Performance of capsule endoscopy for the detection of small intestinal neuroendocrine tumors in familial carcinoid: a prospective single-site study.

BACKGROUND AND AIMS: Small-bowel neuroendocrine tumors (NETs) are slow growing, clinically silent tumors whose prognosis depends on disease stage. Members of kindreds with a familial form of small intestinal NETs (SI-NETs) represent a high-risk population for whom early detection improves disease outcome. Our aim was to determine the utility of small-bowel capsule endoscopy (SB-CE) for screening high-risk asymptomatic relatives from kindreds with familial carcinoid. METHODS: One hundred seventy-four asymptomatic subjects with a family history (≥2 family members) of SI-NETs were screened under Protocol NCT00646022, Natural History of Familial Carcinoid Tumor at the National Institutes of Health. All patients were imaged with SB-CE and 18fluoro-dihydroxphenylalanine (18F-DOPA) positron emission tomography (PET)/CT, and results were independently analyzed. Patients with a positive imaging study underwent surgical exploration. RESULTS: Thirty-five of 174 asymptomatic subjects screened for SI-NETs were positive on either SB-CE or 18F-DOPA PET. Thirty-two of 35 patients with a positive study were confirmed at surgery. SB-CE was positive in 28 of 32 patients with confirmed tumors for a per-patient sensitivity of 87.5%. SB-CE had a specificity of 97.3% and a negative predictive value of 96.5%. The average tumor number and size were 7.7 and 5.0 mm, respectively, and 81.2% of patients had multiple tumors. 18F-DOPA PET/CT had a similar sensitivity of 84% versus surgery. CONCLUSIONS: SB-CE is a sensitive and specific method comparable with 18F-DOPA PET/CT for screening high-risk patients with familial SI-NET. (Clinical trial registration number: NCT00646022.).

Skin and Subcutaneous Tissue Metastases of the Pulmonary Carcinoid Tumor on 68 Ga-DOTATATE PET/CT.

ABSTRACT: Pulmonary carcinoid tumors are a very rare type of neuroendocrine tumor, accounting for only 1% to 2% of all primary lung cancers. Pulmonary carcinoids most commonly metastasize to the mediastinal lymph nodes, liver, and bones. Metastasis of pulmonary carcinoids to the skin and subcutaneous tissue is extremely rare and has been reported in only a small number of cases. We presented 68 Ga-DOTATATE PET/CT findings of an exceptional case of a pulmonary carcinoid tumor with extensive skin, subcutaneous, thyroid, and intramuscular metastases.

Malignant and Benign Tracheobronchial Neoplasms: Comprehensive Review with Radiologic, Bronchoscopic, and Pathologic Correlation.

Tracheobronchial neoplasms are much less common than lung parenchymal neoplasms but can be associated with significant morbidity and mortality. They include a broad differential of both malignant and benign entities, extending far beyond more commonly known pathologic conditions such as squamous cell carcinoma and carcinoid tumor. Airway lesions may be incidental findings at imaging or manifest with symptoms related to airway narrowing or mucosal irritation, invasion of adjacent structures, or distant metastatic disease. While there is considerable overlap in clinical manifestation, imaging features, and bronchoscopic appearances, an awareness of potential distinguishing factors may help narrow the differential diagnosis. The authors review the epidemiology, imaging characteristics, typical anatomic distributions, bronchoscopic appearances, and histopathologic findings of a wide range of neoplastic entities involving the tracheobronchial tree. Malignant neoplasms discussed include squamous cell carcinoma, malignant salivary gland tumors (adenoid cystic carcinoma and mucoepidermoid carcinoma), carcinoid tumor, sarcomas, primary tracheobronchial lymphoma, and inflammatory myofibroblastic tumor. Benign neoplasms discussed include hamartoma, chondroma, lipoma, papilloma, amyloidoma, leiomyoma, neurogenic lesions, and benign salivary gland tumors (pleomorphic adenoma and mucous gland adenoma). Familiarity with the range of potential entities and any distinguishing features should prove valuable to thoracic radiologists, pulmonologists, and cardiothoracic surgeons when encountering the myriad of tracheobronchial neoplasms in clinical practice. Attention is paid to any features that may help render a more specific diagnosis before pathologic confirmation. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Incidental Detection of Dual Spinal Meningiomas on 68 Ga-DOTATATE PET/CT Masquerading as Metastatic Disease in a Patient With Pulmonary Carcinoid Tumor.

ABSTRACT: Simultaneous occurrence of multiple meningiomas of the spine appearing at different neuroaxial levels is extremely rare event. We present the scintigraphic findings of incidentally detected multiple meningiomas of the spine on 68 Ga-DOTATATE PET/CT during the evaluation of a patient with pulmonary carcinoid tumor. These scintigraphic findings could result in a "false-positive" interpretation by exhibiting highly increased uptake similar to that of metastases of neuroendocrine neoplasm. Nuclear medicine physicians should be aware of this potential pitfall in somatostatin receptor imaging to prevent misinterpretation.

Growth Rates of Pulmonary Carcinoid Tumors and Hamartomas.

BACKGROUND: Pulmonary nodule growth is often measured by volume doubling time (VDT), which may guide management. Most malignant nodules have a VDT of 20 to 400 days, with longer VDTs typically observed in indolent nodules. We assessed the utility of VDT in differentiating pulmonary carcinoids and hamartomas. METHODS: A review was performed from January 2012 to October 2021 to identify patients with pathologic diagnoses and at least 2 chest computed tomography scans obtained 6 or more months apart. Visualization software was used to segment nodules and calculate diameter and volume. Volume doubling time was calculated for scans with 1-mm slices. For the remainder, estimated nodule volume doubling time (eVDT) was calculated using nodule diameter. Volume doubling times/eVDTs were placed into growth categories: less than 400 days; 400-600 days; and more than 600 days. RESULTS: Sixty nodules were identified, 35 carcinoids and 25 hamartomas. Carcinoids were larger than hamartomas (median diameter, 13.5 vs 11.5 mm; P = 0.05). For carcinoid tumors, median VDT (n = 15) was 1485 days, and median eVDT (n = 32) was 1309 days; for hamartomas, median VDT (n = 8) was 2040 days and median eVDT (n = 25) was 2253 days. Carcinoid tumor eVDT was significantly shorter than hamartomas ( P = 0.03). By growth category, 1 of 25 hamartomas and 5 of 35 carcinoids had eVDT less than 400 days and 24 of 25 hamartomas and 27 of 35 carcinoids had eVDT more than 600 days. Of 4 carcinoid tumors with metastases, 2 had eVDT less than 400 days and 2 had eVDT more than 600 days. CONCLUSIONS: Growth rate was not a reliable differentiator of pulmonary hamartomas and carcinoids. Slow growing carcinoids can metastasize. Radiologists should be cautious when discontinuing computed tomography follow-up based on growth rates alone.

Differentiating Peripherally Located Pulmonary Noncalcified Hamartoma From Carcinoid Using CT Radiomics Approaches.

OBJECTIVE: This article aimed to differentiate noncalcified hamartoma from pulmonary carcinoid preoperatively using computed tomography (CT) radiomics approaches. MATERIALS AND METHODS: The unenhanced CT (UECT) and contrast-enhanced CT (CECT) data of noncalcified hamartoma (n = 73) and pulmonary carcinoid (n = 54; typical/atypical carcinoid = 13/41) were retrospectively analyzed. The patients were randomly divided into the training and validation sets. A total of 396 radiomics features were extracted from UECT and CECT, respectively. The features were selected by using the minimum redundancy maximum relevance and the least absolute shrinkage and selection operator to construct a radiomics model. Clinical factors and radiomics features were integrated to build a nomogram model. The performance of clinical factors, radiomics, and nomogram models on the differential diagnosis between noncalcified hamartoma and carcinoid were investigated. Diagnostic performance of radiologists was also explored. RESULT: In regard to distinguishing noncalcified hamartoma from carcinoid, the areas under the receiver operating characteristic curves of the clinical, radiomics, and nomogram models were 0.88, 0.94, and 0.96 in the training set UECT, and were 0.85, 0.92, and 0.96 in the training set CECT, respectively. The areas under the curve of the 3 models were 0.89, 0.96, and 0.96 in the validation set UECT, and were 0.79, 0.90, and 0.94 in the validation set CECT, respectively. The nomogram model exhibited good calibration and was clinically useful by decision curve analysis. Nomogram did not show significant improvement compared with radiomics, neither for UECT nor for CECT. Diagnostic performance of radiologists was lower than both radiomics and nomogram model. CONCLUSIONS: Radiomics approaches may be useful in distinguishing peripheral pulmonary noncalcified hamartoma from carcinoid. Radiomics features extracted from CECT provided no significant benefit when compared with UECT.

Complete Regression of Endobronchial Carcinoid Tumor after an Endoscopic Biopsy.

An 80-year-old woman who had been diagnosed with an endobronchial carcinoid tumor visited our hospital for treatment with an endoscopic technique. However, a bronchoscopic examination at our hospital showed spontaneous regression of the tumor at the orifice of the right middle lobar bronchus. Chest computed tomography five months later revealed no local recurrence. This is the second report of an endobronchial carcinoid tumor vanishing after an endoscopic biopsy.

Fully-automated detection of small bowel carcinoid tumors in CT scans using deep learning.

BACKGROUND: Small bowel carcinoid tumor is a rare neoplasm and increasing in incidence. Patients with small bowel carcinoid tumors often experience long delays in diagnosis due to the vague symptoms, slow growth of tumors, and lack of clinician awareness. Computed tomography (CT) is the most common imaging study for diagnosis of small bowel carcinoid tumor. It is often used with positron emission tomography (PET) to capture anatomical and functional aspects of carcinoid tumors and thus to increase the sensitivity. PURPOSE: We compared three different kinds of methods for the automatic detection of small bowel carcinoid tumors on CT scans, which is the first to the best of our knowledge. METHODS: Thirty-three preoperative CT scans of 33 unique patients with surgically-proven carcinoid tumors within the small bowel were collected. Ground-truth segmentation of tumors was drawn on CT scans by referring to available 18 F-DOPA PET scans and the corresponding radiology report. These scans were split into the trainval set (n = 24) and the test positive set (n= 9). Additionally, 22 CT scans of 22 unique patients who had no evidence of the tumor were collected to comprise the test negative set. We compared three different kinds of detection methods, which are detection network, patch-based classification, and segmentation-based methods. We also investigated the usefulness of small bowel segmentation for reduction of false positives (FPs) for each method. Free-response receiver operating characteristic (FROC) curves and receiver operating characteristic (ROC) curves were used for lesion- and patient-level evaluations, respectively. Statistical analyses comparing the FROC and ROC curves were also performed. RESULTS: The detection network method performed the best among the compared methods. For lesion-level detection, the detection network method, without the small bowel segmentation-based filtering, achieved sensitivity values of (60.8%, 81.1%, 82.4%, 86.5%) at per-scan FP rates of (1, 2, 4 ,8), respectively. The use of the small bowel segmentation did not improve the performance ( p = 0.742 $p=0.742$ ). For patient-level detection, again the detection network method, but with the small bowel segmentation-based filtering, achieved the highest AUC of 0.86 with a sensitivity of 78% and specificity of 82% at the Youden point. CONCLUSIONS: The carcinoid tumors in this patient population were very small and potentially difficult to diagnose. The presented method showed reasonable sensitivity at small numbers of FPs for lesion-level detection. It also achieved a promising AUC for patient-level detection. The method may have clinical application in patients with this rare and difficult to detect disease.

Added prognostic value of molecular imaging parameters over proliferation index in typical lung carcinoid: an [18F]FDG PET/CT and SSTR imaging study.

OBJECTIVE: This study was performed to evaluate the prognostic meaning of volumetric and semi-quantitative parameters measured using [18F]FDG PET/CT and somatostatin receptor (SSTR) imaging in patients with typical lung carcinoid (TC), and their relationship with proliferative index (Ki67). METHODS: We retrospectively reviewed 67 patients (38-94 years old, mean: 69.7) with diagnosis of TC who underwent [18F]FDG PET/CT and/or SSTR scintigraphy/SPECT with [111In]DTPA-Octreotide plus contrast-enhanced CT (CECT) at staging evaluation. All patients had Ki67 measured and a follow-up (FU) of at least 1 year. SSTR density (SSTRd) was calculated as the percentage difference of tumor/non-tumor ratio at 4 and 24 h post-injection. At PET/CT, metabolic activity was measured using SUVmax and SUVratio; volumetric parameters included MTV and TLG of the primary tumor, measured using the threshold SUV41%. ROC analysis, discriminant analysis and Kaplan-Meier curves (KM) were performed. RESULTS: 11 patients died during FU. Disease stage (localized versus advanced), SUVratio, SUVmax, Ki67, MTV and TLG were significantly higher in non-survivors than in survivors. ROC curves resulted statistically significant for Ki67, SUVratio, SUVmax, MTV and TLG. On multivariate analysis, stage of disease and TLG were significant independent predictors of overall survival (OS). In KM curves, the combination of disease stage and TLG identified four groups with significantly different outcomes (p < 0.005). Metabolic activity (SUVmax and SUVratio) was confirmed as significant independent prognostic factor for OS also in patients with advanced disease, with the best AUC using SUVmax. In patients with advanced and localized disease, SSTRd proved to be the best imaging prognostic factor for progression and for disease-free survival (DFS), respectively. In localized disease, SSTRd 31.5% identified two subgroups of patients with significant different DFS distribution and in advanced disease, a high cutoff value (58.5%) was a significant predictor of adverse prognosis. CONCLUSION: Volumetric and semi-quantitative parameters measured using [18F]FDG PET/CT and SSTR imaging combined with Ki67 may provide a reference for prognosis evaluation of patients with TC, to better stratify risk groups with the goal of developing individualized therapeutic strategies.

The diagnostic and prognostic role of combined [18F]FDG and [68Ga]-DOTA-peptides PET/CT in primary pulmonary carcinoids: a multicentric experience.

OBJECTIVES: In the present retrospective multicentric study, we combined [68Ga]-DOTA-peptides and [18F]FDG-PET/CT findings aiming to investigate their capability to differentiate typical (TC) and atypical pulmonary carcinoids (AC) and their prognostic role. METHODS: From three centers, 61 patients were retrospectively included. Based on a dual tracer combination we classified PET scans as score 1, [18F]FDG- and [68Ga]-DOTA-peptides negative; score 2, [68Ga]-DOTA-peptides positive and [18F]FDG-negative; score 3, [68Ga]-DOTA-peptides negative and [18F]FDG-positive; score 4, both tracers positive. Moreover, for each patient, the ratios of SUVmax on [68Ga]-DOTA-PET to that on [18F]FDG-PET were calculated (SUVr). RESULTS: Thirty-five patients had a final diagnosis of TC. Twenty-two TC (57%) had positive [68Ga]-DOTA-peptides PET; instead, 21/26 (81%) AC had positive [18F]FDG-PET/CT. On dual-tracer analysis, scores 1, 2, 3 and 4 were 13%, 20%, 43% and 24% for all populations; 17%, 26%, 20% and 37% for TC; 8%, 11%, 73% and 8% for AC. Median SUVr was significantly higher in TC than AC (6.4 vs. 0.4, p = 0.011). The best value of SUVr to predict the final diagnosis was 1.05 (AUC 0.889). Relapse or progression of disease happened in 17 patients (11 affected by AC) and death in 10 cases (7 AC). AC diagnosis, positive [18F]FDG-PET, negative DOTA-PET and dual tracer score were significantly correlated with PFS (p = 0.013, p = 0.033, p = 0.029 and p = 0.019), while only AC diagnosis with OS (p = 0.022). CONCLUSION: PET/CT findings had also a prognostic role in predicting PFS. Dual-tracer PET behavior may be used to predict the nature of pulmonary carcinoids and select the most appropriate management. KEY POINTS: • Combination of [18F]FDG and [68Ga]-DOTA-peptides PET/CT results may help to differentiate between atypical and typical lung carcinoids. • The SUVmax ratio between [18F]FDG and [68Ga]-DOTA-peptides PET may help to differentiate between atypical and typical lung carcinoids. • Histotype and PET/CT features have a prognostic impact on PFS.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): a little known cause of thoracic lesions.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare but important condition to consider when investigating a patient with suspected thoracic malignancy. There is very little known about DIPNECH and it is considered to be a precursor to carcinoid tumour of the lung. This case report aims to increase awareness of this largely unknown and rare condition and to better improve its consideration as a differential diagnosis in patients who remain unresponsive to conventional treatment.

The utility of near infrared autofluorescence imaging for detecting small bowel carcinoid tumors in comparison to DOTATATE PET: A pilot study.

BACKGROUND: Small bowel carcinoid (SBC) primary tumors can be multifocal in 40%-55% of patients and challenging to detect. Near infrared autofluorescence (NIRAF) is used for detection of parathyroid glands. It is unknown if this technology can be used to identify SBCs and how it would compare with current imaging modalities. METHODS: This was a prospective institutional review board-approved pilot study of three patients undergoing resection of SBCs. NIRAF was used to image SBCs and mesenteric lymph nodes intraoperatively and at back table. Findings were compared with preoperative imaging, surgical exploration and pathology. Statistics were performed using Mann-Whitney U test. RESULTS: Eleven SBCs and 12 mesenteric lymph nodes were analyzed. All SBCs had a brighter focal autofluorescence (AF) signal compared to background. Normalized pixel intensity of SBCs was 2.2 (0.7) and normal small bowel 1.4 (0.6) (p < 0.0001). NIRAF was less accurate in detecting occult lymph node metastasis, but was superior to DOTATATE PET for detecting SBCs in two of three patients. CONCLUSIONS: This preliminary report suggests that SBCs exhibit distinctly bright AF signals on NIRAF to create a contrast distinction from normal small bowel. This technology may have a utility as an adjunctive tool for intraoperative detection of occult SBCs.

Volume Doubling Time of Pulmonary Carcinoid Tumors Measured by Computed Tomography.

INTRODUCTION: Pulmonary carcinoid tumor (PCT) is a rare neuroendocrine lung neoplasm comprising approximately 2% of lung cancer diagnoses. It is classified as either localized low-grade (typical) or intermediate-grade (atypical) subtypes. PCT is known clinically to be a slow-growing cancer, however few studies have established its true growth rate when followed over time by computed tomography (CT). Therefore, we sought to determine the volume doubling time for PCTs as visualized on CT imaging. MATERIALS AND METHODS: We conducted a retrospective analysis of all PCTs treated at our institution between 2006 and 2020. Nodule dimensions were measured using a Picture Archiving and Communication System or retrieved from radiology reports. Volume doubling time was calculated using the Schwartz formula for PCTs followed by successive CT scans during radiographic surveillance. Consistent with Fleischner Society guidelines, tumors were considered to have demonstrated definitive growth by CT only when the interval change in tumor diameter was greater than or equal to 2 mm. RESULTS: The median volume doubling time of 13 typical PCTs was 977 days, or 2.7 years. Five atypical PCTs were followed longitudinally, with a median doubling time of 327 days, or 0.9 years. CONCLUSIONS: Typical pulmonary carcinoid features a remarkably slow growth rate as compared to more common lung cancers. Our analysis of atypical pulmonary carcinoid included too few cases to offer definitive conclusions. It is conceivable that clinicians following current nodule surveillance guidelines may mistake incidentally detected typical carcinoids for benign non-growing lesions when followed for less than 2 years in low-risk patients.

Clinicopathological, Oncogenic, and 18F-FDG PET/CT Features of Primary Pulmonary Carcinoid in Resection Specimens.

Objectives: The metabolic parameters which included mean standardised uptake value (SUVmean), metabolic tumour volume (MTV), total lesion glycolysis (TLG), maximum standardised uptake lean body mass (SULmax), and maximum standardised uptake body surface area (SUVbsa) have rarely been investigated in pulmonary carcinoid (PC). This study aimed to retrospectively compare the 18F-FDG PET/CT features of PC subtypes and observe clinicopathological and oncogenic characteristics of PC. Methods: We performed a retrospective review in 60 patients with PC, from January 2016 to November 2021, who underwent the 18F-FDG PET/CT scan. All the PC diagnoses were histopathologic confirmed by surgical samples. The metabolic and morphological features were obtained from 18F-FDG PET/CT images. The ratio of metabolic to morphological lesion volumes (MMVR) was calculated. Results: Sixty patients with PC were consecutively identified, including 39 patients (65.0%) with typical carcinoids (TCs) and 21 (35.0%) with atypical carcinoids (ACs). One (1/21) patient had mutation in BRAF. The ACs have a larger size (P < 0.001), more metastatic lymph nodes (P = 0.011), higher Ki-67 expression (P < 0.001), higher SUVmax values (P = 0.003), higher SUVmean values (P = 0.006), higher SULmax values (P = 0.005), higher SUVbsa values (P = 0.001), higher MTV values (P = 0.033), and higher TLG values (P = 0.002). The multivariate analysis showed that MMVR (P = 0.020) was significantly associated with AC. For predicting AC, the optimal cut-off value of SUVmax, SUVmean, SULmax, SUVbsa, MTV, TLG, and the maximum diameter was 5.19, 3.18, 2.65, 1.47, 4.36, 18.44, and 3.0, respectively. The AUC values of above mentioned parameters was 0.756 (95%CI, 0.631-881; P = 0.001), 0.735 (95%CI, 0.602-868; P = 0.003), 0.736 (95%CI, 0.607-865; P = 0.003), 0.742 (95%CI, 0.612-873; P = 0.002), 0.593 (95%CI, 0.430-755; P = 0.239), 0.680 (95%CI, 0.531-829; P = 0.022), and 0.733 (95%CI, 0.598-868; P = 0.003), respectively. For predicting TC, the optimal cut-off value of the MMVR was 0.92, and the AUC value was 0.780 (95%CI, 0.647-0.913; P < 0.001). Conclusion: 18F-FDG PET/CT can simultaneously reveal the metabolic and morphological characteristics of PC, which is important in the differentiation for histopathologic subtypes.