Journal of Cancer Research and Therapeutics

ORIGINAL ARTICLE
Year
: 2018  |  Volume : 14  |  Issue : 5  |  Page : 1014--1022

Imaging features of Ewing's sarcoma: Special reference to uncommon features and rare sites of presentation


Sujata Patnaik, Jyostnarani Yarlagadda, Rammurti Susarla 
 Department of Radiology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India

Correspondence Address:
Sujata Patnaik
Department of Radiology, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad, Telangana
India

Abstract

Context: Ewing's sarcoma (EWS) commonly involves long bones with a permeative pattern of bone destruction and aggressive interrupted periosteal new bone formation. However, radiological features show wide variation and some presentations are uncommon, leading to diagnostic confusion. This study is aimed at studying the imaging features of proven EWS and highlight the uncommon features and rare sites of presentation. Materials and Methods: The imaging findings of 100 consecutive histopathologically proven EWS were analyzed retrospectively. All uncommon presentations with respect to age and site and morphology of lesion were observed. Results: Most of the patients were below 20 years of age and 8% were younger than 5 years. Other than long bones, ribs, and pelvis, other sites considered to be rare and were noted in 25%. Extraosseous site involvement was 11%. Uncommon features included epiphyseal involvement (4%), sclerosis (4%), expansion of bone (8%), sunray spiculation (10%), calcification in soft tissue (8%), saucerization (4%), pathological fracture (5%), fluid–fluid level (2%), vertebra plana (2%), and lesion crossing the joint (13%). Conclusions: The uncommon observations included incidence in children <5 years (8%) and occurrence in craniofacial bones, spine, scapula, and clavicles and in extraosseous sites such as retroperitoneum, adrenals, or extremity. Uncommon findings included epiphyseal involvement, sclerosis, saucerization, calcification in soft tissue component, and pathological fracture and lesion crossing the joint.



How to cite this article:
Patnaik S, Yarlagadda J, Susarla R. Imaging features of Ewing's sarcoma: Special reference to uncommon features and rare sites of presentation.J Can Res Ther 2018;14:1014-1022


How to cite this URL:
Patnaik S, Yarlagadda J, Susarla R. Imaging features of Ewing's sarcoma: Special reference to uncommon features and rare sites of presentation. J Can Res Ther [serial online] 2018 [cited 2022 Aug 11 ];14:1014-1022
Available from: https://www.cancerjournal.net/text.asp?2018/14/5/1014/230441


Full Text



 Introduction



Ewing's sarcoma (EWS) is a malignant tumor of uncertain histogenesis, which predominantly arises in the bone. It is highly malignant round cell tumor and is the second most common malignancy in children after osteosarcoma. EWS, primitive neuroectodermal tumor (PNET), and Askin's tumor have overlapping features with a common histogenesis and are currently classified as EWS family of tumors. EWS is poorly differentiated tumor arising from bone and soft tissue. PNET arises from soft tissue with neuroectodermal differentiation, whereas Askin's tumor arises from thoracic wall (also known as thoracic wall PNET).

Radiologically, EWS involves long bones presenting as a permeative pattern of bone destruction with an aggressive interrupted type of periosteal new bone formation. However, radiological features can show wide variation. Although large soft-tissue component without calcification is common, at times calcification may be seen. Rare presentations are often caused diagnostic confusion. Hence, we are presenting our experience of unusual presentations of EWS here.

 Materials and Methods



This is a retrospective analysis of the imaging findings of 100 consecutive histopathologically proven cases of EWS. Imaging algorithm was plain radiograph followed by magnetic resonance imaging (MRI) for better characterization of extent and involvement and staging. Computed tomography chest was done for evaluation of lung metastases. All uncommon presentations with respect to age and site and morphology of lesion were observed. Extent, sclerosis, cortical thickening, expansion of bone, sunray spiculations, calcification, saucerization, pathological fracture, fluid–fluid level, crossing of a joint, vertebra plana, lymph node (LN) mets, and any other peculiar feature were looked for and noted in each case.

 Results



This analysis included 100 cases with male predominance (male and female ratio of 70:30). The ages ranged from 2 years to 38 years. Maximum were below 20 years of age and 8 of them were younger than 5 years which is a rare presentation. Bones involved in order of frequency were long bones (n = 38), rib (n = 22), iliac bone (n = 12), vertebrae (n = 7), scapula (n = 3), sacrum (n = 3), craniofacial bone (n = 3), clavicle (n = 1), and extraosseous (n = 11). Sites of lesion other than long bones, ribs, and pelvis were regarded as uncommon, which constituted 25% in our study. Among pelvic bone lesions, sacral involvement is uncommon. Extraosseous sites were 11 (Chest wall – 3, retroperitoneum – 2, adrenal – 1, soft tissue of extremity – 3, and intrathecal – 2) [Table 1] and [Table 2].{Table 1}{Table 2}

There were no characteristic imaging findings of the primary mass. Imaging features are no different from any other mesenchymal tumor and diagnosis was finalized on Histopathological Examination (HPE). Adrenal mass was 3 cm × 3 cm in size with homogeneous tissue attenuation and enhancement. Both the retroperitoneal masses were large heterogeneous lesions with local extension to adjacent organs and one had hemorrhage and calcification. One of the two cases of thecal Ewing's was a heterogeneous mass with solid cystic component and the other was homogeneous. The three cases of extremity soft-tissue EWS were heterogeneous with one showing T1W hyperintensity suggestive of hemorrhage. Two of these cases were in leg and one in the upper extremity. One case had a single metastasis to supraclavicular fossa which was calcified. Meta-diaphyseal lesion extension to epiphysis is seen in three cases which is 3%. Extension of lesion from iliac bone to sacrum (5) and rib lesions to adjacent vertebrae and vice versa noted in 13 cases (13%). All the lesions were from vertebra, rib, and iliac bone. Metastasis at presentation was seen in 18 (lung – 11, bone – 6, LN – 2, and supraclavicular soft tissue – 1). Pulmonary nodules were most commonly present, and in one case, there was lymphangitic carcinomatosis. One case had pulmonary thromboembolism (PTE).

 Discussion



Reinus et al. reviewed the radiography of 373 patients and described the radiological features of EWS way back in 1984. Based on the frequency of occurrence, the findings are divided into three categories – common findings (>30%), uncommon findings (10%–30%), and rare (<10%) in their analysis.[1]

Age

EWS is the second most common malignant tumor of bones in children after osteosarcoma. Peak age incidence is in the second decade. Ages of presentation above 30 and below 5 years are rare.[1] We had 8% cases below 5 years and 8% above 30 years. Most were in the age group between 10 and 20 years of age.

Site

Pelvis, extremities, and ribs account for 86% of cases. Other uncommon sites are spine 4%–6%, scapula 4%–5%, bones of hand/feet 4%–6%, radius, ulna 3%–5%, mandible/maxilla 1%–2%, clavicle 1%, facial bone 0.5%, and sternum 0.2%.[2] Rao and Pampori in 2011 reported one each case of EWS of mandible and maxilla, respectively. Till date, only 19 cases of EWS of jaw have been reported in Indian literature.[3] Our series had 25% uncommon sites of involvement. The vertebral involvement was 7%, skull 3%, clavicle 1%, scapula 3% each, and extraosseous EWS was 11% similar to most of the studies [Figure 1], [Figure 2], [Figure 3], [Figure 4]. Mostly, lesions are diaphyseal and metaphyseal. Epiphysis is the uncommon site of origin (0.5%–2%) and extension to epiphysis is seen in 10% of cases.[2] Four percent of our series had epiphyseal extension or predominant epiphyseal location [Figure 5].{Figure 1}{Figure 2}{Figure 3}{Figure 4}{Figure 5}

Pattern and periosteal reaction

Usually, lesions are aggressive moth-eaten destructive or have a geographic appearance with a wide zone of transition and have lamellated/speculated periosteal reaction. Onion skin and lamellated periosteal are described by Resnick to be common manifestation (57%); speculated periosteal reaction is as less frequent manifestation accounting for 28%.[2] Ten percent of our series revealed sunray speculation [Figure 6]. Sclerotic component is uncommon in primary lesions. Sclerotic component is seen in 32%–40% of cases. This is observed in intraosseous component of lesion (93%) and in flat bone lesion.[4] They are typically having an osteoid appearance (cloud like) represent reactive bone formation and found in lesions affecting flat bone, hands, foot, and ribs. Predominant sclerosis was observed in most of iliac lesions in our experience. Cortex usually shows destruction although roentgengraphically it may not be conspicuous. Endocortical erosion is occasionally masked as a result of cortical thickening caused by endosteal and subperiosteal new bone formation. The thickening of inner surface of cortex causes marked encroachment of medullary cavity. Cortical thickening and sclerosis accounted for 11% of our series [Figure 7]. Cortical thickening (21%), pathological fractures (15%), and expansile lesion remodeling are other rare findings (17%).[1] Pathological fractures (5%) and expansile lesions are rare observations by us (8%) [Figure 8]. Fluid–fluid level is seen rarely in EWS and is due to hemorrhage and is seen in larger lesions.[5] In vertebrae, posterior elements are predominantly involved with gradual involvement of vertebral bodies in 70%, but in 30%, the vertebra body is primarily involved with extension to posterior elements.[6] Destruction of vertebral body leads to collapse and sclerosis.[1] Vertebra plana is a rare finding and is due to the destruction of bone rather than compression fracture. Vertebra plana is seen in 6% cases.[1] Two out of seven in our series had a collapse of vertebral body [Figure 9].{Figure 6}{Figure 7}{Figure 8}{Figure 9}

Extension to adjacent joint

Joint involvement is said to present when there is articular extension that is cortical breakthrough of joint margin and tumor extension on either side of joint. Such joint involvement is seen in 23% of the cases according to literature.[7] Transarticular spread of tumors has been reported in sacroiliac (SI) joint, disc space, and facet joints and is virtually indistinguishable radiologically from septic arthritis.[8] In the present series, it was noted in 13%, there were lesions crossing the joint and majority were costovertebral (n = 7), SI joint (n = 5), and vertebra to vertebra (n = 1) [Figure 10] and [Figure 11].{Figure 10}{Figure 11}

Soft-tissue component

Lytic lesions are usually associated with large soft-tissue component. However, calcification in soft tissue is described as uncommon findings seen in 7%–9%.[2] EWS is incapable of producing osteoid tissue. Calcification in soft-tissue represents remnant of debris of periosteal new bone formation. It may be dystrophic calcification. According to Resnick et al., soft-tissue calcification (7%–9%) and extrinsic erosion (saucerization) (6%) are unusual radiographic findings.[1] Diaphyseal lesion showing cortical erosion is seen as saucerization due to central coarse irregular defect with central crater facing outer surface, occasionally exhibiting a marginal scalloped defect. Saucerization is seen in 6% of cases.[1] Soft-tissue calcification was observed in 8% and saucerization in 4% of cases. One of extraosseous EWS had calcification. Periosteal EWS without involvement of medullary canal accounts for 3% of EWS but can cause extrinsic erosion of bone and similar to that of periosteal osteosarcoma [Figure 12], [Figure 13], [Figure 14].{Figure 12}{Figure 13}{Figure 14}

Spinal lesions are associated with large soft tissue extending to spinal canal. Lumbar vertebra is more commonly involved than thoracic than cervical. In spine, the intervertebral foramina serve as pathway for bidirectional spread of tumor into epidural space or paravertebral gutter. Multicompartmental transgression may result in arterial encasement, disruption of dural sac, cord compression, and nerve root infiltration [9] [Figure 15]. Skull lesions show permeative bone destruction with large soft tissue without calcification. Areas of hemorrhage and necrosis are common. Prognosis is better than EWS of tubular bones. We noted one sphenoid, one frontal, and one maxillary bone involvement [Figure 16] and [Figure 17]. In scapula, there will be fine to patchy osteolysis associated with periosteal reaction with or without calcification in associated soft tissue [Figure 18]. Clavicle involvement is rare and depicted by diffuse infiltration with tiny foci of erosion and uneven sclerosis, periosteal reaction in the form of lamellated type. “Codman triangle” may be seen. Lesion is associated with soft-tissue mass [Figure 2]. Foot involvement is rare and findings are variable. Permeative type of bone destruction is common. Marked sclerosis may be seen. No evidence of calcification noted in soft-tissue component.{Figure 15}{Figure 16}{Figure 17}{Figure 18}{Figure 2}

Extraosseous Ewing's sarcoma

The following criteria should be met to label as extraskeletal EWS: (a) no osseous involvement in MRI, (b) no increase uptake of bone or periosteum adjacent to tumor in static images of bone scintigraphy, (c) lesion consists of small round blue cells with no differentiation features in light microscopy, (d) demonstration of cytoplasmic glycogen.[10] Soft-tissue involvement of EWS is rare and occurs in older age group and has wide distribution. It can occur head, neck, trunk, diaphragm, retroperitoneum, pelvis, or in extremities. Extraskeletal EWS shows no sex predilection; occur in slightly older age and predominant involvement of trunk rather than limb in contrast to skeletal EWS as observed in our series. In a review of literature by Stuart, the extremity involvement is 32%, paravertebral including epidural 15%, cervical 11%, and chest 11%.[10]

The radiological features are nonspecific and present as large soft-tissue mass with or without adjacent cortical thickening/erosion/periosteal reaction. Usually, there will be no osseous involvement at MRI or any abnormal uptake on scintigraphy, and hence, it should be histopathologically confirmed. Lesion adjacent to periosteum may produce extrinsic erosion [Figure 19]. Periosteal thickening, pressure remodeling, and lysis may mimic neurogenic tumor. The extrinsic impression should not be confused with saucerization. In saucerization tumor is arising from bone, resulting in cortical destruction of periosteum and stimulate periosteal reaction [Figure 14]. Since EWS has unique ability to spread through haversian canal without causing microscopic destruction large soft tissue without bony lesion may be observed. However, MRI can show the signal changes. However, cortical thickening, osseous invasion, and aggressive periosteal reaction may be seen in 40% of cases.[5]{Figure 19}{Figure 14}

Smaller tumors are homogeneous and larger one are heterogeneous due to hemorrhage and necrosis. Calcification is atypical and occurs in 10% of cases. These calcifications are faint, amorphous. In retroperitoneum, EWS does not cross midline. They may invade adjacent organ, renal vein, and inferior vena cava similar to renal cell carcinoma.[11] We encountered two cases of retroperitoneal EWS, and both are large having heterogeneous enhancement abutting the kidney and confined to midline. One of these showed calcification [Figure 13]. Adrenal also can be affected by EWS as one of our cases. Peritoneal nodularity and ascites may be seen, and one of retroperitoneal EWS had ascites. Pelvic disease is associated with poor prognosis. Soft-tissue EWS of extremity can virtually arise from any soft tissue of extremity. Lower limb is commonly affected. We had three soft-tissue EWS (2 in lower extremity and 1 upper limb) [Figure 19]. Involvement of spinal epidural space is unusual and only 32 cases are reported with a mean age of 19.1 years and a slight predominance of male. Lumbar epidural space has been most commonly reported site.[12] Lesions have solid enhancing component appearing hypo on T1W and hyper on T2W images and there may be cystic component due to protein, hemorrhage, and necrosis.[13] We had two cases; one in lumbar and one at craniovertebral junction [Figure 20] and [Figure 21]. Paravertebral mass may be present as extramedullary intradural or extradural mass.[11] All our extraosseous EWS were heterogeneous with inhomogeneous enhancement except in case 4.{Figure 13}{Figure 20}{Figure 21}

Metastases

More than 10% of cases may present with multiple metastases. Most common sites are lung, bone, bone marrow, or combination of these in 25%. Incidence of lung metastasis is 80% followed by bone 40% and LN mets is rare.[14] Lymphadenopathy is seen in 0%–12% of cases.[15] We had 18% metastases at presentation and lung was most common 11%, bone 6%, and LN 2%. One case had a soft-tissue deposit. Metastatic bone lesions resemble the primary and often difficult to differentiate. Based on onset and size, the diagnosis is made.

Roentgen appearance of pulmonary metastases is characterized by multiple radiosensitive nodules of varying sizes. No ossification or calcification is observed. Lymphangitic spread hematogenously occurs to lung and then invades lymphatic vessels. Accumulation of tumor cell causes thickening of secondary lobule infiltration. Diagnosis of lymphangitic carcinomatosis is by clinical context excluding the other causes as in our case [Figure 22]. One case had PTE; another had soft-tissue metastasis [Figure 23]. The soft-tissue deposit had calcification. Since EWS do not produce osteoid matrix, when calcification present, it may be due to necrosis or tumor-induced metaplasia.{Figure 22}{Figure 23}

Our study brought out the possibility of a broader spectrum of radiological features in EWS than what is described in earlier literature. The unusual features can add to the diagnostic confusion in some cases. Histopathology is the final diagnostic test in every case.

Summary

EWS are highly malignant tumors. Although described to be most common in 10–20 years of age, they can occur below 5 and above 30 years. Long bones, pelvis, and ribs are common sites but craniofacial bones, spine, scapula, and clavicles are not uncommon sites of occurrence. Extraosseous sites can be in the retroperitoneum, adrenals, or extremity. Although permeative lytic lesion in metadiaphysis with soft-tissue component is common, uncommon findings such as epiphyseal involvement, sclerosis, saucerization, calcification in soft tissue component, and pathological fracture can be encountered at times. Lesion crossing the joint is another frequent observation and has to be differentiated from septic arthritis. Lymphatic spread can also occur, though lung and bones are the most common sites for metastasis. Hence, appropriate modality of investigation is to be chosen for correct diagnosis and treatment of EWS.

Declaration of patient consent

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

Acknowledgment

The authors acknowledge the intellectual concepts and teaching points given by the Emeritus Professor Kakarla Subbarao and the professional support of the Faculty of Departments of Orthopaedics and Pathology, NIMS, Hyderabad, in the conduct of this project.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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