Rare case of primary inferior vena cava leiomyosarcoma on F-18 fluorodeoxyglucose positron emission tomography-computed tomography scan: Differentiation from nontumor thrombus in a background of procoagulant state.

We report a rare case of leiomyosarcoma of the inferior vena cava (IVC) in which F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography-computed tomography (PET-CT) scan provided vital evidence, which led to its diagnosis, in a background of procoagulant state of the patient, where previous ultrasound-Doppler and echocardiography studies were nonspecific and revealed bilateral lower limb deep vein thrombosis with thrombus in IVC. The whole body F-18 FDG PET-CT scan was done in view of no significant improvement in clinical status of the patient over few months in spite of appropriate medical management. FDG PET-CT scan revealed high grade uptake in a large mass lesion occupying the right atrium, extending superiorly into terminal superior vena cava, inferiorly into dilated IVC and probably into hepatic veins. CT guided biopsy of this F-18 FDG avid mass was consistent with the diagnosis of leiomyosarcoma, which however was not amenable to surgery at this stage. F-18 FDG PET-CT accurately differentiated tumor mass from bland thrombus and further had a significant impact on the management, since aggressive surgery combined with adjuvant therapy offers the best outcome for patients with leiomyosarcoma of the IVC.

INTRODUCTION

Leiomyosarcomas of the inferior vena cava (IVC) are primary vascular tumors that are relatively rare.[1] Clinical findings are nonspecific and initial symptoms are relatively minor often presenting a diagnostic challenge.[2] Computed tomography (CT) scan, magnetic resonance imaging (MRI), ultrasound and echocardiography are the modalities allowing early and accurate diagnosis.[2] We report a case of primary IVC leiomyosarcoma, where previous ultrasound-Doppler and echocardiography studies were nonspecific and revealed bilateral lower limb deep vein thrombosis (DVT) with thrombus in IVC. Fluorodeoxyglucose (FDG) positron emission tomography-CT (PET-CT) went on to show an active thrombus which raised the possibility of primary tumour and needed further evaluation.

CASE REPORT

The case we present here is about a 69-year-old female, known hypertensive, diabetic, hypothyroid with chronic kidney disease who presented with bilateral lower limb pitting edema since 2 years. On investigation, she was found to be positive for Factor V Leiden mutation and hyperhomocysteinemia known to be procoagulant state. She was also detected to have bilateral lower limb DVT and distention of hepatic IVC with a thrombus on ultrasound-Doppler, and was started on warfarin. She then presented with acute onset breathlessness, loss of appetite, nausea, generalized weakness and increased frequency of urination of 10-12 days duration. Her investigations revealed urosepsis with acute kidney injury. The bilateral lower limb venous Doppler showed distension of hepatic IVC with a thrombus with partial recanalization as seen by minimal perithrombus color flow. Infrahepatic IVC showed normal color flow. Echocardiography at this stage showed dilated right atrium with normal and collapsing IVC, and mild pulmonary artery hypertension.

The patient was started on intravenous meropenem and the serum creatinine decreased from 3.8 to 1.8 mg%. However in view of absence of improvement in the clinical condition of the patient she was referred for F-18 FDG whole body PET-CT scan to rule out a possible underlying occult malignancy in the presence of procoagulant state. A conventional whole body F-18 FDG PET-CT scan was acquired on a PET-CT scanner (Discovery STE-16, GE healthcare) in three dimensional mode (2 min emission scan/bed position) from head to mid-thigh, 60 min after intravenous injection of 370 MBq of F-18 FDG.

The scan demonstrated abnormal intense uptake of FDG (SUV max 18) in a large mass lesion occupying the right atrium, extending superiorly into terminal superior vena cava, inferiorly into dilated IVC and probably into hepatic veins [Figure 2]. The possibility of a primary IVC neoplasm (upper caval tumor) was raised. The scan also showed right pleural effusion with collapse of the right lung lower lobe; however, there was no abnormal metabolic activity in these [Figure 1]. A CT guided biopsy of the FDG avid mass showed spindle cell tumor expressing desmin and vimentin, but negative for AE1/AE3 and CD117 consistent with the diagnosis of leiomyosarcoma [Figure 3]. The MIB-1 index was low. However, this large upper caval tumor was not amenable to surgery along with multiple other factors.

Figure 2

Coronal and sagittal fused PET-CT images demonstrating intense FDG uptake in the large mass lesion occupying right atrium extending into terminal SVC and inferiorly into dilated IVC

Figure 1

Abnormal intense uptake of FDG (SUV max 18) in a large neoplastic mass lesion occupying right atrium extending superiorly into terminal SVC, inferiorly into dilated IVC and probably into hepatic veins seen on transaxial fused PET-CT images

Figure 3

Histopathology slides demonstrating spindle cell tumour with cells arranged in intersecting fascicles with sclerotic stroma. The individual cells show nuclear atypia with scant cytoplasm on H and E staining. IHC staining shows desmin in tumour cells

In the following weeks, there was sudden deterioration in the clinical condition of the patient. She became breathless, hypotensive and anuric. Repeat echocardiography now revealed a 3.3 cm mass extending from IVC into the right atrium, which was dilated possibly mass/thrombus, and IVC was dilated and noncollapsing. The patient succumbed to her illness shortly after.

DISCUSSION

Leiomyosarcomas of vascular origin are extremely rare tumors with just over 200 cases reported worldwide.[12] They arise most frequently from the IVC and are commonly seen in the sixth decade with a female predominance.[3] Symptoms are nonspecific such as dyspnea, malaise, weight loss, pain abdomen or back pain and may precede the diagnosis by several years.[4] Metastatic disease is reported in fewer than 50% of cases and can involve the liver, lung, lymph nodes or bone.[5] Aggressive surgical treatment is currently recommended due to tumor's slow growth pattern and low metastatic potential, though chemotherapy and/or radiation therapy may serve as adjuncts. Upper caval tumors are least amenable to complete removal by surgery. An increased risk of death is associated with upper IVC segment involvement, lower limb edema, Budd-Chiari syndrome, intraluminal tumor growth and IVC occlusion.[1] Radical tumor resection is associated with better 5-10 year survival rates (49.4% and 29.5% respectively) compared to palliative resection or inoperable. The 5-year cumulative survival rate is 53% and aggressive surgical management combined with adjuvant therapy offers the best treatment for patients with leiomyosarcoma of the IVC.[67]

Computed tomography scan, MRI, ultrasound and echocardiography allow accurate preoperative diagnosis. However, inherent metabolic differences between tumor and bland thrombi on FDG PET-CT can differentiate the two, which has been highlighted in our case. FDG PET-CT is able to further define the tumor extent to assist with appropriate treatment approach, whilst also staging the disease. Also among tumors such as renal carcinomas, pheochromocytomas, hematomas or testicular tumors that can secondarily invade the vena cava, FDG PET-CT can suggest the primary tumor from one of these primary sites which would need further histopathological correlation. Although our patient had predisposing procoagulant state (Factor V Leiden mutation and hyperhomocysteinemia) favoring high probability of bland thrombus rather than a primary neoplasm, an FDG PET-CT done in the initial stages may have detected the tumor earlier, which might have been amenable to surgical excision. An unusual feature of this case is also the high grade FDG uptake in the primary mass, while the other reported case of upper caval tumor in literature showed mild abnormal glucose metabolism.[8]

CONCLUSION

Primary IVC leiomyosarcomas though uncommon, can be accurately differentiated from bland thrombus or secondary invasion by other tumors on FDG PET-CT and can further assist in defining the extent, staging and appropriate treatment planning. Even when the clinical picture favors procoagulant state as etiology rather than malignancy, in the absence of adequate response to anticoagulant therapy or inadequate improvement in the clinical status, an FDG PET-CT scan be worthwhile to diagnose the latter.