopantomagram revealing well-defined multilocular radiolucency, posterior to the roots of 36 tooth involving angle and ramus of the mandible

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Excisional biopsy was performed under local anesthesia, and a specimen was sent for histopathological examination. The gross specimen was soft to firm to hard in consistency, brown, and measured 0.5 cm × 1.5 cm in size.

Upon staining the tissue sections with H and E, the lesion was moderately cellular. The cells were small, minimally pleomorphic, round to oval, and arranged in sheets, cords, and nests. The cytoplasm was minimal, clear/basophilic and nuclei were either vesicular/hyperchromatic. The surrounding fibrous connective tissue exhibited chronic inflammatory cell infiltration, hemorrhage, and necrotic areas [Figure 3]a and [Figure 3]c. There were hyaline eosinophilic areas suggestive of osteoid close to the lesional cells [Figure 3]b. Prominent nucleoli and occasional mitoses were seen in the tumor cells [Figure 3]c. Sheets and nests of lesional cells infiltrated the immature bony trabeculae [Figure 3]d. The provisional histopathological diagnosis was that of a malignant small round blue cell tumor. Immunohistochemistry showed that the tumor cells were positive for CD99 and vimentin and negative for osteocalcin, terminal deoxyribose nucleotidyl transferase (TDT) [Figure 4]a, [Figure 4]b, [Figure 4]c, [Figure 4]d, and AE1/AE3. Thus, based on the above findings, it was finally diagnosed as ES.
Figure 3: Photomicrographs (H and E) showing (a) sheets of small blue round cells with scanty stroma (×10), (b) hyaline eosinophilic areas in close proximity to the lesional cells (×10), (c) minimally pleomorphic round cells and occasional mitoses (×20), (d) lesional tissue infiltrating between immature bony trabeculae (×10)

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Figure 4: Photomicrographs showing (a and b) strong CD99/MIC and vimentin positive and (c and d) negative osteocalcin and TDT IHC staining (IHC, ×10)

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  Discussion Top


ES is a malignant aggressive neoplasm composed of round cells. It chiefly affects the long bones of the hands and legs, with almost half of published cases relating to the pelvis and femur. Whites are most commonly affected.[1] It is more prevalent in youngsters and is rarely seen in children below 5 years of age and older adults. The tumor behaves aggressively, and shows a high probability of micrometastasis at diagnosis. Only 2%–7% of cases occur in the maxillofacial region, with the mandibular ramus being commonly affected. Ninety percent of the lesions occurring in the mandible are the initial lesions, and the remaining 10% represent metastatic deposits.[4] The present case was reported in the mandible of an 8-year-old-girl.

Translocation t (11;22)(q24;q12) is observed in 85% of EFT cases. A chimeric transcript EWS-FLI1 results following the combination of EWS gene (22q12) with the FLI1 gene (11q24). The two types of translocation are type 1 (exon 7 of EWS to exon 6 of FLI1) and type 2 (exon 7 of EWS to exon 5 of FLI1). A translocation t (21;12)(22;12) results in EWS-ERG (Ets-related gene) combination which is observed in 10%–15% of cases. Fusion of EWS gene and a member of ETS family of transcription factors constitute for 1%–5% of translocations.[5]

The clinical findings of head-and-neck ES have been nonspecific and usually involve rapid growth, swelling, and pain. Loosening of teeth, trismus, middle ear infection, and paresthesia are not uncommon when the mandible is involved. Dental infections (abscess) could be the first signs of an intraoral ES.[6] Literature reported that 21% of mandibular ES were diagnosed as dental infections in the beginning. They presented as indurated swellings, accompanied by pain, fever, and lymphadenopathy. The covering mucosa may be normal or erythematous and is rarely ulcerated.[7] Our case showed only a gradually progressive swelling, with intact mucosal covering.

Few cases present with anemia, leukocytosis, elevated erythrocyte sedimentation rate, and C-reactive protein, which could also be seen in dental infections (abscess). Depending on the osteoblastic activity (physiologic and/pathologic) and tissue damage, alkaline phosphatase and lactate dehydrogenase levels also could increase in some patients, as seen in our case.[6],[8]

Radiographic findings serve as the platform for arriving at a final diagnosis of bone tumors. ES presents as a poorly defined radiolucent lesion with cortical erosion and perforation. It shows an infiltrative manner of destruction along with periosteal response.[1] The periosteal reactions of “sun-ray appearance” (radiating spicules of bone) and “onion skin pattern” (laminar periosteal response) remain the standard radiological features of many ES of the long bones. However, they tend to be rare features of jaw lesions.[9] According to the literature, periosteal laminations remain challenging to see because of the complex anatomy of the jaws.[1] In the present case, too, only an osteolytic lesion with multilocular destruction was observed. This imaging pattern is not pathognomonic of ES and is a routine finding in odontogenic tumors/cysts, histiocytosis X, lymphosarcoma, osteogenic sarcoma, rhabdomyosarcoma, neuroblastoma and metastatic carcinoma, etc.[10] As ES/pPNET is an uncommon tumor of the much rarer ES family of tumors, it is frequently not listed in the differentials of osteolytic jaw conditions. Hence, our provisional diagnosis too was that of odontogenic tumor/cyst.

Although roughly 20%–25% of ES family tumors present with metastatic disease which is clinically perceptible at the outset, our case did not feature any.[2]

Histopathologically, ES shows layers of small, poorly differentiated cells with increased nuclear–cytoplasmic ratio, round-to-oval nucleus, and minimal eosinophilic cytoplasm. The hyperchromatic or dark cells often represent maturing reticulum cells or degenerating cells. It shows various growth patterns such as diffuse, lobular, trabecular, and pseudo rosette, with extensive foci of necrosis and hemorrhage. Mitotic figures are uncommon in ES.[1],[5],[8] In 75% of cases, due to the presence of periodic acid–Schiff (PAS)-positive, diastase degradable intracytoplasmic glycogen granules, diagnosis is easy but is not specific, as other tumors with small round cells also turn PAS-positive.[5]

The tumor cells showed solid CD99 or MIC2 membrane positivity and vimentin positivity. They were negative for epithelial differentiation markers AE1/AE3, B- and T-cell marker TDT, and osteoblastic differentiation marker osteocalcin. In the backdrop of the hyaline eosinophilic areas simulating osteoid, a diagnosis of small cell osteosarcoma appeared plausible, but IHC helped rule it out. The lesional cells may show positivity to markers of neuron-specific enolase, synaptophysin, and S-100 protein, depending upon the degree of neuroectodermal differentiation. Immunohistochemistry also helps to rule out tumors such as non-Hodgkin lymphoma, neuroblastoma, rhabdomyosarcoma, mesenchymal chondrosarcoma, retinoblastoma, desmoplastic small round cell tumor, osteosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and melanoma.[5]

71%–84% of ES cases have demonstrated FLI1 nuclear positivity, and thus, a panel of immunohistochemical stains comprising CD99, FLI1, and NSE are usually advised to arrive at a definitive diagnosis. With these being positive in ES/PNET, it can help rule out other CD99-positive round cell lesions (lymphoblastic lymphoma, rhabdomyosarcoma, synovial sarcoma, mesenchymal chondrosarcoma, etc.).[5]

Current treatment of ES involves a combination of surgery, radiation, and chemotherapy that increases the survival rates of patients by 40%–80%. Radiotherapy alone is considered in cases where the primary tumor cannot be removed.[6] It happens that the most advantageous of affected ones present with small lesions with sound margins or well-delineated lesions that are amenable to surgical removal or radiation treatment. Hence, in our case too, surgical excision was undertaken, followed by postsurgical radiotherapy and chemotherapy.

The prognostic factor for a good survival is the bulk or size of the tumor and metastases, if any.[1] As the disease advances, it destroys the cortex, infiltrates the periosteum, and spreads to the soft tissues. Its effect on recurrences thus remains less apparent. Poor prognosis is usually associated with the presence of systemic symptoms, age <10 years, pelvic lesions, the presence of metastases, large tumors, high mitotic rate, and inadequate response to chemotherapy.[8] However, none of these featured in our case.

Due to early detection, tumors arising from the jaw bone hold a better prognosis than long bone tumors.[8] Likewise, even in our case, there have been no recurrences with a follow-up for over 12 months.


  Conclusion Top


ES of the jaw bone is a rare malignancy. It should be well thought out in the differential diagnosis of the commonly occurring odontogenic tumors, cysts, or inflammatory lesions, which occur as osteolytic lesions. The histologic diagnosis coupled with CD99 and FLI1 positivity helps rule out similar-looking small blue round cell tumors. Based on the aggressiveness, risk of metastasis, and clinical presentation, multiple treatment modalities or combinations of it may be adopted.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's parents have given her consent for the patient's images and other clinical information to be reported in the journal. The parents understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Brazão-Silva MT, Fernandes AV, Faria PR, Cardoso SV, Loyola AM. Ewing's sarcoma of the mandible in a young child. Braz Dent J 2010;21:74-9.  Back to cited text no. 1
    
2.
Casaroto AR, Sampieri MB, Soares CT, Santos PS, Yaedu RY, Damante JH, et al. Ewing's sarcoma family tumors in the jaws: Case report, immunohistochemical analysis and literature review. In Vivo 2017;31:481-91.  Back to cited text no. 2
    
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de Alava E, Lessnick LS, Soreson PH. WHO Classification of Tumours of Soft Tissue and Bone. 4. Lyon: International Agency for Research on Cancer, Ewing sarcoma; 2013. p. 306.  Back to cited text no. 3
    
4.
Lopes SL, Almeida SM, Costa AL, Zanardi VA, Cendes F. Imaging findings of Ewing's sarcoma in the mandible. J Oral Sci 2007;49:167-71.  Back to cited text no. 4
    
5.
Desai SS, Jambhekar NA. Pathology of Ewing's sarcoma/PNET: Current opinion and emerging concepts. Indian J Orthop 2010;44:363-8.  Back to cited text no. 5
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6.
Keshani F, Jahanshahi G, Attar BM, Kalantari M, Razavi SM, Hashemzade Z, et al. Ewing's sarcoma in mandibular similar to dental abscess. Adv Biomed Res 2014;3:62.  Back to cited text no. 6
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7.
Margaix-Muñoz M, Bagán J, Poveda-Roda R. Ewing sarcoma of the oral cavity. A review. J Clin Exp Dent 2017;9:e294-301.  Back to cited text no. 7
    
8.
Sharada P, Girish HC, Umadevi HS, Priya NS. Ewing's sarcoma of the mandible. J Oral Maxillofac Pathol 2006;10:31-5.  Back to cited text no. 8
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9.
Gorospe L, Fernández-Gil MA, García-Raya P, Royo A, López Barea F, García-Miguel P. Ewing's sarcoma of the mandible: Radiologic features with emphasis on magnetic resonance appearance. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:728-34.  Back to cited text no. 9
    
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Singh JP, Garg L, Shrimali R, Gupta V. Radiological appearance of Ewing's sarcoma of the mandible. Indian J Radiol Imaging 2003;13:23-5.  Back to cited text no. 10
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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