Advancements in Neuroendocrine Neoplasms: Imaging and Future Frontiers.

Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management.

Imaging of Neuroendocrine Neoplasms; Principles of Treatment Strategies. What Referring Clinicians Want to Know.

ABSTRACT: Neuroendocrine neoplasms (NENs) are a diverse group of tumors that express neuroendocrine markers and primarily affect the lungs and digestive system. The incidence of NENs has increased over time due to advancements in imaging and diagnostic techniques. Effective management of NENs requires a multidisciplinary approach, considering factors such as tumor location, grade, stage, symptoms, and imaging findings. Treatment strategies vary depending on the specific subtype of NEN. In this review, we will focus on treatment strategies and therapies including the information relevant to clinicians in order to undertake optimal management and treatment decisions, the implications of different therapies on imaging, and how to ascertain their possible complications and treatment effects.

Diagnostic Anatomic Imaging for Neuroendocrine Neoplasms: Maximizing Strengths and Mitigating Weaknesses.

ABSTRACT: Neuroendocrine neoplasms are a heterogeneous group of gastrointestinal and lung tumors. Their diverse clinical manifestations, variable locations, and heterogeneity present notable diagnostic challenges. This article delves into the imaging modalities vital for their detection and characterization. Computed tomography is essential for initial assessment and staging. At the same time, magnetic resonance imaging (MRI) is particularly adept for liver, pancreatic, osseous, and rectal imaging, offering superior soft tissue contrast. The article also highlights the limitations of these imaging techniques, such as MRI's inability to effectively evaluate the cortical bone and the questioned cost-effectiveness of computed tomography and MRI for detecting specific gastric lesions. By emphasizing the strengths and weaknesses of these imaging techniques, the review offers insights into optimizing their utilization for improved diagnosis, staging, and therapeutic management of neuroendocrine neoplasms.

Clinical Intricacies and Advances in Neuroendocrine Tumors: An Organ-Based Multidisciplinary Approach.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.

State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms.

ABSTRACT: Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.

An Illustrated Review of the Recent 2019 World Health Organization Classification of Neuroendocrine Neoplasms: A Radiologic and Pathologic Correlation.

ABSTRACT: Recent advances in molecular pathology and an improved understanding of the etiology of neuroendocrine neoplasms (NENs) have given rise to an updated World Health Organization classification. Since gastroenteropancreatic NENs (GEP-NENs) are the most common forms of NENs and their incidence has been increasing constantly, they will be the focus of our attention. Here, we review the findings at the foundation of the new classification system, discuss how it impacts imaging research and radiological practice, and illustrate typical and atypical imaging and pathological findings. Gastroenteropancreatic NENs have a highly variable clinical course, which existing classification schemes based on proliferation rate were unable to fully capture. While well- and poorly differentiated NENs both express neuroendocrine markers, they are fundamentally different diseases, which may show similar proliferation rates. Genetic alterations specific to well-differentiated neuroendocrine tumors graded 1 to 3 and poorly differentiated neuroendocrine cancers of small cell and large-cell subtype have been identified. The new tumor classification places new demands and creates opportunities for radiologists to continue providing the clinically most relevant report and on researchers to design projects, which continue to be clinically applicable.

A revisited history of cacao domestication in pre-Columbian times revealed by archaeogenomic approaches.

Humans have a long history of transporting and trading plants, contributing to the evolution of domesticated plants. Theobroma cacao originated in the Neotropics from South America. However, little is known about its domestication and use in these regions. In this study, ceramic residues from a large sample of pre-Columbian cultures from South and Central America were analyzed using archaeogenomic and biochemical approaches. Here we show, for the first time, the widespread use of cacao in South America out of its native Amazonian area of origin, extending back 5000 years, likely supported by cultural interactions between the Amazon and the Pacific coast. We observed that strong genetic mixing between geographically distant cacao populations occurred as early as the middle Holocene, in South America, driven by humans, favoring the adaptation of T. cacao to new environments. This complex history of cacao domestication is the basis of today's cacao tree populations and its knowledge can help us better manage their genetic resources.

Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards.

The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex. Adrenal cyst and myelolipoma are other benign adrenal lesions and are characterized by their fluid and fat content, respectively. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla. Metastases to the adrenal glands are the most common malignant adrenal tumors. While many of these masses have classic imaging appearances, considerable overlap exists between benign and malignant lesions and can pose a diagnostic challenge. Atypical adrenal adenomas include those that are lipid poor; contain macroscopic fat, hemorrhage, and/or iron; are heterogeneous and/or large; and demonstrate growth. Heterogeneous adrenal adenomas may mimic ACC, metastasis, or pheochromocytoma, particularly when they are 4 cm or larger, whereas smaller versions of ACC, metastasis, and pheochromocytoma and those with washout greater than 60% may mimic adenoma. Because of its nonenhanced CT attenuation of less than or equal to 10 HU, a lipid-rich adrenal adenoma may be mimicked by a benign adrenal cyst, or it may be mimicked by a tumor with central cystic and/or necrotic change such as ACC, pheochromocytoma, or metastasis. Rare adrenal tumors such as hemangioma, ganglioneuroma, and oncocytoma also may mimic adrenal adenoma, ACC, metastasis, and pheochromocytoma. The authors describe cases of adrenal neoplasms that they have encountered in clinical practice and presented to adrenal multidisciplinary tumor boards. Key lessons to aid in diagnosis and further guide appropriate management are provided. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Trans-Holocene Bayesian chronology for tree and field crop use from El Gigante rockshelter, Honduras.

El Gigante rockshelter in western Honduras provides a deeply stratified archaeological record of human-environment interaction spanning the entirety of the Holocene. Botanical materials are remarkably well preserved and include important tree (e.g., ciruela (Spondias), avocado (Persea americana)) and field (maize (Zea mays), beans (Phaseolus), and squash (Cucurbita)) crops. Here we provide a major update to the chronology of tree and field crop use evident in the sequence. We report 375 radiocarbon dates, a majority of which are for short-lived botanical macrofossils (e.g., maize cobs, avocado seeds, or rinds). Radiocarbon dates were used in combination with stratigraphic details to establish a Bayesian chronology for ~9,800 identified botanical samples spanning the last 11,000 years. We estimate that at least 16 discrete intervals of use occurred during this time, separated by gaps of ~100-2,000 years. The longest hiatus in rockshelter occupation was between ~6,400 and 4,400 years ago and the deposition of botanical remains peaked at ~2,000 calendar years before present (cal BP). Tree fruits and squash appeared early in the occupational sequence (~11,000 cal BP) with most other field crops appearing later in time (e.g., maize at ~4,400 cal BP; beans at ~2,200 cal BP). The early focus on tree fruits and squash is consistent with early coevolutionary partnering with humans as seed dispersers in the wake of megafaunal extinction in Mesoamerica. Tree crops predominated through much of the Holocene, and there was an overall shift to field crops after 4,000 cal BP that was largely driven by increased reliance on maize farming.

Lexicon for adrenal terms at CT and MRI: a consensus of the Society of Abdominal Radiology adrenal neoplasm disease-focused panel.

PURPOSE: Substantial variation in imaging terms used to describe the adrenal gland and adrenal findings leads to ambiguity and uncertainty in radiology reports and subsequently their understanding by referring clinicians. The purpose of this study was to develop a standardized lexicon to describe adrenal imaging findings at CT and MRI. METHODS: Fourteen members of the Society of Abdominal Radiology adrenal neoplasm disease-focused panel (SAR-DFP) including one endocrine surgeon participated to develop an adrenal lexicon using a modified Delphi process to reach consensus. Five radiologists prepared a preliminary list of 35 imaging terms that was sent to the full group as an online survey (19 general imaging terms, 9 specific to CT, and 7 specific to MRI). In the first round, members voted on terms to be included and proposed definitions; subsequent two rounds were used to achieve consensus on definitions (defined as ≥ 80% agreement). RESULTS: Consensus for inclusion was reached on 33/35 terms with two terms excluded (anterior limb and normal adrenal size measurements). Greater than 80% consensus was reached on the definitions for 15 terms following the first round, with subsequent consensus achieved for the definitions of the remaining 18 terms following two additional rounds. No included term had remaining disagreement. CONCLUSION: Expert consensus produced a standardized lexicon for reporting adrenal findings at CT and MRI. The use of this consensus lexicon should improve radiology report clarity, standardize clinical and research terminology, and reduce uncertainty for referring providers when adrenal findings are present.

Prevalence of Malignancy in Adrenal Nodules With Heterogeneous Microscopic Fat on Chemical-Shift MRI: A Multiinstitutional Study.

BACKGROUND. Homogeneous microscopic fat within adrenal nodules on chemical-shift MRI (CS-MRI) is diagnostic of benign adrenal adenoma, but the clinical relevance of heterogeneous microscopic fat is not well established. OBJECTIVE. This study sought to determine the prevalence of malignancy in adrenal nodules with heterogeneous microscopic fat on dual-echo T1-weighted CS-MRI. METHODS. We performed a retrospective study of adult patients with adrenal nodules detected on MRI performed between August 2007 and November 2020 at seven institutions. Eligible nodules had a short-axis diameter of 10 mm or larger with heterogeneous microscopic fat (defined by an area of signal loss of < 80% on opposed-phase CS-MRI). Two radiologists from each center, blinded to reference standard results, determined the signal loss pattern (diffuse, two distinct parts, speckling pattern, central loss, or peripheral loss) within the nodules. The reference standard used was available for 283 nodules (pathology for 21 nodules, ≥ 1 year of imaging follow-up for 245, and ≥ 5 years of clinical follow-up for 17) in 282 patients (171 women and 111 men; mean age, 60 ± 12 [SD] years); 30% (86/282) patients had prior malignancy. RESULTS. The mean long-axis diameter was 18.7 ± 7.9 mm (range, 10-80 mm). No malignant nodules were found in patients without prior cancer (0/197; 95% CI, 0-1.5%). Four of the 86 patients with prior malignancy (hepatocellular carcinoma [HCC], renal cell carcinoma [RCC], lung cancer, or both colon cancer and RCC) (4.7%; 95% CI, 1.3-11.5%) had metastatic nodules. Detected patterns were diffuse heterogeneous signal loss (40% [114/283]), speckling (28% [80/283]), two distinct parts (18% [51/283]), central loss (9% [26/283]), and peripheral loss (4% [12/283]). Two metastases from HCC and RCC showed diffuse heterogeneous signal loss. Lung cancer metastasis manifested as two distinct parts, and the metastasis in the patient with both colon cancer and RCC showed peripheral signal loss. CONCLUSION. Presence of heterogeneous microscopic fat in adrenal nodules on CS-MRI indicates a high likelihood of benignancy, particularly in patients without prior cancer. This finding is also commonly benign in patients with cancer; however, caution is warranted when primary malignancies may contain fat or if the morphologic pattern of signal loss may indicate a collision tumor. CLINICAL IMPACT. In the absence of prior cancer, adrenal nodules with heterogeneous microscopic fat do not require additional imaging evaluation.

COVID-19 Infection Related Bowel Perforation.

During an ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus, new discoveries about its complications and treatment are made every day. Bowel perforation is another rarely reported complication due to the virus itself leading to ischemia or can be due to the treatment with antiviral drugs that reduces the integrity of epithelial barriers. This makes the bowel more prone to perforation even in patients with no prior history of bowel disease. We report a case of bowel perforation in a 72-year-old male patient with severe COVID-19 infection.

Hereditary and Sporadic Pheochromocytoma: Comparison of Imaging, Clinical, and Laboratory Features.

BACKGROUND. A considerable fraction of pheochromocytomas initially suspected to be sporadic, whether or not symptomatic, are a result of germline mutations. OBJECTIVE. The purpose of this article is to compare imaging features between hereditary and sporadic pheochromocytomas. METHODS. This retrospective study included 71 patients (39 women, 32 men; median age, 48 years) who underwent adrenal pheochromocytoma resection from January 2002 to October 2021 after preoperative CT or MRI. Two radiologists independently reviewed examinations to assess features of the largest resected pheochromocytoma. Interreader agreement was assessed by prevalence-adjusted bias-adjusted kappa coefficients; a third radiologist resolved discrepancies for further analysis. Genetic testing was used to classify pheochromocytomas as hereditary or sporadic and to classify hereditary pheochromocytomas by germline mutation clusters. Symptoms associated with pheochromocytomas and preoperative biochemical laboratory values were recorded. Groups were compared using Kruskal-Wallis, Fisher exact, and chi-square tests, and false-discovery rate-adjusted p values were computed to account for multiple comparisons. RESULTS. Hereditary pheochromocytoma (n = 32), compared with sporadic pheochromocytoma (n = 39), was associated with younger median age (38 vs 52 years, p = .001) and smaller median size (24 vs 40 mm, p < .001). Interreader agreement for CT and MRI features, expressed as kappa, ranged from 0.44 to 1.00. Hereditary and sporadic pheochromocytoma showed no difference in frequency of calcifications, hemorrhage, cystic change/necrosis, or macroscopic fat on CT, or in frequency of hemorrhage, cystic change/necrosis, macroscopic fat, or microscopic fat on MRI (p > .05). When combining CT and MRI, cystic change/necrosis was observed in 35% of hereditary versus 67% of sporadic pheochromocytomas (p = .10). Hereditary pheochromocytoma, compared with sporadic, had lower frequency of symptoms (31% vs 74%; p = .004) and lower 24-hour urinary normetanephrines (1.1 vs 5.1 times upper limits of normal, p = .006). Among hereditary pheochromocytomas, cystic change/necrosis (when assessable on imaging) was present in 18% and 45% of those with cluster 1 (n = 11) and cluster 2 (n = 21) germ-line mutations, respectively. CONCLUSION. Hereditary pheochromocytomas, compared with sporadic, are detected at a younger age and smaller size, produce lower 24-hour urinary normetanephrines, are less often symptomatic, and may less frequently show cystic change/necrosis. CLINICAL IMPACT. Imaging findings may complement clinical and biochemical features in raising suspicion for a previously unsuspected germline mutation in patients with pheochromocytoma.

Sinogram-based deep learning image reconstruction technique in abdominal CT: image quality considerations.

OBJECTIVES: To investigate the image quality and perception of a sinogram-based deep learning image reconstruction (DLIR) algorithm for single-energy abdominal CT compared to standard-of-care strength of ASIR-V. METHODS: In this retrospective study, 50 patients (62% F; 56.74 ± 17.05 years) underwent portal venous phase. Four reconstructions (ASIR-V at 40%, and DLIR at three strengths: low (DLIR-L), medium (DLIR-M), and high (DLIR-H)) were generated. Qualitative and quantitative image quality analysis was performed on the 200 image datasets. Qualitative scores were obtained for image noise, contrast, small structure visibility, sharpness, and artifact by three blinded radiologists on a 5-point scale (1, excellent; 5, very poor). Radiologists also indicated image preference on a 3-point scale (1, most preferred; 3, least preferred). Quantitative assessment was performed by measuring image noise and contrast-to-noise ratio (CNR). RESULTS: DLIR had better image quality scores compared to ASIR-V. Scores on DLIR-H for noise (1.40 ± 0.53), contrast (1.41 ± 0.55), small structure visibility (1.51 ± 0.61), and sharpness (1.60 ± 0.54) were the best (p < 0.05) followed by DLIR-M (1.85 ± 0.52, 1.66 ± 0.57, 1.69 ± 0.59, 1.68 ± 0.46), DLIR-L (2.29 ± 0.58, 1.96 ± 0.61, 1.90 ± 0.65, 1.86 ± 0.46), and ASIR-V (2.86 ± 0.67, 2.55 ± 0.58, 2.34 ± 0.66, 2.01 ± 0.36). Ratings for artifacts were similar for all reconstructions (p > 0.05). DLIRs did not influence subjective textural perceptions and were preferred over ASIR-V from the beginning. All DLIRs had a higher CNR (26.38-102.30%) and lower noise (20.64-48.77%) than ASIR-V. DLIR-H had the best objective scores. CONCLUSION: Sinogram-based deep learning image reconstructions were preferred over iterative reconstruction subjectively and objectively due to improved image quality and lower noise, even in large patients. Use in clinical routine may allow for radiation dose reduction. KEY POINTS: • Deep learning image reconstructions (DLIRs) have a higher contrast-to-noise ratio compared to medium-strength hybrid iterative reconstruction techniques. • DLIR may be advantageous in patients with large body habitus due to a lower image noise. • DLIR can enable further optimization of radiation doses used in abdominal CT.

Dual-layer dual-energy CT for characterization of adrenal nodules: can virtual unenhanced images replace true unenhanced acquisitions?

PURPOSE: To investigate the diagnostic performance of dual-layer dual-energy CT (dlDECT) in the evaluation of adrenal nodules. METHODS: In this retrospective study, 66 patients with triphasic dlDECT (unenhanced, venous phase (VP), delayed phase (DP)) for suspected adrenal lesions were included. Virtual unenhanced images (VUE) were derived from VP acquisitions. Reference diagnoses were established with true unenhanced (TUE) attenuation, absolute washout, follow-up imaging and pathological data. Attenuation for adrenal lesions and abdominal tissues was acquired on TUE, VUE, VP and DP images. VUE and TUE attenuation were compared in all included tissues. Characterization of adrenal nodules based on TUE and VUE attenuation was investigated. ROC analysis was used to determine an adjusted threshold for diagnosing lipid-rich adenomas. RESULTS: Seventy-three adrenal nodules (mean size: 18.9 ± 8.9 mm) were identified in 66 patients (38 females, 28 males; age: 61 ± 13 years) including adenoma (n = 65), metastases (n = 2), pheochromocytoma (n = 3), adrenocortical carcinoma (n = 1) and myelolipoma (n = 2). Mean attenuation of all included tissues except for the abdominal aorta (p = 0.11) was significantly higher in VUE compared to TUE images, including the attenuation of adrenal nodules (20.0 ± 17.2 vs. 7.1 ± 19.8; p < 0.05). Classification of adrenal adenomas as lipid-rich based on VUE attenuation ≤ 10 HU yielded a sensitivity/specificity of 0.2/1.0, while an adjusted threshold of ≤ 22 HU yielded a sensitivity/specificity of 0.82/0.85. CONCLUSION: dlDECT-derived VUE images overestimated attenuation in adrenal nodules, resulting in low sensitivity for diagnosis of lipid-rich adenomas using the established 10 HU threshold. Based on an adjusted threshold (≤ 22 HU) a higher sensitivity was attained, yet at the expense of a lower specificity, warranting further validation.

Texture Analysis as a Radiomic Marker for Differentiating Benign From Malignant Adrenal Tumors.

OBJECTIVE: The aim of this study was to evaluate the use of texture analysis for differentiation between benign from malignant adrenal lesions on contrast-enhanced abdominal computed tomography (CT). METHODS: After institutional review board approval, a retrospective analysis was performed, including an electronic search of pathology records for all biopsied adrenal lesions. Patients were included if they also had a contrast-enhanced abdominal CT in the portal venous phase. Computed tomographic images were manually segmented, and texture analysis of the segmented tumors was performed. Texture analysis results of benign and malignant tumors were compared, and areas under the curve (AUCs) were calculated. RESULTS: One hundred twenty-five patients were included in the analysis. Excellent discriminators of benign from malignant lesions were identified, including entropy and standard deviation. These texture features demonstrated lower values for benign lesions compared with malignant lesions. Entropy values of benign lesions averaged 3.95 using a spatial scaling factor of 4 compared with an average of 5.08 for malignant lesions (P < .0001). Standard deviation values of benign lesions averaged 19.94 on the unfiltered image compared with an average of 34.32 for malignant lesions (P < .0001). Entropy demonstrated AUCs ranging from 0.95 to 0.97 for discriminating tumors, with sensitivities and specificities ranging from 81% to 95% and 88% to 100%, respectively. Standard deviation demonstrated AUCs ranging from 0.91 to 0.94 for discriminating tumors, with sensitivities and specificities ranging from 73% to 93% and 86% to 95%, respectively. CONCLUSION: Texture analysis offers a noninvasive tool for differentiating benign from malignant adrenal tumors on contrast-enhanced CT images. These results support the further development of texture analysis as a quantitative biomarker for characterizing adrenal tumors.