Chondroblastic Osteosarcoma of the Rib as a Second Primary Malignancy Following Neuroblastoma: A Case Report

Chondroblastic Osteosarcoma of the Rib as a Second Primary Malignancy Following Neuroblastoma: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Chondroblastic Osteosarcoma of the Rib as a Second Primary Malignancy Following Neuroblastoma: A Case Report Darrick L. Yeta, Andinet Dessalegn, Mikyas Befekadu Nigusse, Derek Harrison This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9403276/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background: Second primary malignancies (SPMs) are a well-recognized long-term complication among childhood cancer survivors. Osteosarcoma arising as a secondary malignancy is rare, and chest wall involvement presents unique diagnostic and therapeutic challenges. This case illustrates the clinical course and multidisciplinary management of chondroblastic osteosarcoma in a pediatric patient with prior neuroblastoma. Case Presentation: A 12-year-old girl with a history of stage III neuroblastoma diagnosed at age three presented with a painful right anterior chest wall mass. Imaging revealed an expansile lesion involving the right fourth rib with chest wall extension. Biopsy confirmed chondroblastic osteosarcoma. Following neoadjuvant chemotherapy, she underwent en bloc resection of ribs three through five, with subsequent re-excision to achieve negative margins after initial positive lateral margins. The postoperative course was complicated by right lung collapse requiring intensive care support. Conclusions: SPMs should be considered in childhood cancer survivors presenting with new musculoskeletal complaints, even years after successful treatment of the primary malignancy. Multidisciplinary management with neoadjuvant chemotherapy and aggressive surgical resection, achieving negative margins, is essential for optimizing outcomes in this rare patient population. chondroblastic osteosarcoma second primary malignancy chest wall tumor rib resection neuroblastoma survivor case report Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Background Second primary malignancies (SPMs) are a well-recognized long-term complication among childhood cancer survivors ( 1 , 2 ). Osteosarcoma arising as a secondary malignancy is rare( 2 , 3 ), and treatment outcomes following secondary primary malignancies in childhood cancer survivors are generally poorer than for first primary cancers; for example, survivors diagnosed with SPMs have significantly lower overall survival across multiple cancer types( 4 ). This case is notable for the development of chondroblastic osteosarcoma in a 12-year-old girl with a history of stage III neuroblastoma diagnosed at age three. The tumor involved the anterior chest wall and right fourth rib, extending to adjacent ribs and adhering to the middle lobe of the lung, an anatomic presentation that is uncommon in pediatric secondary malignancies. Reporting this case is important because it illustrates the clinical course, imaging findings, and operative management of a secondary malignancy arising many years after successful treatment of the primary tumor. The case highlights the challenges of managing secondary bone malignancies, including distinguishing recurrent primary disease from a new neoplasm, planning surgical resection with adequate margins, and coordinating neoadjuvant chemotherapy. This report provides practical insight into multidisciplinary decision-making, perioperative care, and short-term functional outcomes in pediatric patients with secondary malignancies, emphasizing the need for vigilant long-term follow-up in childhood cancer survivors. 2. Case Presentation A 12-year-old girl presented with a two-week history of a painful right anterior chest wall mass that she and her family initially perceived as a breast lump. She denied nipple discharge, overlying skin changes, or systemic symptoms. Physical examination revealed a firm, immobile mass in the right breast region with normal overlying breast tissue inferiorly; the skin was unremarkable with no nipple retraction or discharge. Her past medical history was significant for stage III neuroblastoma of the right adrenal gland diagnosed at age three years, with N-MYC amplification and no initial bone or bone marrow metastasis. She had received multimodal treatment including chemotherapy, surgery, radiotherapy, autologous hematopoietic stem cell transplantation, and 13-cis-retinoic acid, and had remained under long-term follow-up thereafter. Timeline of the current episode: presentation to diagnosis took two weeks, followed by nine weeks of neoadjuvant chemotherapy, en bloc resection, re-excision one week later, and discharge after one week in the intensive care unit. Initial mammography demonstrated an ill-defined mass in the right anterior chest wall. Subsequent computed tomography (CT) of the chest revealed an expansile mixed lytic-sclerotic lesion involving the anterior aspect of the right fourth rib with extension into the chest wall and involvement of the underlying pleura (Fig. 1 A and 1 B). Magnetic resonance imaging (MRI) confirmed a large anterior chest wall mass with destruction of the right fourth rib and invasion into the pectoralis major muscle (Fig. 1 C). A bone scan showed increased radiotracer uptake involving the anterior aspects of the right third through fifth ribs, with additional uptake in the left ninth rib, T12 vertebral body, and left tibial shaft (Fig. 2 ). Targeted MRI of these sites demonstrated no metastatic disease, and the findings were considered non-malignant. Following neoadjuvant chemotherapy, repeat CT with three-dimensional reconstruction demonstrated disease limited to the right fourth rib (Fig. 1 D). Ultrasound-guided core needle biopsy of the chest wall mass demonstrated chondromyxoid areas containing atypical neoplastic cells with foci suggestive of osteoid formation (Fig. 3 ). Immunohistochemistry showed strong SATB2 positivity within neoplastic cells, while estrogen receptor and progesterone receptor staining were negative. These findings were consistent with chondroblastic osteosarcoma and excluded recurrent neuroblastoma. Bone marrow evaluation was initially positive for osteosarcoma; however, repeat histologic assessment after definitive surgery showed no bone marrow involvement. The patient received neoadjuvant chemotherapy according to the EURAMOS protocol, but tolerated only nine of the planned twelve weeks due to chemotherapy intolerance. She subsequently underwent definitive surgical resection. Intraoperatively, a large tumor arising from the right fourth anterior rib extended to the anterior axillary line with involvement of the adjacent third rib and anteromedial aspect of the fifth rib (Fig. 4 A). The mass was adherent to the middle lobe of the right lung without pleural metastasis, effusion, or lymphadenopathy. En-bloc resection of the third through fifth right ribs was performed, and the defect was covered with biologic mesh (Fig. 4 B). Lateral margins were positive on initial histopathology analysis; therefore, the patient returned to the operating room one week later for complete resection of the fourth rib to the costovertebral junction, achieving final negative margins. Histological examination of the resected specimen showed approximately 80% tumor necrosis. The postoperative course was complicated by right lung collapse requiring intensive care unit admission, intercostal chest drainage, and high-flow nasal oxygen therapy, with gradual improvement over one week. The patient continued systemic chemotherapy and is now under regular follow-up. She remains tumor-free on the most recent CT chest with no pulmonary metastases. The patient and her family expressed satisfaction with the surgical outcome and her return to normal daily activities. 3. Discussion This case of chondroblastic osteosarcoma of the rib arising as a second primary malignancy nine years after high-risk neuroblastoma illustrates several important surgical and oncologic considerations. Secondary osteosarcoma is rare among childhood cancer survivors, and chest-wall involvement adds unique challenges related to achieving negative margins and thoracic reconstruction. Strengths of this report include the detailed multidisciplinary management that is neoadjuvant chemotherapy per the EURAMOS protocol, en bloc rib resection with re-excision for positive margins, and biologic mesh reconstruction, along with the clear documentation of imaging, histopathology, and short-term outcomes in a resource-limited setting. Limitations are inherent to single-case reports: the findings cannot be generalized, and long-term oncologic and functional outcomes beyond the current follow-up period remain unknown. The etiology of second primary malignancies is multifactorial, with prior radiotherapy and alkylating agents being the dominant risk factors for secondary sarcomas( 2 , 3 ). In this patient, the nine-year latency period after multimodal neuroblastoma therapy, which included radiotherapy, chemotherapy, autologous stem-cell transplantation, and 13-cis-retinoic acid, is consistent with radiation-associated sarcomas( 3 ). Secondary osteosarcoma after neuroblastoma is rarely reported, with only a few previously reported cases( 5 – 7 ). Chest-wall osteosarcoma itself is uncommon in children and carries higher risks of local recurrence and pulmonary metastasis compared with extremity tumors( 8 , 9 ). Management of pediatric chest-wall osteosarcoma centers on complete surgical resection with negative margins, combined with neoadjuvant/adjuvant chemotherapy( 10 ). This case demonstrates the importance of re-excision when margins are initially positive, as well as the value of histologic response assessment (80% necrosis in this patient). Achieving negative margins is critical; positive margins significantly increase local recurrence risk and reduce overall survival( 11 ). Although thoracic osteosarcomas generally carry a poorer prognosis than extremity lesions ( 12 , 13 ), some data suggest that secondary osteosarcomas may have more favorable outcomes when detected early through surveillance ( 14 ). This report underscores the need for lifelong surveillance in childhood cancer survivors and highlights that aggressive surgical management, even in anatomically complex locations, can achieve local control and short-term disease-free survival. 4. Conclusion This case highlights several key management considerations in second primary chest wall osteosarcoma: distinguishing a new primary malignancy from recurrent disease, achieving negative surgical margins in anatomically complex locations, and coordinating multimodal therapy. The patient’s history of prior multimodal treatment for neuroblastoma underscores the importance of long-term surveillance for SPMs, particularly given the latency period of 9 years. Abbreviations SPM – Second primary malignancy CT – Computed tomography MRI – Magnetic resonance imaging Declarations Ethical Approval and consent to participate The institutional review board at our university does not require review for isolated retrospective case reports. Consent for Publication Written informed consent was obtained from the patient’s mother for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Availability of Data and Materials Not applicable Competing interests The authors declare no competing interests. Funding No external funding was received for this work. Author contributions DLY: Primary author, Data collection, literature review, manuscript writing AD: First Assisting surgeon, Operative details, Case supervision, Manuscript review. MBN: Data collection, manuscript editing, and literature review. DH: Lead surgeon, Operative details, Case supervision Acknowledgments Not Applicable References Inskip PD, Curtis RE. New malignancies following childhood cancer in the United States, 1973–2002. Int J Cancer. 2007 Nov 15;121(10):2233–40. doi:10.1002/ijc.22827 Friedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, et al. Subsequent Neoplasms in 5-Year Survivors of Childhood Cancer: The Childhood Cancer Survivor Study. JNCI J Natl Cancer Inst. 2010 Jul;102(14):1083–95. doi:10.1093/jnci/djq238 Bhatia S, Sklar C. Second cancers in survivors of childhood cancer. Nat Rev Cancer. 2002 Feb;2(2):124–32. doi:10.1038/nrc722 Brown AL, Arroyo VM, Agrusa JE, Scheurer ME, Gramatges MM, Lupo PJ. Survival disparities for second primary malignancies diagnosed among childhood cancer survivors: A population‐based assessment. Cancer. 2019 Oct 15;125(20):3623–30. doi:10.1002/cncr.32356 Iwata A, Hirota T, Konno K, Fujimoto T, Sumida S, Sato K, et al. OSTEOSARCOMA AS A SECOND MALIGNANCY AFTER TREATMENT FOR NEUROBLASTOMA. Pediatr Hematol Oncol. 2001 Jan;18(7):465–9. doi:10.1080/088800101750476050 Knott EM, Shah SR, Jones G, Hetherington M, Sharp RJ. Treatment of chest wall osteosarcoma presenting as second primary after treatment of neuroblastoma. J Pediatr Surg. 2012 Sep;47(9):e5–7. doi:10.1016/j.jpedsurg.2012.04.019 Kawashima H, Ogose A, Hotta T, Imai C, Imamura M, Endo N. Secondary osteosarcoma arising from osteochondroma following autologous stem cell transplantation with total-body irradiation for neuroblastoma: A case report. Oncol Lett. 2015 Aug;10(2):1026–30. doi:10.3892/ol.2015.3257 Schwarz RE, Burt M. Radiation-associated malignant tumors of the chest wall. Ann Surg Oncol. 1996 Jul;3(4):387–92. doi:10.1007/BF02305669 Tateishi U, Gladish GW, Kusumoto M, Hasegawa T, Yokoyama R, Tsuchiya R, et al. Chest Wall Tumors: Radiologic Findings and Pathologic Correlation: Part 2. Malignant Tumors. RadioGraphics. 2003 Nov;23(6):1491–508. doi:10.1148/rg.236015527 Harris CJ, Helenowski I, Murphy AJ, Mansfield SA, LaQuaglia MP, Heaton TE, et al. Implications of Tumor Characteristics and Treatment Modality on Local Recurrence and Functional Outcomes in Children With Chest Wall Sarcoma: A Pediatric Surgical Oncology Research Collaborative Study. Ann Surg. 2022 Dec;276(6):e969–75. doi:10.1097/SLA.0000000000004579 Bertrand TE, Cruz A, Binitie O, Cheong D, Letson DG. Do Surgical Margins Affect Local Recurrence and Survival in Extremity, Nonmetastatic, High-grade Osteosarcoma? Clin Orthop. 2016 Mar;474(3):677–83. doi:10.1007/s11999-015-4359-x Qian J, Zhang XY, Gu P, Shao JC, Han BH, Wang HM. Primary thoracic extraskeletal osteosarcoma: a case report and literature review. J Thorac Dis. 2017 Dec;9(12):E1088–95. doi:10.21037/jtd.2017.11.111 Beird HC, Bielack SS, Flanagan AM, Gill J, Heymann D, Janeway KA, et al. Osteosarcoma. Nat Rev Dis Primer. 2022 Dec 8;8(1):77. doi:10.1038/s41572-022-00409-y Yonemoto T, Hosono A, Iwata S, Kamoda H, Hagiwara Y, Fujiwara T, et al. The prognosis of osteosarcoma occurring as second malignancy of childhood cancers may be favorable: experience of two cancer centers in Japan. Int J Clin Oncol. 2015 Jun;20(3):613–6. doi:10.1007/s10147-014-0729-8 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 15 May, 2026 Reviewers agreed at journal 15 May, 2026 Reviewers agreed at journal 14 May, 2026 Reviewers agreed at journal 14 May, 2026 Reviewers invited by journal 14 May, 2026 Editor invited by journal 20 Apr, 2026 Editor assigned by journal 17 Apr, 2026 Submission checks completed at journal 17 Apr, 2026 First submitted to journal 13 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9403276","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":627639711,"identity":"9672a9ed-043b-44ab-8479-87df635a2c06","order_by":0,"name":"Darrick L. Yeta","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIiWNgGAWjYDCCA0CcAIR8UL4chGIjQgtMjTGSFmbcWhiQtCQ2ENLCd/zssw8PatIY2Nh7D3/4mWOTvnba4QcMH8oOM5iz9x/ApkXyTLrxjIRjOQxsPOfSJHu3peVuu51mwDjj3GEGy57DWG0xOJDGDHRMBQObRI4ZA++2w0AtOey/edsOMxjcSMau5fwzqBb5N8Yf/247nG52O4eB+S9Iy/3H2LXcANsCdJgEj4E00JYEsBZGsC3YvS95A2hLwrE0HjaeHDNp2W1phmC/9JxL5zE4k2yANcTOpzEz/qhJluNnP2P88e02G3mz28kPGH6UWcsZHD/4AKs1UMBDhMgoGAWjYBSMAqIBAD+tXf8lsP8jAAAAAElFTkSuQmCC","orcid":"","institution":"MCM Comprehensive Specialized Hospital","correspondingAuthor":true,"prefix":"","firstName":"Darrick","middleName":"L.","lastName":"Yeta","suffix":""},{"id":627639715,"identity":"55186f09-e750-4a93-8f57-9b83a63b39e8","order_by":1,"name":"Andinet Dessalegn","email":"","orcid":"","institution":"MCM Comprehensive Specialized Hospital","correspondingAuthor":false,"prefix":"","firstName":"Andinet","middleName":"","lastName":"Dessalegn","suffix":""},{"id":627639716,"identity":"4c525723-5fe8-4e4b-a503-acf469d21211","order_by":2,"name":"Mikyas Befekadu Nigusse","email":"","orcid":"","institution":"MCM Comprehensive Specialized Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mikyas","middleName":"Befekadu","lastName":"Nigusse","suffix":""},{"id":627639719,"identity":"22cb4fd8-4fa7-4c2e-ab06-4b487423e97a","order_by":3,"name":"Derek Harrison","email":"","orcid":"","institution":"Chris Hani Baragwanath Hospital","correspondingAuthor":false,"prefix":"","firstName":"Derek","middleName":"","lastName":"Harrison","suffix":""}],"badges":[],"createdAt":"2026-04-13 11:24:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9403276/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9403276/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108978735,"identity":"a3347801-0d3c-4bd3-a013-654a1a462ff3","added_by":"auto","created_at":"2026-05-11 11:48:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":657354,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eCT and MRI Imaging of Chest Wall Mass.\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e (A)(B) Axial CT chest: Expansile mixed lytic-sclerotic lesion involving the right fourth rib with extension into the chest wall and involvement of the underlying pleura. (C) MRI chest: Chest wall mass with destruction of the right fourth rib and pectoralis major invasion. (D) CT with three-dimensional reconstruction.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9403276/v1/4ad94956c6aece3b5c974816.png"},{"id":108978787,"identity":"2535db5a-dadb-458b-a8af-3ab21998e66e","added_by":"auto","created_at":"2026-05-11 11:48:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":463214,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eBone Scan: Increased radiotracer uptake involving the anterior aspects of the right third through fifth ribs, with additional uptake noted in the left ninth rib and T12 vertebral body.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eUltrasound-guided core needle biopsy of the chest wall mass demonstrated chondromyxoid areas containing atypical neoplastic cells with foci suggestive of osteoid formation (Figure 3).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9403276/v1/63691482af1d15bc65f09aa5.png"},{"id":108978811,"identity":"6c5c3717-041f-4025-a957-13dea0836050","added_by":"auto","created_at":"2026-05-11 11:48:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":974140,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eHistopathology:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e Core needle biopsy specimen showing chondromyxoid areas with atypical neoplastic cells. Foci of osteoid formation are noted. Features are consistent with chondroblastic osteosarcoma\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9403276/v1/cdad7377654de74a6d239b75.png"},{"id":108978786,"identity":"069070c5-baa3-439f-aeaa-707924cc316d","added_by":"auto","created_at":"2026-05-11 11:48:27","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":844071,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eIntraoperative pictures (A): \u003c/strong\u003e\u003c/em\u003e\u003cem\u003edepicting the mass engulfing the 3\u003c/em\u003e\u003csup\u003e\u003cem\u003erd\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e-5\u003c/em\u003e\u003csup\u003e\u003cem\u003eth\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e ribs during the en bloc resection\u003c/em\u003e\u003cem\u003e\u003cstrong\u003e (B):\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e\u0026nbsp;biologic mesh covering the defect following resection\u003c/em\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9403276/v1/3bf97339de86696b0bcd141a.png"},{"id":108981113,"identity":"6b008ad7-ff9f-4397-bb00-a3989f2fec5d","added_by":"auto","created_at":"2026-05-11 12:14:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3732071,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9403276/v1/9f9b9ed3-aaf0-4aa4-9189-40cfb902dced.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Chondroblastic Osteosarcoma of the Rib as a Second Primary Malignancy Following Neuroblastoma: A Case Report","fulltext":[{"header":"1. Background","content":"\u003cp\u003eSecond primary malignancies (SPMs) are a well-recognized long-term complication among childhood cancer survivors (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Osteosarcoma arising as a secondary malignancy is rare(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), and treatment outcomes following secondary primary malignancies in childhood cancer survivors are generally poorer than for first primary cancers; for example, survivors diagnosed with SPMs have significantly lower overall survival across multiple cancer types(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis case is notable for the development of chondroblastic osteosarcoma in a 12-year-old girl with a history of stage III neuroblastoma diagnosed at age three. The tumor involved the anterior chest wall and right fourth rib, extending to adjacent ribs and adhering to the middle lobe of the lung, an anatomic presentation that is uncommon in pediatric secondary malignancies. Reporting this case is important because it illustrates the clinical course, imaging findings, and operative management of a secondary malignancy arising many years after successful treatment of the primary tumor. The case highlights the challenges of managing secondary bone malignancies, including distinguishing recurrent primary disease from a new neoplasm, planning surgical resection with adequate margins, and coordinating neoadjuvant chemotherapy. This report provides practical insight into multidisciplinary decision-making, perioperative care, and short-term functional outcomes in pediatric patients with secondary malignancies, emphasizing the need for vigilant long-term follow-up in childhood cancer survivors.\u003c/p\u003e"},{"header":"2. Case Presentation","content":"\u003cp\u003eA 12-year-old girl presented with a two-week history of a painful right anterior chest wall mass that she and her family initially perceived as a breast lump. She denied nipple discharge, overlying skin changes, or systemic symptoms. Physical examination revealed a firm, immobile mass in the right breast region with normal overlying breast tissue inferiorly; the skin was unremarkable with no nipple retraction or discharge.\u003c/p\u003e \u003cp\u003eHer past medical history was significant for stage III neuroblastoma of the right adrenal gland diagnosed at age three years, with N-MYC amplification and no initial bone or bone marrow metastasis. She had received multimodal treatment including chemotherapy, surgery, radiotherapy, autologous hematopoietic stem cell transplantation, and 13-cis-retinoic acid, and had remained under long-term follow-up thereafter.\u003c/p\u003e \u003cp\u003eTimeline of the current episode: presentation to diagnosis took two weeks, followed by nine weeks of neoadjuvant chemotherapy, en bloc resection, re-excision one week later, and discharge after one week in the intensive care unit.\u003c/p\u003e \u003cp\u003eInitial mammography demonstrated an ill-defined mass in the right anterior chest wall. Subsequent computed tomography (CT) of the chest revealed an expansile mixed lytic-sclerotic lesion involving the anterior aspect of the right fourth rib with extension into the chest wall and involvement of the underlying pleura (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Magnetic resonance imaging (MRI) confirmed a large anterior chest wall mass with destruction of the right fourth rib and invasion into the pectoralis major muscle (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). A bone scan showed increased radiotracer uptake involving the anterior aspects of the right third through fifth ribs, with additional uptake in the left ninth rib, T12 vertebral body, and left tibial shaft (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Targeted MRI of these sites demonstrated no metastatic disease, and the findings were considered non-malignant. Following neoadjuvant chemotherapy, repeat CT with three-dimensional reconstruction demonstrated disease limited to the right fourth rib (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eUltrasound-guided core needle biopsy of the chest wall mass demonstrated chondromyxoid areas containing atypical neoplastic cells with foci suggestive of osteoid formation (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eImmunohistochemistry showed strong SATB2 positivity within neoplastic cells, while estrogen receptor and progesterone receptor staining were negative. These findings were consistent with chondroblastic osteosarcoma and excluded recurrent neuroblastoma. Bone marrow evaluation was initially positive for osteosarcoma; however, repeat histologic assessment after definitive surgery showed no bone marrow involvement.\u003c/p\u003e \u003cp\u003eThe patient received neoadjuvant chemotherapy according to the EURAMOS protocol, but tolerated only nine of the planned twelve weeks due to chemotherapy intolerance. She subsequently underwent definitive surgical resection. Intraoperatively, a large tumor arising from the right fourth anterior rib extended to the anterior axillary line with involvement of the adjacent third rib and anteromedial aspect of the fifth rib (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). The mass was adherent to the middle lobe of the right lung without pleural metastasis, effusion, or lymphadenopathy. En-bloc resection of the third through fifth right ribs was performed, and the defect was covered with biologic mesh (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB). Lateral margins were positive on initial histopathology analysis; therefore, the patient returned to the operating room one week later for complete resection of the fourth rib to the costovertebral junction, achieving final negative margins. Histological examination of the resected specimen showed approximately 80% tumor necrosis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe postoperative course was complicated by right lung collapse requiring intensive care unit admission, intercostal chest drainage, and high-flow nasal oxygen therapy, with gradual improvement over one week. The patient continued systemic chemotherapy and is now under regular follow-up. She remains tumor-free on the most recent CT chest with no pulmonary metastases. The patient and her family expressed satisfaction with the surgical outcome and her return to normal daily activities.\u003c/p\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eThis case of chondroblastic osteosarcoma of the rib arising as a second primary malignancy nine years after high-risk neuroblastoma illustrates several important surgical and oncologic considerations. Secondary osteosarcoma is rare among childhood cancer survivors, and chest-wall involvement adds unique challenges related to achieving negative margins and thoracic reconstruction.\u003c/p\u003e \u003cp\u003eStrengths of this report include the detailed multidisciplinary management that is neoadjuvant chemotherapy per the EURAMOS protocol, en bloc rib resection with re-excision for positive margins, and biologic mesh reconstruction, along with the clear documentation of imaging, histopathology, and short-term outcomes in a resource-limited setting. Limitations are inherent to single-case reports: the findings cannot be generalized, and long-term oncologic and functional outcomes beyond the current follow-up period remain unknown.\u003c/p\u003e \u003cp\u003eThe etiology of second primary malignancies is multifactorial, with prior radiotherapy and alkylating agents being the dominant risk factors for secondary sarcomas(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In this patient, the nine-year latency period after multimodal neuroblastoma therapy, which included radiotherapy, chemotherapy, autologous stem-cell transplantation, and 13-cis-retinoic acid, is consistent with radiation-associated sarcomas(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Secondary osteosarcoma after neuroblastoma is rarely reported, with only a few previously reported cases(\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Chest-wall osteosarcoma itself is uncommon in children and carries higher risks of local recurrence and pulmonary metastasis compared with extremity tumors(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eManagement of pediatric chest-wall osteosarcoma centers on complete surgical resection with negative margins, combined with neoadjuvant/adjuvant chemotherapy(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). This case demonstrates the importance of re-excision when margins are initially positive, as well as the value of histologic response assessment (80% necrosis in this patient). Achieving negative margins is critical; positive margins significantly increase local recurrence risk and reduce overall survival(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Although thoracic osteosarcomas generally carry a poorer prognosis than extremity lesions (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), some data suggest that secondary osteosarcomas may have more favorable outcomes when detected early through surveillance (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis report underscores the need for lifelong surveillance in childhood cancer survivors and highlights that aggressive surgical management, even in anatomically complex locations, can achieve local control and short-term disease-free survival.\u003c/p\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eThis case highlights several key management considerations in second primary chest wall osteosarcoma: distinguishing a new primary malignancy from recurrent disease, achieving negative surgical margins in anatomically complex locations, and coordinating multimodal therapy. The patient\u0026rsquo;s history of prior multimodal treatment for neuroblastoma underscores the importance of long-term surveillance for SPMs, particularly given the latency period of 9 years.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eSPM \u0026ndash; Second primary malignancy \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCT \u0026ndash; Computed tomography \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMRI \u0026ndash; Magnetic resonance imaging \u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthical Approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThe institutional review board at our university does not require review for isolated retrospective case reports.\u003c/p\u003e\n\u003ch2\u003eConsent for Publication\u003c/h2\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient\u0026rsquo;s mother for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003ch2\u003eAvailability of Data and Materials\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eNo external funding was received for this work.\u003c/p\u003e\n\u003ch2\u003eAuthor contributions\u003c/h2\u003e\n\u003cp\u003eDLY: Primary author, Data collection, literature review, manuscript writing\u003cbr\u003e\u0026nbsp;AD: First Assisting surgeon, Operative details, Case supervision, Manuscript review.\u003cbr\u003e\u0026nbsp;MBN: Data collection, manuscript editing, and literature review.\u003cbr\u003e\u0026nbsp;DH: Lead surgeon, Operative details, Case supervision\u003c/p\u003e\n\u003ch2\u003eAcknowledgments\u003c/h2\u003e\n\u003cp\u003eNot Applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eInskip PD, Curtis RE. New malignancies following childhood cancer in the United States, 1973\u0026ndash;2002. Int J Cancer. 2007 Nov 15;121(10):2233\u0026ndash;40. doi:10.1002/ijc.22827\u003c/li\u003e\n\u003cli\u003eFriedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, et al. Subsequent Neoplasms in 5-Year Survivors of Childhood Cancer: The Childhood Cancer Survivor Study. JNCI J Natl Cancer Inst. 2010 Jul;102(14):1083\u0026ndash;95. doi:10.1093/jnci/djq238\u003c/li\u003e\n\u003cli\u003eBhatia S, Sklar C. Second cancers in survivors of childhood cancer. Nat Rev Cancer. 2002 Feb;2(2):124\u0026ndash;32. doi:10.1038/nrc722\u003c/li\u003e\n\u003cli\u003eBrown AL, Arroyo VM, Agrusa JE, Scheurer ME, Gramatges MM, Lupo PJ. Survival disparities for second primary malignancies diagnosed among childhood cancer survivors: A population‐based assessment. Cancer. 2019 Oct 15;125(20):3623\u0026ndash;30. doi:10.1002/cncr.32356\u003c/li\u003e\n\u003cli\u003eIwata A, Hirota T, Konno K, Fujimoto T, Sumida S, Sato K, et al. OSTEOSARCOMA AS A SECOND MALIGNANCY AFTER TREATMENT FOR NEUROBLASTOMA. Pediatr Hematol Oncol. 2001 Jan;18(7):465\u0026ndash;9. doi:10.1080/088800101750476050\u003c/li\u003e\n\u003cli\u003eKnott EM, Shah SR, Jones G, Hetherington M, Sharp RJ. Treatment of chest wall osteosarcoma presenting as second primary after treatment of neuroblastoma. J Pediatr Surg. 2012 Sep;47(9):e5\u0026ndash;7. doi:10.1016/j.jpedsurg.2012.04.019\u003c/li\u003e\n\u003cli\u003eKawashima H, Ogose A, Hotta T, Imai C, Imamura M, Endo N. Secondary osteosarcoma arising from osteochondroma following autologous stem cell transplantation with total-body irradiation for neuroblastoma: A case report. Oncol Lett. 2015 Aug;10(2):1026\u0026ndash;30. doi:10.3892/ol.2015.3257\u003c/li\u003e\n\u003cli\u003eSchwarz RE, Burt M. Radiation-associated malignant tumors of the chest wall. Ann Surg Oncol. 1996 Jul;3(4):387\u0026ndash;92. doi:10.1007/BF02305669\u003c/li\u003e\n\u003cli\u003eTateishi U, Gladish GW, Kusumoto M, Hasegawa T, Yokoyama R, Tsuchiya R, et al. Chest Wall Tumors: Radiologic Findings and Pathologic Correlation: Part 2. Malignant Tumors. RadioGraphics. 2003 Nov;23(6):1491\u0026ndash;508. doi:10.1148/rg.236015527\u003c/li\u003e\n\u003cli\u003eHarris CJ, Helenowski I, Murphy AJ, Mansfield SA, LaQuaglia MP, Heaton TE, et al. Implications of Tumor Characteristics and Treatment Modality on Local Recurrence and Functional Outcomes in Children With Chest Wall Sarcoma: A Pediatric Surgical Oncology Research Collaborative Study. Ann Surg. 2022 Dec;276(6):e969\u0026ndash;75. doi:10.1097/SLA.0000000000004579\u003c/li\u003e\n\u003cli\u003eBertrand TE, Cruz A, Binitie O, Cheong D, Letson DG. Do Surgical Margins Affect Local Recurrence and Survival in Extremity, Nonmetastatic, High-grade Osteosarcoma? Clin Orthop. 2016 Mar;474(3):677\u0026ndash;83. doi:10.1007/s11999-015-4359-x\u003c/li\u003e\n\u003cli\u003eQian J, Zhang XY, Gu P, Shao JC, Han BH, Wang HM. Primary thoracic extraskeletal osteosarcoma: a case report and literature review. J Thorac Dis. 2017 Dec;9(12):E1088\u0026ndash;95. doi:10.21037/jtd.2017.11.111\u003c/li\u003e\n\u003cli\u003eBeird HC, Bielack SS, Flanagan AM, Gill J, Heymann D, Janeway KA, et al. Osteosarcoma. Nat Rev Dis Primer. 2022 Dec 8;8(1):77. doi:10.1038/s41572-022-00409-y\u003c/li\u003e\n\u003cli\u003eYonemoto T, Hosono A, Iwata S, Kamoda H, Hagiwara Y, Fujiwara T, et al. The prognosis of osteosarcoma occurring as second malignancy of childhood cancers may be favorable: experience of two cancer centers in Japan. Int J Clin Oncol. 2015 Jun;20(3):613\u0026ndash;6. doi:10.1007/s10147-014-0729-8\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"chondroblastic osteosarcoma, second primary malignancy, chest wall tumor, rib resection, neuroblastoma survivor, case report ","lastPublishedDoi":"10.21203/rs.3.rs-9403276/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9403276/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Second primary malignancies (SPMs) are a well-recognized long-term complication among childhood cancer survivors. Osteosarcoma arising as a secondary malignancy is rare, and chest wall involvement presents unique diagnostic and therapeutic challenges. This case illustrates the clinical course and multidisciplinary management of chondroblastic osteosarcoma in a pediatric patient with prior neuroblastoma.\u003c/p\u003e\n\u003cp\u003eCase Presentation: A 12-year-old girl with a history of stage III neuroblastoma diagnosed at age three presented with a painful right anterior chest wall mass. Imaging revealed an expansile lesion involving the right fourth rib with chest wall extension. Biopsy confirmed chondroblastic osteosarcoma. Following neoadjuvant chemotherapy, she underwent en bloc resection of ribs three through five, with subsequent re-excision to achieve negative margins after initial positive lateral margins. The postoperative course was complicated by right lung collapse requiring intensive care support.\u003c/p\u003e\n\u003cp\u003eConclusions: SPMs should be considered in childhood cancer survivors presenting with new musculoskeletal complaints, even years after successful treatment of the primary malignancy. Multidisciplinary management with neoadjuvant chemotherapy and aggressive surgical resection, achieving negative margins, is essential for optimizing outcomes in this rare patient population.\u003c/p\u003e","manuscriptTitle":"Chondroblastic Osteosarcoma of the Rib as a Second Primary Malignancy Following Neuroblastoma: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 10:56:32","doi":"10.21203/rs.3.rs-9403276/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"275235537133373476428905279414742658199","date":"2026-05-15T18:17:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"255502886507979498525000657012832930882","date":"2026-05-15T07:05:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"32417376222536256300488165341401529930","date":"2026-05-14T22:04:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"324540391373565354281877736564086384276","date":"2026-05-14T19:22:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-14T17:36:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-20T09:04:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-17T10:53:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-17T10:53:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2026-04-13T11:08:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"689246dc-e4c0-4386-8265-03cf329d8426","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"275235537133373476428905279414742658199","date":"2026-05-15T18:17:10+00:00","index":38,"fulltext":""},{"type":"reviewerAgreed","content":"255502886507979498525000657012832930882","date":"2026-05-15T07:05:46+00:00","index":37,"fulltext":""},{"type":"reviewerAgreed","content":"32417376222536256300488165341401529930","date":"2026-05-14T22:04:38+00:00","index":36,"fulltext":""},{"type":"reviewerAgreed","content":"324540391373565354281877736564086384276","date":"2026-05-14T19:22:53+00:00","index":35,"fulltext":""},{"type":"reviewersInvited","content":"15","date":"2026-05-14T17:36:06+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T17:38:30+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 10:56:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9403276","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9403276","identity":"rs-9403276","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}