The origin of Ewing's sarcoma in a periosteal location is rare and not clearly documented. Other malignant bone tumors appear to have a somewhat better ...
Sarcom a (1999) 3, 85± 88
ORIG INA L ART ICLE
Periosteal Ewing’s sarcom a: report of two new cases and review of the literature 1
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YEHUDA KOLLEND ER, SHAY SHABAT, ALEXAND ER N IRK IN, JO SEPHINE 2 3 4 1 ISSAKOV, GID EON FLUSSER, OFER M ERIM SK Y & ISAAC M ELLER 1
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The N ational U nit of Orthopedic Oncolog y, The U nit of B one and Soft Tissue Pathology, The D epartm ent of R adiology & The D epartm ent of O ncolog y, The Tel-Aviv Sourasky M edical Center, and Tel-Aviv M edical School, Israel
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Abstract B ackground . The origin of Ewing’s sarcoma in a periosteal location is rare and not clearly documented. Other m alignant bone tumors appear to have a somewhat better prognosis when con® ned between periosteum and bone. Is it the same for periosteal Ewing’s sarcoma? M ethods . We describe two new cases and comprehensively review the literature consisting of 18 documented cases since the condition was ® rst described in 1986 (S.M. Bator. C ancer 58:1781± 4). Results . Periosteal Ewing’s sarcoma differs from the other forms of Ewing’s sarcoma in terms of sex predominance, location of tumor, surgical stage at presentation and typical imaging studies. Eighteen out of the 20 patients were reported to be alive with no evidence of disease. Conclusions . It seems that the prognosis of this rare variant of Ewing’s sarcoma fam ily of tumors might be better but the small number of cases precludes such a ® rm conclusion. Key words: Ew ing’ s sarcom a, per iostea l (periosteum ), bone tum ors, lim b-sparing surger y
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Introduction T he classi® cation of prim ary m alignant bone tum ors is still expanding to include new subtypes based upon th e clin ical pr esen ta tio n , rad io g ra ph ic fe atu res (in clu d in g m o d er n im ag in g m o d a lities su ch as com puted tom ography (CT ), m agnetic resonance im ag ing (M RI), positron emission tomography scan 1± 4 (PET scan) and others, anatom ical localization an d n ew so p histicated m o d er n cyto genetic an d 5± 9 m olecular biology techniques. I t is o b v io u s th at th e classical h isto lo g ical/ m orphological m ethods of classifying bone tum ors are crude and not of suffic ient accuracy to distinguish subtypes. Subtyping is m ost probab ly of prognostic signi® cance, but m ight have therapeutic im plications. M any think that bone tum ors arising in a periosteal location (surface lesions) have a som ewhat better prognosis than those arising in the m edullary cavity 10± 11 of the sam e bones. Ewing’s sarcom a (ES) is one of the best exam ples of a distinctive tum oral disease which, based upon clinical radiological and cytoge1,9 netic param eters, which, is considered today to be a gro u p of d iffe re n t d ise ases. A cco rd in g to th e anatomical site today we recognize three subtypes: (a ) the in trao sseo u s typ e, w h ich is th e m o st
com m on; (b) the extraskeletal or soft tissue type 13± 14 (less com m on); and (c) the ver y rare variant of per iostea l lo cation o f w hich o n ly 18 cases are 15± 19 described in the literature so fa r. . T he ® r st description of periosteal Ewing’s sarcom a (PES) was probab ly that published in 1956 by Sherm an and Soong in a com prehensive radiological review of 111 cases of ES of bone which included a roentgen clas20 si® cation. They described three cases of PES am ong 12 other cases, which they de® ned as ª cortical Ewing’s sarcom a of long bones,º but without m entioning the nam e and obviously based only upon plain X -ray ® lm s and classical histological criteria. T he ® rst wellestablished case report of PES was published in 1986 by Bator et al. 15 H e actually de® ned PES: ª . . . in a periosteal location w ithout extension into either the bon e or ad jac en t soft tissu esº . Since th en fou r additional papers, describing a total of 18 cases, have 16± 19 been published. We add to this list two new cases and review the literature. Case repor ts (1) A 16-year-o ld m ale patient was referred to the Orthopedic Oncology U nit in our center on July 1994. He com plained of a grow ing, large (>10 cm ) painful
Correspondence to: Isaac M eller, T he National U nit of Orthopedic Oncology, Tel Aviv-Elias Sourasky M edical Center, Tel Aviv, Israel. 1357-714 X print/1369-164 3 online/99/020085-0 4 ½
1999 Taylor & Francis Ltd
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mass in the postero-lateral aspect of the distal half of his right thig h, w hich he had experienced for 3 months. H is general condition was good except for low fever for the last few m onths. Physical examination revealed a tender longitudinal m ass along the biceps m uscle in the right distal thigh, 12.5 cm in size. N o palpable lym ph nodes were noted in the groin or other places. Blood tests showed an elevated erythroc yte sedim entation rate (ESR) of 100/120; no r m al w h ite b lo od cell (W B C ) co u nt; n or m al alkaline phosphatase (AP) blood levels; and a slight increase of lactate dehydrogenase (LDH) blood levels. Plain X-ray ® lm s of the thigh and knee region showed priosteal elevation and thickening. O ur differential diagnosis was of an infectious disease, such as prim ary osteom yelitis, or secondary to a soft tissue process or some form of a m alignant surface bone neoplasm . Protocol staging studies included: plain chest X -ray ® lm ; total body bone scan; CT of the lesion and chest; and M RI of the lesion. The CT and MRI of the distal fem ur showed a periosteal/surface lesion, as the m edullary canal and the endosteal surface of the distal fem ur were intact. The system ic bone scan and chest C T were norm al. T he patient underwent an open incisional biopsy under general anesthesia. T he histopathological results indicated a classical ES in a periosteal location. According to AM ST S (Enneking’s) surgical stag ing system the patient was in stage 21 II-B. He received neoadjuvant chem otherapy and, in D ecem ber 1994, underwent a lim b-sp aring operation where the distal half of the right fem ur and knee joint were resected including the lateral ham string muscles and biopsy scar. The defect was replaced by a m odular endoprosthesis. H istopathological evaluation of the specim en showed 100% necrosis and practically no tum or m ass was found. H e continued the sam e chem otherapy until July 1995. T he area was not irradiated and during the follow -up period of 3 years since then he has been free of disease. (2) A 27-year-old m ale patient was referred to our unit on O ctober 1995 because of a painful growing mass in the m edial aspect of his right thigh for 2 ½ months. His general condition was good. Physical exam ination showed a tender longitudinal lesion in the right m id-m edial asp ect of his thigh. T here was no evidence of palp able lym ph nodes in any locations. Blood tests, including ESR, W BC count, AP and LD H, were all norm al. Conventional radiograph of the fem ur showed generalized periosteal thickening, with an area of bulging periosteum and a slight hypo dense region within it. A soft tissue com ponent was noted (Fig. 1). O ur differential diagnosis was either a soft tissue tum or encroaching upon the bone or a m alignant surface bone neoplasm. Staging studies included plain chest X-ray ® lm ; total body bone scan; CT of the lesion and chest and M RI of the lesion. As in the previous case, the C T and M RI of the thigh showed a periosteal/surface lesion without any involvement of the m edullary canal (Fig. 2). System ic bone
F ig. 1. Conventio nal radiog raph of the femur show s generalized periosteal thickening with an area of bulging periosteum and a slight hypodense region within it. A soft tissue com ponent is noted .
scan and chest CT were normal. O n O ctober 1995 he underwent a core needle biopsy. The histopathological result was classical ES in a periosteal location. 21 According to AMST S the patient was in stage II-B. N eo a d ju va n t ch em o th era p y an d p r eo p erative radiotherapy (4500 rad) were given. He underwent a lim b -sp ar in g p ro ced u re w h ere o n e-h alf o f th e m id -fe m o ral sh aft an d a d d u cto r m u scles w ere resected. T he defect was reconstructed with an intram edullary nail and autologous bone graft. Histopathological evaluation of the specimen showed 100% n ecro sis. H e co ntinu ed chem otherapy an d postoperative radiotherapy up till February 1997 and during the follow-up period of 1.5 years the patient has remained free of disease. Review of the literature (18 cases) Eighteen cases, described in ® ve papers published 15± 19 from 1986 to 1994, together with the two new cases, com prise this sur vey. T here were 17 m ale s an d three fem ales aged between 11 and 30 years. Presenting sym ptom s were m entio ned fo r 14 of the 20 patients 15,17± 19 and included: pain (four patients), a m ass (one patient) and a com bination of both in the rem aining nine patients. D uration of sym ptom s varied between 10 days and 4 m onths (m ean, 2 m onths). In 16 cases the tum ors were located in the proxim al long bones (six in the hum erus and 10 in the fem ur), two in the tibia,
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F ig. 2. C T scan of the m id-fem ur show s a per iostea l m ass with a soft tissue com ponent. A scalloping of the cortext is seen. The density of the m edulla appears nor m al.
one in the ® bula and one involving the scapula. In 16 cases the tumor was diaphyseal and in three it was m etadiapheaseal. All patients were at stage II-B at 21 presentation (according to AMSTS), meaning that no metastases were detected in baseline staging studies. N on-surgical treatment included chemotherapy for all 20 patients. For 14 patients details were noted about the method by which chemotherapy was given. In 13 of the 14 cases neoadjuvant chemotherapy was given and in one case adjuvant chemotherapy was given. Precise documentation about the timing of radiation therapy was also noted for 14 of the 20 patients. Of these, ® ve patients received external beam radiation therapy (two patients received only preoperative radiation therapy and three patients received combined pre- and postoperative radiation therapy). All of the remaining six patients received radiation therapy, but whether it was pre- or post-operative was not stated. Hence, 11 of the 20 patients received radiotherapy. N ineteen of the 20 patients had tum ors located in long bones (one was at the scapula). Of these 19 patients, 18 underwent lim b-sp aring surgery and one underwent am putation. Follow-up periods stated in the papers at publication were between 2 m onths and 10 years, w ith a m ean of 3 years. For 11 patients follow-up periods of m ore than 2 years were noted. Two patients were dead, at 1 and 2 years after end of therapy, and the rem aining 18 patients were alive with no evidence of disease. The fate of the patients after the publication of the papers is not know n to us.
Discussion Concerning the clinical presentation and age distribution, no differences between PES and other form s of 1,12,22 ES have been show n. There are differences, however, between PES and the other form s of ES with regard to sex predom inance, location of tum or an d surgical stage at pre sentation . A clear m ale
predom inance is noted in PES (the m ale to fem ale ratio is 5.7:1),15± 19 while in m edullary E S only a slight m ale predom inance, w ith a m ale to fem ale ratio 23,24 of about 1.5:1, is know n and there has been no male predom inance in extraskeletal ES reported.13,14. M ed u llar y 12,23± 24 an d extrao sseo u s 13,14,25 E S develop in both proxim al and distal long bones and ax ial ¯ at bon es. PE S show s a pred om in an ce in proxim al extrem ities and axial PES is uncom m on. Only one case of PES in an axial ¯ at bone (scapula) 16 was reported by Kolar et al. The sm all num ber of cases precludes a real statistical signi® cance to these clinical observations w hich show only trends. In PES, all 20 patients were diagnosed at stage II-B of the disease, with no evidence of distant m etastases. In comparison , m etastases at presentation occur 12,23 in about 25% of cases of m edullary ES and in 13 about 10% of cases of extraskeletal ES. Im aging studies help to con® rm the diagnosis of PES which is de® ned when there is no tumor invasion 10,11,26± 29 of the medullary cavity. . A subperiosteal mass with a periosteal thickening and a Codm an triangle are 10,11,26± 30 diagnostic. These radiological signs appear both in PES and m edullary ES, but PES usually shows a uninterrupted periosteal reaction compared with the `onion skin’ periosteal reaction observed medullary 20 ES. A subperiosteal location and the absence of medullary bone involvement help to distinguish PES 3,4,15± 17,20,31,32 from the other types of ES. Although conventional radiography provides the most useful inform ation for diagnosis and for gauging biological aggressiveness of the tum or, it has som e lim itations in estimating the extent of intram edullary disease in m edullary ES or in soft tissue involve1 m ent. Tumor size and the accurate m argins between the intram edullar y space, the periosteal location and the soft tissue can be adequately determ ined only by 1 im aging studies such as CT or M RI. T he typical picture of PES is of a periosteal tum or which has not invaded the m edullary cavity. 15± 19 Extraskeletal (soft
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tissue) ES tum ors w hich grew enough to invade the periosteum will be de® ned as PE S, so there m ight be an overlap between the two subtypes. Still, the entity of PE S is quite well established, and there is a difference between the periosteal form and the soft tissue form in term s of sex, anatom ical location in bones and staging at diagnosis. At histopathological exam ination, all subtypes of ES, w hether m edullary, extraskeletal or periosteal, appear the sam e. In general, E S consists of uniform , sm all, round or oval highly undifferentiated cells with a pale appearance and scanty cytoplasm . It contains glycogen-positive granules with positive periodic acid± 12± 17,25 Schiff stain. It is not understood w hy PES seem s to have a better progn osis than the other two for m s. T his obser vation is sim ilar to that of a better prognosis in periosteal osteosarcom a and periosteal chondrosar10,11 coma than in their m edullary counterparts. One possible explanation is that the location at the periosteum causes such pain that the patients seek medical help earlier. A nother possible explanation can be found in the cytogenetic pro® le of the patients. N one of the 18 patients in the ® ve articles reviewed, together with our own two patients, underwent cytogenetic analysis. T he reason for this favorable prognosis may be the latter. It is strongly recom m ended that such an analysis is perform ed for PES patients in the future. After review ing the literature it seem s to us that this rare entity should be considered in the differential diagnosis of the ES fam ily of tum ors since there is a possibility that it has a better prognosis than m edullary or soft tissue ES. References 1 Eggli KD, Quiogue T, M oser RP. Ewing’s sarcoma. Radiat Clin North Am 1993; 31(2):325± 37. 2 Hanna SL, Fletcher BD, Kaste SC, et al . Increased con ® d en ce o f diagn osis of E wing sarco m a u sing T2-weighted M R images. M agn Reson Imaging 1994; 12(4):559± 68. 3 Frouge C, Vanel D, Coffre C, et al.The role of magnetic resonance imaging in the evaluation of Ewing sarcoma. Skelet Radiol 1988; 17:387± 92. 4 Vanel D, Contsso G, Couanet D, et al. Com puted tomography in the evaluation of 41 cases of Ewing’s sarcoma. Skelet Radiol 1982; 9:8± 13. 5 M cM anus AP, Gusterson BA, Pinkerton CR, Shipley JM . Diagnosis of Ewing’s sarcoma and related tumors by detection of chromosome 22q12 translocations using ¯ uorescence in situ hybridization on tum or touch imprints. J Pathol . 1995; 176(2):137± 42. 6 Ladanyi M , Lewis R, Jhanwar SC, et al . M DM 2 and CD K4 gene ampli® cation in Ewing’s sarcoma. J Pathol 1995; 175(2):211± 7. 7 Dierick AM, Langlois M , Van-Oostveldt P, Roels H. The prognostic signi® cance of the DN A content in Ewing’s sarcoma: a retrospective cytophotometric and ¯ oe cytometric study. Histopatholog y 1993; 23(4):333± 9. 8 Taylor C, Patel K, Jones T, et al . Diagnosis of Ewing’s sarcoma and peripheral neuroectodermal tumor based on the detection of t(11;22) using ¯ uorescence in situ hybridisation. B r J Cancer 1993; 67(1):128± 33.
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