Large Cell Neuroendocrine Tumors Research Articles

Breast metastasis from large cell neuroendocrine carcinoma of the lung: a case report

BackgroundPrimary breast carcinoma is far more common than breast metastases. Common breast metastases usually come from lymphoma, leukemia, melanoma, and ovarian cancers. Breast metastases from neuroendocrine carcinomas are considered an exceeding rare entity. It has been reported in the literature that the pathological presentation of this particular metastatic tumor is very challenging as it shares many morphological characteristics with primary breast carcinoma.Case presentationWe report a case of a patient with large cell neuroendocrine carcinoma of the lung metastasizes to both breasts. The patient was initially presented with brain metastasis of unknown origin. Further radiological imaging workup showed multiple bilateral breast masses and bilateral lymphadenopathy, which raised concern for secondary lymphoma of the breast. The histopathology of this case was challenging, particularly when triple negative invasive ductal carcinoma diagnosis had been made. Multidisciplinary meetings between medical oncologists, radiologists, and pathologists profoundly helped confirming the diagnosis of metastatic large cell neuroendocrine tumor to the breast.ConclusionLarge cell neuroendocrine carcinoma of the lung is a relatively uncommon diagnosis with generally poor prognosis. Large cell neuroendocrine carcinoma that metastasizes to the breast is even scarcer. Correlation between clinical assessment, radiological imaging, and pathological evaluation is the key in making such an unusual and complex diagnosis. Additionally, radiologists should be aware of metastatic presentations of the breast and avoid confusion with mimicking benign entities or primary breast carcinomas.

P3.13C.09 First-Line Treatments for Advanced Pure Large Cell Neuroendocrine Tumors (LCNEC):Insights from a Global Clinico-Genomic Study

P3.13C.09 First-Line Treatments for Advanced Pure Large Cell Neuroendocrine Tumors (LCNEC):Insights from a Global Clinico-Genomic Study

Predictors of lymph node metastasis and survival in radically resected rectal neuroendocrine tumors: A Surveillance, Epidemiology, and End Results (SEER) database analysis

BackgroundRectal neuroendocrine tumors are uncommon tumor types. Lymph node metastases may occur in up to 40%, potentially impacting decision-making. We aimed to assess risk factors for lymph node metastases of rectal neuroendocrine tumors and their association with overall and cancer-specific survival. MethodsThis retrospective case–control study involved patients with stage I to III rectal neuroendocrine tumors who underwent radical resection. Data were derived from the Surveillance, Epidemiology, and End Results database (2000–2020). Patients with pathologic evidence of lymph node metastases were compared to those without lymph node metastases for baseline patient and tumor characteristics. The main outcomes were lymph node metastases, overall survival, and cancer-specific survival. ResultsIn total, 580 patients (50.9% male; mean age: 58.9 years) were included. The lymph node metastases rate was 37.1%. Independent predictors of lymph node metastases were Grade 2 neuroendocrine tumors (odds ratio: 8.06; P = .001), neuroendocrine carcinoma (odds ratio: 2.59, P = .006), large-cell neuroendocrine carcinoma (odds ratio: 4.89; P = .017), T2 tumors (odds ratio: 6.44; P < .001), T3 tumors (odds ratio: 27.5; P < .001), and T4 tumors (odds ratio: 17.3; P < .001). Lymph node metastases were associated with shorter restricted mean overall survival (40.8 vs 52.7 months; P < .001) and cancer-specific survival (41.3 vs 54.8 months; P < .001). When adjusted for other confounders, the nodal status of rectal neuroendocrine tumors was not independently associated with overall (hazard ratio = 1.56; P = .165) or cancer-specific survival (hazard ratio = 1.69; P = .158). Significant factors associated with worse overall survival and cancer-specific survival were age, tumor size, neuroendocrine carcinomas, large-cell neuroendocrine carcinomas, and the number of positive lymph nodes. ConclusionsLymph node metastases of rectal neuroendocrine tumors were more likely associated with high-grade, large-sized, and T2 to T4 tumors. The number of involved lymph nodes was an independent predictor of overall and cancer-specific survival. Other independent survival predictors were tumor grade, size, and T stage.

Analysis of 25 surgical cases of thymic neuroendocrine tumors and thymic carcinoma

BackgroundThe purpose of this study was to evaluate the clinicopathological characteristics of patients who underwent surgical resection for thymic neuroendocrine tumors (TNET) or thymic carcinoma.MethodsIn this study, we retrospectively evaluated the clinicopathological characteristics of our surgical patients at Fukuoka University Hospital from January 1995 to December 2018.ResultsThere were nine cases of TNET and 16 cases of thymic carcinoma. Regarding the pathological type, the TNET group included three atypical carcinoid cases, two large cell neuroendocrine tumor cases, two small cell carcinoma cases, and two other cases. The thymic carcinoma group included 15 squamous carcinoma cases and one case of adenosquamous carcinoma. Based on the Masaoka-Koga staging system, six TNET cases and 11 thymic carcinoma cases were stage III or IV. The complete resection rate was 77% in the TNET group and 81% in the thymic carcinoma group. Additional chemotherapy and/or radiotherapy was performed in five cases of TNET and 11 cases of thymic carcinoma. The five-year survival rate and five-year disease-free survival rate were 87.5% and 75.0% in the TNET group and 58.9% and 57.1% in the thymic carcinoma group, respectively, with no significant difference between the two groups (P = 0.248 and P = 0.894, respectively). In the univariate analysis, complete resection was a statistically significant prognostic factor (P = 0.017).ConclusionIn this study, no difference in prognosis was observed between TNET and thymic carcinomas. To understand the characteristics of these tumors, further case accumulation and multicenter clinical studies are needed. (243words)

Incidence and prognostic nomogram for resected non-small cell neuroendocrine tumor: A population-based respective study in China and the SEER database

BackgroundPulmonary neuroendocrine tumors, including small cell lung cancer (SCLC) and non-small cell neuroendocrine tumor (NSCLC-NET), have obvious heterogeneity. The comparison between SCLC and NSCLC-NET, and prognostic nomogram of resected NSCLC-NET have not been performed. MethodsWe retrieved data from SEER database. The incidence and prognostic factors were compared between SCLC and NSCLC-NET. By Cox regression, we constructed prognostic nomogram of resected NSCLC-NET. The nomogram was evaluated by ROC, calibration plot and decision curve analysis (DCA) and compared with 8th TNM staging system. A Chinese cohort was used for external validation. ResultsThe age-adjusted incidence of SCLC declined after 1991 but the incidence of NSCLC-NET continuously rose. Patients with typical carcinoid had the best prognosis in both overall survival and lung cancer specific survival, followed by atypical carcinoid, large cell neuroendocrine tumor and SCLC after operation. Patients receiving sleeve resection in NSCLC-NET had longer survival but segmental resection was more recommended in SCLC. High-smoking index was associated with worse overall survival in both SCLC and NSCLC-NET. Histological subtype, age, surgery type, N, M stage and chemotherapy were independent prognostic factors and used to construct prognostic nomogram of resected NSCLC-NET. The nomogram performed well with good discrimination, calibration and clinical usefulness, which was validated by a Chinese cohort (1, 3, 5-year AUC: SEER cohort 0.873, 0.901, 0.875; Chinese cohort 0.867, 0.892, 0.874). Compared to the 8th staging system, the nomogram had higher C-index (0.87 vs 0.728, P < 0.001), clinical usefulness, increasing AUC value over time and improved 68%. ConclusionThe prognostic nomogram of resected NSCLC-NET performed better than the 8th TNM staging system. It may have certain value in risk stratification and survival prediction of patients with resected NSCLC-NET and help clinicians to take measures for high-risk patients in advance.

PP01.50 EMERGE-201: Phase 2 Basket Study of Lurbinectedin Monotherapy in Advanced or Metastatic Solid Tumors

Lurbinectedin (Zepzelca®), a selective inhibitor of oncogenic transcription, received accelerated approval from the US Food and Drug Administration on June 15, 2020, as monotherapy (3.2 mg/m2 by 1-hour IV infusion every 3 weeks) for the treatment of adults with metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Approval was based on overall response rate (ORR; 35.2%) and median duration of response (5.3 months) in a phase 2 study. In addition to SCLC, antitumor activity with lurbinectedin as monotherapy or in combination with additional therapeutic agents has been observed in other advanced solid tumors. The EMERGE-201 study will evaluate the efficacy and safety of lurbinectedin monotherapy in adults with advanced (metastatic and/or unresectable) large-cell neuroendocrine tumor (LCNET) of the lung, as well as in other advanced (metastatic and/or unresectable) solid tumors with high unmet medical needs, including urothelial cancer (UC) and homologous recombination–deficient (HRD) tumor-agnostic malignancies.

Association between tumor response to systemic therapy and patient-reported disease symptoms.

The association of treatment-induced tumor shrinkage with symptom palliation for patients with lung cancer remains unknown. We investigated this correlation using the Edmonton Symptom Assessment System-Revised. Using the in-hospital cancer registry, we identified patients receiving chemotherapy and/or immunotherapy for newly diagnosed advanced or metastatic lung cancer. Tumor response and post-treatment Edmonton Symptom Assessment System-Revised were obtained after 2-3 treatment cycles. Patients were divided into groups with or without >30% unidirectional tumor shrinkage (objective response [OR] or non-OR [N-OR] groups, respectively). They were further classified as good-objective response (>50% unidirectional tumor shrinkage), moderate-objective response (30-50% shrinkage), progressive disease (>20% tumor growth or new lesion) or stable disease (SD; N-objective response and non-progressive disease). The primary endpoint was change in the total Edmonton Symptom Assessment System-Revised score from baseline. The Mann-Whitney U test was used for analysis. In total, 113 patients were enrolled. The total Edmonton Symptom Assessment System-Revised score was significantly more improved in the OR group versus the N-OR group (median: 5 vs. 2, respectively; P=0.013). This association was more prominent in patients with small-cell lung cancer and large-cell neuroendocrine tumor than those with other histology. Sensitivity analyses showed that the total Edmonton Symptom Assessment System-Revised score was more improved in the OR group versus the SD group (median: 5 vs. 3, respectively; P=0.029) and in the 'good-OR' group versus the 'moderate-OR and SD' group (median: 7.5 vs. 2, respectively; P=0.003), suggesting that greater tumor shrinkage led to more symptom amelioration. Tumor shrinkage was associated with Edmonton Symptom Assessment System-Revised score improvement in patients with lung cancer receiving systemic therapy.

Large Cell Neuroendocrine Carcinoma of the Prostate Gland: A Review and Update

It has been documented that the 2016 World Health Organization’s histological classification of prostate cancer has included well-differentiated carcinoid tumours and small- or large-cell poorly differentiated tumours within the category of neuroendocrine tumours. Up to May 2021, only 20 cases of large-cell neuroendocrine tumours of the prostate gland (LCNTPs) had been reported within the literature, among which are nine cases of primary tumours. LCNTPs are a rare histological entity whose evolutive profile and therapeutic potential do differ from those of conventional adenocarcinoma of the prostate gland. Primary neuroendocrine tumours of the prostate gland could be pure or associated with an adenocarcinoma component. Mixed forms of large cell neuroendocrine cancers of the prostate gland (LCNECPs) tend to associated with better prognosis when diagnosed early at a localized stage. Nevertheless, most cases of (LCNTPs) at the time of initial diagnosis could tend to be advanced, locally advanced or metastatic. Even though LCNECPs that are diagnosed initially tend to primary prostate cancers that may be pure primary prostate cancers, few large LCNECPs have been found to be metastatic large cell neuroendocrine carcinomas that had metastasised from other sites of the body for example the lung. Primary LCNECP does tend to manifest similarly to primary adenocarcinoma of prostate gland with lower urinary tract symptoms, haematuria, or signs of obstruction of the upper urinary tract or inability to empty the urinary bladder. Cases of primary LCNECP that manifest tend also to be associated with symptoms related to the sites of the metastases. Serum prostate specific antigen levels tend to be slightly elevated with cases of primary LCNECP, but the levels generally tend not to be as high as most cases of advanced, locally advanced or metastatic primary adenocarcinomas of the prostate gland. Diagnosis of LCNECPs tend to be made pursuant to the undertaking of histopathology and immunohistochemistry staining studies of specimens of the prostate that had been obtained from prostate biopsies, trans-urethral reception of prostate specimens or prostatectomy specimens. The microscopy histopathology examination features of LCNECP the prostate gland have been summarized as follows: (a) Microscopy histopathology examination of LCNECP gland does tend to demonstrate large islands or sheets of tumour cells. (b) Large tumour cells with prominent neuroendocrine features such as salt and pepper chromatin and small nucleoli tend to be visualised upon microscopy examination of specimens of the prostate tumour. (c) High grade features such as lack of glandular formation, frequent mitoses and apoptotic bodies and tumour necrosis tend to be frequent findings upon microscopy examination of specimens of LCNECP. Immunohistochemistry staining features of LCNECP include: (a) At least one of the ensuing neuroendocrine tumour markers should be demonstrated upon immunohistochemistry staining including exhibition of positive immunohistochemistry staining for: chromogranin A, synaptophysin, neuron specific enolase, and CD56 may be positive: It has been stated that immunohistochemistry staining studies may exhibit positive staining in cases of LCNECP with utilization of the following: o TTFI tends to be positive in less than 50% of cases of LCNECP. o Positive AMACR immunohistochemistry staining, but this may be focal or weaker than for adenocarcinoma of the prostate gland. o Positive markers including: PSA, PSMA, NKX3.1 prostein (P501S) tend to be negative in majority of cases of LCNECP, but they could be focally positive in a small subset of the tumours. It has been iterated that in cases of LCNECP, immunohistochemistry staining studies tend to demonstrate negative staining for the ensuing markers: • Urothelial markers such as GATA3, p63, and high molecular weight cytokeratins such as CK5 / 6. • CD99. • Carcinoid tumour of the prostate gland. • PNET/Ewing sarcoma of the prostate gland. • Adenocarcinoma of the prostate gland with focal neuroendocrine differentiation. • Urothelial carcinoma with neuroendocrine differentiation. A high index of suspicion is required in order to diagnose early cases of primary large cell neuroendocrine carcinomas by undertaking early biopsies of prostate glands in all patients who have significant lower urinary tract symptoms if their serum prostate specific antigen (PSA) levels are slightly high or high even if they are commenced on Tamsulosin in an attempt to help improve the symptoms of voiding. There is no consensus opinion on the best management of LCNECP, therefore, there is an urgent need for the establishment of a global multi-centre trial related to various management options for the disease in order to ascertain the best options of management for LCNECP. gland.

Abstract 3496: Transcriptomic classification of lung adenocarcinoma identifies a novel subgroup with a poor survival prognosis

Abstract Lung adenocarcinoma is one-half of all lung cancer and the third deadliest cancer in the world. The traditional classification of lung adenocarcinoma involves invasiveness, growth pattern, presence of mucin, and other histological features. However, this classification provides limited prognostic predictability. Molecular profiles based The Cancer genome Atlas lung adenocarcinoma cohort classified the tumors into the terminal respiratory unit (TRU), proximal proliferative (PP), and proximal infiltrative (PI) based on unsupervised classification, which did not address clinical applicability to the classification. Here, we developed an unsupervised classification with Density-based UMAP (DBU), which identified four transcriptomic profiles for lung adenocarcinoma (Transcriptomic profile, TP1-TP4). We identified a gene signature with 299 genes to develop a supervised classifier, called Ensemble Transcriptomic classifier (ETC), to identify these four subgroups within the total cohort. All TP1 is PI. TP2 is 49.0% TFU and 45.0% PP. TP3 is 76.2% PI and 23.8% PP. TP4 is 54.5% TFU and 45.5% PI. TP1 is characterized by neuroendocrine-like features and clusters with large cell neuroendocrine tumors in cluster analysis. TP3 is squamous-like enriched with cell cycle and DNA repair high and worse prognosis and groups with squamous cell carcinoma in cluster analysis. TP2 has high immune cell infiltration, and TP4 showed low mutational burden and low immune cell infiltration. We validated these subgroups identified in the TCGA cohort in a microarray meta-dataset with DBU, ETC. This classification showed four subgroups in lung adenocarcinoma, which shows potential clinical actionable findings. Citation Format: Khaled Bin Satter, Paul MH Tran, Lynn KH Tran, John Nechtman, Nikhil Patel, Bruno Santos, Diane Hopkins, Nagla Abdel Karim, Jin-Xiong She, Sharad B. Purohit. Transcriptomic classification of lung adenocarcinoma identifies a novel subgroup with a poor survival prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3496.

A combined large-cell neuroendocrine carcinoma and hepatocellular carcinoma tumor in the liver: A rare case report

A combined large-cell neuroendocrine carcinoma and hepatocellular carcinoma tumor in the liver: A rare case report

Abstract P3-12-26: Baseline characteristics and survival of neuroendocrine carcinoma of the breast- A SEER database analysis

Abstract Background: Neuroendocrine carcinoma of the breast (NECB) is a malignancy. The estimated incidence of this type of tumor ranges from less than 1% to 5%. The scarcity of data about these tumors creates a challenge for treatment. Prior studies have reported that clinically most NECB behave as other type of cancer, being more common in post-menopausal women. Using population-based cancer data, our study aims to describe the baseline characteristics, tumor biology, and prognosis of patients with NECB. Methods: Using the SEER database of the National Cancer Institute, we identified 433 cases of NECB diagnosed between 2000 and 2018. We assessed the patient age, sex, race, stage, grade of the tumor and histologic type. The additional information of estrogen receptor (ER), progesterone receptor (PR) and HER2 status were also included when available. Kaplan-Meir methods were used to estimate overall survival (OS). Cox proportional-hazard model was used to create multivariable analysis for OS. Results: We found that 427 (98.6%) of the patient were female, while only 6 (1.3%) patients were male. The mean age of diagnosis was 64 years[JA1] , (SD : 14.2 years). Most patients were White (n= 353, 82%), while 52 (12%) were black, and 27 (6.2%) were other race. About the tumor histology, 375 (86.6%) cases were neuroendocrine tumor not otherwise specified, 30 (6.9%) cases were large cell neuroendocrine tumors and 28 (6.4%) were carcinoid tumor of the breast. ER was positive in 70%, PR was positive in 57% of the patients in which these receptors were tested. 194 patients were assessed for Her 2, and only 6(3%) were her2 positive. 183 (42%) had any chemotherapy use, while 250 (58%) had no known use of chemotherapy. 326 patients had a documented stage, of those 77 (17%) were AJCC stage I, 140 (32%) stage II, 39 (9%) stage III and 70 (16%) stage IV. The[JA2] median OS for stage I, II, III, and IV were not-reached, 129, 45 and 13 months, respectively[JA3] . In the univariate analysis for OS, only for tumor grade 3 (HR = 2.2; 95% CI: 1.98,2.52; p= 0.002) , ER negative (HR = 2.0; 95% CI: 1.86,3.62; p= &amp;lt;0.001), PR (HR = 2.4; 95% CI: 2.1,2.63; p= &amp;lt;0.001), surgery (HR = 0.26; 95% CI: 0.11,0.40; p= &amp;lt;0.001), metastasis (HR = 0.19; 95% CI: 0.04,0.34; p= &amp;lt;0.001), stage IV cancer (HR = 2.3; 95% CI: 2.0,2.5; p= &amp;lt;0.001) were statistically significantly associated with OS. In a multivariate model, including age, histology, grade, ER, PR, stage group, metastasis, surgery and chemotherapy. We found that large cell histology (HR = 2.0; 95% CI: 1.0,4.3; p= 0.04), negative ER (HR = 2.0; 95% CI: 1.2,3.5; p= 0.01), negative PR (HR = 2.5; 95% CI: 1.4,4.4; p= 0.002), treatment with surgery (HR = 0.39; 95% CI: 0.22,0.69; p= 0.001), receiving chemotherapy (HR = 0.5; 95% CI: 0.31,0.79; p= 0.003), negative metastasis at diagnosis (HR = 0.05; 95% CI: 0.024,0.12; p= &amp;lt;0.001), cancer stage (HR = 2.3 for stage II and 7.2 for stage III, p&amp;lt;0.01. Stage I used as reference); were significantly associated with OS. Conclusion: Our study shows that NECB is a rare malignancy, and that the AJCC cancer staging can be used to adequately assess prognosis. Large cell histology, ER/PR negative, and advanced AJCC stage were inversely associated with survival, whereas chemotherapy use, surgery, and no metastasis at diagnosis, were positively associated with survival. As in other histologies of breast cancer, surgery and chemotherapy need to be strongly considered when treating NECB. Citation Format: Alvaro Alvarez Soto, Jesus Anampa. Baseline characteristics and survival of neuroendocrine carcinoma of the breast- A SEER database analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-26.

Large cell neuroendocrine tumor of the gastrointestinal tract with concurrent tubular adenomas

article: Large cell neuroendocrine tumor of the gastrointestinal tract with concurrent tubular adenomas - Gazzetta Medica Italiana - Archivio per le Scienze Mediche 2021 September;180(9):498-502 - Minerva Medica - Journals

MGMT promoter methylation in large-cell neuroendocrine carcinoma

Abstract Introduction: Currently, there is no consensus on the treatment of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in large-cell pulmonary neuroendocrine carcinoma. Some studies have shown that MGMT promoter methylation could be a predictive factor for objective response and survival, but there are few reports on MGMT promoter methylation in pulmonary large-cell neuroendocrine tumors treated with radiotherapy combined with temozolomide. Patient Concerns: An 80-year-old man with large-cell neuroendocrine carcinoma of the lung complained of weakness in the right lower limb. Multiple organ metastases were detected on imaging examination. Diagnosis: Large-cell neuroendocrine carcinoma was confirmed by pathological examination after the surgery. Interventions: The patient had local recurrence four months after surgical treatment that progressed after administration of a variety of chemotherapeutic drugs. Good local control was achieved after local chest radiotherapy. After the occurrence of brain metastasis and multiple organ metastases, brain radiotherapy combined with oral temozolomide was administered. Subsequently, the brain metastases disappeared and metastases in the other organs decreased. Furthermore, the original pathological gene detection showed that the MGMT promoter was methylated. Outcomes: Owing to economic reasons, the patient stopped taking temozolomide and died of liver metastasis with hypoproteinemia four months later. Conclusion: Radiotherapy had a significant effect on the local lesions of this patient with pulmonary large-cell neuroendocrine carcinoma, and temozolomide was effective against systemic lesions in this case with MGMT promoter methylation. Simultaneous treatment with radiotherapy and chemotherapy in this elderly patient was effective, and the side effects were tolerable.

A Novel Strategy for the Diagnosis of Pulmonary High-Grade Neuroendocrine Tumor.

Correctly diagnosing a histologic type of lung cancer is important for selecting the appropriate treatment because the aggressiveness, chemotherapy regimen, surgical approach, and prognosis vary significantly among histologic types. Pulmonary NETs, which are characterized by neuroendocrine morphologies, represent approximately 20% of all lung cancers. In particular, high-grade neuroendocrine tumors (small cell lung cancer and large cell neuroendocrine tumor) are highly proliferative cancers that have a poorer prognosis than other non-small cell lung cancers. The combination of hematoxylin and eosin staining, Ki-67, and immunostaining of classic neuroendocrine markers, such as chromogranin A, CD56, and synaptophysin, are normally used to diagnose high-grade neuroendocrine tumors; however, they are frequently heterogeneous. This article reviews the diagnostic methods of lung cancer diagnosis focused on immunostaining. In particular, we describe the usefulness of immunostaining by Stathmin-1, which is a cytosolic phosphoprotein and a key regulator of cell division due to its microtubule depolymerization in a phosphorylation-dependent manner, for the diagnosis of high-grade neuroendocrine tumors.

S3611 Double Trouble: Primary Lung and Colon Cancer in a Patient With Crohn’s Disease

Introduction: This vignette highlights the development of localized rectal adenocarcinoma and concomitant metastatic large cell neuroendocrine tumor of the lung in a patient with longstanding Crohn’s disease (CD) on Vedolizumab (VDZ). Case Description/Methods: A 61 year old male with a 2 year history of severe, uncontrolled colonic inflammatory CD presented to the ED with weakness, loss of appetite, and a 30lb weight loss over a 1 month period. He had been on VDZ 300mg every 8 weeks for 1 year. A CT chest showed a new 2cm pulmonary nodule with increasing mediastinal and perihilar lymphadenopathy. Bronchoscopy and endobronchial ultrasound were performed for lymph node sampling and revealed a large cell neuroendocrine tumor, which was later found to be metastatic to the brain. The patient was discharged with plans to optimize the VDZ therapy and start cancer treatment. Anticipating the use of immunotherapy, a colonoscopy was performed and revealed active inflammation in the sigmoid colon. Incidentally, an 18mm Is (sessile) polyp was found in the rectum and removed by piecemeal snare polypectomy. Pathology was consistent with invasive colonic adenocarcinoma. A colonoscopy one year earlier had been negative for malignancy. After a careful discussion in the GI tumor board, the decision was made to treat the lung cancer first. Unfortunately, the patient developed sepsis after his first chemotherapy dose and passed away. Discussion: This case illustrates the challenges with CD therapy during active malignancy. CD patients are at increased risk for both colonic adenocarcinoma and pulmonary malignancy. There have been isolated cases linking CD to premalignant diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, suggesting a possible correlation between CD and the highly aggressive large cell neuroendocrine tumor of the lung seen, though data is limited. VDZ has been associated with 24%-31% clinical remission of CD after induction. It was shown to be well tolerated and had a low risk of malignancy in patients with and without a history of prior malignancy. Data is limited on the use of VDZ concurrently with active chemotherapy, though it is presumed have a favorable safety profile given the gut-selective nature of the drug. The development of malignancies in this case is thought to be possibly related to CD and likely unrelated to VDZ. With limited data available, a multidisciplinary discussion between oncology and GI is ideal to develop a tailored treatment plan for CD patients with active malignancy.

S2436 Coincidence or Not? A Rare Case of a Mixed Adenoneuroendocrine Rectal Tumor in the Setting of Ulcerative Colitis

Introduction: For decades it has been known that patients with inflammatory bowel disease (IBD) are at an increased risk for colorectal cancer, with adenocarcinoma being the most common. Risk of colorectal malignancy increases with years since diagnosis of IBD. However, very rarely diagnosed are mixed adenoneuroendocrine carcinomas (MANEC), comprising of at least 30% adenoma and 30% neuroendocrine components. Less than 20 cases have been reported of a MANEC in ulcerative colitis (UC) patients in the literature. Some hypothesize that chronic colonic mucosal inflammation and distant cytokine release eventually lead to MANECs. We present a case of high grade MANEC diagnosed in the setting of UC. Case description/methods: An 85 year old male with a 4-year history of refractory pan-UC with failure of multiple biologics (TNF alpha inhibitors, monoclonal antibodies), mesalamine, and azathioprine presented with worsening diarrhea, fecal urgency, rectal bleeding, muccorhea, and failure to thrive. He was placed on a long steroid taper. Fecal calprotectin was 1380 μg/g. Colonoscopy revealed severe pan-UC and a 4 cm sessile, exophytic, polypoid lesion in the proximal rectum. Biopsies revealed a high grade large cell neuroendocrine tumor positive for chromogranin, synaptophysin, CDX2, and Ki-67 cellular proliferation index of 40-50%. Robotic subtotal proctocolectomy with end ileostomy was performed with rectal specimen pathology revealing a high grade large cell poorly differentiated neuroendocrine carcinoma with low grade adenocarcinoma, consistent with pT3N1a MANEC. Given a single lymph node was positive, the patient is currently seeking oncologic opinion for potential chemotherapy. Discussion: The incidence of MANEC in a UC patient is very rare. To our knowledge, there are only 20 cases describing a MANEC diagnosis in a UC patient. There is now discussion as to whether or not MANECs correlate with IBD, specifically UC. In addition, MANEC lesions are associated with poor survival rates due to diagnosis at advanced stages. The decision to proceed with subtotal proctocolectomy for MANEC in an elderly patient with refractory pan-UC without severe co-morbidities was made due to a higher MANEC related mortality rate compared to other causes. Given the aggressive nature of MANECs, further research should be conducted regarding association between MANECs and UC to guide future diagnosis and treatment.Figure 1.: A 4 cm sessile, exophytic, polypoid lesion in the proximal rectum on colonoscopy status post biopsies revealing a MANEC on pathology.

Large-cell neuroendocrine tumor of the prostate: a\xa0case report and review of the literature

BackgroundPrimitive neuroendocrine prostate neoplasms are rarely reported. This entity comprises carcinoïd tumors and poorly differentiated neuroendocrine tumors, mainly those of the small-cell type. Large-cell-type primitive tumors are exceptional, and only nine cases are reported in the literature. Similar to neuroendocrine tumors of the prostate, large-cell-type primitive tumors may be observed in the context of conventional adenocarcinoma during androgen deprivation therapy or as prostatic metastasis of a distant neuroendocrine tumor, mainly pulmonary neoplasms.Case presentationWe report a Caucasian case of a mixed prostatic carcinoma, with the largest component being the large-cell neuroendocine carcinoma, in a patient who underwent a total prostatectomy for a localized cancer. Diagnostic, histological, therapeutic and evolutive aspects are reported and discussed.ConclusionsLarge-cell primitive prostate neuroendocrine carcinoma is a rare but aggressive histological entity, which can be associated or not with an adenocarcinomatous component. Mixed forms have a better outcome, mainly when diagnosed at an early stage.

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.

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

Real-world survival outcomes with immune checkpoint inhibitors in large-cell neuroendocrine tumors of lung

BackgroundLittle is known regarding the efficacy of immune checkpoint inhibitors (ICI) in patients with advanced large-cell neuroendocrine lung carcinoma (aLCNEC).Methods125 consecutive patients with aLCNEC were identified in the electronic databases...