Primary Bone Tumors: Patterns and Factors Associated With Malignancy Potential

Primary Bone Tumors: Patterns and Factors Associated With Malignancy Potential | 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 Article Primary Bone Tumors: Patterns and Factors Associated With Malignancy Potential Melaku Teshale Gemechu, Tuji Dinka Bikila, Netsanet Abera Asseffa, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6330513/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Malignant bone tumors, also known as primary bone cancers, arise from the bone itself or the surrounding tissues. Understanding their biological nature and associated factors is crucial for early detection, effective treatment, and improved patient outcomes. To the best of our literature review there is no study which investigated factors associated with malignant biological nature of the bone tumor in southeastern region of Ethiopia. Objective: The study aimed to assess the Patterns and factors associated With Malignancy Potential of Primary Bone Tumors. Methods: A 6-year retrospective institution-based cross-sectional study was conducted to review bone biopsy medical records recorded at the pathology department of Hawassa University Comprehensive Specialized Hospital (HUCSH), using 173 study participants; Logistic regressions were conducted to estimate the adjusted odds ratio (AOR) with 95% CI for the association between the independent variables and the malignant biological nature of the bone tumor. Results: The most common affected age groups were those in the second and third decades of life, accounting for 39.9% and 30.6% of cases, respectively. Age range of 20-49 years (AOR=0.192; 95% CI: 0.047-0.778), male gender (AOR=3.806; 95% CI: 1.490-9.725), duration of clinical presentation 0-6 months (AOR=43.09; 95% CI: 38.72-47.38), and duration of clinical presentation 7-12 months (AOR=36.20; 95% CI: 32.73-41.37) showed significant association with malignant bone tumor. Conclusion: Intermediate and malignant tumors were less common than benign bone cancers. Males were more likely to have malignant tumors, but females were more likely to have benign tumors. The most prevalent malignant tumor was osteosarcoma, which was followed by Ewing sarcoma. Adolescence and adulthood are the age groups most commonly affected by bone cancers. These have a big impact on the economy and are the backbone of society. Malignant bone tumors were associated with with age (20–49 years), male sex, and duration of clinical presentation after 0–6 months, and 6–12 months of symptom onset. Biological sciences/Cancer Health sciences/Diseases Primary Bone Tumors Malignancy Potential Associated factors Introduction Bone pathologies are heterogeneous disease entities that are broadly classified as developmental, metabolic, osteomyelitis, necrosis and fracture, and tumors. Bone tumors can be further sub-classified as primary and secondary bone tumors [1] . Biologically, the WHO classification of soft tissue and bone tumors (5th edition) categorizes primary bone tumors as benign, intermediate, and malignant. Intermediate tumors are either locally aggressive or seldom metastasize. Additionally, primary bone tumors are histopathologically classified based on how closely they resemble normal cells or the kind of intercellular matrix they produce as bone forming, cartilage forming, vascular, and others [2,3] . The incidence rates of specific bone sarcomas are age-related. Osteosarcoma, the most common malignant primary bone tumor, has a bimodal age distribution. The first peak occurs during the second decade of life, which accounts for the vast majority of the cases, and the second peak occurs in people aged > 60 years. Due to this age distribution, bone tumors have disproportionately high mortality among teenagers and young adults despite their low incidence [2,4] . Although the actual prevalence of benign bone tumors is unknown, older radiography studies have suggested that a significant portion of the population may have indolent lesions. When symptomatic, the clinical presentation of primary bone tumors is diverse, with variable clinical signs and symptoms including pain, swelling, pathological fractures, and neurovascular compromise, which are non-specific. Benign bone tumors are usually asymptomatic and are often identified incidentally on radiography. However, they can also present with pain, slow-growing mass, or a pathologic fracture. Malignant bone tumors typically present with rapid or worsening pain and swelling. These tumors also have a wide anatomic distribution. The most commonly affected bones were femur, tibia and humerus in decreasing order [2-4] . Due to the histologic variety, nonspecific clinical presentation, diverse age, and anatomic distribution of bone tumors, a suspected case should be reviewed at multidisciplinary team meetings. Multiple diagnostic work-ups are available for primary bone tumors, including laboratory tests, imaging, and biopsy [2] . The most important role of a pathologist is to differentiate between benign and malignant tumors, as this enormously impacts patient morbidity, mortality, and treatment plans. The five basic parameters in this assessment are the age of the patient, the bone involved, the specific area within the bone, the radiographic appearance, and the microscopic appearance. Primarily, a pathologist should be fully informed about the first four parameters before evaluating the fifth parameter [5] . In Ethiopia, 309 new cases of primary bone and cartilage malignant tumors were reported in men in 2015, with crude and age-standardized incidence rates of 0.6 and 1.0 per 100,000 populations, respectively. Similarly, 485 new cases of bone and cartilage tumors in women were reported, with crude and age-standardized incidence rates of 1.0 and 1.3, respectively [6] . In Ethiopia, there are few studies on the histopathologic patterns and factors associated with the malignant biological nature of bone tumors, and there is no data for the southeast region of the country. Previous studies have relied on the older WHO classification of soft tissue and bone tumors. Additionally, the prevalence of primary bone tumors in Ethiopia was not covered by the GLOBOCAN 2020 report [7] . There is also no well-established cancer registry system in Ethiopia. In the absence of such a system, studies like record analyses provide valuable information for understanding the changing trends and patterns of bone tumors. This study is the first study conducted in the southeastern region of Ethiopia using the most recent WHO classification of soft tissue and bone tumors and provides insights into the patterns of primary bone tumors and factors associated with the malignant biological nature of different histologic types. Methods Study area, design, and period A 6-year retrospective institution-based cross-sectional study was conducted to review bone biopsy medical records recorded at the pathology department of Hawassa University Comprehensive Specialized Hospital (HUCSH), Hawassa, Ethiopia, from September 2017 to August 2023. Source population There were a total of 315 bone biopsy specimen reports registered in the pathology department from September 2017 to August 2023. Sample size and Sampling technique /Sampling procedures The minimum sample size (n) was calculated from the source population (N) assuming that the study was presented with a 95% level of confidence ( =1.96), 5 % precision ( = 0.05), and a 50% population proportion, using the following formula to get the minimum sample size: = 384 Final sample size (n f) was determined using the correction formula: n f =n/[1+n/N]=384/(1+384/315) = 173. One-hundred seventy three bone biopsy specimen reports that did not meet the exclusion criteria were selected by convenience sampling method. The exclusion criteria were; reports with incomplete data on two or more variables, reports with inconclusive or descriptive diagnosis, Hematolymphoid tumors (as the diagnostic modality for these tumors was mainly bone marrow aspiration), and reports of incisional biopsy with subsequent excisional biopsy (to avoid duplication of cases). Data collection procedures The hard copies of all biopsy results with histopathologic diagnosis of primary bone tumors were retrieved using biopsy code numbers, and data was collected by trained data collectors. From the histopathologic reports, the study variables including the patient’s region, age, sex, and clinical presentation, location of the tumor, tumor grade, and histologic type were extracted by the principal investigator using a structured data collection checklist. Data analysis procedures The data was checked for completeness, cleaned, and coded, and analyzed using Statistical Package of Social Sciences (SPSS) version 20. A descriptive analysis was done for the frequency and distribution of the disease. Logistic regressions were conducted to estimate the adjusted odds ratio (AOR) with 95% CI for the association between the independent variables and the malignant biological nature of the bone tumor. Ethical consideration Before data collection, ethical clearance and approval was obtained from the Institutional Review Board (IRB) of HUCSH, with a reference number of IRB/043/16. Consent waiver was granted from the IRB to access only secondary data and there were no human participants. Moreover, the study adhered to the principles of the Helsinki Declaration. Data were de-identified both before and after analysis, ensuring full confidentiality. Operational definitions Primary bone tumor: biopsy-proven primary non-hematolymphoid bone tumor and excludes metastatic and tumors of odontogenic origin like ameloblastoma. [8] Clinical presentation: subjective complaint of a patient, which can include one or more symptoms such as swelling, pain, or fracture. [8] Tumor-like lesions- bone lesions with undefined neoplastic behavior currently classified based on histologic features in categories like osteoclastic giant cell-rich tumors and other mesenchymal tumors. [9] Results General and socio-demographic characteristics Cases in this study were comprised of 96 (55.5%) males and 77 (44.5%) females, with a male-to-female ratio of 1.25:1. The age at presentation ranged from 1 to 65 years, with the mean age of presentation being 23.2 years. 89 cases (51.4%) were benign tumors, 17 (9.8%) were intermediate tumors, and 67 (38.7%) were malignant. Conventional osteosarcoma was the commonest histologic diagnosis, accounting for 23.1% of all the cases, next is osteochondroma (15.6%) (Table 1). Distribution of primary bone tumors by age and gender The most common affected age groups were those in the second and third decades of life, accounting for 39.9% and 30.6% of cases, respectively. Benign tumors were more commonly seen in females (55.1%), with a female-to-male ratio of 1.2:1. In contrast, malignant tumors were more common in males (70.1%), with a male-to-female ratio of 2.35. Intermediate tumors were found to have comparable distributions in females and males, with 8 cases (47.0%) and 9 cases (52.9%), respectively. Table 1 and Table 2 show the distribution of cases by age range and gender (Table 2). Clinical presentation The most common clinical presentation was swelling (76.3%), followed by swelling and pain (11%). Other less common clinical presentations include; swelling and fracture in 12 (6.9%) cases, and swelling and systemic symptoms (weight loss, fever, loss of appetite, and easy fatigability) in 3 (1.7%) cases. The remainder of the patients presented with fracture, swelling and discharge. The duration of clinical presentation in months ranged from 1 to 288. The longest durations of clinical presentation were seen in cases of distal femur osteochondroma. Regarding the biological nature of the tumors, duration was variable; benign tumors presented with a mean duration of 32.22 months, with a range of 1 to 288 months, while the mean duration of the malignant tumors was 8.97 months. Intermediate tumors presented with a mean duration of 17.06 months, and a range of 2 to 96 months. Distribution by histologic differentiation Bone-forming tumors accounted for 28.9% of the cases, followed by cartilage-forming tumors (27.2%). Tumors in other mesenchymal tumor categories accounted for 31.8% of the cases. Seventeen (9.8%) of the cases were osteoclastic giant cell rich (OGCR) tumors, and 4 cases (2.3%) of vascular tumors were seen. Conventional osteosarcoma (CO) represented for 80% of the bone-forming tumors. The Mean age of presentation of CO was 20.0 years (age ranges of 6-52 years). This tumor presented with swelling in 70% (mean duration of presentation was 9.33 months, and duration of the symptom ranged 2-72 months). Osteochondroma accounted for 57.4% of the 47 cartilage forming tumors, with mean age of presentation of 21.81 years (age range was 8 to 40 years). Seventeen (63.0%) of these cases presented with swelling (mean duration symptoms was 41 months). Conventional chondrosarcoma (CS) and enchondroma each accounted for 8.5% of the cases. The mean age of presentation for CS was 40.75 years (age ranges 25-51 years), and all the cases were WHO grade 2. Ossifying fibroma constituted 18 cases (32.7%) of the other mesenchymal tumors types, with mean age of presentation of 23.11 years (age range of 9 to 50 years). Ewing sarcoma accounted for 17 cases (30.95%). Ewing sarcoma was also the second most frequent malignant tumor (25.4%). Distribution by histologic differentiation is displayed in table 3 . Histologic features in relation to skeletal distribution The overall skeletal distribution of the tumors was predominantly seen in bones around the knee joint (distal femur and proximal tibia) (31.2%), and jaw bones (21.4%). Benign tumors were frequently seen in the jaw bones (32.6%), followed by the craniofacial bones (19.1%), and the distal femur and proximal tibia (15.4%). Of the 17 intermediate tumors, 41.2% were seen in the distal femur and proximal tibia, followed by the upper extremity (29.4%). Among the 67 cases of malignant tumors, 49.3% were seen in the distal femur and proximal tibia. The distribution of histologic diagnosis based on site is displayed in tables 4 and 5. Factor associated with malignant primary bone tumors Bivariate analysis was done to identify factors associated with non-malignant and malignant primary bone tumors. Age, sex, duration of clinical symptoms, and site of the tumor were significantly associated with a malignant biological nature. For factors that showed significant association in bivariate analysis, multivariate logistic regression analysis was done. In multivariate logistic regression, age range of 20-49 years (AOR=0.192; 95% CI: 0.047-0.778), male gender (AOR=3.806; 95% CI: 1.490-9.725), duration of clinical presentation 0-6 months (AOR=43.09; 95% CI: 38.72-47.38), and duration of clinical presentation 7-12 months (AOR=36.20; 95% CI: 32.73-41.37) showed significant association with malignant bone tumor. In the multivariate logistic regression, the site of the tumor was not associated with the malignant biological nature of primary bone tumors (p > 0.05), (table 6). Discussion In this study, we reviewed 173 cases of primary bone tumors. These tumors are comprised of 51.4% benign, 9.8% intermediate, and 38.7% malignant tumors, with the second and third decades of life being the most commonly affected age groups. Conventional osteosarcoma emerged as the most common histologic diagnosis. The bone tumors predominantly affected the bones around the knee joint (distal femur and proximal tibia) (31.2%), and jaw bones (21.4%). Benign tumors more frequently affected the jaw bones, while nearly half of the malignant tumors cases were located in the distal femur and proximal tibia. The age range of 20-49 years, male sex, and the duration of clinical symptoms, specifically, durations of 0-6 months and 7-12 months were significantly associated with malignant bone tumors. In agreement with other similar studies, primary bone tumors affected the second and third decades of life [1,4,5,8,9] . Although the mean age of presentation is lower than a study wherein 18% cases were plasma cell myeloma (94.44% of these were above the age of 30), plasma cell myelomas were excluded in our study; hence the discrepancy [10] . Another study with different result also included metastasis and Synovial sarcoma (24%, each), which were excluded in the present study [11] . Additionally, the age range of 20-49 years has lower odds of malignant biological nature, with an odds ratio of 0.192 compared to those older than 50 years. This is in agreement with the WHO report [2] . Regarding gender distribution, results from other studies are in agreement with our present study [5,10] . After multivariate logistic regression, this study found that male gender was associated with higher odds of developing malignant bone tumors, with males being 3.806 times more likely to develop malignant bone tumor compared to female patients. This finding aligns with the report in India, where malignant tumors were more commonly seen in male patients [12] . Swelling was the most frequent symptom of clinical presentation in our study, observed in 76.3% of cases, followed by swelling and pain. This finding is consistent with a study at BLSH, Ethiopia [6] . But this figure contrasts with reports from United Kingdom and Zambia, wherein pain and both swelling and pain were the most common clinical symptoms [3,13] . This discrepancy signifies the delay in referral system in Ethiopia, as swelling is typically a late presentation of bone tumors. Patients with duration of clinical presentation of 0-6 months were 43.09 times more likely to have malignant biological nature compared to those who present after 13 months. Similarly, those with duration of symptoms of 7-12 months were 36.206 times more likely to have malignant biological nature compared to patients who presented later than 13 months. This association between a short duration of clinical presentation and bone sarcoma is also supported by a study conducted in Birmingham [14] . The durations of clinical presentation varied depending on the biological nature of the tumor. The median duration of symptoms for malignant bone tumors was 7 months. This differs from the Birmingham study, where the median duration of symptoms reported was 4 months [14] . This discrepancy may be partly explained by disparities in the availability of healthcare facilities and health-seeking behaviors among the source populations. The overall skeletal distribution was predominantly seen in the distal femur &proximal tibia. In agreement with previous studies, these sites were also the common sites for malignant subtypes of bone tumors [5,15] . Benign tumors were frequently seen in the jaw bones (32.6%), followed by the craniofacial bones 17 (19.1%), and the distal femur & proximal tibia 14(15.4%).This was in contrary to a study done in Ethiopia, wherein reported sites of benign tumors were the distal femur and proximal tibia (37%), the short tubular bones of the hands and feet (20%) and a craniofacial bone (14%) [6] . This discrepancy is likely due to the high percentage ossifying fibroma (20.2% vs 6%) and fibrous dysplasia (18.0% vs 12%) in our study; these tumors have higher predilection for jaw and craniofacial bones. The distribution of histologic differentiation in the present study was bone forming (28.9%) and cartilage-forming tumors (27.2%). This was comparable with a previous study[1]. In line with previous studies, osteochondroma was the most common benign tumor. Moreover, osteosarcoma was also the most prevalent histologic type among the malignant tumors [8,16-18] . Limitations of the study This study is not without limitations. Firstly, we used a non-randomized convenience sampling method, which limits the generalizability of the results to the target population. Second, the cross-sectional design cannot infer causality. Thirdly, the majority of submitted specimens for malignant tumors were incisional biopsies, and pathologic staging was not reported. Lastly, in almost all cases, diagnoses were based on morphology, and in some cases, immunohistochemistry (IHC) was strongly recommended to establish the diagnosis. Conclusion In this study, benign bone tumors were more frequently observed than intermediate and malignant tumors. Malignant tumors were common in males, while benign tumors were more common in females. Osteosarcoma was the most common malignant tumor, followed by Ewing sarcoma. Bone tumors primarily affect the adolescent and adult age group. These are the working forces of society and have significant economic implications. Age 20-49 years, male gender, duration of clinical presentation after 0-6 months and 6-12 months of symptom onset were significantly associated with malignant bone tumors. These results also serve as a reference for future scientific research and studies to determine the associated factors and their impacts on clinical outcomes. Declarations Data availability The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Acknowledgments The authors express their special thanks to all the study participants, data collectors, Hawassa University and study hospitals. Authors’ contributions MTG, TDB and NAA were involved in the study design, article selection, analysis and manuscript writing. All the authors were involved in the analysis and manuscript preparation and editing. All the authors read and approved the final draft of the manuscript. All the authors gave their final approval for the version that would be published, agreed on the journal to which the article would be submitted, and agreed to be responsible for all aspects of the work. Funding There was no funding from institutions for this study Disclosure The author reports no conflicts of interest related to this work References Biruk Lambisso NB. Pattern of bone tumours seen at Addis Ababa University, Ethiopia. East Cent Afr J Surg Online. Volume 14 Number 2:25–32. World Health Organization, International Agency for research on cancer, eds. Soft tissue and bone tumours. 5th ed. WHO: 2020 Vol. 3. 2019. . Green NM, Abas S, Sajid S, Cribb GL. Presentation of bone tumours: clinical findings and initial management of patients. Orthop Trauma. 2021 Jun;35(3):108–114. . Wani L, Ashai FB, Banday BM, Ashraf A, Mushtaq S, Itoo MohdS, et al. Primary bone tumours in Kashmir valley a retrospective histopathological study. Int J Basic Appl Sci. 2014 Dec 22;4(1):51. Weyessa TG, Kindie EA, Yefter ET. Histopathological pattern of primary bone tumours at the Black Lion Specialized Hospital, Addis Ababa, Ethiopia: a retrospective cross-sectional, 2015-2019. Pan Afr Med J. 2022;41. Memirie ST, Habtemariam MK, Asefa M, Deressa BT, Abayneh G, Tsegaye B, et al. Estimates of Cancer Incidence in Ethiopia in 2015 Using Population-Based Registry Data. J Glob Oncol. 2018 Dec;(4):1–11. doi: 10.1200/JGO.17.00175. Global Cancer Observatory: Cancer Today: Ethiopia. International Agency for Research on Cancer: WHO: 2022:2. Shah KA, Naqvi QH, Shah SA, Soomro ZI, Akhund MA, Abbasi AN. Evaluation of neoplastic bone lesions: A morphological study at a tertiary care centre. Prof Med J. 2019 Nov 10;26(11):1983–1988. doi: 10.29309/TPMJ/2019.26.11.3751. Omer SM, Salim, Hanan Abdo, Jezan, Hussun Saeed. Morphological Pattern of Bone Lesions: Study of 204 Cases. International Journal of science and Healthcare Research. 2019;4(1):326–31. Aina OJ, Adelusola KA, Orimolade AE, Akinmade A. Histopathological pattern of primary bone tumours and tumour-like lesions in Ile-Ife, Nigeria. Pan Afr Med J. 2018; 29. doi: 10.11604/pamj.2018.29.193.13111. Gururajaprasad C, Damodaran A. M. Histopathological study of tumours of bones and joints. Indian J Pathol Oncol. 2019 Mar 28;6(1):16–24. doi: 10.18231/2394-6792.2019.0003. Gayathri. Spectrum of tumour and tumour-like lesions of bone in a Tertiary Care Hospital in North Karnataka, India. Indian J Pathol Oncol. 2020 Dec 28;5(1):75–80. doi: 10.18231/2394-6792.2018.0014. Sakala D, Munthali J, Mulla Y. Primary Malignant Bone Tumours at the University Teaching Hospital in Lusaka Zambia. Med J Zambia. 2016 Mar 30;43(1):24–30. doi: 10.55320/mjz.43.1.309. Smith G, Johnson G, Grimer R, Wilson S. Trends in presentation of bone and soft tissue sarcomas over 25 years: little evidence of earlier diagnosis. Ann R Coll Surg Engl. 2011 Oct;93(7):542–547. doi: 10.1308/147870811X13137608455055. Paul EJ, Zacharie S, Adrian H, André M, Bruno DD, Roger AG. Primary Malignant Bone Tumors in Cameroon: Epidemiological and Histopathological Data. 2020;2(7). doi: 10.4314/eaoj.v18i1.6. Ghert M, Mwita W, Mandari FN. Primary Bone Tumors in Children and Adolescents Treated at a Referral Center in Northern Tanzania. JAAOS Glob Res Rev. 2019 Mar;3(3):e045. doi: 10.5435/JAAOSGlobal-D-17-00045. Gemechu T. Bone and articular cartilage tumours as seen in the Dept. of Pathology, Faculty of Medicine, Addis Ababa University. 2021;12(2) Ahmad M, Ghani A, Mansoor A, Khan AH. Pattern of malignant bone tumour in northern areas of Pakistan. JPMA J Pak Med Assoc. 1994 Sep;44(9):203–205. Tables Table 1 to 6 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files tablesLatest.docx Cite Share Download PDF Status: Posted Version 1 posted 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-6330513","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":447271617,"identity":"d666f642-a705-4990-a616-37e3c2386728","order_by":0,"name":"Melaku Teshale Gemechu","email":"data:image/png;base64,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","orcid":"","institution":"Wondo Genet Primary Hospital","correspondingAuthor":true,"prefix":"","firstName":"Melaku","middleName":"Teshale","lastName":"Gemechu","suffix":""},{"id":447271618,"identity":"96a74052-ee3e-4852-b768-ae3aa9991d28","order_by":1,"name":"Tuji Dinka Bikila","email":"","orcid":"","institution":"Hawassa University","correspondingAuthor":false,"prefix":"","firstName":"Tuji","middleName":"Dinka","lastName":"Bikila","suffix":""},{"id":447271619,"identity":"fedf529a-a7a6-4f3b-9289-9e191417825c","order_by":2,"name":"Netsanet Abera Asseffa","email":"","orcid":"","institution":"Hawassa University","correspondingAuthor":false,"prefix":"","firstName":"Netsanet","middleName":"Abera","lastName":"Asseffa","suffix":""},{"id":447271620,"identity":"de7cd84a-d9e5-40de-91a4-3d4b30a925ec","order_by":3,"name":"Abraham Kassahun Tadele","email":"","orcid":"","institution":"Hawassa University","correspondingAuthor":false,"prefix":"","firstName":"Abraham","middleName":"Kassahun","lastName":"Tadele","suffix":""},{"id":447271621,"identity":"c60990ad-db52-4d45-ac78-62f14b2585df","order_by":4,"name":"Kalkidan Molla Tegegne","email":"","orcid":"","institution":"Hawassa University","correspondingAuthor":false,"prefix":"","firstName":"Kalkidan","middleName":"Molla","lastName":"Tegegne","suffix":""},{"id":447271622,"identity":"382f714d-ed1a-41c2-a64e-1897d88e74f3","order_by":5,"name":"Abebaw Amare Wodajo","email":"","orcid":"","institution":"Hawassa University","correspondingAuthor":false,"prefix":"","firstName":"Abebaw","middleName":"Amare","lastName":"Wodajo","suffix":""},{"id":447271623,"identity":"2ee3a30f-eb55-49d2-bcd2-0f739896c20d","order_by":6,"name":"Ghion Getnet Engida","email":"","orcid":"","institution":"Hawassa University","correspondingAuthor":false,"prefix":"","firstName":"Ghion","middleName":"Getnet","lastName":"Engida","suffix":""},{"id":447271624,"identity":"5cca9c9e-36cb-4678-8b84-8adcaf4ab0da","order_by":7,"name":"Zenebe Daniel Getachew","email":"","orcid":"","institution":"Woldia University","correspondingAuthor":false,"prefix":"","firstName":"Zenebe","middleName":"Daniel","lastName":"Getachew","suffix":""},{"id":447271625,"identity":"d1f85190-1d61-41f8-8bba-3efa506c9a56","order_by":8,"name":"Adane Tesfaye Anbese","email":"","orcid":"","institution":"Dilla University","correspondingAuthor":false,"prefix":"","firstName":"Adane","middleName":"Tesfaye","lastName":"Anbese","suffix":""}],"badges":[],"createdAt":"2025-03-28 19:38:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6330513/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6330513/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82573313,"identity":"6ae5dbd0-ba30-4cb6-ae0d-b8a9bd7b2f10","added_by":"auto","created_at":"2025-05-13 04:53:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":684467,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6330513/v1/dcfac643-585c-4703-879b-317ca7726c46.pdf"},{"id":82572847,"identity":"8d44053f-12ba-4a1d-b048-8e8d3008eb79","added_by":"auto","created_at":"2025-05-13 04:45:33","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":45942,"visible":true,"origin":"","legend":"","description":"","filename":"tablesLatest.docx","url":"https://assets-eu.researchsquare.com/files/rs-6330513/v1/3b8588352d75a2aaeed5ef7d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Primary Bone Tumors: Patterns and Factors Associated With Malignancy Potential","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBone pathologies are heterogeneous disease entities that are broadly classified as developmental, metabolic, osteomyelitis, necrosis and fracture, and tumors. Bone tumors can be further sub-classified as primary and secondary bone tumors\u0026nbsp;\u003csup\u003e[1]\u003c/sup\u003e. Biologically, the WHO classification of soft tissue and bone tumors (5th edition) categorizes primary bone tumors as benign, intermediate, and malignant. Intermediate tumors are either locally aggressive or seldom metastasize. Additionally, primary bone tumors are histopathologically classified based on how closely they resemble normal cells or the kind of intercellular matrix they produce as bone forming, cartilage forming, vascular, and others\u003csup\u003e[2,3]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe incidence rates of specific bone sarcomas are age-related. Osteosarcoma, the most common malignant primary bone tumor, has a bimodal age distribution. \u0026nbsp;The first peak occurs during the second decade of life, which accounts for the vast majority of the cases, and the second peak occurs in people aged \u0026gt; 60 years. Due to this age distribution, bone tumors have disproportionately high mortality among teenagers and young adults despite their low incidence\u003csup\u003e[2,4]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAlthough the actual prevalence of benign bone tumors is unknown, older radiography studies have suggested that a significant portion of the population may have indolent lesions. When symptomatic, the clinical presentation of primary bone tumors is diverse, with variable clinical signs and symptoms including pain, swelling, pathological fractures, and neurovascular compromise, which are non-specific. Benign bone tumors are usually asymptomatic and are often identified incidentally on radiography. However, they can also present with pain, slow-growing mass, or a pathologic fracture. Malignant bone tumors typically present with rapid or worsening pain and swelling. These tumors also have a wide anatomic distribution.\u0026nbsp;The most commonly affected bones were femur, tibia and humerus in decreasing order\u003csup\u003e[2-4]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eDue to the histologic variety, nonspecific clinical presentation, diverse age, and anatomic distribution of bone tumors, a suspected case should be reviewed at multidisciplinary team meetings. Multiple diagnostic work-ups are available for primary bone tumors, including laboratory tests, imaging, and biopsy\u003csup\u003e[2]\u003c/sup\u003e. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe most important role of a pathologist is to differentiate between benign and malignant tumors, as this enormously impacts patient morbidity, mortality, and treatment plans. The five basic parameters in this assessment are the age of the patient, the bone involved, the specific area within the bone, the radiographic appearance, and the microscopic appearance. Primarily, a pathologist should be fully informed about the first four parameters before evaluating the fifth parameter\u003csup\u003e[5]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn Ethiopia, 309 new cases of primary bone and cartilage malignant tumors were reported in men in 2015, with crude and age-standardized incidence rates of 0.6 and 1.0 per 100,000 populations, respectively. Similarly, 485 new cases of bone and cartilage tumors in women were reported, with crude and age-standardized incidence rates of 1.0 and 1.3, respectively\u003csup\u003e[6]\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn Ethiopia, there are few studies on the histopathologic patterns and factors associated with the malignant biological nature of bone tumors, and there is no data for the southeast region of the country. Previous studies have relied on the older WHO classification of soft tissue and bone tumors. Additionally, the prevalence of primary bone tumors in Ethiopia was not covered by the GLOBOCAN 2020 report \u003csup\u003e[7]\u003c/sup\u003e. There is also no well-established cancer registry system in Ethiopia. In the absence of such a system, studies like record analyses provide valuable information for understanding the changing trends and patterns of bone tumors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study is the first study conducted in the southeastern region of Ethiopia using the most recent WHO classification of soft tissue and bone tumors and provides insights into the patterns of primary bone tumors and factors associated with the malignant biological nature of different histologic types.\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003eStudy area, design, and period\u003c/h2\u003e\n\u003cp\u003eA 6-year retrospective institution-based cross-sectional study was conducted to review bone biopsy medical records recorded at the pathology department of Hawassa University Comprehensive Specialized Hospital (HUCSH), Hawassa, Ethiopia, from September 2017 to August 2023.\u003c/p\u003e\n\u003ch3 id=\"_Toc160891643\"\u003eSource population\u003c/h3\u003e\n\u003cp\u003eThere were a total of 315 bone biopsy specimen reports registered in the pathology department from September 2017 to August 2023.\u003c/p\u003e\n\u003ch2 id=\"_Toc11436732\"\u003eSample size and Sampling technique /Sampling procedures\u003c/h2\u003e\n\u003cp\u003eThe minimum sample size (n) was calculated from the source population (N) assuming that the study was presented with a 95% level of confidence (\u003cimg width=\"8\" height=\"22\" src=\"data:image/png;base64,R0lGODlhCAAWAHcAMSH+GlNvZnR3YXJlOiBNaWNyb3NvZnQgT2ZmaWNlACH5BAEAAAAALAAACAAIAAcAgwAAAAAAAAAAOjqQ22a222a2/5Db/7ZmALZmOtuQOv+2Zv//2wECAwECAwECAwECAwQYEKhAaQFpAIDI/t23hSIJestxIVUgGEAEADs=\" alt=\"image\"\u003e\u0026nbsp;=1.96), 5 % precision (\u003cimg width=\"10\" height=\"22\" src=\"data:image/png;base64,R0lGODlhCgAWAHcAMSH+GlNvZnR3YXJlOiBNaWNyb3NvZnQgT2ZmaWNlACH5BAEAAAAALAAABAAJAAsAhAAAAAAAAAAAOgA6ZgA6kABmtjoAADoAOjoAZjo6kDpmtjqQ22YAAGYAOmY6AGZmAGaQ22a2/5A6AJCQZpDb/7ZmALaQOraQkLbb/7b//9u2Ztv////bkP/btv//tv//2wU7ICCOVVCM4ydFqOg1VAtwySZ2TiBM52woGw9jIaoQbK+YkDVDZGaHGKDS4xgin8ujwIEALIEBRhMAhgAAOw==\" alt=\"image\"\u003e\u0026nbsp;= 0.05), and a 50% population proportion, using the following formula to get the minimum sample size:\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"80\" height=\"32\" src=\"data:image/png;base64,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\" alt=\"image\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u003cimg width=\"87\" height=\"32\" src=\"data:image/png;base64,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\" alt=\"image\"\u003e\u0026nbsp; \u0026nbsp;= 384\u003c/p\u003e\n\u003cp\u003eFinal sample size (n\u003cem\u003ef)\u003c/em\u003e was determined using the correction formula: n\u003cem\u003ef\u003c/em\u003e=n/[1+n/N]=384/(1+384/315) = 173. One-hundred seventy three bone biopsy specimen reports that did not meet the exclusion criteria were selected by convenience sampling method. The exclusion criteria were; reports with incomplete data on two or more variables, reports with inconclusive or descriptive diagnosis, Hematolymphoid tumors (as the diagnostic modality for these tumors was mainly bone marrow aspiration), and reports of incisional biopsy with subsequent excisional biopsy (to avoid duplication of cases).\u003c/p\u003e\n\u003ch2\u003eData collection procedures\u003c/h2\u003e\n\u003cp\u003eThe hard copies of all biopsy results with histopathologic diagnosis of primary bone tumors were retrieved using biopsy code numbers, and data was collected by trained data collectors. From the histopathologic reports, the study variables including the patient\u0026rsquo;s region, age, sex, and clinical presentation, location of the tumor, tumor grade, and histologic type were extracted by the principal investigator using a structured data collection checklist.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e\u003cspan id=\"_Toc160891662\"\u003eData analysis procedures\u0026nbsp;\u003c/span\u003e\u003c/h2\u003e\n\u003cp\u003eThe data was checked for completeness, cleaned, and coded, and analyzed using Statistical Package of Social Sciences (SPSS) version 20. A descriptive analysis was done for the frequency and distribution of the disease. Logistic regressions were conducted to estimate the adjusted odds ratio (AOR) with 95% CI for the association between the independent variables and the malignant biological nature of the bone tumor.\u003c/p\u003e\n\u003ch2\u003eEthical consideration\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eBefore data collection, ethical clearance and approval was obtained from the Institutional Review Board (IRB) of HUCSH, with a reference number of IRB/043/16. Consent waiver was granted from the IRB to access only secondary data and there were no human participants. Moreover, the study adhered to the principles of the Helsinki Declaration. Data were de-identified both before and after analysis, ensuring full confidentiality.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ch2\u003e\u003cspan id=\"_Toc160891661\"\u003eOperational definitions\u0026nbsp;\u003c/span\u003e\u003c/h2\u003e\n\u003cp\u003ePrimary bone tumor: biopsy-proven primary non-hematolymphoid bone tumor and excludes metastatic and tumors of odontogenic origin like ameloblastoma.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[8]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eClinical presentation: subjective complaint of a patient, which can include one or more symptoms such as swelling, pain, or fracture.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[8]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eTumor-like lesions- bone lesions with undefined neoplastic behavior currently classified based on histologic features in categories like osteoclastic giant cell-rich tumors and other mesenchymal tumors.\u0026nbsp;\u003csup\u003e[9]\u003c/sup\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003eGeneral and socio-demographic characteristics\u003c/h2\u003e\n\u003cp\u003eCases in this study were comprised of 96 (55.5%) males and 77 (44.5%) females, with a male-to-female ratio of 1.25:1. The age at presentation ranged from 1 to 65 years, with the mean age of presentation being 23.2 years. 89 cases (51.4%)\u0026nbsp;were benign tumors, 17 (9.8%) were intermediate tumors, and 67 (38.7%)\u0026nbsp;were malignant. Conventional osteosarcoma was the commonest histologic diagnosis, accounting for 23.1% of all the cases, next is osteochondroma (15.6%) (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003ch2 id=\"_Toc160891676\"\u003eDistribution of primary bone tumors by age and gender\u003c/h2\u003e\n\u003cp\u003eThe most common affected age groups were those in the second and third decades of life, accounting for 39.9% and 30.6% of cases, respectively. Benign tumors were more commonly seen in females (55.1%), with a female-to-male ratio of 1.2:1. In contrast, malignant tumors were more common in males (70.1%), with a male-to-female ratio of 2.35. Intermediate tumors were found to have comparable distributions in females and males, with 8 cases (47.0%) and 9 cases (52.9%), respectively. Table 1 and Table 2 show the distribution of cases by age range and gender (Table 2).\u003c/p\u003e\n\u003ch2 id=\"_Toc160891677\"\u003eClinical presentation\u003c/h2\u003e\n\u003cp\u003eThe most common clinical presentation was swelling (76.3%), followed by swelling and pain (11%). Other less common clinical presentations include; swelling and fracture in 12 (6.9%) cases, and swelling and systemic symptoms (weight loss, fever, loss of appetite, and easy fatigability) in 3 (1.7%) cases. The remainder of the patients presented with fracture, swelling and discharge. The duration of clinical presentation in months ranged from 1 to 288. The longest durations of clinical presentation were seen in cases of distal femur osteochondroma. Regarding the biological nature of the tumors, duration was variable; benign tumors presented with a mean duration of 32.22 months, with a range of 1 to 288 months, while the mean duration of the malignant tumors was 8.97 months. Intermediate tumors presented with a mean duration of 17.06 months, and a range of 2 to 96 months.\u0026nbsp;\u003c/p\u003e\n\u003ch2 id=\"_Toc160891678\"\u003eDistribution by histologic differentiation\u003c/h2\u003e\n\u003cp\u003eBone-forming tumors accounted for 28.9% of the cases, followed by cartilage-forming tumors (27.2%). Tumors in other mesenchymal tumor categories accounted for 31.8% of the cases. Seventeen (9.8%) of the cases were osteoclastic giant cell rich (OGCR) tumors, and 4 cases (2.3%) of vascular tumors were seen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConventional osteosarcoma (CO) represented for 80% of the bone-forming tumors. The Mean age of presentation of CO was 20.0 years (age ranges of 6-52 years). This tumor presented with swelling in 70% (mean duration of presentation was 9.33 months, and duration of the symptom ranged 2-72 months). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOsteochondroma accounted for 57.4% of the 47 cartilage forming tumors, with mean age of presentation of 21.81 years (age range was 8 to 40 years). Seventeen (63.0%) of these cases presented with swelling (mean duration symptoms was 41 months). Conventional chondrosarcoma (CS) and enchondroma each accounted for 8.5% of the cases. The mean age of presentation for CS was 40.75 years (age ranges 25-51 years), and all the cases were WHO grade 2.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOssifying fibroma constituted 18 cases (32.7%) of the other mesenchymal tumors types, with mean age of presentation of 23.11 years (age range of 9 to 50 years). Ewing sarcoma accounted for 17 cases (30.95%). Ewing sarcoma was also the second most frequent malignant tumor (25.4%). Distribution by histologic differentiation is displayed in \u003cstrong\u003etable 3\u003c/strong\u003e.\u003c/p\u003e\n\u003ch2 id=\"_Toc160891679\"\u003eHistologic features in relation to skeletal distribution\u003c/h2\u003e\n\u003cp\u003eThe overall skeletal distribution of the tumors was predominantly seen in bones around the knee joint (distal femur and proximal tibia) (31.2%), and jaw bones (21.4%). Benign tumors were frequently seen in the jaw bones (32.6%), followed by the craniofacial bones (19.1%), and the distal femur and proximal tibia (15.4%). Of the 17 intermediate tumors, 41.2% were seen in the distal femur and proximal tibia, followed by the upper extremity (29.4%). Among the 67 cases of malignant tumors, 49.3% were seen in the distal femur and proximal tibia. The distribution of histologic diagnosis based on site is displayed in tables 4 and 5.\u003c/p\u003e\n\u003ch2\u003eFactor associated with malignant primary bone tumors\u003c/h2\u003e\n\u003cp\u003eBivariate analysis was done to identify factors associated with non-malignant and malignant primary bone tumors. Age, sex, duration of clinical symptoms, and site of the tumor were significantly associated with a malignant biological nature.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor factors that showed significant association in bivariate analysis, multivariate logistic regression analysis was done. In multivariate logistic regression, age range of 20-49 years (AOR=0.192; 95% CI: 0.047-0.778), male gender (AOR=3.806; 95% CI: 1.490-9.725), duration of clinical presentation 0-6 months (AOR=43.09; 95% CI: 38.72-47.38), and duration of clinical presentation 7-12 months (AOR=36.20; 95% CI: 32.73-41.37) showed significant association with malignant bone tumor. In the multivariate logistic regression, the site of the tumor was not associated with the malignant biological nature of primary bone tumors (p \u0026gt; 0.05), (table 6).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we reviewed 173 cases of primary bone tumors. These tumors are comprised of 51.4% benign, 9.8% intermediate, and 38.7% malignant tumors, with the second and third decades of life being the most commonly affected age groups. Conventional osteosarcoma emerged as the most common histologic diagnosis. The bone tumors predominantly affected the bones around the knee joint (distal femur and proximal tibia) (31.2%), and jaw bones (21.4%). Benign tumors more frequently affected the jaw bones, while nearly half of the malignant tumors cases were located in the distal femur and proximal tibia. The age range of 20-49 years, male sex, and the duration of clinical symptoms, specifically, durations of 0-6 months and 7-12 months were significantly associated with malignant bone tumors.\u003c/p\u003e\n\u003cp\u003eIn agreement with other similar studies, primary bone tumors affected the second and third decades of life\u003csup\u003e[1,4,5,8,9]\u003c/sup\u003e. Although the mean age of presentation is lower than a study wherein 18% cases were plasma cell myeloma (94.44% of these were above the age of 30), plasma cell myelomas were excluded in our study; hence the discrepancy\u003csup\u003e[10]\u003c/sup\u003e. Another study with different result also included metastasis and Synovial sarcoma (24%, each), which were excluded in the present study\u003csup\u003e[11]\u003c/sup\u003e. Additionally, the age range of 20-49 years has lower odds of malignant biological nature, with an odds ratio of 0.192 compared to those older than 50 years. This is in agreement with the WHO report\u003csup\u003e[2]\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding gender distribution, results from other studies are in agreement with our present study\u003csup\u003e[5,10]\u003c/sup\u003e. After multivariate logistic regression, this study found that male gender was associated with higher odds of developing malignant bone tumors, with males being 3.806 times more likely to develop malignant bone tumor compared to female patients. This finding aligns with the report\u003cem\u003e\u0026nbsp;\u003c/em\u003ein India, where malignant tumors were more commonly seen in male patients\u003csup\u003e[12]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eSwelling was the most frequent symptom of clinical presentation in our study, observed in 76.3% of cases, followed by swelling and pain. This finding is consistent with a study at BLSH, Ethiopia\u003csup\u003e[6]\u003c/sup\u003e. But this figure contrasts with reports from United Kingdom and Zambia, wherein pain and both swelling and pain were the most common clinical symptoms\u003csup\u003e[3,13]\u003c/sup\u003e.\u0026nbsp;This discrepancy signifies the delay in referral system in Ethiopia, as swelling is typically a late presentation of bone tumors.\u003c/p\u003e\n\u003cp\u003ePatients with duration of clinical presentation of 0-6 months were 43.09 times more likely to have malignant biological nature compared to those who present after 13 months. Similarly, those with duration of symptoms of 7-12 months were 36.206 times more likely to have malignant biological nature compared to patients who presented later than 13 months. This association between a short duration of clinical presentation and bone sarcoma is also supported by a study conducted in Birmingham\u003csup\u003e[14]\u003c/sup\u003e. The\u0026nbsp;durations of clinical presentation varied depending on the biological nature of the tumor. The median duration of symptoms for malignant bone tumors was 7 months. This differs from the Birmingham study, where the median duration of symptoms reported was 4 months\u003csup\u003e[14]\u003c/sup\u003e. This discrepancy may be partly explained by disparities in the availability of healthcare facilities and health-seeking behaviors among the source populations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe overall skeletal distribution was predominantly seen in the distal femur \u0026amp;proximal tibia. In agreement with previous studies, these sites were also the common sites for malignant subtypes of bone tumors\u003csup\u003e[5,15]\u003c/sup\u003e. Benign tumors were frequently seen in the jaw bones (32.6%), followed by the craniofacial bones 17 (19.1%), and the distal femur \u0026amp; proximal tibia 14(15.4%).This was in contrary to a study done in Ethiopia, wherein reported sites of benign tumors were the distal femur and proximal tibia (37%), the short tubular bones of the hands and feet (20%) and a craniofacial bone (14%)\u003csup\u003e[6]\u003c/sup\u003e. This discrepancy is likely due to the high percentage ossifying fibroma (20.2% vs 6%) and fibrous dysplasia (18.0% vs 12%) in our study; these tumors have higher predilection for jaw and craniofacial bones.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe distribution of histologic differentiation in the present study was bone forming (28.9%) and cartilage-forming tumors (27.2%). This was comparable with a previous study[1]. \u0026nbsp;In line with previous studies, osteochondroma was the most common benign tumor. Moreover, osteosarcoma was also the most prevalent histologic type among the malignant tumors\u003csup\u003e[8,16-18]\u003c/sup\u003e.\u003c/p\u003e\n\u003ch2 id=\"_Toc160891682\"\u003eLimitations of the study\u003c/h2\u003e\n\u003cp\u003eThis study is not without limitations. Firstly, we used a non-randomized convenience sampling method, which limits the generalizability of the results to the target population. Second, the cross-sectional design cannot infer causality. Thirdly, the majority of submitted specimens for malignant tumors were incisional biopsies, and pathologic staging was not reported. Lastly, in almost all cases, diagnoses were based on morphology, and in some cases, immunohistochemistry (IHC) was strongly recommended to establish the diagnosis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, benign bone tumors were more frequently observed than intermediate and malignant tumors. Malignant tumors were common in males, while benign tumors were more common in females. Osteosarcoma was the most common malignant tumor, followed by Ewing sarcoma. Bone tumors primarily affect the adolescent and adult age group. These are the working forces of society and have significant economic implications. Age 20-49 years, male gender, duration of clinical presentation after 0-6 months and 6-12 months of symptom onset were significantly associated with malignant bone tumors. These results also serve as a reference for future scientific research and studies to determine the associated factors and their impacts on clinical outcomes. \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors express their special thanks to all the study participants, data collectors, Hawassa University and study hospitals.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMTG, TDB and NAA were involved in the study design, article selection, analysis and manuscript writing. All the authors were involved in the analysis and manuscript preparation and editing. All the authors read and approved the final draft of the manuscript. All the authors gave their final approval for the version that would be published, agreed on the journal to which the article would be submitted, and agreed to be responsible for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no funding from institutions for this study\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author reports no conflicts of interest related to this work\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBiruk Lambisso NB. Pattern of bone tumours seen at Addis Ababa University, Ethiopia. East Cent Afr J Surg Online. Volume 14 Number 2:25\u0026ndash;32. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWorld Health Organization, International Agency for research on cancer, eds. Soft tissue and bone tumours. 5th ed. WHO: 2020 Vol. 3. 2019.\u003c/li\u003e\n \u003cli\u003e. Green NM, Abas S, Sajid S, Cribb GL. Presentation of bone tumours: clinical findings and initial management of patients. Orthop Trauma. 2021 Jun;35(3):108\u0026ndash;114.\u003c/li\u003e\n \u003cli\u003e. Wani L, Ashai FB, Banday BM, Ashraf A, Mushtaq S, Itoo MohdS, et al. Primary bone tumours in Kashmir valley a retrospective histopathological study. Int J Basic Appl Sci. 2014 Dec 22;4(1):51.\u003c/li\u003e\n \u003cli\u003eWeyessa TG, Kindie EA, Yefter ET. Histopathological pattern of primary bone tumours at the Black Lion Specialized Hospital, Addis Ababa, Ethiopia: a retrospective cross-sectional, 2015-2019. Pan Afr Med J. 2022;41.\u003c/li\u003e\n \u003cli\u003eMemirie ST, Habtemariam MK, Asefa M, Deressa BT, Abayneh G, Tsegaye B, et al. Estimates of Cancer Incidence in Ethiopia in 2015 Using Population-Based Registry Data. J Glob Oncol. 2018 Dec;(4):1\u0026ndash;11. doi: 10.1200/JGO.17.00175.\u003c/li\u003e\n \u003cli\u003eGlobal Cancer Observatory: Cancer Today: Ethiopia. International Agency for Research on Cancer: WHO: 2022:2.\u003c/li\u003e\n \u003cli\u003eShah KA, Naqvi QH, Shah SA, Soomro ZI, Akhund MA, Abbasi AN. Evaluation of neoplastic bone lesions: A morphological study at a tertiary care centre. Prof Med J. 2019 Nov 10;26(11):1983\u0026ndash;1988. doi: 10.29309/TPMJ/2019.26.11.3751.\u003c/li\u003e\n \u003cli\u003eOmer SM, Salim, Hanan Abdo, Jezan, Hussun Saeed. Morphological Pattern of Bone Lesions: Study of 204 Cases. International Journal of science and Healthcare Research. 2019;4(1):326\u0026ndash;31.\u003c/li\u003e\n \u003cli\u003eAina OJ, Adelusola KA, Orimolade AE, Akinmade A. Histopathological pattern of primary bone tumours and tumour-like lesions in Ile-Ife, Nigeria. Pan Afr Med J. 2018; 29. doi: 10.11604/pamj.2018.29.193.13111.\u003c/li\u003e\n \u003cli\u003eGururajaprasad C, Damodaran A. M. Histopathological study of tumours of bones and joints. Indian J Pathol Oncol. 2019 Mar 28;6(1):16\u0026ndash;24. doi: 10.18231/2394-6792.2019.0003.\u003c/li\u003e\n \u003cli\u003eGayathri. Spectrum of tumour and tumour-like lesions of bone in a Tertiary Care Hospital in North Karnataka, India. Indian J Pathol Oncol. 2020 Dec 28;5(1):75\u0026ndash;80. doi: 10.18231/2394-6792.2018.0014.\u003c/li\u003e\n \u003cli\u003eSakala D, Munthali J, Mulla Y. Primary Malignant Bone Tumours at the University Teaching Hospital in Lusaka Zambia. Med J Zambia. 2016 Mar 30;43(1):24\u0026ndash;30. doi: 10.55320/mjz.43.1.309.\u003c/li\u003e\n \u003cli\u003eSmith G, Johnson G, Grimer R, Wilson S. Trends in presentation of bone and soft tissue sarcomas over 25 years: little evidence of earlier diagnosis. Ann R Coll Surg Engl. 2011 Oct;93(7):542\u0026ndash;547. doi: 10.1308/147870811X13137608455055.\u003c/li\u003e\n \u003cli\u003ePaul EJ, Zacharie S, Adrian H, Andr\u0026eacute; M, Bruno DD, Roger AG. Primary Malignant Bone Tumors in Cameroon: Epidemiological and Histopathological Data. 2020;2(7). \u0026nbsp;doi: 10.4314/eaoj.v18i1.6.\u003c/li\u003e\n \u003cli\u003eGhert M, Mwita W, Mandari FN. Primary Bone Tumors in Children and Adolescents Treated at a Referral Center in Northern Tanzania. JAAOS Glob Res Rev. 2019 Mar;3(3):e045. doi: 10.5435/JAAOSGlobal-D-17-00045.\u003c/li\u003e\n \u003cli\u003eGemechu T. Bone and articular cartilage tumours as seen in the Dept. of Pathology, Faculty of Medicine, Addis Ababa University. 2021;12(2)\u003c/li\u003e\n \u003cli\u003eAhmad M, Ghani A, Mansoor A, Khan AH. Pattern of malignant bone tumour in northern areas of Pakistan. JPMA J Pak Med Assoc. 1994 Sep;44(9):203\u0026ndash;205.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 to 6 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Primary Bone Tumors, Malignancy Potential, Associated factors ","lastPublishedDoi":"10.21203/rs.3.rs-6330513/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6330513/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eMalignant bone tumors, also known as primary bone cancers, arise from the bone itself or the surrounding tissues. Understanding their biological nature and associated factors is crucial for early detection, effective treatment, and improved patient outcomes. To the best of our literature review there is no study which investigated factors associated with malignant biological nature of the bone tumor in southeastern region of Ethiopia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThe study aimed to assess the Patterns and factors associated With Malignancy Potential of Primary Bone Tumors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA 6-year retrospective institution-based cross-sectional study was conducted to review bone biopsy medical records recorded at the pathology department of Hawassa University Comprehensive Specialized Hospital (HUCSH), using 173 study participants; Logistic regressions were conducted to estimate the adjusted odds ratio (AOR) with 95% CI for the association between the independent variables and the malignant biological nature of the bone tumor.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe most common affected age groups were those in the second and third decades of life, accounting for 39.9% and 30.6% of cases, respectively. Age range of 20-49 years (AOR=0.192; 95% CI: 0.047-0.778), male gender (AOR=3.806; 95% CI: 1.490-9.725), duration of clinical presentation 0-6 months (AOR=43.09; 95% CI: 38.72-47.38), and duration of clinical presentation 7-12 months (AOR=36.20; 95% CI: 32.73-41.37) showed significant association with malignant bone tumor.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eIntermediate and malignant tumors were less common than benign bone cancers. Males were more likely to have malignant tumors, but females were more likely to have benign tumors. The most prevalent malignant tumor was osteosarcoma, which was followed by Ewing sarcoma. Adolescence and adulthood are the age groups most commonly affected by bone cancers. These have a big impact on the economy and are the backbone of society. Malignant bone tumors were associated with with age (20–49 years), male sex, and duration of clinical presentation after 0–6 months, and 6–12 months of symptom onset.\u003c/p\u003e","manuscriptTitle":"Primary Bone Tumors: Patterns and Factors Associated With Malignancy Potential","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 04:45:29","doi":"10.21203/rs.3.rs-6330513/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8dcf884c-6aee-4f9c-8809-512b645e84ae","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47606732,"name":"Biological sciences/Cancer"},{"id":47606733,"name":"Health sciences/Diseases"}],"tags":[],"updatedAt":"2025-05-13T04:45:29+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 04:45:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6330513","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6330513","identity":"rs-6330513","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}