Prognostic Immunohistochemistry for Ki-67 and OTP on Small Biopsies of Pulmonary Carcinoid Tumors: Ki-67 Index Predicts Progression-free Survival and Atypical Histology.

Prognostic stratification of pulmonary carcinoids into "typical" and "atypical" categories requires examination of large tissue volume. However, there is a need for tools that provide similar prognostic information on small biopsy samples. Ki-67 and OTP immunohistochemistry have shown promising prognostic value in studies of resected pulmonary carcinoids, but prognostic value when using biopsy/cytology specimens is unclear. Ki-67 immunohistochemistry was performed on small biopsy/cytology specimens from pulmonary carcinoid tumors (n=139), and labeling index was scored via automated image analysis of at least 500 cells. OTP immunohistochemistry was performed on 70 cases with sufficient tissue and scored as positive or negative (<20% tumor nuclei staining). Higher Ki-67 index was associated with worse disease-specific progression-free survival (ds-PFS), with 3% and 4% thresholds having similarly strong associations with ds-PFS ( P <0.001, hazard ratio ≥11). Three-year ds-PFS was 98% for patients with Ki-67 <3% and 89% for patients with Ki-67≥3% ( P =0.0006). The optimal Ki-67 threshold for prediction of typical versus atypical carcinoid histology on subsequent resection was 3.21 (AUC 0.68). Negative OTP staining approached significance with atypical carcinoid histology ( P =0.06) but not with ds-PFS ( P =0.24, hazard ratio=3.45), although sample size was limited. We propose that Ki-67 immunohistochemistry may contribute to risk stratification for carcinoid tumor patients based on small biopsy samples. Identification of a 3% hot-spot Ki-67 threshold as optimal for prediction of ds-PFS is notable as a 3% Ki-67 threshold is currently used for gastrointestinal neuroendocrine tumor stratification, allowing consideration of a unified classification system across organ systems.

Gallbladder carcinoid in a cat.

Carcinoids are rare tumors that originate from neuroendocrine system cells. There has apparently only been 1 report in the veterinary medical literature of a cat with a gallbladder carcinoid, with no long-term follow-up information available from that case. Furthermore, apparently only 9 dogs with gallbladder carcinoids have been reported, again with no long-term follow-up. This case report describes the clinical presentation, surgical appearance, histopathologic and immunohistochemical findings, postoperative adjuvant chemotherapy treatment, and long-term outcome of a domestic longhair cat with a gallbladder carcinoid. The diagnosis of a gallbladder carcinoid in the present case was based on histologic and immunohistochemical findings. Clinical signs of a gallbladder carcinoid are nonspecific and ultrasonographic findings may not be definitive; however, it should be considered as a potential differential diagnosis in cats with lesions of the gallbladder or in the region of the gallbladder. The prognosis is poor, with a potentially high metastatic rate. In the present case, metastasis occurred 7 mo postoperatively despite adjuvant therapy, and the survival time was only 10 mo from the time of diagnosis. Key clinical message: This case report describes the clinical presentation, surgical appearance, histopathologic and immunohistochemical findings, postoperative adjuvant treatment, and long-term outcome of a cat with a gallbladder carcinoid, which should be considered as a potential differential diagnosis in cats with lesions of the gallbladder or in the region of the gallbladder.

Carcinoïde de la vésicule biliaire chez un chat. Les carcinoïdes sont des tumeurs rares qui prennent leur origine des cellules du système neuroendocrinien. Dans la littérature médicale vétérinaire il n'y aurait qu'un seul cas rapporté d'un chat avec un carcinoïde de la vésicule biliaire, sans aucune information de suivi à long terme disponible pour ce chat. Également, il y aurait 9 cas rapportés de chiens avec des carcinoïdes de la vésicule biliaire, mais encore là aucun suivi à long terme. Le cas présenté ici décrit la présentation clinique, l'apparence chirurgicale, les trouvailles histopathologiques et immunohistochimiques, le traitement post-opératoire par chimiothérapie adjuvante, et le devenir à long terme d'un chat domestique à poil court avec un carcinoïde de la vésicule biliaire. Dans le cas présent, le diagnostic de carcinoïde de la vésicule biliaire était basé sur les trouvailles histologiques et immunohistochimiques. Les signes cliniques d'un carcinoïde de la vésicule biliaire sont non-spécifiques et les trouvailles échographiques pourraient ne pas être concluantes; toutefois, il devrait être considéré comme un diagnostic différentiel possible chez des chats avec des lésions à la vésicule biliaire ou dans la région de la vésicule biliaire. Le pronostic est mauvais, avec un risque élevé de métastases. Dans le cas présent, des métastases sont apparues 7 mo post-chirurgie malgré une chimiothérapie adjuvante, et le temps de survie a été de 10 mo à compter du moment du diagnostic.Message clinique clé:Ce rapport de cas décrit la présentation clinique, l'apparence chirurgicale, les trouvaille histologiques et immunohistochimiques, la thérapie adjuvante postopératoire, et le résultat à long-terme pour un chat avec un carcinoïde de la vésicule biliaire, qui devrait être considéré comme un diagnostic différentiel potentiel chez les chats avec des lésions à la vésicule biliaire ou dans la région de la vésicule biliaire.(Traduit par Dr Serge Messier).

Comparison of Octreotide and Vasopressors as First-Line Treatment for Intraoperative Carcinoid Crisis.

BACKGROUND: Intraoperative carcinoid crisis is typically sudden onset of profound hypotension during operations on patients with neuroendocrine tumors. The crisis was thought to be due to massive release of hormones, and perioperative octreotide was recommended as a prophylaxis against the crisis and as first-line treatment. Recent studies show that octreotide does not prevent the crisis and that no massive release of hormones occurs. Therefore, the authors hypothesized that octreotide is not effective for treating the crisis. METHODS: A prospective carcinoid anesthesia database was analyzed for occurrences of crisis. Outcomes were compared between protocols when first-line therapy was bolus octreotide and when it was vasopressors without octreotide. Significance was determined by Student's t test, the Mann-Whitney U test, and Fisher's exact test. RESULTS: Among operations performed with octreotide as first-line treatment (n = 150), crisis occurred for 45 (30 %) patients, the median crisis duration was 6 min, 12 (27 %) patients had crises longer than 10 min, 42 patients (93 %) required subsequent vasopressor administration to resolve the crisis, and 3 (2 %) operations were aborted. Among operations performed with vasopressors as the first-line treatment (n = 195), crisis occurred for 49 (25 %) patients (p = 0.31), the median crisis duration was 3 min (p < 0.001), and no crisis lasted longer than 10 min (p = 0.001). Patients treated with vasopressors were less likely to have multiple crises and had a shorter total time in crisis, a shorter anesthesia time, and no aborted operations (p < 0.05 for all). CONCLUSIONS: First-line octreotide was ineffective treatment for carcinoid crisis, with patients requiring vasopressors to resolve the crisis, and many crises lasting longer than 10 min. First-line vasopressor treatment resulted in significantly shorter crisis durations, fewer crises and aborted operations, and shorter anesthesia times. Vasopressors should be used as first-line treatment for intraoperative crisis, and treatment guidelines should be changed.

Role of orthopedia homebox protein in subclassification of pulmonary carcinoid tumors: Retrospective analysis of 110 cases.

Background: Orthopedia homeobox protein (OTP), highlighted as a sensitive and specific marker for pulmonary carcinoids, may provide a more objective criterion for subclassification. Materials and Methods: A total of 110 patients who underwent surgery for pulmonary carcinoids (2009-2019) were included. Gender, age, application complaint, tumor diameter and location, typical and atypical tumor type, lymph node involvement, stage, recurrence, and survival data were evaluated retrospectively with OTP nuclear staining. Results: The sensitivity of OTP was 66.4%. OTP in subclassifying pulmonary carcinoids was not significant. There was no significant relationship between OTP and lymph node involvement, recurrence, and survival. Conclusion: OTP does not provide significant results in the subclassification of typical and atypical carcinoid tumors and the evaluation of recurrence and survival of carcinoid tumor cases.

Maintaining quality of life after major lung resection for carcinoid tumor.

BACKGROUND: Pulmonary carcinoid is a rare diagnosis with surgery remaining the standard treatment of choice. However, resection may impact patients' daily activities due to decreased lung volume reserve and postoperative pain. Our study aims to compare the impact of different types of surgical resection on the post-operative quality of life with the application of a strict peri-operative pulmonary care program. METHODS: Patients who underwent surgery for bronchopulmonary carcinoid tumors in a tertiary cancer center between August, 2017 and March, 2020 were identified and demographic data was collected. Patients were contacted via phone for the qualitative and quantitative assessment of pain and quality of life, utilizing the Arabic version of Short-form McGill Pain Questionnaire and Activity of Daily Living (ADL) instrument respectively. Lung reserve was assessed before and after surgery. Statistical analysis used Chi-Square for categorical variables and ANOVA for continuous variables. RESULTS: A total of 16 patients underwent different type of resection. The majority were male (n = 10; 63%) with a mean age of 44 years (19-81). Most common clinical stage was stage I (n = 12, 75%) with typical carcinoid features recorded in more than half of the cases (n = 11, 69%). Almost all patients underwent surgical excision (n = 15, 94%) with negative resection margin and no major post-operative complications. Bilobectomy was the most frequent procedure (n = 6, 40%) and video-assisted thoracoscopic surgery (VATS) was utilized in 8 patients (50%). Expected changes were recorded in pre- and postoperative pulmonary function test with an average drop of 10 in FEV1 and 14 mL/min/mmHg in DLCO. The majority of patients (n = 15, 94%) were totally independent doing daily activities. Mild intermittent pain was found in 7 patients (44%) who scored an average intensity of 1.6 out of 10. CONCLUSIONS: Excellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoid tumors with little to no effect on patients' lung function and quality of life in regard to performance status and post-operative pain when a good peri-operative pulmonary, physical rehabilitation, and pain management programs are adopted and strictly implemented.

[Features of surgical treatment of central tracheal and bronchial carcinoid]. / Osobennosti khirurgicheskogo lecheniya tsentral'nogo kartsinoida trakhei i bronkhov.

OBJECTIVE: To analyze features of surgical treatment of central tracheal and bronchial carcinoid. MATERIAL AND METHODS: A retrospective analysis included 115 patients with carcinoid tracheal and bronchial tumors who have been examined and treated from 1974 to the present. The majority of patients (97, 84.3%) had central form of carcinoid of the trachea, bronchi and lungs. Of these, 95 (97.9%) ones underwent surgical treatment. RESULTS: We used pre- and intraoperative diagnostics including bronchotomy. This approach provided organ-sparing surgery with resection and reconstruction of the bronchi and trachea in 71 (74.7%) patients including complete preservation of lung function in 20 (21.1%) cases and lobectomy/segmentectomy with resection and reconstruction of the bronchi in 51 (53.7%) cases. Two patients underwent pneumonectomy with wedge-shaped and marginal resection and reconstruction of tracheal bifurcation. Postoperative complications developed in 4 (4.2%) patients, and 2 (2.1%) ones died. Overall 5-year survival after radical surgeries was 89.2% (100% in typical carcinoid and 78.0% in atypical carcinoid).

Carcinoid syndrome caused by a pulmonary carcinoid mimics intestinal manifestations of ulcerative colitis: A case report.

BACKGROUND: Pulmonary carcinoids are rare, low-grade malignant tumors characterized by neuroendocrine differentiation and relatively indolent clinical behavior. Most cases present as a slow-growing polypoidal mass in the major bronchi leading to hemoptysis and pulmonary infection due to blockage of the distal bronchi. Carcinoid syndrome is a paraneoplastic syndrome caused by the systemic release of vasoactive substances that presents in 5% of patients with neuroendocrine tumors. Due to such nonspecific presentation, most patients are misdiagnosed or diagnosed late and may receive several courses of antibiotics to treat recurrent pneumonia before the tumor is diagnosed. CASE SUMMARY: We report the case of a 48-year-old male who presented with cough, dyspnea, a history of recurrent pneumonitis, and therapy-refractory ulcerative colitis that completely subsided after the resection of a pulmonary carcinoid. CONCLUSION: We report and emphasize pulmonary carcinoid as a differential diagnosis in patients with nonresponding inflammatory bowel diseases and recurrent pneumonia.

Fortuitously detected primary ovarian carcinoid tumor: A case report.

RATIONALE: Carcinoid tumors, derived from the cells of the disseminated neuroendocrine system, are rare, slow-growing neuroendocrine neoplasms that display a relatively indolent disease course. The majority of carcinoids are found within the gastrointestinal tract and bronchopulmonary system. Primary ovarian carcinoids are rare and account for merely 1% of all carcinoid tumors. We describe our experience of a rare case of primary ovarian carcinoid, presenting as chronic constipation, with no other carcinoid symptoms such as flushing, diarrhea, and wheezing. PATIENT CONCERNS: A 51-year-old postmenopausal woman with chronic constipation visited the clinic for routine check-up of her preexisting uterine fibroids. She had undergone hemorrhoidectomy 3 years ago. Physical examination revealed a soft abdomen without direct or rebound tenderness. Transvaginal ultrasonography revealed two subserosal fibroids, which had increased in size compared with previous ultrasonographic findings. A 3 cm hyperechoic mass was also detected in the right ovary. Her blood and urine tests were unremarkable, with no ascites in the pelvic cavity. She had a normal CA-125 level of 5.5 units/mL. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: The patient underwent a robot-assisted hysterectomy and right salpingo-oophorectomy because of enlarging fibroids and the right ovarian mass. Subsequently, based on the pathological and immunohistochemical findings, she was diagnosed with a primary ovarian carcinoid. The mass consisted of the insular and trabecular types of tumor cells. It was positive for pan-cytokeratin and synaptophysin, and the Ki-67 proliferation index was less than 1%. A follow-up positron emission tomography-computed tomography revealed no distant metastasis. Six months postoperatively, the patient was doing well without any signs of recurrence. LESSONS: Primary ovarian carcinoids without teratoma components are rare. It is crucial to make an accurate diagnosis based on the immunohistochemical staining results. Diagnosis in the early stages of the disease are associated with a favorable prognosis, but regular follow-up is mandatory.

In-depth analysis of immunohistochemistry concordance in biopsy-resection pairs of bronchial carcinoids.

Primary diagnosis of bronchial carcinoids (BC) is always made on biopsies and additional immunohistochemistry (IHC) is often necessary. In the present study we investigated the concordance of common diagnostic (synaptophysin, chromogranin, CD56 and INSM-1) and potential prognostic (OTP, CD44, Rb and p16) IHC markers between the preoperative biopsies and resections of in total 64 BCs, 26 typical (41 %) and 38 atypical (59 %) carcinoid tumors. Synaptophysin and chromogranin had 100 % concordance in all resected carcinoids and paired diagnostic biopsies. Synaptophysin was not affected by variable expression in biopsies compared to chromogranin, CD56 and INSM-1. Notably, INSM-1 IHC was false negative in 8 % of biopsies. Of the novel and potential prognostic markers, only CD44 showed 100 % concordance between biopsies and resections, while OTP showed two (4 %) false negative results in paired biopsies. While Rb IHC was false negative in 8 % of biopsies, no strong and diffuse pattern of p16 expression was observed. In this study, most false negative IHC results (85 %, 22/26) were observed in small flexible biopsies. Taken together, our data suggest excellent concordance of synaptophysin and CD44 on the preoperative biopsy samples, while other neuroendocrine markers, Rb and OTP should be interpreted with caution, especially in small biopsies.

[Infectious pneumonia favored by paraneoplastic Cushing syndrome in a pulmonary carcinoid tumor]. / Pneumopathie infectieuse favorisée par un syndrome de Cushing paranéoplasique d'une tumeur carcinoïde pulmonaire.

INTRODUCTION: Ectopic Cushing's syndrome (CS) is a rare condition nevertheless well-known to endocrinologists. The pneumologist may be called upon to treat CS not only because bronchial carcinoid tumors are the most frequent source of ectopic ACTH secretion, but also due to the fact that the immunosuppression induced by hypercorticism favors lower respiratory tract infections. CASE REPORT: We report the case of a female patient presenting with acute respiratory failure secondary to Enterobacter cloacae pneumonia exacerbated by SC. Further investigations confirmed ectopic ACTH secretion and revealed a right upper lobe pulmonary nodule. After appropriate antibiotic therapy, the patient received preoperative adrenolytic treatment. Management by right upper lobectomy resulted in the extraction of a 12mm tumor. Pathological analysis was consistent with the diagnosis of a typical carcinoid tumor. Immunohistochemistry confirmed ACTH secretion by the tumor. Even though the postoperative course showed CS regression, the patient developed adrenal insufficiency. CONCLUSION: Ectopic CS induces immunosuppression, which aggravates lower respiratory tract infections. Search for a pulmonary neuroendocrine tumor should be systematic. Following control of the secretory syndrome by adrenolytic treatment, and if the diagnosis of carcinoid tumor is confirmed, surgical treatment is the preferred option.

A national cancer database analysis of the clinicopathologic characteristics and outcomes of appendiceal malignant mesenchymal tumors.

The present study aimed to assess the characteristics and outcomes of appendiceal malignant mesenchymal tumors. This was a retrospective case-series study of patients with appendiceal malignant mesenchymal tumors in the national cancer database (2005-2019). The main outcomes were overall survival (OS) and short-term mortality. 53 patients (40 GISTs and 13 sarcomas) were included. 92.6% of GIST patients had stage I disease and 76.9% of GISTs were ≤2 cm. Most appendiceal GISTs were treated with appendectomy or partial colectomy whereas half of patients with appendiceal sarcoma underwent hemicolectomy or subtotal colectomy. Only one short-term mortality was recorded in the sarcoma group. One-third of patients with sarcoma had positive surgical margins versus 5.1% of patients with GISTs. GIST patients had longer median OS (117.1 vs 54.8 months) than sarcoma patients.

Atypical thymic carcinoid tumor with ectopic ACTH syndrome in a 33-year-old male patient: A rare case report and literature review.

RATIONALE: Atypical thymic carcinoid tumor is an exceedingly rare thymic neuroendocrine tumor derived from the cells of neuroendocrine system. Misdiagnosis or delayed diagnosis may result in disease progression to advanced stages and eventually leads to a poor prognosis. It is therefore necessary to make a correct diagnosis and provide an adequate treatment. PATIENT CONCERNS: A 33-year-old Chinese male presented with numbness in bilateral lower extremities and general fatigue for a month. Chest computed tomography revealed a superior anterior mediastinal mass. Thymoma was initially considered, given the location of the mass and radiographic presentation. DIAGNOSIS: Microscopic findings showed that the tumor cells are arranged in pseudoepitheliomatous growth or irregular nested growth pattern in a background of fibroconnective tissue, with focal infiltration into adipose tissue. The chrysanthemum-like structure or beam-like structure seen often in typical carcinoid tumor was not identified in this case. The tumor cells are spindled or oval, with focal active mitosis. The immunohistochemical staining showed strong positivity for CD56, CgA and Syn, positivity for CK, ACTH, and TTF-1, negativity for Vimentin, and ki67 labeled proliferation index was up to 10% in focal areas. According to the radiological and pathological findings, the diagnosis of atypical thymic carcinoid was made. INTERVENTIONS: The patient underwent surgical resection of the mass. OUTCOME: No recurrence or metastasis was identified during the follow up. LESSONS: Because of its low incidencen, onspecific clinical symptoms, tissue location, and radiological findings, atypical thymic carcinoid tumor may sometimes be misdiagnosed as thymoma. Attention should be paid to avoid misdiagnosis.

[Three Cases of Appendiceal Goblet Cell Adenocarcinoma in Our Institution].

Appendiceal goblet cell adenocarcinoma(AGCA)is a newly designated pathological term adopted in the 5th edition of the WHO classification. It is synonymous with goblet cell carcinoid, which was previously categorized as a part of appendiceal carcinoid. However, since 2018, it has been classified as a subtype of adenocarcinoma. We have experienced 3 cases of this relatively rare tumor, of which 2 were initially diagnosed with acute appendicitis and were diagnosed with AGCA by pathological examination after an emergency appendectomy. Each of them underwent additional ileocolic resection with lymph node dissection as the second surgery. In the 3rd case, an appendiceal tumor was detected during preoperative examinations for an ovarian tumor. Staging laparoscopy revealed comorbid peritoneal dissemination, and only the appendix and right ovary were removed in the consecutive surgery. The ovarian tumor was pathologically diagnosed as a metastasis of AGCA. In this case, the introduction of oxaliplatin-based systemic chemotherapy after surgery achieved a complete response after more than 2 years. Although no recurrence has been observed in all 3 cases to date, AGCA is considered highly malignant compared to conventional appendiceal carcinoids. Therefore, it is crucial to practice multidisciplinary treatments, including sufficient radical surgery based on a precise diagnosis of AGCA, as is performed for advanced colorectal cancer.

Clinical efficacy of thermal ablation for the treatment of pulmonary carcinoid tumor: a propensity-matched analysis.

OBJECTIVE: To investigate the clinical efficacy of thermal ablation in the treatment of pulmonary carcinoid (PC) tumor. METHODS: Data of patients with inoperable PC diagnosed from 2000 to 2019 were obtained from the SEER database and analyzed according to different therapeutic modality: thermal ablation vs non-ablation. Propensity score matching (PSM) was used to reduce intergroup differences. Kaplan-Meier curves and the log-rank test were used to compare intergroup differences of overall survival (OS) and lung cancer-specific survival (LCSS). Cox proportional risk models were used to reveal prognostic factors. RESULTS: After PSM, the thermal ablation group had better OS (p < .001) and LCSS (p < .001) than the non-ablation group. Subgroup analysis stratified by age, sex, histologic type and lymph node status subgroups showed similar survival profile. In the subgroup analysis stratified by tumor size, the thermal ablation group showed better OS and LCSS than those of the non-ablation group for tumors ≤3.0 cm, not statistically significant for tumors >3.0 cm. Subgroup analysis by M stage showed that thermal ablation was superior to non-ablation in OS and LCSS for patients with M0 stage, but no significant difference was found in subgroups with distant metastatic disease. Multivariate analysis showed that thermal ablation was an independent prognostic factor for OS (HR: 0.34, 95% CI: 0.25-0.46, p < .001) and LCSS (HR: 0.23, 95%CI: 0.12-0.43, p < .001). CONCLUSION: For patients with inoperable PC, thermal ablation might be a potential treatment option, especially in M0-stage with tumor size ≤3 cm.

Clinical characteristics and survival outcomes in patients with primary ovarian carcinoid: A historical cohort study.

INTRODUCTION: Primary ovarian carcinoids are extremely rare ovarian tumors, and there is limited data available on their clinical characteristics and survival outcomes. MATERIAL AND METHODS: We conducted a historical cohort study of 56 patients to investigate their clinical characteristics. The overall survival, disease-specific survival, recurrence-free survival, and potential prognostic factors of these patients were also evaluated. RESULTS: The median age of these patients was 42.0 years (range: 20-71). The average mass and carcinoid size was 7.3 and 0.4 cm, respectively. Elevated tumor marker levels and ascites were observed in 15 and 10 patients, respectively. In 98.2% of the patients, tumors were confined to the ovary, while only one had metastatic disease. Surgery was the mainstay therapy: 37.5% of the patients underwent unilateral salpingo-oophorectomy, 25.0% underwent hysterectomy with bilateral salpingo-oophorectomy, 21.4% underwent ovarian cystectomy, 10.7% underwent comprehensive staging surgery, and 5.4% underwent bilateral salpingo-oophorectomy. Appendectomy and lymphadenectomy were performed in eight and five patients, respectively, but none showed tumor involvement. Chemotherapy was the only adjuvant treatment utilized, and was administered in four patients. Pathological analysis showed that strumal carcinoid was the most predominant subtype, occurring in 66.1% of the patients. The Ki-67 index was reported in 39 patients, 30 of which had an index of no more than 3%, with a maximum of only 5%. Only one relapse occurred after the initial treatment, and that patient experienced recurrences on two occasions, maintaining stable disease after surgery and octreotide therapy. After a median follow-up of 3.6 years, 96.4% of the patients achieved no evidence of disease, while 3.6% were alive with the disease. The 5-year recurrence-free survival rate was 97.9% and no death occurred. No risk factors for recurrence-free survival, overall survival, or disease-specific survival were identified. CONCLUSIONS: The Ki-67 indices were extremely low and prognoses were excellent in patients with primary ovarian carcinoids. Conservative surgery, especially unilateral salpingo-oophorectomy, is preferred. Individualized adjuvant therapy may be considered for patients with metastatic diseases.

Lung neuroendocrine neoplasms: a single centre surgical series and analysis of staging.

BACKGROUND: To review the outcomes of surgically resected lung neuroendocrine neoplasms (LNEN) at a tertiary referral centre and to validate a previously published LNEN-specific staging system (NETL). METHODS: All patients who were identified on histopathology to have LNEN were included. Pre-, intra- and post-operative outcomes were collected, including long-term survival. Patients were staged by both the TNM (seventh and eighth edition) and NETL staging (seventh and eighth edition definitions). Kaplan-Meier (KM) survival analysis was performed according to histopathology and stage, along with uni- and multivariate analyses. RESULT: A total of 132 patients were included in the study, with a median age of 65 years; 55% were female. Typical carcinoid (TC) was the most common pathology (53.4%) followed by large cell neuroendocrine carcinoma (LCNEC - 23.5%), atypical carcinoid (AC - 20.5%) and small cell carcinoma (3.0%). The most common operation performed was a lobectomy (55.3%). Overall survival at 5 years was 80% (100% TC, 78.2% AC, LCNEC 40.9%) and 5-year disease free survival was 76.8% (TC 94.3%, AC 56.8%, LCNEC 56.4%). KM curves showed a trend towards NETL performing better than TNM, however, in multivariate analysis only the histological subtype was found to be significant in our study. CONCLUSION: This is the largest known Australian series of LNEN to date, showing survival comparable to international outcomes. We have demonstrated large variations in outcome, driven by histological grade. The TNM system does not correlate with survival and we have not been able to show that currently proposed NETL staging is superior.