Peritoneal Post-Radiation Angiosarcoma in a Patient With a History of Radiation for Cervical Cancer

Introduction

Post-radiation angiosarcoma (PRA) is a rare, invasive mesenchymal tumor associated with prior cancer radiotherapy. To date, fewer than 400 cases of PRA have been reported. The diagnostic criteria include a history of radiation therapy, the development of a new malignant tumor with a long latency period within the irradiated field, and a histological type distinct from that of the primary tumor if radiation was administered to the original malignancy [1]. The true incidence remains unclear. Unfortunately, the diagnosis of PRA is often delayed, and most cases are highly aggressive. These tumors can develop in any part of the body but are most commonly found on the skin [2,3]. PRA has also been reported in the small intestine, mesentery, and breast [4]. Only a few reports describe vascular sarcoma secondary to radiotherapy for cervical cancer, typically involving the lower abdominal skin [5] or vulva [6]. However, there are almost no reports of peritoneal vascular sarcoma resulting from radiation therapy for cervical cancer. Here, we present a case of peritoneal PRA in a patient with a history of radiation for cervical cancer to highlight this rare clinical entity.

Case Report

A 69-year-old woman presented to our department in July 2024 with abdominal pain (persisting for 1 year) and minor vaginal bleeding (persisting for approximately 4 months). Twenty-two years earlier, she had been diagnosed with stage IIIb cervical squamous cell carcinoma; she had undergone intracavitary radiation therapy (60 Gy), whole pelvic external beam radiation therapy (60 Gy), and 5 cycles of chemotherapy with paclitaxel (420 mg) and cisplatin (220 mg). Follow-up examinations revealed no evidence of recurrence.

One year prior, the patient underwent evaluation at a local hospital for abdominal pain. Test results showed an elevated carbohydrate antigen 125 (CA125) level of 129.06 U/mL, without abnormalities in other tumor markers, routine blood tests, or liver or kidney function. Abdominal computed tomography (CT) and ultrasound revealed a small amount of fluid in the abdominal and pelvic cavities. She subsequently underwent endoscopic examination of the digestive tract and polypectomy, but no tumor was detected. Her abdominal pain partially improved after the procedure. However, approximately 2 months later, she developed minor dark red vaginal bleeding and lower abdominal pain without an apparent cause. There was no nausea, vomiting, bloating, diarrhea, or constipation. Physical examination revealed only mild tenderness and rebound tenderness in the abdominal area. The patient reported a poor appetite and weight loss of 5 kg over the preceding 6 months. Thus, she was referred to our department for further evaluation.

Her CA125 level had increased to 291.8 U/mL, and mild anemia was present (hemoglobin 99 g/L). Positron emission tomography-computed tomography (PET-CT) demonstrated a thickened and hazy liver capsule, omentum majus, and mesentery with increased fluorine-18 fluorodeoxyglucose (18F-FDG) uptake. Enlarged lymph nodes with mildly increased 18F-FDG uptake were noted in the right diaphragmatic angle and hepatogastric space (Figure 1). Based on imaging and laboratory findings, ovarian implant metastasis or peritoneal metastasis from a gastrointestinal primary tumor was suspected; however, no primary lesion was identified on imaging, and only multiple peritoneal nodules were present. No abnormalities were detected in other regions during PET-CT examination. A puncture biopsy of the right upper abdominal omentum revealed a small number of atypical proliferating cells within fibrofatty tissue. After multidisciplinary discussion, poorly differentiated carcinoma was considered, and further surgical exploration with biopsy was recommended.

Intraoperative exploration revealed multiple scattered white nodular and miliary lesions on the diaphragm and peritoneum of both the pelvic and abdominal cavities. Extensive cancerous adhesions were observed in the colon. Pathological examination demonstrated small round cell tumor–like proliferation within fibrous tissue (Figure 2). Immunohistochemical analysis showed positivity for cluster of differentiation 34 (CD34), CD31, friend leukemia integration 1 (FLI1), Ki-67, ETS-related gene (ERG), and myelocytomatosis oncogene (MYC), along with negativity for cytokeratin, smooth muscle actin, S-100 protein, and epithelial membrane antigen. Based on a comprehensive evaluation of the medical history, pathology, and immunohistochemical findings, a diagnosis of PRA was established.

Three months after surgery, the patient underwent 4 cycles of chemotherapy comprising 300 mg of albumin-bound paclitaxel, 300 mg of carboplatin, and 300 mg of bevacizumab. Unfortunately, a CT scan of the upper abdomen before the final chemotherapy cycle revealed new suspicious nodules on the abdominal and intestinal walls, indicating disease progression. Concurrently, the patient experienced fatigue and sharp, knife-like abdominal pain. Four months after surgery, she died of disease progression.

Discussion

Although PRA is an extremely rare condition, its clinical characteristics remain incompletely understood. Our patient had a history of radiation therapy, a long latency period, and a malignant tumor of a different histological type from the primary cervical squamous cell carcinoma. Pathological examination of the nodules revealed small round cell tumor-like proliferation within fibrous tissue, and immunohistochemical staining showed positivity for CD34, CD31 (a highly sensitive endothelial differentiation marker), FLI1, and ERG, all of which are typical vascular markers [7]. These findings confirmed the diagnosis of PRA. Notably, the patient was diagnosed 22 years after radiation therapy, a latency period longer than the typical length reported by Seinen et al [8], who described 35 patients with PRA and an average latency of 7 years (range, 3–25 years). Our patient had received a standard pelvic radiotherapy regimen with a conventional dose of 60 Gy, consistent with doses reported in previous cases [9,10]. These observations suggest that in patients with a history of radiation therapy who develop a new mass within the irradiated field or show a persistent increase in tumor marker levels, PRA should be considered in the differential diagnosis. In the present case, the patient survived approximately 4 months after surgery, which was shorter than the survival time reported by Seinen et al [8]. Some cases without tumor recurrence after treatment have been documented [11,12]. A systematic review of radiation-associated angiosarcoma of the breast reported a poor prognosis, with a median survival period ranging from 10.8 to 33.5 months after histological diagnosis [13], which exceeds the survival duration observed in the present case.

Diagnosing PRA is challenging because it lacks specific early symptoms, and imaging findings often resemble those of other soft tissue sarcomas or metastatic lesions. Imaging modalities such as X-ray, ultrasound, CT, and magnetic resonance imaging, as well as tumor marker measurements (e.g., alpha-fetoprotein, carcinoembryonic antigen, CA125, and carbohydrate antigen 19-9 [CA19-9]), are not definitive for diagnosing peritoneal angiosarcoma. Our patient initially presented with abdominal pain and elevated CA125 levels; other tumor markers, including alpha-fetoprotein, carcinoembryonic antigen, and CA19-9, were within normal limits. Ultrasound and CT findings of the abdominal and pelvic organs were unremarkable. Due to the high suspicion of malignancy, 18F-FDG PET/CT was performed. The scan revealed thickened peritoneum, multiple hypermetabolic nodules, and hypermetabolic lymph nodes, but no clinically significant abnormalities were observed in presumed primary sites of the digestive tract or pelvic cavity. The diagnostic process spanned more than 6 months from symptom onset to establishment of a definitive diagnosis.

Histologically, PRA is characterized by substantially atypical cellular proliferation, often arranged in irregular slit-like or glandular patterns. It is difficult to distinguish angiosarcoma from mesothelioma, epithelioid sarcoma, or papillary hemangioendothelioma based on morphology alone; further immunohistochemical analysis is needed. Mesothelioma typically shows negative staining for CD31 and CD34, whereas epithelioid sarcoma displays CD31 and ERG negativity. In the present case, pathological biopsy did not reveal specific diagnostic features, making the diagnosis particularly challenging. At the time, the rarity of the disease was not fully appreciated, and the working diagnosis favored recurrence or metastasis. PRA was not confirmed until postoperative pathological and immunohistochemical findings demonstrated vascular sarcoma. Given the high aggressiveness and poor prognosis of PRA, regular imaging surveillance with CT or PET/CT is essential to monitor disease progression [14]. When suspicious metastatic or recurrent nodules are identified, pathological biopsy should be performed promptly to confirm the diagnosis. Due to the rarity of PRA, there is no established consensus regarding optimal therapeutic strategies.

Current treatment options for PRA include surgery, chemotherapy, and radiotherapy. To date, radical surgical resection remains the standard of care. Given the high risk of local recurrence and metastasis, adjuvant chemoradiotherapy is often indicated [15]. In the present case, the patient underwent surgery and chemotherapy but died 4 months postoperatively because of disease progression.

The pathogenesis of PRA is not fully understood, but it is generally believed to involve DNA damage and gene mutations induced by radiation therapy. Radiation can cause DNA strand breaks, leading to genetic mutations and chromosomal aberrations that may ultimately result in angiosarcoma [16]. Therefore, more accurate radiotherapy techniques with smaller irradiation fields and lower doses are needed in the future to minimize collateral tissue damage.

Conclusions

Peritoneal angiosarcoma after radiotherapy for cervical cancer is an exceptionally rare condition that poses considerable diagnostic challenges. In our case, the patient presented only with abdominal pain; imaging revealed multiple nodules in the peritoneum and omentum without definitive diagnostic findings. A series of investigations failed to provide conclusive evidence. Thus, long-term cancer survivors presenting with new-onset peritoneal symptoms should be evaluated for possible secondary malignancies. Secondary peritoneal angiosarcoma should be considered in patients with multiple nodules involving the peritoneum and omentum majus, in conjunction with a history of cervical cancer radiotherapy. Early pathological and immunohistochemical assessments are essential for prompt diagnosis and management, which may improve prognosis and survival.