The diagnosis and treatment of the epithelioid sarcomas involving the peripheral nerves

Abstract

Epithelioid sarcomas are rare soft tissue tumors and have possibility to involve the peripheral nerve and present as sensory and motor disorders. The symptoms are similar to those of nerve compression diseases. This situation is extremely rare in clinic and was only reported as several case reports in literature. It can be easily ignored and misdiagnosed in clinic and may bring out severe outcomes. From January 2003 to December 2017, a retrospective analysis of ten patients with epithelioid sarcomas which involved the peripheral nerves was made. The medical data, detailed clinical courses and the follow-up results were stated. In these cases, the tumors invaded the median nerve, ulnar nerve, radial nerve, brachial plexus, sciatic nerve and presented as relative symptoms. Early diagnosis and treatment are the keys to better prognosis. We recommended high-resolution ultrasound as a standard diagnostic tool for nerve compression syndromes not only reveal the morphological structure of the peripheral nerve, but also discover the tumor involving the nerve. Adequate surgical methods including wide resection and lymph node dissection if necessary. The manners of functional reconstruction need to be applied flexibly by the doctors. Postoperative rehabilitation is important for functional recovery. We want to share our experiences in the diagnosis and treatment to overcome this particular condition.

Introduction

Epithelioid sarcomas are rare soft tissue tumors that originate from mesenchymal tissue, which were first reported by Enzinger¹. Epithelioid sarcomas have unclear histogenesis, and most occur in extremities². Thus, epithelioid sarcomas have the possibility to involve the peripheral nerve and present as sensory and motor disorders. The symptoms and signs are similar to those of the nerve compression diseases. The relative cases are extremely rarely reported in literature. These situations are easy to be ignored and misdiagnosed in clinic and may bring out severe outcomes.

In this study, we made a retrospectively analysis of 10 cases of epithelioid sarcomas which involved the peripheral nerves and was misdiagnosed as nerve compression diseases at the beginning of the disease course from 2008 to 2017. Six of 10 cases underwent different manners of functional reconstruction including tendon transfer, suture the nerve directly, nerve transfer and nerve transplantation. Active functional rehabilitation was accomplished by all these patients after functional reconstruction, and good functional recovery was observed. We want to share our experiences in the treatment in these particular conditions.

Patients and methods

From January 2003 to December 2017, a retrospective analysis of the patients with epithelioid sarcomas which involved the peripheral nerves was made. Ten cases were enrolled. A tumor involving the peripheral nerve was confirmed preoperatively through high-resolution ultrasound in all cases. Ultrasound examination was performed on an EPIQ 5 color Doppler equipment. Pre- and intraoperative was done all cases in our study. Electrophysiology study was performed on a Keypoint 9033A07 Electromyograph / Evoked Potentials Equipment, testing electromyography, nerve conduction studies, and somatosensory evoked potentials. All the patients underwent surgery in our department. The tissue sources were originated from the tumor specimens resected intraoperatively in all cases. Immunohistochemical staining was accomplished for accurate pathological diagnosis.

The medical data of the patients were acquired, including gender, age, clinical presentation, the nerve which the tumor involved, tumor size, the disease first misdiagnosed as, the surgical method, and the pathological results. The patients were followed up at least 5 years. The followed-up data included the local recurrence, metastasis and adjuvant treatment. The detailed clinical data were stated in Table 1. The representative preoperative high-resolution ultrasound (Fig. 1), intraoperative (Fig. 2) and postoperative pathology images (Fig. 3) were showed.

Table 1.

The clinical data of the patients with epithelioid sarcoma.

No	Age	Sex	Largest dimension of the tumor (cm)	Location	The nerve which the tumor involved	Misdiagnosed as	Resection extension	Lymph node dissection	Reconstruct the function
1	35	Male	2.5	Elbow	Median nerve	Carpal tunnel syndrome	Extended	/	Tendon transfer
2	38	Female	1.5	Forearm	Ulnar nerve	Cubital tunnel syndrome	Extended	Yes	Tendon transfer
3	34	Male	0.8	Elbow	Ulnar nerve	Cubital tunnel syndrome	Extended	/	Suture directly
4	27	Male	7.5	Elbow	Ulnar nerve	Cubital tunnel syndrome	Extended	Yes	/
5	31	Female	1	Forearm	Radial nerve	Radial nerve neuritis	Extended	/	Tendon transfer
6	69	Male	2	Arm	Radial nerve	Radial nerve neuritis	Extended	/	Nerve transplantation
7	43	Male	11	Axilla to Arm	Branch of the brachial plexus	Cervical spondylosis	Extended	Yes	/
8	49	Male	1.2	Infraclavicular region	Lateral cord	Cervical spondylosis	Extended	/	Nerve transfer
9	62	Male	4	Supraclavicular region	Lower trunk	Thoracic outlet syndrome	Open biopsy	No	/
10	50	Female	12	Buttock	Sciatic nerve	Lumbar disc herniation	Open biopsy	No	/

CK	VIM	EMA	CD34	INI-1	Adjuvant therapy	Local recurrence	Distant metastasis	Survival time after diagnosis (months)	Status
+	+	+	+	-	No	No	No	> 60	Disease-free survival
+	+	+	+	-	No	No	No	> 60	Disease-free survival
+	+	+	+	-	No	No	No	> 60	Disease-free survival
+	+	+	+	-	Radiotherapy	Yes	No	> 60	Survival
+	+	+	+	-	No	No	No	> 60	Disease-free survival
+	+	+	+	-	No	No	No	> 60	Disease-free survival
+	+	+	+	-	Radiotherapy	Yes	Yes (Lung)	8	Died of the disease
+	+	+	+	-	No	No	No	> 60	Disease-free survival
+	+	+	+	-	Radiotherapy, Chemotherapy	/	Yes (Skin)	23	Died of the disease
+	+	+	+	-	Radiotherapy	/	Yes (Lung)	15	Died of the disease

Fig. 1.

Preoperative high-resolution ultrasound images: The typical imaging data of the tumor and the peripheral nerve involved preoperatively shown by the high-resolution ultrasound.

Fig. 2.

Intraoperative figures: the tumros were extended resected in these cases: (A) The first case: The tumor was originated from the median nerve at the elbow. (B) The fourth case: The tumor involved the ulnar at the elbow. (C) The fifth case: The tumor was originated from the deep branch of the radial nerve at the forearm. (D) The seventh case: The tumor involved the branch of the brachial plexus and he brachial artery at the arm.

Fig. 3.

Postoperative pathology images: The representative image of hematoxylin–eosin staining (A), CK (B), VIM (C), EMA (D), CD34 (E) and INI-1 (F) were demonstrated in the figure. (magnification, *200).

Written informed consents for treatment and publication were acquired from the patients or their relatives in all cases. All procedures performed in studies were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration. The study was approved by the ethics committee of Huashan Hospital, Fudan University.

The first case involved the median nerve around the elbow. The symptoms of the patient presented mimic as carpal tunnel syndrome. The patient took mecobalamine and injected corticosteroids at the local hospital. However, the symptom of numbness became worse, and the muscle strength of thumb and index finger flexion gradually lost to Grade 0. A tumor was discovered through high-resolution ultrasound in our hospital. A tumor involved the median nerve around the elbow was confirmed intraoperatively. The intraoperative electrophysiology study confirmed the function of the median nerve loss completely. The tumor was resected with a negative surgical margin according to the frozen pathology. The paraffin-embedded pathological result revealed as epithelioid sarcoma. Tendon transfer was used to reconstruct the function of finger flexion and thumb opposition 9 months postoperatively. The patient was diseased free for over 5 years.

The second case involved the ulnar nerve at the forearm. The patient’s symptoms were presented mimic cubital tunnel syndrome and misdiagnosed at the local hospital and underwent ulnar nerve decompression at the elbow. The symptoms relieved for 2 months and deteriorated rapidly. An ulnar nerve tumor at the forearm and the enlargement of the supratrochlear and axillary lymph nodes were discovered through the high-resolution ultrasound. The tumor involved the ulnar nerve and the enlargement of the supratrochlear and axillary lymph nodes were confirmed during the operation. The tumor was completed resected with a negative margin according to the frozen pathology. The supratrochlear and axillary lymph node dissection was also made. The postoperative pathological result showed as epithelioid sarcoma with lymphatic metastasis. Tendon transfer was used to reconstruct the function of lumbrical muscles one year postoperatively. The patient was diseased free for over 5 years.

The third and the fourth case involved the ulnar nerve around the elbow, and the symptoms presented as cubital tunnel syndrome at first. The third patient was misdiagnosis as cubital tunnel syndrome at the local hospital and injected mecobalamine. However, the symptoms deteriorated rapidly. A small ulnar nerve tumor in the cubital tunnel was discovered through the high-resolution ultrasound. The tumor was confirmed intraoperatively and completed resected with a negative margin according to the frozen pathology. As the small size of the tumor, the ulnar nerve was sutured directly with the flexion of the elbow. The function of the ulnar nerve was partially recovered according to the follow-up. The patient was diseased free for over 5 years.

The fourth patient underwent ulnar nerve decompression at the elbow at the local hospital. However, the symptoms still gradually deteriorated. Besides, a rapidly growing tumor was palpated. A large tumor involved the ulnar nerve and the enlargement of trochlear lymph node were confirmed by high-resolution ultrasound and MRI. Open biopsy was taken at first at our department, and the pathological result showed as epithelioid sarcoma. The tumor together with the ulnar nerve was extensively resected. The lymph node dissection was also made. However, the tumor locally recurred 2 years postoperatively while there was no metastasis. The patient underwent shoulder disarticulation in the other hospital. The patient was survived for over 5 years.

The fifth case involved the deep branch of the radial nerve at the forearm. The patient presented as the muscle strength decline of finger extension. The patient was misdiagnosed as radial nerve neuritis at the local hospital. Mecobalamine was taken for treatment at first. However, the symptoms gradually deteriorated. The patient came to our hospital until the muscle strength of finger extension was Grade 0. A tumor involved the deep branch of the radial nerve was discovered by high-resolution ultrasound. The tumor involved the deep branch radial nerve was discovered intraoperatively. The tumor was completed resected with a negative surgical margin according to the frozen pathology. The postoperative pathological result showed as epithelioid sarcoma. The patient received tendon transfer to reconstruct the motion of thumb and finger extension one year postoperatively. The patient was diseased free for over 5 years.

The sixth case involved the radial nerve at the arm. The symptom of the patient presented as lacking the strength of extension the wrist and fingers and feeling numbness of the dorsal radial side of the hand. The patient went to the local hospital and misdiagnosed as neuritis of radial nerve. Neurotrophic therapy was taken for 6 months. However, the patient’s wrist and finger extension muscles had gradually decreased to Grade 0 power. A tumor involved in the radial nerve at the arm was discovered by high-resolution ultrasound. The tumor was completed resected with a negative surgical margin according to the frozen pathology. The paraffin-embedded pathological result showed as epithelioid sarcoma. The superficial branch of radial nerve was used for nerve transplantation 6 months postoperatively. The motion of wrist and finger extension recovered 10 months after nerve transplantation. The patient was diseased free for over 5 years.

The seventh case involved the branches of the brachial plexus, including ulnar nerve, median nerve and radial nerve. The patient felt numbness of his fingers and went to the local hospital. The patient was diagnosed as cervical spondylosis according to the cervical vertebra MRI. However, the symptom of numbness deteriorated. The muscle strength of intrinsic and extrinsic muscles of hand was gradually decreased to Grade 1 to 2. However, the patient came to our hospital until a large mass was palpated from axilla to arm. A large tumor involved the median nerve, ulnar nerve, radial nerve and the enlargement of supratrochlear and axillary lymph nodes were discovered according to the high-resolution ultrasound and MRI. An open biopsy was taken. The pathological result showed as epithelioid sarcoma. The tumor together with the ulnar nerve, median nerve, radial nerve and brachial artery was extensive resected. The lymph node dissection was also made. A negative surgical margin was confirmed by the frozen pathology. The great saphenous vein was used for vascular transplantation. Pulmonary metastasis was discovered and the patient died of the disease 8 months postoperatively.

The eighth case involved the lateral cord of brachial plexus. The symptoms of the patient presented as the weakness of the elbow flexion and the numbness of the radial side of the hand. The patient was misdiagnosed as cervical spondylosis according to the cervical vertebra MRI at the local hospital. Mecobalamine and cervical gear were used for 1 year. However, the symptoms gradually worsen. The muscle strength of biceps decreased to Grade 0 while the electrophysiology study confirmed the result when he came to our department. The tumor was detected by the high-resolution ultrasound preoperative. A 1.2 cm tumor involved in the lateral cord was discovered through the surgery. The tumor was resected with a negative surgical margin according to the frozen pathology. The postoperative pathological result revealed as epithelioid sarcoma. Oberlin’s ulnar nerve transfer to the biceps motor nerve was accomplished 9 months postoperatively. The function of elbow flexion recovered 8 months after nerve transfer. The patient was diseased free for over 5 years.

The ninth case involved the lower trunk of brachial plexus and the symptoms presented as thoracic outlet syndrome. The patient was misdiagnosis as thoracic outlet syndrome by our department according to the clinical presentation and the electrophysiology study result at first. Conservative treatments such as functional training, mecobalamine and corticosteroids had all be tried. However, the symptoms improved for a short time and gradually deteriorated. At that time, there was no high-resolution ultrasound in our hospital. A surgical release of the lower trunk was done in our department. No tumor was discovered during the surgery. The symptoms improved at first and gradually deteriorated 6 months postoperatively. A large mass was detected by MRI 2 years postoperatively. At that time, the function of intrinsic and extrinsic muscles of hand completely lost. The supraclavicular, subclavicular and axillary lymph node enlargement was detected by ultrasound. An open biopsy for the tumor and the lymph node was made. The pathological result was epithelioid sarcoma with lymph node metastasis. The patient decided to abandon due to the progress of the disease and take radiotherapy and chemotherapy instead. Cutaneous metastasis was discovered according to the follow-up. The patient died of the disease 23 months after the open biopsy.

The tenth case involved the sciatic nerve and presented as sciatica. The patient was misdiagnosed as lumbar disc herniation and took conservative treatment at the clinic in rural areas. The symptoms became worse and a large tumor was discovered by MRI. A tumor originated from the sciatic nerve and the enlargement of the inguinal lymph nodes were discovered by high-resolution ultrasound at our hospital. An open biopsy was made in our department. The pathological result showed as epithelioid sarcoma. Because of her high age, economic reason and strong willing to preserve lower limb function and maintain quality of life, the patient refused to take extended resection. Postoperative radiotherapy was taken. Pulmonary metastasis was discovered and the patient died of the disease 15 months after the biopsy.

Results

From January 2003 to December 2017, 10 patients with epithelioid sarcoma involved the peripheral nerve were enrolled in this study. The age of the patients ranged from 27 to 69 years old. The mean age was 43.8 years old. Seven were male while three were female. The diameters of the three tumors were over 5 cm, while the others were less than 5 cm. The tumors located from the forearm to the supraclavicular region, and one from the buttock. The nerves in which the tumors involved included median nerve, ulnar nerve, radial nerve, brachial plexus and sciatic nerve. None of the tumors presented as a palpable mass at the beginning of the course. All the 10 patients were misdiagnosed as nerve compression diseases. One patient was misdiagnosed as carpal tunnel syndrome, 3 as cubital tunnel syndrome, 2 as radial nerve neuritis, 2 as cervical spondylosis, 1 as thoracic outlet syndrome and 1 as lumbar disc herniation. The detailed clinical data were stated in the table (Table 1).

Only 2 tumors in this research were discovered by a palpable mass preoperatively, while the other tumors were detected by high-resolution ultrasound and/or MRI. These all pointed out that only symptoms, physical examination and electrophysiology study result are not enough for accurate diagnosis. Under these circumstances, without high-resolution ultrasound and/or MRI, misdiagnosis is unavoidable. Misdiagnosis and mistreatment may do severe harm to the patients. The location of most tumors involving the peripheral nerve in the limbs is superficial. For superficial tumors, high-resolution ultrasound is extremely important for diagnosis. The preoperative typical imaging data of the tumor and the peripheral nerve involved shown by high-resolution ultrasound were demonstrated in the figure (Fig. 1).

Enlargements of lymph nodes were also detected in 5 patients by ultrasound and the lymph node metastasis were also confirmed intraoperatively and postoperative pathological results. Whether the patients had lymph node metastasis postoperatively was also detected according to the ultrasound.

Extended resection was done in 8 cases. Two patients underwent partial resection considering the progression of the disease and the advanced age. Lymph node dissection was accomplished in 3 patients with enlargement of lymph nodes. The nerve was sutured directly in 1 ulnar nerve tumor as the tumor was small and the location was around the elbow. As the radial nerve at the arm was removed, the superficial branch of the radial nerve was used for nerve transplantation in 1 case. Oberlin’s ulnar nerve transfer to the biceps motor nerve was accomplished in another case 9 months postoperatively. Tendon transfer was performed for motion reconstruction in 3 cases. The intraoperative photos showed the relationship between the tumors and the peripheral nerves involved were presented in the figure (Fig. 2).

According to the immunohistochemical staining results, CK, VIM, EMA and CD34 were positive while INI-1 was negative in all the samples. The representative image of hematoxylin–eosin staining, positive expression of CK, VIM, EMA, CD34 and negative expression of INI-1 were demonstrated in the figure (Fig. 3).

Three patients took only postoperative radiotherapy, while one took both radiotherapy and chemotherapy. The others didn’t take any adjuvant therapy considering their advanced age and/or economic ability. Local recurrence happened in 2 cases after extended resection. Distant metastasis happened in 3 cases. Three patients died of the disease in 5 years. Seven patients were alive for over 5 years, 6 of which were disease-free for over 5 years. The detailed clinical data were stated in the table (Table 1).

Discussion

Epithelioid sarcomas are rare soft tissue tumors that originate from mesenchymal tissue with a high risk of local recurrence, regional and distant metastases. The tumor can be divided into the proximal type and the distal type². The pathogenesis of the tumor is unknown, and some cases have a history of trauma to the corresponding tumor site^3,4. The only recurrent genetic alteration reported in epithelioid sarcoma as yet is the functional inactivation of INI-1, a key component of the SWI/SNF chromatin remodeling complexes⁵.

The histogenesis of the epithelioid sarcoma is unclear. It can originate from the skin, tendon, muscle, synovium and nerve. The tumor originate from the peripheral nerve is extremely rarely seen in clinic. Most studies were stated as case report in literature. Agarwal⁶, Dorsi⁷, Maeda⁸ and Li⁹ reported an epithelioid sarcoma arising from the sciatic nerve, respectively. Poloni¹⁰ presented an epithelioid sarcoma originated from the common fibular nerve. Harish¹¹, Fujii¹², Uceda¹³ presented an epithelioid sarcoma arising from the median nerve, whose symptoms and signs mimicking carpal tunnel syndrome, respectively. Monacelli¹⁴ stated a case that Dupuytren’s disease simulated epithelioid sarcoma with atypical perineural invasion of the median nerve. Wadhwa¹⁵ presented a case of radial mononeuropathy caused by epithelioid sarcoma. The only case series reported in the literature was stated by Diaz-Perez¹⁶. They presented 2 tumors originated from the sciatic nerve while 1 originated from the ulnar nerve. In our study, we present a large series of this particular condition, which is scarcely reported according to literature and is extremely meaningful in clinic.

In our study, 1 patient was misdiagnosed as carpal tunnel syndrome, 3 as cubital tunnel syndrome, 2 as radial nerve neuritis, 2 as cervical spondylosis, 1 as thoracic outlet syndrome and 1 as lumbar disc herniation. In fact, the tumors invaded the median nerve, ulnar nerve, radial nerve, brachial plexus, sciatic nerve and presented as relative symptoms. To our knowledge, epithelioid sarcomas involving the brachial plexus had not been reported in literature. In 2 cases, the doctors even didn’t discover the tumor through surgery. Many doctors are accustomed to inject corticosteroids under the epineurium just after nerve decompression. If the tumor was not discovered during the surgery, this may stimulate the growth of the tumor.

Only 2 tumors in this research were discovered by a palpable mass preoperatively. Most tumors could not be palpated at the beginning of the disease course due to the deep location or the small size. Doctors might misdiagnose epithelioid sarcomas which involved the peripheral nerve as nerve compression diseases according to the clinical presentations, electrophysiology study result and/or spinal MRI. High-resolution ultrasound is not regularly used for nerve compression disease in clinic. When the sensory and motor disorders were not severe, or the tumor could not be palpated, the doctor might choose corticosteroids for local blocking, which could promote the tumor progression. It was really a challenge for early diagnosis and early treatment. It should be emphasized that excluding tumors is necessary for the patients whose symptoms resembled those of the nerve compression diseases. High-resolution ultrasound can not only reveal the morphological structure of the peripheral nerve, but also find the nerve originated tumor or the tumor which compresses the peripheral nerve. We recommended high-resolution ultrasound as a standard diagnostic tool for nerve compression syndromes.

Clinical presentations and electrophysiology study results are not enough for these conditions. High-resolution ultrasound is recommended to avoid misdiagnosis and mistreatment in clinic. In the cases in our study, the ultrasound image was presented as an irregular, hypo-echogenic mass with clear border, which connected to the fasciculus. It’s inner echogenecity was homogeneously distributed. However, the image of epithelioid sarcomas in both ultrasound and MRI is not typical. It is difficult to distinguish epithelioid sarcomas from benign tumors in most conditions. Compared with MRI, high-resolution ultrasound has several advantages. Firstly, high-resolution ultrasound can show more details of the relationship between the tumor and the peripheral nerve, which can help the surgeons during the surgery. Most tumors involving the peripheral nerves in the extremities are relatively superficial, which can be detected clearly enough by high-resolution ultrasound. Secondly, the enlargement of lymph nodes can be detected more clearly by ultrasound. PET could be considered as another choice with lymph node metastases. However, In our country, the cost of PET is more than 30 times than that of ultrasound. In addition, the cost of PET cannot be reimbursed by medical insurance, while ultrasound can. Thirdly, high-resolution ultrasound can be applied in the patients with claustrophobia. Fourthly, the fee of high-resolution ultrasound is cheaper compared with MRI. However, MRI is more capable for the tumors with deep location. The technique needs by the ultrasound doctor is extremely high for the tumor in the deep location.

It is widely acknowledged that wide local excision and regional lymph nodes dissection were the first choice of treatment (2, 17). Wide local excision could be done by the surgeons in most situations if possible. However, lymphatic metastasis does not exist for most soft tissue sarcomas. Thus, many doctors only focused on hematogenous metastasis and omitted the lymphatic metastasis. Besides, epithelioid sarcomas are often associated with infection, which can also lead to the enlargement of lymph nodes. These all pointed out the importance of preoperative ultrasound. Lymph nodes dissection needed to be done together with the resection of the tumor when enlargement of lymph nodes was detected. Furthermore, ultrasound for lymph node is also important for postoperative follow-up.

Eight cases in our study underwent extended resection. Lymph node dissection was accomplished in 3 patients with enlargement of lymph nodes. According to different situations, 5 patients underwent functional reconstruction by different manners, including tendon transfer, nerve suture, nerve transplantation and nerve transfer. The manners of how to reconstruct the patients’ function need to be applied flexibly by the doctors. Sometimes, the nerve can suture directly after the R0 resection of the tumor, as the size of the tumor is small or the location was around the joint. Compared with using the sural nerve or the superficial branch of the radial nerve for nerve transplantation, tendon transfer may be a better choice for functional reconstruction. However, in 1 case in this study, we used the superficial branch of the radial nerve for nerve transplantation as the tumor originated from the trunk of the radial nerve. As the the trunk of the radial nerve was resected together with the tumor. It is a good choice to use the disused distal side of the radial nerve superficial branch as the transplanted nerve. We took nerve transplantation 6 months postoperatively without local recurrence and metastases. It is well recognized in the literature that the recovery of motor function after radial nerve transplantation is superior to tendon transposition. That was the reason why we chose nerve transplantation in this case. Nerve transfer is another choice. In 1 case, we used Oberlin’s ulnar nerve transfer to the biceps motor nerve to reconstruction the function of elbow flexion. In certain circumstances, dorsal approach in transfer the spinal accessory nerve to the suprascapular nerve, transfer of the long head of triceps nerve branch to the anterior branch of axillary nerve to treat, pronator teres branch and/or brachialis branch transfer to the anterior interosseous nerve, and supinator branch transfer to the posterior interosseous nerve can also been applied. After the removal of the external fixation, all the patients underwent active functional rehabilitations. According to the follow-up, all the functions damaged by the tumors were completely or partially recovered.

The pathological diagnosis of epithelioid sarcomas is of great challenge. In our cases, all the epithelioid sarcomas invaded the peripheral nerves. Core needle biopsy may risk damaging the peripheral nerves. Conversely, fine needle biopsy may not be able to obtain sufficient tissue volume for accurate pathological diagnosis of epithelioid sarcomas. Immunohistochemical staining results were extremely important for differential diagnosis. CK, VIM, EMA, CD34 are usually positive in epithelioid sarcomas. However, almost all the cases of epithelioid sarcomas had loss of expression of INI-1¹⁸. CK is used as the differentiation of epithelial tumors from non-epithelial tumors. VIM is used as the differentiation of epithelial tumors from mesenchymal tumors. The expression of EMA is also positive in many kinds of soft tissue tumors. EMA is also used as the differentiation of epithelial tumors from mesenchymal tumors. CD34 and INI-1 are used as the diagnosis and differential diagnosis of many kinds of tumors. In our study, CK, VIM, EMA and CD34 were almost all positive while INI-1 was all negative in these ten samples according to the immunohistochemical staining results.

Postoperative chemotherapy and radiotherapy are controversial in the literature for epithelioid sarcomas. Traditional studies have suggested the benefit of adjuvant high-dose radiotherapy in reducing the risk of recurrence, maintaining functionality, and improving overall outcomes. Chemotherapy’s role in the treatment of epithelioid sarcomas is far less adequately defined than surgery and radiotherapy¹⁹. However, Kim stated that the clinical benefit of radiotherapy and chemotherapy was observable only in proximal type, but not in distal type²⁰. Besides, Elsamna regarded that whether radiotherapy was performed or not did not matter as long as surgery was undertaken²¹. In our study, 3 patients took only postoperative radiotherapy, while 1 took both radiotherapy and chemotherapy. We could not draw out a conclusion of the effect of radiotherapy or chemotherapy according to our follow-up.

According to the literature, the overall 1-year, 3-year and 5-year survival were 70.7, 56.1 and 50.4%, respectively. The overall recurrence and metastasis rates were 63.4% and 40.3%. Age more than 56 years old, higher tumor grade, tumor size over 5 cm and the presence of metastasis are related to poor prognosis^21,22.

For clinical doctors, this research can provide some certain reference significance. The symptoms of epithelioid sarcomas involving the peripheral nerves are similar to those of the nerve compression diseases, which usually led to misdiagnosis and mistreatment. A palpable mass especially in deep location is too late for the patients. We emphasized the importance of the high-resolution ultrasound in diagnosis. Corticosteroids injection needs discretion. Wide local excision and regional lymph nodes dissection are the first choice of treatment. We should not ignore the lymph node metastasis pre- and postoperatively. The tumor should be resected together with the peripheral nerve involved. A negative surgical margin according to the frozen pathology is essential during the operation. Whether to use tendon transfer, nerve transplantation, nerve transfer or suture the nerve directly for functional reconstruction needs to be applied flexibly by the doctors. Postoperative chemotherapy and radiotherapy are still controversial in the literature. The patients need close follow-up to discovered the local recurrence and/or lymph node metastasis as early as possible.

At last, we should point out our limitations. Firstly, A strong limitation is the lack of pre- and postoperative MRI imaging. As most of our patients underwent preoperative MRI at local hospital. They also underwent postoperative MRI at local through follow-up. This phenomenon is extremely common in our country. Besides, the emphasis on pain was extremely low in the past few years in our country. We did not get enough information about patients’ pain in clinic. Furthermore, the sample of our study is small, and we couldn’t get a definite conclusion of the prognostic factors. A multi-center clinical study, should be conducted to collect more data to overcome the defect. Furthermore, a longer follow-up time is needed.

Conclusions

Epithelioid sarcomas involving the peripheral nerves are extremely rare in both clinic and literature. The symptoms presented were similar to those of the nerve compression diseases, which usually led to misdiagnosis and mistreatment. Early diagnosis and early treatment are the keys to better prognosis. We emphasized the importance of the high-resolution ultrasound in diagnosis. Wide local excision and regional lymph nodes dissection are the first choice of treatment. Functional reconstruction needs to be applied flexibly by the doctors. Postoperative rehabilitation is important for functional recovery.

Through this study, we want to share our experiences in the diagnosis and treatment to overcome this particular condition in clinic.

Author contributions

XJ and CY collected and analyzed the data and wrote the manuscript. CY and LC designed the study and revised the manuscript. TK offered reference advice.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Written informed consents for treatment were acquired from the patients or their relatives in all cases. All procedures performed in studies were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration.

Patient consent for publication

Written informed consents for publication were acquired from the patients or their relatives in all cases.