The clinical course of our case was highly unique in that the tumor recurred as an asymptomatic thrombus in the subclavian vein and had invaded the heart. Microscopic venous invasion during the initial surgery most likely led to an intravenous recurrence. Microscopic venous invasion is associated with a higher risk of recurrence and worse prognosis in cases such as pediatric adrenal cortical tumors, hepatocellular carcinomas, pancreatic cancers, and pancreatic neuroendocrine tumors [12–15]. A clinicopathological study of 24 patients with MPNST demonstrated vascular invasion as a poor prognostic factor [16]. However, few reports are available on recurrent MPNSTs with intravascular invasion. To the best of our knowledge, the present study is the first to report details on the presentation, diagnosis, and treatment of a case of MPNST with microscopic venous invasion extending to the heart. If histology suggests venous invasion, as it did in our case, there is a potential risk of intravenous recurrence and distant metastasis that can progress to a massive tumor thrombus extending to the heart, regardless of the tumor subtype.
Progression of malignant tumors to large vessels has been reported in renal and liver cancers, with a frequency of 3–20% [17–20]. Sarcomas with vascular tissue origins, such as intimal sarcoma [21] and angiosarcoma [22, 23], reportedly extend into large vessels. However, there are a few reports on sarcoma from non-vascular tissues extending into large vessels, including cases of low-grade endometrial stromal sarcoma [24], clear cell sarcoma of the kidney [25], osteosarcoma [26], and renal Ewing’s sarcoma [27]. MPNSTs extending to the great vessels are extremely rare, with only one other case reported in the literature [28]. This previous case presented a diagnostic challenge, and the final diagnosis was made only during the post-mortem examination.
Patients with cancer often have coagulation abnormalities and hence develop thromboses [29]. Although tumor thrombus is rare [30, 31], it is important to differentiate between a bland and a tumor thrombus among patients with cancer. Imaging evaluations such as CT, MRI, fluorodeoxyglucose on PET, and angiography [31] are useful; however, a biopsy is needed to definitively diagnose tumor thrombus in certain cases. Anticoagulant therapy such as heparin is usually ineffective, and surgical resection, chemotherapy, or radiation are, therefore, more common for tumor thromboses [30, 31]. In cases of renal cell carcinoma, complete surgical resection of a tumor thrombus has been reported to result in a 5-year survival rate > 50%, whereas incomplete tumor resection results in a 10% survival rate [31]. Technically, in areas where the proximal part of the involved vessels can be clamped or ligated, tumor thrombus removal includes procedures that prevent tumor cells from disseminating to the proximal side. In cases wherein a tumor thrombus involves the heart and where proximal blood flow cannot be disconnected, cardiopulmonary bypass is necessary. In our case, successfully removing the intracardiac tumor thrombus eventually enabled us to proceed with subsequent radical forequarter amputation for surgical remission.
MPNSTs derived from NF1 often occur in the major nerves, and radical wide resection of the affected nerves results in severe neurological deficits that lead to considerable physical impairment. If large MPNSTs occur in nerves adjacent to major arteries, such as the brachial plexus or femoral nerve, they require amputation at a higher level for radical resection. The frequency of amputation is reported to be 32% in deep and high-grade MPNSTs [32]. In patients with sarcoma, the frequency is reported to be 5% for primary disease and approximately 10% for recurrence [33]. Amputation is more frequent in MPNSTs than in other sarcomas because MPNSTs often occur in the major nerves, and amputation is recommended as a curative surgery to prevent recurrence [32]. If the tumor arises from the brachial plexus, forequarter amputation can be indicated [33–35]. Forequarter amputation involves removal of the arm and shoulder, including the scapula and part of the clavicle. If the tumor involves the chest wall, an extended procedure is performed, including resectioning a part of the chest wall, sometimes in combination with mastectomy or pneumonectomy. Seventy percent of the cases indicated for forequarter amputation are sarcomas, such as undifferentiated pleomorphic sarcoma, osteosarcoma, and synovial sarcoma, while the others are breast cancers and melanomas [35]. According to recent reports, the overall 5-year survival rate after forequarter amputation for malignant tumors of the shoulder girdle is approximately 20–40% [34–39] (Table 1). Complications after forequarter amputation include massive blood loss, wound necrosis, dissection, pneumonia, and atelectasis [34, 35, 38]. In addition, forequarter amputation has a massive impact on the psychological and functional integrity of patients [38]. We aim for the best clinical outcome for patients with NF1 and high-grade MPNST, and accordingly managed, in this case, to perform a wide (R0) resection of the primary tumor with radial nerve sacrifice and intensive adjuvant chemoradiotherapy. Three months after urgent removal of the life-threatening intracardiac tumor thrombus, the residual lesions in the remaining subclavian space increased in size. Given the absence of metastatic disease at the time and the extremely high risk of re-recurrence, we discussed the advantages of radical extended forequarter amputation over the less invasive chemoradiotherapy together with the patient, and she opted for the former. Although the patient underwent another surgery for a solitary metastasis and needed to be closely monitored, she is currently disease-free 2 years after the extended forequarter amputation, which was successfully managed by a multidisciplinary approach.
Table 1
Reference | Year | N | Histology | Survival |
Fanous et al. | 1976 | 21 | 15 sarcoma, 6 carcinoma | 5 year OS 25% (C) |
Bahgia et al. | 1997 | 20 | 18 sarcoma, 2 carcinoma | 5 year OS: 21%, 30% (C) |
Rickelt et al. | 2009 | 40 | 28 sarcoma, 10 carcinoma, 2 ulcer | 5 year OS: 38% for all, 41% for sarcoma |
Puhaindran et al. | 2012 | 26 | Sarcoma & carcinoma | 1 year OS 42 % |
Elsner et al. | 2016 | 30 | 26 sarcoma, 4 carcinoma | 5 year OS 39% (C) |
Tsuda et al. | 2020 | 40 | Bone sarcomas | 5 year OS 30% |
| | | | C: Curative procedure |
Review of past reports with at least 20 patients who have undergone forequarter amputation