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Synovial sarcoma of the transverse colon metastatic to the chest wall after 3 years of follow-up
  1. Viviana Marcela Hidalgo Mora1,
  2. David Ricardo Baquero Zamarra2,
  3. Maria Angelica Cendales3 and
  4. Carlos Edgar Figueroa Avendaño2
  1. 1Universidad Militar Nueva Granada - Hospital Militar Central, Bogota, Colombia
  2. 2Hospital Universitario Mayor - Méderi, Bogota, Colombia
  3. 3Universidad Del Rosario - Hospital Universitario Mayor Méderi, Bogotá, Colombia
  1. Correspondence to Viviana Marcela Hidalgo Mora; viviana.hidalgo{at}urosario.edu.co

Abstract

We report a fifth case of a transverse colon primary synovial sarcoma. A 31-year-old man with history of grade I obesity presented to an outpatient clinic reporting 6 months of intermittent colicky abdominal pain associated with haematochezia and rectal bleeding. Colonoscopy reported a partially obstructive intraluminal tumour lesion located in the transverse colon. There was no evidence of metastatic disease in the extension studies, so the patient was admitted to the hospital for a laparoscopic subtotal colectomy. Histopathology demonstrated intermediate-grade synovial sarcoma. At the third year of follow-up, the patient presented metastases on the chest wall, which required extensive resection and complementary oncological management.

  • colon cancer
  • surgical oncology
  • gastrointestinal surgery
  • pathology

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Background

Colorectal sarcoma is a very rare entity. Existing evidence is limited to only case reports of treatment and evaluation of this pathology. There is not enough literature to establish a consensus on management and treatment. Regardless of the anatomical location, the literature agrees that synovial sarcoma is generally considered an aggressive, high-grade lesion, with a 5-year survival of 60% and a 10-year survival of 50%. The importance of this case lies in the rare involvement of the colon and contributes to the generation of evidence for management of this pathology, being a special case because there are even fewer reports of colonic sarcoma presenting with metastases at follow-up after primary control.

Case presentation

A 31-year-old man, with history of grade I obesity and without personal or family history of gastrointestinal pathology or cancer, showed up at an outpatient clinic with intermittent colic-type abdominal pain of approximately 6 months of evolution associated with rectal bleeding, frequent abdominal distension and constipation. Colonoscopy was performed in an outpatient setting, reporting a tumour lesion 80 cm from the anal border. It was a pseudo-pedicled lesion that generated intussusception and a valve effect causing the patient’s partial obstruction symptoms. A tattoo was made distal to the base of the lesion due to its mobility as well as to locate it during surgery (figure 1). Due to recent gastrointestinal findings and symptoms, a hospital admission was recommended to allow further studies and to prioritise surgical management.

Figure 1

Partially obstructive mass visualised in the mid-distal transverse colon on colonoscopy compromising 70% of the lumen and 40% of the circumference.

Investigations

Abdominal and pelvic CT was performed with findings of a transmural mass in the transverse colon, measuring 6 cm in length, which retracted the wall, without evidence of infiltration of the pericolonic fat. It was not possible to define regional adenomegalies, mesenteric or retroperitoneal (figure 2).

Figure 2

Transverse mass (yellow arrows) as observed on CT of the abdomen and pelvis with contrast: (A) axial, (B) sagittal and (C) coronal.

Contrast chest tomography showed a lesion in the middle lobe in relation to minor fissure that corresponds to intrapulmonary lymph nodes and a nodule with a soft tissue density of 4 mm in the left lower lobe (posterior segment). It was not possible to define the aetiology, but appeared to be benign lesions. For this reason, the patient was evaluated by chest surgery to continue outpatient follow-up.

Differential diagnosis

Among the most common causes of lower gastrointestinal tract obstruction are adenocarcinomas, neuroendocrine tumours, lymphomas and diverticular disease.1 Histologically, the majority of colon cancer is adenocarcinoma. However, clinical, endoscopic and imaging differentiation from synovial sarcoma is challenging due to similar behaviour and characteristics such as bulky presentation and exophytic and polypoid growth projected in the lumen associated with both obstruction and rectal bleeding.2

Treatment

Analysis indicated carcinoembryonic antigen of 0.98 ng/mL, albumin of 4.9 g/dL and total protein of 7.9 g/dL, so the patient was admitted to the hospital and underwent an extended right colectomy by laparoscopy, together with primary laterolateral ileocolonic anastomosis with an oncological R0 margins and a minimally invasive approach. Together, treatment required a total of 7 days of hospitalisation due to a postoperative ileus, which delayed tolerance to oral intake.

Outcome and follow-up

Histopathology reported fusocellular sarcoma involving the entire colon wall with up to 8/10 mitosis, tumour size 5 cm in diameter and focal ulceration, without lymphovascular invasion or perineural invasion. The proximal and distal margins, the caecal appendix and the greater omentum were negative for tumour. Only 1 out of 33 lymph nodes was involved per tumour. Immunohistochemistry study showed positivity for CD99 and transducin-like enhancer 1 (TLE-1), focal for EMA and H-Caldesmon, and negative for CD117, DOG1, CD34, S100, Bcl-2, keratin and cytokeratin cocktail 7, and HHV8 with Ki-67 of 25%–30% (figure 3).

Figure 3

(A) Colon wall showing the presence of a tumour lesion that involves the entire wall of the colon, comprising spindle cells arranged in a random pattern with an atypical irregular nucleus (×4). (B) Atypical spindle cells with irregular pleomorphic nuclei arranged in a random pattern (×10). (C) Atypical spindle cells with an irregular nucleus, elongated with prominent nucleolus, pleomorphically arranged in a random pattern, associated with frequent mitosis (×40). (D) Ki-67 cell proliferation rate of 25%–30% (×10).

During oncological evaluation an intermediate-grade spindle cell sarcoma with histopathology and immunohistochemistry suggestive of synovial sarcoma pT4pN1aG2 was considered. Adjuvant management was indicated with six cycles of ifosfamide plus doxorubicin (first-line chemotherapy), a scheme from which he only received four cycles irregularly, as well as follow-up imaging done 18 months later due to administrative and financial constraints.

Three years later, the patient presented a palpable mass on the chest wall, in the middle third of the right hemithorax. A CT scan showed chest wall mass in the upper third of the right hemithorax with well-defined lobulated contours, predominantly solid with hypodense areas of necrotic appearance inside, measuring 115×102 mm in the axial plane, involving the fifth, sixth and seventh right costal arch.

Additionally, abdominal and pelvic CT, colonoscopy and endoscopy were performed at that time without involvement of other structures of the gastrointestinal tract and no evidence of neither local recurrence nor liver metastases.

In another medical institution, the patient was brought for resection of the lesion and reconstruction of the chest wall with a musculocutaneous flap of the transverse rectus abdominis, with histopathology reporting an undifferentiated malignant tumour that describes a high-grade sarcoma, poorly differentiated with a rhabdoid appearance. During surgery, diaphragmatic compromise, right pulmonary lobe, parietal pleura and pericardium were identified (figure 4), for which reasons the surgery was both hygienic and for improvement of the patient’s quality of life, but it was not R0 character. Postoperatively, he required hospitalisation for 29 days for flap dysfunction. Subsequently, palliative chemotherapy with ifosfamide was initiated because the previous cumulative dose of doxorubicin was unknown; however, it was not well tolerated and he was switched to pazopanib together with comprehensive cancer management.

Figure 4

Block resection of the chest lesion: (A) anterior and (B) posterior.

Discussion

Sarcomas of the colon, rectum and anus are rare, representing approximately less than 0.1% of all malignant pathologies in the lower gastrointestinal tract.3 Among the different types of sarcomas of the colon, leiomyosarcoma is the most frequent.3 4 Synovial sarcoma constitutes between 5% and 10% of all soft tissue sarcomas,5 and according to the Surveillance, Epidemiology and End Results (SEER) registry only 16 (5.8%) sarcomas have occurred in the colon.4

To date, four cases of synovial sarcoma in the colon have been reported. The first was in a young adult, where it was identified on sigmoid polypectomy, <20 mm in its largest diameter, with subsequent segmental resection of the colon without evidence of residual disease.6 The second case was in a paediatric patient which was secondary to intussusception after the splenic angle of the colon, required left hemicolectomy for a tumour lesion of 4×3.7×2.5 cm. No adjuvant chemotherapy was performed, with subsequent complete remission for 6 years, which was the reported follow-up time.7 The third case was of an adult woman with a colo-colonic intussusception in the transverse colon documented on tomography without perforation or obstruction and a colonoscopy revealing the presence of an obstructive mass in the middle of the transverse colon. With biopsies reporting ulcers without evidence of malignancy, she was taken for subtotal colectomy with ileo-descending anastomosis. Pathological evaluation showed an intramural biphasic synovial sarcoma of 9.3×6.5×5.0 cm pT2bpN0G2, with subsequent discharge on the sixth postoperative day and quarterly follow-up.1 The fourth case was of a man in his 40s with a medical history of undifferentiated pleomorphic sarcoma of the left upper arm and adenocarcinoma of the transverse colon; these tumours were successfully resected without subsequent recurrence. According to his medical and family history, genetic testing was performed and revealed a germline large deletion in exon 7 of the MSH2 gene, resulting in Lynch syndrome. Surveillance colonoscopy showed a submucosal tumour-like lesion in the sigmoid colon, 4 mm in size, which was treated by endoscopic mucosal resection without any complication at 6 months of follow-up.8

Synovial sarcoma is a malignant neoplasm of mesenchymal origin with epithelial differentiation. Its aetiology, including any specific cell of origin, remains unknown: neural, myogenic or multipotent mesenchymal stem cells have been weighed up as cause.5 9 It occurs predominantly in older children and young adults between 15 and 40 years, with a peak incidence in the third decade of life and a slight preponderance in men at a ratio of 1.2:1.1 3 5 9 So far, it has not been related to other diseases except for exposure to radiation or trauma in the extremities.5 It arises more commonly in the lower limbs, especially in the periarticular soft tissues (more frequently around the knee), hence the term synovium; however, the term synovium is historical and is misleading as it does not originate from the synovial membrane and no associated markers are expressed. Finally, synovial sarcoma can also occur anywhere in the body, including the oropharyngeal, respiratory, gastrointestinal, genitourinary and nervous systems and in the bone.1 5 9

The molecular genetics of this neoplasm are regarded as pathognomonic and are the diagnostic gold standard for carrying the t(X; 18)(p11.2;q11.2) translocation in 95% of cases of synovial sarcoma, SYT (SSX1, SSX2 or rare SSX4).9 10 Histologically, it is classified into (1) monophasic, which contains predominantly spindle cells related to low Ki-67 and SS18-SSX2 and is more frequent in adults (72%); (2) biphasic, containing spindle and epithelial cells linked with high Ki-67 and SS18-SSX15 9 11 12; and (3) poorly differentiated, usually found in older adults, characterised by necrosis, high mitotic activity, strange mitosis forms and nuclear atypia, as well as small round cell proliferation.5 9 Synovial sarcoma has a differentiation score of 3 based on the FNCLCC (Sarcoma Group of the French Federation of Cancer Centers) classification, where a score is assigned according to subtype and histological differentiation, mitotic count and amount of tumour necrosis; therefore, the minimum grade will always be grade 2 sarcoma with a 5-year survival of 75% and a grade 3 sarcoma with survival of 45%.5 13 14

TLE-1 is an important protein in the Wnt/β-catenin signalling pathway and is strongly associated with the pathophysiology of synovial sarcoma, with predominant expression in the cell nuclei, with an average sensitivity of 94% (95% CI 91% to 97%), a mean specificity of 81% (95% CI 72% to 91%) and a negative predictive value of 96% (95% CI 93% to 98%), which is why it has been identified as an excellent biomarker.10 15 Also, immunohistochemistry in the present case was positive for TLE-1. There are other markers related to synovial sarcoma, such as Bcl-2 (sensitivity 97%; specificity 71%),15 EMA (sensitivity 64%; specificity 91%)15 and cytokeratin (sensitivity 71%; specificity 85%),15 although they are limited by sensitivity and specificity values.5 15

The principles of surgical treatment are similar to those applied to soft tissue sarcomas in general,3 9 and in this case report the oncological principles were also preserved during colon surgery.16 Tumours <5 cm in favourable locations will require only wide local excision,9 14 but larger tumours with significant depth (investing fascia) and an unfavourable histological differentiation (high-risk soft tissue sarcomas) may require chemotherapy, radiation and surgery.9 For a more advanced disease, multimodal treatment may be indicated, involving surgery, radiotherapy, systemic neoadjuvant chemotherapy and/or postoperative adjuvant chemotherapy.9 14

First-line chemotherapy for treatment of synovial sarcoma consists of management with anthracyclines, doxorubicin (60–75 mg/m2) and alkylating agents such as ifosfamide (7.5–9 g/m2) which inhibit DNA transcription and synthesis.9 14 Knowledge of molecular genetics and signalling pathway mutations has revealed other therapeutic targets such as tyrosine kinase inhibitors, for example, pazopanib (approved by the Food and Drug Administration in 2012), which is a potent and selective receptor tyrosine kinase inhibitor acting on multiple targets, resulting in blocking of tumour growth and inhibition of angiogenesis,14 and which showed good results in phase II (EORTC Study 62043) and phase III (PALETTE) studies for metastatic and refractory synovial sarcoma.14 Currently, a study has been started with trabectedin, which inhibits the progression of the tumour cell cycle by delaying the progression of the S phase and inducing G2/M arrest.9 14

Neoadjuvant chemotherapy in adults is still controversial. Its response has been evaluated in patients with synovial sarcoma in the extremities or trunk surface, not in patients with visceral involvement.

A European (Italy, Spain, France and Poland) randomised phase III study compared epirubicin and ifosfamide versus ifosfamide in prolonged infusion at high doses (14 g/m2) in 70 patients with synovial sarcoma. The mean follow-up was 12.3 months with a disease-free survival after 2 years of 71.7% (control) and 64.4% (histotype tailored chemotherapy) (HR: 1.85; 95% CI 0.65 to 5.22). It is important to highlight that radiotherapy, when necessary, was performed either in the preoperative or postoperative setting according to standard practice. Therefore, despite the limitations of the CI and the follow period, full-dose anthracycline plus ifosfamide as neoadjuvant chemotherapy may improve the oncological outcomes of high-risk synovial sarcoma.17

Notwithstanding no cases of synchronous synovial sarcoma of the colon have been reported during follow-up, two case reports of polypoid lesion and intramucosal lesion have been identified; therefore, knowing that 2%–5% of adenomatous polyps are associated with invasive malignancy, colonoscopy surveillance should be performed.16

As can be seen in the case presented in this report, surgical and oncological management has been performed as described in the literature. With a 4-year follow-up of the colon surgery and one year of palliative and partial resection of metastatic disease. During our follow-up there was no evidence of further disease progression and the patient’s functionality was acceptable, with an Eastern Cooperative Oncology Group (ECOG) rating of 2.

Patient’s perspective

It all began when one day I went to the doctor because I was having bloody stools. He requested stool studies thinking it was an intestinal infection, but results didn’t show that. So, he told me that I had to do a colonoscopy and well. - I imagined many scenarios. Your mind always goes to the worst-case scenario, I thought: ‘I have a tumour in my colon’ Everything fell apart - I cried like a baby.

Physicians explained everything to me, really well, and I was admitted to hospital the same day. They made me aware of all the risks, benefits and probable scenarios including the possibility of having at the end an ileostomy. I decided to go through with it, with the help of my family and placing myself in the hands of the angels that appeared along the way. When I woke up after the operation, I felt fine — I had no stoma.

The greatest impact was when the pathology came out, confirming that I had a synovial sarcoma. The surgeons who evaluated me were very surprised, due to the disease’s rarity and nature of the tumour, which fortunately had been completely removed. However, they told me that additional treatment was still necessary with chemotherapy to prevent a relapse.

My treatment was not completed; I only received 4 sessions of chemotherapy and these were not continuous due to the failures of my health care provider. Finally, with the elapsed time and the intermittence of the treatment, the target of chemotherapies was no longer the same; for that reason, my oncologist decided to conclude treatment. That day I was born again and I learned to make the most of the things that life offered me. – The disease had given me a truce, you could say.

But after a while, Oh! Surprise, while I was doing a routine activity, I felt pain in my chest with a small swelling; I didn’t think it was serious, I thought it was a muscle injury. But as time passed, the pain increased and the mass grew. The truth is, I was not afraid. I remembered what happened to me before and I was stronger at heart. A new fight had begun, my cancer had returned and it was more aggressive, it really would change my life forever.

I began with all the corresponding tests and imaging to return to the operating room. As time passed, the mass grew to the point of pressing my ribs and breathing became more difficult - I couldn’t even climb the stairs because I got out of breath. Those days before my chest surgery were not easy at all – I felt suffocated even when just talking.

The truth is that I have always been very optimistic. So, I decided, once again, to put up with it, because I appreciate life so much and I want to continue sharing it with my loved ones, especially my children, they are the true reason to keep on fighting. I was aware that it was a very complex surgery and several specialists participated. After, more than fourteen hours, I was transferred to postoperative care in the ICU.

I was at the hospital ward for much longer, the discharge was postponed because the flap became necrotic. My body took quite a while to repair itself despite of all treatments I received at hospital and then at home. I used to think about the situation over and over, I had around 3 roommates: The last one died due to a metastatic lung disease, that night, I felt the death so close. Seeing my children again, while I was in-hospital, and the support of all my relatives made me fill myself with motivations to get ahead.

I received again 4 chemotherapy sessions, but this time, I felt they were harder than the previous sessions. My whole body hurt and I needed to go to bed most of the time to be able to tolerate the symptoms. Thus, to improve my quality of life, get the possibility of being able to work a few hours, and to have a normal routine like I had before, my oncologist prescribed an oral treatment along with additional medications for pain management.

I hope that this life experience will serve other people who are going through this same situation. It is not easy at all. But having faith in living longer is greater than everything, I just say: Don’t stop fighting, believe in God and don’t lose hope that good times will come.

Learning points

  • Synovial sarcoma is a neoplasm rarely found in the gastrointestinal tract and requires surgical management, when possible, along with radiotherapy and chemotherapy (adjuvant and/or neoadjuvant) according to the presence of poor prognostic factors and the anatomical location.

  • If genetic studies are not available, histopathological and immunohistochemical findings (biomarkers) can guide the diagnosis.

  • Promising advances in molecular biology (signalling pathways), histological subtypes and their genetic correspondence will enhance the development of targeted and individualised therapy.

Ethics statements

Ethics approval

DVO005 1273-CV1266 Universidad Del Rosario (August 12, 2020)

Acknowledgments

The authors would like to acknowledge Compensar Pathology Service (María Islena Beltrán, MD, Oncopathologist; and Adriana Calderón, MD, Pathologist) reviewed the pathology and inmunohistochemestry, Coloproctology Service and Endoscopic Clinics at Hospital Universitario Mayor - Mederi (Bogotá, Colombia).

References

Footnotes

  • Twitter @ViviHidalgoM

  • Contributors VMHM collected patient information, performed the literature review and drafted the paper. DRBZ motivated the patient to write a patient's perspective and revised the draft paper. MAC obtained consent from the patient, translated the patient's perspective and revised the draft paper. CEFA critically reviewed the study proposal, obtained and presented the consent to the institutional (Hospital Universitario Mayor) ethics committee and revised the draft paper.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.