Abstract
Background/Aim: Benign and tumor-like lesions of the hindfoot and ankle are common, whereas malignant entities are rare. Accurate evaluation and timely management of these lesions can be challenging, making it crucial to understand their incidence and anatomic localization. This study retrospectively analyzed the distribution of benign and malignant bone and soft tissue tumors in the hindfoot and ankle. Patients and Methods: This study included patient data from a single center, such as age, sex, histologic diagnosis, and anatomic location over a 12.5 year period. Results: Of the 105 cases reviewed, 19 cases (18.1%) were osseous lesions and 86 cases (81.9%) were soft tissue lesions. The latter were divided into 77 benign and 9 malignant cases, resulting in an overall malignancy rate of 8.6%. The most common osseous lesion was the intraosseous ganglion (n=12). The majority of benign soft tissue lesions (75.3%) were located in the hindfoot, with TGCT, schwannoma, and ganglion cysts being the most common types. The nine malignant cases were distributed among seven entities and were evenly distributed among both regions and sexes. Malignant cases had a higher mean age (59.2 years) compared to benign cases (40.8 years; p=0.001). Conclusion: Tumors, tumor-like lesions, and pseudotumors represent an important aspect of ankle pathology. The majority of focal masses and swellings are benign soft tissue or osseous lesions, but malignant entities can occur and may be mistaken for benign conditions. Preoperative imaging and histopathologic examination are essential, and preoperative presentation to a multidisciplinary tumor board is recommended in unclear cases.
The human ankle and hindfoot, which consist of a complex interplay of bones, joints, ligaments, and soft tissues, are susceptible to a variety of pathologic processes (1-5). Swellings and masses are common clinical conditions presented to healthcare professionals, often triggering a spectrum of differential diagnostic considerations (5-7). While many etiologies are attributed to traumatic injury, inflammatory conditions, degeneration, or circulatory disorders, this article is devoted to an examination of a subset of pathologies that often present both diagnostic challenges and clinical significance: benign and malignant tumors and tumor-like lesions of bone and soft tissue in the ankle and hindfoot region (2, 3, 8-11).
Tumors, pseudotumors, and tumor-like lesions can have a profound effect on ankle function and patient quality of life. Their presence can lead to discomfort, pain, and limitation of mobility, requiring appropriate evaluation and treatment. In addition, malignant tumors of the ankle, although relatively rare, have a significant impact on patient prognosis and survival. Delayed diagnosis of malignancy may affect the choice and effectiveness of treatment options, making early detection and intervention imperative.
This study aimed to provide insight into the distribution patterns of the ankle region, enabling clinicians to accurately evaluate uncertain masses and initiate appropriate diagnostic and treatment strategies.
Patients and Methods
Patient selection and data retrieval. For this study, we conducted a thorough examination of patients who presented with tumors or tumor-like lesions at our institution’s multidisciplinary musculoskeletal tumor board during the period from January 2010 to June 2023. Two independent authors analyzed our institutional database to identify patients.
Ethics approval and consent to participate: Approval of local ethics committee (TU Munich) was obtained (no. 2023-103-S-KH). All patients signed an informed consent form.
Inclusion criteria. To be included in this study, patients had to meet the following criteria:
1) Presentation of tumors between the distal tibia or fibula and the transverse Chopart’s joint, formed by the calcaneocuboid and talocalcaneonavicular joints.
2) A histologically confirmed diagnosis of the tumor.
3) Availability of comprehensive imaging data, including magnetic resonance imaging (MRI).
Exclusion criteria. Patients were excluded from the study if they lacked essential data, such as incomplete medical records, missing imaging studies, or unavailable histologic reports or inconspicuous histological findings, which would compromise the accurate identification of the tumor.
Data collection. A retrospective analysis of the database encompassed a 12.5-year period. We identified a total of 112 bone and soft tissue tumors and tumor-like lesions localized in the hindfoot and ankle regions. Notably, lesions that did not conform to the WHO classification were intentionally retained for inclusion in our study.
Anatomical localization. For localization, the examination area between the distal lower leg and the Chopart’s joint was divided by the joint line of the ankle joint into the ankle above and the hindfoot below. The area for ankle tumors includes the epi-metaphysis of the distal tibia and fibula, as determined by the AO classification (a square of the length as the widest part of the growth plate of tibia and fibula, over the epi-metaphysis of the distal tibia and fibula). In instances where a soft tissue mass extended across both anatomical compartments, we assigned the presumed center of the lesion to the corresponding underlying anatomical region.
Data review and analysis. Patient-specific data, including age at diagnosis, sex, affected side, histologically confirmed diagnosis, and anatomic location, were recorded during medical record review. We performed a comprehensive evaluation of all available imaging studies, including conventional radiographs and cross-sectional imaging. Histologic classification of tumors was available for all cases and was performed by pathologists experienced in the musculoskeletal field. Study variables included tissue of origin (bone or soft tissue), classification of lesion as benign or malignant, anatomic location (hindfoot or ankle), and specific histologic diagnosis.
Statistical analysis. Data collection and subsequent analysis were performed using Microsoft Excel software (Microsoft Excel version 16.78, Microsoft, Richmond, WA, USA) and DATAtab (DATAtab 2023: Online Statistics Calculator. DATAtab e.U. Graz, Austria). The Kolmogorov-Smirnov test was used for analytical testing of the normal distribution of metric variables. For comparison of normally distributed metric variables, the t-test for independent samples was utilized. Levene’s test was performed for equality of variance. Categorical variables were presented as frequency counts and percentages relative to the total number of lesions within each category. Descriptive statistical analysis was employed for demographic data, including mean values, standard deviations, and minimum/maximum values where applicable.
Results
Of the 112 hindfoot and ankle lesions presented in our multidisciplinary tumor board between January 2010 and June 2023, 105 cases met the inclusion criteria. The remaining seven cases revealed nonspecific histologic findings.
Among the 105 evaluated cases, 19 cases (18.1%) were osseous lesions, and 86 cases (81.9%) were soft tissue lesions. The proportion of soft tissue lesions was even higher in the hindfoot (86.1%) compared to the ankle (72.7%).
No malignant entities were observed among the osseous lesions, whereas the soft tissue lesions were divided into 77 benign and 9 malignant lesions. This results in a malignancy rate of 10.5% based on soft tissue lesions and 8.6% based on all cases.
The hindfoot accounted for 68.6% of all lesions, whereas the ankle represented 31.4%. The distribution of bony lesions and malignant lesions was fairly balanced between ankle and hindfoot. Because there were three times as many benign soft tissue lesions in the hindfoot compared to the ankle, the malignancy rate was significantly lower, with 5.6% as opposed to the ankle with 15.2% (Table I).
Distribution of osseous and soft tissue lesions according to their localization and dignity.
All of the 19 osseous lesions observed were benign, with nine occurring in the ankle and ten in the hindfoot. The intraosseous ganglion was the most frequently encountered lesion, comprising almost two-thirds of all observed osseous lesions with a total of 12 cases. It was fairly evenly distributed, with 58.3% in the ankle and the remaining 41.7% in the hindfoot. Moreover, it was found to affect twice as many females as males, with an average age of 41.5 years. The study also identified two lipomas of the bone, a simple bone cyst in the calcaneus, a hemangioma of the bone in the talus, and an osteochondroma and a manifestation of sarcoidosis at the medial malleolus. On average, patients with osseous lesions were 40.4 years old with a standard deviation (SD) of 11.6, ranging from 17 to 60 years (Table II).
Distribution of osseous and soft tissue lesions across the ankle and hindfoot according to location, age, and sex.
Seventy seven out of 105 cases in the hindfoot and ankle were attributed to benign soft tissue lesions, accounting for 73.3% of all lesions. Among these 77 cases, 75.3% (58 cases) occurred in the hindfoot, while only a quarter involved the ankle. The most frequently occurring lesions were TGCT with 19 cases (24.7%), schwannoma with 17 cases (22.1%), ganglion cysts with 9 cases (11.7%), and hemangioma and lipoma with 4 cases each (5.2%). Out of the 18 observed entities, the top 5 accounted for 68.8% of benign soft tissue lesions. Patients with benign soft tissue lesions had a mean age of 40.8 SD 16.7 years, ranging from 9 to 78 years. Notably, the two most common entities, TGCT and schwannoma, were found more frequently in females than in males and showed the above-mentioned preference for the hindfoot (Table II).
The nine malignant tumors observed were all soft tissue tumors, of which four were located in the hindfoot and five in the ankle. Seven different entities were identified, including angiosarcoma and extraskeletal myxoid chondrosarcoma, with each being observed once in both the hindfoot and ankle. The remaining five entities were observed only once. Furthermore, in addition to various sarcomas, a case of lymphoma was observed in a 72-year-old patient. The average age of the patients was 59.2 years with a SD of 18.1 years, ranging from 14 to 76 years. This was higher than the age of patients in the other two groups (p<0.01).
Discussion
Swellings and masses in the complex anatomical area of the ankle and hindfoot are common reasons for medical presentation and can easily be detected due to the relatively thin subcutaneous tissue (7). However, various pathologies can be their cause, such as trauma, infections, metabolic disorders, cardiovascular insufficiency, lymphedema, and tumorous entities. The incidence of the latter is higher than commonly thought. In a large series, 8% of benign and 5% of malignant soft tissue tumors occurred in the foot and ankle (12). Magnetic resonance imaging is essential for distinguishing these lesions, however, the distinction can be challenging in some cases (13, 14).
Understanding the incidence and anatomical distribution patterns of lesions is crucial for accurate assessment and appropriate management (15, 16). This study aimed to comprehensively analyze the bone and soft tissue lesions in the hindfoot and ankle over a 12.5-year period at a German University Hospital. We intentionally decided to include all lesions presented in our multidisciplinary tumor board, including pseudotumor and tumor-like lesions to support clinical practitioners in their daily work. This included diverse histopathological entities including ganglion cysts, epidermoid cysts, gouty tophi or rheumatoid nodules (17).
For the purpose of localization, we adopted the classification system used by Toepfer et al., who expanded the anatomical system proposed by Ruggieri et al. to categorize the foot into forefoot, midfoot, hindfoot, and the ankle (17). For our study, we focused on the hindfoot (talus and calcaneus) and ankle (epi-metaphysis of the distal tibia and fibula), separated by the ankle joint line.
Over the study period, our multidisciplinary tumor board discussed a total of 112 hindfoot and ankle pathologies. Of these, 105 lesions had a confirmed histopathologic diagnosis and were subjected to further evaluation. In general, soft tissue lesions were found to be significantly more frequent, accounting for 81.9% of cases evaluated. Additionally, 8.6% of cases presented to the multidisciplinary musculoskeletal tumor board were found to be malignant, highlighting the importance of accurate clinical and radiological assessment despite the predominance of benign, often harmless alterations (91.4%). In this study, only soft tissue lesions were affected by malignancy, which may be due to the small sample size of cases with osseous lesions. The malignancy rate is lower than that reported in former studies, possibly because we included pseudotumor and tumor-like lesions (6).
Overall, female patients were found to have a slightly higher incidence of 56.2% compared to males with 43.8%. Chou et al. reported an increased incidence of soft tissue and bony lesions of the foot and ankle in women with a rate of 54.9% (18). Interestingly, women were affected approximately twice as often by the three most common entities in our study, TGCT, schwannoma, and intraosseous ganglion. It is possible that differences in footwear, aesthetic demands or body consciousness of women may have contributed to these differences. On the other hand, gout tophi, epidermoid cysts, and chronic synovialitis were only found in male patients. The sex ratio for malignant tumors was relatively even.
The average age of patients diagnosed with malignant diseases was 59.2 years, which was significantly higher than the average age of patients with benign conditions at 40.8 years of age. However, it is important to note that both groups showed a wide range of ages, leading to considerable overlap. Therefore, relying solely on age or sex as a factor should not be sufficient for excluding or confirming a disease in individual cases.
Overall, more than two thirds of all cases occurred at the hindfoot (n=72) and benign soft tissue lesions at the hindfoot represented more than half of all cases (n=58). Benign soft tissue lesions of the ankle were found in 19 cases. Osseus lesions showed a balanced distribution between the ankle and hindfoot. Malignant soft tissue tumors were also evenly distributed between the two study areas, with four cases in the hindfoot and five cases in the ankle. As there were three times as many benign soft tissue lesions in the hindfoot as in the ankle, the malignancy rate in the hindfoot was significantly lower at 5.6% compared to 15.2% in the ankle. On the entity level, the three most common soft tissue entities showed a tendency to appear at the hindfoot rather than the ankle. However, 55.6% of the malignant entities, 47.4% of the osseous lesions, and almost a quarter of the benign soft tissue lesions appeared in the ankle, which underlines the necessity to consider this area (15).
The largest group, benign soft tissue lesions, comprised 18 different entities and accounted for 73.3% of all cases. TGCT had the highest incidence, followed by schwannoma, ganglion cyst, hemangioma, and lipoma. These top five entities accounted for 68.8% of all 77 benign soft tissue lesions.
TGCT, formerly known as pigmented villonodular synovitis (PVNS), was the most common benign soft tissue lesion, with 19 cases and 73.7% of its manifestations at the hindfoot. It is a rare lesion of the synovium that affects joints, tendon sheaths, and bursae and has been reported to be one of the most common soft-tissue tumors of the foot and ankle (15, 18, 19). The ankle is the second most frequently impacted joint, accounting for 14% of diffuse TGCT, after the knee joint with 64% (20). Nevertheless, TGCT can arise from any part of the foot and ankle region (21) and was observed in 13 female and 6 male patients in our study, with an average age of 27.7 years. Previous studies indicate that about 55% of all cases are female, and onset typically occurs in the third to fifth decade of life (21-23). Surgical excision remains the preferred treatment option (24-26). According to a systematic literature review by Siegel et al., the recurrence rate ranges from 7% to 21%, making radiological follow-up necessary (23).
The second most frequent diagnosis was schwannoma, which accounted for 17 cases. Schwannomas are slow-growing solid tumors that originate from Schwann cells in the peripheral nerves (27-29). They have been reported to be relatively rare in the foot and ankle region, with only 9.2%-11.5% of schwannomas being found there (18, 28, 30-32). Toepfer et al. observed 11 cases in 104 benign soft tissue tumors in the foot and ankle region (15). Another study by Ruggieri et al. identified six cases of schwannomas in sixteen benign tumors observed in the hindfoot, excluding pseudotumoral lesions (31). Our analysis revealed a preference of schwannomas for the hindfoot, with 15 out of 17 occurrences observed in this area. The average age was 50.8 years, ranging from 21 to 78 years. These findings are consistent with a review conducted by Hao et al., who reported an average age of 47.4 years and noted that over 80% of the tumors were located on the ankle, heel, and plantar aspect. However, like TGCT, schwannomas can occur in any part of the foot. In contrast to our observations that showed a higher incidence among women (11 cases) compared to men (6 cases), Hao et al.’s study found no sex disparities (27).
In our study, the ganglion cyst was found to be the third most common soft tissue lesion. It has been reported as the most prevalent tumor-like lesion in the foot and ankle region, accounting for approximately 42% of cases and affecting about 6% of the population (33, 34). The cysts are filled with mucopolysaccharides and typically appear near a joint capsule or tendon sheath. They may have communication with these structures and are believed to originate from mucoid degeneration (5, 17, 35, 36). Ultrasound and MRI imaging can effectively visualize and locate these cystic lesions (17, 37).
Hemangioma and lipoma accounted for four cases each, occurring in middle-aged patients without a significant sex preference. According to Kransdorf et al., hemangiomas were found in 8% of the total population (38,484 individuals), with 14% of cases found in the lower extremities (12). Studies on lower extremity hemangiomas have shown varying incidences within the foot, ranging from 4.9% to 28.5% (38, 39). It is widely accepted that these hemangiomas are caused by developmental abnormalities originating from endothelial cells (12, 39). Lipomas, on the other hand, typically arise on the dorsum of the foot (13).
Concerning osseus lesions, we found that intraosseous ganglion cysts were the most common lesion, accounting for 12 out of 19 cases. Previous studies have identified intraosseous ganglia as one of the most prevalent benign lesions (6). The exact cause and development process of these cysts are again not fully understood; however, it is widely believed that they may arise from acute or repetitive trauma, leading to degeneration in the surrounding connective tissue (40-42).
During our study period, a total of nine malignant soft tissue tumors were identified, spread across seven different entities. This shows the rarity, heterogeneity, but also the importance of keeping an eye on possible malignant differential diagnoses in tumors of the foot and ankle and illustrates the need for a histopathological examination (43). It should be emphasized that swelling may occur without the presence of a tumor, and conversely, a tumor may be present without severe swelling. This is especially true for bone tumors, where swelling usually occurs at a later stage (6, 9, 44).
Study limitations. It is important to recognize that the data utilized for this research were obtained from a singular healthcare facility, which may limit the generalizability of our findings. Furthermore, our facility specializes in the treatment of musculoskeletal tumors in patients who typically have more advanced or severe symptoms. This could introduce bias in sample selection and potentially affect the applicability of our results. Most of the cases analyzed underwent surgical intervention, which may have excluded benign and asymptomatic cases not addressed by our multidisciplinary musculoskeletal tumor board.
Conclusion
The purpose of this article was to highlight the often neglected yet critical aspect of tumor and pseudotumor etiologies of ankle pathology and to emphasize its clinical importance. Focal masses and diffuse swellings are common in the foot and ankle, and most are non-neoplastic. We found more soft tissue lesions than osseus lesions. The most common entities in our patient population were TGCT, (intraosseous) ganglion cysts, and schwannoma. However, a variety of malignant entities can occur in any localization and at any age. Unfortunately, sarcomas may initially be small and well demarcated, grow slowly, and therefore may be easily misinterpreted as benign lesions. Therefore, preoperative imaging and postoperative histopathologic examination are mandatory. In our opinion, presentation to an multidisciplinary tumor board is also recommended, and unclear lesions should be confirmed preoperatively by biopsy.
Footnotes
Authors’ Contributions
Conceptualization, F.L., U.L., and N.H.; methodology, C.K. and N.H.; software, C.S.; validation, F.L., S.B., and D.D.; collection, analysis, and interpretation of patient data, C.S.; resources and data curation, F.L.; writing – original draft preparation, C.S.; writing – review and editing, C.S., D.D., F.L., and N.H.; visualization, C.S.; supervision, C.K.; project administration, F.L. All Authors have read and agreed to the published version of the manuscript.
Conflicts of Interest
The Authors have no conflicts of interest to declare in relation to this study.
Funding
No funding was obtained.
- Received April 22, 2024.
- Revision received May 22, 2024.
- Accepted May 24, 2024.
- Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).