Sinonasal NUT-Midline Carcinoma – A Multimodality Approach to Diagnosis, Staging and Post-Surgical Restaging

Nuclear protein testis (NUT) midline carcinoma is a rare malignancy involving predominantly the midline structures of the body. It is characterized by its genotypic feature of BRD4-NUT translocation, which is in contrast with other malignant processes that are usually categorized based on their histologic/phenotypic features. As these tumors may vary in their histologic presentation, they can be misdiagnosed as poorly differentiated carcinomas. Moreover, they are often very aggressive and associated with high mortality. Therefore, it is extremely important to diagnose them early using computed tomography (CT) and magnetic resonance imaging (MRI) and perform staging and restaging using 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT), in addition to accurately identifying them at a microscopic and molecular level. We report a unique case of a sinonasal NUT midline carcinoma that was diagnosed with CT, staged with PET/CT, and restaged using PET/CT and MRI.

Diagnostic yield of FDG PET/CT, MRI, and CSF cytology in nonbiopsiable Neurolymphomatosis as a heralding feature of Diffuse B-cell Lymphoma recurrence.

Neurolymphomatosis (NL) is a rare condition associated with lymphomas in which various structures of the nervous system are infiltrated by malignant lymphocytes. Rarely, it may be the presenting feature of recurrence of lymphoma otherwise deemed to be in remission. It is crucial, as is the case with all types of nodal or visceral involvement of lymphoma, to identify the disease early and initiate treatment with chemotherapy and/or radiation therapy. Positron emission tomography-computed tomography (PET-CT) has been shown to be a sensitive modality for staging, restaging, biopsy guidance, therapy response assessment, and surveillance for recurrence of lymphoma. Magnetic resonance imaging (MRI) is another useful imaging modality, which, along with PET/CT, compliment cerebrospinal spinal fluid (CSF) cytology and electromyography (EMG) in the diagnosis of NL. Performing nerve biopsies to confirm neurolymphomatosis can be challenging and with associated morbidity. The case presented herein illustrates the practical usefulness of these tests in detecting NL as a heralding feature of lymphoma recurrence, especially in the absence of histopathologic correlation.

Quantitative Imaging Analysis of FDG PET/CT Imaging for Detection of Central Neurolymphomatosis in a Case of Recurrent Diffuse B-Cell Lymphoma

Neurolymphomatosis (NL) is a rare disease characterized by malignant lymphocytes infiltrating various structures of the nervous system. It typically manifests as a neuropathy involving the peripheral nerves, nerve roots, plexuses, or cranial nerves. It often presents as a complication of lymphoma, but it can be the presenting feature of recurrent lymphoma. It is essential to identify and initiate treatment early with chemotherapy and/or radiation therapy in all cases of nodal or visceral (including neural) involvement with lymphoma. There are various diagnostic tests that can be used for its detection, such as cerebrospinal spinal fluid (CSF) cytology, electromyography (EMG), magnetic resonance imaging (MRI), and positron-emission tomography/computed tomography (PET/CT). FDG-PET/CT is the standard of care in lymphoma staging, restaging, and therapy response assessment, but has an inherent limitation in the detection of disease involvement in the central nervous system. While that is mostly true for visual assessment, there are quantitative methods to measure variation in the metabolic activity in the brain, which in turn helps detect the occurrence of neurolymphomatosis.

Technical Challenges in the Clinical Application of Radiomics

Radiomics is a quantitative approach to medical image analysis targeted at deciphering the morphologic and functional features of a lesion. Radiomic methods can be applied across various malignant conditions to identify tumor phenotype characteristics in the images that correlate with their likelihood of survival, as well as their association with the underlying biology. Identifying this set of characteristic features, called tumor signature, holds tremendous value in predicting the behavior and progression of cancer, which in turn has the potential to predict its response to various therapeutic options. We discuss the technical challenges encountered in the application of radiomics, in terms of methodology, workflow integration, and user experience, that need to be addressed to harness its true potential.

Molecular Imaging in Genomic Medicine

Molecular imaging is the result of advances in the fields of molecular biology and imaging technology and has become an increasingly important tool in the discovery and understanding of a wide range of pathophysiologic processes, ranging from genetic disorders to malignant conditions. The advancement in molecular pathology techniques has enabled us to study the complex genotype of disease entities and how it impacts their behaviour and natural history. Image‐guided genomic medicine utilises methodologies to integrate genomic and radiologic data to develop insights into the genotype–phenotype relationship, which in turn can guide medical decision‐making and treatment planning

Diffusion weighted and dynamic contrast enhanced MRI as an imaging biomarker for stereotactic ablative body radiotherapy (SABR) of primary renal cell carcinoma

Abstract

Purpose
To explore the utility of diffusion and perfusion changes in primary renal cell carcinoma (RCC) after stereotactic ablative body radiotherapy (SABR) as an early biomarker of treatment response, using diffusion weighted (DWI) and dynamic contrast enhanced (DCE) MRI.

Methods
Patients enrolled in a prospective pilot clinical trial received SABR for primary RCC, and had DWI and DCE MRI scheduled at baseline, 14 days and 70 days after SABR. Tumours <5cm diameter received a single fraction of 26 Gy and larger tumours received three fractions of 14 Gy. Apparent diffusion coefficient (ADC) maps were computed from DWI data and parametric and pharmacokinetic maps were fitted to the DCE data. Tumour volumes were
contoured and statistics extracted. Spearman’s rank correlation coefficients were computed between MRI parameter changes versus the percentage tumour volume change from CT at 6, 12 and 24 months and the last follow-up relative to baseline CT.

Results
Twelve patients were eligible for DWI analysis, and a subset of ten patients for DCE MRI analysis. DCE MRI from the second follow-up MRI scan showed correlations between the change in percentage voxels with washout contrast enhancement behaviour and the change in tumour volume (ρ = 0.84, p = 0.004 at 12 month CT, ρ = 0.81, p = 0.02 at 24 month CT, and ρ = 0.89, p = 0.001 at last follow-up CT). The change in mean initial rate of
enhancement and mean Ktrans at the second follow-up MRI scan were positively correlated with percent tumour volume change at the 12 month CT onwards (ρ = 0.65, p = 0.05 and ρ = 0.66, p = 0.04 at 12 month CT respectively). Changes in ADC kurtosis from histogram analysis at the first follow-up MRI scan also showed positive correlations with the percentage tumour volume change (ρ = 0.66, p = 0.02 at 12 month CT, ρ = 0.69, p = 0.02
at last follow-up CT), but these results are possibly confounded by inflammation.

Conclusion
DWI and DCE MRI parameters show potential as early response biomarkers after SABR for primary RCC. Further prospective validation using larger patient cohorts is warranted.