Tumour Thrombus in Non-Classical Malignancies: A Multitracer PET/ CT Case Series

INTRODUCTION

Tumour thrombus (TT) refers to the intraluminal infiltration of malignant cells into adjacent vascular structures. It constitutes a significant pathological entity with major implications in oncologic staging, prognostication, and treatment planning. Accurate discrimination between TT and bland thrombus (BT) is essential, as this distinction directly influences therapeutic decision-making and prognosis. TT consists of organised aggregates of viable neoplastic cells that are continuous with the primary tumour, in contrast to BT, which is composed predominantly of fibrin and platelet aggregates.^[1] Advanced multimodality imaging, including contrast-enhanced computed tomography, magnetic resonance imaging, and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT), plays a pivotal role in this differentiation by demonstrating features such as contrast filling defects associated with increased intrathrombus metabolic activity.^[2]With the increasing use of various imaging modalities like ⁶⁸Ga-DOTATATE and ⁶⁸Ga-FAPI PET/CT, it is important to recognise TT in these modalities. The increasing use of molecular imaging in the identification and description of TT in malignancies with a traditionally lower incidence of vascular invasion is demonstrated by this case series.

CASE SERIES

Case 1

A 65-year-old male with biopsy-proven gallbladder carcinoma presented with progressive right upper quadrant abdominal pain, anorexia, and unintentional weight loss over three months. Baseline ultrasonography demonstrated a gallbladder mass with suspected hepatic invasion. He was referred for ¹⁸F-FDG PET/CT for comprehensive metastatic work-up and staging. Maximum intensity projection (MIP) (A), fused PET/ CT and corresponding CT images showed an FDG-avid locally advanced gallbladder mass (B, C, red arrows) with extension along the portal and hepatic veins (B, C, white arrows) with a filling defect and vessel expansion, suggestive of tumour thrombus (TT) with SUVmax 11.9 [Fig 1].

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Fig 1: (A) Maximum intensity projection (MIP); (B and C) Fused PET/CT and corresponding CT images showed an FDG-avid locally advanced gallbladder mass (red arrows in B and C) with extension along the portal and hepatic veins (white arrows in B and C) with a filling defect and vessel expansion, suggestive of tumour thrombus (TT) with SUVmax 11.9. FDG: Fluorodeoxyglucose; CT: Computed tomography; PET/CT: Positron emission tomography/computed tomography; SUVmax: Maximum standardised uptake value

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Case 2

A 9-year-old girl, known case of neuroblastoma, with MYCN amplification, post-surgical resection and chemotherapy, was referred for ⁶⁸Ga-DOTATATE PET/CT for disease assessment, before autologous stem cell transplant. She initially presented with an abdominal mass and bone pain, and baseline imaging demonstrated a left adrenal primary with regional nodal involvement. ⁶⁸GaDOTATATE PET/CT showed somatostatin receptor (SSTR) expressing multiple retroperitoneal lymph nodes, thrombus with gross dilatation of the inferior vena cava (IVC), suggestive of TT [Fig 2].

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Fig 2: (A) Maximum intensity projection and fused PET/CT and (B-E) Corresponding CT images (red arrows in B-E) showed somatostatin receptor (SSTR) expressing multiple retroperitoneal lymph nodes. SSTR expressing thrombus with gross dilatation of the inferior vena cava (IVC) noted with SUVmax 12.00, suggestive of TT (white arrows in B and C). Lung fields were unremarkable. PET/CT: positron emission tomography/computed tomography; CT: Computed tomography; SUVmax: Maximum standardised uptake value

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Case 3

A 42-year-old woman, a known case of metastatic left breast malignant phyllodes tumour, status post modified radical mastectomy, presented with progressive left axillary swelling and worsening breathlessness over the past two months. Subsequent contrast-enhanced computed tomography (CECT) demonstrated recurrent chest wall soft tissue thickening with suspected axillary nodal disease and intravascular extension, prompting referral for metabolic restaging. ¹⁸F-FDG PET/CT done for restaging showed low-grade metabolically active cutaneous thickening with an ill-defined soft tissue lesion noted at the surgical site, metabolically active left level I axillary lymph node with infiltration into the left subclavian and brachiocephalic veins, lung nodules, and right adrenal lesion [Fig 3].

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Fig 3: (A) Maximum intensity projection; (B and C) Fused PET/CT and corresponding CT images showed low-grade FDG-avid cutaneous thickening with an ill-defined soft tissue lesion noted at the surgical site (red arrows); (D-I) FDG avid left level I axillary lymph node with infiltration into the left subclavian and brachiocephalic veins (red arrows in D, E, F, H and I), showing TT with SUVmax 11.4. FDG-avid parenchymal nodular lesions in bilateral lung fields (white arrows in F and G) and right adrenal lesion were also noted. FDG: Fluorodeoxyglucose; PET/CT; Positron emission tomography/computed tomography; TT: Tumour thrombus; SUVmax: Maximum standardised uptake value

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Case 4

A 50-year-old male, a known case of squamous cell carcinoma (SCC) of the glottis, status post-surgical resection and adjuvant chemoradiotherapy, presented with progressive mediastinal discomfort, diffuse body pain, and recent onset of exertional dyspnoea over the preceding four weeks. He underwent ⁶⁸Ga-FAPI PET/CT for disease restaging, which showed FAPI-avid metastatic mediastinal lymph nodes, skeletal lesions, and a thrombus in the left brachiocephalic vein and superior vena cava (SVC), likely TT [Fig 4].

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Fig 4: (A) Maximum intensity projection; (B and C) Fused PET/CT and corresponding CT images showed FAPI avid metastatic mediastinal lymph nodes (red arrows); (D and E) skeletal lesions (red arrows) and (F and G) Thrombus in the left brachiocephalic vein and SVC - likely TT (red arrows). TT had SUVmax of 11.1. PET/CT: Positron emission tomography/computed tomography; FAPI: Fibroblast activation protein inhibitor; TT: Tumour thrombus; SUVmax: Maximum standardised uptake value; SVC: Superior vena cava

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Case 5

A 40-year-old male presented with progressive exertional dyspnoea, intermittent chest discomfort, and episodes of palpitations over the past three weeks. Transthoracic echocardiography revealed a large right atrial mass with partial obstruction of venous inflow, prompting tissue diagnosis. Subsequent biopsy confirmed diffuse large B-cell lymphoma (DLBCL). He was then referred for ¹⁸F-FDG PET/ CT for staging, which showed an FDG-avid mass noted in the right atrium with extension into the superior vena cava, reaching up to the right brachiocephalic trunk, suggestive of TT and bilateral lung nodules [Fig 5].

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Fig 5: (A) MIP, fused PET/CT and (B-E) Corresponding CT images showed a FDG-avid mass noted in the right atrium (yellow arrows in B-E) with extension into the superior vena cava, reaching up to the right brachiocephalic trunk, suggestive of TT (white arrows in D and E) with SUVmax 9.9. FDG-avid subpleural and parenchymal nodules were noted in bilateral lung fields (red arrows in B and C). MIP: Maximum intensity projection; CT: Computed tomography; FDG: Fluorodeoxyglucose; PET/CT: Positron emission tomography; SUVmax: Maximum standardised uptake value

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DISCUSSION

In conventional malignancies like renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) demonstrating TT, the presence of TT upstages the disease, thereby dramatically altering the surgical complexity and treatment. For instance, in RCC, vascular invasion upstages the disease from T2 to T3a (renal vein or segmental renal vein involvement), T3b (inferior vena cava below the diaphragm), or T3c (supradiaphragmatic IVC involvement or IVC wall invasion), with each increment significantly increasing perioperative morbidity and mortality. Similarly, in HCC, the presence of macrovascular invasion, particularly portal vein tumour thrombus (PVTT) occurring in 44–66% of cases, mandates classification as Barcelona Clinic Liver Cancer Stage C (advanced), which precludes patients from undergoing surgical resection or liver transplantation. The presence of PVTT reduces median overall survival from approximately 16 months to merely six months in untreated cases, a prognostic impact exceeding that of tumour size alone.^[3]Although vascular invasion is a well-established feature of classical malignancies such as RCC and HCC, its presence in non-classical tumour types is relatively under-recognised and poses substantial diagnostic and therapeutic challenges.

Gallbladder carcinoma represents an exceptionally aggressive biliary malignancy with a dismal prognosis. PVTT in gallbladder carcinoma is exceptionally rare, as the portal vein is infrequently invaded due to the anatomical distance and pressure effects of the gallbladder bed.^[4] When PVTT occurs, it indicates direct invasion through the adjacent liver parenchyma and represents stage T4N0M0 (AJCC 8th edition, IVA), signifying locally advanced disease, with significant implications for resectability and prognosis.^[5]Aggressive surgical intervention, including extended hepatic lobectomy with en bloc tumour thrombectomy and adjuvant chemotherapy regimens, can yield survival benefits and potentially prevent recurrence in the short term.

Neuroblastoma, the most common extracranial malignancy in children, exhibits considerable heterogeneity in biological behaviour and prognosis, ranging from spontaneous regression to metastatic disease refractory to therapy. High-risk neuroblastoma patients, characterised by advanced stage, MYCN amplification, or unfavourable genetics, demonstrate morphologically deformed blood vessels with increased branching patterns, including abnormalities of the lymphatic vasculature.^[6] A case series of children with neuroblastoma and IVC thrombus showed that intravascular extension is associated with disseminated disease and poor outcomes, wherein rapid progression was noted despite chemotherapy and prompt surgery.^[7] The presence of vascular invasion and abnormal microvascularisation patterns necessitates intensified treatment strategies and closer long-term surveillance. Intensive neoadjuvant chemotherapy is recommended to shrink both the primary and any thrombus before surgery, although overall outcomes remain poor.^[8]

Phyllodes tumours constitute a heterogeneous spectrum of stromal breast tumours classified as benign, borderline, or malignant based on mitotic rate, cellular atypia, stromal overgrowth, and margin characteristics. Malignant phyllodes tumours, though rare, pose significant therapeutic challenges and demonstrate a propensity for local recurrence and distant metastasis despite complete surgical resection. Vascular invasion in malignant phyllodes tumours correlates with aggressive behaviour, increased risk of postoperative haemorrhage during surgical resection, and propensity for systemic dissemination via lymphatic and haematogenous routes. A published case of malignant phyllodes with tumour extension into the heart and pulmonary metastases invading the pulmonary veins and a left atrial mass. Despite complex surgery and adjuvant chemotherapy, the patient’s disease rapidly progressed.^[9] Another case report of a malignant phyllodes tumour demonstrated metastatic involvement of the left atrium occurring through direct invasion from mediastinal micro-metastasis and presenting as a left atrial mass causing arrhythmia.^[10] In general, metastatic malignant phyllodes (even without visible thrombus) has a dismal outcome, and the presence of TT further worsens the prognosis.

TT with head and neck malignancies is uncommon and is associated with an unfavourable prognosis. Though TT is not a known feature of glottic SCC, head-and-neck SCCs can rarely invade the cervical veins. Wakasaki et al. reported two rare cases of head and neck squamous cell carcinoma complicated by massive internal jugular vein TT, with an unfavourable prognosis resulting in death within ten months.^[11] Given the paucity of cases, it can still be concluded that venous invasion indicates aggressive disease, essentially treating it as metastatic or very advanced local disease. The authors here underscore the potential role of ⁶⁸Ga-FAPI PET/CT in the detection of TT in a patient who presented with symptoms of mediastinal discomfort post-standard treatment.

TT formation is an extremely rare presentation in patients with lymphoma and can be seen in DLBCL and follicular lymphomas. TT within systemic or portal venous structures in lymphoma is extraordinarily rare, reported in a few documented cases in the literature.^[12] Studies of lymphoma-associated thrombosis show these patients have high rates of venous thromboembolism and recurrence, but specific data on TT in DLBCL are limited.^[13] Usually, most patients with DLBCL and venous invasion are treated like advanced lymphoma with chemotherapy as the mainstay. The presence of intravascular involvement represents an indicator of aggressive disease biology and warrants intensified treatment consideration, potentially including upfront autologous haematopoietic stem cell transplantation in patients achieving complete remission after induction therapy.^[8,14]The authors here highlight a rare presentation of lymphoma as an intra-atrial mass, which was later histopathologically proven to be DLBCL presenting as TT.

Across all five malignancies presented in this case series, TT, as noted from the existing literature as well, did require modification of standard treatment algorithms, often requiring escalation to multimodal approaches, combining surgical resection with systemic chemotherapy and/or radiation therapy. Anticoagulation in the setting of TT remains controversial, lacking robust evidence for improvement in overall survival, but is warranted when concurrent BT develops, with careful consideration of bleeding risk versus cancer-related mortality.^[15]

CONCLUSION

TT in diverse malignancies represents advanced disease with aggressive tumour biology and an overall poorer prognosis, warranting accurate preoperative detection and characterisation. The authors underscore the role of nuclear medicine techniques employing diverse radiotracers in accurately differentiating TT from BT, delineating the true extent of disease burden, and guiding individualised clinical decision-making. Continued research into the molecular mechanisms driving vascular invasion and the development of targeted therapeutic strategies may further refine treatment paradigms; however, the expanding capabilities of hybrid and molecular imaging, as stressed herein, remain pivotal for improving diagnostic confidence, optimising therapeutic planning, and ultimately enhancing patient outcomes in these complex clinical scenarios.