Pulmonary Carcinoid Tumors Research Articles

PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin.

Neuroendocrine tumors (NETs) are often diagnosed from the metastases of an unknown primary tumor. Specific immunohistochemical (IHC) markers indicating the location of a primary tumor are needed. The proprotein convertase subtilisin/kexin type 2 (PCSK2) is found in normal neural and neuroendocrine cells, and known to express in NETs. We investigated the tissue microarray (TMA) of 86 primary tumors from 13 different organs and 9 metastatic NETs, including primary tumor‐metastasis pairs, for PCSK2 expression with polymer‐based IHC. PCSK2 was strongly positive in all small intestine and appendiceal NETs, the so‐called midgut NETs, in most pheochromocytomas and paragangliomas, and in some of the typical and atypical pulmonary carcinoid tumors. NETs showing strong positivity were re‐evaluated in larger tumor cohorts confirming the primary observation. In the metastases, the expression of PCSK2 mirrored that of the corresponding primary tumors. We found negative or weak staining in NETs from the thymus, gastric mucosa, pancreas, rectum, thyroid, and parathyroid. PCSK2 expression did not correlate with Ki‐67 in well‐differentiated NETs. Our data suggest that PCSK2 positivity can indicate the location of the primary tumor. Thus, PCSK2 could function in the IHC panel determined from screening metastatic NET biopsies of unknown primary origins.

Diagnostic significance of somatostatin receptor scintigraphy using <sup>111</sup>In-pentetreotide for recurrence and staging of pulmonary carcinoid tumors: Two case reports

Diagnostic significance of somatostatin receptor scintigraphy using <sup>111</sup>In-pentetreotide for recurrence and staging of pulmonary carcinoid tumors: Two case reports

Predictive Indicators of Survival in Patients With Surgically Resected Lung Carcinoid Tumors at a Greek Medical Center.

IntroductionLung carcinoid tumors are neuroendocrine neoplasms, less frequent than other lung tumors. They are subdivided into typical carcinoids (TC) and atypical carcinoids (AC), according to the rate of mitosis and the presence of necrosis. Lung carcinoids are often asymptomatic and only discovered incidentally. They may also present with cough, wheezing, asthma, and chronic obstructive pulmonary disease, chest pain, and hemoptysis depending on the location of the tumor and, less commonly, present with carcinoid syndrome. In our study, we describe the clinical and pathological features of patients with surgically resected lung carcinoids at our institution over a period of 14 years. We also examine if these features, including age, gender, tumor size, type of carcinoid, stage, nodal involvement, and Ki-67 expression are associated with patients' survival.Materials and methodsWe retrospectively reviewed patients that underwent surgery with a final histologic diagnosis of a pulmonary carcinoid tumor from March 2005 to March 2019. The evaluation included history, physical examination, chest radiographs, computerized tomography of the chest, upper abdomen, and brain, and bone scintiscan. All specimens resected during the surgical procedures were sent for pathological examination, including mediastinal and hilar lymph nodes. The patients' age, gender, tumor size, type of carcinoid, nodal involvement, stage, and Ki-67 expression were recorded and correlated to the patients' survival rates.ResultsThe study included 108 patients - 52 males and 56 females - with a mean age of 51.5 years (range 11-80 years). Atypical carcinoid was the diagnosis in 28 patients (16 males and 12 females) and 80 patients had the diagnosis of typical carcinoid (36 males and 44 females). Tumor size was ≤3.7 cm in 84 patients (68 with TC and 16 with AC) and >3.7 cm in 22 patients (12 with TC and 10 with AC). Sixteen patients had nodal deposits, 12 in N1 nodes and four in N2 nodes. Eighty patients were classified in stage I, 18 patients in stage II, and 10 patients in stage III. None of the patients had distant metastases. The Ki-67 proliferation index was examined in 84 specimens and Ki-67 was <2.5 in 50 patients and ≥2.5 in 34 patients. Of the 108 patients, eight died, all with disease-related death. According to the Cox regression univariate analysis, four factors were correlated to shorter survival: atypical histology, tumor size >3.7 cm, nodal involvement, and advanced stageConclusionsIn conclusion, we found that histological type, tumor size, nodal involvement, and stage are associated with survival in patients with surgically resected lung carcinoids without distant metastases. Other parameters, such as age at operation, gender, and Ki-67 index, did not have a role in survival in these patients according to the Cox regression univariate analysis.

Abstract 5892: Whole-exome and RNA sequencing reveals chromosomal rearrangements associated with the recurrence of pulmonary carcinoid

Abstract Background: The majority of pulmonary carcinoid (PC) tumors can be cured by surgical resection alone, but a significant proportion of patients experience recurrence. As PC is insensitive to conventional chemotherapy and a significant proportion of patients develop metastases, further clarification of the molecular mechanisms of metastasis is needed in order to develop targeted therapeutics. Material and Method: We performed comprehensive whole-exome sequencing (WES) of primary tumors and corresponding normal lung tissues from 14 PC patients (including 4 patients who developed postsurgical distant metastasis) and RNA sequencing of primary tumors from 6 PC patients (including 4 patients who developed postsurgical distant metastasis). Exon array-based gene expression analysis was performed in 25 cases of PC. Results: We identified a total of 139 alterations in 136 genes. MUC6 and SPTA1 were recurrently mutated at a frequency of 21% (3/14) and 14% (2/14), respectively. Mucin protein family genes including MUC2, MUC4 and MUC6 were mutated in a mutually exclusive manner in 36% (5/14). Pathway analysis of the mutated genes revealed enrichment of genes involved in mitogen-activated protein kinase (MAPK) signaling, regulation of the actin cytoskeleton and focal adhesion, and transforming growth factor (TGF)-β signaling. RNA sequencing revealed a total of 8 novel fusion transcripts including one derived from a chromosomal translocation between the TRIB2 and PRKCE genes. All of the 8 fusion genes were detected in primary PCs that had developed metastasis after surgical resection. We identified 14 genes up-regulated in 5 PCs that had relapsed after surgical resection. Conclusions: In this study we identified novel somatic mutations and chromosomal rearrangements in PC by examining clinically aggressive cases that had developed postsurgical metastasis. It will be essential to validate the clinical significance of these genetic changes in a larger independent patient cohort. Citation Format: Akihiko Miyanaga, Mari Masuda, Noriko Motoi, Koji Tsuta, Yuka Nakamura, Nobuhiko Nishijima, Shun-ichi Watanabe, Hisao Asamura, Akihiko Tsuchida, Masahiro Seike, Akihiko Gemma, Tesshi Yamada. Whole-exome and RNA sequencing reveals chromosomal rearrangements associated with the recurrence of pulmonary carcinoid [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5892.

Huge typical pulmonary carcinoid presented with gigantism syndrome

A 27-year-old male patient presented with cough and right-sided, light thoracic pain. His physical appearance showed typical features of gigantism. Subsequently, further diagnostic work-up showed elevated level of growth hormone and a huge tumor of the right lung, identifying a typical pulmonary carcinoid tumor (TPCT). Curative surgery was performed leading to normalization of the elevated growth hormone levels few days after surgery. Two- and five-year follow-up showed no signs of recurrence. Respected to tumor size, we determined the largest TPCT to be reported in medical literature history.

Does 68Ga-DOTA-NOC-PET/CT impact staging and therapeutic decision making in pulmonary carcinoid tumors?

Purpose of this study was to assess the utility of Ga-DOTA-NOC-PET/computed tomography (CT) (Ga-NOC-PET) in tumor detection, pathological differentiation and baseline staging of pulmonary carcinoids as well as to study its impact on therapeutic decision making. Patients who underwent a Ga-NOC-PET for initial evaluation of bronchopulmonary carcinoid tumors from August 2014 to December 2019 were included. Detection rate of Ga-NOC-PET for the primary lesion was calculated by visual estimation of tracer uptake as per Krenning score. SUVmax of typical and atypical carcinoid tumors was measured and difference compared using nonparametric statistical tests. Proportion of patients with distant metastases was also calculated and its impact on intended treatment was assessed. Imaging, histopathology and treatment details of 119 patients were available for analysis. Majority of tumors had an endobronchial location (74.7%) and showed histopathologic features of typical carcinoid (82.3%). Ga-NOC-PET showed a detection rate/sensitivity of 92.4%. Oncocytic variant on histopathology and smaller tumor size accounted for majority of negative results. Typical carcinoids showed significantly higher SUVmax than atypical tumors (median SUVmax 38.4 vs. 15.7, P = 0.002). Metastases to distant sites outside the thorax were seen in 14 patients (11.7%), primarily in liver and bones changing the intent of treatment from surgery to systemic therapy. Ga-NOC-PET detects asymptomatic distant metastatic disease in a sizeable number of patients (11.7%) with pulmonary carcinoid and thus contribute to clinical management by precluding futile surgeries. It shows a high sensitivity for tumor detection and can help differentiate between typical and atypical carcinoid variants by virtue of their variable tracer uptake. PET/CT using Ga-labeled DOTA peptides should be an integral part of diagnostic workup of patients with lung carcinoid.

Sublobar resection versus lobectomy for early-stage pulmonary carcinoid tumors with three centimeters or less in size: A population-based study.

e21062 Background: Pulmonary carcinoids (PCs), comprising of typical carcinoids (TCs) and atypical carcinoids (ACs), are rare low-grade malignant tumors and surgical resection is considered as the standard treatment for early stage PCs. However, it is not clear whether sublobar (Sub-L) resection of PCs would compromise the long-term oncologic outcomes. Here we investigate the equivalency of Sub-L resection versus lobectomy (Lobe) for patients with early stage PCs using the population-based Surveillance, Epidemiology, and End Results (SEER) registry. Methods: The clinical and survival data of early stage PC patients with less or equal 3cm diameter were retrieved. Kaplan-Meier method and log-rank tests were used to assess differences in overall survival (OS). We further performed the subgroup analysis by tumor size (T≤1cm, 1cm &lt; T≤2cm, 2cm &lt; T≤3cm) and patient age ( &lt; 70y and ≥70y). To reduce the bias of inherent retrospective study, we also performed propensity score matching (PSM) analysis by 1:1 fixed ratio nearest neighbor matching using Matchit package in R. Results: In total of 2934 PC patients, including 2741 TCs and 193 ACs, were recruited. 1011(34.46%) and 1923(65.54%) patients received Sub-L resection and lobectomy, respectively. After PSM, there was no significant difference between Sub-L and Lobe group in terms of OS in PC patients (P = 0.33). From the cox regression analysis, it indicated that older age, male gender, larger tumor size, AC histology type and Sub-L surgery were associated with a worse OS. We further performed PSM analysis on TCs and ACs, respectively. For TC patients, it indicated that patients in Lobe group had a much better OS compared to those in Sub-L group (p = 0.0067). In the subgroup analysis, the log-rank tests showed that there was a significant survival advantage for lobectomy in comparison with Sub-L resection for the TC patients with diameter 2cm &lt; T≤3cm (p = 0.0345), but not for those with diameter lower than 2cm. In the subgroup analysis of age, the log-rank test indicated that Lobe group in age &lt; 70 had a better prognosis with statistical difference compared to Sub-L group (p = 0.0032). For ACs, there was no statistic difference between Sub-L and Lobe group after PSM analysis in all the subgroup investigations. Conclusions: Sublobar resection may not significantly compromise the long-term oncologic outcomes in early stage PC patients. However, there is a survival benefit of lobectomy in certain pathological type and population, such as TCs patients with tumor size more than 2cm and age lower than 70-year-old.

MON-250 Late Diagnosis of ACTH-secreting Pulmonary Neuroendocrine Tumor by Repeated 68Ga Dotatate Pet/ct: Influence of Tumor Size in Abnormal Uptake?

Background: 68Ga DOTATATE PET/CT (68Ga-PET) has been proposed as a superior method in identifying ectopic ACTH syndrome (EAS). However, recent systematic review suggests its sensitivity is not as high as believed (1). We report a challenging case of EAS whose source was uncovered only after repeated 68Ga-PET. Clinical Case: A 15‐year-old male presented with rapid onset of typical features of Cushing’s syndrome (CS) and metabolic impairment. Hormone evaluation confirmed severe ACTH-dependent CS. Pituitary transsphenoidal surgery was performed due to positive responses in desmopressin stimulation and high dose dexamethasone suppression test, in addition to a 4 mm nodule in pituitary MRI. No tumor was found in surgical specimen and no hormonal improvement was observed after surgery. Inferior petrosal sinus sampling demonstrated no central to peripheral ACTH gradient. Neck US, thorax/abdomen/pelvis CT were negative and PET-CT/FDG was inconclusive. OctreoScan® identified anomalous uptake on left mediastinum and led the patient to a thoracic surgery (TS) with nodule resection at left hilum. Pathology confirmed ACTH positive 10 mm neuroendocrine tumor (NET) infiltrating a lymph node. The patient had transient clinical and hormonal improvement, with recurrence 7 months later. Thoracic CT (T-CT) showed a 7 mm nodule on inferior segment of superior left lobe, PET-CT/FDG and OctreoScan® were negative but abnormal uptake was verified by 68Ga-PET in subcarinal area. A sub centimetric lymph node was resected and pathology confirmed ACTH positive NET, although the patient did not achieve remission. Octreotide LAR, cabergoline and ketoconazole did not control hypercortisolism and bilateral adrenalectomy was performed. Then, T-CT showed stable lung nodule and 2nd 68Ga-PET was negative. One year later, T-CT evidenced growth of lung nodule to 15 mm and 3rd 68Ga-PET demonstrated for the first time, abnormal uptake in this area. The patient underwent resection of left superior lung lobe along with ipsilateral hilar lymph nodes, and histopathology study revealed an ACTH-secreting atypical pulmonary carcinoid tumor with Ki67 of 10% and 5 out of 11 lymph nodes affected. ACTH fell from 288 to 64 pg/mL after surgery. Conclusion: Despite the high sensitivity attributed to 68Ga-PET, false negatives have been reported. In the present case, primary tumor was evidenced by 68Ga-PET seven years after the first resection of a metastatic lymph node, in the 3rd 68Ga-PET assessment and after tumor growth. This adds to the evidence that further studies are needed to better assess the accuracy of 68Ga-PET for EAS. Reference: [1] Varlamov et al. Diagnostic utility of Gallium‐68‐somatostatin receptor PET/CT in ectopic ACTH‐secreting tumors: a systematic literature review and single‐center clinical experience. Pituitary 2019; 22:445–455

Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence

IntroductionThe majority of pulmonary carcinoid (PC) tumors can be cured by surgical resection alone, but a significant proportion of patients experience recurrence. As PC is insensitive to conventional chemotherapy, further clarification of the molecular mechanisms of metastasis is needed in order to develop targeted therapeutics. MethodsWe performed comprehensive whole-exome sequencing (WES) of primary tumors and corresponding normal lung tissues from 14 PC patients (including 4 patients who developed postsurgical distant metastasis) and RNA sequencing of primary tumors from 6 PC patients (including 4 patients who developed postsurgical distant metastasis). Exon array-based gene expression analysis was performed in 25 cases of PC. ResultsWe identified a total of 139 alterations in 136 genes. MUC6 and SPTA1 were recurrently mutated at a frequency of 21% (3/14) and 14% (2/14), respectively. Mucin protein family genes including MUC2, MUC4 and MUC6 were mutated in a mutually exclusive manner in 36% (5/14). Pathway analysis of the mutated genes revealed enrichment of genes involved in mitogen-activated protein kinase (MAPK) signaling, regulation of the actin cytoskeleton and focal adhesion, and transforming growth factor (TGF)-β signaling. RNA sequencing revealed a total of 8 novel fusion transcripts including one derived from a chromosomal translocation between the TRIB2 and PRKCE genes. All of the 8 fusion genes were detected in primary PCs that had developed metastasis after surgical resection. We identified 14 genes (DENND1B, GRID1, CLMN, DENND1B, NRP1, SEL1L3, C5orf13, TNFRSF21, TES, STK39, MTHFD2, OPN3, MET, and HIST1H3C) up-regulated in 5 PCs that had relapsed after surgical resection. ConclusionsIn this study we identified novel somatic mutations and chromosomal rearrangements in PC by examining clinically aggressive cases that had developed postsurgical metastasis. It will be essential to validate the clinical significance of these genetic changes in a larger independent patient cohort.

Endobronchial masses encountered on fine-needle aspiration biopsy: a focus on unusual entities.

Fine-needle aspiration biopsy (FNAB) is a useful technique in the evaluation of central lung tumors which is commonly encountered in clinical cytology practice. Some of these tumors may show endobronchial, polypoid growth which is readily apparent to the endoscopist. Pulmonary salivary gland-type tumors and carcinoid tumors are overall uncommon in the lung, but these tumors tend to occur centrally and show endobronchial involvement. The prognosis of these tumors is generally better than that of small cell or non-small cell carcinomas of the lung and more conservative surgical resection is often indicated. The identification of salient cytological features and a high index of suspicion when considering the differential diagnosis of a central lung tumor is essential to accurate diagnosis. This review focuses on cytological clues as well as ancillary techniques that may be useful to the practicing cytopathologist.

Transcriptomic data helps refining classification of pulmonary carcinoid tumors with increased mitotic counts.

Pulmonary neuroendocrine neoplasms are classified by WHO as either typical or atypical carcinoids, large cell (LCNEC) or small cell (SCLC) neuroendocrine carcinoma based on mitotic count, morphology, and necrosis assessment. LCNEC with low mitotic count and sharing morphologic features with carcinoids are in a gray zone for classification and their rare prevalence and the paucity of studies precludes proper validation of the current grading system. In this study, we aim to investigate their clinicopathological and transcriptomic profiles. Lung resection specimens obtained from 18 patients diagnosed with carcinoids or LCNEC were selected. Four of them were characterized as borderline tumors based on a mitotic rate ranging between 10 and 30 mitoses per 2 mm2. Comprehensive morphological and immunohistochemical (IHC) evaluation was performed and tumor-based transcriptomic profiles were analyzed through unsupervised clustering. Clustering analysis revealed two distinct molecular groups characterized by low (C1) and high (C2) proliferation. C1 was comprised of seven carcinoids and three borderline tumors, while C2 was comprised of seven LCNEC and one borderline tumor. Furthermore, patients in cluster C1 had a better recurrence-free survival compared with patients in cluster C2 (20% vs 75%). Histological features, IHC profile, and molecular analysis showed that three out of four borderline tumors showed features consistent with carcinoids. Therefore, our findings convey that the current diagnostic guidelines are suboptimal for classification of pulmonary neuroendocrine tumors with increased proliferative index and carcinoid-like morphology. These results support the emerging concept that neuroendocrine tumors with carcinoid-like features and mitotic count of <20 mitoses per 2 mm2 should be regarded as pulmonary carcinoids instead of LCNEC.

Diagnostic and Management Pathways for Pulmonary Carcinoid Tumours in the United Kingdom: Results from the National Lung Neuroendocrine Tumour Pathway Project.

There is inconsistency among published guidelines for the optimal diagnostic and management pathways for patients with typical (TC) or atypical (AC) pulmonary carcinoid tumours. We conducted a UK-wide clinician survey to assess current practice for the diagnosis, management, and follow-up of patients with TC/AC and descriptively compared management between European Neuroendocrine Tumor Society (ENETS) accredited centres of excellence (CoE) and nonaccredited centres (non-CoE). Twenty-seven clinicians (10 CoE; 17 non-CoE) participated. Computed tomography of thorax, abdomen, and pelvis was the most commonly reported diagnostic tool (96% of respondents), and bone scans and gallium somatostatin receptor scintigraphy positron emission tomography (SRS PET) were the least commonly reported (30% and 37% of respondents, respectively). Adjuvant therapy is considered for resected TC/AC by <5% of respondents for patients with stage N0 M0 AC or TC, up to 48% of respondents for patients with AC with R1 disease. Somatostatin analogues were the most commonly reported first-line treatment (63% of respondents), and chemotherapy was the most commonly reported second-line therapy and third-line therapy (33% and 41%, respectively) for unresectable and metastatic disease. Reported frequency of initial follow-up after primary surgery ranged from every 2 months to annual, and total follow-up duration ranged from 2 years to indefinite depending on disease type (TC/AC) and stage. For most diagnostic investigations, the highest reported frequency of use was in CoE, most notably gallium SRS PET (70% CoE vs. 18% non-CoE respondents). 93% of respondents (100% CoE; 88% non-CoE) reported having neuroendocrine tumour- (NET-) specialist multidisciplinary team meetings at their centre; 59% (90% CoE; 41% non-CoE) had a NET Clinical Nurse Specialist (CNS) and 48% (80% CoE; 29% non-CoE) had a lung NET patient database. The survey results suggest variability between UK centres in diagnostic pathways and management of patients with TC/AC and suggest that CoE may be able to offer an improved service to patients.

Ectopic Cushing’s Syndrome as the Initial Presentation of Pulmonary Carcinoid Tumor Managed by Etomidate: A Case Report

Ectopic increase of adrenocorticotropic hormone (ACTH) or ectopic Cushing syndrome is a rare initial presentation of small cell carcinoma and carcinoid tumor of the lung. Here, we reported a 36-year-old male with atypical symptoms of Cushing syndrome managed by Etomidate that had a central pulmonary nodule, and pathologic evaluation of pulmonary lobectomy revealed the diagnosis of well-differentiated, low-grade typical carcinoids of lung. © 2019Tehran University of Medical Sciences. All rights reserved. Acta MedIran 2019;57(7):464-467.

Clinicopathological characteristics and genetic analysis of pulmonary carcinoid tumors: A single-center retrospective cohort study and literature review.

Pulmonary carcinoid tumors, including typical and atypical carcinoids, are well-differentiated neuroendocrine tumors (NETs) that represent 1–2% of all lung cancer cases. In the present study, all cases of well-differentiated NETs diagnosed at Tianjin Medical University General Hospital (Tianjin, China) between 2006 and 2016 were reviewed, and 20 pulmonary carcinoid cases were identified. The clinical features of these cases were summarized, and the results of pathological and imaging examinations were collated. As a low-grade malignant pulmonary neoplasm, the molecular biological mechanism of pulmonary carcinoids is yet to be elucidated. To investigate the underlying molecular mechanisms behind pulmonary carcinoids and to determine an effective molecular targeted therapeutic strategy, next-generation sequencing (NGS) was performed using tissue samples from six patients to determine additional molecular biological characteristics that may help guide targeted therapy. A total of 27 somatic mutations in 21 genes were detected. Of note, mutations in the KIT proto-oncogene receptor tyrosine kinase, Erb-B2 receptor tyrosine kinase 4, MET proto-oncogene receptor tyrosine kinase and insulin-like growth factor 1 genes occurred in two out of six cases. Since treatments for advanced carcinoids are relatively ineffective, molecular profiling may contribute to the identification of novel treatments. In addition, the literature on mutations in pulmonary carcinoids was reviewed and available clinical information and features of this tumor type were summarized.

Ki-67 Labeling Index in Pulmonary Carcinoid Tumors: Comparison Between Small Biopsy and Resection Using Tumor Tracing and Hot Spot Methods.

Pulmonary carcinoids are classified as typical or atypical by assessing necrosis and mitoses, which usually cannot be adequately assessed on small biopsies. Ki-67 is not currently used to grade pulmonary carcinoids, but it may be helpful to determine preliminary grade in biopsies. However, the rate at which Ki-67 could underestimate or overestimate grade on small biopsies has not been well studied. To compare Ki-67 labeling obtained on small biopsies to subsequent resection. Ki-67 was performed on paired biopsy and resection specimens from 55 patients. Slides were scanned using Aperio ScanScope. Labeling index was determined using automated hot spot and tumor tracing methods. The study included 41 typical and 14 atypical carcinoids. Atypical carcinoids were larger and had more distant metastases. Death from disease occurred in 3 patients (all had atypical carcinoids). Median hot spot Ki-67 labeling index was greater in resection compared with biopsy by 0.7% (P = .02). Median tumor tracing Ki-67 was lower in resection compared with biopsy by 0.5% (P < .001). Receiver-operating characteristic analysis showed similar hot spot Ki-67 cutoffs to predict atypical histology (3.5% for biopsy, 3.6% for resection; area under the curve [AUC], 0.75 and 0.74, respectively). Different optimal cutoffs were needed for tracing method based on biopsy (2.1%; AUC, 0.75) compared with resection (1.0%; AUC, 0.67). Hot spot Ki-67 tends to underestimate grade on small biopsies, whereas grade is overestimated by tumor tracing. Hot spot Ki-67 cutoff of 3.5% predicted atypical histology for both biopsy and resection. Different biopsy and resection cutoffs were necessary for tumor tracing, which would make clinical implementation more difficult.

A rare ectopic ACTH secreting atypical pulmonary carcinoid- case report

Pulmonary carcinoids are rare pulmonary neoplasms which account for 1-2% of all lung neoplasms. Pulmonary carcinoid tumors are a rare cause of ectopic ACTH secretion. The incidence of Cushing's syndrome in pulmonary carcinoid tumor is approximately 1%. A case of 25-year-old young male with typical cushingoid appearance presented with headache on and off and episodes of hypertension since 1year.Thoracic CT revealed a nodular region in left lower lobe. The patient underwent left lower lobectomy and histopathology revealed an atypical carcinoid tumor. On immunohistochemistry, tumor cells were positive for CK PAN9, CD117, S100, TTF-1, synaptophysin, chromogranin and negative for P40, CK7, Her-2 and CD99.This case is presented for its rarity.

43 - A comparison of radiological and pathological staging in pulmonary carcinoid tumours

43 - A comparison of radiological and pathological staging in pulmonary carcinoid tumours

Pulmonary carcinoid tumours: incidence, histology, and surgical outcome. A population-based study.

Pulmonary carcinoids (PCs) represent only a minority of all primary pulmonary malignancies but they are the most common type of pulmonary malignancy diagnosed in children and adolescents. In this nationwide study, we analyzed data on all PC tumours in the Icelandic population over a 60-year period and concentrated especially on incidence and patient outcomes. We studied all cases of PCs diagnosed in Iceland in the period 1955‒2015. Histological specimens were re-evaluated and the tumours were staged according to the TNM system (seventh edition). Survival was estimated using the Kaplan-Meier method, with a mean follow-up of 15.7years. Altogether, 88 patients (median age 51.0years, 65.9% women) were diagnosed with PCs in the study period. The incidence increased from 0.19/100,000/year in the first decade (1955‒1964) to 0.58/100,000/year in the last decade (2005‒2015), with a mean increase of 29.0% per decade of the study period (p < 0.001). The rise in incidental detection was, however, not significant. The median tumour diameter was 2.2cm (range 0.4‒7.0) and typical histology was seen in 74 patients (84.1%). The other 14 patients (15.9%) had atypical histology. In all, 90.9% of the patients underwent pulmonary resection, 81.2% of them with lobectomy, with all of them surviving at least 30days postoperatively. Most patients (n = 52, 62.7%) were stage IA at diagnosis, 15 (18.1%) were stage IB, nine (10.8%) were stage IIA, and three were stage IIIA (3.6%). Four patients(4.8%) had distant metastases (stage IV), two of whom had typical histology. Five-year survival was 89.8% for all patients: 93.2% for patients with typical histology and 70.7% for those with atypical histology. The incidence of PCs in Iceland has increased significantly over the last six decades, which cannot be explained by a rise in incidental detection at chest imaging. Most patients have localized disease and a favourable histology, where the long-term outcome is excellent.

Obstructive pneumonia owing to migration of a Teflon pledget at 8\u2009years after surgery for a pulmonary carcinoid tumor: a case report

BackgroundIt is uncommon for a bronchial stump-related complication to develop during the remote postoperative period in a case of obstructive pneumonia owing to migration of the suture material. Here, we describe a case of bronchial obstructive pneumonia that developed owing to migration of the suture material in the airway 8 years after pulmonary resection.Case presentationA 34-year-old woman underwent left lower lobectomy for a pulmonary carcinoid tumor (pT1bN0M0-stage IA) in 2010. She experienced obstructive pneumonia, and chest computed tomography revealed a mass protruding from the bronchial stump to the bronchial lumen in 2018. After treatment for pneumonia, flexible bronchoscopy showed the presence of a fibrous suture material (Teflon pledget) completely obstructing the left second carina. A week later, the Teflon pledget obstructing the bronchial lumen was removed using a flexible bronchoscope with the patient under general anesthesia. The procedure was completed without removing the small amount of granulation tissue because the bronchial lumen opened after removing the Teflon pledget. She has remained asymptomatic for 1 year after removal.ConclusionsIn this case, the complication of obstructive pneumonia developed owing to migration of the non-absorbable suture materials used to suture the bronchial stump. Bronchoscopic management of this rare complication comprised endobronchial removal with the patient under general anesthesia. Given our experience with this case, we believe that such conservative management should allow for excellent results in most instances and avoid the need for reoperation.

DIFFUSE SUBCUTANEOUS NODULES AS A FIRST SIGN OF A METASTATIC PULMONARY NEUROENDOCRINE TUMOR

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Pulmonary neuroendocrine tumors are rare tumors that arise from cells of the endocrine and nervous systems with an incidence rate of 2/100,000 population/year in the United States, comprising 2% of all primary lung cancers. The most common described sites of metastases from Carcinoid tumors are liver , bone , and mediastinal lymph nodes . Subcutaneous metastases from carcinoid tumors are very rare. The behavior of these tumors depends upon their location within the lungs, whether they secrete hormones, or if they have metastasized. This tumors comprise a spectrum of progression, including: low grade neuroendocrine tumors , intermediate grade neuroendocrine tumors and high grade neuroendocrine tumors (large cell neuroendocrine tumors and small cell carcinomas) respectively. CASE PRESENTATION: A 72-year-old latin american female with a past medical history of breast cancer that was previously treated with chemotherapy and radiotherapy 10 years ago. Patient came to the institution due to multiple skin progressively painful enlarged skin nodules, fatigue, generalized weakness and melena of several days of evolution. Physical examination revealed multiple skin nodules measuring from 1 to 4 cm in diameter with the largest measuring 3 x 4 cm in the left neck area extremely tender and firm. A biopsy was performed with histopathology consistent with a carcinoid tumor with moderate amount of cytoplasm and eccentric nuclei. Immunohistochemistry of the neoplastic cells exhibited similar positive staining for the neuroendocrine markers chromogranin A and synaptophysin with positive markers for CD56, pankeratin with a Ki67 of 70%. Staining of the neoplastic cells also was positive for thyroid transcription factor 1 (TTF-1) . These results were consistent with cutaneous metastasis from pulmonary carcinoid tumor by which same cells were also seen by stomach biopsy of nodules present as well. DISCUSSION: Cutaneous metastases of internal malignancies are more common from carcinomas of the lungs, gastrointestinal tract, and breasts. The histology of cutaneous carcinoid metastases typically resembles the primary lesion. However, identifying source is a major role in this cases. Occasionally, the cutaneous metastasis will develop directly over the underlying malignancy but thats not the case in the majority of cases. Thats were histologic stains and cells characteristics play a major role. Our case of cutaneous metastasis of a carcinoid tumor presented as multiple tender subcutaneous nodules. The histology of the lesion was consistent with the known carcinoid tumor of the lung. CONCLUSIONS: Even though neuroendocrine tumors are rare, obtaining an concise clinical history , addressing risk factors and pertinent findings of medical presentation with the appropriate immunohistochemical panels is the cornerstone of this challenging cases when primary site is in doubt. Reference #1: Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practiceCaplin ME, Baudin E, Ferolla P, et al. Reference #2: Primary pulmonary carcinoid tumor: a long-term single institution experience/Primary pulmonary carcinoid tumor.Ryan F. Herde, MD, MS1, Kristine E. Kokeny, MD2, Chakravarthy B. Reddy, MD3, Wallace L. Akerley, MD4, Nan Hu, PhD5, Jonathan P. Boltax, MD3, and Ying J. Hitchcock, MD2. Reference #3: Cutaneous Metastasis of a Pulmonary Carcinoid Tumor Cutis. 2017 May;99(5):E13-E15 DISCLOSURES: No relevant relationships by Christian Castillo Latorre, source=Web Response No relevant relationships by Michael Cruz, source=Web Response No relevant relationships by Omar Mendez Melendez, source=Web Response No relevant relationships by Kelvin Rivera Manzano, source=Web Response