OTP, CD44, and Ki-67: A Prognostic Marker Panel for Relapse-Free Survival in Patients with Surgically Resected Pulmonary Carcinoid.

Although most patients with pulmonary carcinoid (PC) can be cured by surgery, relapse may occur until 15 years after resection in up to 10% of patients. This is unpredictable at the outset, necessitating extensive follow-up (FU). We sought to determine whether an immunohistochemical marker panel (OTP, CD44, and Ki-67) could better indicate relapse-free survival (RFS) and increase uniformity among pathologists regarding carcinoid classification.

Identification of Defined Molecular Subgroups on the Basis of Immunohistochemical Analyses and Potential Therapeutic Vulnerabilities of Pulmonary Carcinoids.

Introduction: Multi-omic studies have identified three molecular separated pulmonary carcinoid (PC) subgroups (A1, A2, B) with distinctive mRNA expression profiles (e.g., orthopedia homeobox protein [OTP], achaete-scute homolog [ASCL1], and hepatocyte nuclear factor 1 homeobox A [HNF1A]).

[Intoxication due to apricot pits].

Background: Apricot seeds are recommended online for their alleged cancer-fighting and energy-boosting properties. However, they contain high levels of cyanogenic glycosides. Ingesting just a few apricot pits (1-3) can result in severe symptoms and fatalities have been reported after consuming more than 20 pits.

Disease relapse in relation to lymph node sampling in lung carcinoid patients.

The predictive value of the extent of peri-operative lymph node (LN) sampling in relation to disease relapse in patients with pulmonary carcinoid (PC) is unknown. Furthermore, post-surgery follow-up recommendations rely on institutional retrospective studies with short follow-ups. We aimed to address these shortcomings by examining the relation between LN sampling and relapse in a population-based cohort with long-term follow-up.

Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites.

Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Treatment options for patients with NENs are limited, in part due to lack of accurate models. We establish patient-derived tumor organoids (PDTOs) from pulmonary NETs and derive PDTOs from an understudied subtype of NEC, large cell neuroendocrine carcinoma (LCNEC), arising from multiple body sites.

Development and verification of new monoclonal orthopedia homeobox (OTP) specific antibodies for pulmonary carcinoid diagnostics.

Background: Orthopedia homeobox (OTP) has shown to be a useful prognostic marker to predict outcome in pulmonary carcinoids, which is also supported by the World Health Organization. However, the discontinuation of the initially used polyclonal antibody and absence of a reliable routinely applicable monoclonal OTP antibody hampers implementation in routine diagnostics. Here, new monoclonal antibodies directed against OTP were developed and verified on formalin-fixed paraffin-embedded tissue of pulmonary neuroendocrine tumors (NETs) for clinical diagnostics.

Differential Orthopedia Homeobox expression in pulmonary carcinoids is associated with changes in DNA methylation.

Limited number of tumor types have been examined for Orthopedia Homeobox (OTP) expression. In pulmonary carcinoids, loss of expression is a strong indicator of poor prognosis. Here, we investigated OTP expression in 37 different tumor types, and the association between OTP expression and DNA methylation levels in lung neuroendocrine neoplasms.

In-depth molecular analysis of combined and co-primary pulmonary large cell neuroendocrine carcinoma and adenocarcinoma.

Up to 14% of large cell neuroendocrine carcinomas (LCNECs) are diagnosed in continuity with nonsmall cell lung carcinoma. In addition to these combined lesions, 1% to 7% of lung tumors present as co-primary tumors with multiple synchronous lesions. We evaluated molecular and clinicopathological characteristics of combined and co-primary LCNEC-adenocarcinoma (ADC) tumors.

Preoperative Biopsy Diagnosis in Pulmonary Carcinoids, a Shot in the Dark.

Introduction: The preferred treatment for pulmonary carcinoids (PCs) is lobectomy, and parenchyma-sparing approaches might be considered for typical carcinoids (TCs). Treatment decisions are based on a preoperative biopsy diagnosis. Following the WHO criteria (2015), definitive diagnosis is only feasible postoperatively, thereby hampering preoperative treatment decisions.

Unique Metastatic Patterns in Neuroendocrine Neoplasms of Different Primary Origin.

Introduction: Neuroendocrine neoplasms (NEN) can originate in different organs, for example, the gastroenteral tract (GE), pancreas (Pan), or lungs (L). Our aim was to examine metastatic patterns for patients with NEN of various primary origins with a special focus on brain metastases to indicate utility for screening.

Methods: All NEN patients except for small cell lung cancer registered in the Netherlands Cancer Registry from 2008 to 2018 were selected.

Orthopedia Homeobox (OTP) in Pulmonary Neuroendocrine Tumors: The Diagnostic Value and Possible Molecular Interactions.

Generally, patients with stage I-IIIa (TNM) pulmonary carcinoid disease have a favourable prognosis after curative resection. Yet, distant recurrence of disease after curative surgery occurs in approximately 1-6% of patients with typical carcinoid and 14-29% in patients with atypical carcinoid disease, respectively. Known predictors of distant recurrence of disease are atypical carcinoid, lymphatic involvement, and incomplete resection status.

Is the sum of positive neuroendocrine immunohistochemical stains useful for diagnosis of large cell neuroendocrine carcinoma (LCNEC) on biopsy specimens?

Aims: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is underdiagnosed on biopsy specimens. We evaluated if routine neuroendocrine immunohistochemical (IHC) stains are helpful in the diagnosis of LCNEC on biopsy specimens.

Methods And Results: Using the Dutch pathology registry (PALGA), surgically resected LCNEC with matching pre-operative biopsy specimens were identified and haematoxylin and IHC slides (CD56, chromogranin-A, synaptophysin) requested.

New Insights into the Molecular Characteristics of Pulmonary Carcinoids and Large Cell Neuroendocrine Carcinomas, and the Impact on Their Clinical Management.

Carcinoids and large cell neuroendocrine carcinomas (LCNECs) are rare neuroendocrine lung tumors. Here we provide an overview of the most updated data on the molecular characteristics of these diseases. Recent genomic studies showed that carcinoids generally contain a low mutational burden and few recurrently mutated genes.

Molecular Subtypes of Pulmonary Large-cell Neuroendocrine Carcinoma Predict Chemotherapy Treatment Outcome.

Previous genomic studies have identified two mutually exclusive molecular subtypes of large-cell neuroendocrine carcinoma (LCNEC): the mutated (mostly comutated with ) and the wild-type groups. We assessed whether these subtypes have a predictive value on chemotherapy outcome. Clinical data and tumor specimens were retrospectively obtained from the Netherlands Cancer Registry and Pathology Registry.

Chemotherapy for pulmonary large cell neuroendocrine carcinomas: does the regimen matter?

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is rare. Chemotherapy for metastatic LCNEC ranges from small cell lung carcinoma (SCLC) regimens to nonsmall cell lung carcinoma (NSCLC) chemotherapy regimens. We analysed outcomes of chemotherapy treatments for LCNEC.

A Population-Based Analysis of Application of WHO Nomenclature in Pathology Reports of Pulmonary Neuroendocrine Tumors.

Introduction: Pulmonary neuroendocrine tumors (pNETs) are difficult to classify. We performed a population-based analysis to investigate the application of pNET nomenclature in daily pathology practice.

Methods: Conclusions from pathology reports (2003-2012) describing carcinoids, (large cell) neuroendocrine carcinomas (NECs), and carcinomas with neuroendocrine features/differentiation were retrieved from the Dutch Pathology Registry by queries on location and diagnosis and screened for terminology.

Neuroendocrine Cancer of the Lung: A Diagnostic Puzzle.

Here we report the case of a pulmonary neuroendocrine tumor (pNET) in which the pathological diagnosis was revised several times over the course of the patient's disease because of atypical behavior of the tumor; consequently, the patient was treated with various treatment schedules.

Clinical features of large cell neuroendocrine carcinoma: a population-based overview.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an orphan disease and few data are available on its clinical characteristics. Therefore, we analysed LCNEC registered in the Netherlands Cancer Registry, and compared data with small cell lung carcinoma (SCLC), squamous cell carcinoma (SqCC) and adenocarcinoma (AdC).Histologically confirmed LCNEC (n=952), SCLC (n=11 844), SqCC (n=19 633) and AdC (n=24 253) cases were selected from the Netherlands Cancer Registry (2003-2012).

Genetics and Epigenetics of Pancreatic Neuroendocrine Tumors and Pulmonary Carcinoids.

In this chapter, we give an overview of the genetic and epigenetic background of neuroendocrine tumors (NETs), in particular pancreatic and pulmonary NETs. Studying the mechanism of disease of the inherited syndromes that feature NETs has provided valuable insights that have revolutionized the therapeutic options for these tumor types: both inhibition of mTOR (mammalian target of rapamycin) signaling and inhibition of angiogenesis have become standard treatments. Although sporadic NETs harbor relatively few somatic gene mutations, these somatic mutations often affect genes that encode epigenetic regulators.