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.

Simultaneous multislice diffusion-weighted imaging versus standard diffusion-weighted imaging in whole-body PET/MRI.

OBJECTIVE: To compare standard (STD-DWI) single-shot echo-planar imaging DWI and simultaneous multislice (SMS) DWI during whole-body positron emission tomography (PET)/MRI regarding acquisition time, image quality, and lesion detection. METHODS: Eighty-three adults (47 females, 57%), median age of 64 years (IQR 52-71), were prospectively enrolled from August 2018 to March 2020. Inclusion criteria were (a) abdominal or pelvic tumors and (b) PET/MRI referral from a clinician. Patients were excluded if whole-body acquisition of STD-DWI and SMS-DWI sequences was not completed. The evaluated sequences were axial STD-DWI at b-values 50-400-800 s/mm2 and the apparent diffusion coefficient (ADC), and axial SMS-DWI at b-values 50-300-800 s/mm2 and ADC, acquired with a 3-T PET/MRI scanner. Three radiologists rated each sequence's quality on a five-point scale. Lesion detection was quantified using the anatomic MRI sequences and PET as the reference standard. Regression models were constructed to quantify the association between all imaging outcomes/scores and sequence type. RESULTS: The median whole-body STD-DWI acquisition time was 14.8 min (IQR 14.1-16.0) versus 7.0 min (IQR 6.7-7.2) for whole-body SMS-DWI, p < 0.001. SMS-DWI image quality scores were higher than STD-DWI in the abdomen (OR 5.31, 95% CI 2.76-10.22, p < 0.001), but lower in the cervicothoracic junction (OR 0.21, 95% CI 0.10-0.43, p < 0.001). There was no significant difference in the chest, mediastinum, pelvis, and rectum. STD-DWI detected 276/352 (78%) lesions while SMS-DWI located 296/352 (84%, OR 1.46, 95% CI 1.02-2.07, p = 0.038). CONCLUSIONS: In cancer staging and restaging, SMS-DWI abbreviates acquisition while maintaining or improving the diagnostic yield in most anatomic regions. KEY POINTS: • Simultaneous multislice diffusion-weighted imaging enables faster whole-body image acquisition. • Simultaneous multislice diffusion-weighted imaging maintains or improves image quality when compared to single-shot echo-planar diffusion-weighted imaging in most anatomical regions. • Simultaneous multislice diffusion-weighted imaging leads to superior lesion detection.

PI-RADS Versions 2 and 2.1: Interobserver Agreement and Diagnostic Performance in Peripheral and Transition Zone Lesions Among Six Radiologists.

BACKGROUND. PI-RADS version 2.1 (v2.1) modifications primarily address transition zone (TZ) interpretation. The revisions also impact peripheral zone (PZ) interpretation, which has received less attention. OBJECTIVE. The purpose of this study was to compare interobserver agreement of PI-RADS version 2 (v2) and v2.1 in the prostate PZ and TZ and perform a pilot comparison of their diagnostic performance in the two zones. METHODS. Six radiologists with varying experience retrospectively assessed 80 prostate lesions (40 PZ, 40 TZ) on MRI in separate sessions for PI-RADS v2 and v2.1. Interobserver agreement was assessed using Conger kappa (κ). For 50 lesions with pathology data, average AUC for detecting clinically significant cancer was compared between versions using multireader multicase statistical methods. Error variance and covariance results informed post hoc power analysis. RESULTS. Interobserver agreement for PI-RADS category 4 or greater was higher for version 2.1 (κ = 0.64) than version 2 (κ = 0.51) in the PZ, but similar for version 2 (κ = 0.64) and version 2.1 (κ = 0.60) in the TZ. The PI-RADS v2.1 DWI descriptor "linear/wedge-shaped" had higher agreement than its predecessor version 2 descriptor "indistinct hypointense" (κ = 0.52 vs κ = 0.18) and yielded 14 more true-negative versus five more false-negative interpretations. The ADC signal descriptor "markedly hypointense," for which only version 2.1 provides a specific definition, had lower agreement in version 2.1 (κ = 0.26) than version 2 (κ = 0.52). Modified TZ T2-weighted category 2 descriptors in version 2.1 had fair agreement (κ = 0.21), and agreement for PI-RADS category 2 in the TZ was lower in version 2.1 (κ = 0.31) than version 2 (κ = 0.57). DWI upgraded a TZ lesion category from 2 to 3 in four patients, detecting two additional cancers. Average AUC was not different between versions 2 and 2.1 for the PZ (AUC, 0.81 vs 0.85; p = .24) or the TZ (AUC, 0.69 vs 0.69; p = .94), though among experienced readers AUC was higher for version 2.1 than version 2 for the PZ (0.91 vs 0.82; p = .001). Overall performance comparison had sufficient power (0.8) to detect a 0.085 difference in AUC. CONCLUSION. Interobserver agreement improved using PI-RADS v2.1 in the PZ but not the TZ. Diagnostic performance improved using version 2.1 only in the PZ for experienced readers. Specific version 2.1 modifications yielded mixed results. CLINICAL IMPACT. The impact of PI-RADS v2.1 in the PZ is notable given the emphasis on version 2.1 TZ modifications. The findings suggest areas in which additional modification could further improve interobserver agreement and performance.

Marginal and joint distributions of S100, HMB-45, and Melan-A across a large series of cutaneous melanomas.

CONTEXT: The distribution of the standard melanoma antibodies S100, HMB-45, and Melan-A has been extensively studied. Yet, the overlap in their expression is less well characterized. OBJECTIVES: To determine the joint distributions of the classic melanoma markers and to determine if classification according to joint antigen expression has prognostic relevance. DESIGN: S100, HMB-45, and Melan-A were assayed by immunofluorescence-based immunohistochemistry on a large tissue microarray of 212 cutaneous melanoma primary tumors and 341 metastases. Positive expression for each antigen required display of immunoreactivity for at least 25% of melanoma cells. Marginal and joint distributions were determined across all markers. Bivariate associations with established clinicopathologic covariates and melanoma-specific survival analyses were conducted. RESULTS: Of 322 assayable melanomas, 295 (91.6%), 203 (63.0%), and 236 (73.3%) stained with S100, HMB-45, and Melan-A, respectively. Twenty-seven melanomas, representing a diverse set of histopathologic profiles, were S100 negative. Coexpression of all 3 antibodies was observed in 160 melanomas (49.7%). Intensity of endogenous melanin pigment did not confound immunolabeling. Among primary tumors, associations with clinicopathologic parameters revealed a significant relationship only between HMB-45 and microsatellitosis (P = .02). No significant differences among clinicopathologic criteria were observed across the HMB-45/Melan-A joint distribution categories. Neither marginal HMB-45 (P = .56) nor Melan-A (P = .81), or their joint distributions (P = .88), was associated with melanoma-specific survival. CONCLUSIONS: Comprehensive characterization of the marginal and joint distributions for S100, HMB-45, and Melan-A across a large series of cutaneous melanomas revealed diversity of expression across this group of antigens. However, these immunohistochemically defined subclasses of melanomas do not significantly differ according to clinicopathologic correlates or outcome.

Melanoma prognostic model using tissue microarrays and genetic algorithms.

PURPOSE: As a result of the questionable risk-to-benefit ratio of adjuvant therapies, stage II melanoma is currently managed by observation because available clinicopathologic parameters cannot identify the 20% to 60% of such patients likely to develop metastatic disease. Here, we propose a multimarker molecular prognostic assay that can help triage patients at increased risk of recurrence. METHODS: Protein expression for 38 candidates relevant to melanoma oncogenesis was evaluated using the automated quantitative analysis (AQUA) method for immunofluorescence-based immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a cohort of 192 primary melanomas collected during 1959 to 1994. The prognostic assay was built using a genetic algorithm and validated on an independent cohort of 246 serial primary melanomas collected from 1997 to 2004. RESULTS: Multiple iterations of the genetic algorithm yielded a consistent five-marker solution. A favorable prognosis was predicted by ATF2 ln(non-nuclear/nuclear AQUA score ratio) of more than -0.052, p21(WAF1) nuclear compartment AQUA score of more than 12.98, p16(INK4A) ln(non-nuclear/nuclear AQUA score ratio) of < or = -0.083, beta-catenin total AQUA score of more than 38.68, and fibronectin total AQUA score of < or = 57.93. Primary tumors that met at least four of these five conditions were considered a low-risk group, and those that met three or fewer conditions formed a high-risk group (log-rank P < .0001). Multivariable proportional hazards analysis adjusting for clinicopathologic parameters shows that the high-risk group has significantly reduced survival on both the discovery (hazard ratio = 2.84; 95% CI, 1.46 to 5.49; P = .002) and validation (hazard ratio = 2.72; 95% CI, 1.12 to 6.58; P = .027) cohorts. CONCLUSION: This multimarker prognostic assay, an independent determinant of melanoma survival, might be beneficial in improving the selection of stage II patients for adjuvant therapy.