Diagnostic Challenges of Cerebral Venous Thrombosis Mimicking Brain Tumor: A Case Report

Introduction

Cerebral venous thrombosis (CVT), a rare cerebrovascular disorder accounting for 0.5% to 3% of stroke cases, poses significant morbidity risks, especially in individuals under 50 years old [1,2]. Its clinical manifestations are often non-specific, including headache, seizure, nausea, and focal deficits, which contribute to diagnostic delays and increased morbidity [3,4]. However, CVT can also occur across all age groups and can present even in the absence of classic risk factors, as demonstrated in our case.

A critical diagnostic challenge arises from imaging mimicry between CVT and brain tumors. On magnetic resonance imaging (MRI), CVT can present as space-occupying lesions with ring-like enhancement and perilesional edema, closely resembling a brain tumor. Misdiagnoses of CVT as a brain tumor have been reported in the literature since 1998 [5], and the term “cerebral venous thrombosis mimicking brain tumor” (CVTMBT) was formally introduced in 2004 [6], yet this entity remains frequently overlooked [7]. This lack of awareness directly contributed to our patient’s initial misdiagnosis and unnecessary craniotomy.

In this report, we present a case of CVT that was initially misdiagnosed as glioma despite comprehensive imaging evaluations, resulting in an unnecessary craniotomy. Through this case and literature review, we identify key features distinguishing CVTMBT from tumors and propose strategies to mitigate diagnostic errors.

Case Report

A 64-year-old man presented with a 1-month history of recurrent headaches and 8 days of pain in the left lower limb. He denied a family history of venous thrombosis, malignancy, recent infection, or trauma. He was a retired office worker with no smoking or alcohol use. Initial laboratory evaluation revealed markedly elevated D-dimer (7.12 mg/L FEU; reference range: 0–0.55 mg/L FEU) with prolonged thrombin time (22 seconds) and prothrombin time (14.9 seconds). Other hematological, biochemical, and coagulation parameters were within normal limits.

Neuroimaging studies revealed findings concerning for glioma. Cranial computed tomography (CT) demonstrated mixed hypodense and hyperdense lesions in the right frontal lobe with poorly defined margins (Figure 1G). MRI (3.0T) showed irregular nodular abnormalities in the same region, characterized by mixed hypointensity and hyperintensity on T1-weighted imaging (T1WI), and hyperintensity on T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery (FLAIR) sequences. Contrast-enhanced MRI revealed heterogeneous ring-like enhancement with surrounding non-enhancing edema (Figure 1A–1E). Contrast-enhanced magnetic resonance venography (CE-MRV, 3.0T with gadolinium) showed no significant abnormalities (Figure 1F). Functional imaging further supported the diagnosis of glioma. Positron emission tomography (PET)-CT identified mild FDG uptake and magnetic resonance spectroscopy (MRS) revealed reduced N-acetylaspartate (NAA) with elevated choline levels (Figure 1H–1I).

Despite the elevated D-dimer level and the presence of peripheral deep vein thrombosis on Doppler ultrasound (posterior tibial and peroneal veins), CVT was not initially suspected. Thrombophilia screening and autoimmune testing were deferred due to the strong radiological impression of glioma. Based on the imaging profile and clinical progression, the case was managed as suspected glioma and he underwent a right frontal-temporal craniotomy for tumor resection 17 days after admission. Intraoperative frozen sections revealed patchy necrosis and scattered tumor-like cells (Figure 2A). Despite the inconclusive intraoperative pathology, no alternative diagnosis such as CVT was considered. The surgical team proceeded under the assumption of glioma, and no antiplatelet or anticoagulant therapy was initiated.

The patient was treated conservatively in the postoperative period. He remained neurologically stable, with no new deficits or perioperative complications. He was discharged on postoperative day 5 with routine follow-up. However, the final histopathological examination revealed thrombotic infarction, characterized by infarct-like changes with vascular thrombosis and loss of nerve fibers (Figure 2B). Intraoperative frozen sections showed scattered atypical cells with hyperchromatic nuclei, initially mimicking glioma. Ancillary studies on permanent sections demonstrated reactive gliosis (GFAP+), CD68+ histiocytic infiltration, and a very low Ki-67 index (<1%), with no neoplastic cells, thereby excluding glioma. At that time, as his symptoms remained stable and he had already been discharged, no immediate treatment modification or vascular evaluation was arranged.

Nine months after the initial surgery, the patient experienced sudden onset of dizziness, nausea, and vomiting, and right-sided limb weakness. Neurological examination revealed somnolence, increased muscle tone, and absent withdrawal reflexes, primarily in the lower limbs. This marked clinical deterioration prompted urgent re-evaluation. Repeat evaluation showed elevated D-dimer levels (5.75 mg/L FEU). Further laboratory testing, including thrombophilia, autoimmune, and malignancy screening, revealed no abnormalities. Cranial CT showed hyperdense lesions in the bilateral frontoparietal regions and superior sagittal sinus (Figure 2C, 2D). This hyperdensity in the superior sagittal sinus had not been evident on the initial CT, which may explain why CVT was not suspected at that time. Given the combination of neurological worsening, persistently elevated D-dimer levels, suggestive imaging findings, and the previous histopathological diagnosis of thrombotic infarction, CVT was finally suspected.

Digital subtraction angiography (DSA) confirmed multiple filling defects in the superior sagittal sinus and right transverse sinus (Figure 2E). The patient underwent mechanical thrombectomy for venous recanalization, followed by anticoagulation therapy. Anticoagulation with warfarin (target INR 2–3) was initiated for 6 months. At 1-month follow-up, the patient adhered fully to anticoagulation therapy, without complications. He expressed relief after correct treatment and regained consciousness with mild residual motor deficits in the lower limbs, suggestive of partial irreversible damage due to delayed diagnosis and treatment (Figure 2F).

Discussion

The patient’s initial MRI findings (heterogeneous ring-enhancement with perilesional edema) alongside PET-CT hypermetabolism and MRS findings of reduced NAA and elevated choline, were all suggestive of glioma, culminating in a misdiagnosis. Similar misdiagnoses occurred in 13 CVTMBT cases [5–12], highlighting 3 major challenges.

First, the imaging mimicry between CVT and brain tumor remains a persistent diagnostic pitfall. As demonstrated in our patient and previously reported cases [5–12], CVTMBT frequently presents as space-occupying lesions with ring-enhancement and perilesional edema on MRI. Moreover, PET-CT and MRS can further confound diagnosis by demonstrating increased metabolic activity and abnormal metabolite ratios [13,14]. These overlapping features contributed to our patient’s unnecessary craniotomy, consistent with 13 previously reported cases in which 8 patients (62%) underwent unindicated surgeries (Table 1).

Second, current diagnostic tools have inherent limitations. D-dimer is one of the most accessible and essential tools for screening CVT [15,16]. However, its level can be influenced by various clinical factors, with a positive predictive value of only 55.7% [15]. Among the 13 reported CVTMBT cases, 8 explicitly mentioned D-dimer levels, of which 5 showed normal results (Table 1). Non-contrast CT has limited sensitivity for early CVT. Contrast-enhanced CT venography (CTV), although recognized as a reliable alternative to DSA for the diagnosis of CVT, has limited diagnostic value for cortical vein thrombosis, with reported sensitivities ranging from 6% to 75% [17]. Similarly, MRV failed to detect early venous abnormalities despite being the non-invasive criterion standard [17], and advanced techniques like PET-CT/MRS generated false-positive tumor signals [18]. These limitations highlight the importance of (1) considering preoperative digital subtraction angiography (DSA) in cases with atypical imaging and thrombotic risk factors, and (2) integrating emerging technologies such as magnetic resonance black-blood thrombus imaging (MRBTI), which showed 92% sensitivity in recent studies [19,20]. The need for improved diagnostic tools for CVT emphasizes the importance of better clinical strategies, especially when patients present with non-specific neurological symptoms [21].

Third, delayed CVT diagnosis is associated with significant morbidity. Our patient developed irreversible motor deficits despite receiving appropriate anticoagulation therapy after diagnosis, echoing previous reports in which up to 40% of CVT cases experienced diagnostic delays exceeding 10 days [22]. This underscores the importance of early differentiation from tumors, as their management differs significantly. Tumors are treated with surgical resection, whereas CVT requires anticoagulation and etiology-directed therapy [23,24]. In retrospect, the final pathology report indicating thrombotic infarction could have prompted earlier consideration of CVT, potentially altering the clinical course.

Unfortunately, current diagnostic guidelines for CVT and brain tumor do not explicitly address CVTMBT as a differential consideration [25,26]. This omission increases the likelihood that clinicians overlook CVTMBT when confronted with atypical imaging findings resembling tumors, thereby raising the risk of misdiagnosis and unnecessary neurosurgical interventions. Our case underscores this gap and highlights the need for future guidelines to give greater emphasis to the differential diagnosis between CVT and brain tumors, ideally incorporating structured diagnostic pathways informed by larger clinical studies.

Conclusions

CVTMBT remains a significant diagnostic challenge that is often overlooked in clinical practice. We recommend preoperative CTV or DSA in cases where D-dimer level is elevated or thrombotic risk factors are present. Early and accurate diagnosis is crucial to prevent unnecessary surgical interventions and reduce avoidable neurological deficits. Future studies should focus on validating emerging imaging techniques, such as MRBTI, and incorporating CVTMBT into diagnostic guidelines to reduce the risk of misdiagnosis, avoid unnecessary surgical interventions, and improve clinical outcomes.