A multidisciplinary approach to the work up and management of pulmonary carcinoid tumors and DIPNECH: a narrative review

Abstract

Background and objective: Low and intermediate grade neuroendocrine tumors of the lung are uncommon malignancies representing 2% of all lung cancers. These are termed typical and atypical pulmonary carcinoid tumors. These can arise in the setting of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). The presentation, workup, management and outcomes of patients with these tumors can overlap with more common lung cancers but differ in that many of these patients have a prolonged clinical course. The objective of this narrative review is to summarize the literature and provide evidence and expert-based algorithms for work up and treatment of pulmonary carcinoids and DIPNECH.

Methods: A search of PubMed and Web of Science databases ending April 15, 2022, with the following keywords "lung carcinoid", "DIPNECH", "lung neuroendocrine," and "bronchopulmonary carcinoid".

Key content and findings: Pulmonary carcinoid tumors benefit from a multidisciplinary approach. Pre-treatment imaging with contrast-enhanced computed tomography, and DOTATATE positron emission tomography is required. Surgical resection is the gold standard for curative intent, and possibly including sublobar resections. Patients can recur or develop new primaries thus emphasizing the importance of surveillance; national guidelines recommend at least a 10-year follow up. A growing body of literature support the use of endobronchial therapy, with long responses documented. Systemic therapy consists of everolimus, somatostatin analogs, peptide receptor radionuclide therapy, and chemotherapy. Diffuse idiopathic pulmonary neuroendocrine tumor cell hyperplasia is rare, but series suggest somatostatin analogs may confer clinical benefit.

Conclusions: Pulmonary carcinoid tumors and DIPNECH are rare. Despite lack of regulatory approvals for advanced disease, multiple options are available but should be sequenced according to the clinical status and disease biology. Each patient should be discussed in a multidisciplinary setting and clinical trials should be considered if available.

Keywords: Lung carcinoid; bronchopulmonary, neuroendocrine; diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH).

Figure 1

Light microscopy of typical and atypical pulmonary carcinoid tumors. (A) Typical carcinoid showing nests of uniform cells with speckled chromatin pattern and moderate amount of cytoplasm; hematoxylin and eosin (H&E), 200×. (B) Arrows showing mitotic figures in an atypical carcinoid; H&E, 400×.

Figure 2

Robotic sleeve resection. The left upper lobe bronchus was sharply transected followed by the left mainstem bronchus proximal to the endobronchial carcinoid. The margins were sent to pathology which were confirmed to be negative and thus airway reconstruction was performed suturing the upper lobe bronchus (superior) to the remaining left mainstem (inferior). The membranous airway has been sutured (A) and the remaining cartilaginous portion was completed with interrupted sutures to account for the differences in size (B).

Figure 3

Endobronchial therapy with cryospray. Row (A) shows the pre-intervention findings of an endobronchial tumor located on the left secondary carina (LC2), located between the left upper lobe and the left lower lobe, followed by the application of cryospray on the tumor for additional ablation post-electrocautery coagulation and the immediate post-intervention image. Row (B) was the first follow-up bronchoscopy six weeks later, which shows a medium-sized ulcerated lesion without tumor recurrence overlying the LC2 carina, with additional application of cryospray to the ulcerated lesion for additional ablation and immediate post-intervention image. Row (C) was the follow-up bronchoscopy eight months post initial endobronchial carcinoid tumor treatment, which showed excellent response without recurrence.

Figure 4

Proposed algorithm for the diagnosis and management of pulmonary carcinoid tumors. PET, positron emission tomography; CT, computed tomography; ACTH, adrenocorticotropic hormone; GHRH, growth hormone releasing hormone; 5-HIAA, 5-hyroxyindoleacetic acid; MRI, magnetic resonance imaging; TC, typical carcinoid; EBT, endobronchial treatment; APC, argon plasma coagulation; PRRT, peptide receptor radionuclide therapy; CAPTEM, capecitabine/temozolomide. This algorithm was partially adopted from (23): Papaporfyriou A, Domayer J, Meilinger M, et al. Bronchoscopic diagnosis and treatment of endobronchial carcinoid: case report and review of the literature. Eur Respir Rev 2Eur Respir Rev. 2021;30(159):200115. Reproduced with permission of the © ERS 2022: European Respiratory Review 30 (159) 200115; DOI: 10.1183/16000617.0115-2020. Published 6 January 2021.

Figure 5

Light microscopy representing neuroendocrine cell hyperplasia and carcinoid tumorlet in a patient with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. (A) Small airway partially damaged by granulation tissue and neuroendocrine cells spilling into the lumen; hematoxylin and eosin (H&E), 100×. (B) Synaptophysin immunostains highlighting the neuroendocrine cells in image A; 100×. (C) Over time, the granulation tissue within the small airway may be replaced by scar; H&E, 100×. (D) Synaptophysin immunostains highlighting the neuroendocrine cells in image B; 100×.

Figure 6

Axial CT image of the lungs (1.25 mm slice thickness, lung windows) demonstrating mosaic attenuation and lung nodules characteristic of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Short arrows delineate several of the multiple bilateral bronchocentric solid circumscribed lung nodules. The background lung parenchyma has heterogeneous CT attenuation reflecting air-trapping and mosaic attenuation. CT, computed tomography.