Recurrent Low-grade endometrial stromal sarcoma metastasized to the common iliac veins, extending into the inferior vena cava and right atrium after 12 years: A case report.

A 51-year-old woman with a history of eight vaginal deliveries presented to our clinic with chronic lower back pain that started six months ago. The patient reported occasional postural dizziness associated with presyncope attacks, pleuritic chest pain, and shortness of breath. Her past medical history included type 2 diabetes, hypertensive, dyslipidemia, and primary hypothyroidism on medications. Additionally, her past surgical history was notable for total abdominal hysterectomy and bilateral salpingo-oophorectomy for LG-ESS roughly 12 years ago, followed by local radiotherapy and hormonal therapy (letrozole, an aromatase inhibitor) for three years without any evidence of recurrence. Allergy history was remarkable for sensitivity to shellfish and intravenous contrast. She was non-smoker with unremarkable social and family history. Upon examination, patient was on a wheelchair, vitally stable, and with body mass index of 30.3 kg/m 2 . The rest of examination was unremarkable. All labs were within normal values. Whole-body computed tomography (CT) for diagnosis was requested. CT of the chest showed a large, intracardiac thrombus within the right atrium extending into the IVC ( Fig. 1 A-B ). CT abdomen and pelvis confirmed the findings of thrombosis of the right common iliac and internal iliac vessels extending into the IVC throughout its entire length as well as extension into the right atrium. Fig. 1 Computed tomography imaging before surgery. (A) coronal and (B) sagittal views showed a large, intracardiac thrombus within the right atrium extending into the IVC. Computed tomography imaging before surgery. (A) coronal and (B) sagittal views showed a large, intracardiac thrombus within the right atrium extending into the IVC. Patient underwent echocardiogram which showed a large mass likely thrombus in the right atrium attached to intra-atrial septum extending into the IVC. An uneventful intravascular IVC lesion biopsy through left common femoral access was performed and histopathology showed a neoplasm in favor of metastatic LG-ESS. The case was reviewed by a multidisciplinary team, leading to cytoreduction of the intravenous tumor via thoracotomy and laparotomy. A median sternotomy was performed, and cardiopulmonary bypass was initiated. The right atrium was opened, allowing complete resection of the mass from the suprahepatic IVC for histopathology, with no attachment to the right atrium, right ventricle, or tricuspid valve. After closing the right atrium and weaning off bypass, three chest tubes were inserted, and the chest was closed. The gynecologic procedure began with a midline laparotomy. The right colon was mobilized leftward, and the Kocher maneuver was used to mobilize the duodenum. The inferior vena cava (IVC) was exposed and dissected to its confluence, with vessel loops controlling both common iliac veins. The left liver lobe was mobilized to access the proximal retrohepatic IVC. A venotomy on the infrarenal IVC revealed a mass attached to the wall, necessitating endarterectomy and extension into the suprarenal segment for complete removal. Backflow from the suprahepatic area was managed by tightening the vessel loop on the suprarenal IVC. Dissection continued into the right common iliac vein, and the external iliac vein was cleared. The inflow from the right internal iliac vein was transected and ligated, while backflow from the left renal vein was controlled. Primary repair of the venotomy was done with 4–0 Prolene. Continuous flow was restored, all inflows and outflows were flushed with heparinized saline, and hemostasis was achieved before closing the abdominal cavity. Estimated blood loss was 4,150 ml, and the patient was monitored for 10 days. Gross examination of the resected tumor specimen revealed multiple fragmented masses ( Fig. 2 A ). The outer surface was tan, red brown, and congested. Upon opening, there was a heterogenous tan brown cut surface with multiple cystic areas. No necrosis was seen ( Fig. 2 B ). Histopathological evaluation of the tumor sections revealed neoplastic growth composed of oval to spindle bland looking cells. These cells were observed in a swirling pattern around arterioles and small capillaries. Low mitotic activity was seen (less than 5 per 10 high power fields). No tumor necrosis was seen. Immunohistochemical evaluation showed tumors were stained diffusely and strongly positive for CD10 ( Fig. 2 C), WT-1, estrogen, and progesterone, while negative for pan-cytokeratin, smooth muscle actin, desmin, DOG1, cyclin-D1, CD117, CD34, CD31, and CD45. The tumoral stromal background was rich in vascular network channels ( Fig. 2 D). The final diagnosis was consistent with metastatic LG-ESS. Fig. 2 Pathological evaluation of the resected specimen. (A) The resected specimen showed tumoral thrombus involving part of the right atrium (RA), part of the right ventricle (RV), inferior vena cava (IVC), common iliac veins. (B) Gross examination of the mass composed of smooth outer surface, the mass inside was composed of glistering surface and cystic spaces, no necrosis seen. (C) Immunohistochemical staining showed strong positivity for CD10 in tumor cells (40x). (D) Microscopic evaluation by histopathology by hematoxylin and eosin stain (H&E) of the lesion showed oval to spindle bland cells proliferating around blood vessels (H&E; 4x). In the inset, high-power magnification of the tumor cells was depicted (H&E; 40x). Pathological evaluation of the resected specimen. (A) The resected specimen showed tumoral thrombus involving part of the right atrium (RA), part of the right ventricle (RV), inferior vena cava (IVC), common iliac veins. (B) Gross examination of the mass composed of smooth outer surface, the mass inside was composed of glistering surface and cystic spaces, no necrosis seen. (C) Immunohistochemical staining showed strong positivity for CD10 in tumor cells (40x). (D) Microscopic evaluation by histopathology by hematoxylin and eosin stain (H&E) of the lesion showed oval to spindle bland cells proliferating around blood vessels (H&E; 4x). In the inset, high-power magnification of the tumor cells was depicted (H&E; 40x). Patient was prescribed an aromatase inhibitor, letrozole 2.5 mg orally daily for 2 months. Follow-up CT scan after two months showed no residual or recurrence ( Fig. 3 A–B ). Fig. 3 Computed tomography imaging after surgery. (A) coronal and (B) sagittal views showed no tumoral thrombus within the inferior vena cava. Computed tomography imaging after surgery. (A) coronal and (B) sagittal views showed no tumoral thrombus within the inferior vena cava.

Nour Naaman: Writing – original draft, Investigation, Formal analysis, Data curation, Conceptualization. Mohammad Alyafi: Writing – review & editing, Visualization, Supervision, Software, Resources, Data curation, Conceptualization. Heitham Albeshri: Writing – review & editing, Supervision, Software, Resources, Methodology, Investigation. Ahmed A Jamjoom: Writing – review & editing, Validation, Supervision, Software, Resources, Methodology, Investigation. Samira AlTurkistany: Writing – review & editing, Supervision, Software, Resources, Methodology. Haneen Al-Maghrabi: Writing – original draft, Software, Methodology, Investigation, Data curation, Conceptualization. Saeed Baradwan: Writing – review & editing, Writing – original draft, Visualization, Validation, Software, Resources, Project administration, Investigation, Formal analysis, Data curation, Conceptualization.

Following leiomyosarcomas, LG-ESS stands as the second most prevalent stromal tumor ( Capozzi et al., 2020 ). One-fourth of LG-ESS patients are asymptomatic; and the most common presenting symptoms comprise abnormal uterine bleeding, pelvic pain, and dysmenorrhea ( Capozzi et al., 2020 ). Notably; approximately half of the patients with LG-ESS often experience tumor recurrence, typically after a significant period of dormancy following surgery ( Akaev et al., 2021 ). Extrauterine pelvic extension of LG-ESS is frequently associated with endometriosis; with the ovary being the most common extrauterine site ( Capozzi et al., 2020 ). In our case; the patient did not have a history of endometriosis and presented to clinical attention with chronic pelvic pain which was attributed to metastatic LG-ESS in the IVC and extending bidirectionally into the right atrium upwardly and common iliac veins downwardly. A precise preoperative diagnosis of LG-ESS remains elusive with the current imaging modalities ( Capozzi et al., 2020 ). Leiomyosarcoma was a potential differential diagnosis in our case besides LG-ESS. However; positive staining for CD10, WT-1, estrogen receptor, and progesterone receptor is typically observed in the immunohistochemistry for LG-ESS ( Chu et al., 2001 ). To a larger degree; CD10 immunoreactivity can be usefully utilized to distinguish between leiomyosarcoma and LG-ESS ( Chu et al., 2001 ). In our case; no cytogenetic testing was done, and we relied mostly on the past medical history in addition to the pathological and immunochemical analyses to confirm the diagnosis. Surgery stands as the cornerstone in managing patients with primary LG-ESS. There is no consensus regarding the role of adjuvant treatment for LG-ESS ( Horng et al., 2016 ). Given the positive expression of estrogen receptor and progesterone receptor by LG-ESS ( Chu et al., 2001 ); hormonal treatment (particularly progestins and aromatase inhibitors) is often utilized ( Chu et al., 2001 ); showing effectiveness in reducing recurrence ( Comert et al., 2019 ). For patients with recurrent LG-ESS; fertility-preserving surgery is not advised. Instead, radical surgery—aiming for optimal debulking with no residual tumor—is the preferred approach when technically feasible. Additionally, hormone therapy and/or chemotherapy can offer substantial survival benefits when used alongside surgical intervention ( Dai et al., 2021 , Quan et al., 2024 , Dai et al., 2024 ). Zhang et al. reported a 56-year-old woman with right thigh pain, who had a hysterectomy and bilateral adnexectomy 12 years ago ( Zhang et al., 2022 ). A contrast-enhanced CT scan revealed thickening of the vaginal stump and multiple nodular shadows; suggesting malignancy. After a multidisciplinary review, leiomyomatosis of the IVC was diagnosed, leading to surgical intervention. The surgeons performed a laparotomy and removed tumors from the IVC and nearby veins. Pathology confirmed LG-ESS, likely from an ovarian venous stump. Following a gynecological consultation, chemotherapy was recommended, and the patient is under follow-up ( Zhang et al., 2022 ). Chi et al. reported a case of a 38-year-old woman who discovered an incidental pelvic mass during a routine physical exam ( Chai et al., 2023 ). Her medical history included a hysteroscopic submucosal myomectomy seven years prior; initially diagnosed as an endometrial stromal nodule, though LG-ESS could not be ruled out. Preoperative imaging was used to evaluate the lesion's extent. The patient underwent radical surgery, including thrombectomy and total hysterectomy with bilateral salpingo-oophorectomy, with the final diagnosis confirming metastatic LG-ESS. Three years post-surgery, she remained alive with no signs of recurrence ( Chai et al., 2023 ). Alswiket et al. reported a case of a 49-year-old woman with a four-month history of shortness of breath and easy fatigability ( Alswiket et al., 2022 ). Her medical history included LG-ESS diagnosed six years prior. Imaging revealed a pulmonary embolism; a suspicious right psoas muscle mass, and a large IVC thrombus. Further investigation indicated a new right atrial mass, a tumoral thrombus in the IVC, along with metastatic lymphadenopathy and pulmonary metastasis. Due to the aggressive nature of the disease, oncological surgeons deemed surgical intervention unfeasible and recommended chemotherapy with a gemcitabine/docetaxel combination, awaiting any improvement in her condition ( Alswiket et al., 2022 ). Our case report contributes to the limited literature on the latent distant metastasis of LG-ESS to blood vessels, highlighting the importance of radical surgical excision and adjuvant hormonal therapy. It underscores the need for thorough preoperative evaluations to identify potential metastatic sites, which can significantly influence treatment decisions. Furthermore, our findings support the ongoing monitoring of patients with a history of LG-ESS, as early detection of metastases may improve outcomes. This work aims to enhance understanding and inform future management strategies for LG-ESS. In conclusion, the occurrence of extrauterine metastasis from LG-ESS to major blood vessels is rare, and treatment should prioritize reducing tumor burden via surgical resection, and this often necessitates multidisciplinary collaboration. Resection of the lesion followed by adjuvant hormonal therapy comprising progestins or aromatase inhibitors significantly impacts the prognosis of patients. Gynecologic oncologists and pathologists must meticulously differentiate between uterine leiomyoma and LG-ESS, and closely monitor high-risk patients during follow-up for potential, latent, local and distant metastases.

Endometrial stromal sarcoma (ESS) tumors stand as extremely uncommon malignant mesenchymal neoplasms, comprising approximately 0.2 % of all malignant uterine malignancies and 10–15 % of all uterine sarcomas. Their occurrence is estimated at 1–2 cases per million women annually ( Rauh-Hain and del Carmen, 2013 ). Morphologically; ESS tumors are manifested by neoplastic cells that appear analogous to the proliferative-phase endometrial stroma ( Akaev et al., 2021 ). The most contemporary cataloguing by the World Health Organization identifies four groups of ESS tumors; namely: endometrial stromal nodule, low-grade ESS (LG-ESS), high-grade ESS (HG-ESS), and undifferentiated uterine sarcoma ( Conklin and Longacre, 2014 ). In general; the prognosis of LG-ESS is favorable; nonetheless, about 50 % of patients encounter tumor recurrence, often occurring following a prolonged period of latency ( Akaev et al., 2021 ). The most frequent site of recurrence is the pelvis; particularly ovaries ( Capozzi et al., 2020 ). Extrauterine recurrent metastasis of LG-ESS to major blood vessels is largely rare phenomenon with few reported cases ( Zhang et al., 2022 , Chai et al., 2023 , Alswiket et al., 2022 ). Herein, we present a case of a 51-year-old Saudi female with recurrent LG-ESS that has metastasized after 12 years to the inferior vena cava (IVC) and extended into the right atrium and common iliac veins.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.