Carcinoid Lung Tumors Guidelines

Updated: Jan 14, 2017
  • Author: Mary C Mancini, MD, PhD, MMM; Chief Editor: Jeffrey C Milliken, MD  more...
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Guidelines

Guidelines Summary

Guidelines Contributor:  Evan S Ong, MD, MS Assistant Professor of Surgery, Section of Surgical Oncology, University of Arizona College of Medicine

Grading and staging

Grading schemes for gastroenteropancreatic neuroendocrine tumors (NETs) use mitotic count; the level of the nuclear protein Ki-67, which is associated with cellular proliferation; and assessment of necrosis. However, for NETs of the lungs and thymus, the World Health Organization (WHO) includes only mitotic count and assessment of necrosis. [32] In its 2015 consensus statement on best practices for pulmonary neuroendocrine tumors, the European Neuroendocrine Tumor Society (ENETS) noted that tumor grading based on a combination of Ki-67, mitotic rate, and necrosis may be of clinical importance but lacks validation. [33]

Under the WHO grading scheme, tumors fall into one of the following three grades:

  • Low-grade tumors, <2 mitoses/10 high power fields (HPFs) and no necrosis
  • Intermediate tumors, 2-10 mitoses/HPF and/or foci of necrosis
  • High grade tumors, >10 mitoses/10 HPF

Whereas the National Comprehensive Cancer Network (NCCN) recommends use of the WHO scheme for grading, it also recommends that tumor differentiation, mitotic rate, and Ki-67 rate be included in the pathology report and that the specific classification and grading scheme be noted to avoid confusion. Clinicians are advised to view histologic grade as a general guide and use clinical judgment to make treatment decisions, particularly in cases of discordance between differentiation and Ki-67 proliferation results. [34]

The European Society of Medical Oncology (ESMO) and NCCN guidelines recommend staging according to the seventh edition of the American Joint Committee on Cancer's AJCC Cancer Staging Manual. [35, 34] Bronchopulmonary carcinoids are staged according to the same system used for other pulmonary malignancies. [36]

The North American Neuroendocrine Tumor Society (NANETS) concluded that although the criteria differ among the various classification systems, the underlying data are similar, and pathology reports should include notation of the systems and parameters used to assign the grade and stage. For NETs of the thorax (including the lungs and thymus), resection margins should be indicated, measuring the distance from the tumor edge to guarantee radical excision on surgical specimens. [37]

Diagnosis

The ENETS guidelines recommend contrast computed tomography (CT) as the gold standard for diagnosis but note that pathology examination is mandatory for their correct classification. Key pathology recommendations include the following [33] :

  • Pulmonary carcinoids (PCs) are well-differentiated NETs and include low-grade malignant tumors (typical carcinoid) and intermediate-grade malignant tumors (atypical carcinoid)
  • Distinguishing a typical carcinoids (TC) from an atypical carcinoid (AC) requires a surgical specimen. Small biopsy and cytology are not adequate
  • Neuroendocrine (NE) immunomarkers (chromogranin A, synaptophysin, and/or CD56/NCAM) may be used to confirm NE nature of tumors especially in biopsy/cytology specimens or surgical specimens. In case of metastatic presentation, positive TTF1 staining is suggestive of a lung or thyroid origin 

Treatment

NCCN treatment recommendations are as follows [34] :

  • Stage I, II, and IIIA - Lobectomy or wedge resection for peripheral low-grade neuroendocrine carcinoma and lymph node dissection or sampling
  • Stage IIIA low grade nonresectable tumors - Radiation therapy
  • Stage IIIA intermediate grade nonresectable tumors - Cisplatin/etoposide and radiation therapy
  • Stage IIIB (except for T4 due to multiple lung nodules) - Cisplatin/etoposide with or without radiation therapy
  • Stage IIIBm (T4 due to multiple lung nodules) or stage IV - Systemic therapy; no preferred regimen; options include cisplatin/etoposide, temozolomide with or without capecitabine, sunitinib, or everolimus; consider octreotide for symptoms of malignant carcinoid syndrome

The NANETS guidelines and the ESMO guidelines are similar to those of the NCCN, with some minor variances. The ESMO guidelines include the following additional recommendations [35] :

  • Bronchoscopic laser excision should be considered a suboptimal treatment and be reserved for inoperable patients or performed as a preoperative disobliterating procedure
  • Lobectomy and sleeve resection are preferred for locoregional tumors and systemic nodal dissection should be performed
  • Pneumonectomy should be avoided

Additionally, NANETS suggests that interferon alfa should be considered for metastatic or unresectable disease. [37]