The Epidemiological Trends of Primary Benign and Malignant Bone Tumors in Iran

Background & objective: The incidence of various tumors is strongly influenced by racial characteristics, and therefore the distribution of benign and malignant lesions follows different epidemiological and pathophysiological patterns in the societies. This study aimed to evaluate the epidemiological trend of primary benign and malignant bone tumors in the Iranian population. Methods: In this cross-sectional study, epidemiological and pathological information related to cases of benign and malignant primary bone tumors registered in the data registry of pathology laboratory of Imam Khomeini Complex hospital in Iran between 2017 and 2022 were assessed. Including criteria was all patient with established pathology diagnosis of bone tumors and excluding criteria was patients with incomplete data. Results: In total, 617 primary bone tumors (233 benign lesions and 384 malignant lesions) were assessed within 5 years between 2017 and 2022. The average age of patients in benign and malignant lesions subgroups was 29.50±16.95 years and 35.30±19.70 years respectively with the highest incidence in the second and third decades of life in both lesion types. Overall, 52.8% of benign tumors and 58.9% of malignant tumors were found in men. The most frequent benign tumors reported in the study periods including osteochondroma found in 30.5%, and enchondroma in 29.2%. Of malignant bone tumors, osteosarcoma was the most prevalent type with an overall prevalence of 32.6% followed by chondrosarcoma (20.8%) and Ewing sarcoma (16.7%). In the case of benign tumors, a decrease in the trend during the last four years was showed, while the trend of malignant tumors was completely upward in the last four years. Conclusion: The epidemiological distribution of primary benign and malignant bone tumors in Iran is similar to global statistics, but with a downward trend in benign masses and vice versa, an increasing trend in malignant tumors in recent years.

 Introduction

Although bone tissue is a common target for all types of cancers, primary bone malignancies are much rarer and account for only 0.2% of all malignancies [1]. Despite being rare, the outcome of such bone malignancies is significant, and the overall survival rate and recurrence-free survival in these malignancies are low. The progress of imaging modalities and molecular techniques regarding the identification of early bone points involved with the tumor has led to the early identification of such lesions, however, in many cases, because the lesion remains asymptomatic until the advanced stages, it is not possible to detect these tumors early in many cases [2, 3]. Additionally, community-based evaluations in various communities have indicated a high variant in the epidemiologic characteristics of primary benign and malignant bone tumors. In developed countries like the United States and the United Kingdom, primary malignant bone tumors are the third leading osteogenic cancer-related death followed by hematopoietic malignancies in different age groups especially among young adults [4, 5]. Even in developed countries, a downward trend in the incidence of these types of tumors can be revealed. In a recent data registry-based study in China, the incidence of primary bone tumors declined by 2.2% in men and 4.8% in women per year, and the rates in urban areas were lower than those in rural areas [6]. Unfortunately, there is very little information about the state of bone tumors in developing countries or the third world, which is due to the lack of a comprehensive data registry system to record cases of bone tumors and the lack of proper follow-up of patient’s prognosis. In a study on the Iranian population, it was found an increasing trend in the incidence of bone sarcomas from 8.59 in 2007 to 11.37 per million person-year in 2015 [7] indicates the increase in the incidence of this type of malignancy during the last decade, despite the modification of scientific instructions for their prevention and treatment.

The best approach to reduce the incidence of various types of cancers is to obtain a clear and comprehensive view of the epidemic characteristics as well as the physiopathological indicators related to them. This issue can only be made possible through the design and management of community-based data registries in large referral centers in the countries for such patients. Also, such a tool provides the possibility of checking the trend of changes in the incidence of various cancers during different years. What we discussed in this study was the evaluation of the epidemiological situation of primary benign and malignant bone tumors and the evaluation of the changes in these characteristics during the last six years.

 Materials and Methods

Imam Khomeini Complex hospital in Tehran, as the largest diagnostic and treatment complex in the country, is considered the largest reference for cancer patients throughout Iran. This diagnostic and treatment center has the most comprehensive data registry regarding the registration and follow-up of all types of cancers, especially bone cancers. In the present study, the aim was to collect epidemiological and pathological information related to cases of benign and malignant primary bone tumors registered in the data registry of this complex between 2017 and 2022. Including criteria was all patient with established pathology diagnosis of bone tumors and excluding criteria was patients with incomplete data. What was focused on in the present studies was, first of all, the evaluation of the demographic characteristics of patients with benign and malignant bone tumors and the site of involvement in these tumors. Then, the change in these parameters during the six years of the study was also evaluated.

Descriptive data were described based on frequency and percentage for qualitative variables and mean and standard deviation for quantitative parameters. Qualitative variables were compared using the Chi-square test and quantitative variables using independent t-tests. The SPSS software version 26.0) was used for data analysis. A p-value < 0.05 was considered significant.

Results

In total, 617 primary bone tumors (233 benign lesions and 384 malignant lesions) were assessed within 5 years between 2017 and 2022. The demographic characteristics of these tumor lesions are summarized in (Table 1).

Characteristics Benign tumors Malignant tumors P value
(n = 233) (n = 384)
Gender, % 0.141
Female 110 (47.2) 158 (41.1)
Male 123 (52.8) 226 (58.9)
Mean age, year <0.001
Side of involvement, % 0.176
Left 107 (45.9) 155 (40.4)
Right 126 (54.1) 229 (59.6)
Site of involvement, % <0.001
Chest wall 11 (4.7) 30 (7.8)
Elbow 3 (1.3) 2 (0.5)
Femur 45 (19.3) 122 (31.8)
Fibula 4 (1.7) 6 (1.6)
Finger 43 (18.5) 9 (2.3)
Hand 2 (0.9) 0 (0.0)
Hip 15 (6.4) 41 (10.7)
Humerus 25 (10.7) 42 (10.9)
Knee 13 (5.6) 14 (3.6)
Leg 8 (3.4) 12 (3.1)
Radius 5 (2.1) 3 (0.8)
Shoulder 11 (4.7) 43 (11.2)
Tibia 32 (13.7) 35 (9.1)
Ulna 6 (2.6) 4 (1.0)
Vertebra 5 (2.1) 20 (5.2)
Wrist 5 (2.1) 1 (0.3)

The average age of patients in benign and malignant lesions subgroups was 29.50±16.95 years (ranged 1 to 79 years) and 35.30±19.70 years (ranged 1 to 91 years) respectively. Regarding age distribution, the age distribution was completely asymmetric, and involvement in both categories of benign and malignant tumors was related to the second and third decades of life (Figure 1).

Concerning sex distribution, 52.8% of benign tumors and 58.9% of malignant tumors were found in men. Overall, the most frequent site involved by benign tumors included the femur (19.3%) followed by fingers (18.5%) and tibia (13.7%), while malignant bone lesions were prominently revealed in the femur (31.8%) followed by the shoulder (11.2%), humerus (10.9%) and hip (10.7%) (Table 1). Regarding the side of involvement, both groups of lesions mainly involved the right side (54.1% of benign tumors and 59.6% of malignant tumors). The different types of benign and malignant tumors are presented in (Figure 2).

The most frequent benign tumors reported in the study periods included osteochondroma found in 30.5%, and enchondroma in 29.2%. Of malignant bone tumors, osteosarcoma was the most prevalent type with an overall prevalence of 32.6% followed by chondrosarcoma (20.8%) and Ewing sarcoma (16.7%). Comparing benign and malignant tumors about baseline characteristics showed no difference in gender (p-value = 0.141), and the side of involvement (p-value = 0.176), however, those who suffered malignant tumors were significantly older (p-value < 0.001) (Table 1). Also, there was a significant difference in the site of involvement between benign and malignant tumors (p-value < 0.001).

The distribution of background characteristics according to the evaluated year is presented in (Tables 2 and 3).

Characteristics Y2017 Y2018 Y2019 Y2020 Y2021 Y2022 p-value
Gender, % 0.657
Female 50.00 45.90 56.20 41.20 38.90 50.00
Male 50.00 54.10 43.80 58.80 61.10 50.00
Mean age, year 26.8±16.5 27.8±16.0 32.4±19.0 34.4±17.3 25.1±14.7 33.5±16.5 0.103
Side of involvement, % 0.43
Left 52.50 42.60 56.20 35.30 41.70 42.90
Right 47.50 57.40 43.80 64.70 58.30 57.10
Site of involvement, % 0.153
Chest wall 0.00 4.90 8.30 8.80 2.80 0.00
Elbow 0.00 3.30 2.10 0.00 0.00 0.00
Femur 17.50 11.50 22.90 23.50 19.40 35.70
Fibula 0.00 1.60 0.00 5.90 2.80 0.00
Finger 15.00 24.60 25.00 5.90 22.20 0.00
Hand 0.00 3.30 0.00 0.00 0.00 0.00
Hip 7.50 6.60 8.30 0.00 2.80 21.40
Humerus 10.00 13.10 8.30 14.70 8.30 7.10
Knee 7.50 6.60 6.20 0.00 8.30 0.00
Leg 2.50 1.60 4.20 0.00 5.60 14.30
Radius 5.00 4.90 0.00 0.00 0.00 0.00
Shoulder 10.00 4.90 4.20 0.00 2.80 7.10
Tibia 10.00 11.50 4.20 32.40 16.70 14.30
Ulna 5.00 0.00 2.10 5.90 2.80 0.00
Vertebra 5.00 1.60 2.10 2.90 2.80 0.00
Wrist 5.00 0.00 2.10 2.90 2.80 0.00

Characteristics Y2017 Y2018 Y2019 Y2020 Y2021 Y2022 p-value
Gender, % 0.47
Female 39.00 40.30 33.30 49.20 40.50 50.00
Male 61.00 59.70 66.70 50.80 59.50 50.00
Mean age, year 35.8±19.7 34.2±21.2 38.0±18.7 30.1±18.9 37.9±19.6 33.8±19.0 0.172
Side of involvement,% 0.758
Left 39.0 45.2 39.40 46.20 36.90 33.3
Right 61.00 54.80 60.60 53.80 63.10 66.70
Site of involvement, % 0.517
Chest wall 10.40 6.50 7.60 7.70 6.00 10.00
Elbow 1.30 0.00 1.50 0.00 0.00 0.00
Femur 27.30 38.70 40.90 32.30 23.80 30.00
Fibula 1.30 1.60 0.00 3.10 2.40 0.00
Finger 2.60 4.80 3.00 0.00 2.40 0.00
Hip 11.70 3.20 4.50 15.40 17.90 0.00
Humerus 9.10 12.90 16.70 9.20 8.30 10.00
Knee 3.90 3.20 3.00 4.60 4.80 0.00
Leg 1.30 3.20 4.50 0.00 4.80 6.70
Radius 1.30 3.20 4.50 0.00 4.80 0.00
Shoulder 7.80 11.30 9.10 13.80 15.50 6.70
Tibia 14.30 8.10 4.50 4.50 7.70 4.80
Ulna 1.30 0.00 0.00 1.50 1.20 3.30
Vertebra 6.50 6.50 3.00 1.50 8.30 3.30
Wrist 0.00 0.00 0.00 1.50 0.00 0.00

No difference was observed in the gender and age distribution of patients with benign or malignant tumors in different years. Also, the side of involvement did not show a significant difference in study years. However, the trend of benign and malignant lesions was completely different during the six years of assessment (p-value = 0.022), so in the case of benign tumors, we were faced with a decrease in the trend during the last four years, while the trend of malignant tumors was completely upward during the last four years (Figure 3).

Discussion

The incidence of various cancers is strongly dependent on racial and genetic characteristics, and therefore the distribution of cancer types in different societies follows different epidemiological and pathophysiological patterns [8-10]. Accordingly, the planning and management of prevention and health related to cancers are completely different in different societies. The first step in presenting this plan is to provide an accurate and correct view of the distribution of these cancers in society, and more importantly, to evaluate the changes in their epidemiological indicators over many years.

What was examined in the first place in the present study was the evaluation of the gender and age distribution of benign and malignant bone tumors in Iran. For this purpose, the data registry of one of the most important referral centers for this type of cancer in the capital of Iran was selected to be considered as a sample of Iranian society. In this study, firstly, it was found that the age distribution of patients in both types of tumors is related to the second and third decades of life, but the incidence of malignant masses occurs a decade later than benign masses. Secondly, in terms of sex ratio, these tumors occur almost equally in both sexes. The mentioned results on tumors-related age distribution are consistent with the results obtained from the global summary [11, 12]. As shown by reviewing the literature, two peaks are observable in primary malignant bone tumor incidence rates in the second decade of life, peaking during adolescence globally, although again in the seventh and eighth decades of life. In this regard, the second peak starts with a gradual increase after the age of 40 years [13]. However, regarding sex distribution, it has been shown that although the age-standardized rates were almost equal among both genders in the first decade of life, they were consistently higher among males as compared to females across all other age groups [14]. However, it should be noted that this is not a consistent finding in all countries, as it has been shown that the sex and age distribution of bone tumors was very different in the Asian and American continents. In this regard, Asia has the lowest incidence rates of primary malignant bone tumors in the second decade of life in both genders however; the incidence of primary malignant bone tumors was the second highest in the elderly age group [15]. In contrast, South America has the highest incidence rates during the second decade of life among all the continents the incidence rates in Europe were similar to those in North America in all the age groups and the incidence rates in Oceania were the lowest among the continents with more developed countries [16]. In summary, what can be expected about the Iranian society is the highest distribution of these types of tumors in the second and third decades of life in both sexes.

Regarding the most prevalent types of benign and malignant tumors, the most frequent benign tumors reported in our society were osteochondroma and enchondroma, while osteosarcoma and chondrosarcoma were the most prevalent primary bone malignant tumors. The prevalence of benign and malignant bone tumors follows a similar pattern in almost all countries of the world [17, 18]. In this regard, regardless of the region, osteosarcoma is the most prevalent primary bone sarcoma, followed by chondrosarcoma and Ewing sarcoma. This finding is in line with previous studies on sarcomas in Taiwan [19], Japan [20], and the United Kingdom [21] as they found a similar order of prevalence for bone sarcomas.

What was of particular interest in the results of the present study was the difference in the trend of changes in the occurrence of two types of benign and malignant tumors in recent years in Iran. In other words, the decrease in the incidence of benign tumors and, on the contrary, the increase in the incidence of malignant tumors during the last six years was quite evident. We think that these trends have been strongly influenced by the COVID-19 pandemic in recent years and, secondly, by the reform of the comprehensive prevention and monitoring programs for the treatment of bone masses in Iran [22]. From the first point of view, the COVID-19 pandemic has had a major impact on the identification and occurrence of malignant tumors [23, 24]. Because, during this pandemic period, the number of visits to medical centers in patients diagnosed with benign tumors has decreased due to the fear of contracting COVID-19. On the other hand, the improvement of diagnostic techniques during the last decade made it possible to diagnose malignant tumors, especially in the early stages of the disease, and therefore we saw more of these cases being recorded in the cancer registry during this decade.

In conclusion, as a final summary, the epidemiological distribution of primary benign and malignant bone tumors in Iran corresponds to the global distribution. The majority of involvement in both tumors was related to the second and third decades of life and the gender distribution was almost the same. The most common benign tumors are osteochondroma and enchondroma while the most frequent malignant tumors are osteosarcoma and chondrosarcoma. The trend of changes in the occurrence of these two types of tumors in society during the last six years has been completely different and includes a decreasing trend in benign tumors and an increasing trend in malignant tumors. Gathering this information will improve the management of these tumors in our country.

Acknowledgments

Statement of Transparency and Principals:

• Author declares no conflict of interest

• Study was approved by Research Ethic Committee of author affiliated Institute.

• Study’s data is available upon a reasonable request.

• All authors have contributed to implementation of this research.

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