Lung Neuroendocrine Tumors Research Articles

Low Risk for All-Cause Mortality Among Patients With Lung Neuroendocrine Tumors Co-Diagnosed With Pituitary Adenoma

Context: Lung neoplasm often co-occur with pituitary adenoma (PA). However, whether co-diagnosis of lung neuroendocrine tumors (LNET) and PA constitute unique entity, and the impact of such co-diagnosis on patients outcome is yet to be defined. Objective: To compare the clinical characteristics of patients with LNET to those co-diagnosed with PA. Design: Retrospective, case-control study including patients diagnosed with LNET or PA between 2000 and 2016. Setting: The Surveillance, Epidemiology and End Results database. Patients: 2,947 patients had LNET, including 2,913 with LNET alone (“Sporadic”) and 34 patients with both LNET and PA (“MENx”). Main Outcome Measure(s): All-cause mortality (ACM). Results: PA preceded LNET diagnosis in 85.3% of patients and had higher rates among LNET patients (34/2,947) than with any cancer (p<0.00001) and compared to patients with non-small cell lung cancer (NSCLC) (15/2,378, p=0.047). MENx patients were younger at diagnosis compared with NSCLC patients and PA (p=0.04). Among patients<60 years with LNET, co-diagnosis with PA was associated with lower ACM risk (Log-rank test, p=0.03). Adjusted ACM risk of patients with “MENx” was lower than sporadic LNET (hazard ratio 0.553, 95% confidence interval 0.309-0.99, p=0.046), especially among Caucasians, and a lower overall-mortality risk in patients <60 years with borderline statistical significance (p=0.071). Conclusions: Patients with both LNET and PA constitute a distinct morbidity and mortality profile compared with sporadic LNET possibly suggesting an undefined MEN syndrome. Additional studies to further investigate the natural course and genetic profile of patients with these neoplasms are needed.

Occult Carcinoid Causes Cushing’s Syndrome

Introduction: Lung neuroendocrine tumors (NETs) are a common cause of ectopic ACTH-secretion. Only 3% of NETs cause Cushing’s syndrome1; the majority are small and may be radiographically occult. Additionally, the responses to dexamethasone, metyrapone, and oCRF can be indistinguishable from that observed in pituitary Cushing’s disease2. These challenges lead to misdiagnosis and unnecessary procedures. Case Description: 45-year-old male presented for resection of right-sided pulmonary carcinoid tumor. He was diagnosed with Cushing’s syndrome in 2011 when he experienced uncontrolled hypertension and excessive weight gain with elevations in cortisol and ACTH levels. He underwent transsphenoidal pituitary resection in May 2011 for a possible pituitary microadenoma. Post-operative worsening hypertension, weight gain, and striae led to bilateral adrenalectomy in November 2011, complicated by retroperitoneal hemorrhage and resuscitation-induced pulmonary edema. On chest CT in early 2012, an 8 mm incidental right pulmonary nodule was documented. 8 years later, chest imaging for mild COVID-19 infection again revealed a right-sided pulmonary nodule. He underwent CT-guided biopsy of the nodule in July 2020 with pathology demonstrating carcinoid histology. Right lower lobectomy was performed. Pre-operative ACTH was 1673 pg/mL (normal: 10-60 pg/mL) and post-operative ACTH was 16 pg/mL. The resected tumor stained positive for ACTH, confirming that carcinoid tumor was the source of Cushing’s for the past decade. Conclusion: The diagnosis of ectopic Cushing’s syndrome can be elusive, leading to surgeries with significant morbidity, as seen in our patient. In one retrospective review, 14% of patients with Cushing’s had transsphenoidal resection before they were diagnosed with an ectopic source3. Ectopic Cushing’s syndrome can be a challenging diagnosis to make and a multidisciplinary approach with close collaboration between endocrinologist, radiologist, surgeon and pathologist may increase the diagnosis accuracy. Citations: 1Kamp, K, Alwani, R A, Korpershoek, E, Franssen, G., de Herder, W W, & Feelders, R A. (2016). Prevalence and clinical features of the ectopic ACTH syndrome in patients with gastroenteropancreatic and thoracic neuroendocrine tumors, European Journal of Endocrinology, 174(3), 271-280. Retrieved Jan 15, 2021, from https://eje.bioscientifica.com/view/journals/eje/174/3/271.xml 2Malchoff CD, Orth DN, Abboud C, Carney JA, Pairolero PC, Carey RM. Ectopic ACTH syndrome caused by a bronchial carcinoid tumor responsive to dexamethasone, metyrapone, and corticotropin-releasing factor. The American Journal of Medicine. 1988;84(4):760-764. doi:10.1016/0002-9343(88)90116-7 3Ioannis Ilias, David J. Torpy, Karel Pacak, Nancy Mullen, Robert A. Wesley, Lynnette K. Nieman,Cushing’s Syndrome Due to Ectopic Corticotropin Secretion: Twenty Years’ Experience at theNational Institutes of Health, The Journal of Clinical Endocrinology & Metabolism, Volume 90, Issue8, 1 August 2005, Pages 4955–4962, https://doi.org/10.1210/jc.2004-2527

A Case of Ectopic Cushing’s Syndrome From a Large Cell Neuroendocrine Lung Tumor With Small Cell Component/Features

Abstract Background: Endogenous Cushing’s syndrome is uncommon in clinical practice. Survival of patients with new onset ectopic Cushing’s syndrome at relapse of small cell lung cancer has been found to be poor, with death occurring within an average of 27.3 days. Case Report: A 61-year-old African American male was seen by endocrinology service for inpatient evaluation of refractory hypokalemia of three months duration requiring recurrent potassium replacement with oral and intravenous therapy. He was inpatient for depressive symptoms and suicidal ideation. His admission lab showed hypokalemia of 2.7 mmol/L associated with elevated serum ACTH and serum cortisol. Past medical history is significant for unresectable large cell neuroendocrine neoplasm of the lung with small cell components/features diagnosed two years prior during lung cancer screening. He received chemotherapy with cisplatin/etoposide at diagnosis. He however had recurrence one year later with distant metastases. He was re-treated with cisplatin/etoposide in addition to palliative radiation therapy to painful bone met in his right hand. Three months prior to admission, imaging showed progression of the cancer with presence of new lesions in the liver for which he received one cycle of Nivolumab monotherapy. Social history was significant for 30-pack year smoking history. Physical exam findings were significant for: elevated blood pressure 167/96 mmHg, tachycardia of 107 bpm, oxygen saturation of 95% on 3-liters of intranasal oxygen, cachexia, absent buffalo hump, absent striae and decreased power in both lower limbs. Lab on supplementation showed serum potassium of 3.6, Serum magnesium of 2.0 and creatinine clearance greater than 60 Serum cortisol was 116.1 (5-25) mcg/dl and ACTH was 268.0 (9-52) pg/ml. An MRI by the referring team did not show a pituitary lesion. Patient was diagnosed with Cushing’s syndrome due to ectopic ACTH-production from a large cell neuroendocrine lung tumor with small cell component/features. Chart review showed his onset of hypokalemia occurred at the same time that imaging showed progression of the tumor three months prior. He was started on Ketoconazole and his cortisol level reduced to 14.0 within forty-eight hours with associated correction and stabilization of hypokalemia. The plan was to “block and replace” cortisol so that oncology could re-start chemotherapy. However, the patient developed acute respiratory decompensation requiring continuous BiPAP. Chest imaging showed progression of lung lesions with post obstructive pneumonia. The patient’s family opted for comfort measures and he was transferred to hospice care where he passed on ten days later. Conclusion: In the setting of lung cancer, new onset paraneoplastic Cushing’s syndrome may have prognostic implications. Clinicians should be aware of this, provide treatment for hypercortisolism and refer early to palliative care.

Outcome of Patients With Metastatic Lung Neuroendocrine Tumors Submitted to First Line Monotherapy With Somatostatin Analogs.

ObjectiveAntiproliferative activity of somatostatin analogs (SSAs) has been demonstrated in digestive neuroendocrine tumors (NETs), but few data have been published in patients with pulmonary NETs. We therefore conducted a retrospective study to provide additional data on the outcome of patients with metastatic lung NETs submitted to front line SSAs.Research Design and MethodsPatients with metastatic lung NET treated with first line SSA-monotherapy (octreotide or lanreotide) in two different reference Institutions were reviewed. Outcome measures were progression-free survival (PFS) overall survival (OS), overall response rate and safety. We also explored prognostic factors associated with PFS.MethodsThe outcome of consecutive patients (pts) with metastatic lung NETs, who underwent first-line treatment with SSAs, recruited from 2014 on 2019 in two Italian reference Institutions, was retrospectively evaluated.ResultsThirty-one patients entered the study: 14 (45.2%) with typical and 17 (54.8%) atypical carcinoid. Six patients (19.4%) had a carcinoid syndrome. 60.0% of patients had Ki-67 ≤ 10%. Two (6.5%) patients obtained a partial response, 24 (77.4%) disease stabilization while 5 (16.1%) had progressive disease. Median progression free survival (PFS) was 28.6 months, median overall survival (OS) was not attained. Ki-67 ≤ 10%, typical carcinoid histotype and non-functioning disease, were associated with a non-significant PFS prolongation. PFS in patients with atypical carcinoids and in those with Ki-67 >10% was greater than 19 months.ConclusionsThe long PFS and OS obtained in this case series suggest that SSAs could be effective as first line approach in the management of patients with progressive, metastatic pulmonary NET.

Relationship between metabolic toxicity and efficacy of everolimus in patients with neuroendocrine tumors: A pooled analysis from the randomized, phase 3 RADIANT-3 and RADIANT-4 trials.

Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors such as everolimus. This post hoc pooled analysis assessed the potential impact of these events on the efficacy of everolimus. Patients with advanced, low- or intermediate-grade pancreatic, gastrointestinal, or lung neuroendocrine tumors received either oral everolimus at 10 mg/d or a placebo in the RAD001 in Advanced Neuroendocrine Tumors 3 (RADIANT-3) and RAD001 in Advanced Neuroendocrine Tumors 4 (RADIANT-4) trials. A landmark progression-free survival (PFS) analysis by central review was performed for patients treated for at least 16 weeks (n = 308) and according to the occurrence of any-grade adverse events (AEs) within this treatment period. The overall PFS with everolimus from the pooled analysis was 11.4 months (95% confidence interval, 11.01-13.93 months), which was consistent with the findings of RADIANT-3 and RADIANT-4. Overall, 19.1% and 9.8% of patients in RADIANT-3 and 11.9% and 6.4% of patients in RADIANT-4 developed any-grade hyperglycemia and hypercholesterolemia, respectively (regardless of the study drug). The duration of everolimus exposure was longer in patients who developed these AEs versus patients without these AEs. Overall, 308 patients were exposed to treatment for at least 16 weeks (hyperglycemia, 39 of 269 patients; hypercholesterolemia, 20 of 288 patients). No association was observed between the development of these AEs and PFS (18.8 and 14.1 months with and without hyperglycemia, respectively, and 14.1 and 14.8 months with and without hypercholesterolemia, respectively). Although limitations apply because of the small number of AEs observed, there was no significant impact of these AEs on PFS; this suggests similar efficacy in the presence or absence of these events.

Incidence and Survival Outcomes in Patients with Lung Neuroendocrine Neoplasms in the United States.

Simple SummaryNeuroendocrine tumors are a rare group of neoplasms characterized by strikingly heterogeneous pathological features and clinical behavior. The incidence and prevalence of these tumors are rising. Studies have reported the incidence and prevalence of neuroendocrine tumors; however, specific data targeting lung neuroendocrine tumors are lacking. We conducted a retrospective analysis using a national database to report the incidence and survival trends of lung neuroendocrine neoplasms. We found that the overall survival and disease-specific survival trends varied significantly not only by stage and histological type but also by age, race, marital status, and insurance type. A small difference was also noted between the rural and urban populations. The rarity of these tumors poses several diagnostic and therapeutic challenges. Our findings generate the following hypothesis that increased awareness of these tumors, as well as better diagnostic modalities, may contribute to a higher incidence. Furthermore, newer therapeutic advances may have caused an improvement in the survival trends in recent years. Such population-based analysis is important to allot resources and guide future research in the field.Background: The incidence and prevalence of neuroendocrine neoplasms (NENs) are rapidly rising. Epidemiologic trends have been reported for common NENs, but specific data for lung NENs are lacking. Methods: We conducted a retrospective analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Associated population data were utilized to report the annual age-adjusted incidence and overall survival (OS) trends. Trends for large-cell neuroendocrine carcinoma (LCNEC) and atypical carcinoid (AC) were reported from 2000–2015, while those for typical carcinoid (TC) and small cell lung cancer (SCLC) were reported from 1988–2015. Results: We examined a total of 124,969 lung NENs [103,890—SCLC; 3303—LCNEC; 8146—TC; 656—AC; 8974—Other]. The age-adjusted incidence rate revealed a decline in SCLC from 8.6 in 1988 to 5.3 in 2015 per 100,000; while other NENs showed an increase: TC increased from 0.57 in 1988 to 0.77 in 2015, AC increased from 0.17 in 2001 to 0.22 in 2015, and LCNEC increased from 0.16 in 2000 to 0.41 in 2015. The 5-year OS rate among SCLC, LCNEC, AC, and TC patients was 5%, 17%, 64%, and 84%, respectively. On multivariable analyses, OS and disease-specific survival (DSS) varied significantly by stage, sex, histological type, insurance type, marital status, and race, with a better survival noted in earlier stages, females, married, insured, Hispanic and other races, and urban population. Similarly, TC and AC had better survival compared to SCLC and LCNEC. Conclusion: The incidence of lung NENs is rising, possibly in part because of advanced radiological techniques. However, the incidence of SCLCs is waning, likely because of declining smoking habits. Such population-based studies are essential for resource allocation and to prioritize future research directions.

The Expression of Anti-Müllerian Hormone Type II Receptor (AMHRII) in Non-Gynecological Solid Tumors Offers Potential for Broad Therapeutic Intervention in Cancer.

Simple SummaryUntil now, only a few studies have examined the AMHRII expression in tumors. Here, with more than 1000 tumor samples and using several complementary techniques we confirmed AMHRII expression in gynecological cancer and demonstrated AMHRII expression in certain non-gynecological cancers such as colorectal cancers. These findings open the way for new therapeutic approaches targeting AMHRII and emphasize the need to better understand the role of AMH/AMHRII in cancer.The anti-Müllerian hormone (AMH) belongs to the TGF-β family and plays a key role during fetal sexual development. Various reports have described the expression of AMH type II receptor (AMHRII) in human gynecological cancers including ovarian tumors. According to qRT-PCR results confirmed by specific In-Situ Hybridization (ISH) experiments, AMHRII mRNA is expressed in an extremely restricted number of normal tissues. By performing ISH on tissue microarray of solid tumor samples AMHRII mRNA was unexpectedly detected in several non-gynecological primary cancers including lung, breast, head and neck, and colorectal cancers. AMHRII protein expression, evaluated by immunohistochemistry (IHC) was detected in approximately 70% of epithelial ovarian cancers. Using the same IHC protocol on more than 900 frozen samples covering 18 different cancer types we detected AMHRII expression in more than 50% of hepato-carcinomas, colorectal, lung, and renal cancer samples. AMHRII expression was not observed in neuroendocrine lung tumor samples nor in non-Hodgkin lymphoma samples. Complementary analyses by immunofluorescence and flow cytometry confirmed the detection of AMHRII on a panel of ovarian and colorectal cancers displaying comparable expression levels with mean values of 39,000 and 50,000 AMHRII receptors per cell, respectively. Overall, our results suggest that this embryonic receptor could be a suitable target for treating AMHRII-expressing tumors with an anti-AMHRII selective agent such as murlentamab, also named 3C23K or GM102. This potential therapeutic intervention was confirmed in vivo by showing antitumor activity of murlentamab against AMHRII-expressing colorectal cancer and hepatocarcinoma Patient-Derived tumor Xenografts (PDX) models.

Preclinical evaluation of [225Ac]Ac-DOTA-TATE for treatment of lung neuroendocrine neoplasms.

There is significant interest in the development of targeted alpha-particle therapies (TATs) for treatment of solid tumors. The metal chelator-peptide conjugate, DOTA-TATE, loaded with the β-particle emitting radionuclide 177Lu ([177Lu]Lu-DOTA-TATE) is now standard care for neuroendocrine tumors that express the somatostatin receptor 2 (SSTR2) target. A recent clinical study demonstrated efficacy of the corresponding [225Ac]Ac-DOTA-TATE in patients that were refractory to [177Lu]Lu-DOTA-TATE. Herein, we report the radiosynthesis, toxicity, biodistribution (BD), radiation dosimetry (RD), and efficacy of [225Ac]Ac-DOTA-TATE in small animal models of lung neuroendocrine neoplasms (NENs). [225Ac]Ac-DOTA-TATE was synthesized and characterized for radiochemical yield, purity and stability. Non-tumor-bearing BALB/c mice were tested for toxicity and BD. Efficacy was determined by single intravenous injection of [225Ac]Ac-DOTA-TATE into SCID mice-bearing human SSTR2 positive H727 and H69 lung NENs. RD was calculated using the BD data. [225Ac]Ac-DOTA-TATE was synthesized with 98% yield, 99.8% purity, and displayed 97% stability after 2days incubation in human serum at 37°C. All animals in the toxicity study appeared healthy 5months post injection with no indications of toxicity, except that animals that received ≥111kBq of [225Ac]Ac-DOTA-TATE had chronic progressive nephropathy. BD studies revealed that the primary route of elimination is by the renal route. RD calculations determined pharmacokinetics parameters and absorbed α-emission dosages from 225Ac and its daughters. For both tumor models, a significant tumor growth delay and time to experimental endpoint were observed following a single administration of [225Ac]Ac-DOTA-TATE relative to controls. These results suggest significant potential for the clinical translation of [225Ac]Ac-DOTA-TATE for lung NENs.

Calcitonin-secreting neuroendocrine neoplasms of the lung: a systematic review and narrative synthesis.

Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.

Challenges in Diagnostic and Systemic Treatment of Metastatic Lung Atypical Carcinoid: a Case Report

Neuroendocrine lung tumors are rare neoplasms, with an increasing incidence in the last thirty years. Metastatic disease is rarely curable. We present the case of a 65-year-old male patient with atypical functional carcinoid of the lung and synchronous liver metastases beginning with carcinoid syndrome treated with somatostatin analogues, chemotherapy and peptide receptor radionuclide therapy, with a good clinical response and remission of the carcinoid syndrome.

Recent advances and current controversies in lung neuroendocrine neoplasms✰.

In the lung, neuroendocrine tumors (NETs), namely typical and atypical carcinoids, and neuroendocrine carcinomas (NECs), grouping small cell carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC), make up for distinct tumor entities according to epidemiological, genetic, pathologic and clinical data. The proper classification is essential in clinical practice for diagnosis, prognosis and therapy purposes. Through an extensive literature survey, three perspectives on lung NENs have been revised: i) criteria and terminology on biopsy or cytology samples of primaries or metastases; ii) carcinoids with elevated mitotic counts and/or Ki-67 proliferation rates; iii) relevance of molecular landscape to identify new tumor entities and therapeutic targets. Furthermore, a dispute about lung NEN development has been raised according to emerging molecular models. We herein provide a pathology update on practical topics in the setting of lung NENs according to the current classification (recent advances). We have also reappraised the development of these tumors by modeling risk factors and natural history of disease (recent controversies). Combining recent advances and controversies may help clarify our biological understanding of lung NENs and give practical information for the clinical decision-making process.

Diagnostic Value of Conventional PET Parameters and Radiomic Features Extracted from 18F-FDG-PET/CT for Histologic Subtype Classification and Characterization of Lung Neuroendocrine Neoplasms.

Aim: To evaluate if conventional Positron emission tomography (PET) parameters and radiomic features (RFs) extracted by 18F-FDG-PET/CT can differentiate among different histological subtypes of lung neuroendocrine neoplasms (Lu-NENs). Methods: Forty-four naïve-treatment patients on whom 18F-FDG-PET/CT was performed for histologically confirmed Lu-NEN (n = 46) were retrospectively included. Manual segmentation was performed by two operators allowing for extraction of four conventional PET parameters (SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)) and 41 RFs. Lu-NENs were classified into two groups: lung neuroendocrine tumors (Lu-NETs) vs. lung neuroendocrine carcinomas (Lu-NECs). Lu-NETs were classified according to histological subtypes (typical (TC)/atypical carcinoid (AC)), Ki67-level, and TNM staging. The least absolute shrink age and selection operator (LASSO) method was used to select the most predictive RFs for classification and Pearson correlation analysis was performed between conventional PET parameters and selected RFs. Results: PET parameters, in particular, SUVmax (area under the curve (AUC) = 0.91; cut-off = 5.16) were higher in Lu-NECs vs. Lu-NETs (p < 0.001). Among RFs, HISTO_Entropy_log10 was the most predictive (AUC = 0.90), but correlated with SUVmax/SUVmean (r = 0.95/r = 0.94, respectively). No statistical differences were found between conventional PET parameters and RFs (p > 0.05) and TC vs. AC classification. Conventional PET parameters were correlated with N+ status in Lu-NETs. Conclusion: In our study, conventional PET parameters were able to distinguish Lu-NECs from Lu-NETs, but not TC from AC. RFs did not provide additional information.

P50.03 Lung Neuroendocrine Tumors. 12-Years Experience of a Single Cancer Institution

Lung neuroendocrine tumors (NETs) are an uncommon group of pulmonary neoplasms that are characterized by neuroendocrine differentiation and relatively indolent clinical behavior. Lung is the second most common frequently involved site. There are no data in Mexican or Latin American populations regarding the clinical and pathologic characteristics as well as the prognosis in patients with NETs.

Value of a patient-reported-outcome measure of carcinoid syndrome symptoms.

Literature on patient-reported outcomes (PRO) of carcinoid syndrome symptoms (CSS) is scarce. We used a patient-reported outcome measure (PROM) to evaluate CSS, the domains of daily life impacted by CSS, the main symptoms that affect daily life, its change according to clinical, biological and morphological evolution, and the risk factors for a poor PRO-CSS score. Patients completed the PRO-CSS, EORTC-QLQ30, and GI-NET21 questionnaires at the time of their clinical, laboratory, and morphological assessments in a multicentre French cohort study from February 2019 to May 2020. In total, 147 patients with metastatic ileal (n =126), lung (n =20), or unknown primitive neuroendocrine tumour but high 5-hydroxyindole-3-acetic acid level (n =1) were included; 42 (32%) received an above-label dose of somatostatin analogues. Fifty-one (35%) patients had a poor PRO-CSS score. Travelling and food restriction were the two main domains affected. Diarrhoea (mean: 2.3/5 on Likert scale), imperiousness (mean of 2.5/5), fatigue (2.2/5), abdominal pain (1.7/5), and flushing episodes (1.5/5) were the main symptoms affecting daily life. The PRO-CSS score was not correlated to the clinical assessment performed by physicians at the baseline and during the follow-up. Patients with a poor PRO-CSS score had a higher tumour burden. PROM-CSS may help physicians make an objective assessment of CSS and its impact in daily practice; this tool could become a key evaluation criterion in clinical trials focusing on CSS.

P50.04 Real-World Survival Outcomes with Immune Checkpoint Inhibitors in Large Cell Neuroendocrine Tumors of Lung

P50.04 Real-World Survival Outcomes with Immune Checkpoint Inhibitors in Large Cell Neuroendocrine Tumors of Lung

ES17.03 Updates in Squamous Cell Carcinoma and Neuroendocrine Tumors of the Lung

ES17.03 Updates in Squamous Cell Carcinoma and Neuroendocrine Tumors of the Lung

P47.11 DLL-3 and ASCL-1 Expression Emerge as Promising Therapeutic Targets in High-Grade Neuroendocrine Lung Tumors: A Preliminary Study

P47.11 DLL-3 and ASCL-1 Expression Emerge as Promising Therapeutic Targets in High-Grade Neuroendocrine Lung Tumors: A Preliminary Study

An Update on the Management of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH).

DIPNECH is caused by an idiopathic proliferation of pulmonary neuroendocrine cells which can lead to bronchiolitis and multifocal lung neuroendocrine tumors. Patients often present with chronic cough and dyspnea. Larger NETs may develop malignant potential. Somatostatin analogs can palliate chronic symptoms, particularly cough. Surgical resection can be considered for relatively large (e.g. >1 cm), progressive tumors.

Percutaneous Image-Guided Core Needle Biopsy of Neuroendocrine Tumors: How Common Is Intraprocedural Carcinoid Crisis?

PurposeTo retrospectively evaluate the incidence of carcinoid crisis, other complications, and physiologic disturbances during percutaneous image-guided core needle biopsy of neuroendocrine tumors (NETs) in the lung and the liver. Materials and MethodsBetween January 2010 and January 2020, 106 computed tomography (CT) or ultrasound (US)-guided core needle biopsies of lung and liver NETs were performed in 95 consecutive adult patients. The mean age was 64 ± 13 years, and 48% were female. The small bowel was the most common primary site (33%, 31/95), and 32 (34%) patients had pre-existing symptoms of carcinoid syndrome. The mean tumor size was 3.2 ± 2.6 cm, and mean number of passes was 3.4 ± 1.6. A 17/18-gauge needle was used in 91% (96/106) of the biopsies. Thirteen (12%) patients received either outpatient or prophylactic octreotide. ResultsNo patients experienced carcinoid crisis or needed octreotide, inotropes, vasopressors, or resuscitation. A single biopsy procedure (0.9%, 1/106) was complicated by bleeding that required angiographic hepatic artery embolization. Changes in pre-biopsy- versus post-biopsy systolic blood pressure and heart rate were -1.6 mm Hg (P = .390) and 0.6 beat/min (P = .431), respectively. Tumor functional status, overall tumor burden, and the elevation of neuroendocrine markers were not associated with intraprocedural physiologic disturbances. There were 4 minor complications (0.4%, 4/106) associated with the biopsy procedure that were not attributed to hormone excretion from tumor manipulation. ConclusionsPercutaneous image-guided core biopsy of NETs is safe, with low complication rate and no definite carcinoid crisis in the current cohort.

Pathology and Classification of SCLC.

Simple SummarySmall cell lung carcinoma (SCLC), is a high-grade neuroendocrine carcinoma defined by its aggressiveness, poor differentiation, and somber prognosis. This review highlights current pathological concepts including classification, immunohistochemistry features, and differential diagnosis. Additionally, we summarize the current knowledge of the immune tumor microenvironment, tumor heterogeneity, and genetic variations of SCLC. Recent comprehensive genomic research has improved our understanding of the diverse biological processes that occur in this tumor type, suggesting that a new era of molecular-driven treatment decisions is finally foreseeable for SCLC patients.Lung cancer is consistently the leading cause of cancer-related death worldwide, and it ranks as the second most frequent type of new cancer cases diagnosed in the United States, both in males and females. One subtype of lung cancer, small cell lung carcinoma (SCLC), is an aggressive, poorly differentiated, and high-grade neuroendocrine carcinoma that accounts for 13% of all lung carcinomas. SCLC is the most frequent neuroendocrine lung tumor, and it is commonly presented as an advanced stage disease in heavy smokers. Due to its clinical presentation, it is typically diagnosed in small biopsies or cytology specimens, with routine immunostaining only. However, immunohistochemistry markers are extremely valuable in demonstrating neuroendocrine features of SCLC and supporting its differential diagnosis. The 2015 WHO classification grouped all pulmonary neuroendocrine carcinomas in one category and maintained the SCLC combined variant that was previously recognized. In this review, we explore multiple aspects of the pathologic features of this entity, as well as clinically relevant immunohistochemistry markers expression and its molecular characteristics. In addition, we will focus on characteristics of the tumor microenvironment, and the latest pathogenesis findings to better understand the new therapeutic options in the current era of personalized therapy.