Anterior Intercostal Heterotopic Ossification: A Rare Cadaveric Case Study with Multimodal Analysis

Anterior Intercostal Heterotopic Ossification: A Rare Cadaveric Case Study with Multimodal Analysis | 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 Research Article Anterior Intercostal Heterotopic Ossification: A Rare Cadaveric Case Study with Multimodal Analysis Subin Hur, Young-Suk Cho, Hye Jung Cho, Gab Gyeong Go, Kwang Il Nam This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4798199/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 3 You are reading this latest preprint version Abstract Heterotopic ossification (HO) is a pathological condition characterized by ectopic bone formation in soft tissues. This study presents a rare case of anterior intercostal HO discovered in a 62-year-old Korean male cadaver during an educational dissection. The HO structure, which connected multiple ribs, underwent radiological examination (X-ray and CT scans) and histological analysis. Radiographic findings revealed that mature bone had formed adjacent to the ribs, surrounded by fibrous tissue. Histological analysis demonstrated a progression from fibrous tissue to mature bone, indicative of endochondral ossification, with no proliferative activity detected in the Ki-67 immunostaining. This case provides valuable insights into intercostal HO's morphological, radiological, and histological characteristics, providing significant information in anatomy and pathology for educational purposes. Heterotopic ossification Anterior intercostal X-ray CT scan Cadaver Figures Figure 1 Figure 2 Figure 3 Introduction Heterotopic ossification (HO) is a pathological process characterized by the formation of extraskeletal bone in soft tissues [ 12 ]. The etiology of HO can be categorized into genetic factors, such as fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH), and non-genetic factors, including neurogenic, post-traumatic, post-surgical, and reactive lesions [ 19 ]. HO can occur in various connective tissues, with areas adjacent to joints particularly susceptible [12. 15]. While HO commonly affects muscles, fascia, tendons, and ligaments near major joints, thoracic manifestations, especially in the intercostal area, are rare [ 1 , 4 ]. Anterior intercostal HO with bridging formation is particularly uncommon, contrasting with the more frequently observed posterior intercostal HO [ 5 , 10 , 13 , 18 ]. The pathogenesis of HO involves local injury and systemic stress, which creates a pro-inflammatory environment that stimulates heterotopic bone formation [ 9 ]. This process typically progresses through early, intermediate, and mature phases [ 20 ], following endochondral or intramembranous ossification pathways or a combination of both [ 3 ]. Terminology for HO often reflects the affected tissue, such as myositis ossificans (MO), for skeletal muscle involvement. However, this nomenclature can be misleading as HO is not specific to muscle [ 12 ]. Differential diagnosis is crucial, as HO may mimic other conditions like osteosarcoma [ 4 ]. Accurate diagnosis relies on patient history, clinical symptoms, imaging, and histological confirmation, emphasizing invasive biopsy for definitive assessment [ 5 , 11 ]. This study presents a rare cadaveric case of anterior intercostal HO, providing morphological, radiological, and histological analyses. The findings contribute valuable insights to education in anatomy and pathology. Case report During an educational dissection at Chonnam National University Medical School, a 62-year-old Korean male cadaver underwent a standard dissection procedure. The authors state that every effort was made to follow all local and international ethical guidelines and laws pertaining to using human cadaveric donors in anatomical research [ 7 ]. The present study was performed in accordance with the requirements of the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013). After removing the skin, superficial fascia, fat, and intercostal muscles, a firm bridged structure was identified in the intercostal area. The structure remained intact after excising the surrounding tissue. The bridged formations were observed between the right fourth and fifth ribs anteriorly (Rt1) (Fig. 1 a), the left side, anterolaterally between the third and fourth ribs (Lt1), as well as anterolaterally between the fourth and fifth ribs (Lt2) and anteriorly between the fourth and fifth ribs (Lt3) (Fig. 1 b). The structure was extracted by cutting the respective ribs for further analysis. Radiographic imaging (X-ray and CT scans) revealed that the peripheral zone near the ribs exhibited bone characteristics due to density variations. At the same time, the remaining part appeared as soft tissue (Fig. 2 a, b, c). Histological analysis confirmed the soft tissue as fibrous tissue through H&E staining (Fig. 2 d, e). The extent of HO varied across the different bridged formations: Rt1 showed a small amount of mature bone at the superior part of the fifth rib, with mostly fibrous tissue throughout. Lt1 displayed more advanced HO than Rt1, extending from the superior part of the fourth rib to the middle of the bridged structure. Lt2 exhibited the most extensive HO, with mature bone formation throughout, except for a small central region of fibro-osteoid tissue. H&E histology revealed a central zone of fibrous tissue, an intermediate zone with hypertrophic cells showing chondrocyte maturation and endochondral bone formation, and a peripheral zone of mature bone adjacent to the ribs (Fig. 3 a, b). Immunohistochemical analysis using anti-Ki67 antibody showed no positive reactive cells, indicating an absence of proliferative activity and suggesting that the HO progression had ceased (Fig. 3 c). This rare cadaveric case report of anterior and anterolateral intercostal HO demonstrates that the ossification process occurred in the past and was arrested at varying stages of progression in different locations. Discussion HO has both genetic and non-genetic etiologies. Rare genetic conditions like FOP and POH exhibit distinct characteristics [ 19 ]. FOP typically emerges in early childhood, following specific ossification patterns throughout the body, while POH involves unpredictable intramembranous ossification [ 8 ]. Non-genetic HO can arise from neurogenic factors (e.g., spinal cord injury, traumatic brain injury), trauma, or surgical procedures [ 15 , 16 ]. Our case presents a rare bridged HO formation in the anterior intercostal area, likely stemming from a traumatic incident approximately a decade before the donor's death. The histopathological mechanism of non-genetic HO remains debated, with descriptions ranging from endochondral to intramembranous processes or a combination of both [ 3 ]. Our research aligns with previous studies on periarticular non-genetic HO, revealing a progression from fibrous tissue to mature bone through endochondral ossification. This process typically involves six distinct stages: perivascular lymphocytic infiltration, lymphocytic migration into soft tissue, reactive fibroproliferation, neovascularity, cartilage formation, and endochondral bone formation [ 3 ]. In our case, the absence of Ki-67 expression suggests that the HO process was complete, with no ongoing proliferation. MO, the most common form of HO, is often misapplied to describe HO, even when it lacks specific muscle involvement or inflammation [ 12 , 16 , 20 ]. In our case, we opted for HO due to the absence of muscular inflammation. Distinguishing HO from malignant soft tissue or osteogenic sarcomas is crucial due to their vastly different prognoses and treatments [ 5 , 11 ]. This differentiation relies heavily on the characteristic “zonation pattern” or “zone phenomenon” observed in HO [ 17 ]. Diagnosis of HO typically relies on a combination of patient history, clinical symptoms, and imaging studies. X-rays serve as the initial imaging modality, while CT scans can detect calcifications at an earlier stage [ 17 ]. MRI is effective for visualizing soft-tissue masses, and ultrasound offers a low-cost method for early detection [ 20 ]. X-ray and CT scans were employed in our case, revealing mature bone formation adjacent to the ribs with a central fibrous tissue component. Histological confirmation through biopsy is often necessary, with careful attention paid to the characteristic zonation pattern of HO [ 11 , 14 ]. Our histological analysis demonstrated a clear progression from fibrous tissue to mature bone, indicative of endochondral ossification. The central zone consisted of fibrous stroma, transitioning to an intermediate zone with hypertrophic cells showing chondrocyte maturation and finally to a peripheral zone of mature bone. This pattern stands in stark contrast to osteosarcoma, where tumor growth is centrifugal, with more mature cells concentrated in the center [ 5 ]. The absence of proliferative activity, as evidenced by negative Ki-67 immunostaining, suggests that the HO, in our case, had reached a stable, non-progressive state. This finding holds important implications for understanding the natural history of HO and potential treatment strategies. Interestingly, our case of anterior intercostal HO with bridged formation is extremely rare. While HO in the chest has occasionally been reported, it typically forms a mass or occurs in the posterior area [ 5 , 10 , 13 , 18 ]. The bridging formation observed in our case could potentially interfere with respiratory function by limiting chest wall mobility [ 4 , 18 ], similar to the effects of flail chest [ 2 ]. However, the lack of medical treatment sought by the donor suggests that the condition may have been asymptomatic or caused minimal discomfort. This study underscores the importance of a comprehensive understanding of HO to avoid unnecessary diagnostics and treatments. It also highlights the value of thorough anatomical, radiological, and histological examinations in accurately identifying and characterizing unusual presentations of HO. Future research could focus on the long-term progression and potential functional impacts of such rare HO formations. Moreover, this case provides valuable insights for educational purposes in anatomy and pathology. It demonstrates the significance of considering HO in differential diagnoses, especially in cases with atypical presentations or locations. The multidisciplinary approach used in this study—combining gross anatomical observation, radiological imaging, and histological analysis—is an excellent model for comprehensively evaluating anatomical anomalies. Conclusion Our case report on anterior intercostal traumatic HO with bridged formation significantly contributes to the literature on HO. It emphasizes the importance of meticulous evaluation and accurate diagnosis of bone-forming lesions, particularly in atypical locations. As our understanding of HO evolves, cases like this provide crucial data points for enhancing diagnostic accuracy and developing targeted treatment strategies. Declarations Competing interests The authors declare no competing interests. Funding sources Not Applicable Author Contribution SB Hur wrote the main manuscript and prepared all figures. YS Cho performed radiological examination. HJ Cho conducted H&E staining. GG Go reviewed the literature. KI Nam was responsible for project development and supervision. All authors reviewed the manuscript. Acknowledgement The authors sincerely thank those who donated their bodies to science so that anatomical research could be performed. The results from such research can potentially increase our collective knowledge and ultimately improve patient care. Therefore, these donors and their families deserve our highest gratitude [6]. Data availability No datasets were generated or analysed during the current study. References Al Khader A, Habaibeh E, Tawalbeh HY, Mansour BM, Mansour SM, Haj Ahmad AN, Owais TT, Odeh H (2023) Myositis ossificans of the chest wall in an 8-year-old boy: a case report of a diagnostic pitfall. Indian J Thorac Cardiovasc Surg 39(2):186–189 Al-Qadi MO (2018) Disorders of the Chest Wall: Clinical Manifestations. Clin Chest Med 39(2):361–375 Foley KL, Hebela N, Keenan MA, Pignolo RJ (2018) Histopathology of periarticular non-hereditary heterotopic ossification. Bone 109:65–70 Greiffenstein P, Adams E, Scheuermann A, Rogers C (2019) Treatment of symptomatic intercostal heterotopic ossification after surgical stabilization of rib fractures: report of two cases and review of the literature. J Thorac Dis 11(Suppl 8):S1106–S1112 Harmon DC, Nielsen GP (1994) Case 38-1994 — a 55-year-old man with a paraspinal mass and a history of radiation treatment of a testicular tumor. N Engl J Med 331(16):1079–1084 Iwanaga J, Singh V, Ohtsuka A et al (2021) Acknowledging the use of human cadaveric tissues in research papers: Recommendations from anatomical journal editors. Clin Anat 34(1):2–4 Iwanaga J, Singh V, Takeda S et al (2022) Standardized statement for the ethical use of human cadaveric tissues in anatomy research papers: Recommendations from anatomical journal editors-in-chief. Clin Anat 35(4):526–528 Kaplan FS, Glaser DL, Hebela N, Shore EM (2004) Heterotopic ossification. J Am Acad Orthop Surg 12(2):116–125 Kim H (2018) Heterotopic Ossification in the Abdominal Wall after Exploratory Laparotomy. J Trauma Inj 31(3):177–180 Koob M, Durckel J, Dosch JC, Entz-Werle N, Dietemann JL (2010) Intercostal myositis ossificans misdiagnosed as osteosarcoma in a 10-year-old child. Pediatr Radiol 40(Suppl 1):S34–37 Lacout A, Jarraya M, Marcy PY, Thariat J, Carlier RY (2012) Myositis ossificans imaging: keys to successful diagnosis. Indian J Radiol Imaging 22(1):35–39 Meyers C, Lisiecki J, Miller S, Levin A, Fayad L, Ding C, Sono T, McCarthy E, Levi B, James AW (2019) Heterotopic Ossification: A Comprehensive Review. JBMR Plus 3(4):e10172 Nuovo MA, Norman A, Chumas J, Ackerman LV (1922) Myositis ossificans with atypical clinical, radiographic, or pathologic findings: a review of 23 cases. Skeletal Radiol 21(2):87–101 Pătru S, Pădureanu V, Rădulescu D, Mititelu RR, Pădureanu R, Băcanoiu M, Matei D (2021) A nontraumatic myositis ossificans case of the forearm: Case report and literature review. Exp Ther Med 21(5):531 Ranganathan K, Loder S, Agarwal S, Wong VW, Forsberg J, Davis TA, Wang S, James AW, Levi B (2015) Heterotopic Ossification: Basic-Science Principles and Clinical Correlates. J Bone Joint Surg Am 97(13):1101–1111 Saad A, Azzopardi C, Patel A, Davies AM, Botchu R (2021) Myositis ossificans revisited - The largest reported case series. J Clin Orthop Trauma 17:123–127 Savvidou O, Papakonstantinou O, Lakiotaki E, Melissaridou D, Korkolopoulou P, Papagelopoulos PJ (2021) Post-traumatic myositis ossificans: a benign lesion that simulates malignant bone and soft tissue tumours. EFORT Open Rev 6(7):572–583 Van Wijck SFM, Wijffels MME (2023) Surgical strategy for treating multiple symptomatic rib fracture malunions with bridging heterotopic ossifications: A case report. Trauma Case Rep. https://doi:10.1016/j.tcr.2023.100825 Vanden BL, Vanderstraeten G (2005) Heterotopic ossification: a review. J Rehabil Med 37(3):129–136 Walczak BE, Johnson CN, Howe BM (2015) Myositis Ossificans. J Am Acad Orthop Surg 23(10):612–622 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editor assigned by journal 26 Jul, 2024 Submission checks completed at journal 25 Jul, 2024 First submitted to journal 24 Jul, 2024 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-4798199","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":332031601,"identity":"66eb236c-97d0-4e96-830b-cd3b16958191","order_by":0,"name":"Subin Hur","email":"","orcid":"","institution":"Department of Medical Sciences 2nd Grade, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Subin","middleName":"","lastName":"Hur","suffix":""},{"id":332031604,"identity":"0e80282c-0945-4434-905c-063776e5d8d2","order_by":1,"name":"Young-Suk Cho","email":"","orcid":"","institution":"Department of Anatomy, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Young-Suk","middleName":"","lastName":"Cho","suffix":""},{"id":332031606,"identity":"e0867422-9151-42ee-a04f-5fceaf0fc7c3","order_by":2,"name":"Hye Jung Cho","email":"","orcid":"","institution":"Department of Anatomy, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Hye","middleName":"Jung","lastName":"Cho","suffix":""},{"id":332031607,"identity":"03f6f233-ca4c-4b19-9ad4-7170563aefad","order_by":3,"name":"Gab Gyeong Go","email":"","orcid":"","institution":"Department of Anatomy, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Gab","middleName":"Gyeong","lastName":"Go","suffix":""},{"id":332031610,"identity":"d20ddd78-86d5-45ea-ae16-8cd84925b9ed","order_by":4,"name":"Kwang Il Nam","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvklEQVRIiWNgGAWjYFAC5gYGhgo2KOcAMTrYGIFazpCshbENxiNGC//8xsaPP+fx5RkcYH74geHMPcJaJI4xNkvzbmMrNjjAZizBcKOYCGuOMTZIM25jS9xwgMGMgeFDAmEd8kBbfv6cA9LC/o04LQbHGNskeBtAWniAttwgQovhscQ2a55jbIkzD/MUSyScIUKL3OHDh2/+qDmW2He8feOHD8eI0AIFx4CpAEgRr4GBoYYEtaNgFIyCUTDiAAAjLTr4zaHz8QAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Anatomy, Chonnam National University Medical School","correspondingAuthor":true,"prefix":"","firstName":"Kwang","middleName":"Il","lastName":"Nam","suffix":""}],"badges":[],"createdAt":"2024-07-25 01:14:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4798199/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4798199/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63370018,"identity":"bfc9dd1f-0ed9-46d2-82a4-a68d66c8740c","added_by":"auto","created_at":"2024-08-27 11:47:09","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":522004,"visible":true,"origin":"","legend":"\u003cp\u003eThe morphology of heterotopic ossification (HO). (a) Between the right fourth and fifth ribs anteriorly (Rt1), (b) between the left anterolateral third and fourth ribs (Lt1), and fourth and fifth ribs (Lt2) and anteriorly between the fourth and fifth ribs (Lt3).\u003c/p\u003e","description":"","filename":"Fig1..jpg","url":"https://assets-eu.researchsquare.com/files/rs-4798199/v1/f84ddeac56e1556a965daa0c.jpg"},{"id":63371367,"identity":"2a6fcf78-0ffc-4a23-b6c5-ece5ec824d0b","added_by":"auto","created_at":"2024-08-27 11:55:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":482382,"visible":true,"origin":"","legend":"\u003cp\u003e(a–e) Radiographic and histological analysis of Lt1 and Lt2: (a) X-ray in the AP view, (b) CT in the AP view, and (c) CT in the PA view showed that Lt1 had mature bone extending from the superior part of the fourth rib to the middle part of the bridged structure, and Lt2 had mature bone almost in contact from the inferior part of the fourth rib to the fifth rib. (d) H\u0026amp;E staining of Lt1 showed that the remaining soft tissue consisted of fibrous tissue. (e) Lt2 showed that fibrous tissue was nearly absent, with the remaining part consisting of fibro-osteoid tissue.\u003c/p\u003e","description":"","filename":"Fig2..jpg","url":"https://assets-eu.researchsquare.com/files/rs-4798199/v1/a7e3fa2db780bd5e56489e22.jpg"},{"id":63370016,"identity":"d5e30e5e-2e0f-49f4-ac1e-71a32daa7af4","added_by":"auto","created_at":"2024-08-27 11:47:09","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":672739,"visible":true,"origin":"","legend":"\u003cp\u003e(a–b) Histological appearance of Rt1 by H\u0026amp;E staining, (a) whole-mount of Rt1, (b) enlarged image of rectangular area shows fibrous tissue in the center area (arrow), endochondral ossification in the intermediate area (empty arrowhead), and mature bone formation in the periphery area (black arrowhead). (c) The IHC appearance of Rt 1 does not show Ki-67 immunoreactivity.\u003c/p\u003e","description":"","filename":"Fig3..jpg","url":"https://assets-eu.researchsquare.com/files/rs-4798199/v1/2a29808a81365de26c789cfb.jpg"},{"id":63371403,"identity":"c385a768-4a35-424d-8af7-07f8c1b628a2","added_by":"auto","created_at":"2024-08-27 11:55:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1915755,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4798199/v1/5c6d0e21-49f9-45ff-8134-bac46a53066a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Anterior Intercostal Heterotopic Ossification: A Rare Cadaveric Case Study with Multimodal Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHeterotopic ossification (HO) is a pathological process characterized by the formation of extraskeletal bone in soft tissues [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The etiology of HO can be categorized into genetic factors, such as fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH), and non-genetic factors, including neurogenic, post-traumatic, post-surgical, and reactive lesions [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. HO can occur in various connective tissues, with areas adjacent to joints particularly susceptible [12. 15].\u003c/p\u003e \u003cp\u003eWhile HO commonly affects muscles, fascia, tendons, and ligaments near major joints, thoracic manifestations, especially in the intercostal area, are rare [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Anterior intercostal HO with bridging formation is particularly uncommon, contrasting with the more frequently observed posterior intercostal HO [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe pathogenesis of HO involves local injury and systemic stress, which creates a pro-inflammatory environment that stimulates heterotopic bone formation [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This process typically progresses through early, intermediate, and mature phases [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], following endochondral or intramembranous ossification pathways or a combination of both [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTerminology for HO often reflects the affected tissue, such as myositis ossificans (MO), for skeletal muscle involvement. However, this nomenclature can be misleading as HO is not specific to muscle [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Differential diagnosis is crucial, as HO may mimic other conditions like osteosarcoma [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Accurate diagnosis relies on patient history, clinical symptoms, imaging, and histological confirmation, emphasizing invasive biopsy for definitive assessment [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study presents a rare cadaveric case of anterior intercostal HO, providing morphological, radiological, and histological analyses. The findings contribute valuable insights to education in anatomy and pathology.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eDuring an educational dissection at Chonnam National University Medical School, a 62-year-old Korean male cadaver underwent a standard dissection procedure. The authors state that every effort was made to follow all local and international ethical guidelines and laws pertaining to using human cadaveric donors in anatomical research [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The present study was performed in accordance with the requirements of the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013). After removing the skin, superficial fascia, fat, and intercostal muscles, a firm bridged structure was identified in the intercostal area. The structure remained intact after excising the surrounding tissue. The bridged formations were observed between the right fourth and fifth ribs anteriorly (Rt1) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea), the left side, anterolaterally between the third and fourth ribs (Lt1), as well as anterolaterally between the fourth and fifth ribs (Lt2) and anteriorly between the fourth and fifth ribs (Lt3) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). The structure was extracted by cutting the respective ribs for further analysis. Radiographic imaging (X-ray and CT scans) revealed that the peripheral zone near the ribs exhibited bone characteristics due to density variations. At the same time, the remaining part appeared as soft tissue (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea, b, c). Histological analysis confirmed the soft tissue as fibrous tissue through H\u0026amp;E staining (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed, e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe extent of HO varied across the different bridged formations:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eRt1 showed a small amount of mature bone at the superior part of the fifth rib, with mostly fibrous tissue throughout.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eLt1 displayed more advanced HO than Rt1, extending from the superior part of the fourth rib to the middle of the bridged structure.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eLt2 exhibited the most extensive HO, with mature bone formation throughout, except for a small central region of fibro-osteoid tissue.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eH\u0026amp;E histology revealed a central zone of fibrous tissue, an intermediate zone with hypertrophic cells showing chondrocyte maturation and endochondral bone formation, and a peripheral zone of mature bone adjacent to the ribs (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea, b). Immunohistochemical analysis using anti-Ki67 antibody showed no positive reactive cells, indicating an absence of proliferative activity and suggesting that the HO progression had ceased (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThis rare cadaveric case report of anterior and anterolateral intercostal HO demonstrates that the ossification process occurred in the past and was arrested at varying stages of progression in different locations.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHO has both genetic and non-genetic etiologies. Rare genetic conditions like FOP and POH exhibit distinct characteristics [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. FOP typically emerges in early childhood, following specific ossification patterns throughout the body, while POH involves unpredictable intramembranous ossification [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Non-genetic HO can arise from neurogenic factors (e.g., spinal cord injury, traumatic brain injury), trauma, or surgical procedures [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Our case presents a rare bridged HO formation in the anterior intercostal area, likely stemming from a traumatic incident approximately a decade before the donor's death.\u003c/p\u003e \u003cp\u003eThe histopathological mechanism of non-genetic HO remains debated, with descriptions ranging from endochondral to intramembranous processes or a combination of both [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Our research aligns with previous studies on periarticular non-genetic HO, revealing a progression from fibrous tissue to mature bone through endochondral ossification. This process typically involves six distinct stages: perivascular lymphocytic infiltration, lymphocytic migration into soft tissue, reactive fibroproliferation, neovascularity, cartilage formation, and endochondral bone formation [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In our case, the absence of Ki-67 expression suggests that the HO process was complete, with no ongoing proliferation.\u003c/p\u003e \u003cp\u003eMO, the most common form of HO, is often misapplied to describe HO, even when it lacks specific muscle involvement or inflammation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In our case, we opted for HO due to the absence of muscular inflammation. Distinguishing HO from malignant soft tissue or osteogenic sarcomas is crucial due to their vastly different prognoses and treatments [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This differentiation relies heavily on the characteristic \u0026ldquo;zonation pattern\u0026rdquo; or \u0026ldquo;zone phenomenon\u0026rdquo; observed in HO [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDiagnosis of HO typically relies on a combination of patient history, clinical symptoms, and imaging studies. X-rays serve as the initial imaging modality, while CT scans can detect calcifications at an earlier stage [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. MRI is effective for visualizing soft-tissue masses, and ultrasound offers a low-cost method for early detection [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. X-ray and CT scans were employed in our case, revealing mature bone formation adjacent to the ribs with a central fibrous tissue component. Histological confirmation through biopsy is often necessary, with careful attention paid to the characteristic zonation pattern of HO [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur histological analysis demonstrated a clear progression from fibrous tissue to mature bone, indicative of endochondral ossification. The central zone consisted of fibrous stroma, transitioning to an intermediate zone with hypertrophic cells showing chondrocyte maturation and finally to a peripheral zone of mature bone. This pattern stands in stark contrast to osteosarcoma, where tumor growth is centrifugal, with more mature cells concentrated in the center [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe absence of proliferative activity, as evidenced by negative Ki-67 immunostaining, suggests that the HO, in our case, had reached a stable, non-progressive state. This finding holds important implications for understanding the natural history of HO and potential treatment strategies.\u003c/p\u003e \u003cp\u003eInterestingly, our case of anterior intercostal HO with bridged formation is extremely rare. While HO in the chest has occasionally been reported, it typically forms a mass or occurs in the posterior area [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The bridging formation observed in our case could potentially interfere with respiratory function by limiting chest wall mobility [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], similar to the effects of flail chest [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, the lack of medical treatment sought by the donor suggests that the condition may have been asymptomatic or caused minimal discomfort.\u003c/p\u003e \u003cp\u003eThis study underscores the importance of a comprehensive understanding of HO to avoid unnecessary diagnostics and treatments. It also highlights the value of thorough anatomical, radiological, and histological examinations in accurately identifying and characterizing unusual presentations of HO. Future research could focus on the long-term progression and potential functional impacts of such rare HO formations.\u003c/p\u003e \u003cp\u003eMoreover, this case provides valuable insights for educational purposes in anatomy and pathology. It demonstrates the significance of considering HO in differential diagnoses, especially in cases with atypical presentations or locations. The multidisciplinary approach used in this study\u0026mdash;combining gross anatomical observation, radiological imaging, and histological analysis\u0026mdash;is an excellent model for comprehensively evaluating anatomical anomalies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur case report on anterior intercostal traumatic HO with bridged formation significantly contributes to the literature on HO. It emphasizes the importance of meticulous evaluation and accurate diagnosis of bone-forming lesions, particularly in atypical locations. As our understanding of HO evolves, cases like this provide crucial data points for enhancing diagnostic accuracy and developing targeted treatment strategies.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eCompeting interests\u003c/strong\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding sources\u003c/h2\u003e \u003cp\u003eNot Applicable\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eSB Hur wrote the main manuscript and prepared all figures. YS Cho performed radiological examination. HJ Cho conducted H\u0026amp;E staining. GG Go reviewed the literature. KI Nam was responsible for project development and supervision. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors sincerely thank those who donated their bodies to science so that anatomical research could be performed. The results from such research can potentially increase our collective knowledge and ultimately improve patient care. Therefore, these donors and their families deserve our highest gratitude [6].\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAl Khader A, Habaibeh E, Tawalbeh HY, Mansour BM, Mansour SM, Haj Ahmad AN, Owais TT, Odeh H (2023) Myositis ossificans of the chest wall in an 8-year-old boy: a case report of a diagnostic pitfall. Indian J Thorac Cardiovasc Surg 39(2):186\u0026ndash;189\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Qadi MO (2018) Disorders of the Chest Wall: Clinical Manifestations. 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J Clin Orthop Trauma 17:123\u0026ndash;127\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSavvidou O, Papakonstantinou O, Lakiotaki E, Melissaridou D, Korkolopoulou P, Papagelopoulos PJ (2021) Post-traumatic myositis ossificans: a benign lesion that simulates malignant bone and soft tissue tumours. EFORT Open Rev 6(7):572\u0026ndash;583\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Wijck SFM, Wijffels MME (2023) Surgical strategy for treating multiple symptomatic rib fracture malunions with bridging heterotopic ossifications: A case report. Trauma Case Rep. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi:10.1016/j.tcr.2023.100825\u003c/span\u003e\u003cspan address=\"https://doi:10.1016/j.tcr.2023.100825\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVanden BL, Vanderstraeten G (2005) Heterotopic ossification: a review. J Rehabil Med 37(3):129\u0026ndash;136\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalczak BE, Johnson CN, Howe BM (2015) Myositis Ossificans. J Am Acad Orthop Surg 23(10):612\u0026ndash;622\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"surgical-and-radiologic-anatomy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sara","sideBox":"Learn more about [Surgical and Radiologic Anatomy](http://link.springer.com/journal/276)","snPcode":"276","submissionUrl":"https://submission.nature.com/new-submission/276/3","title":"Surgical and Radiologic Anatomy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Heterotopic ossification, Anterior intercostal, X-ray, CT scan, Cadaver","lastPublishedDoi":"10.21203/rs.3.rs-4798199/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4798199/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHeterotopic ossification (HO) is a pathological condition characterized by ectopic bone formation in soft tissues. This study presents a rare case of anterior intercostal HO discovered in a 62-year-old Korean male cadaver during an educational dissection. The HO structure, which connected multiple ribs, underwent radiological examination (X-ray and CT scans) and histological analysis. Radiographic findings revealed that mature bone had formed adjacent to the ribs, surrounded by fibrous tissue. Histological analysis demonstrated a progression from fibrous tissue to mature bone, indicative of endochondral ossification, with no proliferative activity detected in the Ki-67 immunostaining. This case provides valuable insights into intercostal HO's morphological, radiological, and histological characteristics, providing significant information in anatomy and pathology for educational purposes.\u003c/p\u003e","manuscriptTitle":"Anterior Intercostal Heterotopic Ossification: A Rare Cadaveric Case Study with Multimodal Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-27 11:47:05","doi":"10.21203/rs.3.rs-4798199/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2024-07-26T07:04:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-25T13:39:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"Surgical and Radiologic Anatomy","date":"2024-07-25T01:11:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"surgical-and-radiologic-anatomy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sara","sideBox":"Learn more about [Surgical and Radiologic Anatomy](http://link.springer.com/journal/276)","snPcode":"276","submissionUrl":"https://submission.nature.com/new-submission/276/3","title":"Surgical and Radiologic Anatomy","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8b2a422d-9859-457e-8ebc-a59958d90c69","owner":[],"postedDate":"August 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-08-27T11:47:05+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-27 11:47:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4798199","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4798199","identity":"rs-4798199","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}