Jie Gao,Yu-Song Yuan,Ting Liu,Hao-Run Lv,Hai-Lin Xu

Abstract

Key words: Imaging examination;Pathological examination;Plantar;Synovial sarcoma;Case report

INTRODUCTION

Synovial sarcoma (SS) was first reported by Knox in 1936,who believed that SS originated from synovial cells[1].In 1938,Berger defined SS as a tumor that occurred in the synovium,bursa,and tendon sheath[2].Later,in 2013,the World Health Organization classified SS as a tumor of indefinite origin[3]that could be divided into single phase,double phase,and poorly differentiated lesions based on its pathological characteristics.SS is the fourth most common soft tissue sarcoma[4],accounting for 5%-10% of soft tissue sarcomas[5].It often occurs in boys and men aged 15-35 years old[6,7],with a male/female ratio of about 1.2：1.0[8,9].SS is commonly found in soft tissues around the large joints of limbs,especially in soft tissues near the knee joint[10].A plantar SS is rare.The 5-year survival of SS patients is 61%-80%,and the 10-year survival is 10%-30%[11,12].

It has been found that SS correlates closely with translocation of chromosomes 18 and X,which generates the SYT-SSX fusion gene now existing in no other disease but SS.Therefore,the molecular cytogenetic examination of T (x;18) (p11.2;q11.2) and SS18-SSX fusion gene transcripts has been considered the most important evidence for diagnosing SS[13].According to reported research[14],the sensitivity of fluorescencein situhybridization (FISH) and reverse transcription-polymerase chain reaction (RPPCR) for identifying SS are,respectively,about 80.0% and 83.8%,and their combined sensitivity is about 92.9%.

At present,there is no effective cure for SS[15].A timely,correct diagnosis and the proper surgical treatment at an early stage are essential for a good prognosis.Kartha and Bumpous[16]reported that performing an operation to remove the tumor with a diameter ＜ 5 cm is the treatment of choice for SS.For an SS with a diameter ＞ 5 cm,radiotherapy is needed prior to the surgery[16,17].In addition,Eilberet al[18]reported a randomized controlled trial showing that radiotherapy after surgery for SS increased the survival rate.

In 2016,Vlenterieet al[10]analyzed 3711 SS patients,among whom 313 had advanced-stage SS.They found that about 56% of the SSs at an advanced stage originated from limbs,and pulmonary metastasis was commonly detected (80%).Compared with other soft tissue sarcomas,metastasis of SS begins at an earlier age(median age,40 years),and men more often experience metastasis than women at the same age (male/female = 191：122).

SS is sensitive to chemotherapy and has a better prognosis than other sarcomas at the same stage[9].Recent research showed that chemotherapy for metastatic SS tumor with ifosfamide or doxorubicin could protract patients’ lives,whereas radiotherapy had no positive effect on patients’ prognosis[19].Trabectedin,a novel,targeted antitumor,cytotoxic drug,has been approved in Europe for treating advanced liposarcomas and leiomyosarcomas[20].Japanese researchers have shown that trabectedin plays a prominent role in repressing the growth of SS cells and has potential for use clinically in the treatment of SS[21].Surgery combined with chemotherapy or radiotherapy as comprehensive treatment for SS in current clinical practice may hopefully improve the survival rate of patients with SS.

We describe herein a case of SS in the plantar region of the foot misdiagnosed due to the patient’s complicated history of plantar trauma and repeated treatment for this atypical manifestation.The patient was misdiagnosed in different hospitals as having plantar fasciitis,soft tissue infection,and inflammatory granuloma.We assess the reason for these misdiagnoses and finally conclude that when a patient’s symptoms are not typical and evidence of the imaging examination is insufficient,a pathological examination is essential for a timely,correct diagnosis,which should be established as early as possible.

CASE PRESENTATION

Chief complaints

A 24-year-old man had a 4-year history of a left plantar injury from which he recovered within several days without treatment and with no mobility obstacles.

History of present illness

Currently,the patient suffered unexplained pain during walking in his left plantar region for almost a week.He noted some swelling in the left plantar area but no fever,chills,or pain.He took some nonsteroidal anti-inflammatory drugs,which partly relieved his walking-induced pain.The pain recurred within 3 d,however,at which time he visited a hospital where he was treated with acupuncture.The pain was once again relieved,although 2 d later it returned,hampering his mobility.He was brought to our hospital in an armchair (Peking University People’s Hospital).

History of past illness

Since the onset of his walking pain,the patient had experienced no problems with his mental state,diet,sleeping,or weight.

Personal and family history

The family history was unremarkable.

Physical examination upon admission

Physical examination showed some swelling in his left plantar region and ecchymosis(1.5 cm × 1.5 cm) with accompanying tenderness at that site.When he back-stretched his left foot,the fourth toe had sharp pain.No mass was found in his left plantar area.

Laboratory examinations

Routine blood examination showed a white blood cell count of 10.06×109/L and Creactive protein level was 9.51 mg/L.

Imaging examination

Plain radiography of his left plantar was normal (Figure 1).Color Doppler ultrasonography showed an inhomogeneous mass in the plantar area of the left foot (Figure 2),and magnetic resonance imaging (MRI) suggested that it could be a benign tumor or tumor-like lesion,such as inflammatory granulation or a giant cell tumor in the tendon sheath (Figure 3).

FINAL DIAGNOSIS

Taking into account the patient's disease history,symptoms,and examination findings,however,his suspected diagnosis was a soft tissue infection in the left plantar area.

TREATMENT

He was treated with antibiotics (cefuroxime,1500 mg,bid,i.v.) for 3 d,which relieved the walking-induced pain,and his laboratory values returned to normal,with a white blood cell count of 6.90 × 109/L and erythrocyte sedimentation rate of 7 mm/h.He was discharged from the hospital on postoperative day 7 and continued to take cefuroxime orally as directed.

On day 11 after his discharge,his pain recurred,and he was again admitted to our hospital,this time demanding that we remove the mass in his left plantar region.Physical examination showed a swelling in the left plantar area and ecchymosis (1.5 cm2× 1.5 cm2) in the left plantar region with accompanying tenderness (Figure 4).The mass had no clear margins with its surroundings,and the blood supply and nerves of the left plantar area were normal.We removed the mass on day 2 after admission,then used cefuroxime infusion as his last hospital stay.The lesion measured 3.0 cm ×1.5 cm × 1.5 cm and was elliptical,lobulated,yellowish gray,and soft (like adipose tissue).It had been located between the foot plantar flexion tendons and metatarsal with clear boundaries.

Figure1 Plain radiography of the patient’s left plantar.

Postoperative pathological examination showed a focal adenoid structure,composed partly of interstitial fibrosis and multinucleated giant cells with scattered hemosiderin deposition.The HE staining showed a sign of tumor cell type (Figure 5).Immunohistochemical staining showed the following：CK (adenoid area) (+),CK7(adenoid area) (+),desmin (-),CD34 (blood vessels) (+),TLE1 (+),S100 (-/+),P63 (-),KP-1 (coenocytes) (+),and KP-1 (+5%).The pathological diagnosis was SS (bipolar).

OUTCOME AND FOLLOW UP

This patient received postoperative chemotherapy with doxorubicin and cyclophosphamide for 2 mo,after which no metastasis was found.

DISCUSSION

This case of SS,with a 4-year history of plantar trauma,the inflammatory symptoms during the treatment,and the indication of a benign mass without a clear boundary on imaging,was easily misdiagnosed.Typical SSs are commonly found in deep soft tissue and manifest as a large mass with slow growth.In addition,they most often are accompanied by focal pain or tenderness.The average incubation of SS is 2-4 years,with some even reaching 20 years[22].The patient discussed herein had an SS in his left plantar region after having experienced plantar trauma 4 years prior.In addition,his symptoms had not presented until about 2 wk before his first visit to the hospital complaining of plantar pain.

Walking-induced pain in the left plantar region in a patient with a history of plantar trauma 4 years prior is not commonly related to a malignant tumor,which caused the misdiagnosis at his first visit.When he was admitted to our hospital,the laboratory and imaging examinations suggested a benign mass due to infection that may have been caused by his prior acupuncture treatment.Thus,he was misdiagnosed as having a left plantar infection,which was relieved by the prescribed antibiotic treatment.When he returned a few days later,combined with the surgical findings,he was misdiagnosed a second time as having an inflammatory granuloma in the left plantar region.The patient was finally diagnosed correctly during the pathological examination as having SS.Without a pathological examination,SS of this kind could easily to be misdiagnosed,which could cause a great loss of the patient’s quality of life.

The mechanism of SS is not fully understood.A few cases have been reported in which SS may have a correlation with the use of radiotherapy[23,24],and some believe that calcified SS may be related to trauma.Murpheyet al[4],however,argued that trauma has nothing to do with SS and that SS causes some clinical symptoms that might increase the possibility of discovering it after trauma.Regretfully,in this case,the patient did not seek for medical help immediately,so no imaging details were available to study whether the plantar trauma that occurred 4 years prior was related to the development of the SS.

Figure2 Doppler ultrasonography showed an inhomogeneous mass in the plantar area of the left foot.

To better understand SS,we searched PubMed for articles about SS published from 1953 to 2017.We found that,except liposarcoma,almost all other soft tissue sarcomas lack peculiar manifestations during imaging examinations,and the diagnostic rate for SS is just 25%[25].The images of SS have no apparent specificity,although there are some peculiar manifestations[26,27].SS commonly manifests on computed tomography(CT) as a heterogeneous mass with low density and inapparent boundaries compared with the normal surrounding tissues.These characteristics may be intensified by different degrees with enhanced CT.On MRI,SS manifests as having clear boundaries and swelling around the mass,mainly equivalent signals on T1-weighted images(mixed with some higher signals) and compound signals in T2-weighted images[4,28],and this is one of the reasons for misdiagnosing SS as a benign tumor.Therefore,whether there is a clear boundary cannot be regarded as proof for distinguishing whether a mass is benign or malignant or the degree of histological differentiation[29,30].

CONCLUSION

The MRI results in this case conform to the characteristics reported above (i.e.,a round mass with a clear boundary and compound signals on T2-weighted images),ensuring its easy diagnosis as a benign tumor.Under such a circumstance,CT should be performed to further determine if it might be SS.If the results do not clearly indicate that it is SS,a pathological examination for the correct diagnosis is needed.

Figure3 Magnetic resonance imaging suggested that the lesion could be a benign tumor or tumor-like lesion,such as inflammatory granulation or a giant cell tumor in a tendon sheath.

Figure4 Physical examination showed a swelling in the left plantar area and ecchymosis (1.5 cm2 × 1.5 cm2) in the left plantar region with accompanying tenderness.

Figure5 Hematoxylin-eosin staining showed a sign of tumor cell type.