Tc-99m Tetrofosmin SPECT-CT as a Guide to Core Needle Biopsy of a Giant Thymoma

Introduction

Single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) is a noninvasive method to evaluate the cardiac perfusion in patients with suspected coronary artery disease (CAD). Moreover, both tracers usually employed for this purpose, i.e., Tc-99m tetrofosmin and Tc-99m 2-methoxyisobutyl isonitrile (MIBI), have also been shown to have oncotropic properties and, occasionally, they may reveal unexpected extracardiac uptake, including tumors in the mediastinal region.

Here, we report the case of a thymoma incidentally discovered in a patient who underwent Tc-99m tetrofosmin SPECT-MPI for suspected myocardial ischemia. A subsequent SPECT-computed tomography (SPECT-CT) has proven to be a very useful tool for both anatomical and functional characterization and as guide to the core needle biopsy of the mass.

Case Report

A 59-year-old male, symptomatic for chest pain, was referred to our nuclear medicine unit to evaluate the presence of significant CAD. The patient underwent a 2-day SPECT-MPI after administration of Tc-99m tetrofosmin (600 MBq [16.2 mCi]/day). Stress test was performed by means of the pharmacological stimulation with regadenoson. The reconstructed images revealed the presence of myocardial ischemia in the mid-basal anterior wall. Simultaneously, a large extracardiac tracer uptake appeared in the mediastinal region [Figure 1]. Therefore, a thoracic SPECT-CT was performed for a better diagnostic evaluation. It revealed a large area of inhomogeneous Tc-99m tetrofosmin accumulation in the anterior mediastinum, with right paramedian development [Figure 2]. The mass showed clear and regular profiles and maximum diameters equal to 6 cm × 5.2 cm × 10.3 cm, with prevalent longitudinal development. It appeared in close contiguity with the right anterolateral profile of the ascending thoracic aorta and, partially, with the left atrium, but cleavable from both. A region of interest (ROI) was drawn in the axial slice showing the maximum uptake around the extracardiac image and, another equal ROI, was placed on the ipsilateral lung for background activity [Figure 3]. Mean count were measured in both ROIs to calculate the uptake ratio. The value obtained resulted in 26. The clinical presentation and metabolic features were highly suggestive of thymoma.

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Figure 1 Single photon emission computed tomography-myocardial perfusion imaging (MPI) results revealing a limited area of ischemia in the mid-basal anterior wall, as shown in the three-axis images and in the bull’s eye MPI images, which depict the entire myocardium. Moreover, a large extracardiac tracer uptake appears in the mediastinal region at raw projection images

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Figure 2 Summed axial slices of single photon emission computed tomography-computed tomography showing an intense uptake of the tracer in the large mediastinal mass, with coexisting multiple areas of reduced uptake (arrows) attributable to intralesional necrosis. These images have proven very useful in guiding the core biopsy in a cranial region of the tumor more suitable for the sampling

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Figure 3 Computed tomography (CT) (a), single photon emission CT (SPECT) (b), and SPECT-CT (c) in the axial view at maximum uptake, revealing a large mass in the anterior mediastinum with intense but heterogeneous Tc-99m tetrofosmin accumulation. Two identical ROIs are positioned, respectively, around the lesion and in the ipsilateral lung for the calculation of the lesion uptake ratio. Maximum intensity projection of SPECT-CT is also shown (d)

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Through a right paramedian access, the mass sampling was performed by an experienced radiologist orienting the cutting needle by means of ultrasound (US) guidance toward the area of greatest uptake of Tc-99m tetrofosmin, in the same axial plane as the SPECT-CT. The subsequent histopathological diagnosis was B1 thymoma [Figure 4].

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Figure 4 The image of the cutting needle is appreciable in an ultrasound plane of the mediastinal lesion (a). Computed tomography (CT) and single photon emission CT images of the most cranial portion of the lesion (b and c), in the same plane as the ultrasound image, have been found useful as a guide to core biopsy. B1 thymoma was composed of a large number of densely packed small lymphocytes and scattered neoplastic epithelial cells with pale round nuclei and small nucleoli. Epithelial cells were immunostained with AE1/AE3 keratins and expressed p40 and CK5/6 as markers of squamous differentiation. Hematoxylin and eosin staining from formalin-fixed paraffin-embedded tissue (d) and CK5/6 immunostain (e) are shown

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The patient was referred to the nearest department of thoracic surgery for surgical resection of the mass, after undergoing revascularization of the anterior descending coronary artery.

Discussion

Here, we present one of the first cases in which hybrid SPECT-CT imaging was deemed useful for planning the US-guided core needle biopsy of a giant thymoma, incidentally detected at raw projection images of a SPECT-MPI.

Thymoma is among the most common tumors of the anterior mediastinum, approximately with an incidence between 20% and 30% of all mediastinal tumors.[1]

According to the World Health Organization, thymomas are classified as type A (including an atypical variant), AB, type B (separated into B1, B2, and B3 thymomas), micronodular thymoma with lymphoid stroma, and metaplastic thymoma. Other rarer thymic epithelial tumors include thymic carcinoma and thymic neuroendocrine neoplasms.[2]

Previous published papers have reported that some thymomas exhibit an inhomogeneous Tc-99m tetrofosmin or Tc-99m MIBI uptake due to the presence of necrotic areas within the mediastinal mass.[34] This feature is particularly evident in our case, as a significant number of areas of necrosis, even several centimeters in length, would have constituted a pitfall in the sampling procedure, resulting in a diagnostic delay and in the need of a further biopsy. On the other hand, the biopsy of an anterior mediastinal mass is not always considered necessary, especially if highly characteristic clinical symptoms are associated. It is known that 30%–50% of patients older than 40 years with thymoma exhibit paraneoplastic syndromes, most commonly myasthenia gravis,[5] but none of this had been found in our patient. Therefore, an US-guided transcutaneous core biopsy was deemed necessary to confirm the suspected diagnosis of thymoma.

Already some authors have described thymic lesions, incidentally detected on Tc-99m tetrofosmin or Tc-99m MIBI SPECT-MPI, and have highlighted the importance to perform a subsequent SPECT-CT for a better anatomical and functional characterization.[67] The tracer uptake has been shown to correlate with regional blood flow and mitochondrial content in cells.[8] Furthermore, the accumulation of Tc-99m tetrofosmin is inversely proportional to the expression of P-glycoprotein, a member of the family of adenosine triphosphate-binding cassette transport proteins, known to be involved in resistance to chemotherapeutic agents in tumor cells: this could explain the lively uptake of the tracer in benign thymomas.[1] In fact, our patient showed a very high uptake ratio of the lesion, much higher than the cutoff (>4) identified by Gratz et al.,[1] reinforcing the suspicion of a benign thymic lesion.

Even due to the large size of the mass, the histological characterization was considered essential to plan the subsequent surgical intervention for mass removal. Hybrid SPECT-CT imaging proved particularly useful for US-guided core biopsy. It allowed the trajectory of the cutting needle to be guided in a substantial portion of vital tissue, avoiding the erroneous sampling of intralesional necrotic tissue and, therefore, providing an adequate sample for the pathologist. In addition, the continuous evolution of SPECT-CT technology is paving the way for new frontiers in precision medicine, extending its applications beyond traditional oncological diagnostics. Recent developments, such as artificial intelligence-assisted image reconstruction and radiomics, enable a more refined quantification of tracer uptake, improving lesion characterization and risk stratification.[9] Moreover, the integration of advanced collimators and cadmium-zinc-telluride detectors enhances sensitivity and spatial resolution, making SPECT-CT an increasingly indispensable tool for both diagnostic and interventional procedures.[10] These innovations not only optimize lesion targeting for biopsies but also hold promise for theranostic applications, where molecular imaging guides personalized treatment strategies. To the best of our knowledge, the one here described seems to be the first case of an anterior mediastinal giant mass sampling on the basis of SPECT-CT images never documented. This further step in the sampling procedure was deemed necessary by the SPECT-CT evidence of multiple areas of necrosis due to the large size of the lesion, among the largest described in the literature, and may represent a potentially useful diagnostic approach for future similar cases.

In conclusion, intrathoracic extracardiac uptake at Tc-99m tetrofosmin SPECT-MPI is a rare but clinically significant event, as it may indicate the presence of diseases characterized by high cellular metabolism, such as solid tumors. Given the large size and heterogeneity of the mass we identified, a further hybrid SPECT-CT study proved valuable not only for a better morphofunctional characterization of the lesion but also as a guide to the US-guided core biopsy, allowing the sampling of tissue with a high concentration of viable cells.