SACRAL MESENCHYMAL CHONDROSARCOMA IN ...

Pediatric Hematology and Oncology, 27:564–573, 2010 C Informa Healthcare USA, Inc. Copyright ISSN: 0888-0018 print / 1521-0669 online DOI: 10.3109/08880018.2010.503333

Case Report

Pediatr Hematol Oncol Downloaded from informahealthcare.com by Hacettepe University on 09/23/10 For personal use only.

SACRAL MESENCHYMAL CHONDROSARCOMA IN CHILDHOOD: A Case Report and Review of The Literature

¨ Serhan Kupeli, MD, MSc and Ali Varan, MD 2 Department of Pediatric Oncology, Institute of Oncology, Hacettepe University, Ankara, Turkey ¨ ˘ Gokhan Gedikoglu 2 Department of Pathology, Faculty of Medicine, Hacettepe University, Ankara, Turkey ¨ ¨ ukpamukc ¨ Munevver Buy ¸ u, MD 2 Department of Pediatric Oncology, Institute of Oncology, Hacettepe University, Ankara, Turkey

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Mesenchymal chondrosarcomas are rare malignant tumors in pediatric age group. The authors present a case of mesenchymal chondrosarcoma located in the sacrum in a 10-year-old-girl that was successfully treated with chemotherapy and radiotherapy after surgical excision. According to the authors’ literature search, the patient is the first reported case of pediatric sacral primary mesenchymal chondrosarcoma. Mesenchymal chondrosarcoma cases in pediatric age group published in English literature was reviewed. Keywords

children, mesenchymal chondrosarcoma, sacrum, treatment

Mesenchymal chondrosarcomas arising from osteoid structures and soft tissues anywhere in the body are among the rarest tumors in childhood [1]. They carry a high malignant potential and tend to occur in young adults [2]. Although most of the lesions are located in skeleton, extraosseous mesenchymal chondrosarcomas arising from pancreas, kidney, parapharyngeal space, and even from intracranial soft tissue were reported [3–9]. Because of the rarity of these tumors, treatment approaches basically depend on single case reports or small case series. In this case report, we aimed to present the first case of pediatric sacral primary mesenchymal chondrosarcoma with literature review.

Received 3 June 2009; Accepted 9 June 2010. Address correspondance to Serhan Küpeli, MD, MSc, Department of Pediatric Oncology, Institute of Oncology, Hacettepe University, 06100, Ankara, Turkey. E-mail: [email protected]

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Sacral Mesenchymal Chondrosarcoma

FIGURE 1 Sacral spinal MRI scan revealed a 30×10 mm mass located anterior to the sacrum.

CASE REPORT A 10-year-old girl has been taken to another hospital because of low back pain existing for 5 months. Sacral spinal magnetic resonance imaging (MRI) revealed a 30 × 10-mm mass located anterior to the sacrum and the


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FIGURE 2 (A) Tumor mainly composed of the small round anaplastic cells and some pleomorphic cells, H&E, ×460. (B) S100 protein positivity were seen in some of the cells, S100 protein, ×460. (C) Tumor focally showed metachromasia with toluidin blue staining, ×460.

tumor excised totally (Figure 1). The patient then referred to our center for further investigation and treatment. Her previous medical and family histories were unremarkable. Physical examination was normal except for sacral longitudinal scarring due to operation. Early pathology report of the previous center was small round cell malign tumor without description of surgical margins. Histopathological examination of the paraphine embedded blocks confirmed the diagnosis of mesenchymal chondrosarcoma in our center. Tumor almost composed of the small round cells. These cells have round/oval hyperchromatic nuclei and scant cytoplasm. Tumoral cells focally produced chondroid matrix (Figure 2). Postoperative MRI taken 45 days after surgery showed a recurring solid mass measured 35 × 17 × 17 mm with contrast at the same localization. Thoracal computed tomography (CT) of the patient revealed millimetrical nodules in lung. A chemotherapy protocol consisting of cisplatin and Adriamycin was initiated. After 3 courses a very good response was attained. A total of 54 Gy radiotherapy was delivered to the sacral mass. The patient was given 8 courses of this chemotherapy regimen. A sacral MRI scan at the sixth month of treatment showed a cystic degeneration without a solid mass. An additional 3 courses vincristin, actinomycin D, and cyclophosphamide chemotherapy was administered before the cessation of teatment. Chemotherapy was stopped in May 2007 without residual or recurrent mass in sacral MRI. The patient is well and free of disease 26 months after cessation of chemotherapy. DISCUSSION Primary tumors of the sacrum including benign aggressive lesions such as aneurysmal bone cyst, osteoblastoma, and giant cell tumor or low-grade malignancies such as chordoma and chondrosarcoma constitute 1% to 4.3% of all bone tumors [9]. Although most of the classic chondrosarcomas are slow growing and low-grade tumors, mesenchymal chondrosarcomas are rapidly



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growing tumors with greater potential to metastasize [10]. Conventional chondrosarcoma of bone makes up 85% of all chondrosarcomas, whereas other several rare types of chondrosarcoma; dedifferentiated, mesenchymal, and clear cell chondrosarcoma together constitute 10% to 15% of all chondrosarcomas [1]. Although mesenchymal chondrosarcomas can be encountered at any age their incidence tend to peak in second and third decade [1, 2]. As seen in literature summary (Table 1), there is no significant sex predilection in childhood. Relatively young age of our patient, recurrence of the totally resected tumor in a short time, and pulmonary metastasis on admission are compliant with reported nature of the mesenchymal chondrosarcomas. Mesenchymal chondrosarcomas can ocur in soft tissues such as in pancreas, kidney, parapharyngeal space, thyroid, and even brain [3–10], as well as in bony structures such as maxilla, mandible, rib, vertebra, talus, ilium, tibia, femur, and skull bones [11–32]. Aprin et al [33] described a 16-year-old female with chondrosarcoma in sacrum and S1 joint but they did not specify the subtype of the chondrosarcoma. Although there are 3 case reports in literature reporting primary sacral mesenchymal chondrosarcomas in 17-, 20-, and 23-year-old patients, the present case is unique in childhood [34–36]. Sacral localization is uncommon for mesenchymal chondrosarcoma in children and deserves special attention. Sacral mesenchymal chondrosarcoma can present with symptoms of a growing mass. Deep pelvic localization and nonspecific sympomatology may cause a delay in diagnosis. In our case the principal complaint was low back pain continuing for 5 months. There was no difficulty nor incontinence in defecation or urination probably because of the relatively small size of the tumor. Physical examination also cannot help to find out a presacral mass, as is the case of our patient. Radiological methods are quite necessary to delineate the extent of osseous and soft tissue involvement. In MRI, mesenchymal chondrosarcoma often contains areas of matrix mineralization, suggesting a chondroid neoplasm and it is relatively less extensive and ill-defined than conventional chondrosarcomas [37, 38]. Although the pathogenesis of the mesenchymal chondrosarcoma is not clear, the transition areas between mesenchymal cells and cartilage indicate precartilage mesenchymal origin [5]. Pathologically it is characterized by undifferentiated small blue round cells mixed with cartilage differentiation [39]. Histopathological differential diagnosis of mesenchymal chondrosarcoma should include small round cell tumors such as lymphoma, neuroblastoma, rhabdomyosarcoma, and others such as osteochondroma, conventional chondrosarcoma, and hemangiopericytoma [40]. Immunohistochemistry may help to differentiate some of these tumors. In the present case, the tumoral cells were not stained with CD99, sinaptophysin, leukocyte common antogen (LCA), desmin, Tdt, CD43, chromogranin, and periodic acid–Schiff (PAS). It was determined focal positivity with S100 protein. Tumoral cells

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Parietal skull Maxilla, skull base Orbit

1/M Paravertebral/intraspinal Suryanarayana [5] 7/F Parapharyngeal space ˙ Spina [6] 14/F Intracranial Abbas [7] 13/F Thyroid Rohrbach [8] 15/F Eye lid Chhem [9] 11/F Brain Kaufman [13] 14/M Rib De Cecio [15] 2 mo/M Parietal skull Marshman [16] 17/F Temporoparietal Crosswell [17] 6 mo/M Frontoparietal ˙ Lee [18] 18/F Intraspinal dura Daita [19] 10/F Spinal dura ˙ Chan [20] 2 cases, Intraspinal NS Reif [21] 3/M Vertebra Kruse [22] NS Cervical spine

15/F 14/F 14/F

3/M Nasal cavity, maxilla, orbit 5 mo/F Orbit 10/F Orbit 15/F Skull base

Gadwal [32] Tuncer [40] Dantonello [2]

Location

Age/sex

Surgery CR CR SubR SubR CR CR CR CR CR SubR CR CR NS CR CR CR CR CR CR NS CR NS

M − − − − − − − − − − − − − − − − − − − + + −

+, NS NS

— 55 Gy 31 Gy — — NS — — — — +, NS — +, NS

— — —

+, NS — 48 Gy 44.4 Gy

Radiotherapy

+, NS NS

− CVA, VAC CEV, IVE, CAV — +, NS NS — — — VCEC — — +, NS

VACD VACD VIDA

— VAC, IEC VIDA VIDA

Chemotherapy

Characteristics of the Pediatric Mesenchymal Chondrosarcoma Patients Reported in Literature

Author/reference

TABLE 1

+, NS NS

— — — — Local, NS NS — — Local, NS — — — —

— — — 1. Local, 2.6 yr 2. Local, 2.8 yr − — —

Recurrence


NS NS

D, 7.2 mo A, 14.4 yr A, 15.3 yr Secondary AML A, 1.4 yr A, 3 mo A, 24 mo A, 68 mo A, 18 mo NS A, NS D, 2 mo D, 1 mo D, 1 mo NS A, 14 mo D, NS

A, 13.1 yr A, 3.5 yr A, 8.4 yr D, 4.4 yr

Outcome

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Cervical spine Thigh Parietal bone Skullbase ˙ Intracerebral Dura mater Jugular foramen Frontoparietal Vagus nerve Mandible Mandible Mandible Maxilla Mandible

Mandible Mandible Mandible Maxilla Femur Tibia NS Sacrum

11/M 10/F 18/F 14/F 14/F 13/F 15/M 13/F 12/F 16/F 12/F 6/M 9/F 2/M

12/M 11/M 8/M 9/M 13/M 11/M 13/M 10/F

NS CR SubR SubR CR CR SubR CR CR CR CR CR CR CR CR CR CR CR +, NS +, NS +, NS CR

− − − − − − − − − + − − − − − − − − + − + + — — — — — — — 54 Gy

— — — 74 Gy — +, NS — — — — — — — — — — — — HDMTX +, NS HDMTX CA, VAC

— — — — — — — — — +, NS — — — —

Local, 1.5 mo

—

+, 10 yr —

—

— Local, NS

— — — — — Local, 21 mo — — — — —

A, 2 yrs A, 10 mo D, 16 mo A, 1 yr D, 8 yr NS A, 35 mo A, 30 mo A, 12 mo A, 22 yr A, 6 yr Lost to follow-up A, 2 yr A, 8 yr with local disease A, 11 yr Lost to follow-up A, 31 yr D, 6 yr D, NS A, 49 mo D, NS A, 27 mo

Note. M = metastasis; CR = complete resection; SubR = subtotal resection; NS = not specified; CVA = cyclophosphamide, vincristine, Adriamycin; VAC = vincristine, actinomycin D, cyclophosphamide; CEV = carboplatin, etoposide, vincristine; IVE = ifosfamide, vincristine, etoposide; CAV = carboplatin, Adriamycin, vinristine; IEC = ifosfamide, epirubicin, cisplatin; VIDA = vincristine, ifosfamide, doxorubicin, actinomycin D; VACD = vincristine, actinomycin D, cyclophosphamide, doxorubicin; CA = cisplatin, Adriamycin; HDMTX = high-dose methotrexate; VCEC = vincristine, cyclophosphamide, etoposide, cisplatin; A = alive; D = died.

Present case

Huvos [45]

Chen [23] Gatter [24] Wu [25] Hoshino [26] Parker [27] Cho [28] Nozaki [29] Chen [30] Jamal [42] Vencio [44]



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were embedded in an eosinophylic matrix and revealed a slight metachromasia with toluidin blue staining. Because different treatment schedules for different kinds of tumors can be designed, it is quite important to know the type of the small round cell tumors. Complete surgical resection is the principal mode of treatment for all subtypes of nonmetastatic chondrosarcoma [1, 2]. In large series that also included adult patients, resection with wide margins is accepted as the gold standard of treatment [41]. In all pediatric mesenchymal chondrosarcoma cases, at least subtotal resection, but mostly complete resection, could have been undertaken [2, 5, 6, 13, 16, 40–45]. On the other hand, wide excision may cause significant morbidity depending on location and degree of invasion of the tumor. Bladder and bowel functional sequelae have been reported due to sacral amputation in an adult with sacral mesenchymal chondrosarcoma [34]. Sar and Eralp [10] have faced permanent urinary and anal incontinence and drop foot after total sacrectomy and lumbopelvic fixation in their sacral chondrosarcoma patients. In our case initially the tumor was removed completely, but due to local recurrence and metastatic spread in a short time after the surgery, adjuvant chemo- and radiotherapy were started instead of second look surgery. Probably the surgical margins were contaminated despite wide resection. Dantonello et al [2] described a patient with mesenchymal chondrosarcoma in skull base in whom the tumor was resected subtotally and recurred locally 2 times. In a large adult series, the authors reported a recurrence rate of 3/7 in patients with sacral chondrosarcoma (11). The high rate of local recurrence should not be forgotten if the surgical margins are not wide enough in patients with mesenchymal chondrosarcoma. There is no general agreement on whether additional chemotherapy, radiotherapy, or both are necessary after surgery. Adjuvant therapy can be considered in patients with incomplete resection. Although chondrogenic tumors are assumed relatively radioresistant due to lower growing rates, mesenchymal chondrosarcoma with a higher fraction of dividing cells can benefit from radiotherapy. Radiotherapy is especially a valuable tool to ensure local control in macroscopic or microscopic residual disease after surgery [1]. Pediatric mesenchymal chondrosarcoma patients were given radiotherapy between 30 and 55 Gy for curative intentions [2, 5, 6]. In pediatric patients the utilization of radiotherapy may be limited because of late adverse effects in tumors around central nervous system, especially before myelinization completed. Similarly in tumors arising from axial skeleton, radiotherapy may compromise proper growing in lower ages. Despite the scarcity of the cases chemotherapy seems to be efficient in mesenchymal chondrosarcoma. Gelderblom et al [1] reported a higher chemosensitivity if the tumor contains high percentage of round cells. In a large series also patients with small cell types of lesions were found to respond well to chemotherapy [44]. Several authors have reported cases



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responding to chemotherapy in pediatric mesenchymal chondrosarcoma [2, 5, 6, 40]. The most commonly used chemotherapeutics are similar to agents that has been shown to be effective in other pediatric soft tissue sarcomas. Cyclophosphamide, vincristine, Adriamycin, ifosfamide, cisplatin, and actinomycin D were the most frequently used agents [2, 5, 6, 40]. Huvos et al [45] reported no response in their 2 patients with mesenchymal chondrosarcoma to high-dose methotrexate administration. With cisplatin and Adriamycin combination chemotherapy a very good response was attained in our case. Kawai et al [46] determined inadequate surgical margin as the only independent adverse prognostic factor for local recurrence and surgical stage for distant metastasis for patients with sarcomas of the pelvic bones. It is likely that in a large series surgical margin and tumor grade were found statistically significant factors for local recurrence and systemic spread, respectively, in multivariate analysis (11). Ten-year survival rates for patients with mesenchymal chondrosarcoma are reported between 28% and 58% in the literature [41, 44, 45]. As pointed out in a study, tumors involving the sacrum has a significantly higher incidence of incomplete surgical margins similar to the presented case [46]. With a diagnosis of a rapidly growing tumor such as mesenchymal chondrosarcoma and inadequate surgical margins, local recurrence is inevitable. Adjuvant chemo- and radiotherapy can be other treatment choices in this setting, with the knowledge of high sensitivity of mesenchymal chondrosarcoma to these treatment modalities. As a result, the risk of the local recurrence because of insufficient resection should be balanced with the high morbidity rate secondary to wide resection in patients with sacral mesenchymal chondrosarcoma. Adjuvant radiotherapy and/or chemotherapy will add much benefit in this highly malignant type of chondrosarcoma. Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. REFERENCES [1] Gelderblom H, Hogendoorn PCW, Dijkstra SD, et al. The clinical approach towards chondrosarcoma. Oncologist. 2008;13:320–329. [2] Dantonello TM, Int-Veen C, Leuschner I, et al. Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults: experiences of the CWS and COSS study groups. Cancer. 2008;112:2424–2431. [3] Oh BG, Han YH, Lee BH, et al. Primary extraskeletal mesenchymal chondrosarcoma arising from the pancreas. Korean J Radiol. 2007;8:541–544. [4] Kaneko T, Suzuki Y, Takata R, et al. Extraskeletal mesenchymal chondrosarcoma of the kidney. Int J Urol. 2006;13:285–286. [5] Suryanarayana KV, Balakrishnan R, Rao L, Rahim TA. Parapharyngeal space mesenchymal chondrosarcoma in childhood. Int J Pediatr Otorhinolaryngol. 1999;50:69–72. [6] La Spina M, Dollo C, Giangaspero F, et al. Intracranial mesenchymal chondrosarcoma with osteoid formation: report of a pediatric case. Childs Nerv Syst. 2003;19:680–682.


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