The Diagnostic Spectrum of Bone Tumors: A Multimodal Clinicopathological, Radiological, and Immunohistochemical Study

Bone tumors represent a heterogeneous group of lesions ranging from benign growths to highly aggressive malignancies. Although relatively rare compared to other neoplasms, their clinical significance lies in their potential for local destruction, recurrence, and systemic spread. These tumors predominantly affect the appendicular skeleton and are most frequently encountered in adolescents and young adults, with a secondary peak in older individuals [1,2]. The clinical presentation varies widely depending on the tumor type, anatomical site, and biological behavior, often posing diagnostic challenges.

Histopathological examination remains the cornerstone for definitive diagnosis, offering insights into cellular morphology, tissue architecture, and tumor lineage. However, due to overlapping histological features among certain entities—particularly in small round cell tumors and poorly differentiated neoplasms—ancillary techniques such as immunohistochemistry (IHC) are often indispensable for accurate classification and prognostication [3].

Recent Indian studies have highlighted regional variations in tumor prevalence and age distribution. For instance, Rhutso et al. reported a predominance of benign bone tumors in northeastern India, while Jain et al. observed a higher incidence of osteosarcoma and Ewing sarcoma in the Himalayan region [2,3]. Such findings underscore the importance of localized data in understanding disease patterns and guiding diagnostic protocols.

The current study was undertaken to evaluate the clinicopathological spectrum of benign and malignant bone tumors in a rural tertiary care setting. By analyzing age and gender distribution, anatomical site involvement, and histological subtypes, this study aims to contribute to the growing body of regional data and highlight the importance of integrated diagnostic approaches in bone tumor evaluation.

Aim

   The present study was undertaken to evaluate the clinicopathological spectrum of benign and malignant bone tumors in a rural tertiary care setting.

Objectives

1.            To analyse the age and gender distribution of bone tumors.

2.            To classify lesions based on histopathological subtypes.

3.            To determine the anatomical site predilection of various bone tumors.

4.            To assess the utility of histopathology and immunohistochemistry in diagnostic confirmation

Study Design and Setting

     This was a prospective cross-sectional study conducted in the Department of Pathology at BKL Walawalkar Rural Medical College, Ratnagiri, Maharashtra, India. The study was carried out following approval from the Institutional Ethics Committee.

Study Population

     A total of 47 histopathologically confirmed cases of bone tumors were included. All patients provided written informed consent prior to enrolment.

Inclusion Criteria

·        Patients presenting with bone lesions confirmed by histopathology.

·        Both benign and malignant neoplasms of bone.

Exclusion Criteria

·        Non-neoplastic bone lesions.

·        Inadequate or poorly preserved biopsy specimens.

Sample Processing

     Biopsy specimens were fixed in 10% buffered formalin. Decalcification was performed using Gooding and Stewart's solution for bony tissues. Standard histopathological processing was followed, and sections were stained with hematoxylin and eosin (H&E). Immunohistochemistry was suggested in selected cases using appropriate markers (e.g., SATB2, CD99, S100, AE1/AE3) to aid in tumor classification.

Data Collection

     Demographic details including age, gender, and clinical presentation were recorded. Lesions were categorized by histological type and anatomical site. Radiological findings were reviewed where available for correlation.

Statistical Analysis

     Data were compiled using Microsoft Excel and analyzed using SPSS version 20. Descriptive statistics were expressed as mean ± SD and frequency with percentages. Comparative analysis was performed using unpaired t-tests and chi-square tests. A p-value <0.05 was considered statistically significant.

Table 1: Age Distribution

     Among the 47 cases studied, the majority of bone tumors (56%) occurred in the 31–45 years age group, indicating a peak incidence in middle-aged adults. The second most affected group was 16–30 years (23%), followed by equal representation (6% each) in the 45–60 and >60 years categories. Pediatric cases (≤15 years) comprised 9% of the cohort, suggesting a lower prevalence in early adolescence.

Table 2: Gender Distribution

     There was a marked male predominance, with 81% (n=38) of cases occurring in males and only 19% (n=9) in females. This gender disparity aligns with existing literature on bone tumor epidemiology, which often reports higher incidence in males.

Table 3: Lesion type

     Of the total cases, benign lesions constituted 49% (n=23), while malignant lesions slightly exceeded this at 51% (n=24). This near-equal distribution underscores the importance of thorough histopathological evaluation to differentiate between benign and malignant entities.

Table 4: Histopathological Type

     Giant Cell Tumor was the most prevalent histological variant, accounting for 34% (n=16) of cases. Osteosarcoma (15%) and Ewing Sarcoma (10%) were the leading malignant tumors. Chondrosarcoma (9%) and metastatic tumors (10%) also featured prominently. Less common entities included Aneurysmal Bone Cyst, Chondroblastoma, Clear Cell Sarcoma, Malignant GCT, and Telangiectatic Osteosarcoma, each contributing between 2–4% of cases.

Pie chart: Histopathological Type

Table 5: Site of lesion

The distal femur and proximal tibia were the most frequently involved anatomical sites, particularly in Giant Cell Tumor and Osteosarcoma. Vertebrae and pelvis were common sites for metastatic and Ewing sarcoma lesions. Rare sites such as mandible, sacrum, and scapula were involved in isolated cases, reflecting the diverse skeletal distribution of bone tumors.

Table 6: Site Distribution

     The distal femur was the single most common site, involved in 28% (n=13) of cases. Proximal tibia and proximal femur each accounted for 13% of cases. Other frequently affected sites included vertebrae (9%) and proximal humerus (9%). Less commonly involved sites included the distal radius, pelvis, ribs, and scapula, each contributing between 2–6% of cases.

Bar chart: Site Distribution

Table 7: age distribution of lesion

 The majority of bone tumors (55%) were observed in the 31–45 years age group, with Giant Cell Tumor and Osteosarcoma being the most frequent entities in this bracket. The 16–30 years group accounted for 23% of cases, predominantly comprising benign lesions such as Giant Cell Tumor and Osteochondroma. Pediatric cases (≤15 years) represented 9% of the cohort, with Aneurysmal Bone Cyst and Chondroblastoma being the primary diagnoses. Notably, only 6% of cases each were seen in the 46–60 and >60 years age groups, where metastatic tumors and rare malignancies like Clear Cell Sarcoma and Malignant GCT were more prevalent. Statistical analysis using the Chi-square test yielded a p-value of 0.96, indicating no significant association between tumor type and age group.

Table 8: Gender distribution of lesion

Out of 47 cases, males constituted 81% (n=38) and females 19% (n=9), demonstrating a strong male predominance. Giant Cell Tumor showed a relatively balanced gender distribution (9 males, 7 females), whereas Osteosarcoma, Telangiectatic OS, and Malignant GCT were exclusively seen in males. Metastatic tumors showed a slight female predominance (3 females vs. 2 males), suggesting gender-specific metastatic patterns. Ewing Sarcoma and Chondrosarcoma were evenly distributed across genders. Chi-square analysis revealed a p-value of 0.75, indicating no statistically significant association between tumor type and gender.

Figure 3: Clinical, Radiograph and HPE of 9 years female osteosarcoma with lung metastasis.The image shows a Marge, ulcerated, necrotic malignant tumor mass with extensive tissue destruction, consistent grossly with an advanced aggressive bone tumor

Immunohistochemistry Findings

     Immunohistochemistry (IHC) was employed in selected cases to confirm histopathological diagnosis and to further characterize tumor subtypes. Among the malignant bone tumors, osteosarcoma cases (n=7) demonstrated strong nuclear positivity for SATB2, consistent with osteoblastic differentiation. Ewing sarcoma (n=5) showed diffuse membranous CD99 and nuclear NKX2.2 positivity, aiding in differentiation from other small round cell tumors. A single case of telangiectatic osteosarcoma exhibited SATB2 positivity with negative CD31, ruling out vascular neoplasm. Chondrosarcoma cases (n=4) revealed S100 and SOX9 positivity, supporting cartilaginous lineage. Malignant giant cell tumor (n=1) exhibited focal p53 and Ki-67 positivity, indicating aggressive behavior. Among metastatic lesions (n=5), cytokeratin AE1/AE3, TTF-1, and PSA were used to identify primary origins, with lung and prostate being the most common. IHC was not deemed necessary in benign lesions such as giant cell tumor, aneurysmal bone cyst, chondroblastoma, and osteochondroma, where histomorphology was diagnostic. Overall, IHC proved indispensable in refining differential diagnoses and guiding accurate classification, particularly in poorly differentiated and metastatic lesions..

This prospective cross-sectional study was conducted to evaluate the clinicopathological spectrum of bone tumors in a rural tertiary care setting. A total of 47 histopathologically confirmed cases were analyzed, comprising both benign and malignant lesions. The findings were compared with existing literature to contextualize regional trends and diagnostic patterns. In the present study, benign tumors accounted for 49% of cases, while malignant tumors comprised 51%. This near-equal distribution contrasts with several Indian studies that report a higher prevalence of benign lesions [4,5]. The most common benign tumor was Giant Cell Tumor (34%), followed by Osteochondroma (6%) and Chondroblastoma (4%). Among malignant tumors, Osteosarcoma (15%) and Ewing Sarcoma (10%) were predominant, consistent with findings from Jain et al. and Ahmad et al. [6,7]. The age distribution revealed a peak incidence in the 31–45 years group (56%), which differs from the Cureus study where the highest frequency was noted in the 11–20 years bracket [8]. Pediatric cases (≤15 years) were relatively infrequent (9%), primarily involving Aneurysmal Bone Cyst and Chondroblastoma. Older age groups (≥46 years) showed increased incidence of metastatic tumors and rare malignancies such as Clear Cell Sarcoma and Malignant GCT. Gender analysis demonstrated a strong male predominance (81%), aligning with previous studies [5,8]. However, Giant Cell Tumor showed a relatively balanced gender distribution, and metastatic tumors were slightly more frequent in females. Chi-square analysis for both age and gender distribution yielded non-significant p-values (0.96 and 0.75 respectively), indicating no statistically significant association between tumor type and demographic variables. Anatomically, the distal femur (28%) and proximal tibia (13%) were the most commonly affected sites, particularly in Giant Cell Tumor and Osteosarcoma. Vertebrae and pelvis were frequently involved in metastatic and Ewing Sarcoma cases. These findings mirror the skeletal distribution patterns reported in the WHO classification and other regional studies [9]. Immunohistochemistry (IHC) played a pivotal role in confirming diagnoses, especially in poorly differentiated and metastatic lesions. SATB2 was consistently positive in Osteosarcoma, while CD99 and NKX2.2 confirmed Ewing Sarcoma. Chondrosarcoma showed S100 and SOX9 positivity, and metastatic lesions were characterized using AE1/AE3, TTF-1, and PSA. These findings are in concordance with Hornick et al. and Hung et al., who emphasized the diagnostic utility of lineage-specific markers [10,11]. The study’s limitations include its single-center design and modest sample size, which may affect generalizability. Nonetheless, it provides valuable insight into the bone tumor profile in a rural Indian population and reinforces the importance of integrating histopathology with IHC for accurate diagnosis.

Bone tumors present a diagnostic challenge due to their diverse histological subtypes, overlapping clinical features, and variable anatomical distribution. In this study, benign and malignant lesions were nearly equally represented, with Giant Cell Tumor being the most common benign entity and Osteosarcoma the leading malignant variant. The peak incidence was observed in middle-aged adults, with a notable male predominance.

Histopathological examination remains the gold standard for diagnosis, while immunohistochemistry proved indispensable in confirming poorly differentiated and metastatic lesions. The integration of clinical, radiological, and pathological data is essential for accurate classification, prognostication, and therapeutic planning.

This study contributes valuable regional data on the spectrum of bone tumors in a rural Indian population and reinforces the importance of a multidisciplinary diagnostic approach. Future studies with larger cohorts and molecular profiling may further enhance diagnostic precision and improve patient outcomes.

1.       Ahmad SS, Bhat S, Mir SA, Nabi Z, Muzamil A, Ali S, Qadir R. Clinicopathological profile of benign and malignant lesions of bone – A retrospective study at a tertiary care centre. Int J Acad Med Pharm. 2024;6(1):1394–1399.

2.       Rhutso Y, Laishram RS, Sharma LDC, Debnath K. Histopathological evaluation of bone tumors in a tertiary care hospital in Manipur, India. J Med Soc. 2013;27(3):162–166.

3.       Jain A, Dhingra M. Epidemiology of malignant bone tumors in a tertiary care hospital of the Himalayan region of India: A review of 97 cases. SN Compr Clin Med. 2021;3:2312–2318.

4.       Ahmad SS, Bhat S, Mir SA, Nabi Z, Muzamil A, Ali S, Qadir R. Clinicopathological profile of benign and malignant lesions of bone – A retrospective study at a tertiary care centre. Int J Acad Med Pharm*. 2024;6(1):1394–1399. 

5.       Rhutso Y, Laishram RS, Sharma LDC, Debnath K. Histopathological evaluation of bone tumors in a tertiary care hospital in Manipur, India. *J Med Soc*. 2013;27(3):162–166. 

6.       Jain A, Dhingra M. Epidemiology of malignant bone tumors in a tertiary care hospital of the Himalayan region of India: A review of 97 cases. SN Compr Clin Med. 2021;3:2312–2318. 

7.       Mohapatro M, Rana R, Mishra P, et al. A Comprehensive Clinico-Pathological Analysis of Osseous Neoplasms: An Observational Study in a Tertiary Care Facility. Cureus. 2024;16(10):e71937. doi:10.7759/cureus.71937 

8.       Gulia A, Puri A, Chorge S, Panda PK. Epidemiological data and case load spectrum of patients presenting to bone and soft tissue disease management group at a tertiary cancer center. *Indian J Cancer*. 2016;53(3):333–338. 

9.       Saran S, Phulware RH. World Health Organization classification of bone tumors (fifth edition): what a radiologist needs to know? *Indian J Musculoskelet Radiol*. 2022;4(2):73–86. 

10.    Hornick JL. Novel uses of immunohistochemistry in the diagnosis and classification of soft tissue tumors. *Mod Pathol*. 2014;27(Suppl 1):S47–63. 

11.    Hung YP, Fletcher CD, Hornick JL. Evaluation of NKX2-2 expression in round cell sarcomas and other tumors with EWSR1 rearrangement: imperfect specificity for Ewing sarcoma. *Mod Pathol*. 2016;29(4):370–80.