Both GCTS and FTS are lesions that are more common in the synovium, synovial sac, tendons, and tendon sheaths of joints [1]. L-GCTS and FTS are very similar in terms of location,age, and clinical features, and imaging examinations are also difficult to diagnose before surgery. A clear diagnosis needs to be based on pathological histology or even immunohistochemical staining. Analyzing and comparing the clinical and pathological characteristics of two types of lesions is of great significance for us to further understand these two types of lesions and make accurate diagnosis and differential diagnosis.
GCTS can occur at any age, with a high incidence age range of the third to fourth decades, and it is more common in females than males. It often presents as slowly growing painless small nodules with a diameter generally less than 3cm, commonly found near small joints such as fingers, palms, and wrists. It is the second most common soft tissue tumor in these areas after ganglion cysts [2-4]. In recent years, there have been reports of tumors occurring in other rare areas such as the posterior pharyngeal wall and the anterior cruciate ligament of the femur [8, 9], indicating that this tumor can also occur in some uncommon areas and should be taken seriously in clinical diagnosis and treatment. It is generally a single nodule, but there are also reports of multiple nodules [10]. Among the 241 cases we collected, 237 were single nodules, and 4 had 2-3 nodules; Most cases occur in middle-aged and young adults (20-60 years old), with an average age of 40 years old. The most common area is near the small joint of the right hand. Most preoperative clinical manifestations are painless nodules with slow growth, with a disease course ranging from half a month to 10 years. The average maximum diameter of the nodules after surgical resection is 1.8cm. The above is basically consistent with literature reports [2-4]. D-GCTS and PVNS are usually more common in large joints, such as the knee and shoulder joints, and are often invasive. They can damage joint structure, lead to joint function degeneration, and are prone to recurrence, even malignant transformation [11]. Compared with them, L-GCTS is more common near small joints and less common near large joints such as shoulder, knee, and elbow joints. It usually grows slowly and rarely causes damage to surrounding joints and tendons. However, continuous growth can sometimes damage surrounding bone and tendon tissues, which can affect the recovery of joint function [12]. And if not completely removed, there is also a risk of recurrence or even malignant transformation [4]. Among the 241 cases we collected, 5 cases were found to have invaded the surrounding bone through preoperative imaging and intraoperative examinations, all of which had a disease course of 5-10 years. Therefore, we suggest that patients with painless small nodules in areas such as hands and feet should seek medical attention in a timely manner if conditions permit, in order to clarify the nature of the disease and avoid its continuous growth, which may damage the surrounding bone and tendons and affect the subsequent recovery of joint and other functions. In addition, among the 241 cases, 6 were recurrent cases, and L-GCTS resection surgery was previously performed in our hospital or another hospital, which once again suggests that although it is a benign tumor, there is a risk of recurrence of L-GCTS.
Compared to L-GCTS, FTS is relatively rare, and large-scale studies on various aspects at home and abroad are relatively rare [5, 6]. It mainly focuses on case reports of cases in uncommon parts [13-15]. Therefore, like L-GCTS, FTS can also occur in some uncommon parts, which should be taken seriously in the clinical diagnosis and treatment process. FTS can also occur in any age group, with a high incidence age range of the third to fifth decades[5, 6]. Different from L-GCTS, FTS generally has more male patients than female patients [5] , and there are also reports of cases with similar incidence rate between men and women [6]. FTS is also common near small joints such as the wrist, palm, and fingers [5]. Cases of FTS occurring near larger joints such as the elbow, shoulder, knee, and ankle are relatively rare. Among these large joints, FTS is more common in the knee joint [16]. Like L-GCTS, FTS clinical symptoms often manifest as slow growing painless nodules [5, 6]. We collected 41 cases of FTS, with an onset age of 5-73 years and an average age of 35 years, most of which occurred in middle-aged and young adults (20-60 years old), consistent with literature reports; But perhaps due to the small amount of data we have, our cases mostly occur near the small joint of the left hand, which is inconsistent with literature reports and also different from L-GCTS. The clinical manifestations of most cases before surgery are slow growing painless nodules, with a disease course ranging from 10 days to 6 years. The average maximum diameter of the nodules after surgical resection is 1.9 cm, which is consistent with literature reports. Perhaps because our data volume is not large enough, the incidence rate of women in our group is slightly higher than that of men, which is not consistent with the literature report, but the difference is not significant. Compared with L-GCTS, FTS has less damage to surrounding bones and tendons, with only a few reports [7, 17,18]. In the study of 138 FTS samples by Chung EB et al. [5], only two cases showed damage to surrounding bone. Compared with L-GCTS, ensuring a clean surgical resection resulted in a lower recurrence rate of FTS. The 7 cases reported by Millon et al. [19] were followed up for 9 months to 3 years after complete surgical resection, and no recurrence occurred. In the study of 138 FTS samples by Chung EB et al. [5], the recurrence rate was 24%. The main reason for the high recurrence rate in this group of cases was analyzed, and it was believed that the tumor was often lobulated, which may lead to incomplete surgical resection. Therefore, it was emphasized that the tumor should be completely removed during surgery to reduce its recurrence rate.
By comparing the L-GCTS and FTS cases we collected and combining previous literature reports, we found that apart from L-GCTS being more common than FTS, the two cases are very similar in terms of clinical features, disease course, age of onset, lesion size, and overall appearance. In our cases, the two cases have slightly different common sites (L-GCTS is more common in the right hand, while FTS is more common in the left hand,but the difference is not significant). Preoperative imaging examinations such as ultrasound, X-ray and MRI sometimes make it difficult to make a clear diagnosis of both [20, 21]. In our case, 200 cases of L-GCTS underwent preoperative imaging examinations such as ultrasound, X-ray, or MRI. Among them, 178 cases had preoperative diagnosis consistent with postoperative pathological diagnosis, with a diagnosis rate of 89.0%. 38 cases of FTS underwent imaging examinations such as ultrasound, X-ray, or MRI. Among them, 21 cases had preoperative diagnosis consistent with postoperative pathological diagnosis, with a diagnosis rate of 55.3%. The main reason for the low diagnostic rate of preoperative imaging examinations is that imaging examinations are difficult to distinguish between the two,and possibly because of the low incidence rate of FTS, it is easy for preoperative imaging examination to misdiagnose it as L-GCTS. Therefore, relying solely on clinical features and imaging examination results to distinguish between the two can sometimes be challenging. However, in histopathology, L-GCTS is mainly composed of monocytes, multinucleated giant cells, foam like macrophages, inflammatory cells and fibroblasts with different proportions. Irregular fissures and glandular tubular structures can be seen in the stroma, collagen degeneration can be seen in some areas, and deposition of hemosiderin can be seen in some areas. Foam like macrophages are often distributed in sheets or maps. There are two types of monocytes. One type is small, round or spindle shaped, with light stained cytoplasm and round or kidney shaped nuclei, often with nuclear grooves; Another type of monocyte has a larger volume, epithelioid appearance, eosinophilic cytoplasm, round nucleus, and vacuolar shape. Mononuclear cells show mitotic figures with an average of 3-5/10HPF, but this cannot be used as evidence of malignancy. Osteoclastoid multinucleated giant cells are formed by the fusion of monocytes, with varying numbers of nuclei ranging from 3 to several hundred, dark red cytoplasm, and irregular shapes. Immunohistochemical staining showed that monocytes, foam like histiocytes and multinucleated giant cells in L-GCTS were positive for CD68, CD163 and Vimentin, some monocytes could also express Desmin, and SMA positive in focal fibroblasts [1, 2, 3]. According to the histological morphology, FTS can be divided into classical FTS and cellular fiber of tendon sheath (CFTS). Under the microscope, FTS often has clear boundaries. Classic FTS tumors have low cell density, loose arrangement, spindle shaped, mild morphology, no atypia, background collagenization, sparse arrangement of central tumor cells, high density around the tumor, and thin-walled slit like blood vessels visible in the stroma, which can be secondary to mucinous degeneration, cystic transformation, cartilage and ossification. A small amount of lymphocytes and plasma cells infiltrate the stroma, and individual mitotic figures can be seen. Polynuclear giant cells were occasionally seen in the areas with abundant cells, but the aggregation of foam cells was lacking. CFTS is often accompanied by classic FTS regions, and tumor cells are usually more abundant, arranged in short bundles or striations. Sometimes, there is a histological morphology similar to nodular fasciitis, and interstitial changes are the same as classical FTS [1, 5]. Therefore, L-GCTS and FTS exhibit differences in tissue morphology and immunohistochemical staining, and can be distinguished based on histopathology and immunohistochemistry.
In addition, in molecular genetics, most GCTS tumor cells carry chromosome translocation of 1p13 (CSF1 gene), often resulting in 2q35 (COL6A3) fusion, which promotes high expression of CSF1 mRNA in tumor cells. Tumor cells with high expression of CSF1 mRNA can regulate the growth, proliferation, differentiation, and osteoclast production of mononuclear macrophages [22]. Chromosomal translocation in tumor cells leads to the aggregation of a large number of reactive CD68 positive macrophages [23]. Research on FTS in molecular genetics is relatively rare. Carter et al. [24] used fluorescence in situ hybridization to detect rearrangements of the USP6 gene in 6 out of 9 CFTS cases. Mantilla et al. [25] found 7 out of 11 CFTS cases with USP6 gene rearrangement through second-generation sequencing. In the study by J Cui et al. [5] , it was found that 11 out of 20 cases of CFTS had USP6 gene rearrangements, and 1 case of classical FTS had USP6 gene rearrangements, suggesting that both CFTS and classical FTS can detect USP6 gene rearrangements. Therefore, the expression of L-GCTS and FTS in molecular genetics is also significantly different.
In summary, L-GCTS and FTS are very similar in terms of clinical features, disease course, predilection site, predilection age, tumor size, and tumor appearance. Sometimes, imaging methods such as ultrasound, X-ray, and MRI may also be difficult to distinguish between the two. The identification of the two mainly relies on histopathology and immunohistochemistry, and the two also have different molecular genetic manifestations. Although both L-GCTS and FTS are benign tumors, their recurrence rates and other prognostic factors differ. Therefore, it is necessary to clearly distinguish between the two.