Multidisciplinary Treatment in Pulmonary Metastasis of a Mesorectal Angiosarcoma Achieving Complete Remission
Angiosarcoma (AS) is a rare and highly malignant mesenchymal tumor, accounting for approximately 2% of adult soft tissue sarcomas. The prognosis for AS is generally poor due to its high rates of metastasis and recurrence. Studies have shown that 19% of patients present with metastases at the time of initial diagnosis, and 74% experience relapse and progression. The median survival for AS patients is 3.4 years, which drops to just 10 months for those with metastatic disease. Given these challenges, a multidisciplinary approach to treatment is often advocated, combining surgical resection with radiation, chemotherapy, immunotherapy, and anti-angiogenic therapy. This article presents a case of a 26-year-old man with a mesorectal-derived intermediate hemangioendothelioma (HAE) who developed pulmonary metastasis of AS within a year of initial treatment. The case is notable for its rare primary location, atypical clinical course, and successful multidisciplinary treatment, particularly the use of selective arterial infusion (SAI) chemotherapy prior to metastasectomy.
The patient initially presented with increasing anterior sacral pain and altered defecation habits over a three-month period. Physical examination revealed a hard, inflexible tumor located anterior to the rectum, approximately 4 cm from the dentate line. Magnetic resonance imaging (MRI) showed a tumor measuring 6.0 × 5.5 × 5.0 cm, closely adjacent to the right seminal vesicle and compressing the rectum and prostate. Positron emission tomography-computed tomography (PET-CT) confirmed high glucose metabolism in the right pelvic cavity, indicating tumor activity. However, no abnormalities were detected in a chest X-ray or colonoscopy. Diagnostic aspiration guided by ultrasonography suggested a mesenchymal tissue-derived borderline tumor. After a multidisciplinary consultation, the decision was made to proceed with immediate surgical resection. Prior to surgery, sperm was retrieved and preserved in case the spermatophore and sperm ducts were compromised during the procedure. The tumor, measuring 5.5 × 4.5 × 4.3 cm, was successfully resected with clear margins (R0 resection) using an extra-low Dixon surgery technique.
Histopathological examination revealed a fibrous capsule with substantial hemorrhage and necrosis. The tumor was primarily composed of hyperplastic spindle cells with partial vascular-lumen-like structures. Immunohistochemistry (IHC) showed positive staining for CD31 (++), CD34 (+), and Ki-67 (50%), with some cells exhibiting heteromorphism. These findings confirmed a diagnosis of intermediate HAE (T2N0M0). No additional postoperative treatment was administered, and the patient was discharged after phase I incision healing.
One year later, the patient returned with symptoms of cough, chest pain, and hemoptysis. A chest CT revealed nodules in the middle lobe of the right lung and the lower lobes of both lungs, accompanied by pleural effusion. PET-CT showed enhanced glucose metabolism in these nodules, while MRI confirmed no recurrence at the primary site or other metastatic signs. Neo-adjuvant chemotherapy was initiated using SAI, infusing 200 mg of carboplatin and 100 mg of paclitaxel into the metastases via the right internal thoracic artery and bilateral bronchi arteries. After two cycles of SAI chemotherapy, CT imaging showed reduced inflammation and clearer margins of the metastases. The patient subsequently underwent metastasectomy in both lungs, performed at four-week intervals. During this period, a third round of SAI was administered to the left lung metastasis. Pathological analysis confirmed AS in the right middle and left lung metastases, while the right lower metastasis was identified as HAE. IHC results for the metastases were CD31 (+), F8 (+), CD34 (+), Ki-67 (40%), P53 (8%+), and epithelial growth factor receptor (EGFR) (+).
Whole-genome sequencing and RNA analysis of the left metastasis and adjacent normal pulmonary tissue revealed no targeted therapy-related somatic mutations. However, annotation analysis suggested potential sensitivity to anthracyclines and ifosfamide with relatively low toxicity. Consequently, the patient received three rounds of postoperative chemotherapy with 3 g of ifosfamide and 20 mg of pegylated liposomal doxorubicin. Follow-up imaging in November 2017 showed no signs of recurrence, and the patient fathered a child in April 2018.
The case highlights several important aspects of AS and HAE. HAEs are vascular neoplasms with borderline biological behavior, intermediate between benign hemangiomas and malignant AS. Some researchers hypothesize that HAE represents an intermediate state of endothelial dedifferentiation. This case demonstrates that both HAE and AS can coexist in pulmonary metastases, suggesting a possible association between these two pathological types.
Prognostic factors for AS include the presence of metastases at diagnosis, visceral or deep soft tissue location, tumor size greater than 5 cm, tumor necrosis, and the absence of surgical excision. Despite achieving R0 resection in the initial surgery, the patient developed pulmonary metastasis within a year. Current treatment strategies for AS include surgical resection, wide-field radiotherapy, and adjuvant chemotherapy. For localized AS, complete surgical resection remains the only curative approach. Adjuvant radiation or chemotherapy may improve local control and long-term survival. In cases of non-cutaneous AS, combination chemotherapy with doxorubicin and ifosfamide is preferred, with gemcitabine and docetaxel as alternatives for patients with cardiac dysfunction. Anti-VEGF targeted therapies, such as bevacizumab, sorafenib, and pazopanib, have shown modest efficacy in clinical trials.
For advanced or metastatic AS, systemic therapy is the mainstay of treatment. However, surgical resection of metastatic lesions remains a critical component of treatment when feasible. Studies have shown that complete resection of metastases is a key factor in long-term survival, with 5-year survival rates ranging from 18% to 44% after pulmonary metastasectomy (PM). SAI, a novel method of neoadjuvant chemotherapy, allows for high drug concentrations in tumors while minimizing systemic side effects. In this case, SAI successfully stabilized the metastases, enabling complete resection and preventing recurrence.
In conclusion, AS is a rare and highly malignant mesenchymal tumor with diverse manifestations. The use of multidisciplinary treatment approaches, including SAI and PM, can significantly improve outcomes for patients with metastatic AS. This case underscores the importance of a tailored treatment strategy that combines surgical, chemotherapeutic, and targeted therapies to achieve complete remission and long-term survival.
doi.org/10.1097/CM9.0000000000000663
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