Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype

B. C. M. Hermans, J. L. Derks, H. J. M. Groen, J. A. Stigt, R. J. van Suylen, L. M. Hillen, E. C. van den Broek, E. J. M. Speel, A-M C. Dingemans*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Introduction: Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (P1) 40-80%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small-cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small-cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up.

Methods: Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next-generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1).

Results: All patients had NO or N1 disease. Median overall survival (OS) was 12 months (95% confidence interval (CI) 5.5-18.5 months). Mean Ki-67 PI was 59% (range 15-100%). In 6/11 LCNEC Ki-67 PI was 40% (17 months (95% CI 11-23 months) vs 5 months (95% CI 0.7-9 months), P = 0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67

Conclusion: Stage IV LCNEC with a solitary brain metastasis and NO/N1 disease show in the majority of cases Ki-67 PI

Original languageEnglish
Pages (from-to)1600-1606
Number of pages7
JournalEndocrine Connections
Issue number12
Publication statusPublished - Dec 2019


  • large cell neuroendocrine carcinoma
  • solitary brain metastasis
  • prognosis
  • Ki-67
  • LUNG

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