Rectal synovial sarcoma: A case report and review of the literature

INTRODUCTION

Synovial sarcoma (SS) is a malignant mesenchymal neoplasm of uncertain origin that accounts for 5 to 10% of all soft tissue sarcomas and can involve any anatomical site.^[1] It can occur in various anatomical regions, although it is most frequently found in the lower extremity, followed by the trunk, head, and neck. Primary gastrointestinal (GIT) SS are exceptionally uncommon, with retroperitoneal involvement being present in less than 1% of cases. Lymph nodal metastasis occurs in 3-7%, and up to 70% of individuals with SS may experience local recurrence and distant metastasis. Morphologically categorized as monophasic (MSS), biphasic (BSS), or poorly differentiated (PDSS).^[2] These different histologic subtypes can considerably overlap with one another and with other types of neoplasms. The monophasic type consists of uniform spindle cells; BSS is morphologically characterized via the coexistence of the spindle cell component and an epithelial element, which might often be arranged in glandular structures, nests, or cords that vary in quantity. In both types, the mitotic activity is limited. The poorly differentiated type includes primitive round or spindle cells that may have a rhabdoid appearance and exhibit a high mitotic count. The chromosomal translocation t(X;18) (p11.2;q11.2) fuses the SS18 (SYT) gene to the SSX gene and is seen as a founding event in the oncogenic development of synovial sarcoma.^[3] However, the actual transformative event of the chimeric SYT-SSX gene product has not been absolutely elucidated. For GIT SS, most of the literature includes case reports and case series. This article discusses diagnosis, treatment, and literature review in synovial sarcoma.

CASE REPORT

A 30-year-old lady presented to our surgical oncology outpatient department with rectal bleeding and perineal discomfort, having no chronic illness. On general and local examination, the patient had a performance status of Eastern Cooperative Oncology Group (ECOG) 0; vitals had been within normal limits; the abdomen was soft without organomegaly; on rectal examination, the rectal mucosa was smooth with a mass palpable on the right lateral aspect 4 cm from the anal verge.

Laboratory tests revealed a carcinoembryonic antigen (CEA) level of 1.39 ng/ml. Imaging studies, including contrast-enhanced computed tomography (CECT) of the abdomen and pelvis, showed a 9.3* 8.3* 6 cm mass located in the right ischiorectal and isochronal fossa, with no signs of distant metastasis [Figure 1]. MRI pelvis demonstrated a 9.6* 6.2 cm lesion in the right ischiorectal and isochronal fossa extending superelevated with mass effect on the anorectal junction, uterus, and bladder.

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Figure 1: Pre NACT CECT abdomen and pelvis 9.3*8.3*6 cm Right ischiorectal fossa, isochronal fossa lesion extending up to the perineal skin right side. Star highlights the tumour in both images in relation to the rectum. NACT: Neoadjuvant chemotherapy, CECT: Contrast-enhanced computed tomography

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Further Ultrasonography (USG)-guided biopsy of the lesion done was suggestive of differential diagnoses between biphasic synovial sarcoma and carcinosarcoma, with morphological and immunohistochemical features favoring the first diagnosis. Immunohistochemistry (IHC) tests were positive for CK7 and CK20 and negative for CDX2, CD10, PAX8, and Bcl2.

The case was discussed at an MDT (multidisciplinary tumor board) and planned for 3 cycles of neoadjuvant chemotherapy (NACT) with Doxorubicin, Ifosfamide, and Mesna, followed by surgical treatment, abdominopelvic resection (APR).

Post- NACT review MRI pelvis suggests reduced size to 6.3* 4.5* 7*5 cm in the right ischiorectal and isochronal fossa without levator ani infiltration [Figure 2].

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Figure 2: Post NACT MRI pelvis 6.3*4.5*7.5 cm lobulated mass in the right ischiorectal and isochronal fossa without levator ani infiltration. Star highlights the tumour in both images in relation to the rectum. NACT: Neoadjuvant chemotherapy, MRI: Magnetic resonance imaging

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With prior consent and explaining the necessity and complications of surgery, the patient is posted for APR. In APR distal sigmoid is mobilized, ureter and gonadal vessels identified and preserved, superior rectal artery dissected from origin and ligated, colon is mobilized and mesocolon is divided, total mesolectal excision done, mobilization of rectum with excision of mass with adjoining adherent structures done till levator muscle, colon transected, anus sutured with purse string suture, teardrop incision is made, dissection continued till levator muscle insertion, pudendal and hemorrhoids vessel ligated, mesorectum separated from anterior presacral fascia, pubococcygeus and puborectalis muscle divided, sigmoid colon, rectum and mass removed with adherent gluteal muscle and sent for Histopathology examination (HPE), pelvic floor closed with interrupted suture and skin closure done with drain insitu. Intraoperatively, an 8*5*6 cm bilobed mass adherent to the right lateral wall of the rectum extended up to the lateral pelvic wall and levator ani muscle with involvement of the gluteus muscle [Figure 3].

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Figure 3: A specimen of APR with the finding of an 8*5*5 cm bilobed mass adherent to the right lateral wall of the rectum reaching up to the lateral pelvic wall and levator ani muscle with involvement of the gluteus muscle. APR: Abdominopelvic resection

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Postoperative perineal wound infection with serous fatty discharge was present and managed conservatively; the rest was uneventful.

DISCUSSION

Synovial sarcoma is a rare soft tissue malignancy, often affecting adolescents and young adults. Morphologically categorized into monophasic synovial sarcoma (MSS), biphasic synovial sarcoma (BSS), and poorly differentiated synovial sarcoma (PDSS). subtypes. The defining genetic feature of SS is chromosomal translocation t(X;18)(p11;q12), which fuses the SS18 gene with SSX family genes (SSX1, SSX2, or SSX4), ensuring in SYT-SSX fusion, initiating tumorigenesis. Current research has explored the molecular genetics of SS, focusing on SYT-SSX fusion and identifying biomarkers such as PAX8 and estrogen receptor expression.^[4]

IHC markers in SS typically show positivity for CK, EMA, Bcl-2, CD99, TLE 1, and the SS18-SSX fusion protein, while markers such as CD34, S100, desmin, myogenic, and Sox10 are generally negative.^[5] In comparison, carcinosarcoma normally expresses AE1/AE2, vimentin, desmin, CD10, p16, p53, and PAX8 in IHC testing.

Morphologically, many differentials are present for MSS, BSS, and PDSS [Table 1].

The primary concern for differentiating synovial sarcoma from other mesenchymal tumors, like GIST (Gastrointestinal stromal tumors), leiomyomas, leiomyosarcomas, schwannomas, and solitary fibrous tumors, is that they share common morphological features, making accurate diagnosis reliant on immunohistochemical staining and molecular analysis.

Biphasic synovial sarcoma, though more common in the extremities, can occasionally present in the GIT in less then 1%, which includes the rectum. Among GIT, the most common location is the stomach, followed by the colorectal, small intestine, gastroesophageal junction, and esophagus.

Rectal SS often present with non-specific symptoms like rectal bleeding, abdominal pain, mimicking other GIT disorders. Diagnosis generally entails imaging like CECT or MRI of the abdomen and pelvis, accompanied by image-guided core needle biopsy requiring IHC.

In imaging, USG is non-specific and shows a heterogeneous hypoechoic mass. Computed tomography (CT) scan, along with a soft tissue heterogeneous density mass, additionally suggests calcification if present. The MRI is the modality of choice, showing the triple sign in T2WI observed as imaging characteristics due to the area of necrosis, cystic degeneration, dystrophic calcification, and fibrotic band. T1WI shows the lesion isointense to muscle, and T1 with contrast enhancement is prominent and may be diffuse (40%), heterogeneous (40%), or peripheral (20%).^[6]

The selection between APR and extra levator abdominopelvic resection (ELAPE) remains a subject of discussion.^[7] While APR is the standard procedure for advanced lower rectal cancer, it carries a higher risk of positive circumferential resection margins (CRM+) and intraoperative perforation (IOP) due to the complex anatomy of the rectum. These factors can increase the chance of local recurrence of the tumor.

After the introduction of cylindrical APR, a European multicenter study showed that with the use of cylindrical APR, the rate of CRM+ reduced from 49.6% to 20.3%, and the incidence of IOP fell from 28.2% to 8.2%, and this study recommended the adoption of ELAPE instead of cylindrical APR.^[8] But ELAPE is seen to increase the perineal wound infection, perineal hernia, compared to APR, and also a large pelvic defect requires reconstruction of the pelvic floor using Myocutaneous flap (gluteal rotation/advancement flaps, inferior gluteal artery myocutaneous island transposition flaps, transverse rectus/vertical rectus abdominis, and gracilis) or human acellular dermal matrix or biological mesh closure.

For neoadjuvant therapy, neoadjuvant chemotherapy or chemoradiation are evaluated in single- or multicenter studies in high-grade tumors; however, most data speak about extremity sarcoma management. A randomized study that compared surgery alone versus neoadjuvant chemotherapy followed by surgery in 134 evaluable patients with high-risk tumors (tumors ≥8 cm of any grade, grade II/III tumors <8 cm, grade II/III locally recurrent tumors, or tumors with inadequate surgery) did not show a major survival benefit for patients receiving chemotherapy. The estimated 5-year disease-free survival (DFS) rate was 52% for the nochemotherapy arm and 56% for the chemotherapy arm. The corresponding 5-year overall survival (OS) rate for both arms was 64% and 65%, respectively.^[9] Another single-institution study involving 48 patients with high-grade extremity soft tissue sarcoma (STS) (≥8 cm), the outcome of patients treated with neoadjuvant chemoradiation with the MAID (mesna, doxorubicin, ifosfamide, and dacarbazine) regimen followed by surgery and adjuvant chemotherapy with the same regimen was superior.^[10] The RTOG9514 study followed the same protocol. Long-term follow-up data of these studies confirmed that neoadjuvant chemoradiation followed by resection and adjuvant chemotherapy with a doxorubicin-based regimen improves local control and OS and DFS rates in patients with high-grade STS of extremity and body wall. Another ongoing trial, STRASS II, is evaluating the role of neoadjuvant chemotherapy in high-risk retroperitoneal STS.

Available evidence from meta-analyses^[11,12] and randomized clinical trials^[13,14] suggests that adjuvant chemotherapy improves recurrence-free survival (RFS) in patients with STS of extremities. However, it is not clear if the conclusions from these trials are applicable to retroperitoneal/intra-abdominal sarcomas, and thus care should be individualized.

Chemotherapy with single agents (dacarbazine, doxorubicin, epirubicin, or ifosfamide) or anthracycline-based combination regimens (doxorubicin or epirubicin with ifosfamide and/or dacarbazine) has been widely used for patients with advanced, unresectable, or metastatic disease.

There are case reports and case series for GIT SS; most of them emphasize clinical-pathological and IHC features.

A study conducted by Domenika Ortiz Requena and his colleagues in 18 cases of GIT SS over a span of 9 years, with the stomach as the most common site of SS, followed by the colorectum, found 14 having MSS, 2 BSS, and 2 PDSS, having SS18:SSX2/SSX1/SSX4 gene fusion. They concluded GIT SS as an aggressive tumor with an adverse outcome.^[2]

Another study by Junlin Zhang et al. summarized 68 cases of SS in the GIT; they concluded that with higher age and large-sized tumors (>5 cm), there may be a high risk of progression to demise after diagnosis. In the author’s case report, SS stained + with vimentin, CD99, Bcl2, EMA, and MiB-1 suggest MSS.^[15]

Marc Ladanyi and team have retrospectively analyzed the clinical behavior of SS in SYT-SSX Fusion type, in which they observed 25% are BSS and 74% are MSS. The median and 5yr OS were 6.1 years and 13.7 years, respectively. OS was better in SYT-SSX2 cases and size <5 cm tumor. Age, sex, histological type, and axial versus peripheral primary site had no impact on overall survival. SSX fusion type appears to exert an impact on prognosis.^[16]

Ho Xuan Tuan published a rare case of perineal SS in a 17-year-old male. MRI allows for identification of the triple sign, and a core needle biopsy was done for tumor grade and IHC. Post wide local excision, HPE reveals monophasic SS, and anthracycline-based CT was given postoperatively. The patient died after 1 year.^[17]

Silvia Stacchiotti and Brian Andrew Van Tine mentioned the SS treatment prospect. They focused on the pharmacologic management of SS, both in the curative setting, where the standard approach is wide surgical excision combined with radiotherapy and/or (neo)adjuvant chemotherapy as appropriate, and in the palliative setting. In advanced disease, chemotherapy with anthracyclines and/or ifosfamide, trabectedin, or pazopanib has been demonstrated to be more active compared with other soft tissue sarcomas. These include targeted agents, immunotherapy, and metabolic therapies.^[18]

A Khan, et al. reported a case of SS of descending colon in which they noted a polyp in the descending colon subjected to polypectomy, HPE exhibits SS, IHC stains SS18-SSX fusion protein, which is considered aggressive and high grade with metastatic ability, so prompt diagnosis and early management are important for better patient outcome.^[19]

Michael R. Freund and team assessed the significance of resection in rectal sarcoma in 133 patients representing only 0.03% of the whole rectal cancer NCDB database over a period of 16 years. They observed a mean age of 65 years, with a mean tumor size of 6.1 cm, and an OS 22.5%. They concluded rectal malignancy is very rare with a poorer prognosis, and undergoing surgery with curative intent with a negative margin may confer better OS.^[20]

In our case, we worked up a 30-year-old lady with rectal biphasic SS as per our institute protocol and discussed the case with the MDT, where 3 cycles of NACT (Doxorubicin, Ifosfamide, and Mesna) were planned. Post-NACT, there is a moderate reduction in the size of the tumor from 9.3*8.3*6 cm to 6.3*7.5*4.5 cm. Further, the patient was subjected to APR.

HPE suggests a poorly differentiated neoplasm with D/D of carcinosarcoma and biphasic synovial sarcoma. The tumor is 12*9.7*3.4 cm, showing glandular structure and spindle cells [Figure 4]. The tumor is infiltrating through the muscularis propria into the peri-colonic tissue, and 5 out of 6 LNs are positive without ENE. IHC positive for CK7, CK20, SS18-SSX/SS18, and IHC negative for Bcl2, CD10, CDX2, PAX8, PR, and TLE, favoring biphasic synovial sarcoma.

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Figure 4: Biphasic Synovial Sarcoma histopathology, having spindle cells 1 and gland-like epithelial structures 2. Stain is hematoxylin and eosin, 10X.

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Compared to previous literature, this case has a younger age of presentation (30 years vs. >50 years), size >5 cm, poorly differentiated neoplasm, and biphasic SS on HPE and IHC, without metastasis, and underwent APR for a negative margin (in preference to ELAPE), favoring the aggressive nature of the disease and high risk. There are no established recommendations; however, the best mode is extensive surgical resection with tumor-free margins, followed by chemoradiation/chemotherapy or neoadjuvant chemotherapy/radiation, followed by surgical resection and adjuvant chemotherapy/radiation.

Prognosis for SS varies according to tumor size, location, grade, morphology, age at diagnosis, mitosis activity, IHC, and presence of metastasis at diagnosis. Generally, SS is aggressive with a poor prognosis, but the biphasic variant has a good outcome compared to MSS and PSS.^[6] The 5- and 10-year survival rates for adults with SS are 62% and 52%, respectively.^[21]

Data availability statements: All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

The CARE Checklist has been completed by the authors for this case report,^[22] attached as online supplementary material.

CONCLUSION

Rectal biphasic synovial sarcoma is an exceedingly rare malignancy with a generally poor prognosis; however, surgical resection with a negative margin may confer better overall survival. Our review and evaluation of SS in the rectum and other GIT found that patients with aging or a large tumor size (≥ 5 cm) have a higher risk and poor prognosis. We advocate that SS be considered inside the differential for any spindle cell lesion in the digestive tract. IHC is to be considered in making the differential for SS.