Challenges in the Diagnosis and Management of Well-Differentiated Neuroendocrine Tumors of the Lung (Typical and Atypical Carcinoid): Current Status and Future Considerations

Abstract

Neuroendocrine tumors (NET) of the lung represent approximately 25% of all primary lung tumors and can be classified as low grade (typical carcinoids), intermediate grade (atypical carcinoids), or high grade (large cell neuroendocrine carcinoma or small cell lung carcinoma). Low-and intermediate-grade lung NET are increasingly recognized as biologically distinct from high-grade lung NET based on clinical behavior and underlying molecular abnormalities. This review summarizes current knowledge and challenges in the diagnosis and management of low-and intermediate-grade lung NET. Accurate histopathologic classification of lung NET is critical to determining appropriate treatment options but can be challenging even for experts. For low-and intermediate-grade lung NET, surgery remains the mainstay of treatment for localized disease.Although no standard systemic therapy has been established for the treatment of advanced, unresectable disease, a number of promising treatment options are emerging, including somatostatin analogs, temozolomide-based chemotherapy, targeted therapy with mammalian target of rapamycin or vascular endothelial growth factor inhibitors, and peptide receptor radionuclide therapy. Given the difficulty in accurately diagnosing these tumors, and the paucity of data supporting establishment of standard systemic therapy options, management of patients within the setting of a multidisciplinary team, including specialists with expertise in NET, is recommended. Ongoing and future clinical trials hopefully will provide stronger evidence to support treatment recommendations for low-and intermediate-grade lung NET. The Oncologist 2015;20:1123-1131Implications for Practice: Treatment of neuroendocrine tumors (NET), particularly those of lung origin, continues to evolve. This review seeks to educate oncologists on the most up-to-date options and supporting data regarding management of two rare lung neoplasms, typical and atypical carcinoid tumors. Although surgical resection has been the mainstay of treatment, several systemic options have been studied in the treatment of NET of various origins that may potentially play a role in treating typical carcinoid tumors and atypical carcinoid tumors.

Do we really care about incidental lung nodules?—Review of atypical lung carcinoid and a proposal for systematic patient follow up

“…Mitoses <2 would signify a TC and >10 would signify LCNEC (4). Carcinoid tumors can be diagnosed with cytological assessment, but differentiating between ACs and TCs requires a resected specimen (4). IHC can strengthen the diagnosis in cases of equivocal histology.…”

“…Common NET IHC markers are chromogranin A (CgA), CD56, synaptophysin, and neuron-specific enolase. CgA can be used to detect tumor recurrence as it is associated with tumor burden, but this should be done with caution as unrelated factors can cause CgA levels to rise (4). Since the release of the 7 th edition of TNM staging criteria designed by the American Joint Committee on Cancer, carcinoid tumors now have TNM parameters (same as for NSCLC) (4).…”

“…CgA can be used to detect tumor recurrence as it is associated with tumor burden, but this should be done with caution as unrelated factors can cause CgA levels to rise (4). Since the release of the 7 th edition of TNM staging criteria designed by the American Joint Committee on Cancer, carcinoid tumors now have TNM parameters (same as for NSCLC) (4). Interpretation of the minor histological differences between the various NETs leads to interobserver variability and delays accurate diagnosis (3).…”

“…Patients may also present with symptoms of Cushing syndrome and carcinoid syndrome (bronchospasm, flushing, and diarrhea). Carcinoid syndrome symptoms signify carcinoid metastasis to the liver (4). The 50% of all patients with ACs have lymph node metastases at the time of due to its indolent course (5).…”

“…The 5-year survival rate is inversely related to the tumor stage at presentation. The rate of metastases and recurrence is worse for ACs compared to typical lung carcinoids (TCs) (2,4,5). ACs may be detected as an incidental central or peripheral pulmonary nodule.…”